Evaluation of Immune Deficiency. Initial Work Up by Primary by knu24191

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									Evaluation of Immune Deficiency.
        Initial Work Up by
    Primary Care Physicians

    B. Bhushan Sharma, M.D., FAAP
      Pediatric Infectious Diseases
Review few children who presented with
infections suspicious of immunodeficiency
 Discuss the four arms of the immune system
Understand the various types of primary and
secondary immunodeficiencies
Know when to suspect immunodeficiency in a
Be able to initiate work up of a child suspected
of immunodeficiency
                   Case #1
3-month-old Hispanic girl with 2-week history of lymph
node swelling in neck and skin abscesses
A cousin died at a young age after undergoing bone
marrow biopsy in Mexico (diagnosis – unknown)
CBC – WBC 21K; normal H/H and platelet count
Culture of lymph node – Candida lusitaniae
Lymph node biopsy – necrotizing granulomatous
Chemiluminescence – Particulate stimulate <1 NOI
(>65); Soluble stimulate <1 NOI (>329)
Recurrent skin abscesses – Staphylococcus aureus,
Serratia marcescens, etc
               Case #2
13-year-old girl developed viral
meningoencephalitis twice within a year
and has history of recurrent herpes
simplex infection. In addition, she started
having recurrent ear and sinus infections.
History of hypothyroidism and vitiligo
Low serum IgG, IgM and IgA levels and
defective functional antibody formation
              Case #3
A 2-year-old boy was diagnosed with
Streptococcus pneumoniae meningitis in
1982. One year earlier, he was treated for
Haemophilus influenzae type b meningitis
No evidence of skull fracture or CSF leak
from nose or ear
CH50 – 0
Complement 2 (C2) - low
               Case #4
3-year-old girl presented to clinic with oral
thrush not responsive to oral nystatin
drops, but to oral fluconazole. Oral thrush
would recur once fluconazole was
stopped. She had received oral antibiotics
for otitis media a few months back. No
use of corticosteroids.
CBC – normal
HIV antibody - reactive
   The 4 Arms of Immune System
       and Their Jurisdiction
1. Humoral (B cell)
        Encapsulated organisms (S. pneumo; H. flu)
2. Cellular (T cell)
        Viruses (herpes, varicella, CMV)
        Fungi (candida, aspergillus)
        Protozoa (Pneumocystis carinii, toxoplasma)
        Bacteria (mycobacterium)
  The 4 Arms of Immune System
      and Their Jurisdiction
3. Phagocytic
      Fungi (aspergillus)
      Bacteria (low-virulence organisms)
4. Complement
      Bacteria (encapsulated organisms)
Classification Of Immunodeficiency
 Primary               Secondary
 – Inherited           –   Medications
 – Spontaneous         –   Malignancies
    genetic mutation   –   Infections
                       –   Protein wasting
                       –   Diabetes
                       –   Splenectomy
  Primary Immunodeficiency
A Primary Immunodeficiency (PI) disease results
whenever one or more essential parts of the immune
system is missing or not working properly at birth
because of a genetic defect
About 400 children are born in the United States with a
serious PI each year. The number of Americans now
living with a PI is estimated to be between 25,000 and
Very serious inherited immunodeficiencies become
apparent almost as soon as a baby is born. Many more
are discovered during the baby’s first year of life
Others—usually the milder forms—may not show up until
people reach their twenties and thirties
  Primary Immunodeficiency
Currently, the World Health Organization lists
over 70 PIs and the numbers are increasing
Among the rarest forms of immune deficiency is
Severe Combined Immune Deficiency (SCID).
SCID has been reported in small numbers, while
some deficiencies, like DiGeorge Anomaly, are
diagnosed more commonly
At the other extreme, an immune disorder called
Selective IgA Deficiency may occur in as many
as one in every 300 persons.
Catch the Big Fish
        Catch the Big One
DiGeorge syndrome       Common variable
Ataxia-telangiectasia   immunodeficiency
Hyper-IgM               (CVID)
Hyper-IgE (Job’s)       Leukocyte adhesion
                        deficiency (LAD)
 Catch the Big One: X-Linked
X-linked SCID         Chronic
X-linked              granulomatous
agammaglobulinemia    disease (CGD)
(Bruton’s)            Wiskott-Aldrich
X-linked hyper-IgM    syndrome
X-linked              Properdin deficiency
Catch the Small One

