Breast
Pathology
1
Lymphatic drainage Anatomy of Breast
2
Extension of metastasis:
Cervical,
Supraclavicular,
Groin
Lymphnodes
3
Clinical Clues to Early Detection
Lump 70%
Self detection 90%
Pain/nipple discharge/ erosion/retraction/
enlargement/ itchy nipple/
red hard breast/ axillary mass
Back/bone pain/ jaundice/ weight loss
Upper and Outer Quadrant lump
4
Right breast mass with
"peau d'orange"
skin retraction,
muscle retraction, and
non tender axillary
lymphadenopathy
44 yr old WF with a 1 year history of right breast mass and
pain, refused hospitalization for a probable carcinoma of the
right breast when seen by her doctor six months prior to
admission.
Four weeks prior to admission, the patient developed nausea,
vomiting, coughing, shortness of breath, fatigue and increasing
weakness. 5
Early disease: Advanced disease:
1. Palpable mass 1. Fixation of the mass to the chest
2. Breast pain wall
3. Nipple discharge 2. Axillary lymphadenopathy
4. Ulceration 3. Edema of the arm
5. Skin- Dimpling / Edema/ 4. Breast enlargement
Erythema 5. Ulceration
6. Axillary mass 6. Supraclavicular lymphadenopathy
7. Scaling of the nipple 7. Back pain
(Paget's disease) 8. Bone pain
9. Jaundice
10. Weight loss
6
Paget’s Disease
7
Paget’sDisease of the Nipple:
Manifests as an eczematous or psoriaform plaque. It
is a skin manifestation of an underlying ductal
adenocarcinoma of the breast.
8
A 48-year-old woman had experienced a prolonged history of chronic
eczematous dermatitis of the nipple and areolar area for several
years.
The lesion did not respond to topical treatment, and it progressively
distorted the nipple with expansion into the surrounding skin.
Note a markedly scaly, crusted, and deformed nipple with a
thickened, irregularly outlined adjacent nipple-areola complex.
An excisional biopsy confirmed the diagnosis of mammary Paget
disease.
The patient developed an infiltrating ductal carcinoma of the
underlying breast tissue with axillary lymph metastasis.
She was treated by mastectomy and radiation. No metastatic tumor
was noted in the axillary lymph node.
She was alive and well
3 years after treatment.
9
Infiltrating Duct Carcinoma
The specimen consists of the skin of the breast (black arrows) with underlying
breast tissue.
The blue arrows point to a poorly circumscribed yellow white mass which is the
neoplasm.
10
Breast Cancer
Incidnce:192,000/yr
10% hereditary
Risk>-3-7 times
BRCA1 either inherited or somatically mutated with loss of
heterozygosity may remove suppression of cell growth by
gene product
11
The BRCA1 and BRCA2
(or Breast Cancer 1 and 2) genes
Responsible for all cases of familial ovarian cancer and
approximately half of all cases of familial breast cancer.
Carrier of the BRCA1 and BRAC-2 Gene have a 15-45% chance of
developing ovarian cancer compared to a 1.5% risk for non-
carriers.
BRAC1-2 is associated with early onset breast cancer.
increase the risk of a second cancer. A woman with the mutation
has an increased risk of ovarian cancer following breast cancer.
12
Red flags for hereditary cancers include:
A diagnosis of cancer at an early age.
Several family members with cancer.
Relatives with more than one type of cancer.
A history of bilateral cancer. This means cancer in both eyes or both breasts.
A history of multiple primary cancers in one person where one cancer was
cured and another was diagnosed in later life.
Rare or unusual cancers such as male breast cancer
Ashkenazi or eastern European ancestry - these groups have been found to be
at a higher risk for certain genetic mutations.
13
Cause for Concern:
Any woman family member has had both breast and ovarian
cancer.
More than 3 women from the same side of the family have had
breast or ovarian cancer.
Any woman family member has had breast or ovarian cancer
before the age of 50.
Any man in the family has had breast cancer.
14
inherited BRCA2 mutation?
Both men and women who inherit a BRCA2 mutation have an
increased chance for developing breast cancer.
Women who have an altered BRCA2 gene appear to have a similar
risk of developing breast cancer compared with women with BRCA1
mutations.
The risk for ovarian cancer is also increased. Studies suggest that the
ovarian cancer risk is between 16 and 27 percent.
15
?Heredity- BrCa – 10% of all, & 40% under 30 are gene
related
BRCA 1 on chr.17 (85% risk for BrCa & 50% for OvCa); also
colon & prostate Ca
BRCA2 in M- male BrCa and melanomas
Identical twin sibling at risk for same Cancer
16
Epidemiology
Affects 1 of 9 women in the U.S.
