What infectious work-up should be done before starting high-dose immunosuppression, e.g. methylprednisolone (corticosteroid) pulse?

Pre-Immunosuppression Infectious Screening

Before initiating high-dose methylprednisolone pulse therapy, you must screen for tuberculosis, hepatitis B, Strongyloides, and consider HIV testing, with empirical antimicrobial coverage for suspected active infections until culture results return negative. 1, 2

Mandatory Screening Tests

Tuberculosis Screening

• Perform tuberculin skin test or interferon-gamma release assay (IGRA) in all patients 1, 2
• If latent tuberculosis or tuberculin reactivity is present, initiate chemoprophylaxis before starting methylprednisolone 1
• Close monitoring for reactivation is essential during prolonged therapy 1

Hepatitis B Virus (HBV) Screening

• Screen all patients with HBsAg, anti-HBc, and anti-HBs before initiating immunosuppressive treatment 3, 1
• Hepatitis B reactivation can occur even in patients with resolved infection 1
• Patients with positive anti-HBc require antiviral prophylaxis 4
• Consult hepatology for monitoring and antiviral therapy decisions in HBV-positive patients 1

Strongyloides Screening

• Rule out Strongyloides (threadworm) infestation, particularly in patients who have spent time in tropical regions or have unexplained diarrhea 1, 2
• Corticosteroid-induced immunosuppression can lead to hyperinfection syndrome with potentially fatal gram-negative septicemia 1

HIV Testing

• Consider HIV testing as part of baseline infectious workup 5
• This helps stratify infection risk and guide prophylaxis decisions 2

Additional Screening Based on Clinical Context

Amebiasis

• Rule out latent or active amebiasis in patients with tropical exposure or unexplained diarrhea 1
• Corticosteroids may activate latent amebiasis 1

Varicella Zoster and Measles Status

• Document immunity status to varicella and measles 1
• Non-immune patients require counseling about avoiding exposure 1
• If exposure occurs, prophylaxis with varicella zoster immune globulin or immunoglobulin may be indicated 1

Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis Considerations

PJP prophylaxis should be considered when high-dose corticosteroids (>30 mg prednisone-equivalent) will be used for >4 weeks, or with moderate doses (≥15 to <30 mg) for ≥8 weeks 2

• Methylprednisolone pulse therapy typically exceeds these thresholds 2
• The infectious risk is dose-dependent and duration-dependent 2, 6

Context-Specific Infectious Workup

For Neurological Presentations Requiring Pulse Steroids

When methylprednisolone is being considered for neurological immune-mediated conditions (e.g., aseptic meningitis, encephalitis, myelitis):

• Initiate empirical IV acyclovir until viral PCR results are negative 5
• Perform lumbar puncture with: cell count, protein, glucose, Gram stain, bacterial culture, HSV PCR, and other viral PCRs based on clinical suspicion 5
• Consider empirical antibacterial therapy until CSF culture results return 5

For Pulmonary Presentations

When considering high-dose steroids for grade 2 or higher pulmonary toxicity:

• Obtain infectious workup including: nasal swab, sputum culture and sensitivity, blood culture and sensitivity, urine culture and sensitivity 5
• Consider bronchoscopy with bronchoalveolar lavage if infection remains in differential 5
• COVID-19 evaluation per institutional guidelines 5

Critical Timing Considerations

The infectious screening should ideally be completed before initiating methylprednisolone, but in life-threatening situations, empirical antimicrobial coverage should be started concurrently with steroids while awaiting results 5

• For suspected CNS infections, do not delay acyclovir while waiting for PCR results 5
• For suspected bacterial infections, initiate empirical antibiotics until cultures are negative 5

Baseline Laboratory Assessment

Beyond infectious screening, obtain:

• Complete blood count with differential 3
• Liver and kidney function tests 3
• Blood glucose (diabetes increases adverse effect risk significantly) 3, 6
• Blood pressure and weight 3

Common Pitfalls to Avoid

• Do not assume resolved hepatitis B infection is safe - reactivation can occur even with anti-HBc positivity alone 1
• Do not skip Strongyloides screening in endemic area exposure - hyperinfection syndrome is potentially fatal 1
• Do not delay empirical antimicrobial therapy in suspected active infections - waiting for screening results can worsen outcomes 5
• Diabetic patients have 81% incidence of adverse effects with methylprednisolone - require enhanced monitoring 6

Infection Risk Stratification

The infectious risk with methylprednisolone pulse therapy is substantial:

• Doses >30 mg prednisone-equivalent place patients in high-risk category 2
• Infectious complications occurred in 13.4% of patients receiving pulse methylprednisolone in one cohort 6
• No severe infections were identified with cumulative doses <1.5g, but infections increased with higher cumulative doses 6
• The risk is both dose-dependent and duration-dependent 1, 2, 6