How to manage a patient with rheumatoid arthritis, Sjögren's syndrome, and myositis, who is currently diagnosed with myocarditis and has an active infection, while on immunosuppressive medications such as mycophenolate mofetil (Cellcept) or methotrexate (Trexall)?

Management of Rheumatoid Arthritis, Sjögren's Syndrome, and Myositis with Active Infection and Myocarditis

Immediately discontinue mycophenolate mofetil and methotrexate in the presence of active infection and myocarditis, as these immunosuppressive agents increase susceptibility to serious infections and the combination of myocarditis with active infection represents a life-threatening emergency requiring full immunosuppression withdrawal. 1, 2, 3

Immediate Actions for Active Infection with Myocarditis

Discontinue All Immunosuppressive DMARDs

• Stop mycophenolate mofetil immediately as it increases risk of bacterial, fungal, protozoal, and viral infections that may lead to fatal outcomes, and the FDA label explicitly warns against use during active infection 3
• Stop methotrexate immediately as it should be used with extreme caution in the presence of active infection and is usually contraindicated in patients with immunodeficiency, with potentially fatal opportunistic infections including Pneumocystis carinii pneumonia reported 2
• The American College of Rheumatology guidance for COVID-19 (applicable to all active infections) recommends holding immunosuppressants including mycophenolate mofetil and methotrexate when documented infection is present 1

Myocarditis Management Takes Priority

• Initiate high-dose corticosteroids (methylprednisolone 1-2 mg/kg IV or prednisone 1 mg/kg/day orally) for myocarditis treatment, as this is the first-line therapy despite active infection, because myocarditis represents a medical emergency with high mortality 1, 4, 5
• Obtain cardiac troponin levels (preferably high-sensitivity troponin I which is myocardium-specific), 12-lead ECG, echocardiography, and cardiac MRI to assess extent of myocardial involvement 5
• Monitor for life-threatening complications including arrhythmias, heart block, and acute heart failure 5
• Avoid NSAIDs completely as they increase inflammation and mortality in myocarditis 5

Infection Management Strategy

Identify and Treat the Infection Aggressively

• Obtain cultures (blood, urine, sputum as indicated) and imaging to identify infection source before starting empiric antimicrobials 1
• Consider opportunistic infections given immunosuppressed state: test for Pneumocystis jirovecii, CMV, fungal infections, and reactivated viral infections (HBV, HCV) 2, 3
• Initiate broad-spectrum antimicrobials empirically while awaiting culture results, then narrow based on sensitivities 1
• Monitor for polyomavirus-associated nephropathy (PVAN), JC virus-associated PML, and CMV infections which are reported with mycophenolate mofetil use 3

Balance Immunosuppression with Infection Risk

• Continue high-dose corticosteroids for myocarditis despite infection as the mortality risk from untreated myocarditis exceeds infection risk, but ensure aggressive antimicrobial coverage 1, 5
• Do not restart mycophenolate mofetil or methotrexate until infection completely resolves and clinical manifestations normalize 1, 4
• For steroid-refractory myocarditis (clinical deterioration despite methylprednisolone), consider adding abatacept or intravenous immunoglobulin (IVIG) as rescue therapy, as these have been successfully used in glucocorticoid-refractory cases 1, 6

Monitoring During Acute Phase

Cardiac Monitoring

• Serial cardiac troponins and ECG monitoring for arrhythmias and conduction abnormalities 5
• Echocardiography to assess ventricular function and wall motion abnormalities 5
• Cardiac MRI can monitor resolution of inflammation once patient stabilizes 5
• Restrict all physical activity for 3-6 months as premature activity increases mortality and sudden death risk 5

Myositis Monitoring

• Serial creatine kinase (CK), ESR, and CRP levels to monitor disease activity 4
• Assess for bulbar symptoms (dysphagia, dysarthria, dysphonia) and respiratory muscle weakness which indicate severe disease 1, 4
• Test for anti-acetylcholine receptor antibodies if myasthenia gravis overlap suspected, as this combination has ominous prognosis with high mortality 1, 4, 7

Infection Monitoring

• Daily assessment for worsening infection signs: fever, hemodynamic instability, respiratory compromise 1
• Monitor complete blood count for neutropenia (mycophenolate mofetil causes severe neutropenia in up to 3.6% of patients) 3
• Liver and renal function tests given methotrexate's hepatotoxicity and nephrotoxicity risks 2

Rheumatic Disease Management During Recovery

When Infection Resolves

• Taper corticosteroids gradually once myocarditis improves and infection clears, monitoring for both cardiac function and rheumatic disease flare 1, 5
• Consider restarting conventional synthetic DMARDs (hydroxychloroquine, sulfasalazine) before mycophenolate mofetil or methotrexate, as these have lower infection risk 1
• If rheumatic disease flares during steroid taper, use low-dose glucocorticoids (≤10 mg prednisone equivalent/day) rather than restarting mycophenolate mofetil or methotrexate immediately 1

Long-term Immunosuppression Strategy

• For patients with history of vital organ-threatening rheumatic disease (which includes myocarditis), immunosuppressants should not be dose-reduced once infection clears and patient stabilizes 1
• Mycophenolate mofetil can be restarted once infection completely resolves, CK normalizes, and cardiac function stabilizes, as it has shown efficacy in resistant myositis 8, 6
• Methotrexate can be restarted at 15-25 mg/week once liver function tests normalize and infection clears 1, 2
• For Sjögren's syndrome specifically, mycophenolate mofetil may be beneficial for systemic manifestations once infection resolves 9

Critical Pitfalls to Avoid

• Never continue mycophenolate mofetil or methotrexate during active infection as both FDA labels explicitly warn against this, with potentially fatal consequences 2, 3
• Do not delay corticosteroid initiation for myocarditis even with active infection, as untreated myocarditis has higher mortality than infection risk with steroids 1, 5
• Do not use NSAIDs for symptom control as they worsen myocarditis outcomes 5
• Do not allow physical activity during acute myocarditis phase as this dramatically increases sudden death risk 5
• Do not restart immunosuppressants prematurely before infection fully resolves, as this may lead to overwhelming sepsis 1, 3