Evaluation for Immunologic Deficiency Syndromes

The pediatrician must be able to decide whether the patient presenting with increased infections has an underlying immunodeficiency. Immunodeficiency could be primary (congenital) or acquired. e.g. secondary to HIV infection, cancer, or chemotherapy.  Primary immunodeficiencies are generally determined and can present early or at birth.  Many follow simple mendelian inheritnce and are due to single gene defects, e.g. chronic granulomatous disease, and Wiskott Aldrich Syndrome.  The incidence of primary deficiency syndromes is 1/10000 and is greater in boys than girls.  The most common primary immunodeficiencies are humoral: selective IgA deficiency and IgG subtype deficiency.

 Components of Immune System
    Innate
        Evolutionary amore ancient and serves as the first line of defense.  Recetors are genetially determined and have broad specificity abut limited flexibility
           1.  Phagocytic system- include neutro;hils and macrophages,  Deficiencies     typically present with pyogenic infections.
            2. Complement system- enhance inflammation and cell lysis.  Coplement deficiencies may present with autoimmunity and recurrent neiserrial infections.

    Adaptive
         Requires DNA rearrangement for recptor formation and is designed to porvice flexibility and individualized response to a varitety of antigens.
              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.

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 (ataxia telangectasia, abscesses (CGD), eczema( WAS), impetigo, alopecia
  6. Dysmorphic features ( DiGeorge's Syndrome with facial abnormalities)
  7. Albinism (Chediak Higashi Syndrome)
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 innate 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- Assesses oxidative burst for intracellualr killing of phagocytes.  Positive result suggests chronic granulomatous disease. 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. Geha RS, Notarangelo LD et al. Primary immunodeficiency diseases, an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol (120) 2007 776-794.
  5. Notarangelo LD. Primary Immunodeficiencies. J Allergy Clin Immunol Supplement 2 (125) 2010 776-794. S182-194

  7. Segel G, Halterman J.Evaluation of Neutropenia in Pediatric PracticePediatrics in Review January 2008