Increases with increasing age
More frequent in women of low parity with first child after 30
Increased in obesity
Increased in women with history of atypical hyperplasia
Increased in women with history of breast carcinoma
Increased in women with mother or sibling with breast cancer
Increased in women with mutations in BRCA1 or BRCA2 genes
17
Clinical Nature
Neoplasm spreads to regional (axillary) lymph nodes and then to distant
sites including lungs, liver, and bones
Treatment and prognosis dependent on tumor size and presence of
metastatic disease in lymph nodes or distant sites (stage) and estrogen
and progesterone receptor status
Therapy includes local treatment (surgery and/or radiation treatment of
the breast) and systemic therapy if warranted with either anti-estrogens
(if the neoplasm is receptor positive) or chemotherapy
18
? Male Breast Cancer
High prevalence in certain parts of Africa, a higher incidence of estrogen receptor
positivity and more aggressive clinical behavior.*
Estimated new cases and deaths from breast cancer in the United States;
American Cancer Society.: Cancer Facts and Figures 2008.
New cases:
182,460 (female)
1,990 (male)
Deaths: 40,480 (female)
450 (male)
*Eur J Cancer. 1998 Aug;34(9):1341-7.
19
Male Breast Facts
Men with a BRCA2 mutation have a 6 percent lifetime risk of breast
cancer — about 100 times more than other men's risk.
Inherited mutations in the cell-cycle checkpoint kinase 2 (CHEK-2) gene
and the p53 gene
Radiation exposure
Klinefelters Syndrome (XXY syndrome)
30% cases have excess of HER2 (human epidermal growth factor receptor-
2) protein expression
20
Reduced Androgen Activity
Exposure to estrogen.
Liver disease.
Excess weight. Obesity may be a risk factor for breast cancer in men,
because it increases the number of fat cells in the body. Fat cells convert
androgens into estrogen, increasing the amount of estrogen in your body
and, therefore, your risk of breast cancer.
Excessive use of alcohol
21
FIBROCYSTIC BREAST DISEASE
Fibrocystic breast “condition” or fibrocystic breast “change.”
Estrogen-dependent, most commonly in women 30-50 (still producing
estrogen).
Changes are probably variants of normal: gross and microscopic cysts,
papillomatosis, adenosis, fibrosis, and ductal hyperplasia.
22
Fibroadenoma/ Fibrocystic Disease
The pale grey cut surfaces show a
Benign cysts filled by serous fluid
bulging glistening appearance often have this blue color when
due to the predominant loose viewed from the outside.
fibrous stroma rich in
mucopolysaccharides. Note well
defined outline
23
FIBROCYSTIC BREAST DISEASE
SIGNS / SYMPTOMS
Pain, tenderness, palpable masses, usually multiple and bilateral,
worse or sometimes only present during the luteal phase.
Fluctuation in size of the cysts.
“Suspicious” masses should be biopsied.
Aspiration of a dominant cyst and / or Bx and /or MMG should be
considered to assist in the Dx, although a MMG negative for
malignancy does not R/O malignancy- only Bx rules out malignancy.
24
FIBROCYSTIC BREAST DISEASE
TREATMENT
Hormonal therapy theoretically the ticket, but not
practical long term due to side-effects, risks, etc,
although these rules can be bent for patients at the
extreme end of the symptomatic spectrum.
Avoidance of caffeine, Vitamin E 440 IU/d.
25
NIPPLE DISCHARGE
In the non-lactating female, the top 3 causes are:
1) Duct ectasia.
2) Intraductal papilloma.
3) Carcinoma.
26
NIPPLE DISCHARGE
Evaluate:
1) The nature of the discharge- serous, bloody, purulent, milky.
2) Associated w/ a mass?
3) Unilateral or bilateral.
4) Single or multiple duct discharge.
5) Expressed or spontaneous.
6) Single site, or multiple sites.
7) Relation to menses.
8) Premenopausal or postmenopausal.
9) On estrogen or OCPs?
27
NIPPLE DISCHARGE
“A 40 year old female comes in with a 2 month history of a spontaneous
bloody discharge from her right breast. On exam you are able to express
blood with pressure in the upper outer quadrant of the breast. There is no
palpable mass. Your DDx would include…….”
28
NIPPLE DISCHARGE
GALACTORRHEA
The discharge of milk from the non-lactating breast.
Caused by hyperprolactinemia- can be due to: prolactin-
producing adenoma of the pituitary, hypothyroidism, anti-
psychotic medication, and other screwy things- see pg 1113.
A serum prolactin should be done. If elevated, a cause should
be sought.
29
NIPPLE DISCHARGE
EVALUATION
All patients should have a history and PE looking for the 9
things listed.
When localization is not possible, there is no palpable mass,
the discharge is not bloody, and the MMG is normal, the
patient should be followed every 3 months for a year, w/ a
repeat MMG in 6-12 months if the discharge persists.
30
NIPPLE DISCHARGE
EVALUATION
ALL PATIENTS W/ A UNILATERAL, BLOODY DISCHARGE
SHOULD HAVE AT LEAST AN EXAM AND A MAMMOGRAM.
