Infection & Immunity 2: Objectives by h1519w

VIEWS: 21 PAGES: 137

									                               Third Year Clerkships

                                    Fall 2007
                                     last updated 11/8/2007

                                      Christopher B. Kolar

This study guide has been created in the course of my studies at the University of Wisconsin
School of Medicine and Public Health. It is intended as an exam review of the required learning
objectives. It references a variety of course materials, including lecture, Power Point, assigned
readings, and sometimes outside sources. While I have attempted to make it as thorough, specific,
and accurate as possible, I cannot guarantee this, so use it at your own risk. If you have any
questions or comments, or have found an error within the text, please feel free to contact me.

                                                              COLOR KEY:
                                                              • red:    diseases
                                                              • blue:   medications
                                                              • orange: enzymes and compounds
                                                              • pink:   microorganisms
                                                              • gray:   supplemental information

                                                              FORMAT KEY:
                                                              • margins: 1”
                                                              • tab stops: 0.25”
                                                              • font:      Times New Roman
                                                              • size:      10
                                                                              Infection & Immunity 2: Objectives (page 2 of 137)

Approach to the Normal Newborn
                                                                                                               CHAPTER 1

1.     List the information from the history of pregnancy, labor, and delivery obtained from the parents or medical
       record that has implications for the health of the newborn.

- prenatal interview
   - social history:        length of marriage
   - pregnancy history:     ease / difficulty of conception
                            problems during this or previous pregnancies
     - PMH:                 medications now being used
                            past history of problems with children
     - AODA history:        alcohol, smoking habits
     - family history:      past history of problems with children
                            medical, genetic problems of other family members

     - other concerns:      plans for postnatal care
                            - breastfeeding vs. bottle feeding
                            - safety, general care concerns

- initial evaluation of the normal newborn
   - delivery record:        length of delivery
                             duration of ruptured membranes
                             mother’s course during labor
                             condition of the infant at birth (APGAR score)

     - infant chart:        maternal factors
                            - blood type and Rh factor
                            - serology and hepatitis B status
                            - HIV status
                            infant factors
                            - vital signs (esp. heart, respiration)
                            - I/O (urination and passage of meconium)

- initial physical examination of the normal newborn
   - general:          comfortable appearance
                       pink color
                       flexion of all four extremities
   - skin:             birthmarks
   - head:             normal head circumference
   - face:             normal face
                       absence of stigmata of recognizable syndromes
   - eyes:             irises round, of the same color
   - nose:             nares symmetrical
   - ears:             pinnae normal, of the same shape
   - mouth:            palate intact
                       no teeth or masses
   - chest:            respirations symmetrical, effortless
   - heart:            absence of an audible murmur
                       heart rate normal, regular in rhythm
   - abdomen:          round, convex abdomen
                       absence of palpable masses
   - genitalia, male: penile meatus in the proper place
                       both testes palpable, of the same size
                                                                               Infection & Immunity 2: Objectives (page 3 of 137)

     - genitalia, female: labia majora, minor present
                          vaginal opening present
     - extremities:       10 fingers, 10 toes
                          arms of the same size, legs of the same size
                          full abduction of the hips
     - back:              straight spine
                          absence of dimples in the midline
     - CNS:               flexor tone is greater than extensor tone
                          both hands fisted
                          strong infant cry

     BOX: Hip Dysplasia
      The Ortolani and Barlow maneuvers are used to check for developmental dysplasia of the hip.

        • Barlow:       adduction of flexed hips, bringing femoral head from anterior to posterior (bring together)
        • Ortolani:     abduction of flexed hips, bringing femoral head from posterior to anterior (spread apart)

- common newborn vital signs
   - heart rate:     120-160 /min
   - respirations:   30-60 /min
   - blood pressure: 60-70 mmHg systolic
   - temperature:    97.7-99.3°F (pediatric fever is > 100.4°F)
   - glucose (PRN): > 40 mg/dL

2.     List the components of the APGAR score.

- APGAR score
  - function: evaluation of the well-being of newborn infants at the time of delivery
  - method:   repeated twice, at 1 and at 5 minutes
  - clinical: most normal infants will not score a perfect 10 (lose a point for color)

     TABLE: APGAR Score
                                     0                                 1                                 2
      Appearance                   blue                   body pink, extremities blue                   pink
      Pulse                       absent                          < 100 bpm                          > 100 bpm
      Grimace                     absent                           grimace                   grimace and cough / sneeze
      Activity                     limp                   some flexion in extremities              active motion
      Respiration                 absent                        slow, irregular                     good, crying

3.     Discuss criteria for appropriate discharge of a newborn from the nursery.

- issues for discharge
   - jaundice:         jaundice within 24 h requires evaluation
                       - ABO incompatibility
                       - exaggerated physiologic jaundice (generally physiologic only after 2-3 days)
                       - breast milk jaundice
   - weight loss:      infants expected to lose weight at birth
                       - 3-5 oz weight loss first day
                       - 3-5 oz weight loss second day
                                                                             Infection & Immunity 2: Objectives (page 4 of 137)

                         - bottle-fed infants return to normal at days 7-10
                         - breastfed infants return to normal at days 10-14
     - feeding:          breastfeeding issues may include:
                         - comfort of the mother
                         - ease of the baby with getting on the breast
                         - sucking ability
                         - mother’s milk “coming in” (often takes 3-4 days)
     - outputs:          urination, passage of meconium within 12 h
     - temperament:      development of a personality within an infant
     - new findings:     repetition of the physical exam and notation of new findings

X. Discuss the risks and benefits of circumcision

- circumcision
   - function:           benefits include
                         - decreased UTIs
                         - decreased STDs
                         - decreased penile cancer
     - complications:    possible risks include:
                         - bleeding
                         - infection
                         - poor cosmetic result
                         - pain

Health Maintenance Visit
                                                                                                              CHAPTER 2

1.     Describe the components of a health supervision visit, including health promotion, injury prevention, and
       immunizations for newborns, infants, toddlers, and school-aged children.

     BOX: Components of a Health Supervision Visit
      In general, a health supervision visit is
        focused on three major components:

        • health promotion
        • injury prevention
        • immunizations

- newborn (1-4 weeks)
   - feeding:        feeding schedule often erratic
                     weight loss in initial 3-4 days, regain birth weight at 10-14 days
   - sleep:          generally 12-14 hours per day, but only 3-4 hours at a time
   - crying:         may cry for 3-5 hours per day in first month of life, which gradually diminishes
                     colicky babies may continue to have severe crying after first 3 months
                                                                          Infection & Immunity 2: Objectives (page 5 of 137)

- early infancy (1-6 months)
   - feeding:         reduced need for middle of night feeds
   - sleep:           regular sleeping schedule (through the night) by 3-4 months
                      “Back to Sleep”
   - development:     responsive, smiling, able to make different sounds
   - temperament:     development of a personality
   - safety:          baby-proofing home
   - parenting:       consideration of returning to work and child care arrangements

- late infancy (6-12 months)
   - feeding:          introduction of strained, then junior foods
                       weaning from breast / bottle (usually by first year)
   - sleep:            sleeping through the night (generally by 3-4 months; some regression at 9-10 months)
   - development:      development of normal stranger anxiety
   - safety:           increasing mobility
                       baby-proofing of home (mandatory by 6-12 months)
   - parenting:        adjustment to increasing independence

- early childhood (1-2 years)
   - feeding:          eating meals with family
   - sleep:            napping during the day
                       sleeping in own room
   - development:      first steps
                       enjoyment of reading
                       television (limit to 1-2 hours / day maximum)
   - temperament:      differences in personality
   - social:           introduction to playmates
                       interactions with siblings
   - parenting:        child care arrangements

- toddler (2-3 years)
   - parenting:       discipline issues
   - development:     toilet training (median 33 months, bowel before bladder)
                      enuresis (may be normal until 4-5 years of age, should not fuss over bedwetting)
                      recognition, naming of objects
                      appropriate developmental behaviors (running, up and down stairs, throwing balls)
   - temperament:     expression of different emotions
   - social:          taking turns, sharing
   - parenting:       time for fun, play with child

  BOX: Immunizations
   The current vaccination schedule recommends 7 vaccination
     series in the young pediatric population, including:

     • hepatitis B (Hep B)
     • diphtheria, tetanus, pertussis (DTaP)
     • pneumococcus (PCV)
     • inactivated polio (IPV)
     • Haemophilus influenza, type B (Hib)
     • measles, mumps, rubella (MMR)
     • varicella
                                                                             Infection & Immunity 2: Objectives (page 6 of 137)

     In addition, selected populations are recommended to have 2
       additional vaccines:

       • hepatitis A
       • influenza

2.   Discuss the appropriate use of screening tools (neonatal screening, developmental screening, hearing and
     vision screening, lead screening, anemia screening, and tuberculosis testing).

- Denver Developmental chart
  - function:      evaluation of developmental progress
  - method:        comparison of normal ranges on four dimensions
                   - gross motor
                   - fine motor-adaptive
                   - language
                   - personal-social

- Pediatric Symptoms Checklist
   - function:       evaluation of behavioral problems
   - method:         30 questions about behavior, 0 - 2 points for each question
   - interpretation: based on total score
                     - preschool child:    > 24 points suspicious
                     - school age child:   > 28 points suspicious

- neonatal screening battery
   - function:        early detection of several diseases
                      - hypothyroidism
                      - phenylketonuria
                      - sickle cell disease
                      - inborn errors of metabolism (IEM)
   - method:          blood test at 24 hours (or at first health maintenance visit)

- other screening tests
   - hearing
   - vision
   - lead levels
   - anemia screening
   - tuberculosis testing

3.   Explain the usefulness of longitudinal data in assessing growth.

- CDC growth charts
  - function:       evaluation of growth progress
  - method:         percentile ranking of growth for height and weight
  - interpretation: segregation into normal growth tract near 12 months
                    gross disparities or sudden changes from normal tract require further evaluation
  - clinical:       separate charts available for specific diseases (e.g. Down syndrome, cystic fibrosis)
                                                                                Infection & Immunity 2: Objectives (page 7 of 137)

4.     State age-appropriate examples of anticipatory guidance about nutrition, sleep, safety, and discipline for the
       neonate, infant, toddler, and school-aged child.

- infant (0-1 year)
   - hazards:           keep crib sides raised
                        do not leave child unattended on tables or beds
                        provide constant supervision
                        keep plastic bags and balloons away from children
                        do not put anything around the child’s neck
                        do not allow the child to play with small objects
                        select an experienced baby sitter (at least 13, able to handle common emergencies)
                        check heating systems annually
                        place operable window guards on all windows
                        do not place the child in a walker

     - burns:           do not smoke in the home (most deaths due to home fires are smoking-related)
                        develop an escape plan
                        buy a fire extinguisher
                        install a smoke alarm
                        do not drink or carry hot liquids when holding the child
                        erect barriers around space heaters

     - water:           never leave the child alone in or near a tub, pail, toilet, or pool of water
                        fence in pool or hot tub on all 4 sides

     - automobile:      never place an infant in front of an air bag
                        seat a child in the rear of the car

     - bicycle:         do not carry children younger than 12 on bicycles

     - firearms:        remove all guns from places children live and play

- toddler (1-4 years)
   - hazards:         never leave small children alone in the home
                      select an experienced baby sitter (at least 13, able to handle common emergencies)
                      keep plastic bags and balloons out of reach
                      small objects and certain foods may block the child’s airway
                      mechanical garage doors may crush a child
                      place operable window guards on all windows in your home
                      keep small children out of the yard while lawn mower is in use
                      use gates on stairways
                      place baby’s crib away from windows
                      check for hazards in homes your child may visit
                      report any history of injuries to the pediatrician

     - firearms:        remove all guns from places children live and play

     - poisonings:      keep medicines and hazardous products out of sight and reach of children
                        dispose of old medicines
                        purchase medicines with child-resistant safety caps
                        inspect walls for peeling paint
                        learn first aid for poisoning (keep Ipecac, ask poison control before using)
                        check heating and ventilation systems annually

     - burns:           do not use electrical appliances within reach of a child in the bathroom
                        keep electrical cords out of a child’s reach
                                                                              Infection & Immunity 2: Objectives (page 8 of 137)

                      keep matches, lighters out of the reach of children
                      do not smoke in the home (most deaths due to home fires are smoking-related)
                      develop an escape plan
                      buy a fire extinguisher
                      install a smoke alarm
                      check hot water temperature (should be < 120°F)
                      keep pots and pans out of the reach of children

  - water:            never leave the child alone in or near a tub, pail, toilet, or pool of water
                      always wear a Coast Guard-approved life jacket
                      fence in pool or hot tub on all 4 sides
                      do not let children swim without supervision

  - bicycle:          use an approved child carrier

  - automobile:       keep children properly restrained in a properly-sized car safety seat
                      never leave a child alone in a car
                      seat children in the rear seat of the car
                      never put children in front of passenger air bags
                      buckle up and lock up
                      young children should not play in driveways or near busy streets

  - toys:             inspect toys for safety hazards

- school-age children (5-9)
   - firearms:         remove all guns from places children live and play

  - household:        never let children this age operate a lawn mower or ride on one
                      report any history of injuries to the pediatrician
                      check heating and ventilation systems annually

  - burns:            develop an escape plan
                      do not smoke in the home (most deaths due to home fires are smoking-related)
                      do not let children play with fire or fireworks
                      buy a fire extinguisher
                      install smoke alarms

  - water:            teach children how to swim
                      teach and enforce the rules of swimming and diving safety
                      be sure your child wears a life jacket when on a boat

  - automobile:       booster seat on every trip for all children from 40-80 lb (until about 4’9”)
                      never seat a child in front of a passenger air bag

  - pedestrian:       teach pedestrian safety skills

  - bicycle:          teach and enforce bicycle safety rules
                      wear a bicycle helmet

  - recreation:       wear protective gear during sports
                      all children should wear an approved equestrian helmet when riding a horse

- preadolescent children (10-12 years)
   - firearms:        do not play with guns

  - burns:            check that your home has a smoke alarm
                                                                                   Infection & Immunity 2: Objectives (page 9 of 137)

     - bicycle:             never ride with passengers on your bike
                            always wear a helmet when riding a bike

     - automobile:          buckle up

     - pedestrian:          follow safety rules when crossing the street

     - water:               never play near water without an adult nearby

     - farm:                farm equipment is dangerous for children

5.     Describe major developmental milestones of the neonate, infant, toddler, and school-aged child.

                  Please see the accompanying document on developmental milestones.


X. Know the basics of each of the immunizations offered to pediatric patients, including the covered disease(s),
   type of vaccine, contraindications to use, and number of doses in the series.

- Hep B vaccine
  - disease:                hepatitis B
  - function:               induce immunity, protect against carrier status, reduce risk of vertical transmission
  - classification:         protein (recombinant HBsAg)
  - contraindications:      anaphylaxis to previous Hep B vaccine
  - series:                 3 dose series, begin at birth

- DTaP vaccine
  - disease:                diphtheria, tetanus, pertussis
  - function:               protect against serious complications
                            - apnea and upper airway obstruction
                            - tetany and infant death
     - classification:      toxoid (tetanus, pertussis)
                            immunogen (acellular pertussis)
     - contraindications:   immediate anaphylactic reaction to previous vaccine
                            encephalopathy within 7 days of vaccine
                            +/– progressive neurologic disorder of unknown etiology
     - series:              5 dose series, begin at age 2 mo.

- PCV vaccine
   - disease:               pneumococcus
   - function:              protect against serious morbidity / mortality
   - classification:        capsular polysaccharide
   - contraindications:     anaphylaxis to previous PCV
   - series:                4 dose series

- IPV vaccine
   - disease:               polio
   - function:              protect against serious disease (last case in U.S. in 1979)
                            - aseptic meningitis
                            - persistent flaccid paralysis (1 in 250)
     - classification:      two variations
                            - injected: inactivated virus
                                                                               Infection & Immunity 2: Objectives (page 10 of 137)

                         - oral:       live virus (no longer used due to 1 in 750,000 incidence of paralytic polio)
  - contraindications:   hypersensitivity to streptomycin, neomycin, polymyxin B
                         anaphylaxis to previous IPV
  - series:              4 dose series, begin at age 2 mo.

- Hib vaccine
  - disease:             Haemophilus influenza, type b
  - function:            protect against serious bacterial infection
                         - meningitis, encephalitis
                         - epiglottitis
                         - bacteremia
  - classification:      capsular polysaccharide
  - contraindications:   anaphylaxis to previous Hib
  - series:              3-4 dose series, begin at age 2 mo.

- MMR vaccine
  - disease:             measles, mumps, rubella
  - function:            protect against serious disease
                         - measles, mumps cause significant morbidity to the primary host
                         - rubella is mild in the host, but can cause fetal complications if acquired in pregnancy)
  - classification:      live, attenuated
  - contraindications:   anaphylaxis to vaccine, neomycin, or eggs
                         immunodeficiency (except HIV), immunosuppressive therapy including chemotherapy
  - series:              2 shot series, begin at 1 year

- varicella vaccine
   - disease:            chicken pox, shingles
   - function:           protect against serious disease
                         - mortality: >100 deaths/year, of which 80% are not immunodeficient
                         - morbidity: bacterial superinfection, encephalitis, hepatitis, arthritis, glomerulonephritis
  - classification:      live, attenuated (Oka strain)
  - contraindications:   T cell immunodeficiency
                         ≥ 14 days of high dose corticosteroids within past month
                         anaphylaxis to vaccine or neomycin (safe for people with egg allergy)
  - series:              2 dose series, begin at 1 year

- meningococcal vaccine
  - disease:           Neisseria meningitidis
  - function:          protects against serious disease
                       - protects against A, C, Y, and W135 strains
                       - despite common perception, meningitis far more common in HS juniors / seniors vs. college
  - classification:    conjugate vaccine
  - contraindications: none
  - series:            1 dose, administer after age 11-12 years

- Hep A vaccine
  - disease:             hepatitis A
  - function:            protects against prolonged non-serious illness
                         - 30-70% of infected children develop prolonged symptomatic infection
                         - spread of HAV infection within child care settings often before recognition of the index case
                         - though non-fatal and with no long-term complications, is a difficult and prolonged illness
  - classification:      inactivated
  - contraindications:   hypersensitivity to vaccine
                         pregnancy (?)
                                                                                Infection & Immunity 2: Objectives (page 11 of 137)

     - series:              2 dose series, begin age 1 year

- Gardasil
  - disease:                human papillomavirus (HPV)
  - function:               protects against cervical cancer
                            - prevents infection by HPV strains 6, 11, 16, and 18
                            - needs to be administered prior to exposure
     - classification:      recombinant capsid protein
     - contraindications:   immunosuppressed
     - series:              3 dose series over 6 months, administer at age 9-12

     BOX: Vaccine Schedule
      For the absolutely ridiculous requirement of memorizing the soon to be forgotten information regarding vaccine
        dose schedules, the following mnemonic / pattern can be used:

         “Henry doesn’t particularly invest his money very meticulously; he gambles.” / 3-5443-22-123

         • Hep B                    henry             3 dose series     (begin at birth)

         • DTaP                     doesn’t           5 dose series     (begin at age 2 mo.)
         • PCV                      particularly      4 dose series     (begin at age 2 mo.)
         • IPV                      invest            4 dose series     (begin at age 2 mo.)
         • Hib                      his               3-4 dose series   (begin at age 2 mo.)

         • MMR                      money             2 dose series     (begin at age 1 year)
         • varicella                very              2 dose series     (begin at age 1 year)

         • meningococcus:           meticulously      1 dose series     (administer after age 11-12 years)
         • Hep A:                   he                2 dose series     (optional; begin at age 1 year)
         • Gardasil:                gambles           3 dose series     (optional; begin at age 9-14 years)

Adolescent Medicine
                                                                                                                  CHAPTER 3

1.     Identify and describe the sequence of the physical changes of puberty (i.e. Tanner staging).

- Tanner breast stages
   - stage 1:     preadolescent (papilla elevation only)
   - stage 2:     breast budding, widening of areola, elevation of mound of subareolar tissue
   - stage 3:     continued enlargement, widening of areolae without separation of contours
   - stage 4:     secondary mound of areola, papilla above plane of enlarging breast
   - stage 5:     mature breast, areola and breast in one plane, erect papilla
                                                                           Infection & Immunity 2: Objectives (page 12 of 137)

- Tanner hair stages
   - stage 1:     preadolescent (absent)
   - stage 2:     long, straight, coarse hair at base of penis or central labia
   - stage 3:     dark, coarse, curly hair spread sparsely over base of penis or mons veneris
   - stage 4:     abundant, adult-type hair limited to mons or pubis
   - stage 5:     extension to medial thigh
   - stage 6:     extension to umbilicus (normal in males only)

- Tanner male genital stages
   - stage 1:    preadolescent
                                                                              Infection & Immunity 2: Objectives (page 13 of 137)

     - stage 2:       enlargement of testes and scrotum, thinning and pigmentation of scrotum
     - stage 3:       phallic enlargement, further enlargement of testes and scrotum
     - stage 4:       further enlargement; darkening of scrotal skin
     - stage 5:       mature size, shape

                  FIGURE: Tanner Stages (Male Genitals and Hair)
                  Note that genital changes are dependent on testosterone maturation, while hair development is
                  dependent on adrenergic development. Consequently, Tanner stages need not be congruent.

2.     List the components of health supervision for an adolescent, such as personal habits, pubertal development,
       immunizations, acne, scoliosis, sports participation, and indications for pelvic exam.

- adolescent health supervision
   - components:       focuses of adolescent medicine include:
                       - personal habits
                       - pubertal development
                       - immunizations
                       - acne
                       - scoliosis
                       - sports participation
   - clinical:         ensure confidentiality (except suicide, homicide, or gross personal risk)
                       interview away from parent
                       speak at the level of the adolescent

     BOX: Components of Adolescent Health Supervision
      The social history of an adolescent focuses largely on
                                                                           Infection & Immunity 2: Objectives (page 14 of 137)

        risk-taking behaviors. The important issues are
        commonly remembered through the use of the
        mnemonic “HEADSS.”

        • home
        • education
        • activities
        • drugs, alcohol, cigarettes
        • sexuality
        • suicidality / abuse

     BOX: Indications for a Pelvic Exam
      The indications for a pelvic exam include:

        • symptoms of a possible STD
        • unexplained pelvic or abdominal pain
        • partner with known or suspected STD
        • more than 6 months since last pelvic exam
        • never had a pelvic exam
        • multiple / high risk partners since last exam
        • frequent unprotected sex since last exam
        • victim of a sexual assault
        • routine screening

3.     Describe the common risk-taking behaviors of adolescents, such as alcohol and other drug use, sexual
       activity, and violence.

     BOX: Adolescent Risk Behaviors
      Adolescence is a time when risk-taking behavior
       becomes increasingly frequent. Some of the
       common risky behaviors include:

        • youthful drinking
        • risky driving
        • sexual activity
        • alcohol and other drug use
        • dangerous weapon use

- substance abuse
   - epidemiology:       25% of HS students smoke 1 or more cigarettes / day
                         90% have tried alcohol, 70% have tried cigarettes, 60% have tried marijuana
     - history:          begin asking at age 10
     - examination:      generally not useful unless previously suspected
     - laboratory:       urine or blood screen for drug metabolites
     - management:       anticipatory guidance; involvement of family in acute danger

- sexual activity
   - epidemiology:       50% of HS students are non-virgins (males > females)
                                                                                 Infection & Immunity 2: Objectives (page 15 of 137)

                           1 million adolescent pregnancies / year
                           25% of sexually active teenagers acquire an STI
     - history:            begin at age 8; clarify number, contraception, STI risks / history, menstruation history
     - examination:        testicular exam, pelvic exam
     - laboratory:         Pap smears, urinalysis
     - management:         drug therapy, pregnancy workup

- violence
   - epidemiology:         11.6 deaths / 100,000 teenagers
                           20x higher in African Americans vs. Caucasians
                           9% of boys, 1% of girls in HS carry a gun
     - history:            important questions include:
                           - substance abuse
                           - seat belt use
                           - access to weapons
                           - gang involvement / behavior of friends
     - management:         do not scold, lecture, or be judgmental when discussing risk factors

4.     Explain the contributions of unintentional injuries, homicide, suicide, and HIV / AIDS to the morbidity and
       mortality of adolescents.

     BOX: Adolescent Causes of Death
      Adolescent causes of death tend to be primarily
       behavioral. The leading physical cause of death,
       malignancy, finishes a distant fourth overall.

         1.   injury
         2.   homicide
         3.   suicide
         4.   malignancy
         9.   HIV / AIDS

5.     Describe the features of common mental health problems in adolescence, including school failure, attention
       deficit, body image, eating disorders, depression, and suicide.

- anorexia nervosa
   - disorder:             eating disorder characterized by low body weight (<85 th percentile)
                           - self starvation with or without compensatory behaviors
                           - symptoms ego-syntonic (not distressing; patient in denial)
     - etiology:           significant environmental and genetic influences
     - epidemiology
        - prevalence:      4% of adolescents and young adults
        - age:             onset between age 10-30
        - gender:          women >> men
     - symptoms:           self starvation, excessive dieting, laxative abuse, amenorrhea
     - management:         hospitalization
                           positive reinforcement of normal eating and weight gain
                           pharmacotherapy (TCAs, MAO inhibitors)
     - prognosis:          lethal in 10% of cases (starvation, suicide, electrolyte disturbance)
                                                                           Infection & Immunity 2: Objectives (page 16 of 137)

  DSM-IV Criteria: Anorexia Nervosa
    A:   body weight < 85% of expected
    B:   intense fear of weight gain or becoming fat, despite being underweight
    C:   disturbance in perception of body weight or shape, denial of seriousness of current weight
    D:   amenorrhea (postmenarchal females)

    • binge-eating / purging type: regular engagement in binging, purging, laxatives during current episode
    • restricting type: no regular engagement in binge / purge behavior

- bulimia
   - disorder:         eating disorder characterized by binge eating and compensatory behaviors
                       - generally maintain normal weight
                       - symptoms ego-dystonic (distressing; patient more likely to seek help)
  - etiology:          significant environmental and genetic influences
  - epidemiology
     - prevalence:     1-3% of adolescent and young females
     - gender:         women >> men
     - geography:      developed countries > undeveloped countries
  - symptoms:          binge eating
                       compensatory behaviors (purging, laxatives, fasting, exercise, etc.)
  - management:        individual psychotherapy, cognitive behavioral therapy, group therapy
                       pharmacotherapy (SSRIs, TCAs)

  DSM-IV Criteria: Bulimia Nervosa
    A: recurrent binge-eating, characterized by:
       1.) eating an excessive amount of food in a discreet period of time (2 hours)
       2.) sense of lack of control over eating during the episode
    B: recurrent inappropriate compensatory behavior (binge/purge, diuretics, fasting, excessive exercise)
    C: binge eating and compensatory behaviors occur 2x / week for 3 months on average
    D: self evaluation unduly influenced by body weight and shape
    E: does not occur exclusively during anorexia nervosa episodes

    • purging type: use of self-induced vomiting, misuse of laxatives, diuretics, or enemas
    • nonpurging type: only other compensatory behaviors (fasting, excessive exercise)

- childhood depression
   - disorder:       depression in children
   - epidemiology:   underdiagnosed
   - symptoms:       manifestations of childhood depression vary by age
                     - pre-school:       separation anxiety, school refusal, somatic symptoms
                     - school-age:       school refusal, learning problems, psychosomatic problems
                     - teenage:          resembles adult depression, but includes symptoms of acting out
   - treatment:      varies by age
                     - pre-school:       play therapy, family counseling
                     - school-age:       anti-depressants can help
                     - teenage:          similar to adult depressive disorders
   - clinical:       suicide is the 3rd leading cause of death in adolescents
                     - family involvement is crucial
                                                                             Infection & Immunity 2: Objectives (page 17 of 137)

                       - hospitalization is necessary for the suicidal adolescent

- suicide
   - epidemiology:     3rd leading cause of death in adolescents
                       - tripled in the last 30 years
                       - 25% of girls, 14% of boys have seriously contemplated suicide
  - history:           identification of risk factors
                       - depression
                       - conflict with friends, family, or a romantic interest
                       - educational or legal problems
                       - substance abuse
                       - presence of guns in the home
  - physical exam:     indicators are rare, but may include:
                       - weight loss
                       - scars related to suicide attempt
                       - physical signs of drug abuse
  - management:        family involvement
                       mandatory hospitalization of adolescent suicide attempts

  BOX: Suicide Risk Factors
   The risk factors for suicide include:

      • depression
      • conflict with friends, family, or a romantic interest
      • educational or legal problems
      • substance abuse
      • presence of guns in the home
      • previous suicide attempt
      • organized plan

- attention deficit hyperactivity disorder (ADHD)
   - disorder:         inability to maintain attention, manifested by behavioral problems
   - etiology:         coexisting disorders include:
                       - autism
                       - conduct disorder
                       - Tourette’s disorder
                       - mood disorder
   - epidemiology:     most commonly diagnosed child psychiatric disorder
                       - affects males more commonly than females (6:1)
                       - runs in families, along with alcoholism and antisocial personality disorder
   - symptoms:         characterized by:
                       - inability to maintain attention
                       - poor impulse control
                       - low frustration tolerance
                       - excessive activity level
   - management:       assess for other disorders
                       use special education classrooms with a high teacher to student ratio
                       avoid distractions at home
                       behavior modification
                       stimulants (effective in 75% of children )
   - prognosis:        most common outcome is normal
                       50% maintain some impulsivity, 25% develop antisocial personality disorder
                                                                          Infection & Immunity 2: Objectives (page 18 of 137)

 DSM-IV Criteria: Attention Deficit / Hyperactivity Disorder (ADHD)
  A: either:
     1) inattentive:                  at least 6 of 9 symptoms for at least 6 months
     2) hyperactive/impulsive:        at least 6 of 9 symptoms for at least 6 months
          symptoms must be maladaptive and inconsistent with developmental level
  B. some symptoms cause impairment before age 7
  C. some impairment is present in two or more settings
  D. clear evidence of clinically-significant impairment in social, academic, or occupational functioning
  E. symptoms are not better explained by another disorder

  • ADHD, combined type:                        A1 and A2 both met for the past 6 months
  • ADHD, predominantly inattentive type:       A1, but not A2, met for the past 6 months
  • ADHD, predominantly hyperactive type:       A2, but not A1, met for the past 6 months

  • partial remission

  hyperactive/impulsive symptoms (9)
  • fidgets, squirms
  • leaves seat inappropriately
  • runs about or climbs excessively
  • difficulty playing quietly
  • often “on the go,” “driven by a motor”
  • often talks excessively
  • blurts out answers before questions completed
  • difficulty awaiting turn
  • often interrupts or intrudes on others (butts into conversations or games)

  inattentive symptoms (9)
  • misses details, careless mistakes
  • difficulty sustaining attention
  • doesn’t seem to listen when spoken to
  • doesn’t follow instructions, doesn’t complete assignments or chores
  • difficulty organizing
  • avoids or dislikes tasks requiring sustained mental effort
  • loses things
  • easily distracted by outside stimuli
  • often forgetful in daily activities

