What is the treatment for tuberculous (TB) arthritis with a superimposed Aspergillus infection in a patient with active Rheumatoid Arthritis (RA)?

From the Guidelines

Treatment of tuberculous arthritis with superadded aspergillus infection in active rheumatoid arthritis requires a multifaceted approach, prioritizing the control of both infections while managing the underlying autoimmune condition, with the goal of minimizing morbidity, mortality, and improving quality of life. First, initiate anti-tuberculosis therapy with a standard four-drug regimen: isoniazid (5 mg/kg/day), rifampin (10 mg/kg/day), ethambutol (15 mg/kg/day), and pyrazinamide (25 mg/kg/day) for 2 months, followed by isoniazid and rifampin for an additional 10 months, as recommended by the American Thoracic Society (ATS)/CDC–Approved Regimen 1. Concurrently, treat the aspergillus infection with voriconazole (loading dose of 6 mg/kg IV twice daily on day 1, followed by 4 mg/kg IV twice daily, transitioning to oral therapy at 200 mg twice daily) for at least 6-12 weeks, with treatment duration guided by clinical response, as per the guidelines for the management of opportunistic infections in inflammatory bowel disease 1. For rheumatoid arthritis management, temporarily discontinue immunosuppressive medications like TNF inhibitors and methotrexate during the initial intensive phase of antimicrobial treatment, and consider using low-dose prednisone (5-10 mg daily) to control RA symptoms while minimizing immunosuppression, in line with the EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs 1. Some key points to consider in the treatment approach include:

• The importance of early initiation of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis, as recommended by the EULAR task force 1
• The need for regular monitoring of disease activity and adjustment of treatment accordingly, with the goal of achieving remission or low disease activity, as emphasized by the EULAR recommendations 1 and the systematic literature review on the efficacy of conventional synthetic DMARDs, glucocorticoids, and tofacitinib 1
• The consideration of safety aspects in the choice of DMARDs, including the potential risks and benefits of different treatment options, as highlighted by the systematic literature review on the safety of synthetic and biological DMARDs 1
• The importance of a multidisciplinary approach, involving rheumatologists, infectious disease specialists, and other healthcare professionals, to ensure comprehensive care and optimal outcomes for patients with tuberculous arthritis and superadded aspergillus infection in active rheumatoid arthritis. Regular monitoring is essential, including liver function tests, complete blood counts, and renal function tests to assess for medication toxicity, and surgical debridement may be necessary to remove infected synovial tissue and drain abscesses. Once the infections show significant improvement, gradually reintroduce disease-modifying antirheumatic drugs (DMARDs), preferably starting with hydroxychloroquine or sulfasalazine which have less immunosuppressive effects, as recommended by the EULAR task force 1. This complex treatment approach balances the need to control both infections while managing the underlying autoimmune condition, with the goal of minimizing morbidity, mortality, and improving quality of life.

From the FDA Drug Label

For Treatment of Tuberculosis Isoniazid is used in conjunction with other effective anti-tuberculosis agents. The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease Because of the insufficient data, military tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 month therapy. The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease.

Treatment Approach: To treat tuberculous arthritis with a superadded Aspergillus infection in active Rheumatoid arthritis, a combination of anti-tubercular and anti-fungal agents should be used.

• Anti-tubercular therapy: Isoniazid, rifampicin, and ethambutol can be used in combination for the treatment of tuberculosis, including bone and joint tuberculosis.
• Anti-fungal therapy: Treatment for Aspergillus infection should be initiated concurrently.
• Adjunctive therapy: Corticosteroids may be considered to reduce inflammation and prevent further joint damage.
• Duration of treatment: Treatment should be continued for at least 12 months, as recommended for bone and joint tuberculosis.
• Monitoring: Regular monitoring of the patient's condition, including clinical and radiographic findings, is essential to assess the response to treatment and adjust the treatment regimen as needed.

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From the Research

Treatment Approach

To treat tuberculous arthritis with superadded Aspergillus infection in active Rheumatoid arthritis, the following points should be considered:

• The treatment of tuberculosis (TB) typically involves a combination of antibiotics, such as isoniazid, rifampin, pyrazinamide, and ethambutol 5, 6, 7, 8, 9.
• The presence of Aspergillus infection may require additional antifungal treatment, but there is no direct evidence in the provided studies to support this.
• Rheumatoid arthritis (RA) is an autoimmune disease that requires separate treatment, which may involve disease-modifying antirheumatic drugs (DMARDs), biologics, or other medications.

Drug Interactions and Pharmacokinetics

• The pharmacokinetics of anti-TB drugs can be affected by various factors, including human immunodeficiency virus (HIV) infection, formulation factors, gender, age, and previous TB treatment 6.
• Drug-drug interactions between anti-TB drugs and other medications, including those used to treat RA, should be carefully considered to avoid adverse effects or reduced efficacy 8.

Treatment Outcomes

• The effectiveness of anti-TB treatment can be measured by sputum conversion rates, treatment outcomes, and adverse event rates 7, 9.
• Fixed-dose combination (FDC) formulations of anti-TB drugs may have advantages over separate-drug formulations, including improved sputum conversion rates and reduced death rates 9.

Limitations

• There is no direct evidence in the provided studies to support the treatment of tuberculous arthritis with superadded Aspergillus infection in active Rheumatoid arthritis.
• Further studies are needed to investigate the optimal treatment approach for this complex condition.