Primary Immunodeficiencies

◆B-cell defects (encapsulated bacteria + giardia + enterovirus)

• •Bruton X-linked agammaglobulinemia: boys >6 mo (after maternal IgG wanes); recurrent sinopulmonary infections; absent B cells + all immunoglobulins low; absent lymphoid tissue (no tonsils); BTK mutation. Tx: IVIG monthly
• •Selective IgA deficiency: MOST COMMON primary immunodeficiency; often asymptomatic; sinopulmonary + GI (Giardia); anaphylaxis with IgA-containing blood products (use washed PRBCs)
• •Common variable immunodeficiency (CVID): adult onset (15–35); ↓ IgG ± IgA/IgM; recurrent infections, autoimmune disease, lymphoma; replace IgG
• •Hyper-IgM syndrome (CD40L deficiency, X-linked): ↑IgM + ↓ other isotypes; PJP, Cryptosporidium (intractable diarrhea)

◆T-cell / combined (viruses, fungi, opportunistic)

• •DiGeorge (22q11.2 deletion): CATCH-22 — Cardiac (truncus arteriosus, TOF), Abnormal facies, Thymic aplasia (T-cell deficiency), Cleft palate, Hypocalcemia (parathyroid agenesis)
• •SCID: 'bubble boy'; absent T cells (± B cells); recurrent severe infections in first months; thrush, chronic diarrhea, FTT; bone marrow transplant curative
• •Wiskott-Aldrich (WATER / WAITER): X-linked; Wiskott = thrombocytopenia + Eczema + Recurrent infections; ↑IgE/IgA, ↓IgM; risk of lymphoma; WAS gene
• •Ataxia-telangiectasia: cerebellar ataxia + spider angiomas + ↑AFP + IgA deficiency; ATM gene (DNA repair); ↑lymphoma risk
• •Hyper-IgE (Job syndrome): coarse facies + cold abscesses + retained primary teeth + eczema + ↑↑IgE + eosinophilia; STAT3 mutation
• •Chronic mucocutaneous candidiasis: T-cell dysfunction → recurrent Candida of skin/mucosa

◆Phagocyte defects (catalase+ organisms, skin/abscess infections)

• •Chronic granulomatous disease (CGD): X-linked NADPH oxidase deficiency; recurrent infections with CATALASE+ organisms (Staph, Burkholderia, Serratia, Nocardia, Aspergillus); abnormal dihydrorhodamine flow test (replaces nitroblue tetrazolium)
• •Chediak-Higashi: AR; giant granules in neutrophils + albinism + peripheral neuropathy + recurrent pyogenic infections (Staph, Strep); LYST gene
• •Leukocyte adhesion deficiency (LAD-1): delayed umbilical cord separation (>30 days) + recurrent skin/mucosal infections WITHOUT pus + ↑↑neutrophils; CD18/integrin deficient

◆Complement deficiencies

• •C5–C9 (terminal/MAC): recurrent Neisseria (gonorrhea, meningococcus)
• •C1 esterase inhibitor deficiency: hereditary angioedema → face/airway swelling; AVOID ACE inhibitors; treat with C1 inhibitor concentrate, ecallantide, or icatibant. Do NOT use epinephrine/antihistamines/steroids (bradykinin-mediated, not histamine)
• •C3: severe pyogenic infections (encapsulated)

Infection pattern clues