Secondary Immunodeficiency Disorders

SID Intro - Acquired Immune Gaps

• Secondary Immunodeficiencies (SIDs): Acquired, not congenital, defects in the immune system.
• Far more prevalent than Primary Immunodeficiencies (PIDs).
• Onset typically later in life, resulting from extrinsic factors.
• Key Causes/Mechanisms:
  • Infections (e.g., HIV targeting CD4+ T-cells).
  • Malnutrition (impaired cell-mediated immunity, phagocyte function).
  • Immunosuppressive drugs (e.g., corticosteroids, chemotherapy).
  • Chronic diseases (e.g., diabetes, uremia, malignancies).
  • Loss of immunoglobulins (e.g., nephrotic syndrome, protein-losing enteropathy).

⭐ Malnutrition is globally the leading cause of secondary immunodeficiency, affecting cell-mediated immunity, antibody production, and phagocytic function.

SID Causes - The Immune Wreckers

📌 MIDAS for common causes:

• Malnutrition:
  • Protein-Energy Malnutrition (PEM) - most common global cause, impairs cell-mediated immunity, phagocyte function, antibody synthesis.
• Infections:
  • Viral: HIV (progressive ↓CD4+ T-cells), Measles (transient immunosuppression), CMV, EBV.
  • Bacterial: Tuberculosis.
• Drugs:
  • Immunosuppressants: Corticosteroids (broad effects), Cyclosporine, Tacrolimus.
  • Chemotherapy agents (myelosuppression).
  • Biologics (e.g., anti-TNF agents).
• Autoimmune/Malignancy:
  • Autoimmune diseases: Systemic Lupus Erythematosus (SLE).
  • Malignancies: Leukemia, Lymphoma, Multiple Myeloma.
• Systemic/Stress:
  • Chronic diseases: Renal failure, Liver disease, Diabetes Mellitus.
  • Protein loss: Nephrotic syndrome, protein-losing enteropathy.
  • Other: Major burns, Trauma, Post-splenectomy, Extremes of age.

⭐ HIV infection is the most common cause of severe secondary immunodeficiency worldwide, characterized by a profound depletion of CD4+ T-lymphocytes.

Pediatric HIV - Viral Immune Sabotage

• Transmission: Primarily vertical (mother-to-child): in-utero, intrapartum, breastfeeding.
• Pathogenesis: HIV targets CD4+ T-cells → progressive immunodeficiency.
• Diagnosis (<18m): HIV DNA/RNA PCR (maternal Ab interfere with antibody tests). Two positive virologic tests confirm.
• Staging (WHO): Clinical + CD4 counts.
  • Severe immunodeficiency: CD4 <25% (<1yr), <20% (1-3yr), <15% (3-5yr), or <200 cells/µL (≥5yr).
• Management: Lifelong Antiretroviral Therapy (ART). OI prophylaxis (e.g., PCP if CD4 <25% or <1500 cells/µL in infants <1yr).
• PMTCT: Maternal ART, infant ARV prophylaxis.

⭐ Early ART (first 12 weeks of life) in HIV-infected infants drastically ↓mortality & ↑neurodevelopmental outcomes.

Other SIDs & Workup - Spotting Trouble

• Key SIDs:
  • Malnutrition: Globally most common; impairs CMI, phagocyte function, IgA.
  • Drug-induced: Corticosteroids, chemotherapy, immunosuppressants (e.g., biologics).
  • Infections: HIV (depletes CD4+ T-cells), Measles (transient suppression).
  • Protein loss: Nephrotic syndrome, protein-losing enteropathies (↓immunoglobulins).
  • Asplenia/Splenectomy: Increased risk from encapsulated bacteria (Pneumococcus, Hib).
• Spotting Trouble (📌 SPUR infections):
  • History: Severe, Persistent, Unusual, Recurrent infections; adverse vaccine reactions; family Hx.
  • Exam: Failure to thrive (FTT), lymphadenopathy, hepatosplenomegaly, chronic eczema.
  • Initial Labs: CBC with differential (lymphopenia, neutropenia), ESR/CRP.

⭐ HIV is the most common infectious cause of secondary immunodeficiency worldwide, primarily targeting CD4+ T-lymphocytes.

High‑Yield Points - ⚡ Biggest Takeaways

• Malnutrition is the leading global cause of secondary immunodeficiency.
• HIV infection causes CD4+ T-cell depletion, a major secondary immunodeficiency.
• Immunosuppressive drugs like corticosteroids and chemotherapy are common iatrogenic causes.
• Hematologic malignancies (e.g., leukemia, lymphoma) frequently lead to immune defects.
• Protein-losing states (e.g., nephrotic syndrome) result in hypogammaglobulinemia.
• Splenectomy ↑ risk of infection by encapsulated organisms.
• Chronic infections (e.g., tuberculosis, measles) can suppress host immunity.