Principles of Pediatric Nutrition, Fluids, and
                                                                                                            CHAPTER 4
                                                                                 Infection & Immunity 2: Objectives (page 19 of 137)

1.       Describe the advantages of breastfeeding and describe common difficulties experienced by breastfeeding

- breastfeeding
   - epidemiology:           increase from 50% to 60% in rates of breastfeeding in the last 10 years
   - method:                 begin on the breast on which the baby last nursed
                             - first feedings: 5-10 minutes (5 on each breast)
                             - later feedings: 20-30 minutes, with 2-3 hour interval between
     - guidelines:           some breastfeeding through at least 1 year of age
                             - exclusive breastfeeding for first 6 months
                             - introduce other foods thereafter and begin to wean
     - contraindications:    galactosemia
                             active, untreated TB
                             herpetic lesion on breast
                             drug use (drugs of abuse, antimetabolites)
     - clinical:             recognized as the optimum food for infants

     BOX: Advantages of Breastfeeding
         Breastfeeding has numerous advantages over formula feeding, including:

           • nutritional:       nutritional components are of human origin and well-tolerated
                                caloric content (20 kcal / oz) ideal for quantity ingested
                                contains vitamin D, fluoride, and iron
                                contains growth factors (EFG, lactoferrin, cortisol)
           • hypoallergenic: protein (80% whey, 20% casein) is of human origin
           • immunogenic:       contains bacteriophagic elements (macrophages, IgA)
                                - leads to decreased rates of diabetes, IBD, lymphoma
                                - in the short term, leads to decreased AOM, URI, UTI, and diarrhea
           • probiotic:         lower pH promotes lactobacillus 1
           • social / maternal: promotes bonding between mother and infant
                                reduces stress and postpartum bleeding, and prolongs amenorrhea
                                leads to earlier return to prepregnancy weight
           • financial:         $750-$1,200 /year savings

         lactobacilli are our friends

- formula feeding
   - guidelines:             use when mother has unrelenting difficulties with breastfeeding, including:
                             - anxiety of feeding (“not getting enough”)
                             - maternal fatigue
                             - personal choice
     - clinical:             mother should not be made to feel guilty about switching to formula

     BOX: Facts about Formula
         Formula is becoming increasingly sophisticated and more like breast milk. The following are some general
           comments about formula relative to breast milk:

           • similar caloric content (20 kcal / oz)
           • similar content of lactose
                                                                                 Infection & Immunity 2: Objectives (page 20 of 137)

        • variably smaller (< 80:20) ratio of whey to casein
        • protein is based in cow milk, and is thus more allergenic
        • animal fats are skimmed and a variety of vegetable oils is added
        • lactose-free soy preparations are available
        • mineral contents are different, but all formulas contain vitamin and iron supplement

      lactobacilli are our friends

X. Understand the basic elements of breast milk and the various formulas available.

- breast milk
   - composition
      - calories:         20 kcal/oz
      - protein:          whey, casein (80:20), lactoferrin, IgA
      - CHO:              lactose
      - fat:              triglyceride
      - minerals:         Na+, K+, Cl-, Ca2+, Mg2+ (lacks iron, vitamin K, vitamin D, zinc)

  - indications:          recommended through 1 year of age
                          - exclusive breastfeeding for first 6 months
                          - introduce other foods thereafter and begin to wean

  - contraindications:    may wish to switch to formula when mother has unrelenting difficulties with breastfeeding
                          - anxiety of feeding (“not getting enough”)
                          - maternal fatigue
                          - personal choice

- cow’s milk formulas
   - examples:          Similac, Enfamil, LactoFree, NeoCure, Carnation Follow-Up
   - indications:       less expensive, first line formula
   - contraindications: feeding difficulties
                        allergies to cow milk

- soy protein formulas
   - indications:    alternative to cow milk formulas in healthy term infants
                     - galactosemia
                     - lactose intolerance
                     - IgE-mediated allergy to cow milk
                     - vegetarian-based diet

  - contraindications:    not recommended for:
                          - preterm infants with birth weight < 1800 g
                          - prevention of colic or allergy
                          - cow milk protein-induced enterocolitis or enteropathy

- hydrolysate formulas
   - examples:      Alimentum, Nutramigen, Pregestimil

  - composition
     - calories:          20 kcal/oz
     - protein:           casein or whey hydrolysate
                                                                                     Infection & Immunity 2: Objectives (page 21 of 137)

       - CHO:               sucrose, corn syrup solids, corn starch, tapioca starch
       - fats:              medium chain triglycerides (absorb without micelles), vegetable oil

     - indications:         useful for:
                            - intolerance to cow milk, soy milk formula
                            - fat malabsorption
                            - short gut syndrome
                            - severe chronic diarrhea
                            - liver disorders (cholestasis, biliary atresia, cystic fibrosis)

     - contraindications:   carries several disadvantages, including:
                            - poor taste (sulfated amino acids)
                            - greater cost
                            - high osmolarity

     - clinical:            the more extensive the hydrolysis, the lesser the antigenicity and the greater the price

- elemental formulas
   - examples:       Neocate, EleCare, Vivonex

     - composition
        - calories:         20 kcal/oz
        - protein:          free amino acids
        - CHO:              glucose polymers, sucrose, modified starch
        - fat:              medium chain triglycerides, vegetable oil

     - indications:         used in:
                            - severe food allergy
                            - malabsorption
                            - transition from total parenteral nutrition

2.     Determine the caloric intake required to promote growth of an infant.

- infant feeding
   - characteristics:       begins at a rate of every 3-4 hours, with intake of 2-3 oz per feeding
                            feedings gradually grow larger, further apart
     - intake
        - calories:         120 kcal / kg
        - water:            100-150 mL / kg
        - protein:          2-3 g/kg/day
        - lipids:           3.8-6.0 g/kg/day
        - CHO:              40-50% of total calories
        - calcium:          400-600 mg/day
        - iron:             6-10 mg/day

     TABLE: Average Quantity of Feedings
      age           average quantity
                    of individual feeding
      1 – 2 weeks   2-3 oz      (60-90 mL)
      3 – 8 weeks   4-5 oz      (120-150 mL)
      2 – 3 months  5-6 oz      (150-180 mL)
      3 – 4 months  6-7 oz      (180-210 mL)
      5 – 12 months 7-8 oz      (210-240 mL)
                                                                               Infection & Immunity 2: Objectives (page 22 of 137)

3.     Discuss the addition of solids to an infant’s diet.

- addition of solids
   - timing:             6-12 months
   - process:            gradual progression from cereal to solids
                         - at 4-6 months, begin supplementing iron-fortified, single-grain infant cereal, using a spoon
                         - begin introducing baby foods one at a time, 1 week interval therein
                         - progress towards less pureed “junior foods” as the infant approaches 1 year of age
     - clinical:         introduction of vegetables before fruits is thought to reduce “sweet tooth”

4.     Explain fluid and calorie requirements based on weight.

- calculation of caloric requirements
   - method:            calculated by two approximately similar methods
                        - 100:50:20 rule
                        - 4:2:1 rule
   - interpretation:    basic daily caloric maintenance requirements are the sum of:
                        - 100 kcal / kg (for the first 10 kg body weight)
                        - 50 kcal / kg     (for the second 10 kg body weight)
                        - 20 kcal / kg     (for each kg body weight after)
                        basic hourly caloric maintenance requirements are the sum of:
                        - 4 kcal / kg      (for the first 10 kg body weight)
                        - 2 kcal / kg      (for the second 10 kg body weight)
                        - 1 kcal / kg      (for each kg body weight after)

- calculation of fluid requirements
   - method:             1:1 rule
   - interpretation:     1 mL fluid required for each kcal expended

     CALCULATION: Caloric and Fluid Requirements
      - problem:        Calculate the maintenance caloric and fluid requirements of a 37 kg child.
      - calculation:    • kcal required = 100 kcal/kg x 10 kg (represents 0-10 kg)
                                             + 50 kcal/kg x 10 kg (represents 11-20 kg)
                                             + 20 kcal/kg x 17 kg (represents 21-37 kg)
                                         = 1000 kcal + 500 kcal + 340 kcal
                                         = 1840 kcal

                        • fluids required =    1 mL fluid / kcal x 1840 kcal
                                          =    1840 mL

     BOX: Summary of Caloric, Fluid, and Electrolyte Requirements
      • caloric:        100:50:20     (100 kcal/kg for 1st 10 kg, 50 kcal/kg for 2nd 10 kg, 20 kcal/kg thereafter)
      • fluid:          1:1           (1 mL fluid for each 1 kcal expended)
      • electrolyte:    2.5           (2.5 mEq Na+, 2.5 mEq K+ for each 100 kcal expended)

5.     Identify the physical exam findings associated with dehydration.
                                                                          Infection & Immunity 2: Objectives (page 23 of 137)

- dehydration
   - disorder:       insufficiency of fluids
   - etiology:       three basic causes
                     - low intake:           poor appetite
                     - high output:          vomiting, diarrhea, burns
                     - high metabolism: sepsis
  - diagnosis:       largely clinical diagnosis based on history and physical exam findings
     - HEENT:        dry or cracked mucous membranes, absent tears
     - CV:           orthostatic or low blood pressure, increased heart rate, “thready” pulses
     - GU:           low to absent urine output
     - skin:         increased capillary refill, delayed retraction, tenting
  - management:      fluid bolus to stabilize vital signs
                     maintenance + deficit fluids to replenish estimated losses

  TABLE: Dehydration Findings and Fluid Deficit
    description              deficit 1 findings
    mild dehydration            5%     • dry mucus membranes
                                       • extreme thirst
                                       • dry, warm skin
                                       • low UOP
                                       • flushed face
                                       • headache, weakness, dizziness
                                       • arm or leg cramps
                                       • crying with few or no tears
                                       • sleepy or irritable
    moderate dehydration       10%     • fainting
                                       • tachycardia
                                       • rapid and deep breath
                                       • severe cramps
                                       • bloated stomach
                                       • low blood pressure
                                       • heart failure
                                       • sunken fontanel
                                       • sunken eyes
                                       • crying with few or no tears
                                       • lack of skin elasticity
    severe dehydration         15%     • rapid weak pulse
                                       • cold hands and feet
                                       • rapid breathing
                                       • cyanosis
                                       • confusion
                                       • lethargy
    refers to % of body weight lost

X. Differentiate marasmus and kwashiorkor.

- marasmus
  - disorder:        protein AND calorie deficiency
  - examination:     physical characteristics include:
                     - excessive weight loss (muscle and fat)
                     - dehydration
                     - thin, dry hair
                                                                               Infection & Immunity 2: Objectives (page 24 of 137)

                          - inelastic skin

- kwashiorkor
   - disorder:            protein deficiency
   - examination:         physical characteristics include:
                          - loss of muscle mass
                          - soft-pitting edema (masks weight loss)
                          - dry, brittle hair
                          - skin lesions, peeling infections
                          - low serum [albumin]

Behavioral Pediatrics and Child Abuse
                                                                                                                 CHAPTER 5

1.     Describe the typical presentation of common behavioral problems and issues in different age groups,
               • newborn / infants: sleep problems, colic
               • toddler: temper tantrums, toilet training, feeding problems
               • school age: enuresis, attention deficit, encopresis, autism
               • adolescence: eating disorders, risk-taking behavior

- newborn / infants
   - sleep problems:      difficulty or slowness in being able to sleep
                          resistance in going to sleep
                          inability to return to sleep after waking

     - colic:             continued crying beyond 3-5 hours / day after first 3 months of life

     BOX: Colic
      The rule of 3’s for colic is as follows:

         • 3 hours / day
         • 3 days / week
         • 3 weeks / month

- toddler
   - temper tantrums: defiant behavior and acting out that is:
                      - excessive for the child’s age
                      - associated with frustration, such as an inability to complete a task

     - toilet training:   inability to maintain fecal / urinary continence, resulting from:
                          - general developmental problems
                          - excessive parental expectations (e.g. 20% of children still wet the bed at 5 years old)

     - feeding problems: inability to properly maintain feeding hygiene, resulting from:
                         - general developmental problems
                         - excessive parental expectations
                                                                               Infection & Immunity 2: Objectives (page 25 of 137)

- school age
   - enuresis:          continued bed wetting beyond 5 years of age, possibly indicative of:
                        - stress and secondary emotional problems
                        - anatomic / neurologic defect

     - ADHD:            poor ability to focus, characterized by:
                        - attention deficit:    poor listening, inability to complete tasks, loses things, distractible
                        - hyperactivity:        fidgeting, squirming, talking excessively, blurting out answers

     - encopresis:      continued inability to control bowels beyond 4 years of age, possibly indicative of:
                        - Hirschsprung disease and other neurologic causes
                        - attention deficit problems
                        - psychopathology

     - autism:          syndrome characterized by
                        - deficiency in communication
                        - deficiency in social interactions
                        - repetitive, stereotypical behaviors

- adolescence
   - eating disorders: excessive concern with food
                       female athlete triad (disordered eating, amenorrhea, osteoporosis)
                       general health problems

     - risk behavior:   sexual expression
                        alcohol and other drug use
                        firearm experimentation
                        risky automobile use

2.     List characteristics of the history and physical examination that should trigger concern for possible physical,
       sexual, and psychological abuse and neglect; e.g. inconsistency in the history, unexplained delays in seeking
       care, injuries with specific patterns or distributions on the body, or injuries incompatible with the child’s

- non-accidental trauma
   - disorder:       child abuse

     - etiology:        generally seen with high risk parents, children, and social situations

     - risk factors
        - parent:       abused as child, not nurtured
                        low self esteem

       - child:         unwanted / unplanned, stepchild
                        difficult (deformed, retarded, colic, behavioral problems)
                        poor bonding (⅓ of all abused children are ex-premies)

       - situation:     social isolation (functionally single parent)
                        stress (divorce, marriage, poverty, drugs, new child)

     - diagnosis
        - general:      high index of clinical suspicion combined with suggestive history / findings

       - history:       inconsistencies in the history, lack of history
                                                                              Infection & Immunity 2: Objectives (page 26 of 137)

                         unexplained delays in seeking care

       - physical:       any trauma under age 3
                         recurrent injury
                         pathognomonic injuries
                         - round “cigarette burn” scars
                         - marks suggesting rope or strap burns
                         - suspicious scars / bruises at various stages of healing
                         - burns in pattern suggesting immersion (e.g. “stocking” burns)
                         retinal hemorrhage in otherwise normal child (suggesting “shaken baby” syndrome)

       - imaging:        multiple fractures at varying stages of healing
                         hairline, tendon-avulsion fractures
                         meningeal tears in absence of injury
                         unexplained subdural hematoma

     - management:       admit the child and report to police or social services
                         utilize “I” statements
                         - “I’m concerned this may not be accidental”
                         - “I’m required by law to look into this
                         use “non-accidental injury” vs. “abuse

     BOX: Acute Stress in Children
      Children may react to acute stress situations, such as abuse, in
       varying ways. This may include:

        • withdrawal or sadness
        • development of new and excessive anxieties or fears
        • acting out with anger and expression

3.     Describe the medical-legal importance of a full, detailed, carefully-documented history and physical
       examination in the evaluation of child abuse.

- abuse of children
   - epidemiology:       1 in 7 victims of sexual assault is under the age of 6
                         females comprise 82% of all juvenile victims
                         1 in 4 victims of sexual assault under the age of 12 are boys
                         regarding relationship to the offender (1999 data):
                         - 47% related
                         - 49% acquaintances
                         - 4% strangers
     - process:          reassure the parent / caretaker
                         defer forensic interviewing to those who are specifically trained
                         if you must question the child:
                         - you are not responsible for investigation / determination of crime
                         - NO leading or suggestive questions (most important for children < 10 years old)
                         - W questions are usually okay (who, what, when, where), but not why or how
                         - avoid using the word “hurt”
                         if information is provided by the child:
                         - define the child’s vocabulary
                         - document if statements are spontaneous or in response to questions
                                                                              Infection & Immunity 2: Objectives (page 27 of 137)

                         - document exactly what the child was asked, and the child’s verbatim response
                         - document what was happening when the disclosure was made
     - examples:         “Has anyone ever touched you in a way / place that made you feel uncomfortable”
     - clinical:         mandated reporting
                         - must report all cases of suspected child abuse and neglect
                         - understood as reasonable cause to suspect, not definitive proof

     BOX: Leading Questions
      Leading questions are those that:

        • contain the answer
        • contain a choice of answers
        • contain the name of the suspect before the child identifies the person
        • contains the interviewer’s assumptions
        • explains or offers explicit details of the alleged offense

- abuse of adolescents
   - epidemiology:     33% of sexual assaults occur when victims are between the ages of 12-17
                       rate of victimization by an intimate partner is greatest between ages of 16-24
                       1 in 5 HS females experience physical and/or sexual abuse at the hands of a dating partner
   - process:          define sexual assault for the adolescent
                       separate from caregivers who may be abusers
                       ask in successive visits
   - examples:         questions should be specific and direct
                       - “Are you ever frightened by your boyfriend’s temper?”
                       - “Has your boyfriend ever hurt you or threatened to hurt you?”
                       - “Has your boyfriend ever forced you to have sex when you didn’t want to?”

4.     Summarize the responsibilities of the “mandatory reporter” to identify and report suspected child abuse.
       Know to whom such a report should be made.

- mandatory reporting
  - guideline:        must report all cases of suspected child abuse / neglect
                      - understood as reasonable cause to suspect
                      - does not include the further responsibility to provide definitive proof
  - process:          Ann. Stat. § 48.981: “Any mandated reporter who has reasonable cause to suspect that a child
                      has been abused or neglected shall report immediately by telephone or personally to the
                      county department, sheriff, or police department.”
  - clinical:         “good faith” reporting is legally protected from civil or criminal prosecution

     BOX: Exceptions to Mandated Reporting
      In order to allow children to obtain confidential “health care services,”
        WI Statute 48.981 (2m) permits exceptions to mandatory reporting in
        the following circumstances:

        • family planning services
        • pregnancy testing
        • obstetrical health care or screening
        • diagnosis and treatment for an STI
                                                                                Infection & Immunity 2: Objectives (page 28 of 137)

     These exceptions are not applicable in the following circumstances:

       • sexual contact with a caregiver
       • mental illness or deficiency
       • age / immaturity (incapable of understanding)
       • physical inability to communicate unwillingness
       • reasonable doubt as to voluntary participation

Socioeconomic and Cultural Issues in Pediatrics;
      Underserved Curriculum
                                                                                                                  CHAPTER 6

1.   Describe barriers that prevent children from gaining access to health care, including financial, cultural, and
     geographic barriers.

- socioeconomic disparities
   - increased exposure to infectious or environmental agents (lead, pesticides)
   - malnutrition and effects on physical growth
   - decreased access to immunizations and other important health care
   - incomplete treatment of chronic diseases
   - lack of access to safe, nurturing environments
   - increased exposure to violence

- racial and ethnic disparities
   - forced residence in neighborhoods carrying greater health risks
   - stress and discrimination
   - development under imposed stigma of inferiority
   - bias on the part of health care providers (intentional or unintentional)

X. List 5 factors, other than lack of affordable health insurance, that can cause a family to be classified as

- factors in a person being “underserved”
   - access:            lack of access to affordable health insurance
   - education:         illiteracy or learning disabilities
   - occupation:        under or unemployed as with seasonal employees or LTE (limited term employee)
   - housing:           homeless or "doubling up" with relatives or friends
   - nutrition:         food insecurity
   - transportation: no money for gas, need for mass transportation
   - exposures:         pathogens and carcinogens at home and work
   - social conditions: crime in the home or community
   - stress:            chronic medical conditions, social isolation, family violence
   - mental illness:    paranoia, depression
                                                                             Infection & Immunity 2: Objectives (page 29 of 137)

     - personality:        resiliency vs. depression, helplessness, coping mechanisms
     - continuity of care: lack of a “medical home”

X. Know the determinants of health care needs in terms of the ICARE mnemonic.

   - injury prevention:      strategies in keeping children safe from injury (discipline, supervision, hazardous areas)
   - communication:          special needs for communication
   - access:                 access to affordable health care
   - resources:              meeting basic needs (food, shelter, child care)
   - emotional health:       effect of current life situation on well-being and mental health

X. Understand how to effectively utilize an interpreter in patient doctor interactions.

- tips on utilizing an interpreter
   - use approved, qualified interpreters
   - do not depend on children, relatives, or friends to interpret
   - have a brief preinterview meeting with the interpreter
   - speak directly to the patient, not the interpreter
   - speak at an even pace in relatively short segments
   - do not hold the interpreter responsible for what the patient does or does not say
   - avoid jargon or technical terms
   - do not say anything that you do not want the patient to hear
   - know that a lack of English-speaking ability is not a reflection of low cognitive function
   - be patient

X. List several strategies for overcoming obstacles to follow-up.

- overcoming obstacles to follow-up
   - seize the moment
   - address obstacles to follow-up immediately
   - ensure a method of communication
   - utilize reminders
   - if the family does miss the scheduled follow-up, don’t give up

Ethical Issues in Pediatric Practice;
      Ethics Curriculum
                                                                                                               CHAPTER 7

1.     Describe the practical applications of the major ethical principles (i.e. justice, beneficence, non-malfeasance,
       respect for autonomy).

ethical principles
- four box approach to ethics
   - medical indications
                                                                            Infection & Immunity 2: Objectives (page 30 of 137)

  - patient preferences
  - quality of life
  - contextual features

    TABLE: Four Box Approach to Ethics
           medical indications          patient preferences
     • medical facts              • patient goals and values
     • goals of treatment         • patient understanding
     • options to avoid harm

             quality of life                  contextual features
     • freedom from pain                • institutions
     • independence                     • legal repercussions

- guiding ethical principles
   - autonomy
      - definition:     right to choose treatment or refuse therapy
      - importance:     informed adult patient of sound mind is fully able to decide their own therapy
      - clinical:       protecting autonomy
                        - consent forms
                        - do not resuscitate (DNR) orders
                        - advance medical advice (AMA) forms

  - non-malfeasance
     - definition:  primum non nocere (first do no harm)
     - importance:  painful, risky, or burdensome therapy

  - beneficence
     - definition:    duty to assist patients
     - importance:    fundamental goal of physicians is to benefit the patient
                      - patient-centered: class of medicine that respects patient autonomy above all else
                      - paternalism: class of medicine that practices beneficence over autonomy
  - fairness
     - definition:    justice
     - importance:    situations of limited resources
                      - emergency medicine:       not allowed to turn away patients
                      - intensive care:           allocated on first-come basis
                      - organ transplants:        allocated on recommendations of council

  BOX: Guiding Ethical Principles
   • autonomy:            right to choose treatment or refuse therapy
   • non-malfeasance:     first do no harm
   • beneficence:         duty to assist patients
   • fairness:            social justice

case studies
- ethical issues in newborns
   - case:             premature infant with possible or probable mortality, requiring significant resuscitation

  - issues:           Should the infant be resuscitated?
                      Should the parents be allowed to decide if the infant is resuscitated?
                                                                           Infection & Immunity 2: Objectives (page 31 of 137)

                      Under what circumstances may treatment be withdrawn?
                      Who should make the decisions, and by what process?

  - guidelines:       physicians may recommend against / refuse to provide treatment
                      parents may make the decision unless clearly acting against the “best interests” of the child
                      treatment may be withdrawn if it offers minimal to no benefit, against the parents’ wishes
                      difficult issues and disagreements should be resolved by medical ethics boards

  BOX: Best Interests
   The “best interests” of the child are debatable. For an infant with a good chance of survival but a high
     probability of morbidity, the best interest is probably to maintain support. However, for an infant with almost
     no chance of survival despite extensive procedures, the best interests may be to withdraw further care.

- ethical issues in young children
   - case:              young child with chronic but treatable illness who no longer wishes to cooperate with care

  - issues:           Should the pediatrician respect the child’s refusal?
                      Should the parents punish the child for noncompliance?

  - guidelines:       children considered “immature” cannot refuse treatment
                      - should be encouraged to verbalize feelings and become involved in care
                      - should be informed at least about nature of condition, treatment, and prognosis
                      childhood perceptions of illness should not be ignored, but compliance is expected

- ethical issues in adolescents
   - case:              adolescent with leukemia, with parents, refuse blood transfusions on religious grounds

  - issues:           Should the adolescent’s and family’s wishes be respected?
                      Should the decision be allowed to result in the adolescent’s death?

  - guidelines:       adolescent decisions can be given consideration if the teenager can:
                      - make virtually all decisions about daily affairs
                      - come and go reasonably independently
                      - make and keep medical appointments
                      - articulate needs and follow recommendations
                      - understand risks and benefits of proposed treatments
                      if judged competent to do so, adolescents are not bound by paternalism

  BOX: Emancipated Minors
   Emancipated minors are judged fully able to make all decisions regarding their health care if they are:

      • living independently
      • members of the military
      • parents of their own children

   Even if not considered legally emancipated, many states hold that adolescents are permitted legal consent for
     STIs, pregnancy and contraception, and abortion services.

- ethical issues in end of life care
   - case:              child with trauma is maintained on life support with a grim prognosis
                                                                            Infection & Immunity 2: Objectives (page 32 of 137)

     - issues:          Should a physician withhold or withdraw treatment?
                        How should a child’s last days be spent?

     - guidelines:      treatment may be clearly withheld or withdrawn after a diagnosis of brain death
                        - no distinction between withholding or withdrawing of treatment
                        - more flexibility if there is little cortical function but criteria for brain death not met
                        last days may be spent in hospital, hospice, or at home, per wishes of physicians and parents

Infectious Diseases
                                                                                                              CHAPTER 9

1.     Identify generally accepted pharmacologic therapy for the following conditions:
                • acute otitis media
                • streptococcal pharyngitis
                • sepsis / meningitis
                • pneumonia
                • sinusitis
                • urinary tract infection
                • cellulitis
                • lymphadenitis

- acute otitis media (AOM)
   - epidemiology:    most common diagnosis in children (300,000 provider visits / year)

     - etiology:        most common organisms are S. pneumoniae, H. influenzae, M. catarrhalis

     - pathophysiology: children more prone due to anatomy of eustachian tubes

     - diagnosis
        - general:      clinical diagnosis by examination of eardrums showing evidence of:
                        - inflammation
                        - effusion
       - history:       preceding / concurrent URI, fever, irritability, ear pain
       - physical:      pneumatic otoscope examination showing:
                        - erythema
                        - tympanic membrane thickening
                        - engorgement of blood vessels
                        - loss of normal light reflex, bony landmarks
                        - decreased mobility of the tympanic membrane
       - laboratory:    tympanocentesis only in immunocompromised, recurrent infection

     - differential:    otitis media with effusion (OME)
                        otitis externa
                        foreign body
                        referred pain

     - management:      antibiotic therapy in children with evidence of AOM
                                                                            Infection & Immunity 2: Objectives (page 33 of 137)

                      - amoxicillin:    first line therapy, effective against S. pneumoniae and H. influenzae
                      - Augmentin:      useful in cases of difficult to treat ear infections
                      - cephalosporins: effective against H. influenzae and M. catarrhalis

- streptococcal pharyngitis
   - epidemiology:   uncommon in children younger than 2

  - etiology:         viral (most common overall)
                      S. pyogenes (most common bacterial)

  - diagnosis
     - general:       clinical evaluation with use of rapid strep, cultures
     - history:       sudden onset sore throat, fever, headache, generally no rhinorrhea or congestion
     - physical:      tonsillar exudate, palatal petechiae, strawberry tongue, rash, urticaria
     - laboratory:    rapid strep, culture, serology (ASO Ab, DNAse B)

  - differential:     infectious causes may include:
                      - other causes of pharyngitis
                      - peritonsillar abscess
                      - retropharyngeal abscess
                      - epiglottitis
                      noninfectious causes may include:
                      - allergy
                      - trauma
                      - burns, smoke, toxins
                      - psychosomatic
                      - referred pain

  - management:       antibiotic therapy to prevent sequelae (symptomatic improvement of perhaps 12 hours)
                      - penicillin:      first line therapy
                      - amoxicillin:     effective substitute due to improved palatability
                      - macrolides:      useful in β-lactam allergic patients

- bacterial meningitis / sepsis
   - epidemiology:    bacterial meningitis has mortality of 5-10% with best treatments available
                      highest mortality with S. pneumoniae

  - etiology:         enteric pathogens in infants
                      encapsulated bacteria in older infants and children

                      TABLE: Etiology of Bacterial Meningitis
                       age              etiology
                       0 to 3 mo.       S. agalactiae
                                        E. coli
                                        L. monocytogenes
                       3 mo. to 5 years S. pneumoniae
                                        N. meningitidis
                                        H. influenzae type b
                       age > 5 years    S. pneumoniae
                                        N. meningitidis
                       any age          M. tuberculosis

  - pathophysiology: invasion of respiratory epithelium (IgA protease)
                                                                          Infection & Immunity 2: Objectives (page 34 of 137)

                     evasion of complement system (capsular polysaccharide)
                     replication in the blood, infection of CSF
                     production of inflammatory response (may be largely responsible for long term sequelae)

  - diagnosis
     - general:      careful history, physical examination, and frequent reevaluation
     - history:      recent symptoms of URI, with further symptoms based on age
                     - young children: irritability, anorexia, vomiting, inconsolable crying; lethargy, seizure
                     - older children: headache, back pain, stiff neck, photophobia, mental status change
    - physical:      vital signs (fever, bradycardia, hypotension)
                     pain and limitation of motion of neck
                     Kernig sign (pain with extension of knee while hip flexed)
                     Brudzinski sign (spontaneous flexion of knee and hip with passive flexion of neck)
                     detailed neurologic examination
    - laboratory:    CSF abnormalities (cloudy, elevated cell count, high PMNs, high protein, low glucose)
                     Gram stain and culture of CSF
                     electrolyte abnormalities, SIADH
                     CT / MRI (required with comatose patients or with focal neurologic findings)

  - differential:    aseptic meningitis (viral: normal protein and glucose, normal culture)
                     fungal meningitis
                     brain abscess / tumor

  - management:      dexamethasone to reduce inflammatory response
                     antibiotics per age of the child
                     - 0-12 weeks:      ampicillin + cefotaxime / aminoglycoside
                     - 3 mo.-18 y:      cefotaxime / ceftriaxone + vancomycin

- pneumonia
   - etiology:       most are viral, some are bacterial

                     TABLE: Etiology of Pneumonia
                       age              etiology
                       0 to 1 mo.       GBS (S. agalactiae)
                                        Gram negative enterics
                                        L. monocytogenes
                       1 to 3 mo.       C. trachomatis
                                        viral (RSV, parainfluenza)
                                        S. pneumoniae
                                        B. pertussis
                                        S. aureus
                       3 mo. to 5 y.    viral (RSV, parainfluenza, influenza, adeno, rhino)
                                        S. pneumoniae
                                        H. influenzae
                                        M. pneumoniae
                                        M. tuberculosis
                       5 y. to 15 y.    M. pneumoniae
                                        C. pneumoniae
                                        S. pneumoniae
                                        M. tuberculosis
                       Data from McIntosh K, N Engl J Med 346(6): 429-37

