Abstract
BACKGROUND: The pathophysiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood compared to the other subtypes of MCD, which has contributed to limited treatment options and poor prognosis for iMCD patients. The pathogenesis of iMCD is thought to be mediated in part by dysregulation of interleukin (IL)-6. CASE PRESENTATION: We present a case report of a 39-year-old Caucasian man with siltuximab-refractory iMCD. He presented with severe lower extremity lymphedema and wounds. His disease progressed through standard-of-care siltuximab. Due to his severe disease-related morbidity, he contracted recurrent infections, often complicated by sepsis. Ultimately, he required a left lower extremity amputation. CONCLUSION: The first-line and only United States Food and Drug Administration-approved therapy for iMCD is siltuximab, an anti-IL6 agent. However, it is clear that the pathogenesis of iMCD is more complex than strictly an IL-6-driven disease as siltuximab only showed a 34% durable response rate in clinical trials. Cytokine and proteomic profiling have shown normal IL-6 levels in many patients with iMCD. Further efforts to understand the mechanisms and etiology of iMCD are needed, particularly for siltuximab-refractory patients.