What is the management approach for a patient on leflunomide (a disease-modifying antirheumatic drug (DMARD)) who develops a brain abscess?

Management of Brain Abscess in a Patient on Leflunomide

For patients on leflunomide who develop a brain abscess, immediate discontinuation of leflunomide with drug elimination procedure using cholestyramine or charcoal is essential, followed by neurosurgical aspiration or excision of the abscess and 6-8 weeks of appropriate antimicrobial therapy. 1, 2

Immediate Management Steps

1. Diagnostic Confirmation

   • MRI is strongly recommended for diagnosis of brain abscess (strong recommendation, high certainty) 1
   • Blood cultures should be obtained in all patients (present in 28% of cases) 1

2. Leflunomide Management

   • Immediately discontinue leflunomide 2
   • Initiate drug elimination procedure with:
     • Cholestyramine 8g three times daily for 11 days, OR
     • Activated charcoal 50g four times daily for 11 days 2
   • This washout procedure is critical as leflunomide has a long half-life and continued immunosuppression may worsen infection outcomes 2, 3

3. Neurosurgical Intervention

   • Aspiration or excision of brain abscess is strongly recommended whenever feasible (strong recommendation, low certainty) 1
   • Samples should be sent for:
     • Aerobic and anaerobic cultures
     • Histopathological analysis
     • Molecular-based diagnostics if cultures are negative (conditional recommendation, moderate certainty) 1

Antimicrobial Therapy

Empiric Treatment:

• For immunocompromised patients (including those on DMARDs like leflunomide):
  • 3rd-generation cephalosporin AND metronidazole (strong recommendation, moderate certainty)
  • PLUS trimethoprim-sulfamethoxazole AND voriconazole (conditional recommendation, low certainty) 1

Duration:

• Continue antimicrobial treatment for 6-8 weeks (conditional recommendation, low certainty) 1
• Intravenous administration is preferred; early transition to oral antimicrobials is not routinely recommended 1

Adjunctive Treatments

• Corticosteroids: Recommended only for treatment of severe symptoms due to perifocal edema or impending herniation (strong recommendation, low certainty) 1
• Antiepileptics: Primary prophylaxis with antiepileptics is not recommended (conditional recommendation, very low certainty) 1

Monitoring and Follow-up

1. Imaging Follow-up

   • Immediate imaging for clinical deterioration
   • Otherwise, regular interval imaging (approximately every 2 weeks) until clinical cure is evident 1
   • Be aware that radiological resolution may lag behind clinical improvement by 3-6 months 1

2. Repeat Neurosurgical Intervention

   • Consider if clinical deterioration occurs
   • Almost always required if no reduction in abscess volume after 4 weeks 1

Special Considerations for Leflunomide Patients

• Leflunomide increases susceptibility to opportunistic infections, including severe infections that may be fatal 2, 3
• Case reports have documented brain abscess development in rheumatoid arthritis patients on leflunomide 3
• The immunosuppressive effects of leflunomide may mask typical signs of infection (e.g., fever may be absent) 3, 4
• Infections may progress rapidly in patients taking leflunomide, making early intervention critical 5

Pitfalls to Avoid

1. Delayed diagnosis: Brain abscess may be misdiagnosed as CNS involvement of rheumatic disease in immunosuppressed patients 4
2. Inadequate drug elimination: Failure to perform leflunomide washout may lead to continued immunosuppression and poor outcomes 2, 5
3. Immune Reconstitution Inflammatory Syndrome (IRIS): Radiological worsening after immunosuppressant withdrawal may represent IRIS rather than treatment failure 6
4. Inadequate duration of antimicrobial therapy: Premature discontinuation of antibiotics may lead to relapse 1
5. Missing opportunistic pathogens: Consider atypical organisms including fungi, Nocardia, and mycobacteria in immunosuppressed patients 1, 4

By following this structured approach, the management of brain abscess in patients on leflunomide can be optimized to improve outcomes in this life-threatening condition.