Abstract 4362016: Targeted Management of Severe Myocarditis and Myositis in Drug-Induced Hypersensitivity Syndrome Using Precision Medicine

Abstract

Description of Case: A healthy 44-year-old male with a recent travel history from Rwanda to the United States, presented with a maculopapular rash on his face, extending to his torso and extremities. The patient presumed the rash was a reaction to sun exposure or soap allergy, and thus medicated with acetaminophen and ibuprofen due to concomitant fever and myalgia. On admission, lab workup was notable for eosinophilia of 10% (absolute eosinophil count 0.9x10^9/L) with elevated inflammatory markers (CRP and ESR). The patient was started on broad-spectrum antibiotics and empirically treated with ivermectin given concern for a parasitic infection. He underwent extensive evaluation, including skin biopsies revealing non-specific inflammatory and eczematous processes. Additionally, his infectious workup was notable for HHV-6, Hepatitis B, and HSV (presenting as stomatitis). He was ultimately diagnosed with DiHS/DRESS (attributable to ibuprofen use), started on dexamethasone, and discharged on prednisone. Three days later, he presented again, with worsening myalgia, progressive maculopapular rash, and diffuse ST elevations. He was urgently taken to the cardiac catheterization lab, with no occlusions identified in the coronary arteries. A cardiac MRI confirmed a diagnosis of myocarditis. Skin, muscle, and cardiac biopsies demonstrated severe inflammatory myopathy, likely a complication of DiHS/DRESS. The patient was started on solumedrol, cyclosporine, and IVIG. Despite treatment, he had persistent myalgia and muscle weakness. In the setting of concurrent myositis, ongoing myocarditis, and multiple infections, he underwent RNA Sequencing, where a mutation in the JAK/STAT pathway was identified. To avoid further loss of functionality and potentially life-threatening consequences, the patient was started on tofacitinib with, surprisingly, a notable improvement in clinical symptoms. Discussion: Cardiac involvement and skeletal muscle myositis are under-recognized manifestations of DiHS/DRESS, with immune-mediated necrotizing myositis/myocarditis representing the most severe form. Due to the high morbidity and mortality associated with these complications, patients should be aggressively treated with high-dose systemic corticosteroids to avoid fibrosis of the myocardium and irreversible damage. The use of precision medicine can be critical, particularly in treatment-resistant patients, to improving clinical outcomes and providing expedited targeted medical therapy.