CONSIDER REFERRAL FOR EXCISION OF THE INVOLVED DUCT.
ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF
SOME SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS
OF AGE.
31
BREAST CANCER
Stats.
Risk factors.
Association w/ other malignancies.
ERT.
Genetic mutations- BrCa1, BrCa2, p53 gene.
Imaging, biopsy.
32
BREAST CANCER
“Most women w/ breast cancer have no identifiable risk
factor.”
“There is no history of breast cancer among female relatives
in over 75% of patients.”
1-2% of patients w/ a prior Dx of breast cancer will develop a
second primary in the other breast.
33
BREAST CANCER
ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF SOME
SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS OF AGE.
REGARDLESS OF WHAT THE MAMMOGRAM SAYS.
A MMG NEGATIVE FOR MALIGNANCY DOES NOT R/O MALIGNANCY-
ONLY BX RULES OUT MALIGNANCY
34
BREAST CANCER
RANDOM CLINICAL PEARLS
60% of breast cancers develop in the upper-outer quadrant.
SYMPTOMS-
1) A painless lump is the presenting symptom in 70% of
patients w/ breast cancer.
2) Less often: discharge, pain, skin retraction, itching of the
nipple, redness, generalized hardness.
35
BREAST CANCER
RANDOM CLINICAL PEARLS
PHYSICAL FINDINGS- hard, non-tender mass, fixed, poorly
delineated margins. Skin or nipple retraction.
36
BREAST CANCER
SCREENING
1)Self-breast exams for those interested in it at any age, those
after age 50, and those at increased risk of breast cancer.
2)ALSO: yearly exams by a clinician and annual mammograms
every 1-2 years after age 40, and yearly after age 50.
3)A breast cancer can be detected on MMG 2 years before they
can be palpated.
37
WHEN TO ORDER A
MAMMOGRAM
1) FOR SCREENING.
2) TO EVALUATE EACH BREAST AFTER THE Dx OF BREAST
CANCER.
3) TO EVALUATE A BREAST MASS OR OTHER
ABNORMALITY.
4) TO LOOK FOR A PRIMARY WHEN A METASTASIS OF
ADENOCARCINOMA IS FOUND.
5) TO SCREEN PRIOR TO BIOPSY OR COSMETIC
PROCEDURES.
6) FOLLOW-UP AFTER BREAST-CONSERVING SURGERY
AND RADIATION.
38
DISORDERS DUE TO PHYSICAL
AGENTS
39
HYPOTHERMIA, HEAT DISORDERS.
BURNS.
ELECTRIC SHOCK.
IONIZING RADIATION.
40
Hypothermia: Cold exposure
Skin temp 37.8°C) rapid pulse (>120-140)
Exhibit nausea/ vomiting/ myalgia/ thirst/headache/ fatigue/ hysteria/
psychosis. Can progress to heat stroke.
Keep cool. Hydrate 1-2L in 2 hrs/salt/ fans/ice pack
44
Heat Disorders
Heat Stroke: Life threatening. Rectal temperature >41°C. Cerebral
dysfunction/ impaired consciousness/ high fever/ Absence of sweating
At risk- very young and very old
Patients on medications- anticholinergis/antihistamines
Can be seen in marathon runners
High mortality-collapse/convulsions/coma
Reduce core temperature rapidly- ice water immersion/ evaporative
cooling
45
Alpha radiation consists of
helium-4 nucleus and is readily
stopped by a sheet of paper.
Beta radiation, consisting of
electrons, is halted by an
aluminium plate.
Gamma radiation is eventually
absorbed as it penetrates a
dense material. Lead is good at
absorbing gamma radiation,
due to its density
46
47
Radiation Effects
Skin-Mucus membrane- redness/ loss of hair/ exfoliation/
thermal burns
BMD/ Pericarditis
Pneumonitis
Oropharyngeal ulcers
Hepatitis/ nephritis
Gonads
Radiation sickness: nausea/ anorexia/ exhaustion
Therapy- Serial lymphocyte counts/ chelation for
radioisotopes
48
Classification OF BURNS
Only second- and
third-degree burns
are included in
calculating the total
burn surface area,
since first-degree
burns usually do
not represent
significant injury
49
First-degree burns affect only the
outer layer of the skin. They cause
pain, redness, and swelling.
Second-degree (partial thickness)
burns affect both the outer and
underlying layer of skin. They
cause pain, redness, swelling, and
blistering.
Third-degree (full thickness) burns
extend into deeper tissues. They
cause white or blackened, charred
skin that may be numb.
50
Electrical injuries - uncommon occurrence
500-1000 resultant deaths occur per
year
Factors- the voltage, current
strength, resistance to flow,
duration of contact, pathway of
flow, and type of current.