  - pathophysiology: pulmonary parenchymal infection secondary to:
                                                                            Infection & Immunity 2: Objectives (page 35 of 137)

                      - defects in host defenses protecting the lung
                      - inhalation of a large inoculum
                      - hematogenous infection
  - diagnosis
     - general:       combined clinical and radiologic findings, with empiric treatment
     - history:       varies with etiology
                      - viral:       prodromal rhinorrhea, cough, fever, pharyngitis, apnea
                      - bacterial: abrupt onset of fever, cough, chest pain, chills, development of hypoxia
     - physical:      varies with etiology
                      - viral:       irritable, fever, tachypnea, tachycardia, mild hepatosplenomegaly
                      - bacterial: toxic, respiratory symptoms, rash; M. pneumoniae with fever, headache, cough
     - laboratory:    CBC with differential
                      blood culture
                      chest radiograph (bacterial more commonly lobar; viral more commonly diffuse)
                      sputum (children > 12) for Gram stain, culture, acid fast smear and culture
                      direct viral examination of nasopharyngeal specimens
                      M. pneumoniae IgM and IgG
                      pulse oximetry

  - differential:     bacterial vs. viral

  - management:       admission of:
                      - infants < 2-3 months
                      - children with underlying immunodeficiency, metabolic disease, cardiopulmonary disease
                      - respiratory distress, hypoxia, sepsis, dehydration, poor compliance
                      antibiotics based on etiology
                      - amoxicillin:      S. pneumoniae
                      - erythromycin: atypical (C. trachomatis, C. pneumoniae, M. pneumoniae)
                      - doxycycline: atypical
                      - cephalosporin: S. aureus
                      - vancomycin: MRSA
                      - acyclovir:        HSV
                      - ganciclovir:      CMV

- sinusitis
   - etiology:        can be infectious (bacterial, fungal, viral), allergic, or autoimmune
                      - 30% of cases worldwide secondary to S. pneumoniae
                      - second-most common cause is H. influenzae

  - pathophysiology: inflammation of the paranasal sinuses, spread by airborne, droplet, or contact transmission
                     predisposing factors include:
                     - impaired mucociliary function
                     - obstruction of sinus ostia
                     - immune defects
                     - increased risk of microbial invasion

  - diagnosis
     - general:       clinical diagnosis based on long-standing URI symptoms
     - history:       cough, low grade fever, facial pain, headache, thick discharge, bad breath
                      symptoms persisting beyond 10-14 days
     - physical:      sinus pain
     - laboratory:    CT maxi; many false positives

  - differential:     allergies, pertussis (non-immunized patients)

  - management:       symptomatic relief and observation
                                                                            Infection & Immunity 2: Objectives (page 36 of 137)

                      amoxicillin: first line antibiotic

- urinary tract infection (UTI)
   - epidemiology:     common in children, with risk factors including:
                       - female gender
                       - uncircumcised male infants
                       - vesicoureteral reflux (VUR)

  - etiology:         community-associated:        E. coli, Enterococcus, S. aureus, S. saprophyticus
                      iatrogenic / nosocomial:     Pseudomonas, coagulase-negative staph

  - pathophysiology: colonization of the periurethral area
                     hematogenous source (generally 1st 8-12 weeks of life)

  - diagnosis
     - general:       urinalysis with suspicious symptoms
     - history:       “frequency, urgency, pain on urination”
                      - young children: fever, crying on urination, frequency, hematuria, GI symptoms, poor growth
                      - older children: fever, chills, malaise, hematuria, flank pain, new onset enuresis
     - physical:      CVA tenderness, uncircumcised
                      generally to rule out other causes (masses, trauma)
     - laboratory:    rapid screening (dipstick for nitrite, esterase)
                      urine cultures (100,000 cfu/mL in clean-voided method)

  - differential:     asymptomatic bacteruria

  - management:       diagnostic studies
                      - renal ultrasound:                    check for hydronephrosis
                      - voiding cystourethrogram (VCUG): check for reflux
                      - DMSA scan:                           check for anatomical scarring
                      - radionucleotide scan:                consideration of obstruction
                      antibiotic therapy (cephalosporin, TMP/SMA, amoxicillin, nitrofurantoin)

- cellulitis
   - etiology:        S. pyogenes, S. aureus, many others

  - pathophysiology: acute inflammation of connective tissue underlying the skin
                     - direct invasion
                     - hematogenous dissemination

  - diagnosis
     - general:       clinical
     - history:       differs slightly with etiology
                      - S. pyogenes:     trauma; prodromal illness (fever, pharyngitis, chills, abdominal pain )
                      - S. aureus:       recent local trauma
     - physical:      rapidly-advancing rash with poorly demarcated borders

  - differential:     other etiologies of rash

  - management:       bed rest, elevation
                      - S. pyogenes (GAS): amoxicillin
                      - S. aureus:         cephalosporins, vancomycin

- lymphadenopathy / lymphadenitis
   - etiology:      numerous causes, both infections and non-infections
                                                                            Infection & Immunity 2: Objectives (page 37 of 137)

                     - viral:       EBV, CMV, measles, rubella, VZV, HSV, HIV, adenovirus
                     - bacterial:   S. pyogenes, Brucella spp., Leptospira spp., Ehrlichia spp.
                     - parasitic:   Toxoplasma gondii, Trypanosoma cruzii
                     - malignant:   lymphoma, leukemia, neuroblastoma, histiocytosis
                     - other:       medications, JRA, SLE, infection-associated hemophagocytic syndrome
                                    granulomatous disease, sarcoidosis, vasculitis

- pathophysiology: reactive lymphadenopathy from systemic or local infection
                   lymphadenitis (direct bacterial infection) from S. pyogenes, S. aureus in 80% of cases

- diagnosis
   - general:        detailed history, exam, and laboratory support
   - history:        rate of enlargement, other illness, travel, sick contacts, animal contacts, HIV history
   - physical:       description of involved nodes, hepatomegaly / splenomegaly, skin rash
   - laboratory:     elevated WBC, ESR
                     other tests based on history; biopsy if no clear other results

- differential:      Kawasaki disease
                     branchial cleft cyst, thyroglossal duct cyst
                     thyroid goiter
                     lymphoma, Hodgkin disease

- management:        depends on underlying illness

BOX: Pharmacology of Common Pediatric Infectious Diseases
 The antibiotic treatment of pediatric infectious disease varies with the cause.

 • acute otitis media:              amoxicillin (S. pneumoniae, H. influenzae)
                                    cephalosporins (H. influenzae, M. catarrhalis)

 • streptococcal pharyngitis:       penicillin (first line)
                                    amoxicillin (more palatable)
                                    macrolides (for β-lactam allergies)

 • sepsis / meningitis:             ampicillin + cefotaxime / aminoglycoside (0-12 weeks)
                                    cefotaxime / ceftriaxone + vancomycin (3 mo.-18 years)

 • pneumonia:                       amoxicillin (S. pneumoniae)
                                    erythromycin, doxycycline (atypical; Chlamydia, Mycoplasma)
                                    cephalosporins (S. aureus), vancomycin (MRSA)
                                    acyclovir (HSV), ganciclovir (CMV)

 • sinusitis:                       amoxicillin (first line)

 • urinary tract infection:         cephalosporin, TMP/SMX, nitrofurantoin, amoxicillin

 • cellulitis:                      amoxicillin (GAS)
                                    cephalosporin, vancomycin (S. aureus)

 • lymphadenitis:                   depends on underlying etiology
                                                                               Infection & Immunity 2: Objectives (page 38 of 137)

2.     Describe the clinical presentation of the following conditions:
               • common cold
               • chicken pox
               • roseola
               • bronchiolitis
               • influenza
               • croup

- common cold
   - epidemiology:    3-8 colds per year common in children
   - etiology:        Rhinovirus (most common), coronavirus, RSV, parainfluenza, adenovirus, influenza
   - pathophysiology: upper respiratory tract infection with airborne, droplet, or contact transmission
                      - incubation period of 2-5 days
                      - symptoms secondary to production of inflammatory mediators
                      - course from 3-7 days
   - diagnosis
      - general:      clinical
      - history:      low grade fever, mild irritability, nasal discharge (clear → cloudy), cough (dry → productive)
      - physical:     not seriously ill, with signs including:
                      - erythematous pharynx with mildly enlarged tonsils
                      - otitis media (viral or secondary bacterial)
                      - clear chest with occasional wheezes
                      - occasional viral exanthem
                      - mucopurulent nasal discharge in some cases
      - laboratory:   rapid diagnosis of RSV, parainfluenza, influenza, adenovirus for certain populations
                      - severely ill
                      - immunocompromised

     - differential:     sinusitis

     - management:       supportive care (fluids and rest)
                         - OTC medications are of no benefit in pediatric populations
                         - antibiotics only with secondary bacterial AOM or sinusitis

- chicken pox
   - epidemiology:       common in children

     - etiology:         varicella zoster virus (VZV)

     - pathophysiology: generalized pruritic vesicular rash
                        - contagious from 1-2 days prior to onset of rash until lesions have crusted
                        - establishes latent infection, with reactivation resulting in herpes zoster (shingles)
                        - primary infection much more mild in children

     - diagnosis
        - general:       clinical (history and examination)
        - history:       antecedent contact within 10-21 days, no history of immunization, prodromal fever / malaise
        - physical:      pruritic rash on face, neck, trunk → outward
                         - small papules → vesicles → crusts
                         - multiple stages of healing
       - laboratory:     Tzank smear, culture (not routine); blood culture if bacterial superinfection suspected

     - management:       supportive care
                         - acyclovir: immunocompromised, severely ill
                                                                            Infection & Immunity 2: Objectives (page 39 of 137)

                       - antibiotics: cover S. pyogenes, S. aureus in suspected superinfection
                       vaccination of children 12 months or older

                FIGURE: Varicella Rash

- roseola (exanthem subitum, sixth disease)
   - epidemiology:    etiologic seroprevalence > 100% in children > 2 years of age

  - etiology:          HHV-6 (occasionally HHV-7)

  - pathophysiology: latent in mononuclear cells, replication in salivary glands
                     reactivation of virus only in immunosuppressed patients

  - diagnosis
     - general:        clinical
     - history:        abrupt onset of high fever lasting 3-7 days, occasional GI symptoms
     - physical:       high fever, normal viral signs, rash 1-2 days after fever breaks

  - differential:      occult bacteremia, other sources of infection (e.g. UTI)

  - management:        supportive care, antipyretic therapy

                FIGURE: Roseola

- bronchiolitis
   - epidemiology:     most common in children younger than 1 year of age
                       - 100,000 infants hospitalized annually, mortality from 0.5-1.5%
                       - peak disease November – April

  - etiology:          most commonly RSV; also parainfluenza, adenovirus
                                                                            Infection & Immunity 2: Objectives (page 40 of 137)

  - pathophysiology: obstructive pulmonary disease
                     - viral proliferation in respiratory epithelium leading to edema, necrosis
                     - peribronchial lymphocytic proliferation
  - diagnosis
     - general:      clinical diagnosis, with physical exam to determine severity and necessity for hospitalization
     - history:      lethargy, irritability, apnea, poor feeding; cold symptoms in older children
     - physical:     low grade fever, tachypnea, tachycardia
     - laboratory:   rapid tests, culture, pulse ox or ABGs

  - differential:     other infectious causes
                      congestive heart failure
                      aspirated foreign body

  - management
    - treatment:      hospitalization, rehydration, supplemental O2, pharmacologic agents in immunocompromised
    - prophylaxis:    due to cost, used only in extremely high risk patients (primi, respiratory disease)
                      - RSV IVIG
                      - RSV MAb (palivizumab [Synergis])

- influenza
   - epidemiology:    highest attack rates in school-age children, 90% of deaths in age > 65

  - etiology:         influenza virus (Orthomyxoviridae); A and B subtypes cause human disease

  - pathophysiology: difficult for immune system to respond
                     - antigenic shift: circulating H and N surface proteins reassort (influenza A)
                     - antigenic drift: random mutations over time

  - diagnosis
     - general:       clinical diagnosis with appropriate epidemiology; PE to rule out bacterial superinfection
     - history:       young children: viral URI symptoms
                      older children: abrupt onset fever, headache, myalgia, sore throat, nonproductive cough
                                          - fever: 3-5 days
                                          - myalgia: 2 weeks
    - physical:       ears, lungs, heart, abdomen, CNS, musculoskeletal to rule out competing causes
    - laboratory:     rapid diagnostic tests available; other labs to rule out bacterial causes

  - differential:     other viral URI

  - management:       supportive care
                      antiviral agents in immunocompromised or severely ill
                      - amantadine, rimantadine: effective against influenza A
                      - zanamivir, oseltamivir: effective against influenza A, B
                      annual vaccination, especially in susceptible populations

- croup
   - epidemiology:    common viral illness in children < 3, boys > girls
   - etiology:
   - pathophysiology: laryngotracheobronchitis
                      - swelling, edema → narrowing of subglottic space, irritation of vocal cords
                      - does not affect adults who have larger baseline airways

  - diagnosis
     - general:       clinical diagnosis, with detailed exam to assess severity of illness
     - history:       antecedent URI, barking cough, hoarseness, inspiratory stridor
                                                                              Infection & Immunity 2: Objectives (page 41 of 137)

       - physical:      stridor, retractions, decreased air entry, cyanosis, level of consciousness
       - laboratory:    “steeple sign” on radiology

     - differential:    laryngeal foreign body
                        retropharyngeal abscess
                        H. influenzae type b epiglottitis

     - management:      supportive care
                        - cool, humidified air:     alleviates stridor
                        - nebulized racemic epi:    reduces airway obstruction in hospitalized patients
                        - steroid therapy:          decreases severity, duration of symptoms

3.     Discuss the workup of fever of unknown origin

- fever of unknown origin (FUO)
   - etiology:      concern for infectious diseases, such as viral (58% of cases), bacterial (8% of cases)

     - pathophysiology: elevation of body temperature
                        - secondary to effects on hypothalamic thermoregulatory center
                        - results from cytokines produced in response to infection or inflammation

     - diagnosis
        - general:      evaluation to rule out serious bacterial infections (SBIs)
        - history:      duration and height of fever, method of measurement, use of antipyretics
                        behavior, appetite, activity level
       - physical:      vital signs (fever, hypothermia, tachypnea, irregular respirations, apnea, hypotension)
                        skin exam (cyanosis, poor perfusion, rashes)
                        other signs (meningeal signs [Kernig, Brudzinski signs], pneumonia, murmur, MSK infection)
       - laboratory:    sepsis evaluation of all infants < 1 month
                        - CBC, blood culture, urinalysis, urine culture
                        - lumbar puncture and CSF examination / culture
                        varied recommendations beyond 1 month of age
                        - low risk children: careful observation (esp. those above 3 months)
                        - high risk children: full sepsis evaluation

     - differential:    viral illness
                        bacterial infections (meningitis, UTI)

                        TABLE: Bacterial Infections
                         age               etiology
                         0 to 3 mo.        E. coli, Klebsiella
                                           S. agalactiae
                                           L. monocytogenes
                         3 mo. to 5 years  S. pneumoniae
                                           N. meningitidis
                                           H. influenzae type b
                                           S. pyogenes (GAS)
                         age > 5 years     N. meningitidis
                                           S. pneumoniae
                         any age           M. tuberculosis

     - management:      hospitalization for infants < 1 month, high risk children 1-3 months
                                                                              Infection & Immunity 2: Objectives (page 42 of 137)

                         careful consideration of antibiotic use
                         - obtain appropriate cultures first
                         - do not use in older children with unremarkable lab results
                         careful consideration of antipyretic therapy
                         - antipyretics for discomfort, wait until after medical evaluation if possible
                         - acetaminophen, ibuprofen common
                         - no aspirin in children (Reye syndrome, which causes fatty liver, encephalopathy)

     - clinical:         normal diurnal variation of body temperature (higher in afternoon vs. morning)
                         oral and rectal measurements underestimate core body temperature
                         - rectal:     core body temperature
                         - oral:       - 0.5°C
                         - axillary:   - 1.0°C

4.     List the age-appropriate differential diagnosis for pediatric patients presenting with a positive Mantoux skin
       test (PPD).

- Mantoux skin test
  - function:            screening test for tuberculosis

     - method:           injection of 5 tuberculin units of PPD intradermally, read 48 hr later

     - interpretation:   positive test is defined as differing levels of induration based on the patient population
                         • ≥ 15 mm: positive at any age
                         • ≥ 10 mm: positive with underlying disease, travel risks, exposures, incarceration, drugs
                         • ≥ 5 mm: positive with close contacts, immunosuppressed, + imaging / clinical signs

     - differential:     false positives associated with:
                         - nontuberculous mycobacteria (e.g. Mycobacterium avium-intracellulare)
                         - prior BCG vaccine

                         false negatives associated with:
                         - miliary tuberculosis
                         - immunosuppression

5.     Generate an age-appropriate differential diagnosis and initial diagnostic and therapeutic plan for each
       patient presenting with one of the following:
                • sore throat
                • cough / wheeze
                • lymphadenopathy
                • fever / rash
                • otalgia
                • stridor

- common causes of sore throat
   - infectious:     streptococcal pharyngitis
                     viral pharyngitis
                     infectious mononucleosis
                     group A strep (GAS)
                                                                        Infection & Immunity 2: Objectives (page 43 of 137)

  - neoplastic:        Hodgkin disease
  - congenital:        reflux esophagitis
  - allergic:          allergic rhinitis
  - traumatic:         foreign body
  - endocrine:         subacute thyroiditis

- common causes of cough / wheeze
   - anaphylaxis
   - angioedema
   - aspiration
   - bronchitis
   - cystic fibrosis
   - epiglottitis
   - foreign body
   - irritant inhalants
   - masses
   - pneumonia
   - pulmonary embolism

- common causes of lymphadenopathy
   - viral:          EBV, CMV, measles, rubella, VZV, HSV, HIV, adenovirus
   - bacterial:      S. pyogenes, Brucella spp., Leptospira spp., Ehrlichia spp.
   - parasitic:      Toxoplasma gondii, Trypanosoma cruzii
   - malignant:      lymphoma, leukemia, neuroblastoma, histiocytosis
   - other:          medications, JRA, SLE, infection-associated hemophagocytic syndrome
                     granulomatous disease, sarcoidosis, vasculitis

- common causes of fever / rash
   - infectious:     opportunistic infections (CMV, toxoplasma)
                     viral illnesses (measles, rubella, HHV-6, HHV-7, parvovirus B19, varicella zoster)
                     bacterial illnesses (Streptococcus pyogenes, Staphylococcus aureus)
   - inflammatory:   autoimmune diseases
                     vasculitis (e.g. Kawasaki disease)
   - metabolic:      Graves disease (hyperthyroidism)

- common causes of otalgia
   - acute serous otitis media
   - ear trauma
   - foreign body
   - otitis externa
   - otitis media
   - tumor
   - impacted cerumen

- common causes of stridor
   - anaphylaxis
   - croup (laryngotracheobronchitis)
   - diphtheria
   - epiglottitis
   - foreign body
   - laryngitis
                                                                              Infection & Immunity 2: Objectives (page 44 of 137)

                                                                                                              CHAPTER 10

1.     Describe the transition from the intrauterine to the extrauterine environment, including temperature
       regulation, cardiovascular / respiratory adjustment, glucose regulation, and initiation of feeding.

- temperature regulation
   - process:         maturation of temperature control
                      - shivering and sweating
                      - hypothalamic temperature control
   - timing:          first three postnatal months and beyond
   - clinical:        suggests a more ominous cause for fever (>100.4°F) in first 3 months
                      difficulty related to high surface area relative to weight vs. adults (3:1)

- cardiovascular adjustment
   - process:         establishment of normal circulation
                      - closure of foramen ovale within atrial membrane
                      - closure of ductus arteriosus
                      - inflation of the lungs
   - timing:          begins with first breath outside the womb
   - defects:         persistent pulmonary hypertension of the newborn
                      congenital heart defect

- respiratory alveolarization
   - process:          alveolarization
                       - growth of pulmonary capillaries in approximation with the epithelium
                       - differentiation of epithelial cells into type I and type II (surfactant-producing) cells
   - timing:           begins at 28 weeks, but primarily occurs postnatally
   - defects:          respiratory distress syndrome (RDS, hyaline membrane disease)

- glucose regulation
   - process:        establishment of normal glucose regulation after loss of transplacental source
                     - hormonal and metabolic changes
                     - initial reliance on glycogen and fat stores
   - timing:         first week of life
   - defects:        hypoglycemia in preterm infants (lack glycogen, fat stores)

- initiation of feeding
   - process:           establishment of normal enteral feedings
   - timing:            first days of life

     BOX: Transition to the Extrauterine Environment
      The transition from the intrauterine to the extrauterine environment involves a number of significant changes,

        • establishment of normal temperature regulation
        • formation of normal fetal circulation, including closure of the ductus arteriosus and foramen ovale
                                                                              Infection & Immunity 2: Objectives (page 45 of 137)

       • respiratory alveolarization, including growth of pulmonary capillaries and differentiation of type II cells
       • establishment of normal glucose regulation
       • initiation of feeding

     Preterm infants, for a number of reasons, have difficulties in all of these adaptations, often requiring significant
       medical therapy while their bodies mature.

2.   List the differential diagnosis and complications for the following common problems that may occur in the
               • jaundice
               • respiratory distress
               • apnea
               • anemia

- jaundice
   - differential
      - unconjugated: physiologic jaundice

                        hemolytic anemia
                        - hereditary spherocytosis
                        - G6PD deficiency
                        - pyruvate kinase deficiency
                        - galactosemia
                        - hemoglobinopathies
                        - Rh or ABO incompatibility
                        - infection
                        - drugs (e.g. vitamin K)

                        - chronic fetal hypoxia
                        - maternal-fetal or twin-twin transfusion
                        - delayed cord clamping
                        - gestational diabetes mellitus (GDM)

                        hematoma / hemorrhage
                        - birth trauma
                        - pulmonary hemorrhage
                        - intraventricular hemorrhage

                        glucuronyl transferase defect
                        - type I (Crigler-Najjar syndrome)
                        - type II deficiency
                        - Gilbert syndrome
                        - drugs (e.g. novobiocin)
                        - Lucey-Driscoll syndrome

                        metabolic disorders
                        - galactosemia
                        - hypothyroidism
                        - maternal diabetes mellitus

                        increased enterohepatic circulation
                                                                          Infection & Immunity 2: Objectives (page 46 of 137)

                      - intestinal obstruction
                      - ileus
                      - swallowed blood

                      alterations of bilirubin-albumin binding
                      - aspirin
                      - sulfonamides
                      - acidosis

    - conjugated:     extrahepatic biliary obstruction

                      intrahepatic cholestasis
                      - infection
                      - metabolic disorders
                      - hyperalimentation

  - complications:    kernicterus (bilirubin encephalopathy)
                      - abnormalities of tone
                      - lethargy
                      - high pitched cry
                      - arching of the back and spine (retrocollis)
                      - fever
                      - permanent neurologic deficits

- respiratory distress
   - differential (airway / pulmonary abnormalities)
      - nasal:           choanal atresia
      - oral:            macroglossia (Beckwith-Wiedemann syndrome)
                         microglossia (Pierre Robin sequence
      - neck:            congenital goiter
                         cystic hygroma
      - larynx:          laryngomalacia
                         subglottic stenosis
                         vocal cord paralysis
                         laryngeal web
      - trachea:         vascular ring
                         tracheoesophageal fistula
                         bronchial stenosis / atresia
                         tracheal stenosis / agenesis
      - lungs:           pulmonary hypoplasia
                         congenital diaphragmatic hernia
                         congenital lobar emphysema
                         pulmonary sequestration
                         pulmonary lymphangiectasia

  - differential (lung disease)
     - acute:           respiratory distress syndrome
                        transient tachypnea of the newborn (TTN)
                        aspiration syndromes (e.g. meconium, blood, amniotic fluid)
     - chronic:         bronchopulmonary dysplasia (BPD)
                        Wilson-Mikity syndrome

  - differential (nonpulmonary disease)
                       persistent pulmonary hypertension of the newborn (PPHN)
                                                                           Infection & Immunity 2: Objectives (page 47 of 137)

                       metabolic abnormalities (e.g. acidosis, hypothermia)
                       congestive heart failure
                       central nervous system

  - complications:     atelectasis
                       air leak syndrome (e.g. pneumothorax, pneumomediastinum, pneumopericardium)
                       pulmonary interstitial emphysema (PIE)
                       pulmonary hemorrhage
                       chronic lung disease

- apnea
   - differential:     prematurity
                       impaired oxygenation
                       metabolic disorders
                       intracranial pathology
                       gastroesophageal reflux
                       thermal instability

  - complications:     cyanosis
                       respiratory distress
                       congenital / neurologic abnormalities

- anemia
   - differential
      - blood loss:    obstetric causes
                       - abruptio placentae, placenta previa
                       - cord rupture, hematoma
                       - fetomaternal / fetoplacental bleeding
                       - twin-twin transfusion
                       - anomalous vessels (e.g. vasa previa, velamentous insertion)

                       neonatal causes
                       - iatrogenic (e.g. phlebotomy, surgical bleeding)
                       - intracranial bleeding
                       - cephalohematoma
                       - gastrointestinal hemorrhage
                       - rupture of liver or spleen

     - hemolysis:      immune
                       - Rh, ABO, or minor blood group incompatibility
                       - maternal autoimmune disease
                       - drug-induced hemolysis

                       - hereditary RBC disorders
                       - RBC membrane defects (e.g. spherocytosis, elliptocytosis)
                       - metabolic defects (e.g. G6PD, pyruvate kinase)
                       - hemoglobinopathies
                       - infection
                       - disseminated intravascular coagulation (DIC)
                       - vitamin E deficiency
                       - microangiopathic hemolytic anemia (e.g. cavernous hemangioma)

     - ↓ production:   anemia of prematurity
                                                                           Infection & Immunity 2: Objectives (page 48 of 137)

                         Diamond-Blackfan syndrome
                         congenital leukemia
                         viral infection

     - complications:    poor weight gain
                         persistent tachycardia
                         supplemental O2 requirements

     BOX: Differential Diagnosis of Anemia
      In general, postnatal anemia is related to one of three causes:

        • blood loss (neonatal or obstetric causes)
        • hemolysis (immune and nonimmune causes)
        • diminished production of RBCs

3.     Describe the effects of each congenital infection in the TORCH acronym.

- congenital toxoplasmosis
   - etiology:        Toxoplasma gondii (frequently carried by domestic cats, esp. in feces)
   - sequelae:        chorioretinitis
                      intracranial periventricular calcifications

- congenital rubella
   - etiology:       rubella virus (exceedingly common; primary infection during pregnancy is harmful)
   - sequelae:       cataracts
                     hearing loss
                     heart lesions
                     blueberry muffin spots (skin lesions associated with extramedullary hematopoiesis)

- congenital cytomegalovirus (CMV) infection
   - etiology:       cytomegalovirus (opportunistic infection)
   - sequelae:       mental retardation

- congenital herpes simplex
   - etiology:        herpes simplex virus (HSV) (effects often manifest after first week of life)
   - sequelae:        skin, eye, mouth lesions
                      multiorgan system failure

     BOX: TORCHS Infections
      The common congenital infections can be remembered by the mnemonic “TORCHS,” which stands for:

        • toxoplasmosis
        • other (HIV ME agents: HIV, influenza, varicella-zoster, mumps, enterovirus)
        • rubella
                                                                           Infection & Immunity 2: Objectives (page 49 of 137)

      • cytomegalovirus (CMV)
      • herpes simplex
      • syphilis

4.   List common medical and metabolic disorders (e.g. hearing loss, hypothyroidism, phenylketonuria,
     hemoglobinopathies) detected through newborn screening programs.

