What is the best approach to manage a patient with rheumatoid arthritis and Sjögren's syndrome overlap, who has developed myositis and now presents with an active infection?

Management of Rheumatoid Arthritis-Sjögren's Syndrome Overlap with Myositis and Active Infection

Immediately withhold all immunosuppressive therapy until the active infection is fully treated and resolved. 1

Immediate Infection Management Priority

• Halt all DMARDs, biologics, and immunosuppressive agents (methotrexate, mycophenolate, rituximab, cyclophosphamide, calcineurin inhibitors) during active infection 1
• Minimize or discontinue glucocorticoids to the lowest possible dose that prevents adrenal crisis if the patient has been on chronic therapy; ideally reduce to <10 mg prednisone equivalent daily or discontinue entirely if safe 1
• Identify and aggressively treat the infection with appropriate antimicrobials based on culture data and clinical presentation 1
• Monitor closely for infection resolution with serial clinical assessments, inflammatory markers (CRP, ESR), and imaging as indicated 1

Post-Infection Therapeutic Restart Strategy

Once infection has completely resolved, restart immunosuppression using the following hierarchy:

First-Line Therapy for This Overlap Syndrome

Mycophenolate mofetil is the preferred agent for restarting therapy given its efficacy across all three conditions (RA, Sjögren's, and myositis) 1, 2

• Mycophenolate addresses the myositis component effectively 1
• It is conditionally recommended as first-line for ILD if present (common in overlap syndromes) 1
• Dose: 15-20 mg/m²/week for methotrexate or standard mycophenolate dosing (1-3 g/day) 1, 3

Alternative First-Line Options

If mycophenolate is contraindicated or not tolerated:

• Methotrexate (15-20 mg/m²/week, preferably subcutaneous) for RA and myositis control 1, 3
• Azathioprine as an alternative immunosuppressant 1
• Rituximab (1 g every 2 weeks × 2 doses) for severe or refractory disease, particularly if there is concern for vasculitis or lymphoma risk in Sjögren's 1, 3

Glucocorticoid Bridging (Short-Term Only)

• High-dose glucocorticoids (oral or IV) may be used for 3 months or less as bridging therapy when restarting immunosuppression 1
• Critical caveat: If there is any systemic sclerosis overlap phenotype, glucocorticoids significantly increase scleroderma renal crisis risk, especially at doses >15 mg/day prednisone equivalent 1, 3
• Taper aggressively as clinical improvement occurs 1

Multidisciplinary Coordination Requirements

• Infectious disease consultation for complex or severe infections before restarting immunosuppression 1
• Rheumatology as primary coordinator with input from pulmonology (if ILD present), neurology (if neuropathy from Sjögren's), and cardiology (if myocarditis concern with myositis) 1, 2
• Shared decision-making with the patient regarding infection risk versus disease activity is essential 1

Monitoring After Immunosuppression Restart

• Assess for infection recurrence with clinical evaluation every 2-4 weeks initially 1
• Monitor disease activity across all three conditions: joint counts for RA, muscle strength/CK for myositis, sicca symptoms for Sjögren's 1
• Screen for ILD progression with pulmonary function tests every 3-6 months if ILD present 1, 2
• Laboratory monitoring: CBC, comprehensive metabolic panel, CRP/ESR every 4-8 weeks on immunosuppression 1

Critical Pitfalls to Avoid

• Never restart immunosuppression with active infection present, as this dramatically increases morbidity and mortality risk 1
• Avoid prolonged high-dose glucocorticoids (>15 mg/day for >3 months) due to infection risk, osteoporosis, and potential scleroderma renal crisis if overlap features present 1, 3
• Do not use TNF inhibitors as first-line in this overlap syndrome; they are not recommended for myositis or Sjögren's and have limited data in overlap syndromes 1
• Do not delay DMARD initiation once infection clears, as untreated inflammatory disease leads to irreversible organ damage 1, 2

Severe/Refractory Disease Considerations

If disease remains active despite first-line therapy after infection resolution:

• Cyclophosphamide (0.5 g every 2 weeks × 6 doses) for severe myositis or rapidly progressive ILD 1, 3
• IVIG (intravenous immunoglobulin) for refractory myositis, particularly if infection risk remains high 1
• Calcineurin inhibitors (cyclosporine, tacrolimus) as steroid-sparing agents 1