Ohm's law: ‘voltage is equal to
current times resistance’
high voltage above 500-1000 V
household appliances work at 110 V
Current is the volume of electron
flow –DC or AC
Frequency 60 Hz
Resistance-impedance to electron
flow and usually depends on the
water content of a conducting
material low-voltage electrical injury
51
Respiratory muscle paralysis
occurs at 20-50 mA.
Ventricular fibrillation may
develop at 50-120 mA and
Asystole, at currents greater than
2 A.
Flash burns- an electrical arc does
not enter the body but just
causes a severe thermal injury
and singe nearby hairs
Ventricular fibrillation is more
common with low-voltage AC;
Delayed arrhythmias can occur
up to 12 hours
52
Low-voltage burns
Thermal burns caused by
prolonged contact; usually
at least several seconds of
contact are required.
They almost exclusively
occur in the hands of adults
and in the mouths of
children. Children may
chew on extension cords
and receive an oral burn
53
About TASER!
Deliver sequential DC pulses, up to 50,000 V
Deaths from TASER use have been reported
A superficial puncture wound
The most serious complications are from trauma subsequent
to the shock.
54
Lightning
A type of high-voltage DC electrical
injury
Mild-superficial burns with associated
loss of consciousness, amnesia,
confusion, and tingling
Moderate injuries-may include seizures,
respiratory arrest, and cardiac stunning
Severe lightning injuries-cause
cardiopulmonary arrest, with a very low
survival rate.
55
INFECTIOUS DISEASES
56
NOSOCOMIAL INFECTION
“Those not present or incubating at the time of hospital admission and
developing 48-72 hours after admission.”
5% of hospitalized patients develop one.
Carry a 5% mortality rate.
Most common are urinary tract infections.
Catheters of all types are associated w/ increased risk of an infection.
Are more often multiple drug resistant.
57
NOSOCOMIAL INFECTION
When looking at cultures, distinguish between colonization and infection.
PREVENTION- the most effective method of preventing nosocomial
infections is handwashing.
Hand disinfectants.
Change central catheters every 3-4 days.
Attention to all catheters as a possible source of fever / infection.
58
INFECTIONS IN DRUG USERS
1) SKIN INFECTIONS- Staph aureus, oral flora (Strep, Pepto-sctreptococci),
gram negatives, depending on injection site, practices etc.
2) HEPATITIS- B,C, AND D, ALSO A. can have multiple episodes w/ different
agents
3) ASPIRATION PNEUMONIA-
4) TB-
5) PULMONARY SEPTIC EMBOLI- from venous thrombi or right-sided
endocarditis.
59
INFECTIONS IN DRUG USERS
6) STDs-
7) AIDS-HIV
8) INFECTIVE ENDOCARDITIS-
9) VASCULAR INFECTIONS- septic thrombophlebitis, mycotic aneurysms.
10) OSTEOMYELITIS AND SEPTIC ARTHRITIS-
60
INFECTIONS IN DRUG USERS
TREATMENT
Work-up, cultures etc followed by broad-spectrum antibiotics
effective against resistant Staph and others, nafcillin or
vancomycin combined with gentamicin, depending on CXR, while
awaiting culture results.
61
ACUTE INFECTIOUS DIARRHEA
1INFLAMMATORY NON-INFLAMMATORY
Presence of an invasive pathogen, Milder, small bowel disease.
parasite, or a toxin. Usually viral
Colon commonly affected: frequent, stools are larger volume,
bloody, small-volume stools, often non-bloody, watery, w/
fever, cramps, tenesmus, urgency. nausea, vomiting, cramps,
usually no fever.
The Bugs: Shigella, Salmonella,
Campylobacter, Yersinia, invasive E The Bugs: Viruses: Norwalk
virus, enteric adenoviruses,
coli, Entamoeba histolytica, astrovirus, coronavirus;
Clostridium dificile (esp in the recently- Vibriones: Vibrio cholera,
hospitalized) . Vibrio parahemolyticus
Test for fecal leucocytes is positive.
Stool culture identifies the bug.
62
ACUTE INFECTIOUS DIARRHEA
NON-INFLAMMATORY
Bugs (cont)- enterotoxin-producing E coli, Giardia lamblia,
cryptosporidium, agents causing food-borne gastroenetritis (Staph aureus,
Bacillus cereus, Clostridium perfringens).
TREATMENT
Fluid replacement, electrolytes.
Most acute diarrheas resolve within 3-4 days.
Those that do not, or those that appear inflammatory, stool cultures
should be done.
63
ACUTE INFECTIOUS DIARRHEA
TREATMENT
Therapy if cultures are positive for: Shigella, E coli 0157:H7,
and Campylobacter.
For the rest, antibiotic treatment has not been shown to alter
the natural history of the disease, and in fact may prolong the
carriage of the bug and lead to relapse/recurrence.
Giardiasis treated with metronidazole (Flagyl)
Routine use of antibiotics is discouraged due to the
emergence of resistant organisms.