- Wisconsin Newborn Screening Disorders
  - argininosuccinic acidemia (ASA)
  - biotinidase deficiency
  - citrullinemia (type II & II)
  - congenital adrenal hyperplasia (CAH)
  - congenital hypothyroidism
  - cystic fibrosis
  - fatty acid oxidation (12)
  - galactosemia
  - hearing screening
  - hemoglobin S- β thalassemia
  - hemoglobin S/C disease
  - hemoglobin variants
  - homocystinuria
  - hypermethioninemia
  - hyperphenylalaninemia
  - maple syrup urine disease
  - organic acidemia (15)
  - phenylketonuria
  - sickle cell disease
  - tyrosinemia (type I, II & III)

                                                                                                           CHAPTER 11

1.   Discuss the difference between a malformation syndrome and an association.

- definitions
   - malformation: clinically significant abnormalities in form or function secondary to errors in morphogenesis
   - deformations: disruption of development secondary to environmental factors

- malformation sequence
  - pathogenesis:    single malformation leading secondarily to related developmental consequences
  - example:         Pierre Robin sequence
                     - malformation: failure of growth of mandible during early gestation
                     - effects:       cleft palate, glossoptosis
                                                                               Infection & Immunity 2: Objectives (page 50 of 137)

- malformation syndrome
  - pathogenesis:    recognizable pattern of related anomalies arising from a single identifiable etiology
  - example:         trisomy 21 (Down syndrome)
                     - etiology:       extra copy of chromosome 21
                     - effects:        malformations of the CNS, craniofacies, heart, and limbs

2.     Describe the genetic basis and clinical manifestations of the following syndromes, malformations, and
                • chromosomal: trisomy 21, Turner syndrome, Klinefelter syndrome
                • single gene:    Marfan syndrome, cystic fibrosis, sickle cell disease
                • X-linked:       Duchenne muscular dystrophy, hemophilia A
                • teratogenic:    fetal alcohol syndrome

- trisomy 21 (Down syndrome)
   - disorder:      triploidy of chromosome 21 secondary to:
                    - chromosomal nondisjunction     (92.5% of cases)
                    - Robertsonian translocation     (4.5% of cases)
                    - mosaicism                      (3% of cases)

     - epidemiology:     1 in 800 live births

     - classification:   chromosomal anomaly

     - pathogenesis:     imbalance of cellular protein products, leading to developmental abnormalities

     - manifestations (external)
       - head:            microcephaly, large anterior fontanelle, flat occiput
       - eyes:            upward slanting palpebral fissures, epicanthal folds, white Brushfield spots in iris
       - ears:            flattened upper part of helices of ears
       - nose:            flattened nasal bridge
       - mouth:           large tongue, small teeth
       - hands:           brachydactyly (shortening of hands and fingers), simian crease
       - skin:            doughy consistency
       - genitals:        microphallus

     - manifestations (internal)
       - cardiovascular: ASD, VSD, AV canal, valvular disease
       - gastrointestinal: duodenal atresia, tracheoesophageal fistula, annular pancreas, imperforate anus, Hirschsprung
       - developmental: growth retardation, mental retardation
       - neurologic:       hypotonia, seizures, presenile dementia
       - endocrine:        hypothyroidism, hyperthyroidism, male infertility (100%)
       - hematologic: neonatal leukemoid reaction, leukemia
       - skeletal:         joint hypermobility, atlantoaxial instability, cervical spine osteoarthritis

     TABLE: Quad Screen Results
                          AFP 1     HCG 2             UE 3         Inhibin A
       trisomy 21         ↓         ↑                 ↓            ↑
       trisomy 18         ↓         ↓                 ↓
       NTD 4              ↑
       AFP: alpha-fetoprotein
       HCG: human chorionic gonadotropin
       UE: unconjugated estriol
       NTD: neural tube defects
                                                                         Infection & Immunity 2: Objectives (page 51 of 137)

             FIGURE: Down Syndrome

- Turner syndrome
  - disorder:         monoploid X
  - epidemiology:     1 in 5000 live female births
                      - single leading cause of first trimester spontaneous abortion
                      - 99% of conceptuses die due to severe hydrops fetalis secondary to lymphatic obstruction
  - classification:   chromosomal anomaly
  - pathogenesis:     imbalance of cellular protein products, leading to developmental abnormalities
  - manifestations
     - physical:      unusual facial appearance
                      webbing of the neck
                      shield chest
                      cubitus valgus
                      puffiness of the hands and feet, short fourth metacarpals, spoon-shaped nails
     - developmental: short stature, failure of development of secondary sexual characteristics
     - cardiac:       coarctation of the aorta, aortic valve stenosis, dissecting aortic aneurism
     - renal:         horseshoe kidney, collecting system duplication
     - reproductive: infertility (nearly universal)

             FIGURE: Turner Syndrome

- Klinefelter syndrome
  - disorder:        47,XXY (with some additional X chromosome aneuploidies)
  - epidemiology:    1 in 1000 live births
  - classification:  chromosomal anomaly
  - pathogenesis:    imbalance of cellular protein products, leading to developmental abnormalities
  - manifestations
     - physical:     effects manifest primarily in adolescence and may include:
                     - hypogonadism and absence of male secondary sexual characteristics
                     - tall stature with long extremities
                     - gynecomastia
                     - central obesity
                                                                           Infection & Immunity 2: Objectives (page 52 of 137)

    - neurologic:     normal intelligence, immature behavior (possibly)
    - reproductive:   infertility

             FIGURE: Klinefelter Syndrome

- Marfan syndrome
  - disorder:         connective tissue disorder
  - epidemiology:     1 in 10,000 live born infants
  - classification:   single gene disorder, autosomal dominant
  - pathogenesis:     defect in fibrillin 1 on chromosome 15, essential in connective tissue formation
  - manifestations
     - skeletal:      dolichostenomelia (tall, thin), arachnodactyly (spider-like fingers)
                      pectus excavatum / carinatum, kyphoscoliosis
                      joint laxity
    - ocular:         high myopia, ectopia lentis, decreased visual acuity
    - cardiac:        aortic insufficiency, dissecting aortic aneurysm
                                                                              Infection & Immunity 2: Objectives (page 53 of 137)

              FIGURE: Marfan Syndrome
              Historians contest whether or not Lincoln had Marfan Syndrome

- cystic fibrosis
   - disorder:          membrane channelopathy
   - epidemiology:      1 in 2,000 in northern European white populations
   - classification:    single gene disorder, autosomal recessive
   - pathogenesis:      defect in CFTR, a chloride channel (ΔF508 most common), leading to:
                        - chronic respiratory disease
                        - blockage of the intestinal tract and digestive malabsorption
  - manifestations
    - respiratory:      chronic cough, wheezing, pneumonia, sinusitis, bronchiectasis, polyps
    - GI:               jaundice, meconium ileus, steatorrhea, rectal prolapse, failure to thrive,
                        abdominal pain, edema, hypoproteinemia, anemia, portal HTN
    - physical:         digital clubbing, high Cl- sweat

- sickle cell disease
   - disorder:          hemoglobin defect
   - epidemiology:      1 in 400 African Americans (1 in 10 are carriers)
   - classification:    single gene disorder, autosomal recessive
   - pathogenesis:      G6V substitution on β-globin of heme, leading to formation of Hb S and:
                        - reversible polymerization in reduced O2 tension
                        - intravascular and extravascular hemolysis
  - manifestations:     acute vascular occlusion (painful)
                        splenic sequestration crises and recurrent splenic infection
                        end organ impairment and infarction
                        - bone infarction
                        - avascular necrosis
                        - acute chest syndrome
                        - cerebrovascular accidents
                        - cutaneous ulcers

- Duchenne muscular dystrophy
  - disorder:       muscle defect
  - epidemiology:   1 in 3,500 live-born males
  - classification: single gene disorder, X-linked recessive
  - pathogenesis:   mutation in dystrophin gene leading to structural instability of muscles, high breakdown
  - manifestations: waddling gate (discovered by age 3), Gower sign
                    excessive falling
                    cardiopulmonary complications (usually die by age 20)
                                                                         Infection & Immunity 2: Objectives (page 54 of 137)

              FIGURE: Gower sign

- hemophilia A
   - disorder:         hemorrhagic disorder
   - epidemiology:     1 in 5,000 live-born males (most common hemorrhagic disorder in children)
   - classification:   single gene disorder, X-linked recessive
   - pathogenesis:     factor VIII deficiency leading to defective clot formation
   - manifestations:   excessive bleeding with minor trauma (high risk for intracranial bleeds)
                       recurrent hemarthrosis, secondary arthritis
                       easy bruising

- fetal alcohol syndrome (FAS)
   - disorder:        multiple congenital defects
   - epidemiology:    3-5 in 1,000 children (more have fetal alcohol spectrum disorders)
   - classification:  teratogen exposure disorder
   - pathogenesis:    effects of alcohol on early prenatal development
   - manifestations: prenatal and postnatal growth deficiency
                      developmental delay
                      skeletal and cardiac abnormalities
                      characteristic facial appearance
                      - small palpebral fissures
                      - hypoplastic philtrum
                      - thin upper vermilion
                      - micrognathia
                                                                           Infection & Immunity 2: Objectives (page 55 of 137)

                  FIGURE: Fetal Alcohol Syndrome

3.     Discuss the effects of maternal health and potentially teratogenic agents (including alcohol and retinoic
       acid) on the fetus and child.

- maternal factors in fetal illness
  - infection:          toxoplasma, rubella, CMV, herpes simplex, HIV, varicella

     - illness:          diabetes, phenylketonuria

     - exposures:        nonprescription drugs   (alcohol, cocaine, heroin, marijuana)
                         prescription drugs      (thalidomide hydantoin, warfarin, cis-retinoic acid)
                         environmental exposures (radiation, methylmercury)

- Accutane embryopathy
  - disorder:       congenital developmental disorder
  - epidemiology:   affects 70% of pregnancies in which mother is exposed during first trimester
  - classification: teratogen exposure disorder
  - pathogenesis:   maternal exposure to cis-retinoic acid during pregnancy, leading to multiple defects
  - manifestations: severe craniofacial disorders
                    cardiac defects
                    DiGeorge malformation sequence (hypoparathyroidism, T-cell deficiency)

4.     Explain the use of chromosome studies in the diagnosis of genetic disorders.

- evaluation of genetic disorders
   - imaging:          chest radiogram
                       ultrasound evaluation
                       electrocardiogram (ECG)
   - diagnostics:      fluorescent in situ hybridization
                       direct DNA testing
                       chromosomal analysis

- chromosomal analysis
   - method:         karyotype analysis of three cell types
                     - peripheral blood lymphocytes       (3 day turnaround)
                     - skin fibroblasts                   (2-3 weeks)
                     - bone marrow cells                  (1 day)
   - indication:     detection of three or more abnormalities

     BOX: Karyotype analysis
                                                                             Infection & Immunity 2: Objectives (page 56 of 137)

      Karyotype analysis is only indicated in the presence of three or more detectable abnormalities. It is not
       indicated for isolated cleft lip or palate unless other malformations are present.

5.    Discuss the role of genetics in common multifactorial conditions (e.g. pyloric stenosis, neural tube defects).

     TABLE: Causes of Major Congenital Anomalies
      etiology                           prevalence
      single gene mutations              7.5%
      chromosomal abnormalities          6.0%
      known teratogen exposures          6.5%
      multifactorial conditions          20.0%
      undetermined                       60.0%

- neural tube defects
   - disorder:        failure of closure of the neural tube, with varying manifestation:
                      - anencephaly
                      - meningocele
                      - meningomyelocele
   - epidemiology:    1 to 5 in 1,000 liveborn infants
   - classification:  multifactorial genetic disorder
   - pathogenesis:    related to multiple factors, both genetic and non-genetic
                      particularly associated with maternal folate deficiency during first month of pregnancy
   - manifestations: obstructive hydrocephalus
                      neurogenic bowel and bladder
                      orthopedic problems (joint contracture, clubfoot deformity, scoliosis, paraparesis)

- hypertrophic pyloric stenosis
   - disorder:       obstruction of gastric outflow
   - epidemiology:   boys > girls; incidence of 5 in 1000 (boys), 1 in 1000 (girls)
   - classification: multifactorial genetic disorder
   - pathogenesis:   hypertrophy of muscles of the pyloric sphincter
   - manifestations: originates in fetal life, but effects often manifest late in the first month, including:
                     - projectile vomiting
                     - dehydration
                     - electrolyte abnormalities (hypochloremic alkalosis)

Developmental Disabilities
                                                                                                             CHAPTER 12

1.    Explain the management strategies for common chronic illnesses seen in children, such as cerebral palsy.

- management strategies of developmental disabilities
  - mental retardation:   explain the meaning of “mental retardation”
                          - significant stigma, misinformation associated with diagnosis
                                                                               Infection & Immunity 2: Objectives (page 57 of 137)

                              - utilize proper diagnostic terminology
                              aid in accessing appropriate evaluation and information
                              monitor progress of the patient, especially for deterioration

     - cerebral palsy:        treat motor disabilities
                              - motor deficits may not manifest as early as other deficits
                              - interventions should be done as early as possible when symptoms and signs are mild
                              treat associated deficits
                              promote good physical and emotional help and family support
                              aid in access to proper educational and vocational services
                              aid in prevention / minimization of potential complications

     - autistic spectrum:     applied behavioral analysis (highly individualized, highly structured)
                              psychotropic medications for behavioral control
                              aid in accessing and interpreting information regarding new and unorthodox therapies

     - learning disability:   careful multidisciplinary assessment
                              - standard psychological assessment to document cognitive potential
                              - educational evaluation to pinpoint areas of strength and weakness
                              - individual therapy (e.g. IEP) to address problems
                              - other therapy as needed (occupational, speech, psychological)

2.     Describe the classification of cerebral palsy.

- spastic cerebral palsy
   - spastic diplegia:        both legs
   - spastic quadriparesis:   both arms and legs (more severe in lower extremities)
   - spastic triplegia:       both lower legs and one arm
   - spastic hemiparesis:     arm and leg on one side of body (more involvement in arm)
   - spastic monoplegia:      one limb (usually mild, often a misdiagnosed hemiplegia)

- dyskinetic cerebral palsy
   - athetosis:             slow, writhing movements of the face and distal extremities
   - dystonia:              rhythmic twisting movements of trunk and proximal limbs with changes in muscle tone
   - chorea (uncommon): rapid irregular jerky movements of face and extremities

- mixed cerebral palsy
  - spastic athetoid:         spasticity, athetoid (continuous, writhing) movements
  - spastic ataxic:           spasticity, unsteadiness, nystagmus, dyskinetic and uncoordinated movements

     BOX: Classification of Cerebral Palsy
      The three major groups in the classification of cerebral palsy are spastic, dyskinetic, and mixed.

         • spastic:           characterized by hypertonia
         • dyskinetic:        characterized by hypertonia and hypotonia, manifesting as involuntary movements
         • mixed:             characterized by mixed features

3.     Discuss the initial evaluation and need to refer a patient with evidence of developmental delay or

- developmental screening
                                                                             Infection & Immunity 2: Objectives (page 58 of 137)

     - function:         early detection of developmental delay
     - methods:          general developmental surveillance (i.e. developmental milestones)
                         screening tools for “at risk” children
     - clinical:         the importance of early detection of developmental delay includes:
                         - improved developmental outcome
                         - improved family functioning

     BOX: Developmental Delay
      Due to the natural history of childhood development, delays may present at different ages in different ways. In
       general, this is seen as:

         • infancy:              motor delay
         • toddler / preschool:  language delay
         • school / adolescence: learning problems

      Generally, the earlier the occurrence of the developmental disability, the more severe the condition.

4.     Describe how abnormal findings on the development screening tools would suggest a diagnosis of
       developmental delay, autism, pervasive developmental delay, and mental retardation.

- mental retardation
  - disorder:        deficit of intellectual functioning with concurrent limitations in adaptive skills
  - epidemiology:    2.5% of population by definition (2 SD below the mean)
  - classification:  mild, moderate, severe, and profound based on IQ
                     - mild:        IQ = 50-70 (85% of individuals with mental retardation)
                     - moderate: IQ = 35-50 (10%)
                     - severe:      IQ = 20-35 (4%)
                     - profound: IQ < 20           (1%)
  - screening:       learning delays, language delays
  - clinical:        often associated with other disabilities, including cerebral palsy, autism

- cerebral palsy
   - disorder:           deficit of movement and posture
   - epidemiology:       2-3 per 1000 live births (most common childhood motor disability)
   - classification:     spastic, dyskinetic, and mixed based on characteristics
                         - spastic:         hypertonia
                         - dyskinetic:      hypertonia and hypotonia → involuntary movements
                         - mixed:           mixed features
     - screening:        gross motor, fine motor-adaptive deficits

- pervasive developmental disorders (PDDs)
   - disorder:       autism is the extreme of PDDs, and is a developmental disorder manifested by:
                     - impaired communication
                     - impaired socialization
                     - repetitive, stereotyped patterns of behavior
   - epidemiology:   2-5 per 10,000; males > females (4:1)
   - classification: autistic spectrum disorders include:
                     - autism:               impairment of communication and socialization; stereotyped behavior
                     - Asperger syndrome: impairment of socialization
                     - Rett syndrome:        severe delays in girls after initially normal development
                     - CDD:                  cognitive, social regression in children who were normal up to 2 years
   - screening:      language, personal-social deficits
                                                                            Infection & Immunity 2: Objectives (page 59 of 137)

- learning disabilities
   - disorder:          broad range of disorders resulting in difficulties in academic achievement
   - epidemiology:      2-10% of children and adults, males > females (4:1)
   - classification:    encompasses deficits in listening, speaking, reading, writing, reasoning, math, & social skills
   - screening:         language deficits, other screening tests

     BOX: Denver Developmental Screening Test
      The Denver Developmental Screening Test (DDST; Denver Scale) is the most widely-used, highly sensitive
        screening tool for developmental delays. It assesses childhood performance in four areas, including:

        • language
        • fine motor-adaptive
        • gross motor
        • personal-social

                                                                                                            CHAPTER 13

1.     Describe the differences between a benign heart murmur and a pathologic murmur.

- heart murmurs
   - epidemiology:      extremely common in children (5-90% depending on the study)
                        - vast majority of heart murmurs are benign
                        - 5% represent pathologic heart murmurs

     - evaluation:      workup for a heart murmur includes:
                        - history and physical
                        - chest radiography
                        - electrocardiogram

                        grading heart murmurs
                        • 1/6: very faint, may not hear in all positions
                        • 2/6: soft murmur, readily detectable
                        • 3/6: moderately loud
                        • 4/6: easily detectable with palpable thrill
                        • 5/6: very loud, heard with stethoscope lightly on chest
                        • 6/6: extremely loud, can be heard with stethoscope off chest

     - diagnosis:       diagnosis of a benign heart murmur requires:
                        - confident recognition of classic ausculatory features of a specific murmur
                        - history with no evidence for heart disease
                        - physical exam with no history of heart disease
                        - observation of normal growth and development
                                                                           Infection & Immunity 2: Objectives (page 60 of 137)

     BOX: Pathologic Heart Murmur
      Certain characteristics of the physical examination suggest a more pathologic cause for a heart murmur. These

        • symptomatic (dyspnea, poor feeding)
        • diastolic (exception of venous hum)
        • systolic ≥ 3/6
        • heave, thrill
        • loud or fixed split S2
        • cyanosis
        • abnormal pulses
        • abnormal CXR or EKG

2.     List the common acyanotic heart lesions.
3.     List the common cyanotic heart lesions.

- acyanotic heart lesions
   - L → R shunts:        atrial septal defect (ASD)
                          ventricular septal defect (VSD)
                          AV septal defect (AV canal)
                          patent ductus arteriosus

     - obstructive:         pulmonic stenosis
                            aortic stenosis
                            coarctation of the aorta

- cyanotic heart lesions
   - ↓ pulmonary flow:      critical pulmonic stenosis
                            tetralogy of Fallot
                            tricuspid atresia
                            Ebstein anomaly of tricuspid valve

     - ↑ pulmonary flow:    transposition of the great arteries
                            truncus arteriosus
                            hypoplastic left heart (HLHS)
                            total anomalous pulmonary venous return (TAPVR)

     BOX: Cyanotic Heart Lesions
      Common congenital cyanotic heart lesions can be remembered as the “five T’s” as follows:

        • tetralogy of Fallot
        • transposition of the great vessels
        • tricuspid atresia
        • truncus arteriosus
        • total anomalous pulmonary venous return

4.     Describe the appropriate evaluation of syncope.
                                                                            Infection & Immunity 2: Objectives (page 61 of 137)

- syncope
   - disorder:          temporary loss of consciousness and postural tone

     - pathophysiology: secondary to any one of:
                        - primary decrease in cerebral perfusion
                        - global decrease in cardiac output
                        - abnormality in peripheral vascular tone
                        - decrease in cerebral substrate delivery

     - diagnosis
        - history:      can help to differentiate causes
                        - history of cardiac disease:     →more ominous causes
                        - prodromal symptoms:             → vasovagal syncope
                        - sudden onset of symptoms: → cardiac causes
       - physical:      vital signs, orthostatic signs, careful cardiac evaluation
       - laboratory:    initial evaluation with ECG and blood chemistries; further workup for specific causes
                        - vasovagal:        minimal
                        - cardiogenic:      24 hour Holter monitor, transtelephonic ECG, echo

     - differential:    differential causes include:
                        - vasovagal:       interruption of normal vasomotor tone
                        - cardiac:         obstruction of left-sided flow
                        - arrhythmogenic: secondary to abnormal heart rhythm
                        - orthostatic:     failure of vascular compensatory responses to postural change
                        - vagovagal:       vagal stimulation → bradycardia (NG tube, visceral distension, etc.)
                        - other:           seizures, migraines, hypoglycemia, hypoxemia, hysterical

     - clinical:        even benign causes are dangerous due to unpredictability (i.e. driving)

5.     Discuss the common causes of chest pain in children.

- chest pain
   - epidemiology:      3rd to headache and abdominal pain in terms of commonality of complaint

     - pathophysiology: varies widely

     - diagnosis
        - history:      careful history that addresses concerns of parents and patients
                        note quality of interactions between child, family members (secondary gain, psychogenic)
       - physical:      inspection, examination, palpation, percussion
       - laboratory:    should be minimal unless specific findings point to an organic cause

     - differential:    pulmonary causes
                        - asthma
                        - bronchitis
                        - tracheitis
                        - pneumonia
                        - foreign body
                        - pneumothorax
                        - pleuritis
                        - pleurodynia (Devil’s grip)
                        - intraabdominal irritation of the diaphragm

                        cardiac causes
                                                                             Infection & Immunity 2: Objectives (page 62 of 137)

                        - dysrhythmia
                        - mitral valve prolapse
                        - aortic stenosis
                        - hypertrophic cardiomyopathy (IHSS) with obstruction
                        - myocarditis
                        - pericarditis
                        - coronary artery anomalies (congenital, aneurysm)
                        - sickle cell angina

                        gastrointestinal causes
                        - esophagitis and gastroesophageal reflux
                        - achalasia
                        - foreign body
                        - esophageal spasm

                        other causes
                        - scoliosis and other spinal deformities
                        - psychogenic (anxiety, hyperventilation syndrome)

6.     List the age-appropriate differential diagnosis for pediatric patients presenting with a heart murmur.

differential diagnosis of murmurs
- systolic ejection murmurs
   - benign:           innocent systolic murmur (vibratory)
                       flow murmur
                       - hemodynamic effect (fever, hyperthyroidism, severe anemia)
                       - athlete heart
                       atrial septal defect (incidental)

     - pathologic:      aortic stenosis
                        pulmonary stenosis
                        hypertrophic cardiomyopathy
                        atrial septal defect

- pansystolic murmurs
   - regurgitation:   tricuspid regurgitation
                      mitral regurgitation

     - anatomic:        ventricular septal defect

- diastolic murmurs
   - early:             atrial regurgitation
                        pulmonary regurgitation

     - middiastolic:    mitral stenosis
                        tricuspid stenosis

etiology of murmurs
- aortic stenosis
   - etiology:      generally arise from three etiologies
                    - calcific:        age-associated
                    - congenital:      bicuspid valve with secondary calcification
                    - rheumatic:       commisural fission

     - pathogenesis:    multiple mechanisms
                                                                            Infection & Immunity 2: Objectives (page 63 of 137)

                      - mechanical stress
                      - autoimmune degeneration
                      - atherosclerotic injury response with inflammation

  - symptoms:         worse with exertion, requires substantial reduction in valve size
                      - angina
                      - exertional syncope
                      - dyspnea on exertion

  - differential:     senile calcification
                      congenital heart disease
                      rheumatic heart disease

- aortic regurgitation
   - etiology:         primary cusp abnormalities
                       primary aortic root abnormality (annular dilation)

  - pathogenesis:     compensation

  - symptoms:         progressive dyspnea
                      preserved exercise tolerance

  - differential:     rheumatic heart disease
                      congenital heart disease
                      ascending aortic aneurysm
                      aortic dissection
                      medication (e.g. fenfluramine)

- mitral stenosis
  - etiology:         rheumatic heart disease

  - pathogenesis:     fusion of the mitral apparatuses (commissures, cusps, chordae tendinea)

  - symptoms:         left atrial enlargement
                      atrial fibrillation
                      hemoptysis (from hemorrhage in the pulmonary vasculature)
                      severe pulmonary hypertension
                      right heart enlargement (chronic pulmonary hypertension

  - differential:     rheumatic fever
                      congenital heart disease
                      bacterial endocarditis

- mitral regurgitation
  - etiology:          anatomical disruption

  - pathogenesis:     abnormalities of / damage to normal anatomy
                      - valve leaflets:     coapt by interdigitation of the scallops; high SA relative to orifice area
                      - chordae tendinea: anchoring strands that suspend leaflet tips, attach to papillary muscle
                      - papillary muscles: extensions of trabeculae that support, contract to hold leaflets

  - symptoms:         depends on phase of disease
                      - acute:    decompensated CHF
                      - chronic:  often asymptomatic
                                                                            Infection & Immunity 2: Objectives (page 64 of 137)

     - differential:    myxomatous degeneration
                        infective endocarditis
                        collagen vascular disease (Marfan’s)
                        rheumatic heart disease

common innocent murmurs of childhood
- Still’s murmur
   - epidemiology:   usually heard ages 2-7
   - characteristics
      - type:        systolic ejection murmur
      - quality:     vibratory buzzing, twanging, musical
      - location:    LLSB
      - properties:  louder supine than upright

- pulmonary ejection murmur
   - epidemiology:   heard at any age
   - characteristics
      - type:        systolic ejection murmur (diamond-shaped), just before S2
      - quality:     blowing, high pitched
      - location:    LUSB
      - properties:  louder supine than upright

- venous hum
   - etiology:          increased blood flow to the head
   - epidemiology:      usually heard ages 3-6
   - characteristics
      - type:           continuous
      - quality:        humming
      - location:       low anterior neck
      - properties:     loudest in sitting position
                        - accentuated with turning head away from murmur
                        - disappears when turning head toward murmur or when supine

- peripheral pulmonic stenosis
   - etiology:       turbulence from relative discordance in size between larger PA, branch pulmonary arteries
   - epidemiology:   infancy only (disappears by 3-6 months)
   - characteristics
      - type:        systolic ejection murmur
      - quality:     low frequency
      - location:    lateral chest, axillae, back

Endocrinology and Disorders of Growth
                                                                                                            CHAPTER 14

1.     Describe variants of normal growth in healthy children (e.g. familial short stature and constitutional delay).

- constitutional delay of growth and puberty
                                                                           Infection & Immunity 2: Objectives (page 65 of 137)

  - disorder:           childhood short stature and delayed puberty
  - etiology:           familial
  - epidemiology:       most common cause of delayed puberty in the U.S.A.
  - diagnosis
     - general:         careful history and physical examination, observation, and bone age determination
     - history:         family history of delayed puberty
     - physical:        normal growth velocity
     - laboratory:      bone scan
                        - height age << chronological age
                        - bone age << chronological age
  - prognosis:          late entry into puberty with completion of growth at normal adult percentile
                        - slow early growth, subsequent growth parallel to but often below 5 th percentile
                        - delay in epiphyseal closure extends growth period, ultimately permitting normal height
                        - prepubertal growth rate deceleration is exaggerated
  - clinical:           medical attention often sought by males due to differences from peers

                FIGURE: Constitutional Delay of Growth

- intrinsic or genetic short stature
   - disorder:         long-lasting short stature secondary to genetic factors
   - etiology:         familial
   - diagnosis
      - general:       careful history and physical examination, observation, and bone age determination
      - history:       short parents
      - physical:      growth chart tracking at the mid-parental height
                       - boys:        MPH = 0.50 · [height FATHER + (height MOTHER + 5”)]
                       - girls:       MPH = 0.50 · [(height FATHER – 5”) + height MOTHER]
      - laboratory:    bone scan
                       - height age << chronological age
                       - normal bone age
   - differential:     disparity between MPH and predicted adult height (> 3”) may indicate other causes
                       - defects in bone growth        (e.g. mild hypochondroplasia)
                       - chromosomal disorders         (e.g. Turner syndrome)
                       - in utero insults              (e.g. SGA infants)
                       - post natal insults            (e.g. cranial-spinal irradiation)
                                                                               Infection & Immunity 2: Objectives (page 66 of 137)

                           - dysmorphic syndromes       (e.g. Russell-Silver syndrome)
     - prognosis:          puberty will commence at normal age, with completion of growth near current percentile

                   FIGURE: Intrinsic Short Stature

     BOX: Interpreting Growth Charts
      The normal range of growth is between the 3rd and the 97th percentile. In interpreting growth charts, the
        following general points should be considered:

        • height of parents has only minor impact on birth weight
        • crossing percentile lines is common during the first two years of life (genetic channeling)
        • downward crossing of percentile lines between 12 and 30 months may indicate constitutional delay
        • crossing of more than one percentile line (up or down) during childhood or adolescence is worrisome

2.     Describe the clinical features and presentation of diabetes mellitus.
3.     Explain the management strategies for the treatment of diabetes.

