Secondary immunodeficiencies

Secondary Immunodeficiencies - When Defenses Fail

• Acquired defects in the immune system; more common than primary immunodeficiencies.
• Causes:
  • HIV/AIDS: Depletes CD4+ T-cells. AIDS is defined by a CD4+ count <200 cells/mm³.
  • Immunosuppressive therapy: Corticosteroids, chemotherapy, anti-rejection drugs.
  • Malignancy: Especially hematologic (leukemia, lymphoma).
  • Malnutrition: Impairs T-cell and complement function.

⭐ Patients with AIDS are highly susceptible to EBV-associated lymphomas, such as primary CNS lymphoma.

Etiologies - The Usual Suspects

• Most Common Cause Worldwide: Malnutrition (protein-energy malnutrition).
• Infections:
  • HIV/AIDS: The most frequent cause in developed nations. Depletes CD4+ T-helper cells, leading to opportunistic infections.
  • Other viruses (e.g., Measles, CMV), bacteria, and fungi can cause transient or chronic immunosuppression.
• Neoplasms:
  • Especially hematologic malignancies (Leukemia, Lymphoma, Multiple Myeloma) that disrupt normal hematopoiesis and immune cell function.
• Iatrogenic/Medical Treatment:
  • Chemotherapy & Radiation: Cytotoxic effects on rapidly dividing immune cells.
  • Immunosuppressants: Corticosteroids, calcineurin inhibitors, biologics (e.g., anti-TNF).
  • Splenectomy: ↑ risk from encapsulated bacteria (e.g., S. pneumoniae, H. influenzae).
• Metabolic & Other:
  • Diabetes Mellitus: Impaired neutrophil function.
  • Uremia, Cirrhosis, Autoimmune diseases (e.g., SLE).

⭐ In HIV infection, a CD4+ T-cell count below 200 cells/μL is a defining criterion for AIDS and signals severe immunodeficiency.

HIV & AIDS - The Master Saboteur

• Virus: Lentivirus (a retrovirus). RNA genome is reverse transcribed into DNA.
• Key Proteins: gp120 (attachment to host CD4), gp41 (fusion & entry).
• Cellular Targets: CD4+ T-cells, macrophages, and dendritic cells.
• Pathogenesis: Progressive ↓ in CD4+ T-cell count, leading to immunodeficiency.

Clinical Course & Diagnosis

• Acute Phase: Flu-like/mononucleosis-like syndrome, viremia.
• Latent Phase: Asymptomatic, viral replication in lymph nodes.
• AIDS: CD4+ count < 200 cells/mm³ OR presence of AIDS-defining illness.
• Diagnosis: ELISA (screening), Western Blot (confirmatory), PCR (viral load).

⭐ Coreceptor Tropism: HIV uses CCR5 (early infection) or CXCR4 (late infection) coreceptors to enter T-cells. This is a key drug target (e.g., Maraviroc).

Workup & Management - Spotting and Supporting

• Initial Screen: CBC with differential (lymphopenia?), quantitative immunoglobulins (IgG, IgM, IgA), and HIV testing are paramount.
• Functional Assessment: Check specific antibody titers post-vaccination (e.g., Tetanus, Diphtheria) to assess B-cell function.
• Cellular Analysis: Flow cytometry to enumerate lymphocyte subsets (CD4+, CD8+, B-cells, NK cells) if lymphopenia is present.

⭐ In HIV, a CD4+ T-cell count < 200 cells/μL is an AIDS-defining illness, signaling severe immunodeficiency.

• Management:
  • Treat the underlying condition.
  • IVIG replacement for significant antibody deficiency.
  • Antimicrobial prophylaxis (e.g., PCP prophylaxis).
  • ⚠️ Avoid live-attenuated vaccines.

High‑Yield Points - ⚡ Biggest Takeaways

• HIV/AIDS is the most frequent cause of secondary immunodeficiency, leading to the depletion of CD4+ T-cells.
• Iatrogenic immunosuppression from corticosteroids, chemotherapy, and post-transplant drugs is a very common clinical scenario.
• Malnutrition, particularly protein deficiency, is a leading global cause of impaired immunity.
• Chronic diseases like diabetes mellitus, chronic kidney disease, and lymphoma significantly increase infection susceptibility.
• Asplenia dramatically increases the risk of sepsis from encapsulated bacteria.