Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.

Dispenzieri A, Fajgenbaum DC. Overview of castleman disease. Blood. 2020;135(16):1353–64.
Jiang JP, Shen XF, Du JF, Guan WX. A retrospective study of 34 patients with unicentric and multicentric castleman’s disease: experience from a single institution. Oncol Lett. 2018;15:2407–12.
Yu JY, Oh IJ, Kim KS, Kim YI, Lim SC, Kim YC, et al. Castleman’s disease presenting as a tracheal mass. Ann Thorac Surg. 2014;97(5):1798–800.
van Rhee F, Voorhees P, Dispenzieri A, Fosså A, Srkalovic G, Ide M, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132:2115–24.
Cronin DMP, Warnke RA. Castleman disease: an update on classification and the spectrum of associated lesions. Adv Anat Pathol. 2009;16(4):236–46.
Soumerai JD, Sohani AR, Abramson JS. Diagnosis and management of Castleman disease. Cancer Control. 2014;21:266–78.
Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646–57.
Pierson SK, Stonestrom AJ, Ruth JR. Quantification of plasma proteins from idiopathic multicentric castleman disease flares and remissions reveals “chemokine storm” and separates clinical subtypes. Blood. 2017;130:3592.
Palestro G, Turrini F, Pagano M, Chiusa L. Castleman’s disease. Adv Clin Path. 1999;3(1–2):11–22.
Parravicini C, Corbellino M, Paulli M, Magrini U, Lazzarino M, Moore PS, et al. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman’s disease. Am J Pathol. 1997;151:1517–22.
Tabata S, Higuchi T, Tatsukawa S, Narimatsu K, Takeo H, Matsukuma S, et al. Idiopathic multicentric castleman disease with autoimmune hemolytic anemia and production of anti-drug Antibody against Tocilizumab. Intern Med. 2019;58:3313–8.
Sun DP, Chen WM, Wang L, Wang Z, Liang JH, Zhu HY, et al. Clinical characteristics and immunological abnormalities of Castleman disease complicated with autoimmune diseases. J Cancer Res Clin Oncol. 2021;147(7):2107–15.
Ocio EM, Sanchez-Guijo FM, Diez-Campelo M.Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena. Am J Hematol. 2005;78:302–5.
Shahani L. Castleman’s disease in a patient with melanoma: the role of VEGF. BMJ Case Rep. 2012;2012:bcr0720114519.
Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol. 2016;3(4):e163–75.
Sudha Reddy VR, Samayam P, Ravichander B, Bai U. Autoimmune hemolytic anemia: mixed type - a case report. Indian J Hematol Blood Transfus. 2011;27(2):107–10.
Webster D, Ritchie B, Mant MJ. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematol. 2004;75(4):258–9.
Marcelin A-G, Aaron L, Mateus C, Gyan E, Gorin I, Viard JP, et al. Rituximab therapy for HIV-associated Castleman disease. Blood. 2003;102(8):2786–8.
Berentsen S, Barcellini W. Autoimmune hemolytic anemias. N Engl J Med. 2021;385:1407–19.
Bower M, Newsom-Davis T, Naresh K, Merchant S, Lee B, Gazzard B, et al. Clinical features and outcome in HIV-associated multicentric castleman’s disease. J Clin Oncol. 2011;29(18):2481–6.
Pria AD, Pinato D, Roe J, Naresh K, Nelson M, Bower M. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients. Blood. 2017;129(15):2143–7.
Dong Y, Zhang L, Nong L, Wang L, Liang Z, Zhou D, et al. Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease. Ann Hematol. 2018;97(9):1641–7.
van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fosså A, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966–74.
van Rhee F, Casper C, Voorhees PM. Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials. Lancet Haematol. 2020;7:e209–17.
Casper C, Chaturvedi S, Munshi N, Wong R, Qi M, Schaffer M, et al. Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-IL6 monoclonal antibody) in patients with multicentric castleman disease. Clin Cancer Res. 2015;21:4294–304.
Iskandar A, Hwang A, Dasanu CA. Severe warm-antibody autoimmune hemolytic anemia due to multicentric Castleman disease: responding to rituximab. J Oncol Pharm Pract. 2019;25(8):2016–8.
Röth A, Barcellini W, D’Sa S, Miyakawa Y, Broome CM, Michel M, et al. Sutimlimab in cold agglutinin disease. N Engl J Med. 2021;384(14):1323–34.
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