- type 1 diabetes mellitus
   - disorder:        absolute insulin deficiency

     - etiology:           autoimmune pancreatic β cell destruction

     - epidemiology
        - prevalence:      5% of patients with diabetes mellitus
        - ethnicity:       more common in Caucasians (particularly in the Northern Hemisphere)
                           less common in African Americans, native Americans, Southern Hemisphere
       - gender:           males = females

     - pathophysiology: autoimmune destruction of pancreatic β cells (T-cell mediated pathology)
                        environmental trigger thought to initiate immune process in genetically-susceptible people
                        - postulated factors include viruses, toxins, proteins
                        - more recently, hygiene theory (lack of exposure to certain infectious agents) proposed
                        associated with development of autoantibodies
                        clinical onset is abrupt, but pathologic course occurs over months to years
                                                                           Infection & Immunity 2: Objectives (page 67 of 137)

                      80-90% of β cells must be destroyed before hyperglycemia occurs

  - diagnosis
     - history:       classic symptoms, other symptoms, often with antecedent illness
                      - classic:     polyuria, polydipsia, polyphagia
                      - others:      blurry vision, fatigue, extremity numbness, recurrent infection, poor healing
    - laboratory:     abnormal glucose tolerance test
                      ketosis, effects related to diabetic ketoacidosis

  - treatment:        insulin replacement

  BOX: Presentation of Type 1 Diabetes Mellitus
   The presentation of diabetes mellitus, type 1, is often characterized by the following:

      • age:          < 30 years old
      • gender:       females > males
      • history:      no family history, but possibly family history of autoimmune disease
      • status:       lean, recent weight loss
      • symptoms:     classic symptoms (polyuria, polydipsia, polyphagia)
      • laboratory:   ketosis common

- diabetic ketoacidosis (DKA)
   - disorder:        severe complication of diabetes, primarily seen in type 1

  - etiology:         often triggered by stress in a person with insulin deficiency
                      - omission or reduction of insulin
                      - infection
                      - major medical illness
                      may be the initial manifestation of DM2
                      idiopathic (20%)

  - epidemiology:     14% of all hospital admissions of patients with diabetes
                      16% of overall diabetic mortality (50% in age < 24)

  - pathophysiology: poor stress response
                     - profound lack of effective insulin
                     - increased counterregulatory hormones

  - presentation:     syndrome of hyperglycemia, ketosis, acidosis, and dehydration
                      - hyperglycemia:    increased production by liver, decreased utilization by body
                      - ketosis:          increased lipolysis, leading to ketogenesis
                      - acidosis:         increased ketone bodies
                      - dehydration:      osmotic diuresis (dehydration, electrolyte depletion, hypotonicity)

  - diagnosis
     - general:       usually obvious, especially in a known diabetic
     - history:       symptoms may include:
                      - polyuria / polydipsia, nausea / vomiting, anorexia, abdominal pain
                      - weakness / lethargy, headache / myalgia, “dyspnea”
    - physical:       signs may include:
                      - intravascular volume depletion, mental status changes (stupor → coma)
                      - hyperpnea (Kussmaul respirations), acetone breath
                      - hypothermia, hyporeflexia, “acute abdomen”
                                                                            Infection & Immunity 2: Objectives (page 68 of 137)

    - laboratory:     characterized by electrolyte abnormalities
                      - ↓ Na+:          lost in diuresis (can be normal / high)
                      - ↓ K+:           lost in diuresis , shifted to extracellular space (can be normal / high)
                      - ↓ phosphate:    lost in diuresis , shifted to extracellular space (acidosis)
                      - ↓ HCO3-:        buffer acidosis

  - treatment:        ICU monitoring and therapy
                      - insulin replacement
                      - fluid replacement
                      - correction of acidosis, dehydration, hyperglycemia, and ketosis
                      - aggressive monitoring and treatment of electrolytes

  - complications:    cerebral edema
                      - rare complication of DKA seen primarily in children
                      - rapid progression to deep coma; often fatal

  - prognosis:        mortality of 5-17%

- type 2 diabetes mellitus
   - disorder:        hyperglycemia characterized by a variable combination of:
                      - insulin resistance
                      - impaired insulin secretion

  - etiology:         strong familial inheritance in the presence of environmental risk factors

  - epidemiology:     90-95% of all cases of diabetes mellitus
     - prevalence:    overall prevalence of 8%
     - ethnicity:     Native Americans > African Americans > Hispanic Americans > Caucasian Americans
     - age:           increasing prevalence with age (15% at age ≥ 65, 25% at age ≥ 85)
     - onset:         average age of diagnosis at 50 years
     - trends:        steadily increasing since the 1940s
                      significant increase in type 2 proportion of childhood diabetes

  - pathophysiology: variable combination of insulin resistance and impaired insulin secretion

  - diagnosis
     - history:       obesity, older age, gradual onset, often with family history
     - laboratory:    abnormal glucose tolerance test

  - treatment:        core of therapy is lifestyle intervention (more effective even than pharmacologic intervention)

  BOX: Presentation of Type 2 Diabetes Mellitus
   The presentation of diabetes mellitus, type 2, is often characterized by the following:

     • age:               > 30 years old (though increasing in young children due to obesity epidemic)
     • history:           obesity, family history
     • status:            may report recent weight gain
     • symptoms:          none or mild; may already have onset of some complications
     • laboratory:        ketosis common

  TABLE: Diabetes Mellitus Clinical Presentation (Type 1 vs. Type 2)
                                 type I                              type II
                                                                                 Infection & Immunity 2: Objectives (page 69 of 137)

         other names                      “insulin-dependent”                 “non-insulin-dependent”
                                          “juvenile onset”                    “adult onset”
         age of onset                     < 35 years old                      > 35 years old
         type of onset                    abrupt (days to weeks)              gradual (weeks to months)
         precipitating factors            altered immune response             obesity
                                          environmental stressors             genetic predisposition
         insulin response
         • pancreatic insulin             negligible / absent                 present
         • response to glucose            negligible / absent                 decreased
         • response to meals              negligible / absent                 normal 1
         • insulin resistance             negligible / absent                 present
         symptoms                         polydipsia                          frequently none or mild

                                          usually lean at onset               associated with obesity
         stress response                  ketoacidosis                        hyperglycemia without ketosis 2
         treatment                        insulin for all patients            diet / exercise usually effective
                                                                              insulin in 20-30%
         normal in absolute terms, but insufficient for glycemic control
         insulin levels are usually sufficient to prevent lipolysis

4.        Describe the workup for precocious puberty.

- definitions
   - gonadarche:            ovarian or testicular development
   - thelarche:             breast budding in females (nl. age 8)
   - adrenarche:            maturation of the adrenal axis, production of secondary sexual characteristics (nl. age 6-8)
   - menarche:              first menstrual cycle (nl. age 12-14)
   - gynecomastia:          male breast development

- precocious puberty
   - disorder:       early pubertal changes (before age 8 in girls, age 9 in boys)

     - etiology:            common cause varies with gender (90% idiopathic in girls, most organic in boys)

     - epidemiology:        more common complaint in girls

     - classification:      central vs. peripheral
                            - central:         early withdrawal of CNS inhibition of GnRH release
                            - peripheral:      increased sex steroid production in absence of increased LH / FSH secretion

                            isosexual vs. heterosexual
                            - isosexual:       pubertal changes consistent with the patient genotype
                            - heterosexual: pubertal changes inconsistent with the patient genotype

     - diagnosis
        - general:          careful history and physical, with lab work to differentiate causes

          - history:        recent onset rapid growth, behavioral disturbances, body odor, vaginal discharge / bleeding
                            - history of CNS malformation, trauma, tumor, poorly treated CAH
                            - androgens, estrogens, marijuana as a cause of gynecomastia in females
                                                                              Infection & Immunity 2: Objectives (page 70 of 137)

                         - family history could point towards familial precocious puberty

       - physical:       differentiate from pseudoprecocious puberty
                         - enlarged testicles:              pituitary gonadotropins, tumor
                         - only secondary characteristics:  adrenal etiology
                         - café au lait spots:              neurofibromatosis, McCune-Albright syndrome

       - laboratory:     numerous tests available
                         - ultrasound:              enlargement of uterus, adnexa in true precocious puberty
                         - adrenal androgens:       rule out precocious adrenarche
                         - ACTH stimulation test:   rule out late onset CAH
                         - TSH, T4:                 rule out hypo- and hyperthyroidism as a cause
                         - GnRH stimulation test:   rise of LH above 5 ng/mL suggestive of central precocious puberty
     - differential
        - male:          isosexual changes
                         - central:    familial, CNS disease (hamartoma, postirradiation, chronic androgens, CAH)
                         - peripheral: testicular tumor, testotoxicosis, adrenal rest tumor, CAH

                         heterosexual changes
                         - estrogenization (adrenal adenoma / carcinoma, teratoma
                         - marijuana use

       - female:         isosexual changes
                         - central:    familial, CNS disease (hamartoma, postirradiation, chronic androgens, CAH)
                         - peripheral: granulosa cell tumor, McCune-Albright syndrome

                         heterosexual changes (androgenization)
                         - CAH
                         - androgen-producing tumor (adrenal adenoma / carcinoma, teratoma)
                         - polycystic ovarian disease
                         - exposure to exogenous androgens

     - management:       differs with etiology
                         - central:         monthly GnRH (binds pituitary receptors and inhibits growth)
                         - peripheral:      determination of underlying cause

     BOX: Evaluation of puberty
      The onset of puberty is specific to the nation and gender. In the United States, the following definitions are
        used to delineate abnormal onset of puberty:

         • precocious puberty
            - females: pubertal changes before age 8
            - males:    pubertal changes before age 9

         • delayed puberty
            - females: no thelarche by age 14 or menarche by age 15
            - males:    no testicular changes by age 15

5.     List the differential diagnosis for ambiguous genitalia.
                                                                             Infection & Immunity 2: Objectives (page 71 of 137)

- ambiguous genitalia
   - disorder:       abnormal differentiation of genitalia

     - differential:    true hermaphroditism

                        female pseudohermaphroditism
                        - maternal ingestion or production of androgens
                        - congenital adrenal hyperplasia (CAH)

                        male pseudohermaphroditism
                        (defects of testicular differentiation and development)
                        - XX male syndrome
                        - mixed gonadal dysgenesis
                        - persistent Müllerian duct syndrome

                        (defects of testosterone synthesis)
                        - congenital adrenal hyperplasia
                        - 17,20-desmolase deficiency
                        - 17-hydroxysteroid deficiency
                        - Leydig cell hypoplasia

                        (defects of testosterone metabolism)
                        - androgen insensitivity syndrome, complete
                        - androgen insensitivity syndrome, incomplete

     - clinical:        rapid evaluation necessary to determine appropriate sex for rearing

6.     Discuss the abnormal lab findings in patients with Cushing syndrome.

- Cushing’s syndrome
  - disorder:      clinical manifestations of glucocorticoid excess, regardless of etiology

     - etiology:        ACTH-dependent
                        - Cushing’s disease             (60-70% of endogenous causes)
                        - ectopic ACTH syndrome         (15-20% of endogenous causes)

                        - adrenal adenoma               (5% of endogenous causes)
                        - adrenal carcinoma             (5% of endogenous causes)
                        - iatrogenic                    (most common overall cause)

     - presentation:    effects of glucocorticoid excess (see below)

     - diagnosis
        - principles:   all causes of Cushing’s are associated with loss of normal diurnal cortisol rhythm
                        all causes of hypercortisolism are characterized by a variable degree of resistance to the
                             suppressive effect of an administered glucocorticoid (e.g. dexamethasone)

       - history:       primarily glucocorticoid, but some mineralocorticoid effects

       - laboratory:    general laboratory findings are non-specific
                        - ↑ PMNs, ↓ lymphocytes, ↓ eosinophils (glucocorticoid toxicity)
                        - hypokalemic alkalosis
                        - fasting hyperglycemia
                        - hypercalciuria
                                                                         Infection & Immunity 2: Objectives (page 72 of 137)

                      assessment of cortisol secretion
                      - urinary free cortisol
                      - serum cortisol
                      - salivary cortisol

    - procedures:     24 h urinary free cortisol measurement
                      serum cortisol measurement
                      overnight dexamethasone suppression test
                      non-suppressed midnight salivary cortisol

  BOX: Presentation of Cushing Syndrome
   The presentation of Cushing syndrome, regardless of etiology, is general manifestations of glucocorticoid
     excess, with some mineralocorticoid effects. These include:

     • central obesity
     • moon facies
     • hirsutism
     • amenorrhea
     • hypertension
     • muscle wasting / weakness
     • osteoporosis / vertebral compression
     • abdominal striae
     • acne
     • psychological symptoms
     • easy bruisability
     • glucose intolerance

- differentiation of Cushing’s subset
   - serum ACTH measurement
      - function:       differentiation of ACTH-dependent from non ACTH-dependent causes
      - interpretation: based on ACTH levels
                        - absent ACTH:        favors adrenal adenoma or carcinoma
                        - measurable ACTH: favors ACTH-dependent (may be normal in Cushing’s disease)
                        - very high ACTH: favors ectopic ACTH

  - suppression tests
     - function:       differentiation of Cushing’s disease from other causes
     - method:         administration of dexamethasone, with cortisol measurement after 1-2 days
     - interpretation: based on cortisol levels
                       - < 50% baseline:      favors Cushing’s disease
                       - no change:           favors adrenal tumors or ectopic ACTH
     - accuracy:       approximately 80%
                       - some ectopic ACTH syndrome is suppressible
                       - some pituitary Cushing’s disease is nonsuppressible

  - corticotropin releasing hormone (CRH) stimulation test
     - function:       differentiation of Cushing’s disease from other causes
     - method:         measurement of baseline and sequential ACTH after IV bolus of CRH
     - interpretation: increased ACTH > 50% (or cortisol > 20%) is diagnostic of Cushing’s disease

  - imaging studies
     - function:      assessment
                                                                                 Infection & Immunity 2: Objectives (page 73 of 137)

                         - incidental findings in the adrenal / pituitary glands are common
                         - imaging only done after a confirmed biochemical diagnosis of Cushing’s syndrome

       - methods:        radiologic imaging
                         - adrenal:       CT, MRI, 131I scan
                         - pituitary:     MRI

                         petrosal sinus ACTH sampling
                         - function:       gold standard imaging study
                         - method:         bilateral sampling performed before and after CRH administered
                         - interpretation: useful for differentiating pituitary ACTH from ectopic ACTH
                                           pituitary source: petrosal / peripheral > 3:1
                                           ectopic source: petrosal / peripheral < 1.5:1
                         - clinical:       lateralization is uncertain

                         octreotide scan
                         - function:        localize carcinoids and islet cell tumors
                         - method:          octreotide is an analog of somatostatin

     TABLE: Differentiating Cushing’s Syndrome
                          ACTH levels    dexamethasone challenge
      Cushing’s disease   normal / ↑     cortisol suppressed
      ectopic ACTH        ↑↑             no suppression
      adrenal neoplasm    ↓↓             no suppression

7.     List the presenting signs of hypothyroidism.

- hypothyroidism
   - disorder:           deficient thyroid hormone

     - etiology:         Hashimoto’s thyroiditis      (most common cause)
                         thyrotoxicosis treatment     (most common iatrogenic cause)

     - epidemiology:     prevalence of overt disease in 0.1 to 0.2%
                         subclinical disease (positive TPO) in 5-15%

     - diagnosis
        - history:       numerous nonspecific symptoms (see below)
        - laboratory:    dyslipidemia, hypercholesterolemia, hyponatremia, elevated CK

     - treatment:        thyroxine (T4)

     - clinical:         always correct cortisol deficiencies first, as failure to do so could precipitate an adrenal crisis

     BOX: Presenting Signs of Hypothyroidism
      The presentation of hypothyroidism is highly variable, and includes numerous non-specific symptoms. Some of
        these include:

         • fatigue, depression
         • cognitive / mental impairment (especially if occurring in infancy)
         • weight gain (morbid obesity is rarely the result of hypothyroidism)
                                                                                 Infection & Immunity 2: Objectives (page 74 of 137)

         • dry skin, coarse hair, brittle nails
         • constipation
         • myalgia
         • menorrhagia, infertility, galactorrhea
         • bradycardia, exertional dyspnea
         • delayed relaxation phase of DTRs
         • hypothermia / cold intolerance

                                                                                                                 CHAPTER 15

1.     Describe the common pediatric symptoms of gastroesophageal reflux.

- gastroesophageal reflux disease (GERD)
   - disorder:       effortless reflux of gastric contents into the esophagus

     - epidemiology:      present in virtually all infants, but few experience complications

     - pathophysiology: insufficiency of the lower esophageal sphincter
                        - transient relaxations
                        - diminished baseline tone
                        - large hiatal hernias
                        - delayed gastric emptying

     - signs / symptoms: apnea, bradycardia
                         failure to thrive
                         - irritability
                         - bleeding
                         - anemia
                         - strictures
                         - Barrett esophagus
                         chest pain
                         Sandifer syndrome
                         respiratory distress
                         - chronic cough
                         - asthma
                         - aspiration pneumonia
                         - nocturnal cough

     - diagnosis
        - history:        differentiate vomiting (effortful) and reflux (effortless)
        - physical:       rarely helpful, but some findings may be important
                          - distention: suggests obstruction
                          - “olive”:     suggests hypertrophic pyloric sphincter
                                                                              Infection & Immunity 2: Objectives (page 75 of 137)

       - laboratory:    metabolic acidosis (alkalosis suggests gastric outlet obstruction or cystic fibrosis)

     - differential:    infectious gastritis
                        - pyloric stenosis
                        - achalasia
                        - inflammatory bowel disease
                        - adhesions
                        inborn errors of metabolism
                        increased intracranial pressure
                        - tumor
                        - hydrocephalus
                        - bleeding
                        metabolic acidosis
                        - Reye syndrome
                        - salicylate poisoning
                        - diabetic acidosis

     - management:      conservative observation in most cases
                        - thickening of formula (though not proven to help)
                        - positional therapy (30-degree upright stance after feedings)
                        medical therapy generally not beneficial
                        surgery (Nissen fundoplication) only for severe disease and severe complications including:
                        - severe respiratory disability
                        - failure to thrive
                        - esophagitis with stricture formation
                        - Barrett esophagus

2.     List the age-appropriate differential diagnosis for pediatric patients presenting with each of the following
       symptoms: acute abdominal pain, chronic abdominal pain, vomiting, acute diarrhea, and chronic diarrhea.

- differential diagnosis of acute abdominal pain
   - vascular:               vasculitis
                             Henoch-Schönlein purpura
                             vascular insufficiency
                             sickle cell disease

     - inflammatory:         appendicitis
                             bacterial enterocolitis
                             mesenteric lymphadenitis
                             urinary tract infection
                             viral gastroenteritis
                             gall bladder disease
                             pelvic inflammatory disease

     - neoplastic:           malignancy
                                                                 Infection & Immunity 2: Objectives (page 76 of 137)

  - drug / degenerative:   food poisoning

  - idiopathic / iatrogenic: obstruction (adhesions)

  - congenital:            Meckel diverticulum

  - autoimmune:            acute rheumatic fever

  - traumatic / anatomic: abdominal trauma
                          ectopic pregnancy
                          incarcerated hernia
                          renal stones
                          testicular torsion
                          obstructive nephropathy

  - endocrine / metabolic: diabetes mellitus

  BOX: Common Causes of Acute Abdominal Pain
   There are numerous possible etiologies for acute
     abdominal pain. The most common of these include:

     • appendicitis
     • bacterial enterocolitis
     • dietary indiscretion
     • food poisoning
     • mesenteric lymphadenitis
     • pharyngitis
     • urinary tract infection (UTI)
     • viral gastroenteritis

- differential diagnosis of chronic / recurrent abdominal pain
   - vascular:               Mittelschmerz
                             sickle cell disease
                             collagen vascular disease

  - inflammatory:          irritable bowel syndrome
                           food allergy
                           peptic ulcer disease
                           recurrent pancreatitis
                           parasitic infection
                           inflammatory bowel disease
                           H. pylori infection
                           urinary tract infection

  - neoplastic:            abdominal mass / malignancy

  - drug / degenerative:   lactose intolerance
                                                                           Infection & Immunity 2: Objectives (page 77 of 137)

                           heavy metal poisoning

  - idiopathic / iatrogenic: psychogenic
                             abdominal epilepsy

  - congenital:            cystic fibrosis
                           familial Mediterranean fever

  - autoimmune:            ---

  - traumatic / anatomic: constipation
                          mesenteric cyst
                          enteric cyst (duplication)

  - endocrine / metabolic: hyperthyroidism

  BOX: Common Causes of Chronic Abdominal Pain
   There are numerous possible etiologies for chronic
     abdominal pain. The most common of these include:

     • irritable bowel syndrome (functional)
     • psychogenic
     • lactose intolerance
     • constipation

- vomiting
   - vascular:               ---
   - inflammatory:           infectious gastroenteritis
                             systemic infection
  - neoplastic:              ---
  - drug / degenerative: toxic ingestions
  - idiopathic / iatrogenic: ---
  - congenital:              ---
  - autoimmune:              ---
  - traumatic / anatomic: pyloric stenosis
                             mass neurologic effect (brain tumor, hydrocephalus, bleeding)
                             inflammatory bowel disease

  - endocrine / metabolic: overfeeding
                           inborn errors of metabolism
                           metabolic acidosis (Reye syndrome, diabetic ketoacidosis)
                           late onset obstructions

  BOX: Vomiting
   The most common cause of vomiting in all age groups is
     infectious gastroenteritis.

- acute diarrhea
                                                                           Infection & Immunity 2: Objectives (page 78 of 137)

  - vascular:                ---
  - inflammatory:            infection (viral, bacterial, other)
                             systemic infection
  - neoplastic:              ---
  - drug / degenerative: food poisoning
  - idiopathic / iatrogenic: overfeeding (infant)
                             antibiotic association
  - congenital:              ---
  - autoimmune:              ---
  - traumatic / anatomic: ---
  - endocrine / metabolic: hyperthyroidism

  BOX: Common Causes of Acute Diarrhea
   The most common cause of acute diarrhea in all age
     groups is infectious gastroenteritis, including one or
     more of the following:

      • rotavirus
      • norovirus
      • E. coli
      • Campylobacter jejuni
      • Salmonella
      • Shigella
      • Yersinia enterocolitica
      • Clostridium difficile

- chronic diarrhea
   - vascular:               ---

  - inflammatory:            postinfectious diarrhea
                             gluten-induced enteropathy (celiac disease)
                             irritable bowel syndrome
                             inflammatory bowel disease
                             immunodeficiency (primary HIV)

  - neoplastic:              secretory tumors (neuroblastoma)
                             intestinal tumors

  - drug / degenerative:     chronic laxative abuse

  - idiopathic / iatrogenic: chronic antibiotic use

  - congenital:              intractable diarrhea of infancy
                             cystic fibrosis
                             Hirschsprung disease

  - autoimmune:              eosinophilic gastroenteritis

  - traumatic / anatomic: constipation with encopresis
                          intestinal lymphangiectasia
                          blind loop
                                                                                Infection & Immunity 2: Objectives (page 79 of 137)

                             short bowel

     - endocrine / metabolic: carbohydrate malabsorption (lactose intolerance)
                              food allergy (cow milk, soy protein)
                              pancreatic insufficiency

     BOX: Common Causes of Chronic Diarrhea
      There are numerous possible etiologies for chronic
        diarrhea. The most common of these include:

        • intractable diarrhea of infancy
        • postinfectious diarrhea
        • carbohydrate malabsorption (lactose intolerance)
        • overfeeding
        • allergic (cow’s milk, soy protein intolerance)
        • cystic fibrosis
        • gluten-induced enteropathy (celiac disease)
        • irritable bowel syndrome
        • inflammatory bowel disease
        • giardiasis
        • constipation with encopresis

3.     List the clinical differences between Crohn’s disease and ulcerative colitis.

- inflammatory bowel disease (IBD)
   - disorder:     non-specific, non-infectious, chronic inflammation of the intestinal tract
                   - group of inflammatory conditions of the large (and sometimes small) intestine
                   - shares underlying features, mechanisms, and therapies with some rheumatoid disorders

                         manifests as any one of the following:
                         - Crohn’s disease (ileocolitis, colitis, small bowel, perianal, etc.)
                         - ulcerative colitis
                         - ulcerative proctitis
                         - indeterminate colitis

     - etiology:         environmentally triggered immune dysregulation in a genetically susceptible individual
                         - precise etiology is currently unknown
                         - thought to be secondary to ubiquitous, commensal intestinal bacteria

                         effect of environmental factors
                         - smoking:                 worsens Crohn’s disease, protective against ulcerative colitis (UC)
                         - appendectomy:            protective against UC
                         - NSAIDS:                  worsens both Crohn’s, UC
                         - oral contraceptives:     effect is debatable
                         - breastfeeding:           protective against both Crohn’s, UC
                         - hygiene hypothesis:      increasing incidence of IBD may be secondary to better hygiene
                                                                         Infection & Immunity 2: Objectives (page 80 of 137)

- epidemiology
   - geography:    more common in Western civilizations (North America, UK, Scandinavia)
   - prevalence:   1-2 million IBD patients in the U.S.
   - incidence:    10,000 new cases/year in the U.S.
                   - since 1960, U.S. incidence of UC has been stable, but Crohn’s has increased 8-10x
                   - currently, incidence of ulcerative colitis and Crohn’s disease is equal in the U.S.
  - ethnicity:     more common in Jewish people

- genetics:        non-Mendelian inheritance
                   - 10-30% of patients with IBD have a positive family history of IBD
                   - stronger genetic association for Crohn’s than for ulcerative colitis

                   involved genes
                   - NOD2 (CARD15): susceptibility to fibrostenosing Crohn’s (chromosome 16)
                   - IL-23 receptor: associated with IBD (important role in activating inflammation)

- pathogenesis:    tissue damage secondary to inappropriate, ongoing immune response
                   involved cells known to originate outside the gut because:
                   - marrow transplant can cure IBD
                   - Crohn’s disease recurs in transplanted bowel

- properties:      Crohn’s disease and ulcerative colitis share the following properties:
                   - bowel inflammation
                   - no proven etiologic agent
                   - patterns of familial occurrence
                   - systemic manifestations

- treatment:       goals of therapy include:
                   - induce and maintain remission
                   - avoid toxicity from medications
                   - provide adequate quality of life

- clinical:        the most common disorders are ulcerative colitis and Crohn’s disease
                   - ulcerative colitis: affects the colon proximally from the rectum
                   - Crohn’s disease:    affects any part of the digestive tract (regional enteritis)

TABLE: Clinical Features of Inflammatory Bowel Disease (IBD)
                        ulcerative colitis                          Crohn colitis
  distribution          distribution continuous with rectum         segmental distribution
  rectal involvement    usually involves rectum (98%)               commonly involves rectum (80%) 1
  terminal ileum        ---                                         usually involves terminal ileum
  mucosa                diffuse involvement of mucosa               mucosa with ulcers, fissures, cobblestone
  serosa                ---                                         congested, thickened serosa
  fistulas              ---                                         fistulas
  pseudopolyps          pseudopolyps                                pseudopolyps
  strictures            ---                                         structures
  inflammation          diffuse mucosal, submucosal inflammation patchy, transmural inflammation
  ulceration            mucosal, submucosal ulcers                  deep ulcers
  crypt abscess         crypt abscesses                             crypt abscesses
  granulomata           ---                                         granulomata common (60%)
  fibrosis (serosal)    ---                                         serosal fibrosis common
  though previously believed otherwise, Crohn colitis commonly involves the rectum
                                                                            Infection & Immunity 2: Objectives (page 81 of 137)

4.     Explain the causes of pediatric gastrointestinal obstruction.

- common etiologies of pediatric gastrointestinal obstruction
   - omphalocele
   - gastroschisis
   - umbilical hernia
   - Meckel diverticulum
   - diaphragmatic hernia
   - esophageal atresia / tracheoesophageal fistula
   - hypertrophic pyloric stenosis
   - duodenal obstruction / stenosis
   - jejunoileal atresia
   - meconium ileus; rule out:
      - cystic fibrosis
      - Hirschsprung disease
      - hypothyroidism
   - malrotation / midgut volvulus
   - enteric duplications
   - intussusception
   - anorectal anomalies / imperforate anus
   - inguinal hernia

5.     Differentiate causes of upper vs. lower gastrointestinal bleeding.

- gastrointestinal bleeding: age-based differential diagnosis
   - newborns:         hemorrhagic gastritis / stress lesions
                       hemorrhagic disease of the newborn
                       anal fissure
                       swallowed maternal blood
                       necrotizing enterocolitis
                       Hirschsprung disease
                       midgut volvulus
                       cow’s milk protein allergy

     - children:        anal fissures
                        Mallory-Weiss tears
                        hemorrhagic gastritis / stress lesions
                        acid-peptic disease
                        portal hypertension and varices
                        Henoch-Schönlein purpura
                        hemolytic-uremic syndrome

- gastrointestinal bleeding: location-based differential diagnosis
   - upper GI:         neonatal conditions
                       - swallowed maternal blood
                       - hemorrhagic disease of the newborn
                       - hemorrhagic gastritis / stress lesions
                       acid/alkali disease
                       - esophagitis
                       - gastritis / duodenitis
                       - peptic ulcers
                       esophageal / gastric varices
                       Mallory-Weiss tear
                                                                             Infection & Immunity 2: Objectives (page 82 of 137)

                        swallowed blood (oropharyngeal)

     - lower GI:        anal fissure
                        - neonatal ischemia
                        - infection (bacterial, parasitic, viral [immunocompromised])
                        - allergic (cow’s milk protein, soy protein, eosinophilic gastroenteropathy)
                        inflammatory bowel disease
                        antibiotic-induced colitis
                        midgut volvulus
                        juvenile polyps and tumors
                        vascular malformations
                        Meckel diverticulum
                        duplication (enteric cysts)
                        nodular lymphoid hyperplasia
                        vascular abnormalities
                        - Henoch-Schönlein purpura
                        - hemolytic-uremic syndrome
                        - autoimmune vasculitis
                        - infectious vasculitis
                        - ischemia
                        foreign body

6.     Describe the treatment of pediatric constipation.

- constipation
   - pathophysiology: generally related to functional dysmotility or voluntary withholding
                      - often related to difficulty with toilet training or fear of defecation
                      - prolonged constipation may enlarge the rectal vault

     - symptoms:        failure to defecate
                        anorectal pain (often results in frequent, small defecations)
                        involuntary leakage (often with claims of no urge to defecate)

     - diagnosis
        - general:      usually diagnosed by history and physical
        - history:      toilet habits, toilet training, family history of constipation and IBS
        - physical:     muscle tone, rectal tone, abdominal contents, rectal contents
        - laboratory:   generally only necessary in atypical cases, Hirschsprung disease, or chronic disease

     - differential
        - functional:   functional constipation
                        painful defecation (fissure, trauma)
       - psychogenic: stool withholding
       - dietary:       breastfeeding
                        low fiber
       - anatomic:      Hirschsprung disease
                        intestinal pseudo-obstruction
                        anal atresia / stenosis
       - drugs:         narcotics
       - neuromuscular: hypotonia
                                                                             Infection & Immunity 2: Objectives (page 83 of 137)

                        spinal cord lesions
                        sacral malformations
       - metabolic:     cystic fibrosis
                        hypocalcemia / hypercalcemia
       - infectious:    typhoid fever

     - management
       - functional:    chronic behavioral therapy in addition to:
                        - malt extract / lactulose
                        - added fiber, stool softeners, cathartics (senna)
                        - enemas, renal cathartics
                        - oral / nasogastric electrolytes

       - Hirschsprung: surgery (endorectal pull-through)

Hematology and Oncology
                                                                                                             CHAPTER 16

1.     Explain the presentation and diagnosis of hematopoietic malignancy (e.g. acute lymphocytic leukemia /

- acute lymphocytic leukemia / lymphoma
   - disorder:       lymphocyte (T- and B-cell) cancer

     - etiology:        often idiopathic

     - epidemiology:    among childhood malignancies:
                        - acute lymphocytic leukemia:         80%
                        - acute myelocytic leukemia:          20%
                        - chronic myelocytic leukemia:        <1%

     - pathophysiology: acquired genetic abnormality in a marrow stem cell
                        - usually found in common myeloid precursor (CMP) or colony-forming unit (CFU)
                        - hematopoietic stem cell (HSC) generally normal; repopulation possible after chemotherapy

     - presentation
        - symptoms:     fever, fatigue, bone / joint pain, bleeding, anorexia, abdominal pain
        - signs:        hepatomegaly, anterior mediastinal mass
        - laboratory:   lymphocytosis, extensive peripheral blast cells, anemia, thrombocytopenia, infection

     - diagnosis
        - general:      suspected leukemia requires extensive evaluation
        - history:      detailed medical history, recent exposures, travel history
        - physical:     attention to petechiae, lymphadenopathy, hepatomegaly
        - laboratory:   diagnostic evaluation requires extensive laboratory testing
                        - heme:       CBC, PT, PTT, fibrinogen
                                                                              Infection & Immunity 2: Objectives (page 84 of 137)

                                      bone marrow aspirate
                         - FEN/GI:    chem 10, amylase, uric acid, BUN, bilirubin, LDH, LFT
                         - GU:        urinalysis
                         - I&I:       immunoglobulins, varicella titer, blood culture
                         - CV/resp:   chest x-ray, KUB, ultrasound
                         - CNS:       lumbar puncture

     - differential:     other possibilities may include:
                         - infection
                         - marrow failure
                         - marrow infiltration
                         - hemophagocytic syndrome
                         - anemia
                         - thrombocytopenia
                         - neutropenia
                         - hepatosplenomegaly

     - management
       - goal:           achieve remission by removal blasts, while preserving hematopoietic stem cells
       - methods:        chemotherapy
                         - induction:     initial extensive treatment, to cause clinical reduction of blasts
                         - consolidation: further repeat cycles while patient in remission, to prevent relapse
                         bone marrow transplant

     - prognosis:        most children achieve long term remission, most adults relapse

     - clinical:         chloromas are subcutaneous or periosteal tumor infiltrates found only in AML

2.     Describe the clinical features of common solid tumors (e.g. brain tumor, Wilms tumor).

- brain tumors
   - epidemiology:       most common solid tumor in U.S. children
      - prevalence:      2.5-3.6 per 100,000
      - gender:          boys > girls (1.2:1)
      - age:             median age of 6.5 at diagnosis

     - classification:   common brain tumors in children include:
                         - astrocytoma:       50%
                         - medulloblastoma: 20%
                         - ependymoma:        9%
                         - craniopharyngioma: 5%

