MCD describes a heterogeneous group of poorly understood diseases involving proinflammatory hypercytokinemia that ultimately results in systemic inflammatory symptoms, generalized lymphadenopathy, multiple organ system dysfunction, and even death. HHV-8 is responsible for MCD in immunosuppressed patients (ie, HHV-8–associated MCD), but there is a cohort of HHV-8–negative patients with MCD, referred to as idiopathic MCD (iMCD), in which the etiology remains unknown. No formal diagnostic criteria exist for iMCD, and knowledge is limited to small case series and case reports (Fajgenbaum DC, et al. Blood. 2014;123:2924-2933). Fajgenbaum and colleagues presented a systematic literature review of 129 cases of iMCD, in which the clinical features and therapeutic options for this disease were elaborated (Fajgenbaum DC, et al. Blood. 2014;124. Abstract 4861).
The most frequently reported clinical features for iMCD include fever, enlarged liver and/or spleen, pleural effusion, edema, and weight loss. The most frequently reported laboratory abnormalities include elevated C-reactive protein, anemia, hypergammaglobulinemia, hypoalbuminemia, elevated IL-6, and positive antinuclear antibody. Overall, 27 patients were diagnosed with a malignancy before (N = 5), concurrently with (N = 12), or after (N = 10) the diagnosis of iMCD.
The most frequently used first-line therapies for this patient population included corticosteroid monotherapy, combinations of cytotoxic chemotherapies that incorporated regimens with cyclophosphamide and rituximab, and anti–IL-6 therapies (eg, siltuximab and tocilizumab) without a cytotoxic agent. Thalidomide, bortezomib, anakinra, and intravenous immunoglobulin were used less frequently.
In these patients there was no disease response (21%), partial response (42%), or complete response (37%) to first-line therapies. Failure of first-line therapy (ie, disease relapse, death, or additional treatment) was reported in 41% of patients, and the median time to treatment failure was 6 months. Overall, 22% of patients died by the time of the most recent follow-up (median, 28 months); the median length of survival among fatal cases was 26 months. The most common causes of death were septic shock, multiorgan failure (including renal and cardiac), pulmonary complications, and malignancy.
This study identified a significant proportion of patients with MCD who are HIV-negative and HHV-8–negative (iMCD). Despite the many limitations of analyzing case reports, this study provides the most comprehensive data on patients with HHV-8–negative MCD to date. A global natural history study and Castleman’s disease registry are urgently needed to gather more extensive data on MCD.
