特発性多中心性キャッスルマン病

The clinical diagnosis and treatment processes of four children with Castleman disease admitted to Guangzhou Women and Children's Medical Center, Guangzhou Medical University, from March 2021 to December 2024 were retrospectively analyzed. Among them, three cases were unicentric Castleman disease, presenting as abdominal pain with ileocecal ulceration, concomitant classical Hodgkin lymphoma, and choledochal cyst, respectively. One case was severe idiopathic multicentric Castleman disease involving lymph nodes in the neck and axillary regions, presenting with fever, abdominal distension, generalized edema, fatigue, anemia, hepatic dysfunction, polyserous effusion, and other systemic manifestations. The three unicentric cases underwent complete surgical resection of enlarged lymph nodes. The case with abdominal pain received subsequent enteral nutrition and oral thalidomide therapy. The case complicated with Hodgkin lymphoma received chemotherapy according to the Hodgkin lymphoma protocol. The severe multicentric case was treated with rituximab combined with vincristine, pirarubicin, cyclophosphamide, and prednisone. All four cases achieved complete remission during 6 to 30 months of follow-up. Clinical manifestations of Castleman disease in children lack specificity. Surgical resection remains the main treatment for unicentric cases, while treatment regimens for multicentric cases are more varied. The overall prognosis is favorable. Further studies are needed to determine the optimal treatment for Castleman disease complicated by gastrointestinal ulcers and severe idiopathic multicentric Castleman disease.

Renal involvement of IgG4-related disease (IgG4-RD), collectively termed IgG4-related kidney disease (IgG4-RKD), most commonly manifests as tubulointerstitial nephritis (TIN) but can also manifest as membranous glomerulonephritis (MGN) and acute interstitial nephritis (AIN) as a histologic subtype of IgG4-related TIN (IgG4-TIN). IgG4-related retroperitoneal fibrosis (IgG4-RPF) can cause obstructive kidney disease with or without active parenchymal IgG4-RKD. IgG4-RD is a clinicopathological diagnosis, requiring correlation of clinical, laboratory, radiological, and histological findings to identify features of IgG4-RD and rule out mimickers. Histopathologic features of IgG4-RD in tissue include a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, typically accompanied by so-called "storiform" fibrosis. Important mimics of IgG4-RKD include infection, malignancy, antineutrophil cytoplasmic autoantibody (ANCA)-associated disease, idiopathic multicentric Castleman disease, Rosai-Dorfman-Destombes disease and Sjögren Disease (SjD). Mimickers of IgG4-RPF include lymphoma, Erdheim-Chester disease, and idiopathic RPF. IgG4-RKD and IgG4-RPF are responsive to the systemic therapies used for IgG4-RD in general. Corticosteroids are the traditional first line therapy; however, B cell-targeted therapies, including rituximab, inebilizumab, and obexelimab are more potent and less toxic than steroids. Further trials are currently being conducted on newer medications that target signaling pathways and immune cells involved in the pathogenesis of IgG4-RD. Early recognition and treatment are critical to prevent irreversible organ damage. This review summarizes the current understanding of the pathogenesis, clinical spectrum, diagnostic approach, and management strategies for IgG4-RD, IgG4-RKD, and IgG4-RPF.

INTRODUCTION: Castleman disease (CD) is a rare, heterogeneous group of disorders driven by dysregulated cytokine signaling, particularly interleukin‑6 (IL‑6). Over the past decade, monoclonal antibody (mAb) targeting IL‑6, its receptor, and B‑cell antigens have transformed the management of idiopathic multicentric Castleman disease (iMCD) and related subtypes. AREAS COVERED: In this review, the authors discuss evidence for mAbs in CD, focusing on siltuximab, tocilizumab, and rituximab, as well as investigational biologics beyond anti-IL-6 and CD20. PubMed/MEDLINE was searched from database inception to May 2026 using terms including 'Castleman disease,' 'siltuximab,' 'tocilizumab,' 'rituximab,' and 'TAFRO,' with emphasis on mAbs in clinical trials, consensus guidelines, real-world cohorts, and mechanistic studies. EXPERT OPINION: IL-6 blockade remains the foundation of iMCD therapy, and rituximab continues to play a critical role in HHV‑8-associated MCD and iMCD, including idiopathic plasmacytic lymphadenopathy (IPL). However, emerging data increasingly support subtype‑specific and severity‑adapted strategies. Future progress will depend on early identification of IL-6-refractory disease, biomarker-driven treatment selection, and rational combination strategies for aggressive phenotypes such as iMCD-TAFRO.

Idiopathic multicentric Castleman disease (iMCD) is a benign lymphoproliferative disease characterized by generalized lymphadenopathy and systemic inflammatory symptoms, occurring in individuals without infection with human immunodeficiency virus (HIV) or Kaposi sarcoma-associated herpesvirus (KSHV). iMCD is typically subclassified into iMCD-TAFRO, which is characterized by thrombocytopenia, ascites, fever, reticulin fibrosis, and organomegaly; iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL), which follows a chronic disease course with persistent lymphadenopathy, marked polyclonal hypergammaglobulinemia, and prominent plasma cell infiltration in lymph nodes; and iMCD-not otherwise specified (iMCD-NOS), which lacks features of both TAFRO syndrome and the IPL phenotype. Pleural thickening and effusion are extremely rare manifestations of iMCD-NOS. Herein, we present a rare case of iMCD-NOS presenting with unilateral pleural thickening and pleural effusion. A 76-year-old Japanese man was referred for further evaluation of a massive left-sided pleural effusion with tracheal compression. Fluorodeoxyglucose positron emission tomography/computed tomography showed increased uptake in the thickened pleura and multiple lymph nodes. Histopathological examination of a mediastinal lymph node demonstrated medullary and lymphoid follicular hyperplasia without structural destruction, while biopsy of the thickened pleura showed infiltration of lymphocytes and plasma cells without dysplasia. The patient was treated with corticosteroids and tocilizumab, resulting in marked improvement in symptoms and pleural effusion. This case highlights the importance of considering pleural and lymph node biopsies for accurate diagnosis and of not excluding iMCD in patients with unilateral pleural thickening accompanied by multiple lymphadenopathies.

Idiopathic multicentric Castleman disease (iMCD) is rare and life-threatening; although siltuximab is standard first-line therapy, a substantial proportion of patients are refractory or experience relapse. We report a 31-year-old woman with HHV-8-negative iMCD with idiopathic plasmacytic lymphadenopathy (IPL; iMCD-IPL), intractable to five prior lines of therapy, who declined siltuximab and enrolled in ChiCTR1900025419. After fludarabine/cyclophosphamide lymphodepletion, she received 1 × 106 CAR + T cells/kg of autologous CD19 CAR T cells on day 0. Grade 1 cytokine release syndrome (Tmax 38.2°C) resolved with supportive care; no ICANS occurred. CAR transgene levels expanded (peaking on day +11) and remained detectable through day +58, and flow cytometry showed CD19+ B-cell depletion from day +7 to day +198. By day +198, she met CDCN criteria for complete biochemical and clinical response with normalization of inflammatory markers and hematologic recovery. Panhypogammaglobulinemia was managed with intravenous immunoglobulin replacement. At > 12 months post-infusion, she remains in complete, treatment-free remission. This observation supports a B-cell-centric model for refractory iMCD-IPL and motivates prospective evaluation of CD19 CAR T-cell therapy.