How to manage a febrile and tachycardic patient on long-term prednisone and rituximab for myasthenia gravis?

Management of Febrile Tachycardia in Immunosuppressed Myasthenia Gravis Patient

This patient requires immediate hospitalization with urgent infectious workup, cardiac monitoring with troponin/ECG, and empiric broad-spectrum antibiotics while holding rituximab until infection is excluded. The combination of long-term prednisone and rituximab creates profound immunosuppression with risk for serious infections, and the tachycardia may signal sepsis, myocarditis, or both 1.

Immediate Assessment and Monitoring

Critical Cardiac Evaluation

• Obtain immediate ECG and troponin levels to rule out immune-related myocarditis, which can co-occur with myasthenia gravis in up to 10% of cases and carries 23% mortality even with aggressive treatment 2.
• Initiate continuous telemetry monitoring given the tachycardia and risk of life-threatening arrhythmias or heart block 2.
• Check creatine kinase (CK) and CK-MB to evaluate for concurrent myositis, as the "triple M" syndrome (myositis, myasthenia, myocarditis) frequently presents together 2.
• Obtain brain natriuretic peptide (BNP) and echocardiogram if troponin is elevated 2.

Infectious Workup Priority

• Draw blood cultures immediately before antibiotics given the profound immunosuppression from both chronic prednisone and rituximab 1.
• Check complete blood count with differential, inflammatory markers (ESR, CRP), and comprehensive metabolic panel 2.
• Screen for opportunistic infections including cytomegalovirus, herpes simplex virus, varicella zoster, and reactivated hepatitis B/C, as rituximab causes prolonged hypogammaglobulinemia and serious infections 1.
• Obtain chest X-ray to evaluate for pneumonia 2.
• Consider urinalysis and urine culture as a common infection source 1.

Management Algorithm

If Troponin is Elevated (Any Grade)

• Admit to ICU with cardiology consultation immediately 2.
• Permanently discontinue rituximab for any evidence of myocardial involvement 2.
• Initiate methylprednisolone 1 g IV daily for 3-5 days (pulse dosing) if grade 2 or higher cardiac involvement, as high-dose steroids show better outcomes than lower doses 2.
• If no improvement within 24 hours, add infliximab, IVIG, mycophenolate, or antithymocyte globulin 2.
• Note: Infliximab is contraindicated if heart failure develops 2.

If Infection is Confirmed or Suspected

• Start empiric broad-spectrum antibiotics immediately after cultures are drawn, covering typical and opportunistic pathogens 1.
• Hold rituximab until infection resolves, as serious infections require discontinuation 1.
• Monitor for tumor lysis syndrome if patient has any underlying lymphoproliferative process, though less likely in this autoimmune context 1.

If Both Cardiac and Infectious Concerns

• Prioritize infection treatment while simultaneously managing cardiac complications, as infections can trigger myocarditis 2.
• Continue high-dose steroids for cardiac protection while treating infection aggressively 2.

Myasthenia Gravis-Specific Considerations

Respiratory Monitoring

• Assess negative inspiratory force (NIF) and vital capacity (VC) to establish baseline respiratory muscle strength, as myasthenic crisis can be precipitated by infection 3.
• Monitor for bulbar symptoms (dysphagia, dysarthria) that increase aspiration risk 3.

Medication Review

• Avoid fluoroquinolones, aminoglycosides, and macrolides as empiric antibiotics, as these worsen myasthenia gravis 3.
• Continue pyridostigmine if patient is on it, but be prepared to escalate to IVIG or plasmapheresis if myasthenic crisis develops 3.

Rituximab Safety in This Context

Hold or Discontinue Decision

• Temporarily hold rituximab until infection is excluded or treated, as serious infections mandate discontinuation 1.
• If cardiac involvement is confirmed, permanently discontinue rituximab 2.
• The patient's long-term rituximab use increases risk for hypogammaglobulinemia (>11 months post-exposure) and opportunistic infections 1.

Hepatitis B Reactivation Risk

• Check HBsAg and anti-HBc immediately if not recently done, as HBV reactivation can occur up to 24 months after rituximab completion and can be fatal 1.
• If evidence of prior HBV infection exists, consult hepatology for antiviral prophylaxis 1.

Common Pitfalls to Avoid

• Do not attribute tachycardia solely to fever without cardiac workup—myocarditis presents with nonspecific symptoms like myalgia and shortness of breath that overlap with infection 2.
• Do not delay antibiotics while awaiting cardiac workup completion in a febrile immunosuppressed patient 1.
• Do not use normal temperature (36.5°C) to exclude serious infection—chronic steroid use blunts fever response 1.
• Do not restart rituximab without infectious disease and cardiology clearance if either complication is identified 1.

Prognosis and Follow-Up

• If myocarditis is diagnosed, mortality remains 23% despite aggressive immunosuppression, with conduction abnormalities being the mode of death 2.
• If infection without cardiac involvement, prognosis depends on organism and rapidity of treatment initiation 1.
• Long-term rituximab has shown good efficacy in refractory myasthenia gravis (95% improvement rates), but requires careful monitoring for infectious complications 4.