64
ACUTE INFECTIOUS DIARRHEA
TREATMENT
TREAT THOSE:
1) WITH INVASIVE DISEASE.
2) WITH SYMPTOMS BEYOND 4 DAYS.
3) WITH > 8-10 STOOLS PER DAY.
4) WHO ARE IMMUNOCOMPROMISED.
Use anti-spasmodics (Immodium etc) only in those without
invasive/inflammatory disease (fever, bloody stools).
65
TRAVELER’S DIARRHEA
80% are bacterial.
The Bugs: enterotoxigenic E coli, Campylobacter, Shigella, less frequently
Aeromonas, Salmonella, Entamoeba histolytica, Giardia lamblia. Viruses:
adenoviruses, rotaviruses.
Occurring within 1 week of travel, usually benign and self-limiting,
resolves within 1-5 days.
Frequent, loose BM’s, watery, non-bloody, cramps, N/V, no fever
66
TRAVELER’S DIARRHEA
If stools are bloody, or fever is present → stool cultures and treatment.
Empiric treatment w/ Cipro 500 mg bid for 3-5 days, other
fluoroquinolones, trim-sulfa.
Specific treatment may change w/ culture results, but often not.
See text re prophylaxis.
67
HIV INFECTION
68
Post Exposure: Early Symptoms
Flu-like illness within a month or two after exposure to the
virus. This illness may include
Fever
Headache
Tiredness
Enlarged lymph nodes
69
Later Symptoms
Asymptomatic 10-15 years
During the asymptomatic period, the virus is actively
multiplying
Results in a decline in the number of CD4 positive T (CD4+)
cells
70
Late Symptoms (?AIDS)
The first signs of infection are large lymph nodes, or swollen glands that may be
enlarged for more than 3 months.
Other symptoms often experienced months to years before the onset of AIDS
include:
Lack of energy
Weight loss
Frequent fevers and sweats
Persistent or frequent yeast infections (oral or vaginal)
Persistent skin rashes or flaky skin
Pelvic inflammatory disease in women that does not respond to treatment
Short-term memory loss
Frequent and severe herpes infections that cause mouth, genital, or anal sores, or
shingles
71
“Opportunistic infections” = AIDS
Coughing and shortness of breath
Seizures and lack of coordination
Difficult or painful swallowing
Mental symptoms such as confusion and forgetfulness
Severe and persistent diarrhea
Fever
Vision loss
Nausea, abdominal cramps, and vomiting
Weight loss and extreme fatigue
Severe headaches
Coma
72
CD4+ (Helper) T cell Counts
Normal >800-1600
Risk increases for counts <400
AIDS if <200
Diagnosis – ‘HIV positive’- carrier of the disease
ELISA screen usually positive 1-3 months after exposure (up to 6 months)
Likely to develop antibodies to the virus-within 6 weeks to 12 months
Western blot technique required to confirm ELISA test
73
?THERAPY
No Cure!
reverse transcriptase (RT) inhibitors
(Nucleoside/nucleotide inhibitors)
protease inhibitors, interrupt the virus from making copies
of itself at a later step in its life cycle
fusion inhibitors - Fuzeon (enfuvirtide or T-20)
highly active antiretroviral therapy, or HAART
74
?Side Effects
Bone marrow depression
Pancreatitis/ Polyneuritis
GI and Respiratory symptoms
Other severe reactions, including death
75
Therapy for opportunistic infections
Foscarnet and ganciclovir to treat CMV (cytomegalovirus) eye infections
Fluconazole to treat yeast and other fungal infections
TMP/SMX (Bactrim® or Septra®) (trimethoprim/sulfamethoxazole) or
pentamidine to treat PCP (Pneumocystis carinii pneumonia)
Cancer therapy for NHL/ Kaposi’s Sarcoma
76
LYME DISEASE
Lyme borreliosis, caused by Borrelia burgdorferi, a spirochete.
The vector is the ixodid tick, of which there are 4 genomic
groups.
Mostly seen in the northeast, north central, and mid-Atlantic
states.
Accuracy of diagnosis is suspect, as patients are diagnosed
with Lyme disease in areas where there is no known
host/cycle for B burgdorferi.
Concerns about over diagnosis. See text.
77
LYME DISEASE
CLINICAL
3 STAGES
1) STAGE 1- EARLY LOCALIZED INFECTION.
2) STAGE 2- EARLY DISSEMINATED INFECTION.
3) STAGE 3- LATE PERSISTENT INFECTION.
78
LYME DISEASE
CLINICAL
STAGE 1 - EARLY LOCALIZED INFECTION
ERYTHEMA MIGRANS.
1 week-10 days after the tick bite, at the site of the tick bite
Flat, slightly raised lesion, seen in areas of tight clothing- groin, axillae, thigh.
Classic description is the “Bull’s Eye” lesion, but a more heterogenous lesion is
common.
50% have a flu-like illness.
Resolves w/ out treatment in 3-4 weeks.
