CASE REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Case Report: Endothelial-Targeted Bridging Therapy for a TTP-Like Phenotype in Fulminant iMCD-TAFRO
Provisionally accepted
- 1Sun Yat-sen Memorial Hospital, Guangzhou, China
- 2Huidong County People's Hospital, Huizhou, China
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Abstract Background: iMCD-TAFRO (the TAFRO clinical subtype of idiopathic multicentric Castleman disease (iMCD)) is characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Diagnosis is challenging due to its rarity, nonspecific early presentation, and overlap with sepsis, lymphoma, and thrombotic microangiopathy (TMA). Endothelial injury is increasingly recognized as a central driver of its severe complications. Case Presentation: A previously healthy 20-year-old woman presented with rapid progression of fever, anasarca, jaundice, and respiratory failure. Laboratory findings revealed severe thrombocytopenia, microangiopathic hemolytic anemia, markedly elevated IL-6, and critically reduced ADAMTS13 activity (5.41%) without an inhibitor by a Bethesda assay, in a sample obtained before the first therapeutic plasma exchange (TPE) and before any fresh frozen plasma (FFP) infusion, suggesting a cytokine-driven thrombotic thrombocytopenic purpura (TTP)-like syndrome. Extensive workup excluded primary infections and malignancies. Diagnosis of iMCD-TAFRO was confirmed by a lymph-node core biopsy showing features consistent with Castleman disease with plasmacytosis. Conclusion: This case highlights that iMCD-TAFRO can manifest as a fulminant, endotheliopathy-dominated syndrome in young adults, mimicking primary TTP. The severe ADAMTS13 deficiency in this context likely results from consumption due to endothelial activation rather than an immune-mediated process. This distinction is critical for appropriate management. Management and Outcome: Prior to definitive diagnosis, an endothelium-directed bundle was initiated, including TPE plus adjunctive FFP infusion, corticosteroids, and anisodamine for microcirculatory support; stabilization occurred in the context of multimodal supportive care. Upon diagnostic confirmation, targeted anti-IL-6 therapy (siltuximab) led to significant clinical improvement. Despite a subsequent relapse with pulmonary hypertension, intensified immunosuppression achieved complete 3 remission at one-year follow-up. This case illustrates a pathophysiology-informed bridging bundle to stabilize endothelial and microcirculatory dysfunction while pursuing definitive diagnosis and targeted cytokine blockade in severe iMCD-TAFRO.
Keywords: case report, endotheliopathy, Idiopathic multicentric castleman disease, iMCD‑TAFRO, Interleukin-6 inhibition, therapeutic plasma exchange, thrombotic microangiopathy, TTP‑like thrombotic microangiopathy
Received: 27 Dec 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Du, Wu, Li, Gan, Yu, Xie and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiangshao Fang
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