Idiopathic multicentric Castleman disease (iMCD) – Introduction
iMCD is a rare disorder that could potentially be life-threatening. In a retrospective analysis in the the US, the annual incidence of iMCD was 3.1–3.4 cases per million. In the same study, the prevalence of iMCD was estimated at 6.9–9.7 cases per milllion.1*
Abbreviations: iMCD, idiopathic multicentric Castleman disease; NOS, not otherwise specified; US, United States; TAFRO, thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly.
References: 1. Mukherjee S, Martin R, Sande B, Paige JS, Fajgenbaum DC. Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6-directed therapy. Blood Adv. 2022;6(2):359-367. 2. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646‑1657.
Abbreviations: iMCD, idiopathic multicentric Castleman disease; NOS, not otherwise specified; US, United States; TAFRO, thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly.
References: 1. Mukherjee S, Martin R, Sande B, Paige JS, Fajgenbaum DC. Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6-directed therapy. Blood Adv. 2022;6(2):359-367. 2. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646‑1657.
Idiopathic multicentric Castleman disease (iMCD) – Prognosis
iMCD requires timely diagnosis and treatment at the point of diagnosis to support best possible outcomes.
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iMCD is a chronic disease that can progress in the absence of treatment and can lead to severe comorbidities and death.1–3
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Patients with iMCD have poorer outcomes than many cancers, including Stage II colon cancer, Stage III breast cancer, and progressive non‑Hodgkin lymphoma.4
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In a retrospective analysis of US claims data, a higher proportion of patients with iMCD presented with organ failure and/or thrombotic events, compared with a non-iMCD matched cohort.5*
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The same analysis found that patients with iMCD had higher prevalence of several malignancies, compared with a non-iMCD matched cohort.5*
Abbreviations: iMCD, idiopathic multicentric Castleman disease.
References: 1. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 2. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 3. Yu L, Tu M, Cortes J, et al. Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood. 2017;129(12):1658-1668. 4. Sitenga J, Aird G, Ahmed A, Silberstein PT. Impact of siltuximab on patient-related outcomes in multicentric Castleman's disease. Patient Relat Outcome Meas. 2018;9:35-41. 5. Mukherjee S, Kanhai K, Kauffman D, et al. Organ dysfunction, thrombotic events and malignancies in patients with idiopathic multicentric castleman disease: a population‑level US health claims analysis. Leukemia. 202;36(10):2539-2543.
Abbreviations: iMCD, idiopathic multicentric Castleman disease.
References: 1. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 2. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 3. Yu L, Tu M, Cortes J, et al. Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood. 2017;129(12):1658-1668. 4. Sitenga J, Aird G, Ahmed A, Silberstein PT. Impact of siltuximab on patient-related outcomes in multicentric Castleman's disease. Patient Relat Outcome Meas. 2018;9:35-41. 5. Mukherjee S, Kanhai K, Kauffman D, et al. Organ dysfunction, thrombotic events and malignancies in patients with idiopathic multicentric castleman disease: a population‑level US health claims analysis. Leukemia. 202;36(10):2539-2543.
Idiopathic multicentric Castleman disease (iMCD) – Potential causes
The idiopathic form of CD has no known cause.
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Unlike other lymphoproliferative disorders, a dysregulated overproduction of interleukin-6 (IL-6) is a common pathological driver of iMCD and its symptoms.1,2
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In severe cases, a life-threatening cytokine storm can occur, followed by organ failure and death.2
Abbreviations: iMCD, idiopathic multicentric Castleman disease; IL-6, interleukin-6; VEGF, vascular endothelial growth factor.
References: 1. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 2. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman Disease in the 21st Century: An Update on Diagnosis, Assessment, and Therapy. Clin Adv Hem & Onc. 2010;8:486–98.
Abbreviations: iMCD, idiopathic multicentric Castleman disease; IL-6, interleukin-6; VEGF, vascular endothelial growth factor.
References: 1. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 2. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman Disease in the 21st Century: An Update on Diagnosis, Assessment, and Therapy. Clin Adv Hem & Onc. 2010;8:486–98.
Idiopathic multicentric Castleman disease (iMCD) – Diagnosis
Undiagnosed idiopathic multicentric Castleman disease (iMCD) patients exhibit a wide spectrum of possible symptoms.
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There is no ‘typical’ iMCD patient and undiagnosed patients have a range of possible symptoms which will see them under the care of a variety of specialists, e.g., hematologists, rheumatologists, immunologists.1
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Patients are usually referred for an (excisional) lymph node biopsy by their clinician, who has noticed symptoms that require further investigation.1
Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; AOSD, adult-onset Still disease; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HHV-8, human herpesvirus-8; HL, Hodgkin lymphoma; HLH-MAS, hemophagocytic lymphohistiocytosis macrophage activation syndrome; IgG4, IgG4-related disease; iMCD, idiopathic multicentric Castleman disease; JIA, juvenile idiopathic arthritis; M-HLH, malignancy associated hemophagocytic lymphohistiocytosis; NHL, non‑Hodgkin lymphoma; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; V-HLH, viral hemophagocytic lymphohistiocytosis.
References: 1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646‑1657.
Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; AOSD, adult-onset Still disease; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HHV-8, human herpesvirus-8; HL, Hodgkin lymphoma; HLH-MAS, hemophagocytic lymphohistiocytosis macrophage activation syndrome; IgG4, IgG4-related disease; iMCD, idiopathic multicentric Castleman disease; JIA, juvenile idiopathic arthritis; M-HLH, malignancy associated hemophagocytic lymphohistiocytosis; NHL, non‑Hodgkin lymphoma; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; V-HLH, viral hemophagocytic lymphohistiocytosis.
References: 1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646‑1657.