79
56,300 people were newly infected with HIV in 2006 (the
most recent year that data are available).
Over half (53%) of these new infections occurred in gay and
bisexual men.
Black/African American men and women were also strongly
affected and were estimated to have an incidence rate than
was 7 times as high as the incidence rate among whites.
80
LYME DISEASE
CLINICAL
STAGE 1 - EARLY LOCALIZED INFECTION
Atypical lesions or lesions that go unnoticed lead to misdiagnosis.
Asymptomatic cases not common- 7% incidence of asymptomatic
seroconversion.
81
LYME DISEASE
CLINICAL
STAGE 2 - EARLY DISSEMINATED INFECTION
Hematogenous or lymphatic spread.
Wide variety of symptoms.
Days to weeks after the tick bite.
SKIN- secondary lesions not in the area of the tick bite, similar to the
lesions in stage 1 but smaller.
CNS- headache, stiff neck.
MUSCULOSKELETAL- migratory pains in joints, muscles, tendons.
Fatigue and malaise.
82
LYME DISEASE
CLINICAL
STAGE 2 - EARLY DISSEMINATED INFECTION
Neurologic & musculoskeletal symptoms last hours to weeks, fatigue is
persistent.
See text for what happens next- the organism sequesters itself in certain
areas and produces focal symptoms: cardiac, neurologic, encephalitis, etc.
83
LYME DISEASE
CLINICAL
STAGE 3 – LATE PERSISTENT INFECTION
Months to years after initial infection.
Possibly an immunologic event rather than persistent
infection – see pg 1490.
Again: Skin, Neurologic, and Musculoskeletal.
MUSCULOSKELETAL-
Up to 60%. Sxs are highly variable.
Arthritis, joint pain w/out objective findings, chronic synovitis.
84
LYME DISEASE
CLINICAL
STAGE 3 – LATE PERSISTENT INFECTION
NERVOUS SYSTEM
Both peripheral and central.
“Subacute encephalopathy”- memory loss, mood swings, sleep
disturbance.
Axonal polyneuropathy.
85
LYME DISEASE
CLINICAL
STAGE 3 – LATE PERSISTENT INFECTION
SKIN
ACRODERMATITIS CHRONICUM ATROPHICANS
Can occur up to 10 years later.
Not common in the U.S., mostly in Europe due to a different species of B
burgdorferi.
86
LYME DISEASE
CLINICAL
Dx based on both clinical and lab findings.
Dx CRITERIA: Exposure to a “potential tick habitat” within 30 days prior to
developing erythema migrans WITH:
1) Erythema migrans Dx’d by a physician, OR
2) One late manifestation, AND
3) Laboratory confirmation.
87
LYME DISEASE
CLINICAL
LAB
See text for details of the assay, the ELISA, western blot, etc.
Detect antibodies to B. burgdorferi.
See text for Dx criteria by the American College of Physicians. True
positives vs. false positives. Read this. Really.
“Patients w/ non-specific symptoms without objective signs of Lyme
disease should not have serologic testing done.” In this setting, false
positives occur more commonly than true positives.
88
LYME DISEASE
TREATMENT
Tetracycline, ampicillin, ceftriaxone, azithromycin, cefuroxime, imipenem.
A Dx of Erythema migrans by a physician warrants immediate treatment w/ no
other diagnostic tests.
Treatment dependent on clinical manifestations, see table 34-4 pg 1492.
Again see pg 1493 for precaution about Dx (and, thus, treatment) being a clinical
one w/ CONFIRMATION by serologic tests, and that the serologic tests are fraught
w/ difficulty.
Beware of the patient presenting demanding treatment for his/her Lyme disease.
89
LYME DISEASE
TREATMENT
Oral therapy for most cases, weeks usually.
IV therapy for patients with neurologic / CNS manifestations.
Most patients will have prompt resolution of symptoms within 4 weeks of
completing therapy.
“True treatment failures are uncommon.”
See pg 1493 re patients treated for Lyme Disease who have persistent symptoms,
and how continuing to treat them, at least for Lyme Disease, is not productive
Life long immunity is not complete, pts are subject to re-infection.
90
CLINICAL FINDINGS
1) SYSTEMIC COMPLAINTS-
Fever, night sweats, weight loss, even in the absence of an infection, but a
work-up is in order for the patient w/ fever.
2) SINOPULMONARY DISEASE-
PNEUMOCYSTIS JIROVECI (yee row vet zee)- the “new”, though not yet
universally accepted, name of Pneumocystis carinii, and its pneumonia is
the most common opportunistic infection associated w/ AIDS. Formerly
called PCP pneumonia.
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CLINICAL FINDINGS
2) SINOPULMONARY DISEASE-
Sxs of PCP can be vague, findings non-specific.
Dx is made based on CXR sputum cultures.
Most cases of PCP occur at CD4 counts below 200, at which point
prophylaxis is given the uninfected patient.
