Immunodeficiency syndromes - acquired
Description
- Immune dysfunction arising from an external cause acting on a previously normal immune system - distinct from primary (genetic) immunodeficiency
- Two broad groups: HIV/AIDS (the paradigm acquired immunodeficiency) and secondary immunodeficiency from drugs, malignancy, malnutrition, or organ/protein loss
Epidemiology
- HIV - low but ongoing incidence in Australia, concentrated in specific risk networks; late diagnosis remains a major driver of AIDS-defining illness
- Secondary immunodeficiency - increasingly common given widespread use of B-cell depleting biologics (rituximab), long-term corticosteroids, and an ageing population with haematological malignancy
Aetiopathogenesis
HIV
- Retrovirus infects CD4+ T-cells via gp120-CD4/CCR5 or CXCR4 co-receptor binding -> progressive CD4 depletion + immune dysregulation
- Untreated - progressive decline in CD4 count over years -> AIDS-defining illnesses once CD4 <200 cells/uL (or specific opportunistic infections/malignancies regardless of count)
Secondary (drug/disease-induced)
| Cause | Mechanism |
|---|---|
| Corticosteroids (chronic, high-dose) | Broad suppression of cell-mediated immunity and neutrophil function |
| Rituximab / other anti-CD20 | B-cell depletion -> secondary hypogammaglobulinaemia, can be prolonged/permanent |
| Chemotherapy | Neutropenia, lymphopenia |
| CLL, myeloma, other B-cell malignancy | Intrinsic hypogammaglobulinaemia from clonal B-cell/plasma cell dysfunction |
| Malnutrition | Impaired lymphocyte proliferation, thymic atrophy |
| Nephrotic syndrome / protein-losing enteropathy | Urinary/GI immunoglobulin loss |
| Splenectomy/hyposplenism | Loss of splenic macrophage filtering -> inc risk of encapsulated organism sepsis |
| Diabetes, uraemia, cirrhosis | Multifactorial innate and adaptive immune impairment |
Diagnosis
HIV
- 4th-generation Ag/Ab combination screening test, confirmatory testing, then HIV RNA viral load + CD4 count to stage
- Screen for opportunistic co-infections at diagnosis (TB, hepatitis B/C, syphilis, toxoplasma serology)
Secondary immunodeficiency
- Serum immunoglobulins (IgG, IgA, IgM) - quantify hypogammaglobulinaemia
- FBE + differential - neutropenia, lymphopenia
- Pneumococcal/tetanus vaccine response testing if borderline immunoglobulins - functional antibody response, not just the level, determines significance
- Blood film for Howell-Jolly bodies (hyposplenism)
- Identify and address the underlying driver (drug review, malignancy work-up, nutritional/protein-loss assessment)
Management
HIV
- Combination ART for everyone at diagnosis, regardless of CD4 count - start as soon as practicable
- Opportunistic infection prophylaxis by CD4 threshold:
- CD4 <200 - PJP prophylaxis (co-trimoxazole)
- CD4 <150 - consider histoplasmosis prophylaxis (endemic areas)
- CD4 <50 - MAC prophylaxis (azithromycin), CMV retinitis surveillance
- Prophylaxis ceases once CD4 recovers above threshold on effective ART
- Screen for and treat co-infections (TB, viral hepatitis)
Secondary immunodeficiency - by presenting problem
- Recurrent sinopulmonary infection with confirmed hypogammaglobulinaemia + poor vaccine response - immunoglobulin replacement therapy (IVIG/SCIG)
- Reduce/stop the causative drug where possible (steroid-sparing strategy, space out rituximab dosing) - balanced against the need to treat the underlying disease
- Hyposplenism - lifelong penicillin prophylaxis (or macrolide if penicillin-allergic) in high-risk patients, vaccination (pneumococcal, meningococcal, Hib, annual influenza), medical alert card, early antibiotics for febrile illness
- Vaccinate proactively before planned immunosuppression (e.g. before elective splenectomy or rituximab) where possible - post-treatment responses are blunted
- Treat the underlying malignancy/malnutrition/protein-losing state where feasible
Associations
- HIV - opportunistic infections (PJP, toxoplasmosis, CMV, cryptococcus, MAC), AIDS-defining malignancies (Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer)
- Hyposplenism - overwhelming post-splenectomy infection (encapsulated organisms - S. pneumoniae, H. influenzae, N. meningitidis)
- Secondary hypogammaglobulinaemia - recurrent sinopulmonary infections, bronchiectasis if longstanding/unrecognised
Natural history & complications
- HIV on effective ART - near-normal life expectancy, viral suppression prevents transmission (U=U, undetectable = untransmittable)
- Untreated HIV - progressive immunodeficiency, AIDS, death from opportunistic infection/malignancy
- Secondary immunodeficiency - often reversible if the causative drug/disease is addressed; rituximab-induced hypogammaglobulinaemia can persist for years after the last dose
- Overwhelming post-splenectomy infection carries high mortality but is largely preventable with vaccination and prompt antibiotic access
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