     - diagnosis:        interference with normal function

     - management:       multiple modalities of treatment may be required
                         - surgery:        required in 80%
                         - radiation:      required in 60%
                         - chemotherapy: required in 40%

- neuroblastoma
   - epidemiology:       most frequent extracranial solid tumor in children
      - prevalence:      8% of childhood malignancy
      - age:             80% occur before age 5

     - pathophysiology: arise from sympathetic nervous system
                                                                          Infection & Immunity 2: Objectives (page 85 of 137)

  - presentation:     associated with several paraneoplastic syndromes based on location
                      - opsoclonus-myoclonus-myoclonic jerking and conjugate, shooting eye movements
                      - intractable secretory diarrhea, hypokalemia, dehydration

  - diagnosis:        bone marrow aspiration and biopsy
                      tumor mass biopsy
                      collection of urine for catecholamines
                      staging imaging (CT, MRI)

  - management:       chemotherapy, surgery
                      bone marrow transplant in selected patients

  - prognosis:        poor; unlike other solid tumors, 60-70% associated with metastasis at diagnosis

- Wilms tumor
  - epidemiology:     third most common solid tumor in children
     - prevalence:    7% of childhood malignancy
     - age:           80% occur before age 5

  - pathophysiology: arise from nephrogenic rests, which are persistent immature renal tissues

  - presentation:     abdominal mass, pain (usually unilateral)
                      enlarging mass (from hemorrhage into the tumor)

  - diagnosis:        often found incidentally during bathing or pediatrician examination

  - clinical:         frequently associated with WAGR syndrome
                      - Wilms tumor
                      - aniridia
                      - genitourinary abnormalities
                      - retardation
                      frequently associated with Beckwith-Wiedemann syndrome
                      - gigantism
                      - macroglossia

  BOX: Diagnostic Evaluation of Pediatric Solid Tumors
   A suspected solid tumor requires an extensive evaluation, including:

      • history
      • physical examination
      • BUN, LDH, total bilirubin, LFT, chem 10
      • PT, PTT, fibrinogen
      • varicella titer
      • imaging studies of the primary tumor
      • bone marrow aspirate
      • tumor markers

  TABLE: Epidemiology of Pediatric Solid Tumors
   tumor                        prevalence 1
   brain tumors                      75%
   • astrocytoma
                                                                           Infection & Immunity 2: Objectives (page 86 of 137)

       • medulloblastoma
       • ependymoma
       • craniopharyngioma
       neuroblastomas                         8%
       Wilms tumors                           7%
       bone tumors                            5%
       • osteosarcoma
       • Ewing sarcoma
       soft tissue tumors                     3%
       • sarcoma
       • rhabdomyosarcoma
       germ cell tumors                      <1%
       represents percentage of all solid tumors in children

3.     Develop the differential diagnosis for a patient with anemia.

- anemia
   - disorder:           quantitative deficiency of hemoglobin (>2 S.D. below mean)

     - presentation:     symptoms and signs differ with degree of anemia and acuteness of onset
                         - chronic: pallor, fatigue, headache, lightheadedness
                         - acute:   cardiovascular symptoms

     - diagnosis
        - history:       family history, dietary history, exposures, blood loss
        - physical:      pallor, CHF signs, jaundice, adenopathy, hepatosplenomegaly
        - laboratory:    CBC, peripheral smear, reticulocyte count
                         bilirubin, LDH, Coombs test

classification of anemia
- hemorrhagic anemia

- production anemia
   - microcytic:              iron deficiency
                              lead poisoning
                              5’ nucleotidase deficiency

     - macrocytic:            folate, B12 deficiency
                              Diamond-Blackfan anemia
                              myelodysplastic syndrome

     - normocytic:            viral suppression
                              transient erythroblastopenia of childhood
                              Diamond-Blackfan anemia
                              aplastic anemia
                              renal failure

- destruction anemia
   - intrinsic:               hemoglobinopathy
                              - sickle cell syndromes
                              - thalassemia
                              - other unstable hemoglobins
                                                                         Infection & Immunity 2: Objectives (page 87 of 137)

                           - hereditary spherocytosis
                           - hereditary elliptocytosis
                           - glucose 6-phosphate dehydrogenase (G6PD) deficiency
                           - pyruvate kinase deficiency
                           - glutathione reductase deficiency

  - extrinsic:             immune
                           - autoimmune (idiopathic, infection, drugs)
                           - ABO/Rh incompatibility
                           - microangiopathic (sepsis, DIC, HUS, TTP, prosthetic heart valve)
                           - hypersplenism

differential diagnosis of anemia
- microcytic anemia (MCV < 80 fL)
  - inherited:             α-thalassemia
                           Hb E disease
                           inherited sideroblastic anemia

  - acquired:              iron deficiency
                           anemia of chronic disease
                           lead poisoning

- normocytic anemia (MCV of 80-100 fL)
   - reticulocytosis:   acute blood loss

  - reticulocytopenia:     kidney disease
                           chronic disease
                           bone marrow disorder
                           mixed disorder
                           coexistent iron deficiency
                           vitamin B12 deficiency

- macrocytic anemia (MCV > 100 fL)
  - megaloblastic:      vitamin B12 deficiency
                        folate deficiency
                        orotic aciduria
                        Lesch-Nyhan syndrome

  - non-megaloblastic
     - reticulocytosis:    bleeding

    - reticulocytopenia:   liver disease
                                                                              Infection & Immunity 2: Objectives (page 88 of 137)

4.     List the age-appropriate differential diagnosis for pediatric patients presenting with neutropenia.

- neutropenia: differential diagnosis in pediatric patients
   - congenital:      Kostmann syndrome
                      Shwachman-Diamond syndrome
                      congenital benign neutropenia
                      cyclic neutropenia

     - acquired:              drug-induced
                              infection (suppression and destruction)

5.     Discuss common causes of lymphadenopathy.

- generalized lymphadenopathy: differential diagnosis in pediatric patients
   - bacterial infection:    pyogenic bacterial infection
                             typhoid fever

     - fungal infection:               histoplasmosis

     - viral infection:                EBV (infectious mononucleosis)

     - parasitic infection:            toxoplasmosis

     - inflammatory disease:           systemic lupus erythematosus (SLE)
                                       juvenile rheumatoid arthritis (JRA)
                                       serum sickness

     - neutrophil disorder:            chronic granulomatous disease
                                       leukocyte adhesion deficiency

     - storage disease:                Gaucher disease
                                       Niemann-Pick disease

     - malignancy:                     ALL
                                       acute myeloid leukemia
                                       Hodgkin lymphoma
                                       non-Hodgkin lymphoma
                                                                               Infection & Immunity 2: Objectives (page 89 of 137)


- localized lymphadenopathy: differential diagnosis in pediatric patients
   - occipital / postauricular: local scalp infection
                                roseola (HHV-6)

  - preauricular:               chlamydia

  - submaxillary / submental: dental caries / abscesses
                              bacterial gingivitis
                              herpes simplex stomatitis

  - cervical:                   viral infections
                                respiratory viruses
                                bacterial infections (URI, S. aureus, head and neck impetigo, TB, Mycobacteria)
                                parasitic (toxoplasma)
                                inflammatory (Kawasaki, sarcoidosis)
                                malignancy (Hodgkin disease, non-Hodgkin lymphoma, ALL, histiocytosis X

  - supraclavicular:            Hodgkin disease
                                non-Hodgkin lymphoma
                                metastatic solid tumors (rhabdomyosarcoma, carcinoma

  - axillary:                   arm infection (cellulitis, impetigo)
                                catscratch disease
                                rat bite fever
                                rheumatoid fever

  - epitrochlear:               infection of the forearm / hand (cellulitis)

  - mediastinal (radiographic): tuberculosis
                                Hodgkin disease
                                non-Hodgkin lymphoma
                                systemic lupus erythematosus

  - inguinal:                   lower extremity infections
                                STIs (lymphogranuloma venereum, chancroid, HSV, syphilis)

  - iliac:                      bacterial adenitis (S. pyogenes, S. aureus)
                                                                              Infection & Immunity 2: Objectives (page 90 of 137)


     - popliteal:                 distal infection

6.     List the clinical manifestations of bleeding disorders.

- acquired coagulation inhibitors
   - disorder:       acquired coagulopathy

     - etiology:         generation of coagulant-specific circulating antibodies (usually IgG)
                         - alloantibodies: factor replacement therapy for hemophiliacs
                         - autoantibodies: spontaneous appearance in elderly patients with no previous history
                                           frequently associated with factor VIII deficiency
                         most common in severe hemophiliacs (recognition of replaced factor as foreign)

     - diagnosis:        prolonged PT or PTT, with failure of correction in mixing studies

     - management:       porcine factor VIII
                         bypassing agent (e.g. recombinant factor VIIa)

- Bernard-Soulier syndrome
  - disorder:        primary hemostasis deficiency secondary to platelet defect

     - etiology:         congenital deficiency of Gp Ib (vWF receptor)

     - pathophysiology: insufficient vWF-dependent adhesion, problematic in arterial circulation

     - presentation:     mild thrombocytopenia, large circulating platelets

- diffuse endothelial injury
   - pathology:        insufficient inhibition of clotting

     - etiology:         causes include:
                         - malignant hypertension
                         - solid organ rejection
                         - bone marrow transplantation
                         - specific chemotherapy drugs
                         - vasculitis

     - management:       plasmapheresis (response to therapy is highly uncertain)

- disseminated intravascular coagulation (DIC)
   - disorder:       multiple effects of systemic thrombin, plasmin generation (bleeding and thrombotic)
                     - consumption of coagulation factors
                     - depletion of inhibitors
                     - microangiopathy (secondary to deposition of fibrin-rich clots in small vessels)
                     - bleeding
                     - various degrees of organ dysfunction

     - etiology:         syndrome (NOT a codable diagnosis) resulting from various underlying causes
                         - infection
                         - malignancies
                         - leukemia
                         - liver disease
                                                                          Infection & Immunity 2: Objectives (page 91 of 137)

                     - obstetric complications
                     - massive trauma
                     - surgery
                     - shock

  - pathophysiology: excessive thrombin and/or plasmin activity in systemic circulation
                     - systemic inflammatory response (activation of cytokines and coagulation)
                     - release of procoagulant material (i.e. tissue factor) into circulation

  - presentation:    may cause both bleeding or clotting symptoms

  - diagnosis:       thrombocytopenia
                     RBC fragmentation
                     prolonged PT, PTT
                     elevated FDP and D-dimer
                     decreased fibrinogen
                     depletion of antithrombin, α2-antiplasmin

  - management:      resolution of the underlying condition
                     consideration of FFP, platelet replacement (severe cases)

- drug-induced immune thrombocytopenia
   - disorder:     thrombocytopenia secondary to drug-induced destruction

  - etiology:        complication of certain drugs (penicillin, sulfonamides, quinine compounds)

  - pathophysiology: drug-dependent antibody-mediated destruction of platelets

  - diagnosis:       careful history is critical
                     - herbal remedies
                     - non-prescription medications
                     - foods (tonic water contains quinine
                     during evaluation of thrombocytopenia, all non-essential drugs should be stopped

- factor XI deficiency
   - disorder:        mild bleeding tendency

  - etiology:        inherited deficiency of factor XI (autosomal recessive)

  - epidemiology:    increased prevalence in Ashkenazi Jew population; similar symptoms found in families

  - presentation:    variable, may include:
                     - menorrhagia
                     - epistaxis
                     - post-partum bleeding
                     - hematuria

  - management:      administration of fresh frozen plasma (FFP) to bring XI to target levels of ~30-45%

  - clinical:        increased bleeding after ingestion of aspirin, surgery

- Glanzmann’s thrombasthenia
  - pathology:     primary hemostasis deficiency secondary to platelet defect
                                                                             Infection & Immunity 2: Objectives (page 92 of 137)

  - etiology:         congenital deficiency of Gp IIb/IIIa (fibrinogen receptor)

  - pathophysiology: insufficient platelet aggregation

  - diagnosis:        deficient platelet aggregation in response to multiple agonists

- hemolytic-uremic syndrome (HUS)
   - disorder:       clotting disorder (similar to TTP, but with dominant renal involvement)

  - etiology:         frequently related to enteropathogenic bacteria expressing Shiga toxin (e.g. E. coli 0157:H7)

  - pathophysiology: endothelial injury secondary to Shiga toxin

  - presentation:     bloody diarrhea
                      neurologic signs (seizures, change in mental status)
                      renal insufficiency

- hemophilia A and B
   - disorder:      insufficient clotting

  - etiology:         inherited deficiency of intrinsic tenase (X-linked recessive)
                      - hemophilia A: factor VIII deficiency (80-85% of congenital hemophilia)
                      - hemophilia B: factor IX deficiency

  - presentation:     based on severity of symptoms
                      - mild:      generally asymptomatic until challenged by specific trauma, surgery
                      - moderate: similar bleeding, frequently associated with minor trauma
                      - severe:    spontaneous joint and deep tissue bleeds

  - complications:    development of high titer inhibitors (antibodies against transfused clotting factor)
                      treatment-related blood-borne infections (HIV, hepatits)

  - management:       specific factor VIII or IX replacement
                      - purified from human plasma and subjected to viral inactivation techniques
                      - synthesized from recombinant DNA technology

- idiopathic (autoimmune) thrombocytopenic purpura (ITP)
   - disorder:       thrombocytopenia secondary to autoimmune platelet destruction

  - etiology:         autoimmune / idiopathic

  - pathophysiology: autoimmune destruction of platelets in presence of normal bone marrow production
                     - anti-platelet autoantibodies, often directed against Gp Ib or Gp IIb/IIIa complexes
                     - result in Fc-dependent splenic destruction (similar to extravascular hemolysis)

  - presentation:     acute form:       seen in children; frequently secondary to infection, and often self-limiting
                      chronic form:     seen in adults; spontaneous remission is unusual

  - diagnosis:        diagnosis of exclusion (absence of other causal conditions)

  - management:       guided by severity
                                                                           Infection & Immunity 2: Objectives (page 93 of 137)

                      - observation
                      - glucocorticoids
                      - intravenous immune globin (IVIG)
                      - splenectomy
                      - synthetic thrombopoietic growth factors

- liver disease
   - disorder:        acquired coagulopathy

  - etiology:         hepatitis; numerous other disorders

  - pathophysiology: decreased synthesis of coagulation factors (V, VII, IX, X, XI)

  - management:       FFP replacement causes temporary improvement
                      most do not respond to vitamin K replacement
                      local sites (gastritis, esophageal varices) may require specific treatment

  - clinical:         may be complicated by DIC, hyperfibrinolysis

- microangiopathic hemolytic anemia (MAHA)
  - disorder:       intravascular hemolysis

  - etiology:         various

  - pathophysiology: physical shearing of RBC

  - diagnosis:        symptoms of intravascular hemolysis
                      - RBC fragmentation (schistocytes)
                      - anemia
                      - elevated LDH
                      - elevated reticulocyte count

  - differential:     presence of coagulopathy:       disseminated intravascular coagulation (DIC)
                      absence of coagulopathy:        thrombotic thrombocytopenic purpura (TTP)
                                                      hemolytic-uremic syndrome (HUS)
                                                      diffuse endothelial injury (e.g. malignant HTM, vasculitis)

- non-thrombocytopenic purpura (vascular purpura)
   - increased transmural pressure
      - acute:        valsalva with coughing, vomiting
      - chronic:      venous stasis

  - decreased mechanical strength
     - inherited:   Ehlers-Danlos syndrome
     - acquired:    connective tissue or vessel defects (scurrvy, amyloid infiltration, glucocorticoids, aging)

  - endothelial damage
     - infection:    Ricketts, viral
     - trauma:       factitious purpura (usually involving suction device applied to the skin)
     - embolism:     cholesterol or fat
     - inflammation: serum sickness, vasculitis

- thrombotic thrombocytopenic purpura (TTP)
   - disorder:     clotting disorder

  - etiology:         severe deficiency (<5% activity) of vWF-cleaving protease
                                                                             Infection & Immunity 2: Objectives (page 94 of 137)

                      - commonly an acquired disease
                      - acute episodes triggered by infection, pregnancy, medications, other endothelial injury

  - pathophysiology: formation of ultra-large vWF multimers
                     - development of autoantibody inhibitors against vWF-cleaving protease (ADAMTS-13)
                     - predisposition to spontaneous platelet aggregation, deposition in small vessels

  - complications:    thrombocytopenia
                      neurologic signs (seizures, change in mental status)
                      renal insufficiency

  - management:       plasma exchange or plasma infusion (due to presence of vWF-cleaving protease in plasma)
                      steroids, other immunosuppressive therapy

- vitamin K deficiency
   - disorder:       acquired coagulopathy

  - etiology:         antibiotic therapy
                      nutritional deficiency
                      biliary obstruction (due to biliary salt necessity for proper vitamin K absorption)
                      malabsorption syndromes
                      ingestion of warfarin or related compounds

  - pathophysiology: vitamin K required for post-translational γ-carboxylation of Gla domain:
                     - proteases:      prothrombin, factors VII, IX, and X
                     - anticoagulants: protein C, protein S

  - presentation:     bleeding symptoms

  - diagnosis:        prolongation of PT, PTT (isolated PT prolongation is most common)

  - management:       oral or parenteral vitamin K
                      - begins replenishing coagulation factors in 24 hours
                      - 2-3 days required for maximal effects
                      administration of fresh frozen plasma with serious bleed at presentation

- von Willebrand disease (vWD)
   - disorder:       moderate bleeding tendency secondary to qualitative or quantitative vWF deficiency
                     - proportional decrease in vWF antigen, ristocetin cofactor activity, and factor VIII activity
                     - bleeding symptoms primarily result from diminished factor VIII (vWF is a carrier protein)

  - etiology:         type I: inherited quantitative deficiency (autosomal dominant)

  - presentation:     mucocutaneous bleeding
                      soft tissue/joint tissue bleeding

  - diagnosis:        bleeding symptoms
                      low vWF antigen (usually <20%)
                      positive family history

  - management:       mild quantitative deficiencies (Type I): desmopressin (vasopressin analog)
                      - stimulates release of endogenous vWF from endothelial cells
                      - exhibits tachyphylaxis, generally given every 12-24 hours in limited numbers
                                                                               Infection & Immunity 2: Objectives (page 95 of 137)

                         qualitative deficiencies (Type 2) or severe quantitative deficiencies (Type 3)
                         - replacement factor VIII preparations that contain factor VIII-vWF complex
                         - antifibrinolytic agents such as EACA (ε-aminocaproic acid)

     TABLE: Laboratory Abnormalities in Coagulopathies
                               PT                    PTT                    platelets              factor levels
       hemophilia A            normal                prolonged              normal                 VIII decreased
       hemophilia B            normal                prolonged              normal                 IX decreased
       factor VII deficiency prolonged               normal                 normal                 VII decreased
       vitamin K deficiency prolonged                prolonged              normal                 normal
       liver disease           prolonged             prolonged              normal                 decreased 1
       DIC                     prolonged             prolonged              decreased              decreased
       vWD                     normal                normal 2               normal 3               normal 4
       thrombocytopenia        normal                normal                 decreased              normal
       factor VII made in endothelial cells; levels not decreased in liver disease
       can be prolonged
       decreased in type IIB vWD
       VIII decreased in type III vWD

Allergy and Immunology
                                                                                                               CHAPTER 17

1.     Describe the clinical features of atopic dermatitis.
2.     List the differential diagnosis for atopic dermatitis.
3.     Explain the treatment strategies for atopic dermatitis and seasonal allergies.

- atopic dermatitis
   - epidemiology:       5-10% of children affected

     - diagnosis:        clinical evaluation, based on the following features:
                         - skin lesions that are pruritic, dry, scaly, and often erythematous
                         - skin lesions that have a typical distribution
                         - chronic relapsing course
                         - positive family medical history for atopic disease

     - differential:     other possibilities are usually characterized by the following features:
                         - seborrheic dermatitis:     usually begins on scalp and side of nose, with greasy lesions
                         - diaper dermatitis:         affects diaper area (usually spared in atopic dermatitis)
                         - contact dermatitis:        generally not chronic and recurring; related to exposure
                         - tinea:                     usually found in skin folds
                         - histiocytosis X:           generally hemorrhagic (petechia)
                         - psoriasis:                 raised plaques, sharply demarcated, irregular borders / scales
                                                      usually on scalp, knees, elbows, genitalia
                         - pyoderma:                  generally pustular
                         - scabies:                   usually in intertriginous areas, other family members affected
                                                                              Infection & Immunity 2: Objectives (page 96 of 137)

                       further possibilities include:
                       - immunodeficiency disorders (Wiskott-Aldrich, SCID, hyper-IgE syndrome)
                       - metabolic disorders (phenylketonuria, histidinemia)
                       - acrodermatitis enteropathica
                       - ectodermal dysplasia

  - management:        behavioral
                       - avoidance of irritants (soap, detergents, solvents, chemicals, wool / acrylic clothing)
                       - dress with loose-fitting clothes
                       - avoid overheating
                       - trim fingernails often
                       maintain skin hydration
                       - short baths / showers 1-3 times per day (do not limit bathing)
                       - use of lubricants (creams, mineral oil, petroleum jelly) to trap moisture
                       pharmacologic therapy
                       - corticosteroids:      decrease pruritus, reduce inflammation, cause vasoconstriction
                       - antihistamines:       reduce pruritus
                       - antiinflammatory: alternative agents include topical tacrolimus, pimecrolimus

              FIGURE: Atopic Dermatitis
              Atopic dermatitis is characterized by skin lesions that are pruritic, dry, scaly, and often erythematous.
              They have a typical distribution, and the disorder follows a chronic, relapsing course.

- allergic rhinitis
   - etiology:         can be seasonal or perennial
                       - seasonal: reactions to trees, grasses, weeds
                       - perennial: reactions to dust mite allergens, pet dander, mold spores

  - epidemiology:      10-20% of children affected

  - pathophysiology: IgE-mediated (type 1) mast cell release of allergic mediators
                     - early phase reactions: within 20 minutes of exposure
                     - late phase reactions:  6-12 hours after exposure

  - symptoms:          chronic recurrent sneezing
                       nasal congestion
                       pruritus of the nose, eyes, ears, and soft palate (the “allergic salute”)
                       clear rhinorrhea
                       post nasal drip
                       allergic shiners, Dennie-Morgan lines

  - diagnosis
     - history:        nature, frequency, seasonality, duration, location, intensity
     - physical:       allergic shiners (darkening of the lower eyelids from venous stasis)
                       Dennie-Morgan lines (creasing of the lower eyelids from intermittent edema)
                                                                                   Infection & Immunity 2: Objectives (page 97 of 137)

                         absence of digital clubbing
       - laboratory:     associated with eosinophilia
                         specific allergens can be identified by:
                         - skin testing
                         - RAST testing

     - differential:     upper respiratory viral infections
                         chronic sinusitis

     - complications:    sinusitis
                         nasal polyposis (mostly adults)
                         otitis media
                         allergic conjunctivitis

     - management:       environmental control measures (most effective for symptoms caused by indoor allergies)

                         mediator antagonists
                         - antihistamines:            control sneezing, nasal pruritus, rhinorrhea
                         - adrenergic agents:         control congestion
                         - anticholinergics:          control rhinorrhea
                         - leukotriene inhibitors:    treatment of asthma, with occasional use in allergic rhinitis

                         antiinflammatory agents
                         - topical corticosteroids: control inflammation, some symptoms (including congestion)
                         - cromolyn sodium:         control inflammation, virtually no side effects

                         - function:        alter allergen-specific T-cell responses to reduce cytokines (e.g. IL-4, IL-5)
                         - method:          subcutaneous administration of increasing doses of allergen
                         - adverse:         local swelling (common), anaphylaxis (rare)
                         - clinical:        efficacy confirmed in several studies
                                            may be tried if environmental controls, medical therapy are ineffective

4.     Describe common presentations of food allergy.

- IgE-mediated food allergy
   - pathophysiology: IgE-mediated (type 1) mast cell hypersensitivity reaction to allergic mediators
                      - protein antigens enter bloodstream, distribute to target organs
                      - antigens locally activate sensitized mast cells, producing symptoms

     - etiology:         common food antigens vary with age
                         - children: eggs, peanuts, milk, soy, wheat, fish
                         - adults:   nuts, peanuts, seafood, eggs, shellfish
                         many childhood allergies later disappear

     - epidemiology:     less than 2-5% of the general population

     - symptoms
        - cutaneous:       urticaria (hives), angioedema
                           generalized pruritus
                           atopic dermatitis
       - gastrointestinal: itching / edema of the mouth or tongue
                           nausea, vomiting, diarrhea
                           abdominal pain
       - respiratory:      rhinoconjunctivitis (itching, rhinorrhea, congestion)
                                                                           Infection & Immunity 2: Objectives (page 98 of 137)

                      stridor (hoarseness)
    - systemic:       anaphylaxis (multisystemic disorder characterized by hypotension)
    - neurologic:     migraine, seizure
                      feeling of “dread”
                      behavioral problems (public perception; this is NOT supported by controlled studies)

  - diagnosis
     - history:       reactions within 30 minutes of ingestion food
                      symptoms involve allergic target organ(s)
                      reactions are reproducible
    - physical:       exclude other causes
    - laboratory:     skin test / RAST:     detection of food-specific IgE
                      elimination diet:     exclude suspected food for 1-2 weeks, reevaluate
                      food challenge:       double-blinded, placebo-controlled (gold standard method)
                                            - time consuming, and can produce severe reactions
                                            - done under medical supervision, w/ preparations to treat anaphylaxis
                      GI clinic:            consultation if symptoms are still unexplained

  - management:       exclude offending food from diet
                      patient education
                      - emergency treatment (diphenhydramine, epinephrine, transport)
                      - reading of food labels
                      epinephrine for emergency treatment
                      consider Medic-Alert bracelet
                      periodic reassessment (children frequently become tolerant)

  - prognosis:        some allergies go away with time
                      - children tend to lose sensitivity, and absolute avoidance may hasten loss of allergy
                      - allergies to peanuts, “tree nuts,” and seafood tend to be lifelong

- anaphylaxis
   - pathophysiology: acute, systemic, severe allergic reaction
                      - occurs in both atopic and nonatopic individuals
                      - variable presentation based on differential release of mediators

  - etiology:         exposure to an allergen to which a susceptible person has become sensitized
                      - foods:          nuts, peanuts, milk, eggs, soy, seafood, wheat  (IgE-mediated)
                      - medication:     penicillin                                      (IgE-mediated)
                      - physical:       exercise, other strenuous work                  (non-IgE-mediated)

  - symptoms:         may include any of the following:
                      - urticaria, angioedema
                      - nausea, vomiting, diarrhea
                      - wheezing, shortness of breath
                      - arrhythmia
                      - hypotension (hallmark symptom)
                      - death

  - treatment:        epinephrine
                      - administration: aqueous epinephrine 0.01 mL/kg/dose IM (thigh) of 1:1000 dilution
                                        repeat as needed every 20-30 minutes, maximum 3 doses
                      - mechanism:      blood vessel constriction
                                        prevention of mast cell degranulation
                                        relaxation of airway smooth muscles
                                                                                Infection & Immunity 2: Objectives (page 99 of 137)

                         supportive care
                         - oxygen
                         - IV fluids

                         other medications
                         - glucocorticosteroids:        prevent late phase reaction
                         - H1 and H2 antihistamines:    prevent further reaction by blocking unaffected receptors
                         - pressors:                    used if response to epinephrine is lacking

     BOX: Treatment of Anaphylaxis
      Anaphylaxis is treated with IM epinephrine, 0.01 mL/kg/dose IM in a 1:1000 dilution, injected directly into the
       thigh. Know this or you fail medical school.