TB- as well as atypical Mycobacteria such as Mycobacterium avium.
COMMUNITY-ACQUIRED PNEUMONIA- the most common cause of
pulmonary disease in HIV.
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CLINICAL FINDINGS
2) SINOPULMONARY DISEASE-
SINUSITIS- tends to be chronic.
NONINFECTIOUS PULMONARY DISEASE- Kaposi’s sarcoma, non-Hodgkin’s
lymphoma.
3) CNS DISEASE
TOXOPLASMOSIS.
LYMPHOMA.
AIDS DEMENTIA.
CRYPTOCOCCAL MENINGITIS- w/ Cryptococcus neoformans.
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CLINICAL FINDINGS
3) CNS DISEASE
HIV MYELOPATHY.
PROGRESSIVE MULTIFOCAL LEOKOENCEPHALOPATHY (PML).
4) PERIPHERAL NERVOUS SYSTEM
INFLAMMATORY POLYNEUROPATHIES.
SENSORY NEUROPATHY.
MONONEUROPATHIES.
Treatment aimed at symptomatic relief- Neurontin (gabapentin).
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CLINICAL FINDINGS
5) RHEUMATOLOGIC
ARTHRITIS.
OTHER RHEUMATOLOGIC SYNDROMES- lupus, Reiter’s
syndrome, psoriatic arthritis.
6) MYOPATHY
Proximal muscle weakness.
Need to distinguish it from the myopathy as a side effect of
zidovudine therapy.
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CLINICAL FINDINGS
7) RETINITIS
CMV- most common retinal infection in HIV.
8) ORAL LESIONS
ORAL CANDIDIASIS.
HAIRY LEUKOPLAKIA- caused by EBV.
ANGULAR CHELITIS.
APHTHOUS ULCERS.
9) GASTROINTESTINAL
ESOPHAGEAL CANDIDIASIS-
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CLINICAL FINDINGS
9) GASTROINTESTINAL
HEPATIC DISEASE- various infections, and progression from the chronic
carrier state of hepatitis B and C to cirrhosis, liver failure, and carcinoma.
BILIARY DISEASE- cholecystitis, sclerosing cholangitis.
ENTEROCOLITIS- COMMON. Bacteria: Campylobacter, Salmonella,
Shigella. Viruses: CMV, adenoviruses. Protozoans:
Cryptosporidium,Giardia, Entamoeba histolytica, Isospora.
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CLINICAL FINDINGS
9) GASTROINTESTINAL
ENTEROCOLITIS- symptomati patients should have stool
culture, O&P. If negative, colonoscopy, Bx. If all negative
presumptive Dx of AIDS Enteropathy.
GASTROPATHY- inadequate acid production → increased
susceptibility to Campylobacter, Salmonella, Shigella, poor
absorption of drugs.
MALABSORPTION- idiopathic vs infection with
Cryptosporidium, Mycobacterium avium.
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CLINICAL FINDINGS
10) ENDOCRINE
HYPOGONADISM.
ADRENAL INVOLVEMENT AND HYPOFUNCTION.
THYROID DYSFUNCTION.
11) SKIN MANIFESTATIONS
HERPES SIMPLEX.
HERPES ZOSTER.
MOLLUSCUM CONTAGIOSUM.
FOLLICULITIS, FURUNCULOSIS, IMPETIGO
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CLINICAL FINDINGS
12) HIV-RELATED MALIGNANCIES
ANAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA- from HPV.
CERVICAL DYSPLASIA AND CARCINOMA- from HPV.
13) GYNECOLOGIC MANIFESTATIONS
VAGINAL CANDIDIASIS.
CERVICAL DYSPLASIA AND NEOPLASIA.
PID.
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CLINICAL FINDINGS
14) INFLAMMATORY REACTIONS
IMMUNE RECONSTITUTION SYNDROMES OR “IRIS.”- as the immune
system improves and CD4 count rises with initiation of antiretroviral
therapy.
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RISK TO HEALTHCARE
PROFESSIONALS
RISK
Risk of HIV transmission from a single needle stick from an
HIV-infected patient is about 1:300.
Risk is higher w/: deep puncture, large inoculum, high viral
load.
Risk from mucous membrane exposure is too low to
quantitate.
Follow universal precautions, no recapping, etc.
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RISK TO HEALTHCARE
PROFESSIONALS
NEEDLE STICK CONSELING, PROPHYLAXIS
After a needle-stick, counseling, HIV testing, baseline, retested at 6
weeks, 3 months, 6 months.
POST-EXPOSURE PROPHYLAXIS
Treatment w/ zidovudine reduces seroconversion by 79%.
Providers should be offered some form of post-exposure prophylaxis.
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RISK TO HEALTHCARE
PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS
Therapy modified in the face of source-patient who has a high viral load,
drug resistance.
Prophylaxis should begin ASAP, continued for 4 weeks.