         of Infancy
              Diagnosing PI
Sometimes the signs and symptoms of a PI are so
severe, or so characteristic, that the diagnosis is obvious
Many conditions can produce an immunodeficiency, at
least temporarily, and most children who seem to have
"too many" infections are not, in fact, suffering from an
Experts estimate that 50 percent of the children who see
a doctor for frequent infections are normal
Another 30 percent may have allergies, and 10 percent
have some other type of serious disorder
Just 10 percent turn out to have a primary or secondary
Work Up of Immunodeficiency
Physical examination
Laboratory tests
        The Patient’s History
Species (of infecting organism)
Symptom-free intervals
Response to therapy (oral versus parenteral)
What, besides a PI, might explain the high rate of
Normal immune responses can be suppressed by many
factors, including malnutrition, injuries such as burns,
certain types of drugs (e.g., corticosteroids), some
diseases, such as leukemia, and some infections,
including infectious mononucleosis, chicken pox, etc
      Infection History - Site
Sinopulmonary       Hepatorenal
Gastrointestinal    Central nervous
Bone                system
Skin                Lymphatic
      The Patient’s History
Growth and development
Adverse reaction to live vaccines
Adverse reaction to blood transfusion
Autoimmune disorders
          Family History
Have any family members or relatives ever
been diagnosed with PI or shown an
unusual susceptibility to infections?
Have there been any infant deaths from
Were only boys affected?
Dr Dan Plunket

        August 9, 1983
        Rocky Mountain
        Spotted Fever
        Take home points
        Take Home Point
When a child who is immunologically
normal develops a string of infections, they
are usually mild and short-lived, and the
child recovers completely in between
  The Physical Examination
Is the child well-nourished and growing
A severely immunodeficient child is likely
to look sickly and pale
Very often the child is underweight and
lags behind in growth and development
  The Physical Examination
– Chronic otitis media
– Sinusitis
Oral mucosa
– Candidiasis
– Gingivitis
  The Physical Examination
– Absent tonsils/nodes
– Diffuse lymphoid hyperplasia
Respiratory tract
– Digital clubbing
– Rales
– Wheezing
  The Physical Examination
– Eczema
– Petechiae
– Pyoderma/abscesses
– Telangiectasia
– Micrognathia, short philtrum, ear anomalies
– Short-limbed dwarfism
  The Physical Examination
Musculoskeletal system
– Arthralgia/arthritis
– Dermatomyositis
– Lupus-like syndrome
Neurological system
– Ataxia
– Encephalitis/meningitis
        Take Home Point
An active, robust, healthy-looking child is
less likely to have a serious immune
 Ten Warning Signs of Primary
Eight or more ear infections in 1 year
Two or more serious sinus infection in 1
Two or more months on antibiotics with
little effect
Two or more pneumonias within 1 year
Two or more deep-seated infections
 Ten Warning Signs of Primary
Recurrent, deep skin or organ abscesses
Persistent thrush in mouth or elsewhere
on skin, after age 1 year
Need for intravenous antibiotics to clear
Failure of an infant to gain weight or grow
Family history of PI
Work Up of Immunodeficiency
Physical examination
Laboratory tests
  Initial Laboratory Work-Up
Complete blood count and differential
– Absolute neutrophil count <1,500/mm3
– Absolute lymphocyte count <2,500/mm3
– Cell morphology
Quantitative immunoglobulins (G,M,A)
– Age specific norms
– IgG1 constitutes 70% of IgG
Normal Immunoglobulin Levels
        Vary with Age
           Initial Work-Up
Anergy panel
– Skin test reactivity limited until 1-year of age
– 75% of children 12-36 months of age respond
  to Candida
Complement profile (CH50)
– Total hemolytic complement
– Low or nondetectable levels in deficient states
        Directed Work-Up
Chest x-ray
Cultures (blood, CSF, stool)
Sweat chloride
Consider referral to Immunologist or
Pediatric Infectious Disease physician
      Advanced Work-Up
IgG subclasses
Immunization titers
Complement component assays
Nitroblue tetrazolium test (NBT)
      Advanced Work-Up
Flow cytometry
Mitogen stimulation studies
Myeloperoxidase stain
Chemotaxis studies
Dr. Plunket and Movies

             • Last take home point


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