Definition of Immunocompromised
An immunocompromised host has an alteration in phagocytic, cellular, or humoral immunity that increases the risk of infectious complications or opportunistic processes, including patients with breaches in skin or mucosal defense barriers. 1
Primary Categories of Immunocompromise
The Centers for Disease Control recognizes three main categories based on severity 1:
1. Severe Immunosuppression (Non-HIV)
- Congenital immunodeficiency 1
- Hematologic malignancies (leukemia, lymphoma) 1
- Generalized malignancy 1
- Chemotherapy with alkylating agents or antimetabolites 1
- Radiation therapy 1
- High-dose corticosteroids: ≥20 mg/day prednisolone for ≥2 weeks, or ≥2 mg/kg body weight 1
2. HIV Infection with AIDS
- Patients with HIV who have developed acquired immunodeficiency syndrome 1
3. Limited Immune Deficits
Primary vs. Secondary Immunodeficiency
Primary (Inherited) Immunodeficiencies 1
- B lymphocyte defects (humoral immunity impairment) 1
- T lymphocyte defects (cell-mediated and humoral immunity) including severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome 1
- Complement deficiencies 1
- Phagocytic cell defects 1
Secondary (Acquired) Immunodeficiencies 1
- HIV infection 1
- Solid organ or hematopoietic transplantation 1
- Immunosuppressive medications: corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, anti-TNF agents, monoclonal antibodies, other biologics 1
- Splenectomy 1
Practical Clinical Classification
The World Society of Emergency Surgery provides a functional three-tier system for risk stratification 1, 2:
Class A (Minimal Risk)
- Healthy patients with no or well-controlled comorbidities 1, 2
- No immunocompromise 1, 2
- Infection is the main clinical problem 1, 2
Class B (Moderate Risk)
- Major comorbidities and/or moderate immunocompromise 1, 2
- Currently clinically stable 1, 2
- Infection can rapidly worsen prognosis 1, 2
Class C (Severe Risk)
- Important comorbidities in advanced stages and/or severe immunocompromise 1, 2
- Infection worsens an already severe clinical condition 1, 2
- Requires multidisciplinary team management 1, 2
Additional High-Risk Factors
Beyond formal immunocompromise definitions, certain conditions increase susceptibility to infections 1, 2:
- Low serum albumin concentration 1, 2
- Advanced age 1, 2
- Obesity 1, 2
- Active smoking 1, 2
- Malnutrition 1
- Ischemia from vascular disease or irradiation 1, 2
Important Clinical Caveats
There is no clear-cut definition or single biological test to quantify immunosuppression. 1 The degree of immunocompromise exists on a spectrum and must be assessed individually by the treating physician 1.
Combination immunosuppressive therapy significantly increases infection risk beyond single-agent therapy. 1 For example, IBD patients on corticosteroids plus anti-TNF agents have higher risk than those on monotherapy 1.
Disease-specific considerations matter: Patients with inflammatory bowel disease are not inherently immunocompromised by their disease alone, but become so through immunomodulatory treatment 1. Similarly, the specific type of primary immunodeficiency determines which infections pose the greatest risk 1.
Corticosteroid dosing thresholds: Most experts agree that prednisone ≥20 mg/day for ≥14 days causes clinically significant immunosuppression, though shorter courses at higher doses or prolonged alternate-day therapy may also impair immunity 1.