Not 100% effective at reducing seroconversion.
“Safe sex” talk also needs to happen.
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RISK TO HEALTHCARE
PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE
Hard data does not exist, but there are similarities between the immune
response following transcutaneous and mucosal exposure.
Regimen similar to that for needle sticks in healthcare workers.
Not recommended after 72 hours.
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RISK TO HEALTHCARE
PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE
Should occur w/ appropriate counseling re how to prevent further
exposure- clean needles, “safe” sex, etc.
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PROGNOSIS
Improving.
1995- 50,610 deaths.
1999- 16,273 deaths.
The ticket is access to healthcare and appropriate
antiretroviral therapy w/ ability to monitor CD4 counts, viral
loads, to tailor therapy to each patient, including appropriate
prophylaxis etc.
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PREVENTION OF PERINATAL
TRANSMISSION
In the absence of prophylaxis, between 13% and 40% of
infants born to HIV+ women become infected.
Risk is higher w/ vaginal birth, high viral loads.
Also transmitted via breast milk- HIV+ women should NOT
breast feed.
PREVENTION
Treatment antepartum, intrapartum, and postpartum reduces
transmission by as much as 2/3.
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Antimycotics Affecting Membrane
Structure/Function
Ketoconazole (nizoral®)/ Itraconazole (sporanox®) / Fluconazole
(diflucan®)(safest) (imidazoles):
cryptococcus, blastomycosis, candida species, dermatophytes
Amphotericin-B: toxic but useful for systemic fungal infections
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Other Antifungal •Terbinafine:
•( lamisil®)
Agents •Dermatophytes, nail
infections (onychomycosis)
•Nystatin: •Blocks ergosterol
(mycostatin®) synthesis
•GI upset/Headaches
•Local application to
skin, mucus
membranes •AZOLES- clotrimazole,
•Candida species,- oral (lotrimin®), miconazole,
(micatin®)
and vaginal thrush, •Vulvovaginal candidiasis
intertrigo •Dermatophytes,
•Tinea: corporis/ pedis/ cruris
•Seborrheic dermatitis
•Pityriasis versicolor
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5-Flucytosine (ancobon®)
• analog of endogenous nucleotide
• competitively inhibits RNA synthesis
• mammalian cells unable to convert parent drug to metabolites
- bone marrow toxicity - anemia, leukopenia
• resistance due to altered metabolism of 5-flucytosine can
emerge rapidly; use combination therapy
- Cryptococcal meningits
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HAART facts:
• Inpatients that fail to take the three • A very effective combination
drugs for a week, there is a rise in therapy for HIV consists of-
viral load. zidovudine (AZT), lamivudine
(3TC) and protease inhibitor
• Non-compliance (Indinavir)
• The HAART is very expensive, for •A major problem with these
example the combination of complicated drug regimens is
compliance!
zidovudine/lamivudine/protease Partly related to drug side/toxic
inhibitor costs effects
$20,000 (US) per year
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Anti-Hepatitis Agents
Hepatitis B- Hepatitis C-genotype 2,3
Lamivudine- Interferon alfa-2b-
cytosine analog (97% suppression 15-30% response (on no therapy) / 98% clearance
in 2 weeks) recurs in 80% after on therapy
ceasing therapy
Peg* interferon alfa-2a
Adefovir-
Peg interferon alfa-2b- increased ½ life,
nucleoside analog
less frequent dosing;
Interferon alfa-2b- loss of
not superior to IF-alfa2b
HBeAg 30% improvement
*Peg= Poly Ethylene Glycol
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Ribavarin (Virazole®)
Guanosine analog
Effective against influenza A, B, resp. syncytial virus, HCV, HIV-1
Avialable anti flu therapy: neuraminidase inhibitors
Tamiflu :(Osletamivir)
Relenza : (Zanamivir)
?Flu vaccines-
Trivalent inactivated vaccine (TIV)
Live attenuated influenza virus (LAIV)
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Antimycobacterial Drugs
• tuberculosis (Mycobacteria)
Overview
• among the leading causes of death from infectious disease (primarily
tuberculosis)
• infections are among the most difficult to cure
Special Characteristics of Mycobacteria
• slow growth rate
- relatively resistant to antibiotics that depend on a rapid rate of division
- dormancy is possible (long-term treatment; months-years)
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At risk group for Tb
Older individuals Clinical features-
Immune suppressed group- HIV/ Weight loss
Steroid & Immunosuprressant Night fever and sweats
drug users Dry hacking cough
Diabetics Hemoptysis
Alcoholics Lymphadenopathy
Diagnostic tool: Manotux Tubercular meningitis
(tuberculin) skin test
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Standard therapy:
1. Isoniazid Drug side effects-
2. Rifampin Hepatitis
3. Pyrazinamide Neuritis
4. Ethambutol Optic neuritis/ color blindness
All 4 Drugs for first 2 months
Drugs 1&2 only for next 4 months
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