Concomitant Castleman syndrome and secondary progressive multiple sclerosis: a case report

Abstract

Case Presentation: 42-year-old female patient presented with neurological symptoms at age 20, including sensory changes, motor incoordination, urinary incontinence, and left brachio-crural paresis, leading to a multiple sclerosis (MS) diagnosis. Over the course of the disease, she experienced multiple relapses and severe visual impairment. Treatments included glatiramer acetate, natalizumab (discontinued due to positive JC virus serology), fingolimod, and alemtuzumab, with the last cycle completed in 2021. The patient evolved to the secondary progressive form of the disease. During follow-up, she developed systemic comorbidities, including diabetes mellitus, Hashimoto's thyroiditis, chronic gastrointestinal symptoms, and lymphadenopathy, resulting in a Castleman syndrome diagnosis in 2023. Colonoscopy biopsies showed lymphoid follicular hyperplasia in the ileum and colon. Recent brain magnetic resonance imaging demonstrated multiple confluent oval lesions in the white matter and cerebellar hemispheres, consistent with chronic demyelinating disease. From a neurological standpoint, she maintains limb weakness, predominantly on the left side, without new relapses since 2017. Discussion: The association between MS and Castleman syndrome is rare. Most described cases occur in patients treated with high-efficacy immunomodulatory therapies, such as alemtuzumab. This agent promotes deep lymphocyte depletion followed by disordered immune reconstitution, which may favor secondary autoimmune diseases and aberrant lymphatic activation via interleukin-6 production, a central axis in Castleman syndrome pathophysiology. The presence of multiple systemic autoimmune manifestations in this patient reinforces the hypothesis of sustained immune dysregulation potentially aggravated by sequential high-efficacy therapies. There is currently no evidence that MS alone is a predisposing factor for Castleman syndrome Final Comments: This report describes a rare case of Castleman syndrome occurring after intensive immune modulation for secondary progressive MS. It emphasizes the need for clinical vigilance regarding systemic and lymphoproliferative manifestations in patients undergoing high-efficacy immunomodulatory treatments. Further studies are necessary to clarify the pathophysiological mechanisms of this rare association.