                                                                                                                CHAPTER 18

1.     Describe the pathophysiology and clinical features of cystic fibrosis.

  - definition:          cystic fibrosis transmembrane conductance regulator (CFTR)
     - size:             250,000 bases
     - location:         chromosome 7
  - function:            cAMP-dependent Cl- channel in apical membrane of epithelial cells
                         - sweat glands: passive resorption of Cl- (follows Na+)
                         - respiratory:      failure of Cl- secretion
     - clinical:         over 1000 described mutations
                         - mutations can result in altered function or decline in synthesis
                         - most common: ΔF508 (70% of mutations; in first nucleotide binding fold)

- cystic fibrosis
   - disorder:           defect in cAMP-dependent chloride channel (CFTR), leading to:
                         - pancreatic and GI dysfunction
                         - respiratory dysfunction
                         - reproductive dysfunction
                         - sweat gland abnormalities

     - etiology:         autosomal recessive genetic disorder

     - epidemiology:     most common disease affecting North American Caucasians
                         - incidence of 1 in 4000 live births
                         - carrier rate of 1 in 29

     - pathophysiology
        - respiratory: infection, chronic inflammatory response
                       - hyperinflation, increased incidence of reactive airway disease, localized bronchiectasis
                       - nasal polyps (15%) and sinusitis (93-100%)
                                                                            Infection & Immunity 2: Objectives (page 100 of 137)

    - GI:            obstruction of the GI tract (meconium ileus)
    - hepatobiliary: obstruction of ductules in the liver, hepatic duct, and gall bladder
    - pancreatic:    obstruction of pancreatic ducts by secretions and cellular debris
                     - inflammation, necrosis, and fibrosis
                     - decreased secretion of pancreatic enzymes and bicarbonate
                     - fat and vitamin (A, D, E, K) malabsorption, some protein malabsorption
    - skin:          decreased reabsorption of NaCl
    - reproductive: bilateral absence of the vas deferens, scarring, thickened cervical secretions

  - presentation
     - respiratory:  chronic cough, wheezing, pneumonia, sinusitis, bronchiectasis, polyps
                     chronic infection with P. aeruginosa, S. aureus
    - GI:            meconium ileus
    - hepatobiliary: jaundice, steatorrhea, rectal prolapse, failure to thrive, abdominal pain, portal hypertension
    - pancreatic:    greasy, oily, foul-smelling stool
    - skin:          non-specific irritating rash, dehydration (hyponatremic hypochloremic metabolic alkalosis)
    - reproductive: male infertility

  - diagnosis
     - history:        respiratory and GI symptoms
     - physical:       clubbing
     - laboratory:     cystic fibrosis mutation screening
                       sweat chloride test by quantitative pilocarpine iontophoresis
                       - sweat chloride < 30 mEq/L:              normal in a newborn
                       - sweat chloride < 40 mEq/L:              normal in a toddler or older individual
                       - sweat chloride 40-60 mEq/L:             borderline
                       - sweat chloride > 60 mEq/L:              abnormal; positive for cystic fibrosis

  - treatment
     - respiratory:    antibiotics, clearance, bronchodilators, corticosteroids, transplantation
     - pancreatic:     enzymes, fat-soluble vitamin supplementation, high calorie diet

presentation of cystic fibrosis
- respiratory signs and symptoms
   - chronic cough:             airway inflammation and thick secretions
   - wheezing:                  increased incidence of reactive airway disease
   - recurrent pneumonia:       lower respiratory infections due to colonization
   - sinusitis:                 Cl- channel defect in paranasal sinuses
   - nasal polyps:              etiology unknown
   - bronchiectasis:            abnormal dilation of small airways, leading to poor clearance of secretions
   - clubbing:                  rounded, abnormal appearance of fingernails and toenails

- gastrointestinal signs and symptoms
   - prolonged jaundice:                           Cl- channel defect in bile ducts
   - meconium ileus:                               can lead to intestinal perforation; pathognomic for CF
   - steatorrhea:                                  exocrine pancreatic insufficiency
   - rectal prolapse:                              fat in stool, poor muscle tone, increased abdominal pressure
   - failure to thrive:                            loss of calories in stool
   - recurrent abdominal pain:                     malabsorption of fat and protein
   - distal intestinal obstruction syndrome:       equivalent to meconium ileus
   - edema, hypoproteinemia, and anemia:           malabsorption of protein, hypoalbuminemia
   - portal hypertension:                          rare; due to Cl- channel defect in biliary tract

- presentation in children
                                                                           Infection & Immunity 2: Objectives (page 101 of 137)

     - positive family history
     - meconium ileus at birth
     - recurrent respiratory tract infections
     - malabsorptive stools
     - hyponatremic hypochloremic dehydration
     - rectal prolapse
     - failure to thrive

- presentation in adults
   - chronic sinusitis
   - nasal polyposis
   - recurrent respiratory tract infections
   - clubbing
   - malabsorptive stools
   - infertility

treatment of cystic fibrosis
- pulmonary disease
   - antibiotics:                 oral, IV, or nebulized (aminoglycosides)
   - airway clearance:            manual or electric percussor postural drainage
                                  positive expiratory pressure (PEP) valve by mask or mouthpiece
                                  flutter or acapella
                                  high frequency oscillatory chest compression (Vest therapy)
     - bronchodilators
     - mucolytics
     - anti-inflammatory agents
     - gene therapy
     - lung transplantation:      end stage disease intervention
                                  64-70% one year survival rate at experienced centers
                                  limited by availability, complications
                                  - rejection
                                  - obliterative bronchiolitis
                                  - immunosuppressive therapy complications

- pancreatic disease
   - pancreatic enzymes
   - fat-soluble vitamin supplements in water-soluble form
   - high calorie diet

2.     Explain the management strategies for asthma.

- asthma
   - disorder:          reversible obstructive lung disease

     - etiology:        numerous triggers including:
                        - allergic reactions
                        - infections
                        - exercise
                        - occupational
                        - medication
                        - circadian variation (night-time sleep)

     - epidemiology:    4-7% of the general population, with increasing incidence and general onset in childhood
                                                                          Infection & Immunity 2: Objectives (page 102 of 137)

  - pathophysiology: cell-mediated inflammatory cascade in response to stimulus, as mediated by:
                     - mast cells
                     - eosinophils
                     - macrophages
                     - neutrophils
                     - bronchial epithelial cells
                     - T-lymphocytes
                     - fibroblasts

                      general properties include:
                      - reversible airway obstruction
                      - hyperresponsiveness
                      - airway inflammation and remodeling

  - diagnosis
     - general:       clinical diagnosis
     - history:       cough, wheeze, shortness of breath, intermittent symptoms, family history
     - examination:   wheezing; more severe symptoms with severe disease
     - laboratory:    CBC, sputum allergen test, CXR, ECG
                      PFT showing obstruction, reversibility, hyperresponsiveness

  - differential:     COPD
                      lung cancer
                      pulmonary embolism
                      heart failure
                      recurrent aspiration
                      vocal cord dysfunction
                      muscle weakness

  - management:       modalities of therapy include:
                      - medication
                      - patient education
                      - removal of environmental risk factors
                      - treatment of underlying conditions

  - prognosis:        gradual, mild loss of function over time; more pronounced in smokers

  - clinical:         having normal lung function does not exclude asthma

management of asthma
- modalities of therapy
  - medications
    - bronchodilators
       - β-agonists: effective short term relief
       - theophylline: narrow therapeutic index, generally used in nocturnal asthma
       - ipratropium: can be added to or used in place of β-agonists in patients with:

    - anti-leukotrienes
       - zafirlukast: leukotriene receptor antagonist, good for mild persistent asthma
       - montelukast: leukotriene receptor antagonist, good for mild persistent asthma
                                                                              Infection & Immunity 2: Objectives (page 103 of 137)

       - antiinflammatory agents
          - corticosteroids: primary therapy for asthma patients with persistent symptoms
          - cromolyn:        mild antiinflammatory effect, not bronchodilation; minimally effective

     - environmental control
        - dust mite:    bedding encasements, wash weekly, limit stuffed animals, reduce humidity
        - pets (cat):   do not have them in the house; at minimum, not in the bedroom
        - cockroach:    remove as many food and water sources as possible
        - molds:        clean out sources of mold

     - patient education
        - disease processes
        - the role of different medications
        - inhaler technique
        - treatment plans
        - action plans for treatment of attacks
        - psychosocial support

     - treatment of underlying or associated conditions

     BOX: Treatment of Asthma
      The basic modalities of therapy in asthma include:

         • medication (bronchodilators, anti-leukotrienes, antiinflammatory agents)
         • environmental control
         • patient education
         • treatment of underlying or associated conditions

- medication plan
  - mild:                 quick relief (short-acting inhaled β2-agonist)

     - moderate:          daily long-term control
                          - anti-inflammatory: inhaled corticosteroid, cromolyn, or nedocromil
                          - consider:           long-acting bronchodilator (LABA, theophylline), leukotriene modifier

     - persistent:        daily long-term control
                          - anti-inflammatory: inhaled corticosteroid (consider increased dose)
                          - consider:           long-acting bronchodilator (LABA, theophylline), leukotriene modifier

     - severe:            daily long-term control
                          - inhaled corticosteroid
                          - LABA or SR theophylline
                          - may need oral corticosteroid

3.     List a differential diagnosis for wheezing.

- wheezing: differential diagnosis
  - anaphylaxis
  - aspergillosis
  - aspiration
                                                                        Infection & Immunity 2: Objectives (page 104 of 137)

     - asthma
     - bronchomalacia, tracheomalacia
     - cancer, carcinoid syndrome
     - chronic bronchitis
     - COPD
     - emphysema
     - foreign body
     - left ventricular failure
     - occupational asthma
     - polyarteritis nodosa
     - pulmonary edema
     - pulmonary eosinophilia
     - respiratory infection
        - bronchiectasis
        - bronchitis
        - common cold
        - croup
        - pneumonia
        - pulmonary aspergillosis
     - stridor

                                                                                                         CHAPTER 19

1.     Discuss the differential diagnosis of hypotonia in an infant.

- hypotonia
   - disorder:        diminished resistance to passive movement around a joint
   - pathophysiology: may result from:
                      - primary lesions of the CNS
                      - CNS abnormalities secondary to systemic disorders
   - diagnosis
      - history:      recent illness, onset / course, involvement, pregnancy history, family history
      - physical:     rule out systemic disorders, check for dysmorphic features, assess degree of involvement
      - laboratory:   goal-directed based on suspected causes
                      - Down syndrome:                  chromosomal studies
                      - hypothyroidism:                 thyroid studies
                      - cerebral lesion:                imaging studies (CT, MRI)
                      - seizure disorders:              EEG
                      - anterior horn cell disease:     genetic studies
                      - passive myasthenia gravis: edrophonium (Tensilon) test
                      - myopathy:                       electrodiagnostic studies, biopsy

     - differential
        - systemic:     chromosomal disorders (Down syndrome, Prader-Willi syndrome)
                        Ehlers-Danlos syndrome
                                                                            Infection & Immunity 2: Objectives (page 105 of 137)


       - cerebral:       hypoxic-ischemic encephalopathy (HIE)
                         intraventricular hemorrhage

       - anterior horn: infantile progressive spinal muscular atrophy type I (Werdnig-Hoffmann disease)

       - peripheral:     peripheral neuropathy

       - NMJ:            myasthenia gravis

       - myopathy:       myotonic dystrophy
                         congenital muscular dystrophy
                         mitochondrial encephalopathy

     - management:       supportive care meeting respiratory and nutritional requirements
                         specific therapy depending on diagnosis

2.     Describe the clinical features of epilepsy.

- epilepsy
   - disorder:        recurrent convulsive or nonconvulsive seizures
   - pathophysiology: abnormal synchronization of neuronal pool discharges
                      - generalized:     discharge from deep midline structures of the brain
                      - partial (focal): discharge in a localized area of the brain
                                         - simple:     consciousness not impaired
                                         - complex: consciousness impaired
   - diagnosis
      - history:      particularly important, as examiner often cannot witness seizure
      - physical:     assessment after seizure is completed, focusing on:
                      - features of focality, deep tendon reflex asymmetry
                      - mental status, cranial nerve function, funduscopy
                      - skin (neurocutaneous disorders such as neurofibromatosis, tuberous sclerosis)
                      - evidence of nonaccidental trauma
      - laboratory:   electroencephalogram (EEG)
                      routine blood studies only if a metabolic cause is suggested
                      neuroimaging only if:
                      - seizures are focal
                      - EEG interpretation suggests underlying focality
                      - seizures accompany a neurocutaneous disorder

     - differential:     psychogenic seizures
                         breath-holding spells
                         night terrors

     - management:       pharmacologic treatment based on type of seizure
                         - seizures will not result in brain damage
                         - medications may have to be changed frequently
                         - may be able to taper and stop medications after a 2 year seizure-free period

- nonepileptic paroxysmal events: clinical features
                                                                            Infection & Immunity 2: Objectives (page 106 of 137)

     - psychogenic seizures:      maintain consciousness
                                  normal EEG during attack
                                  no postictal behavior
                                  frequently combative during attack

     - breath-holding spells:     mainly between 1-2 years of age
                                  precipitating event before attack
                                  breath-holding after crying
                                  pallor or cyanosis, then limpness

     - syncope:                   usually follows emotional episode
                                  may have orthostatic hypotension
                                  normal EEG

     - night terrors:             paroxysmal sleep disturbance
                                  normal EEG during attacks

- seizure disorders: clinical features
   - generalized tonic-clonic: involvement of all extremities
                                 tonic, clonic components
                                 loss of consciousness
                                 postictal phase common

     - absence / petit mal:       last a few seconds
                                  no aura
                                  unusual body movement
                                  child unaware of occurrence
                                  EEG with 3 Hz spikes

     - juvenile myoclonic epilepsy: genetically determined
                                    generalized seizures with myoclonic jerking in the morning

     - complex partial:           blunted consciousness
                                  strange behavior and speech

     - simple partial:            localized motor or sensory symptoms
                                  no impairment of consciousness
                                  may become generalized

     - infantile spasms:          brief, sudden muscular contractions
                                  begin at 3-9 months of age
                                  associated with retardation

3.     List the age-appropriate differential diagnosis for pediatric patients presenting with each of the following
       symptoms: headache, seizures.

- seizures: differential diagnosis
   - systemic illness: febrile seizures
                        heat stroke
                        infection (tapeworms)

     - CNS conditions: eclampsia
                       meningitis / encephalitis
                       head trauma
                                                                      Infection & Immunity 2: Objectives (page 107 of 137)

                        brain tumor
                        cerebral hemorrhage

  - CV / respiratory: respiratory distress
                      breath-holding spells
                      whooping cough
                      myocardial infarction

  - gastrointestinal:   liver failure
                        kidney failure

  - metabolic:          hypoglycemia
                        Reye syndrome

  - substance:          drug / alcohol abuse and overdose
                        alcohol withdrawal (delirium tremens)

- headache: differential diagnosis
   - CNS:             vascular headache (migraine)
                      tension headache
                      brain tumor
                      head trauma
                      pseudotumor cerebri (signs / symptoms of elevated ICP, with no mass found)
                      subarachnoid hemorrhage
                      cerebrovascular accident
                      trigeminal neuralgia

  - HEENT:              glaucoma
                        eye strain

  - infection:          common cold
                        meningitis / encephalitis
                        ear infection
                        dental infections
                        sinus infection
                        sinus blockage
                        severe cough

  - lifestyle:          alcohol abuse / hangover
                        stress / tension
                        fatigue / tiredness
                        excessive smoking

  - iatrogenic:         spinal tap treatment

  - systemic:           hypertension
                        heat stroke
                                                                            Infection & Immunity 2: Objectives (page 108 of 137)

                        thyroid disease
                        kidney failure
                        lead poisoning / exposure

     - psychiatric:     psychogenic pain syndromes

                                                                                                             CHAPTER 20

1.     Generate an age-appropriate differential diagnosis and initial diagnostic and therapeutic plan for each
       patient presenting with the following: hematuria, proteinuria.

- hematuria
   - disorder:          blood in the urine
                        - macroscopic: causing a change to visual inspection
                        - microscopic: abnormal RBCs in the urine not causing change in color

     - pathogenesis:    glomerulonephritis secondary to:
                        - immunologic abnormalities
                        - coagulopathies
                        - biochemical defects
                        - direct toxic effects

     - presentation:    present in one of three ways:
                        - onset of gross hematuria
                        - onset of urinary or other symptoms with the incidental finding of microscopic hematuria
                        - incidental finding of microscopic hematuria during a health evaluation

     - diagnosis
        - history:      may be asymptomatic; otherwise may involve:
                        - renal:           hematuria, edema, hypertension (with or without oliguria)
                        - nonspecific:     fever, anorexia, weakness, headache
                        - extrarenal:      rash, joint involvement, GI bleeding, pleuritis
       - physical:      complete physical examination to rule out competing causes
       - laboratory:    urine dipstick
                        - negative:        rules out hematuria
                                           dark urine suggests foods, dyes, drugs, metabolites, crystals
                        - positive:        no RBCs suggests hemoglobinuria or myoglobinuria
                                           > 5 RBCs confirms hematuria
                        other diagnostic studies may include:
                        - ASO, C3, C4, ANA titers
                        - imaging studies (ultrasound, VCUG, radionucleotide, CT)
                        - renal biopsy

     - differential:    large differential diagnosis; can be remembered by ABCDEFGHI T
                                                                          Infection & Immunity 2: Objectives (page 109 of 137)

                      - anatomical                   (hydronephrosis, cystic disease)
                      - bladder / kidney infection   (UTI)
                      - coagulation / hematology     (sickle cell trait / disease, leukemia)
                      - drugs
                      - exercise
                      - familial hematuria           (Alport syndrome, thin basement membrane disease)
                      - glomerulonephritis
                      - HHU                          (hypercalciuria-hyperuricosuria-urolithiasis)
                      - interstitial nephritis
                      - trauma / tumor               (Wilms tumor)

  - management:       glomerulonephritis therapy depends on etiology, severity
                      - salt and water restriction
                      - dialysis
                      - steroids, cyclophosphamide (SLE)
                      - plasma exchange

- proteinuria
   - disorder:        protein in the urine

  - pathophysiology: predictor of progressive renal damage, both a marker and a cause
                     - hypoalbuminemia from loss of protein in the urine
                     - edema from loss of oncotic pressure
                     - hyperlipidemia from subsequent increase in lipoprotein synthesis, decreased breakdown

  - presentation:     frequently present with periocular swelling, often confused with allergy
                      other symptoms and signs include:
                      - ascites
                      - pleural effusion
                      - scrotal / labial edema

  - diagnosis
     - history:       careful history necessary, detailing:
                      - growth / development, polydipsia / polyuria, hearing loss, visual problems
                      - perinatal events, previous infections, bladder dysfunction
                      - medication history, family history
    - physical:       generally unremarkable, can be useful to distinguish nonrenal causes
    - laboratory:     initial evaluations
                      - urine dipstick
                      - protein : creatinine ratio, 24h urine collection
                      - urinalysis
                      further evaluation (when indicated)
                      - renal ultrasonography
                      - serum C3 and C4, ANA
                      - hepatitis B and C
                      - HIV testing

  - classification:   proteinuria classified by times in which it is observed
                      - transient proteinuria:    associated with fever, dehydration, stress, or exercise
                      - orthostatic proteinuria: generally benign, though may be an indicator of later disease
                      - persistent proteinuria: multiple proteinuria > 1+ by dipstick; requires investigation

  - differential (nephrotic syndrome)
     - primary:        minimal change nephrotic syndrome
                       focal and segmental glomerulosclerosis
                       membranous nephropathy
                                                                            Infection & Immunity 2: Objectives (page 110 of 137)

                        membranoproliferative glomerulonephritis
                        congenital nephrotic syndrome

       - secondary:     diabetes
                        systemic lupus erythematosus
                        HBV, HCV, syphilis, HIV, malaria
                        Alport syndrome
                        sickle cell disease
                        drug-induced nephrotic syndrome

     - management:      normal protein intake (elevated intake may worsen proteinuria, does not improve albumin)
                        pharmacologic therapy
                        - corticosteroids: drug of choice in childhood nephrotic syndrome
                        - ACE inhibitors: patients with steroid-resistant nephrotic syndrome
                        - IV albumin:      cases of severe edema
                        renal biopsy in nonresponsive disorder

     - complications:   increased risk of infection (loss of Ig)
                        thromboembolic events (hypercoagulability states)
                        growth retardation (corticosteroids)

     BOX: Nephrotic Syndrome
      The nephrotic syndrome can be remembered by the mnemonic PALE:

        • proteinuria            (generally ≥ 3.5 g/day)
        • hypoalbuminemia
        • hyperlipidemia         (elevated cholesterol and triglycerides)
        • edema

2.     Describe the treatment and workup for a child with a UTI.

- urinary tract infection (UTI)
   - disorder:         infection of the urinary tract

     - epidemiology:    common in children
                        - first months of life:     uncircumcised males at increased risk
                        - thereafter:               females at increased risk

     - etiology:        common organisms differ with age or situation
                        - general:     E. coli, Enterococcus, Staphylococcus, GBS
                        - adolescence: S. saprophyticus
                        - iatrogenic:  Pseudomonas, Candida, Corynebacterium, coagulase-negative Staph

     - pathophysiology: retrograde infection most common; hematogenous generally only in first 8-12 weeks of life
                        predisposing factors include:
                        - urinary tract obstruction
                        - vesicoureteral reflux
                        - nephrogenic bladder
                        - urolithiasis
                        - presence of foreskin
                                                                             Infection & Immunity 2: Objectives (page 111 of 137)

                          - voiding dysfunction
                          - constipation
                          - sexual abuse
                          - sexual intercourse
                          - uroepithelial deficiency with increased bacterial adherence
                          - antibiotic therapy
                          - poor personal hygiene

     - presentation:      signs and symptoms differ with age
                          - young children:    fever, dyspareunia, frequency, hematuria, GI symptoms, poor growth
                          - old children:      frequency, urgency, pain on urination
                                               fever, chills, malaise, flank pain, new onset enuresis

     - diagnosis
        - history:        consider UTI in any child younger than age 2 with unexplained fever
        - physical:       assess degree of illness, rule out sepsis / meningitis
                          - vital signs
                          - CVA tenderness, flank or abdominal mass or tenderness, palpable bladder
                          - genitalia for signs of trauma or infection
       - laboratory:      urinalysis and culture
                          - clean catch when possible, catheterization when appropriate or contamination suspected
                          - evaluate leukocyte esterase, nitrite, urine microscopy
                          imaging for urologic abnormalities
                          - renal ultrasound
                          - voiding cystourethrogram (VCUG)
                          - renal vascular conductance (RVC)
                          - nuclear renal scan (DPTA)
                          - renal cortical scintigraphy (99mTc-labeled DMSA)
                          - CT / MRI

     - differential:      asymptomatic bactiuria

     - management:        antibiotic therapy (cephalosporin, TMP/SMX, amoxicillin)
                          prophylactic antibiotics
                          • < 2 months:      cephalexin, amoxicillin
                          • ≥ 2 months:      TMP/SMX, nitrofurantoin
                          surgical reimplantation in severe vesicoureteral reflux (VUR)

     - clinical:          VCUG, renal ultrasound in any girl younger than 5, or any boy, with febrile UTI

     BOX: Urine Culture Diagnostic Criteria
      Positive criteria for urine culture vary with the method by which urine was obtained.

         • clean-voided method:                 > 100,000 cfu/mL
         • indwelling catheter:                 > 10,000 cfu/mL
         • single (straight) catheterization:   > 1,000 cfu/mL
         • aseptic methods:                     presence of any bacteria

3.     List a differential diagnosis for nephritic syndrome in a child.

- nephritic syndrome
   - disorder:       hematuria associated with other features, including
                                                                           Infection & Immunity 2: Objectives (page 112 of 137)

                          - proteinuria
                          - azotemia
                          - RBC casts
                          - oliguria / anuria
                          - hypertension

     - differential
        - focal:          IgA nephropathy
                          chronic liver failure
                          celiac sprue
                          dermatitis herpetiformis
                          Henoch-Schönlein purpura
                          Alport syndrome
       - diffuse:         focal glomerulosclerosis
                          membranoproliferative glomerulonephritis
                          - malaria
                          - HBV, HCV, chronic infection
                          - sickle cell disease
                          - SLE
                          - hemolytic uremic syndrome
                          rapidly progressing glomerulonephritis

     BOX: Nephritic syndrome
      Features of the nephritic syndrome can be remembered by the mnemonic PHARAOH:

         • proteinuria
         • hematuria
         • azotemia
         • RBC casts
         • oliguria
         • anuria
         • hypertension

                                                                                                            CHAPTER 21

1.     Discuss the presentation, workup, and treatment of JRA.

- juvenile rheumatoid arthritis (JRA)
   - disorder:       inflammatory arthritis of children

     - epidemiology:      most common rheumatic disease in children in the United States
        - prevalence:     140-180 per 100,000 children
        - age:            onset after age 8 months, before age 16 years
                                                                        Infection & Immunity 2: Objectives (page 113 of 137)

- pathophysiology: classified into four types based on early clinical features
                   - pauciarticular JA
                   - polyarticular JA
                   - systemic JA
                   - spondyloarthropathy

- diagnosis
   - history:       consider age, developmental level in descriptions of symptoms

  - physical:       document number, severity of involved joints
                    examine for nonarticular pathology
                    - fever, rash
                    - pneumonitis, pericarditis
                    - hepatosplenomegaly, lymphadenopathy, coagulopathy
                    - tachycardia, tachypnea, irritability
                    look for signs of inflammatory damage
                    - anterior uveitis: inflammation of the middle layer of the eye (uvea)
                    - synechia:         irregular pupillary margins

  - laboratory:     no specific confirmatory tests, but some tests useful for evaluation
                    - autoantibodies (ANA, rheumatoid factor)
                    - synovial fluid analysis (esp. if joint infection being considered)
                    - imaging studies (assess severity of synovitis, cartilage involvement)

- differential
   - trauma:        direct trauma (can rule out with history and lab findings)
   - infection:     acute rheumatic fever
                    lyme arthritis
  - neoplasm:       leukemia (20% present with bone pain)

- management:       first and second line therapy
                    - NSAIDs
                    - methotrexate, low dose         (persistent synovitis, radiologic evidence of joint damage)
                    - intraarticular corticosteroids (persistent synovitis ≥ 3-6 months)
                    - sulfasalazine                  (spondyloarthropathy)

                    refractory disease
                    - methotrexate, weekly
                    - systemic corticosteroids
                    - TNF inhibitors                (etanercept, infliximab)
                    - immunosuppressive agents      (azathioprine, cyclosporin A, cyclophosphamide)
                    - IV immune globulin            (systemic manifestations)
                    - surgery                       (uncontrolled joint damage)

                    TABLE: Indications for Corticosteroid Therapy in JRA
                     therapy             indication
                     high dose systemic  • symptomatic pericarditis, pneumonitis, cerebritis
                                         • coagulopathy
                                         • macrophage activation syndrome
                                         • severe uveitis unresponsive to topical therapy
                     low dose systemic   • significant anorexia
                                         • failure to thrive
                                         • pain, joint limitations limiting quality of life
                     local therapy       • uveitis
                                         • persistent synovitis in ≤ 3 joints
                                                                             Infection & Immunity 2: Objectives (page 114 of 137)

     - prognosis:       depends on classification
                        - pauciarticular:            generally good, though blindness / joint damage can ensue in some
                        - polyarticular:             after 15 years, 15% significantly disabled
                        - systemic:                  after 15 years, 15% significantly disabled
                        - spondyloarthropathy:       variable, may develop into ankylosing spondylitis

     TABLE: Clinical Presentation of Juvenile Arthritis
                        pauciarticular          polyarticular               systemic                   spondyloarthropathy
      joint pattern     large joints            small and large             polyarticular              large joints
                        asymmetric              symmetric                   oligoarticular             lower extremity
                        lower extremity                                                                enthesitis
      extraarticular    ---                     constitutional              high fevers                psoriasis
                                                                            salmon macular rash        uveitis
                                                                            hepatomegaly               urethritis
                                                                            splenomegaly               keratoderma
                                                                            adenopathy                 blenorrhagica
                                                                            anemia                     IBD
      uveitis             20-30%                    20-30%                  rare                       common
      • WBC count         normal                    8,000-15,000            15,000-30,000              8,000-15,000
      • hemoglobin        normal                    10-12                   6-10                       normal
      • ESR               5-40                      20-80                   50-150                     5-60
      • ANA               60%                       40-50%                  < 10%                      < 10%
      • RF                negative                  20% (usually older)     negative                   rare

2.     List the diagnostic features of Kawasaki disease (see chapter 13).

- Kawasaki disease
  - disorder:      generalized vasculitis of unknown etiology

     - epidemiology:    endemic and epidemic patterns
        - prevalence:   9 per 100,000 in the United States
        - age:          80% of cases in children younger than 8
        - ethnicity:    more prevalent in children of Asian ancestry

     - pathophysiology: one of the most common cause of acquired heart disease in children
                        four pathologic stages
                        - stage 1:   acute vasculitis, coronary involvement; pancarditis (first 2 weeks)
                        - stage 2:   persistent coronary vasculitis, coronary aneurisms   (2-4 weeks)
                        - stage 3:   coronary inflammation begins to subside              (4-8 weeks)
                        - stage 4:   scar formation, calcification, stenosis              (> 8 weeks)

     - diagnosis
        - general:      clinical diagnosis based on 5 criteria (must have fever, 4 of 5 remaining criteria)
        - history:      three phases
                        - acute:      skin, mucous membrane manifestations
                        - subacute: mild clinical disease, thrombocytosis, development of coronary aneurisms
                        - chronic: resolution of symptoms and laboratory abnormalities
       - physical:      careful cardiac examination
                                                                          Infection & Immunity 2: Objectives (page 115 of 137)

       - laboratory:    multiple modalities
                        - CBC:                 elevated WBC count, mild anemia
                        - urinalysis:          sterile pyuria, proteinuria
                        - ECG:                 prolonged PR or QT intervals, ST-T wave changes, dysrhythmia
                        - echocardiogram:      aneurisms; may need to repeat at 6-8 weeks

     - differential:    infectious diseases
                        - measles
                        - scarlet fever
                        - staphylococcal scalded skin syndrome
                        - Rocky Mountain spotted fever
                        allergic drug reactions
                        Stevens-Johnson syndrome
                        juvenile rheumatoid arthritis
                        mercury poisoning

     - management:
       - acute phase:   reduce inflammation, prevent development of coronary artery aneurisms
                        - IVIG
                        - aspirin
                        - heparin / warfarin

       - chronic phase: depends on assessment of patient’s risk
                        - follow-up ECG, echocardiograms at 6-12 month intervals
                        - coronary angiography
                        - exercise stress testing

     BOX: Diagnostic Criteria of Kawasaki Disease
      Diagnosis of Kawasaki disease is criteria-based. Making the diagnosis requires fever and 4 of 5 criteria, which
        may be remembered by the following mnemonic:

         “Be careful when riding a Kawasaki motorcycle; you might get creamed.”

         • conjunctivitis        (non-exudative)
         • rash                  (polymorphous non-vesicular)
         • edema / erythema      (involving hands or feet)
         • adenopathy            (cervical, often unilateral)
         • mucosal involvement   (erythema or fissures or crusting)

3.     Describe the diagnosis and treatment of lupus.

- systemic lupus erythematosus (SLE)
   - disorder:       systemic connective tissue disease characterized by:
                     - autoimmune destruction of tissues
                     - association of serum antibodies

                        may affect any organ system, but most commonly affects:
                        - joints
                        - skin
                        - kidneys
                                                                        Infection & Immunity 2: Objectives (page 116 of 137)

                   - lungs
                   - nervous system
                   - serosal membranes
                   generally characterized by relapses and remissions

- etiology:        unknown

- epidemiology:    disease of young females
   - incidence:    2-8 per 100,000 people
   - prevalence:   40-60 per 100,000 people
   - race:         higher in African Americans
   - gender:       female >> male (85% female, 15% male)
   - age:          higher in younger (premenopausal) women

- pathophysiology: immune complex-mediated autoimmune disease
                   - production of high avidity IgG autoantibodies
                   - triggers may be infectious, environmental, or hormonal

                   tissue destruction secondary to activation of the inflammatory cascade
                   - B cell hyperactivity:    results in production of copious Ig immune complexes
                                              - secondary to elevated cytokines (IL-6, IL-10)
                                              - B cell downregulation is inadequate
                   - T cell hyperactivity:    results in T cell-mediated tissue destruction
                                              - total number of T cells is decreased
                                              - T cell downregulation is inadequate

- presentation:    extensive variability in clinical manifestations (see below)

- diagnosis:       requires at least 4 of 11 criteria, either simultaneous or serial (MD SOAP BRAIN):
                   - malar rash
                   - discoid rash
                   - serositis
                   - oral ulcers
                   - arthritis
                   - photosensitivity
                   - blood (hematologic) disorder
                   - renal disorder
                   - antinuclear antibody (ANA)
                   - immunologic disorder
                   - neurologic disorder

                   associated with numerous antibody abnormalities

                   TABLE: Autoantibody Antigens in Lupus
                                           SLE           drug-induced LE
                    native DNA             40%                  ---
                    denatured DNA          70%               75-80%
                    histones               70%                >95%
                    SM antigen             30%                  ---
                    nuclear RNP            30%                  ---
                    ribosomal RNP          10%                  ---
                    SS-A/Ro                35%                  ---
                    SS-B/La                15%                  ---

- management
                                                                            Infection & Immunity 2: Objectives (page 117 of 137)

    - general:        patient education regarding disease manifestations
                      frequent visits (monthly) during active disease
                      - examination: mucosal ulcers, hair loss, skin defects, pleuropericarditis
                      - laboratory:     CBC, creatinine
                      - immunology: complement, dsDNA antibodies

    - mild:           rashes, arthralgias, leukopenia, anemia, arthritis, fever, fatigue
                      - NSAIDs
                      - prednisone, low dose
                      - hydroxychloroquine
                      - rest, exercise, sun block

    - moderate:       mild disease + mild organ system involvement
                      - NSAIDs
                      - hydroxychloroquine
                      - methotrexate, low dose
                      - mycophenolate mofetil, azathioprine, cyclosporine

    - severe:         life-threatening organ system involvement
                      - corticosteroids, high dose
                      - cyclophosphamide, high dose
                      - plasma exchange

  BOX: Diagnostic Criteria of Systemic Lupus Erythematosus
   Diagnosis of systemic lupus erythematosus (SLE)
     requires physician documentation of at least 4 of 11
     criteria, either simultaneously or serially:

     • malar rash
     • discoid rash
     • serositis (pleuritis, pericarditis)
     • oral ulcers
     • arthritis
     • photosensitivity
     • blood disorder
     • renal disorder
     • antinuclear antibody (ANA)
     • immunologic disorder
     • neurologic disorder (psych, seizures)

   These symptoms can be remembered using the
     mnemonic “MD SOAP BRAIN.” They can be
     promptly forgotten after the exam.

