How to assess for immunosuppression in a patient with current skin infections and potential underlying medical conditions, such as those taking corticosteroids (corticosteroids) or biologics (biologic agents)?

Assessment for Immunosuppression in Patients with Current Skin Infections

In patients with current skin infections, assess for immunosuppression by first ruling out infectious causes, then obtaining a detailed medication history (especially corticosteroids and biologics), followed by targeted laboratory testing including complete blood count, immunoglobulin levels, HIV testing, and screening for latent tuberculosis and hepatitis B. 1, 2

Initial Clinical Assessment

Rule Out Alternative Infectious Etiologies First

• The first requirement is ruling out any other etiology of the skin problem, such as an infection, an effect of another drug, or a skin condition linked to another systemic disease before attributing the infection to immunosuppression 1
• Perform thorough physical examination of the skin including mucosal areas, assess for fever, enlarged lymph nodes, and signs of systemic involvement 1
• Obtain cultures and consider skin biopsy to identify specific pathogens (bacterial, fungal, viral, or atypical organisms like nontuberculous mycobacteria) 2, 3

Critical Medication History

• Document all immunosuppressive medications including corticosteroids (dose and duration), biologics (anti-TNF agents, anti-IL-17, anti-IL-23, checkpoint inhibitors), and conventional immunosuppressants (methotrexate, azathioprine, cyclosporine, mycophenolate mofetil) 1, 4
• Corticosteroids reduce resistance to new infections, exacerbate existing infections, increase risk of disseminated infections, and mask signs of infection—with infectious complications increasing with higher dosages 4
• Recent intra-articular corticosteroid injections can predispose to atypical infections like nontuberculous mycobacteria, particularly in patients on biologics 3

Laboratory Evaluation

Essential Baseline Testing

• Complete blood count with differential to assess for leukopenia, lymphopenia, or neutropenia suggesting bone marrow suppression or primary immunodeficiency 1
• Comprehensive metabolic panel including liver and kidney function tests 1
• Quantitative immunoglobulin levels (IgG, IgA, IgM) to screen for common variable immunodeficiency (IgG <5 g/L plus low IgA or IgM) or hypogammaglobulinemia 1

Infectious Disease Screening

• HIV serology should be performed, as HIV enteropathy and opportunistic infections are well-documented causes of immunosuppression 1
• Tuberculosis screening with interferon-gamma release assay (IGRA) such as QuantiFERON Gold or T-SPOT.TB is preferred over tuberculin skin testing in patients already on immunosuppressive therapy, as tuberculin testing is not valid in this population 1, 5
• If IGRA is indeterminate in high-risk patients (those on biologics, corticosteroids, close TB contacts, or from endemic countries), repeat testing with new specimen or tuberculin skin test is required 5
• Hepatitis B serologic testing (HBsAg, anti-HBs, anti-HBc) and hepatitis C antibody before initiating or continuing immunosuppressive therapy, as reactivation can occur 1, 4

Additional Testing Based on Clinical Context

• Chest radiograph if tuberculosis screening is positive or if pulmonary symptoms are present 1, 5
• Stool studies including PCR and immunoassays if gastrointestinal symptoms suggest parasitic infections (Giardia, Strongyloides) 1, 4
• Consider testing for amebiasis in patients with unexplained diarrhea who have spent time in tropical regions 4

Risk Stratification for Specific Conditions

High-Risk Populations Requiring Enhanced Surveillance

• Recent immigrants from high-prevalence TB countries, injection drug users, residents of congregate settings (prisons, homeless shelters), healthcare workers with TB exposure 1
• Patients with diabetes mellitus, chronic renal failure, hematological conditions, or those requiring prolonged high-dose corticosteroid therapy 1
• Patients on combination immunosuppression (anti-TNF agents plus methotrexate or azathioprine carry 13-fold increased TB reactivation risk) 6

Specific Immunosuppressive Drug Considerations

• Corticosteroids can activate latent amebiasis, exacerbate systemic fungal infections, and cause Strongyloides hyperinfection with potentially fatal gram-negative septicemia 4
• Biologics, particularly anti-TNF agents, carry 4.7-fold increased risk of TB reactivation compared to placebo 6
• Checkpoint inhibitors (anti-PD-1, anti-CTLA-4) can cause immune-related adverse events but also paradoxically increase infection risk when treated with high-dose corticosteroids for toxicity management 1

Management Algorithm for Confirmed or Suspected Immunosuppression

Immediate Actions for Active Skin Infections

• Immunocompromised patients with skin infections of unknown etiology require very broad-spectrum empirical coverage: vancomycin (30-60 mg/kg/day targeting trough 15-20 μg/mL) PLUS an antipseudomonal beta-lactam (cefepime, meropenem, or piperacillin-tazobactam) 2
• Delaying broad-spectrum antibiotics while awaiting culture results can lead to rapid deterioration 2
• After 48-72 hours, de-escalate based on clinical response, culture results, and biopsy findings 2

Ongoing Monitoring Requirements

• Maintain high index of suspicion for tuberculosis throughout treatment and for 6 months after discontinuation of immunosuppressive therapy 1
• Annual TB screening may be considered in high-risk patients on biologics longer than 1 year using locally available IGRA 1
• Periodic assessment for new infections, including screening for nonmelanoma skin cancer in patients on chronic immunosuppression 1
• Monitor for varicella zoster and measles exposure—if exposed, prophylaxis with varicella zoster immune globulin or immunoglobulin may be indicated 4

Critical Pitfalls to Avoid

• Never use Bactrim monotherapy empirically in immunocompromised patients with skin infections—this leaves dangerous gaps in coverage for Pseudomonas, Streptococcus, and anaerobes 2
• Do not rely on tuberculin skin testing in patients already established on immunosuppressive therapy (methotrexate, biologics, corticosteroids)—use IGRA instead 1, 5
• Avoid starting or continuing biologics without first excluding active TB disease through symptom screening, chest radiography, and potentially sputum cultures 6
• Do not overlook atypical organisms (nontuberculous mycobacteria, fungi, parasites) in patients on combination immunosuppression or those with recent invasive procedures 3
• Corticosteroids mask signs of infection, so absence of fever or inflammatory markers does not exclude serious infection 4