What is the increased risk of infection in an adult with Behcet's disease taking 150mg Imuran (azathioprine) daily and 5mg prednisone daily?

Infection Risk with Azathioprine 150mg and Prednisone 5mg Daily in Behçet's Disease

The combination of azathioprine 150mg daily and prednisone 5mg daily carries a moderate infection risk that is significantly lower than high-dose immunosuppression, but still requires vigilant monitoring for bacterial, viral, and opportunistic infections.

Risk Stratification for This Specific Regimen

Azathioprine 150mg Daily Risk Profile

• At 150mg daily (approximately 2-2.5 mg/kg for most adults), azathioprine causes moderate immunosuppression that increases susceptibility to infections, though monotherapy does not typically cause marked infection risk 1
• The FDA label explicitly warns that patients receiving azathioprine are at increased risk for bacterial, viral, fungal, protozoal, and opportunistic infections, including reactivation of latent infections 2
• Bone marrow suppression occurs in 5-30% of patients on azathioprine, with leukopenia being dose-dependent and potentially increasing infection susceptibility 1
• Varicella zoster virus infections occur more commonly in patients receiving azathioprine 1

Prednisone 5mg Daily Risk Profile

• At 5mg daily, prednisone is below the threshold for high-risk immunosuppression (≥10mg daily for general infection risk, ≥20mg daily for opportunistic infections) 3, 4
• The FDA label states that infection risk with corticosteroids is dose-dependent, and this low dose represents minimal individual risk 5
• Moderate doses (≥10mg/day) increase relative risk of all infectious events by 1.30-fold, while any dose increases opportunistic infection risk by 1.67-fold 3

Combination Therapy Amplification Effect

• The critical concern is that combination immunosuppressive therapy dramatically amplifies infection risk beyond additive effects: single agent use has an OR of 2.9 for opportunistic infections, while two agents combined have an OR of 14.5 3
• Even though each individual drug is at a moderate dose, the combination significantly increases infection susceptibility 6, 1

Specific Infection Risks to Monitor

Bacterial Infections

• Upper respiratory tract infections, serious pneumonias, skin infections, bacteremia, and sepsis are the primary bacterial concerns 6
• At 5mg prednisone, the risk for Pseudomonas aeruginosa is lower than the 10mg threshold identified by respiratory guidelines, but azathioprine adds additional risk 4
• Patients over 50 years of age on this combination are at highest risk for opportunistic bacterial infections 6

Viral Infections

• Varicella zoster virus (VZV) reactivation is a specific concern with azathioprine therapy 1
• Herpes simplex, CMV, and EBV infections are possible, particularly with combination therapy 6
• The FDA label warns that varicella and measles can have serious or fatal courses in non-immune patients on corticosteroids 5

Opportunistic Infections

• The combination creates moderate risk for opportunistic infections including oral/esophageal candidiasis, herpes zoster, and potentially tuberculosis reactivation 6
• At prednisone 5mg daily, Pneumocystis jirovecii prophylaxis is NOT routinely indicated (reserved for ≥20mg for ≥4 weeks) 6

Essential Monitoring Protocol

Hematologic Surveillance

• Weekly complete blood counts including platelet counts during the first month 2
• Twice monthly CBC for the second and third months 2
• Monthly CBC thereafter, or more frequently if dose changes occur 2
• Prompt dose reduction or temporary withdrawal if rapid fall in leukocyte count or persistent leukopenia develops 2

Clinical Monitoring

• Instruct patients to report immediately any evidence of infection, fever, sore throat, unexpected bruising or bleeding 1, 2
• Monitor for signs of VZV exposure in non-immune patients; consider varicella zoster immune globulin prophylaxis if exposure occurs 1, 5
• Regular assessment for respiratory symptoms, skin infections, and systemic signs of infection 6

Preventive Strategies

Vaccination Considerations

• Update all vaccines BEFORE starting immunosuppression, including pneumococcal, influenza (intramuscular), hepatitis B, and HPV 6
• Live vaccines are contraindicated once on azathioprine 1, 2
• The CDC permits shingles vaccine in patients on <20mg prednisone daily and azathioprine at rheumatic disease doses, though this should be given before starting therapy when possible 6
• Killed vaccines may have diminished efficacy on this regimen 1

Infection Screening

• Screen for latent tuberculosis if not previously done, though routine TB screening is not required before azathioprine monotherapy 1
• Consider EBV serology, particularly in younger patients, though routine screening remains controversial in adults 6
• Screen for hepatitis B before starting therapy, as reactivation can occur 5

Critical Caveats and Pitfalls

Common Monitoring Errors

• Mild lymphopenia is common with azathioprine and does not necessarily require dose reduction unless levels fall below 0.5 × 10^9/L 1
• Infection can occur even with normal blood counts, so normal CBC does not rule out infection risk 1
• Delayed hematologic suppression may occur, requiring ongoing vigilance beyond the first few months 2

Patient-Specific Risk Factors

• Age >65 years, diabetes, chronic liver disease, chronic kidney disease, or malnutrition substantially increase infection risk 6, 3
• Recent antibiotic use (within 3 months) increases risk of resistant organisms 4
• Active underlying Behçet's disease activity itself may increase infection susceptibility 6

Management of Infections

• Consider temporary withdrawal of azathioprine if serious infection develops, particularly VZV 1
• Prompt use of appropriate antivirals for herpesvirus infections 1
• Do not increase azathioprine dose intentionally to lower white blood cell count, as leukopenia does not correlate with therapeutic effect 2

Behçet's Disease-Specific Context

• Azathioprine at 2.5mg/kg/day (approximately 150-175mg for most adults) has been shown to control progression of Behçet's eye disease 7
• This combination is commonly used in Behçet's disease and represents standard therapy for moderate disease activity 7, 8
• The infection risk must be balanced against the risk of disease progression, particularly ocular complications that can lead to blindness in 20% of affected patients 7