- clinical manifestations of SLE
   - cutaneous:        malar rash
                       discoid lesions
                       subacute cutaneous rash
                       Raynaud’s phenomenon
                                                                            Infection & Immunity 2: Objectives (page 118 of 137)

                        livedo reticularis (diffuse, blanching, fishnet pattern, associated with APLA)
                        bullous, erythematous patches on knuckles of fingers (rare)

     - mucosal:         mucosal ulcers (painless, punched out, erythematous)

     - musculoskeletal: joint inflammation
                        Jaccoud’s arthropathy (painless reversible subluxation)
                        myosis (rare)

     - pulmonary:       pleuritis
                        interstitial lung disease
                        pulmonary hemorrhage
                        reactive airways
                        pulmonary hypertension

     - cardiac:         pericarditis
                        conduction defects
                        myocardial involvement (patchy fibrosis, minimal inflammation, Ig deposits, possible CHF)

     - renal:           glomerulonephritis
                        - mesangial lupus nephritis
                        - mild focal glomerulonephritis
                        - diffuse proliferative glomerulonephritis
                        - membranous glomerulonephritis
                        - interstitial / tubular nephritis

     - neurologic:      CNS involvement
                        - psychiatric disorders (delirium, psychosis, affective disorders)
                        - cognitive disorders
                        - seizure
                        - stroke
                        - myelopathy (rare)
                        - meningitis (rare)
                        PNS involvement
                        - cranial neuropathy
                        - peripheral neuropathy

     - hematologic:     various blood disorders
                        - anemia              (50-75%)
                        - leukopenia          (75%)
                        - thrombocytopenia (15-25%)
                        - leukocytosis        (less common)
                        - thrombocytosis      (less common)

                                                                                                             CHAPTER 22

1.     Define the common primary skin lesions (macule, papule, plaque, nodule, vesicle, bulla, pustule).
                                                                         Infection & Immunity 2: Objectives (page 119 of 137)

- common primary skin lesions
   - macule:         circumscribed, flat, nonpalpable discoloration of size < 1 cm
   - papule:         superficial elevated solid lesion of size < 1 cm
   - patch:          circumscribed, flat, nonpalpable discoloration of size > 1 cm
   - plaque:         superficial elevated solid lesion of size > 1 cm
   - nodule / tumor: raised solid lesion with indistinct borders and a deep palpable portion, size > 1 cm
                     - subcutaneous: skin moves freely over nodule
                     - dermal:          skin does not move over nodule
   - vesicle:        circumscribed collection of free fluid, size < 1 cm
   - bulla:          circumscribed collection of free fluid, size > 1 cm
   - cyst:           raised lesion containing a palpable sac filled with liquid or semisolid material
   - pustule:        vesicle containing pus
   - wheal:          tense, edematous, transitory plaque secondary to extravasation into the dermis

             FIGURE: Primary Skin Lesions

- common secondary skin lesions
   - scale:           epidermal thickening
   - crust:           dried serum
   - fissure:         crack or split
   - erosion:         loss of epidermis (superficial)
   - ulcer:           loss of epidermis and dermis (deeper)
   - lichenification: thickening (especially epidermis) with skin line accentuation
   - scar:            thickening, fibrous tissue
   - atrophy:         loss of substance (thinning)
   - excoriation:     linear erosion

             FIGURE: Secondary Skin Lesions
                                                                        Infection & Immunity 2: Objectives (page 120 of 137)

2.   List the common rashes of infancy.

- erythema toxicum
   - disorder:        common benign rash of newborns
   - etiology:        idiopathic
   - morphology:      erythematous papules / pustules associated with multiple erythematous macules
   - location:        commonly on face, trunk, proximal extremities
   - management:      self-limiting, will resolve within several weeks

             FIGURE: Erythema Toxicum

- transient neonatal pustular melanosis
   - disorder:        common benign rash of newborns
   - etiology:        idiopathic
   - morphology:      vesicles, superficial pustules, and pigmented macules
   - location:        commonly on face, palms, and soles
   - management:      self-limiting

             FIGURE: Transient Neonatal Pustular Melanosis

- stork bite lesion
   - disorder:        benign vascular birthmark
   - etiology:        blood vessel malformation
   - morphology:      flat, vascular lesion
   - location:        nape of neck
   - management:      observation, laser therapy
                                                                       Infection & Immunity 2: Objectives (page 121 of 137)

             FIGURE: Stork Bite Lesion

- port wine stain
   - disorder:      benign vascular birthmark
   - etiology:      blood vessel malformation
   - morphology:    darker, red blue, flat vascular lesions
   - location:      often seen on the head
   - management:    observation, laser therapy

             FIGURE: Port Wine Stain

- hemangioma
   - disorder:      vascular birthmark
   - etiology:      blood vessel malformation and proliferation of endothelial cells
   - morphology:    raised vascular lesion
                    - enlarge in first 6-9 months of life, begin to flatten
                    - most flatten to skin level prior to 10 years of age
  - location:       nonspecific
  - management:     observation, laser therapy
                    - more aggressive treatment required with obscured vision or airway
                    - may require antibiotic therapy (commonly against S. aureus) if they ulcerate
                                                                              Infection & Immunity 2: Objectives (page 122 of 137)

                 FIGURE: Hemangioma

- diaper dermatitis
   - disorder:          rash of the diaper region
   - etiology:          secondary to combined effects of:
                        - skin wetness
                        - pH elevation of the diaper-covered skin (urease activation)
                        - friction of the diaper against the skin
  - morphology:         large erythematous patch, sometimes with peripheral erythematous red papules
  - location:           diaper region
                        - contact dermatitis: frequently avoids skin folds
                        - candidiasis:           located in skin folds, associated with peripheral papules
  - management:         topical lubricants, topical corticosteroids, topical antifungal agents (e.g. nystatin)

                 FIGURE: Diaper Dermatitis (Candida)

- acne
   - disorder:          common pediatric rash
                        - generally seen with onset several years prior to adolescence
                        - occasionally seen in infants at age 2-6 weeks
  - etiology:           obstruction of sebaceous follicles leading to infection and inflammation
  - morphology:         blackheads, papules, and pustules
  - location:           face, upper chest, upper back
  - management:         treatment depends on severity
                        - mild:       peroxide, topical retinoic acid
                        - moderate: peroxide, topical retinoic acid, topical / oral antibiotics
                        - severe:     topical retinoic acid, referral to dermatologist
                        not affected by diet or scrubbing
                                                                          Infection & Immunity 2: Objectives (page 123 of 137)

             FIGURE: Neonatal Acne

- atopic dermatitis (eczema)
   - disorder:        pruritic, excoriating rash of allergic origin
   - etiology:        allergic
   - morphology:      excoriated lesions
   - location:        face and other body sites
   - differential:    differentiate from contact dermatitis and scabies
                      - contact dermatitis: history of exposure to poison ivy or oak; initial vesicular lesions
                      - scabies:              worse in hands and feet, often seen in other family members
   - management:      environmental controls, skin hydration, topical corticosteroids

             FIGURE: Atopic Dermatitis

- seborrheic dermatitis
   - disorder:       scale rash of physiologic origin
   - etiology:       physiologic overproduction of sebum
   - morphology:     greasy scale on a base of erythema
   - location:       sebum-producing areas of scalp, face, and trunk
   - management:     mineral oil prior to washing hair; topical steroids
   - clinical:       cradle cap: seborrheic dermatitis involving scalp of infants

             FIGURE: Seborrheic Dermatitis
                                                                           Infection & Immunity 2: Objectives (page 124 of 137)

- psoriasis
   - disorder:        patchy rash secondary to inflammation and excessive skin production
   - etiology:        may occur secondary to streptococcal infection
   - epidemiology:    uncommon in children
   - morphology:      guttate lesions (small papules 2-4 mm in size)
   - location:        central trunk with extension to proximal, then distal extremities
   - management:      topical steroids, topical tar preparation, topical vitamin D analog, UV light therapy

             FIGURE: Guttate Psoriasis

- pityriasis rosea
   - disorder:        common “pine tree” skin condition seen in children and adolescents
   - etiology:        idiopathic
   - morphology:      small, oval-shaped erythematous papules and plaques with scale
   - location:        seen on back parallel to lines of skin stress, giving a “pine tree” appearance
   - management:      self-limiting in 6-10 weeks; topical steroid or moistures if symptomatic

             FIGURE: Pityriasis Rosea

- urticaria (hives)
   - disorder:        allergic reaction forming raised skin welts
   - etiology:        allergic response to insect bites, infection, drugs, food, cold, trauma, heat, or exercise
   - morphology:      central wheal with surrounding flare of erythema
   - location:        non-specific
   - management:      avoidance of causative agent; antihistamines
                                                                      Infection & Immunity 2: Objectives (page 125 of 137)

            FIGURE: Urticaria (Hives)

- palpable purpura
   - disorder:       purpura secondary to small vessel inflammation
   - etiology:       inflammation and bleeding of small skin vessels; may be bacterial or viral in origin
   - morphology:     erythematous, non-blanching papules
   - location:       nonspecific
   - management:     may signal severe disease (e.g. Henoch-Schönlein purpura) and should be investigated

            FIGURE: Palpable Purpura

- vitiligo
   - disorder:       autoimmune depigmentation
   - etiology:       autoimmune destruction of melanocytes
   - morphology:     localized areas of absence of pigmentation, with sharp demarcation from surrounding skin
   - location:       generally symmetrical involvement of arms, legs, or trunk
   - management:     potent topical steroids, UV therapy; difficult to treat adequately
                                                                        Infection & Immunity 2: Objectives (page 126 of 137)

              FIGURE: Vitiligo

- alopecia areata
   - disorder:       acute hair loss
   - etiology:       autoimmune destruction of hair follicles
   - morphology:     complete hair loss in a local area
   - location:       usually on the scalp
   - differential:   tinea capitis (would give positive fungal smear)
   - management:     spontaneous regrowth in 95% of cases; steroids, contact sensitization helpful

              FIGURE: Alopecia Areata

- nevi
   - disorder:       pigmented lesion of the skin
   - etiology:       sun-induced
   - morphology:     brown to tan macules
   - location:       sun-exposed areas
   - differential:   melanoma (ABCD)
   - management:     basic sun protection
                     - keep infants < 6 months of age out of direct sunlight
                     - use minimum SPF 15 sunscreen for infants and children > 6 months of age
                     - wear protective clothing
                     - avoid sun exposure between 10 a.m. and 4 p.m.
                                                                          Infection & Immunity 2: Objectives (page 127 of 137)

               FIGURE: Dysplastic Nevus

     BOX: Melanoma
      The features concerning for malignant melanoma can be remembered by the mnemonic ABCD:

        • asymmetry
        • border irregularity
        • color variation
        • diameter > 6 mm

3.    Describe childhood infections commonly associated with rash.

- bacterial infections
   - etiology:         cuts and injuries secondarily infected with S. aureus or S. pyogenes
   - morphology:       may manifest as:
                       - small fluid-filled vesicles that rupture easily
                       - erosions developing a honey-colored thick crust
   - location:         areas of previous injury
   - management:       topical mupirocin, oral antistaphylococcal antibiotics

               FIGURE: Scarlet Fever
                                                                          Infection & Immunity 2: Objectives (page 128 of 137)

- fungal infections
   - etiology:        frequently secondary to Candida albicans
   - morphology:      localized erythematous plaques with scale
   - location:        named based on location of rash
                      - tinea corporis: infected skin
                      - tinea capitis:   infected scalp
  - management:       topical antifungal agents, close follow-up

             FIGURE: Tinea Corpora

- scabies
   - disorder:        pruritic skin infestation, may be shared among multiple members of a family
   - etiology:        Sarcoptes scabiei
   - morphology:      pruritic, excoriated areas
   - location:        most intense on hands and feet, but seen in other areas
   - management:      whole body permethrin cream, fumigation

             FIGURE: Scabies

- head lice
   - disorder:        pruritic scalp infestation, may pass from child to child
   - etiology:        Pediculosis capitis
   - morphology:      often asymptomatic, but may be pruritic
   - location:        scalp, primarily occipital regions
   - management:      topical permethrin, malathion
                                                                         Infection & Immunity 2: Objectives (page 129 of 137)

              FIGURE: Head Lice Nits

- viral infections
   - disorder:        viral rash
   - etiology:        viral infection
   - morphology:      nonspecific morbilliform eruption (macules, papules) of the trunk, face, and extremities
                      specific morphologies may include:
                      - measles: associated with fever, cough, rhinitis, conjunctivitis
                      - rubella:     faint, pink macules on the face (somewhat nonspecific)
                      - varicella: papules → vesicles (tear drop) → crusts; multiple stages of healing
                      - HSV:         grouped vesicles on an erythematous base, usually on mouth or hand
                      - HPV:         discreet, raised thickening of skin (warts)
                      - molluscum: umbilicated lesions from 0.5-8 mm in size
     - management:    resolution of viral illness

              FIGURE: Nonspecific Viral Rash

4.    Complete the Pediatric Dermatology module found online at:


Trauma, Ingestions, and Burns
                                                                                                          CHAPTER 23

1.    List the symptoms of and describe the initial emergency management of shock.

- shock
                                                                       Infection & Immunity 2: Objectives (page 130 of 137)

- disorder:         insufficient flow of blood to tissues

- pathophysiology: differences in pediatric patients may worsen severity / presentation of shock
                   - greater total body surface area per weight
                   - less subcutaneous fat
                   - elevated metabolic rate
                   - larger head, smaller oral cavity, larger tongue, more anterior larynx
                   - less respiratory reserve
                   - increased skeletal compliance (including ribs)
- diagnosis
   - history:      concise history focusing on mechanism of injury and surrounding events
   - physical:     primary survey (ABCs)
                   - airway and “C” spine
                   - breathing
                   - circulation
                   - disability (neurological)
                   - exposure
                   secondary survey
                   - comprehensive physical examination
                   - should be orderly, include a rectal examination to determine anal tone and occult blood
   - laboratory:   depends on mechanism, ability to assess, and nature of injuries, and may include:
                   - radiographic studies (“C” spine, chest, pelvis)
                   - blood tests (CBC, hematocrit, type and match, ABG)
                   - urinalysis

- differential:     must differentiate etiology
                    - hypovolemic: tachypnea, tachycardia; hypotension as a late finding
                    - obstructive:     tachypnea, breath sounds CTA, distant heart sounds, neck vein distension
                    - cardiogenic:     EKG, history
                    - neurogenic:      hypovolemia without tachycardia
                    - septic:          tachycardia, normotension, failure to improve with resuscitation

- management:       initial steps occur in conjunction with the primary survey
                    - airway:           immobilization, ventilation / intubation, talking
                    - breathing:        assess for pneumothorax
                    - circulation:      two large-bore peripheral IV lines, bolus fluids, packed RBCs
                    - disability:       rapid neurologic assessment: pupils, Glasgow coma scale
                    - exposure:         detailed examination, Foley placement
                    consultation with appropriate specialists
                    counseling to parents

TABLE: Glasgow Coma Scale
 feature                                            score
   • open spontaneously                               4
   • open to speech                                   3
   • open to pain                                     2
   • no response                                      1
 verbal response 1
   • oriented (coos, babbles)                         5
   • confused (irritable cries)                       4
   • inappropriate words (cries to pain)              3
   • incomprehensible sounds (moans to pain)          2
   • no response                                      1
 motor response
   • obeys (normal spontaneous movements)             6
                                                                              Infection & Immunity 2: Objectives (page 131 of 137)

         • localizes (withdraws to touch)                    5
         • withdraws (withdraws to pain)                     4
         • abnormal flexion                                  3
         • abnormal extension                                2
         • no response                                       1
       TOTAL SCORE 2                                       3-15
       parentheses indicate findings in preverbal children
       a score of 8 or less may indicate intracranial hypertension

2.     Demonstrate the ABCDE assessment as a means for identifying who requires immediate medical attention
       and intervention.

     TABLE: Immediate Management of the Injured Child
      component   management
      airway      • protect neck with rigid cervical collar
                  • assess for airway obstruction
                     - chin lift / jaw thrust maneuver, if needed
                     - prepare for endotracheal intubation, if needed
      breathing   • administer 100% O2
                  • place on continuous pulse oximetry monitoring
                  • assess for quality and asymmetry of breath sounds
                  • assess for work of breathing
      circulation • attach cardiac monitor leads
                  • obtain IV access with two large-bore catheters
                  • assess for signs of peripheral perfusion (pulses, capillary refill)
                  • control hemorrhage
      disability  • brief neurological examination
                  • level of consciousness (AVPU)
                     - alert
                     - responds to verbal commands
                     - responds to pain
                     - unresponsive
                  • pupillary size and response to light
      exposure    • undress patient to assess for other injuries

3.     Describe the acute signs and symptoms of accidental or intentional ingestion of acetaminophen, iron,
       alcohol, narcotics, and tricyclic antidepressants.

- acetaminophen
   - pathogenesis:       formation of N-acetyl-p-benzoquinoneimine (NABQI)
                         - highly reactive oxidant and electrophile
                         - pathologic to liver if glutathione metabolism is insufficient
     - presentation:     progressive
                         - early:      asymptomatic → nausea, vomiting, abdominal pain
                         - late:       liver failure, vascular collapse, seizure, coma, death
     - management:       N-acetylcysteine (restores depleted glutathione)

- alcohol
   - pathogenesis:       general end organ toxicity
   - presentation:       lethargy, ataxia, hypoglycemia
   - management:         finger stick glucose to evaluate hypoglycemia
                                                                               Infection & Immunity 2: Objectives (page 132 of 137)

                         thiamine, folate administration
                         naloxone (if opioid ingestion is suspected)

- iron
   - pathogenesis:       deposition in liver, pancreas, myocardium, endocrine glands, joints, and skin
                         pills resemble M&Ms, and are attractive to younger children
     - presentation:     vomiting, abdominal pain, hypotension
     - management:       gastric lavage

- opioid narcotics
   - pathogenesis:       CNS depression
   - presentation:       pinpoint pupils, coma, respiratory depression
   - management:         supportive care, naloxone for severe overdose

- tricyclic antidepressants
   - pathogenesis:     sympathomimetic
   - presentation:     tachycardia, hypertension, mydriasis, excitation, diaphoresis, delirium, seizures
   - management:       activated charcoal, supportive care

4.     Explain the role of the Poison Control Center (1-800-222-1222) and other information resources in the
       management of the patient with an accidental or intentional ingestion.

- Poison Control Center
   - resources:       Poison Control Center resources include:
                      - POISINDEX (computerized bank of medicinal, industrial, and environmental toxins
                      - library of toxicologic reference texts
                      - staff of medical toxicologists
   - function:        Poison Control Centers are there to:
                      - give access to available resources
                      - supply telephone numbers for area experts
                      - aid in predicting symptoms occurring with a given toxin
                      - help direct clinician in the safest course of therapy
   - contact:         1-800-222-1222 (routes to local poison control center)

5.     Describe the immediate emergency management of children with toxic ingestions.

- toxic ingestions: immediate emergency management
   - disorder:        ingestion of a toxin

     - pathophysiology
        - accidental:  more common in younger children momentarily unsupervised
                       generally involves single agents in clinically unimportant quantities

       - intentional:    more common in adolescents and adults
                         generally involves multiple substances in significant quantities

     - diagnosis
        - history:       confirm ingestion, determine the potential severity
                         - identity
                         - quantity
                         - time / course of ingestion
                         - route of administration
                         - accidental vs. intentional
                                                                           Infection & Immunity 2: Objectives (page 133 of 137)

       - physical:      assess cardiorespiratory stability, vital signs, and neurologic function
                        examine for evidence of syndromes, odors indicative of certain ingestions

       - laboratory:    necessity depends on history, clinical appearance, and intent
                        - observation for minor accidental ingestions
                        - “worst case scenario” for any intentional ingestions
                        possibly useful studies may include:
                        - drug screens
                        - toxin blood levels
                        - routine labs
                        - radiographs (selected toxins)

     - differential:    assessment and differential must include:
                        - whether a poisoning has occurred
                        - whether the patient is or is likely to become ill
                        - whether non-toxicologic disease processes may be occurring
                        - what treatment is needed to minimize morbidity
                        - urgency of intervention

     - management:      primary and secondary surveys
                        - irrigation of contaminated surfaces
                        - emesis / gastric lavage
                        - activated charcoal
                        - cathartics

Pediatric Intensive Care
                                                                                                            CHAPTER 24

1.     List common causes of shock in the pediatric population.

     TABLE: Common Causes of Pediatric Shock
      type               etiology
      hypovolemic        • vomiting
                         • diarrhea

      distributive            • anaphylaxis
                              • sepsis
                              • CNS injury

      cardiogenic             • dysrhythmia
                              • pericardial effusion
                              • congenital heart defect
                              • myocarditis
                              • cardiomyopathy
                                                                            Infection & Immunity 2: Objectives (page 134 of 137)

2.     List the symptoms of and describe the initial emergency management of shock, airway obstruction, and
       status epilepticus in pediatric patients.

- shock
   - disorder:           insufficient flow of blood to tissues

     - pathophysiology: differences in pediatric patients may worsen severity / presentation of shock
                        - greater total body surface area per weight
                        - less subcutaneous fat
                        - elevated metabolic rate
                        - larger head, smaller oral cavity, larger tongue, more anterior larynx
                        - less respiratory reserve
                        - increased skeletal compliance (including ribs)
     - diagnosis
        - history:      concise history focusing on mechanism of injury and surrounding events
        - physical:     primary survey (ABCs)
                        - airway and “C” spine
                        - breathing
                        - circulation
                        - disability (neurological)
                        - exposure
                        secondary survey
                        - comprehensive physical examination
                        - should be orderly, include a rectal examination to determine anal tone and occult blood
        - laboratory:   depends on mechanism, ability to assess, and nature of injuries, and may include:
                        - radiographic studies (“C” spine, chest, pelvis)
                        - blood tests (CBC, hematocrit, type and match, ABG)
                        - urinalysis

     - differential:     must differentiate etiology
                         - hypovolemic: tachypnea, tachycardia; hypotension a late finding
                         - obstructive:     tachypnea, breath sounds CTA, distant heart sounds, neck vein distension
                         - cardiogenic:     EKG, history
                         - neurogenic:      hypovolemia without tachycardia
                         - septic:          tachycardia, normotension, failure to improve with resuscitation

     - management:       initial steps occur in conjunction with the primary survey
                         - airway:           immobilization, ventilation / intubation, talking
                         - breathing:        assess for pneumothorax
                         - circulation:      two large-bore peripheral IV lines, bolus fluids, packed RBCs
                         - disability:       rapid neurologic assessment: pupils, Glasgow coma scale
                         - exposure:         detailed examination, Foley placement
                         consultation with appropriate specialists
                         counseling to parents

- upper airway obstruction
   - disorder:      obstruction of conducting respiratory pathways

     - pathophysiology: predisposition to upper airway obstruction in children
                        - smaller airway
                        - presence of the cricoid membrane (mucosal tissue that swells when irritated)
                        - potential loss of upper airway tone during sleep

     - presentation:     stridor
                                                                             Infection & Immunity 2: Objectives (page 135 of 137)

     - diagnosis:        in general, diagnostic procedures should be minimized until airway is secured

     - differential
        - infectious:    viral croup
                         pharyngeal / peritonsillar abscess
                         severe hypertrophy of tonsils or adenoids

       - congenital:     webs
                         vocal cord paralysis
                         tracheomalacia / laryngomalacia
                         subglottic stenosis
                         vascular abnormalities (hemangioma, vascular rings)

       - acquired:       trauma (external or internal)
                         foreign body aspiration

       - CNS:            head trauma
                         CNS infection
                         status epilepticus
                         neuromuscular disorders
                         drug-induced dysfunction (e.g. narcotics, anesthetics, tranquilizers)

     - management:       cardiorespiratory monitoring
                         precautions for emergency airway access
                         administration of O2 and / or racemic epinephrine
                         bronchoscopy (with precautions for epiglottitis patients)

- status epilepticus
   - disorder:           persistent, severe seizure activity lasting more than 30 minutes

     - pathophysiology: patients in status epilepticus are at risk for:
                        - loss of patency of airways
                        - development of aspiration pneumonia
                        - blood pressure instability (early hypertension, late hypotension)
                        - hypoxia / hypercarbia
                        - acidosis
                        - hyperthermia
                        - electrolyte abnormalities
                        - increased cerebral blood flow, cerebral O2 consumption

     - diagnosis:        obvious from history, physical exam

     - management:       primary assessment
                         intravenous anticonvulsants
                         - diazepam, lorazepam are common first line agents
                         - phenytoin effective (though slow onset) in refractory tonic-clonic seizures
                         inhalational anesthetics, short acting barbiturates if other measures are unsuccessful
                         continuous EEG, cardiovascular monitoring

3.     Describe the clinical findings for each of the diagnoses in the following table:

     TABLE: Pediatric Emergencies
                                                                       Infection & Immunity 2: Objectives (page 136 of 137)

   problem                   common differential                   other considerations
   airway obstruction /      • croup                               • peritonsillar abscess
      respiratory distress   • bronchiolitis                       • retropharyngeal abscess
                             • asthma
                             • pneumonia
                             • foreign body aspiration
                             • anaphylaxis

   altered mental status     • head injury                         • intussusception
      (delirium, lethargy)   • increased ICP
                             • substance abuse
                             • encephalitis / meningitis
                             • diabetic ketoacidosis
                             • hypoglycemia
                             • nonaccidental trauma
                             • shock
                             • hypoxemia

   apnea                     • acute life-threatening event        • cardiac dysrhythmia
                             • seizure                             • breath-holding spell
                             • RSV / pertussis
                             • GERD
                             • sepsis

   ataxia                    • post-infectious                     • ingestion
                                                                   • tumor

   GI bleeding               • Meckel’s diverticulum               • inflammatory bowel disease
                             • fissure                             • allergic colitis
                             • intussusception                     • peptic ulcer disease

   proptosis                 • thyroid abnormality                 • CNS tumor
     (exophthalmos)                                                • orbital cellulitis

   seizure                   • encephalitis / meningitis           • tumor
                             • status epilepticus
                             • febrile seizure
                             • ingestion
                             • hypoxemia
                             • shock
                             • electrolyte disturbance

   shock                     • sepsis                              • burn
                             • severe dehydration                  • neurogenic shock
                             • diabetic ketoacidosis               • ductal-dependant heart lesion
                             • anaphylaxis                         • adrenal insufficiency
                             • congestive heart failure
                             • ingestion

common clinical findings in pediatric emergencies
• adrenal insufficiency: fatigue, weakness, vomiting, diarrhea, hypotension, hyperpigmentation, shock
• allergic colitis:      diarrhea, abdominal pain, weight loss, anemia, worsening with particular exposures
• ALTE:                  cyanosis (ATLE: acute life-threatening event)
                                                                            Infection & Immunity 2: Objectives (page 137 of 137)

• anaphylaxis:               angioedema, urticaria, pruritus, anxiety, hypotension, vomiting
• asthma:                    cough, wheeze, dyspnea
• bronchiolitis:             cough, wheeze, dyspnea
• burn:                      stridor, respiratory distress, edema, signs of inhalation edema, shock
• CNS tumor:                 progressive focal neurologic signs, seizures, elevated ICP, phantom odors / tastes
• congestive heart failure: dyspnea, edema, altered mental status, diaphoresis, increased JVP
• croup:                     stridor, barking cough
• cyanotic heart lesion:     cyanosis, lethargy, onset in newborn period, shock
• diabetic ketoacidosis:     abdominal pain, N / V, anorexia, lethargy, apathy, Kussmaul respirations, coma
• electrolyte disturbance: seizure, altered mental status
• encephalitis / meningitis: fever, headache, nuchal rigidity, altered mental status, photophobia, irritability
• febrile seizure:           generalized seizure associated with fever
• fissure:                   abdominal pain, rectal bleeding
• foreign body aspiration: stridor
• GERD:                      vomiting, reflux, irritability, esophagitis, dysphagia, chest pain
• head injury:               seizures, nausea, vomiting, loss of consciousness, leaking CSF, Battle’s sign
• hyperthyroidism:           weakness, irritability, palpitations, arrhythmia, weight loss, heat intolerance
• hypoglycemia:              diaphoresis, tachycardia, pallor, paresthesia, anxiety
• hypothyroidism:            hypotonia, fatigue, constipation, weight gain, brittle fingernails, cold intolerance
• hypoxemia:                 cyanosis, tachypnea, tachycardia
• IBD:                       abdominal pain, vomiting, diarrhea, hematochezia, weight loss
• increased ICP:             headache, nausea, vomiting, altered consciousness, ocular palsies, papilledema
• intussusception:           nausea, bilious vomiting, abdominal pain, “red currant jelly” stool, irritability
• Meckel’s diverticulum: rectal bleeding, intestinal obstruction, acute abdomen
• neurogenic shock:          hypovolemia without tachycardia
• nonaccidental trauma: suspicious history, suggestive scarring, unexplained subdural hematoma
• orbital cellulitis:        fever, proptosis, restricted eye movement, swelling / redness of eye lids
• peptic ulcer disease:      abdominal pain, N/V, anorexia, weight loss, hematemesis, melena
• peritonsillar abscess:     pharyngitis, laryngitis, fever, lymphadenopathy, peritonsillar swelling
• pneumonia:                 fever, headache, fatigue, joint pain, productive cough
• retropharyngeal abscess: pharyngitis, fever, neck stiffness, odynophagia, cough
• RSV / pertussis:           cold symptoms, bronchiolitis, “whooping cough”
• seizure:                   numbness, loss of memory, staring spells, tachycardia, muscular spasms
• sepsis:                    tachycardia, normotension, failure to improve with resuscitation
• severe dehydration:        headache, dizziness, dry mucous membranes, lethargy, low UOP, sunken eyes
• shock:                     tachypnea, tachycardia, hypotension
• status epilepticus:        persistent seizure activity lasting > 30 minutes
• substance abuse:           syndromes associated with specific substances

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