# Case Report: Endothelial-targeted bridging therapy for a TTP-like phenotype in fulminant iMCD-TAFRO

## TL;DR

A young woman with a rare disease resembling thrombotic thrombocytopenic purpura was successfully treated with a combination of therapies targeting endothelial dysfunction and inflammation.

## Contribution

This case report introduces an endothelial-targeted bridging therapy for fulminant iMCD-TAFRO mimicking TTP, emphasizing pathophysiology-informed treatment strategies.

## Key findings

- Severe ADAMTS13 deficiency in iMCD-TAFRO likely results from endothelial activation rather than immune-mediated processes.
- Multimodal supportive care including TPE, FFP, corticosteroids, and anisodamine stabilized endothelial dysfunction before targeted anti-IL-6 therapy.
- Intensified immunosuppression achieved complete remission after a relapse with pulmonary hypertension.

## Abstract

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, non-specific early presentation, and overlap with sepsis, lymphoma, and thrombotic microangiopathy (TMA). Endothelial injury is increasingly recognized as a central driver of its severe complications.

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.

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.

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 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.