Successful Treatment of Autoimmune Hemolytic Anemia Associated with Multicentric Castleman Disease by Anti-Interleukin-6 Receptor Antibody (Tocilizumab) Therapy

Abstract

We describe herein the successful treatment of severe autoimmune hemolytic anemia (AIHA) in a patient with multicentric Castleman disease (MCD) by humanized anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) therapy. Inflammatory anemia is commonly reported; however, AIHA is a very rare complication of MCD. In 1996, a 45-year-old Japanese woman was referred to our hospital because of generalized lymphadenopathy, anemia and skin eruptions. Lymph node biopsy demonstrated MCD. She was treated with prednisolone (1 mg/kg/day), which improved the anemia and skin eruptions. In 2009, she suddenly developed Coombs-positive hemolytic anemia. The blood count was as follows: hemoglobin 4.7 g/dl, platelets 490 × 10⁹/l and white blood cell count 9.8 × 10⁹/l. Both direct and indirect Coombs’ tests were strongly positive. She was treated with 8 mg/kg tocilizumab every 2 weeks. One month later, her hemoglobin levels rose dramatically to 10.9 g/dl and her haptoglobin level, hypergammaglobulinemia and clinical symptoms had also markedly improved. To the best of our knowledge, this is the first report of the efficacy of tocilizumab in AIHA associated with MCD. The well-established role of IL-6 in the pathogenesis of MCD may have been responsible for the improvement in the AIHA associated with MCD. Anti-IL-6 receptor antibody treatment could be an attractive therapeutic approach for AIHA associated with MCD.

Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases

“…These diseases include systemic autoimmune diseases such as systemic lupus erythematosus 74-76, systemic sclerosis 77, polymyositis 78, vasculitis syndrome including giant cell arteritis 79-84, Takayasu arteritis 79, 82, 85-87, cryoglobulinemia 88, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis 89 and rheumatoid vasculitis 90. The application of tocilizumab may also extend to organ-specific autoimmune diseases including Crohn's disease 91, relapsing polychondritis 92, 93, acquired hemophilia A 94, autoimmune hemolytic anemia 95, 96, as well as to chronic inflammatory diseases such as adult-onset Still's disease 97-113, amyloid A amyloidosis 114-120, polymyalgia rheumatica 79, 84, 121, remitting seronegative symmetrical synovitis with pitting edema 122, Behcet's disease 123, 124, uveitis 125, graft-versus-host diseases 126, 127, and tumor necrosis factor receptor-associated periodic syndrome 128 ( Table 1 ). Some studies have reported that tocilizumab is efficacious for spondyloarthritis 129-135, although others observed only minor effects 136-138.…”

Castleman's disease of a submandibular mass diagnosed on Fine Needle Cytology: Report of a case with histopathological, immunocytochemical and imaging correlations

“…Furthermore, excess production of interleukin-6 (IL-6) plays an important role in the pathogenesis of the CD (27). Giant lymph node hyperplasia is generally treated with surgery (28).…”

Lymphoproliferative Disorders of the Lung

“…During the lytic phase, replication may be detected in the blood, and viral genes such as viral interleukin-6, are expressed. Most of the clinical effects of MCD are secondary to the presence of viral cytokines such as viral interleukin-6 [122][123][124] .…”