What is the best treatment approach for a patient with rheumatoid arthritis, Sjögren's syndrome, and myositis who now presents with myocarditis?

Treatment of Myocarditis in a Patient with Rheumatoid Arthritis, Sjögren's Syndrome, and Myositis

Immediately discontinue any checkpoint inhibitor therapy if present, initiate high-dose intravenous methylprednisolone (1-2 mg/kg/day, typically 70 mg/day or higher), establish continuous cardiac telemetry monitoring, and urgently consult cardiology for potential mechanical circulatory support given the high mortality risk of myocarditis in this clinical context. 1

Immediate Recognition and Risk Assessment

Myocarditis in the setting of myositis carries a mortality rate significantly higher than idiopathic inflammatory myopathy (approximately 20% versus less than 10%), making this a medical emergency requiring aggressive intervention. 1

Critical Initial Evaluation

• Obtain troponin I (not troponin T, which can be falsely elevated by skeletal muscle involvement), electrocardiography, and echocardiogram immediately. 1
• Troponin levels ≥1.5 ng/mL are associated with a 4-fold increased risk of major adverse cardiac events (cardiovascular death, cardiogenic shock, cardiac arrest, or hemodynamically significant complete heart block). 1
• Normal cardiac enzymes cannot completely rule out myocarditis in this population. 1, 2
• Cardiac MRI should be obtained urgently if troponin is elevated or clinical symptoms suggest cardiac involvement. 1, 2
• Establish continuous telemetry monitoring due to risk of life-threatening arrhythmias and heart block. 1

Assessment for Concurrent Life-Threatening Manifestations

• Evaluate for myasthenia gravis (present in 12.5% of myositis cases with myocarditis), bulbar symptoms (dysphagia, dysarthria, dysphonia), and respiratory failure, as these mandate even more aggressive therapy. 1, 3
• Approximately 42% of patients with checkpoint inhibitor-related myocarditis have concurrent severe immune-related adverse events, most commonly myositis and myasthenia gravis. 1

First-Line Treatment Protocol

Glucocorticoid Therapy

High-dose systemic glucocorticoids are mandatory first-line treatment, with intravenous methylprednisolone pulses (10-20 mg/kg or 250-1000 mg for 1-5 consecutive days) preferred over oral prednisone in the setting of myocarditis. 1, 2, 4

• The median dosage used in reported cases is 70 mg/day, but higher doses are appropriate for myocarditis. 1
• High-dose steroids result in better treatment response, and lower-dose corticosteroid therapy is associated with elevated troponin and higher rates of major adverse cardiac events. 1
• Corticosteroids are FDA-approved for systemic dermatomyositis and acute rheumatic carditis. 4

Additional Immunosuppressive Therapy

Intravenous immunoglobulins (IVIG) should be administered in up to 20% of severe cases, particularly when there is poor response to corticosteroids or life-threatening manifestations. 1, 3

Plasma exchange should be performed in approximately 10% of patients, especially with inadequate response to initial therapy. 1, 3, 2

Management of Glucocorticoid-Refractory Disease

Rescue Therapy Options

For severe glucocorticoid-refractory myocarditis, abatacept has demonstrated resolution after plasma exchange was unsuccessful, making it the preferred rescue agent. 1

• Alemtuzumab (another T-cell directed therapy) has been successfully used in glucocorticoid-refractory myocarditis. 1
• Due to the lack of effective therapy and high mortality rate of myositis complicated with myocarditis, these agents should be considered as rescue therapy in refractory situations despite limited data on tumor response impact. 1

Agents to Avoid

Infliximab has been used in six patients but was successful in only one, making it a poor choice for myocarditis. 1

Second-Line and Steroid-Sparing Agents

Once the acute myocarditis is controlled and the patient is stabilizing, consider the following for long-term management of the underlying autoimmune conditions:

• Mycophenolate mofetil is the preferred second-line agent. 1, 3, 2
• Methotrexate can be used but should be initiated cautiously after cardiac stabilization. 1, 3, 2
• Azathioprine has been used but carries risk of pancreatitis. 1
• Hydroxychloroquine may be considered for Sjögren's syndrome manifestations. 1

Hemodynamic Support and Advanced Therapies

Approximately 2% to 9% of patients with myocarditis have hemodynamic instability requiring inotropic agents or mechanical circulatory devices such as extracorporeal life support, with these patients having approximately 28% mortality or heart transplant rate at 60 days. 5

• Early cardiology involvement is mandatory for consideration of mechanical circulatory support. 1
• Approximately 75% of patients admitted with uncomplicated myocarditis have a mortality rate of approximately 0%, but those with acute heart failure or ventricular arrhythmias have a 12% rate of in-hospital mortality or need for heart transplant. 5

Critical Pitfalls to Avoid

• Do not rely on troponin T alone, as it is expressed by skeletal muscle including regenerating tissue and can be falsely elevated without myocardial involvement; use troponin I for cardiac specificity. 1
• Do not assume normal cardiac enzymes exclude myocarditis in this population. 1, 2
• Do not use lower-dose corticosteroids in the setting of myocarditis, as this is associated with worse outcomes. 1
• Do not delay treatment while awaiting endomyocardial biopsy; when clinical suspicion is high, treatment should be offered empirically before confirmatory pathologic testing. 1

Management of Pre-Existing Autoimmune Conditions

The baseline immunosuppressive regimen for rheumatoid arthritis and Sjögren's syndrome should be kept at the lowest dose possible during acute myocarditis management, with glucocorticoids ideally below 10 mg prednisone per day once the acute crisis resolves. 1

• Patients with pre-existing rheumatoid arthritis experience flares in 47/86 cases (55%), and those with Sjögren's syndrome in 3/7 cases (43%), but less than 10% require stopping therapy during a flare. 1
• Cardiovascular disease in rheumatoid arthritis occurs a decade earlier than controls and carries cardiovascular risk equivalent to diabetes mellitus, requiring aggressive control of systemic inflammation. 6