Evaluation for Immunologic Deficiency Syndromes

The pediatrician must be able to decide whether the patient presenting with increased infections has an underlying immunodeficiency. The incidence of primary deficiency syndromes is 1/10000 and is greater in boys than girls. 

Four Components of Immune System

  1. B-cell or humoral immunity. Deficiencies result in recurrent infections usually with encapsulated organisims or failure to respond to antibiotics. 
  2. T- cell or cell mediated immunity- usually present with unusual infections including viral and protozoal.
  3. Phagocytic system- represent the first line of defense and include neutrophiles and macrophages
  4. Complement system- enhance inflammation and cell lysis.
Clinical Features of Immunodeficiency
  1. Increased number of upper and lower respiratory infections especially otitis, sinusitis and pneumonia
  2. Increased use of antibiotics without apparent improvement
  3. Severe bacterial infections- meningitis, osteomyelitis, lung abscess and empyema
  4. Diarrhea and malabsorption
  5. Failure to grow and gain weight
  6. Opportunistic infections
  7. Routine viral infections that are unusually severe (chickenpox)
  8. Autoimmune reactions
  9. Hematologic changes including hemolysis, anemia, thrombocytopenia, and neutropenia.
  10. Difficulty in eradicating oral thrush
  11. + family history of immune disorders including HIV
Pertinent Findings on Physical Examination
  1. Poor growth and chronically ill appearance
  2. Absence or decreased lymph tissue including tonsils
  3. Enlarged liver and spleen
  4. Thrush
  5. Skin changes including petechiae, telangectasia, abscesses, eczema, impetigo, alopecia
  6. Dysmorphic features ( DiGeorge's Syndrome with facial abnormalities)
Initial Screening Tests for Immunodeficiency (make sure that you are using pediatric values)
  1. CBC
    1. Neutrophile number and morphology
    2. Platelet count and size
    3. Presence of anemia and evidence of hemolysis, Howell Jolly bodies
    4. Absolute lymphocyte count-> 3000 in infants and 1500 in older children
  2. Measurement of Quantitative Immunoglobulins(IgG, IgM, IgA) Low levels may also be secondary to GI and Renal losses. Check albumin level as well.
  3. Measurement of Isohemmoglutinins. These are IgM subclass and present unless blood type AB
  4. Skin tests for Candida, mumps, and tetanus. May be affected by steroid use and severe illness. Positive skin test essentially rules out T cell dysfunction.  Need immunization record
  5. Total Hemolytic Complement. Measure the ability to lyse antibody coated sheep RBCs. Low or absent indicates a defect at some site in the complement cascade. 
  6. Nitro blue tetrazolium test- measures phagocytic function. 
  7. Chest xray- presence of thymus and chronic lung changes
  8. HIV test.
After an initial evaluation, if immunodeficiency is suspected based on history, physical examination, and laboratory results, an evaluation should be performed by a pediatric immunologist. 

Treatment
           1. Manage infections aggressively and prophylaxis
           2. Insure immunizations
           3. Nutrition and monitor growth
           4. IVIG replacement
           5. May require Bone Marrow transplant

References

  1. Dizon Joseph G, Goldberg, Bruce J., Kaplan, Michael S How to Evaluate Suspected Immunodeficiency. Pediatric Annals. November 1998.
  2. Mamlok RJ. Primary Immunodeficiency Disorders. Primary Care; Clinics in Office Practice. 1998; 25(4):739-758.
  3. Boxer Laurence. Neutrophil Abnormalities. Pediatrics in Review February 2003
  4. Segel G, Halterman J.Evaluation of Neutropenia in Pediatric PracticePediatrics in Review January 2008