At the Special Program, Fajgenbaum also presented an overview of MCD’s clinical features. iMCD can occur at any age, he said, but it typically affects individuals in the fourth and fifth decades of life, and it is more common in men than in women. The clinical spectrum ranges from waxing and waning mild lymphadenopathy with B-symptoms to more severe cases involving intense inflammation, hepatosplenomegaly, vascular leak syndrome with anasarca, pleural effusions and ascites, organ failure, and even death. Acute episodes can display significant clinical overlap with acute viral illnesses and autoimmune diseases. Skin involvement in the form of cherry hemangioma often occurs.
Clinical differences can be observed between ethnic groups. Patients of Asian descent often display large violaceous skin lesions and interstitial pneumonitis, and Polynesian patients demonstrate a mild clinical course despite significant biochemical derangements. The laboratory findings frequently include anemia, elevated erythrocyte sedimentation rate, C-reactive protein, IL-6, VEGF, and fibrinogen; positive antinuclear antibody, antierythrocyte autoantibodies, and antiplatelet antibodies; and proteinuria, hypoalbuminemia, polyclonal marrow plasmacytosis, polyclonal hypergammaglobulinemia, and thrombocytosis or thrombocytopenia.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, a paraneoplastic syndrome involving VEGF and other cytokine secretion by malignant plasma cells, can demonstrate significant clinical and histopathologic overlap with iMCD, such as volume overload, renal disease, and cherry hemangioma. Approximately 37% to 60% of POEMS cases have elements of Castleman’s disease histopathology, and many patients with iMCD may also demonstrate features of POEMS, including immunoglobulin A monoclonal gammopathy of undetermined significance.
The frequent association between POEMS and iMCD may occur because the malignant, POEMS-driving plasma cells secrete cytokines that also cause iMCD-like reactive lymph node changes, rather than separate diseases co-occurring. In addition, many other neoplastic, infectious, and autoimmune diseases are reported to co-occur with iMCD, including lymphoma, myeloma, meningioma, melanoma, adult-onset Still’s disease, juvenile idiopathic arthritis, sarcoidosis, amyloidosis, myasthenia gravis, and glomerulonephritides.
