Recurrent infections evaluation

Recurrent Infections - Spotting the Pattern

• B-cell/Antibody Defects: Recurrent sinopulmonary infections with encapsulated bacteria (S. pneumoniae, H. influenzae), enteroviral meningoencephalitis.
• T-cell/Combined Defects: Opportunistic infections - Pneumocystis jirovecii pneumonia (PJP), chronic mucocutaneous candidiasis, severe viral illness (CMV, EBV).
• Phagocytic Defects: Skin/organ abscesses, pneumonia, osteomyelitis. Catalase-positive organisms are key (Staph. aureus, Serratia, Aspergillus).
• Complement Defects: Recurrent invasive infections with encapsulated bacteria, especially Neisseria meningitidis.

⭐ Exam Pearl: Markedly reduced or absent tonsils and lymph nodes on physical examination should raise strong suspicion for a T-cell or combined immunodeficiency like SCID.

Infection Patterns - The Immune Whodunit

• B-cell (Antibody) Defects:

  • Recurrent sinopulmonary infections (otitis, sinusitis, pneumonia) & GI infections.
  • Pathogens: Encapsulated bacteria (S. pneumoniae, H. influenzae), enteroviruses.

• T-cell (Cellular) Defects:

  • Severe, opportunistic infections with low-virulence organisms.
  • Pathogens: Fungi (Candida, PCP), viruses (CMV, EBV, VZV), intracellular bacteria (Listeria).

• Phagocyte Defects (e.g., CGD, LAD):

  • Recurrent skin/soft tissue abscesses, poor wound healing, periodontitis, granulomas.
  • Pathogens: Catalase-positive organisms (S. aureus, Serratia, Aspergillus).

• Complement Defects:

  • Early (C1-C4): ↑ Sinopulmonary infections, ↑ autoimmune disease (SLE).
  • Terminal (C5-C9): ↑ Invasive infections with Neisseria species.

⭐ Patients with terminal complement (C5-C9) deficiency are particularly susceptible to recurrent Neisserial (e.g., N. meningitidis) infections.

Diagnostic Workup - The Immune Detective's Kit

Initial workup begins with simple, broad tests before proceeding to specialized assays based on the pattern of infection.

• Screening Tests:

  • Complete Blood Count (CBC) with differential: Check for neutropenia, lymphopenia.
  • Erythrocyte Sedimentation Rate (ESR) / C-Reactive Protein (CRP): Markers of inflammation.

• Tier 2 Investigations (Guided by History):

⭐ Dihydrorhodamine (DHR) Test: The DHR flow cytometry test is the gold standard for diagnosing Chronic Granulomatous Disease (CGD), being more sensitive and quantitative than the older Nitroblue Tetrazolium (NBT) test.

• B-cell defects cause recurrent sinopulmonary infections by encapsulated bacteria after 6 months; check immunoglobulin levels.
• T-cell defects lead to early-onset opportunistic infections (fungal, viral); use lymphocyte subset analysis.
• Phagocytic defects (e.g., CGD) present with recurrent skin abscesses; the best test is the DHR assay.
• Recurrent Neisseria infections strongly suggest terminal complement (C5-C9) deficiency; screen with CH50.
• The initial investigation for suspected immunodeficiency is a Complete Blood Count (CBC) with differential.