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Internal Medicine

Primary immunodeficiencies (PID)

Disorders in which part of the body’s immune system is missing or does not function normally due to a primary cause (usually genetic).

figure-12
Schematic representation of points in immunologic development at which dysfunction or deficiency can occur in the various primary immunodeficiencies. 1. Reticular dysgenesis; 2. Aplastic anemia; 3. Chronic granulomatous disease; 4. Severe combined immune deficiency (SCID); 5. DiGeorge syndrome; 6. Coronin-1 A deficiency; 7. X-linked agammaglobulinemia (XLA); 8. Common variable immunodeficiency (CVID). | Bellanti, JA (Ed). Immunology IV: Clinical Applications in Health and Disease. I Care Press, Bethesda, MD, 2012

Classification

International Union of Immunological Societies:

Nine classes of primary immunodeficiencies:

  1. Combined T and B–cell immunodeficiencies
  2. Predominantly antibody deficiencies
  3. Other well-defined immunodeficiency syndromes
  4. Diseases of immune dysregulation
  5. Congenital defects of phagocyte number, function, or both
  6. Defects in innate immunity
  7. Autoinflammatory disorder
  8. Complement deficiencies
  9. Phenocopies of primary immune deficiencies
figure-22
Relative distribution of the primary immunodeficiencies according to a more traditional classification. | Stiehm ER, editor. Immunologic disorders in infants and children. 5th ed. Philadelphia: Elsevier, Inc.; 2004

Diagnosis

European Society of Immunodeficiencies (ESID) warning signs for suspicion of PID:

  1. ≥ 4 new infections in a year
  2. ≥ 2 serious sinus infections in a year
  3. ≥ 2 cases of pneumonia in a year
  4. ≥ 2 months of antibiotics without effect
  5. Failure of an infant to gain weight or grow normally
  6. Recurrent deep skin infections or organ abscesses
  7. Persistent oral thrush, or candidiasis elsewhere beyond infancy
  8. Need for IV antibiotics to clear infections
  9. ≥ 2 deep-seated infections (e.g. meningitis, cellulitis)
  10. Family history of immunodeficiency

Screening investigations:

  • Total and differential leukocyte counts, leukocyte morphology
  • HN serology
  • X-ray chest
  • Delayed skin tests (Candida, tetanus toxoid)

Specific investigations:

  • Blood levels of immunoglobulins: IgG, IgA, IgM; IgG subclasses
  • Blood group isohemagglutinins (for functional IgM)
  • Anti-diphtheria and anti-tetanus antibodies (functional IgG)
  • Lymphocyte subsets: CD3, CD4, CD8, CD19, CD16
  • Mitogen stimulation tests (response to phytohemagglutinin)
  • Nitroblue tetrazolium (NBT) dye reduction test
  • CHSO, complement component assays
  • Mannan-binding lectin assay
  • Enzyme assays: adenosine deaminase, purine nucleoside phosphorylase
  • HLA typing
  • Bacterial killing
  • Chemiluminescence studies

Management

Haematopoietic stem cell transplantation (HSCT):

  • Done in early infancy
  • Cannot be carried out for children with ataxia-telangiectasia

Immunoglobulin therapy:

  • Types:
    • Intravenous (IVIg)
    • Subcutaneous (ScIg)
    • Intramuscular (IMIg)
  • Composition: 90% monomeric IgG + IgA & IgM
  • Dose: 0.4-0.6 g/kg every 3-4 weeks
  • Complications:
    • Short-term: Anaphylaxis, chills or rigors
    • Long-term: Hepatitis C infection

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