title: Rituximab as a therapeutic tool in severe mixed cryoglobulinemia.
abstract: Type II mixed cryoglobulinemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, sustained by proliferation of oligoclonal cells. Systemic B cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (rituximab). Similar effects could be expected in type II MC. Twelve patients, mean age 61.9 years (range 37-76), 11 with HCV infection genotype 2a2c (4 cases) or 1b (6 cases) and 3 (1 case) and symptomatic type II MC with systemic manifestations, including renal involvement, marrow clonal restriction, large necrotizing ulcers, and polyneuropathy, were considered eligible for rituximab therapy because of resistance or intolerance to conventional therapy or important bone marrow infiltration. Rituximab was administered intravenously at a dose of 375 mg/m2 on days 1, 8, 15, and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, and laboratory parameters. Levels of proteinuria, hematuria, erythrocyte sedimentation rate, cryocrit, rheumatoid factor, and IgM decreased while C4 values increased and HCV viral load remained stable during short- and medium-term observation. Bone marrow abnormalities were found to reverse to normal. Constitutional symptoms disappeared or ameliorated. No acute or delayed side effects were seen. Based on this experience and a number of reports published in the last 5 years, Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC with signs of systemic vasculitis.
authors.affiliation: Centro Multidisciplinare di Ricerche di Immunopatologia e Documentazione su Malattie Rare, Struttura Complessa a Direzione Universitaria di Immunologia Clinica (CMID), Ospedale S.G. Bosco, L.go Donatore del Sangue 3, 10154, Torino, Italy. dario.roccatello@unito.it
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.forename: Simone
authors.initials: S
authors.lastname: Baldovino
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Giachino
authors.forename: Morteza
authors.initials: M
authors.lastname: Mansouri
authors.forename: Carla
authors.initials: C
authors.lastname: Naretto
authors.forename: Debora
authors.initials: D
authors.lastname: Di Simone
authors.forename: Simona
authors.initials: S
authors.lastname: Francica
authors.forename: Roberto
authors.initials: R
authors.lastname: Cavallo
authors.forename: Mirella
authors.initials: M
authors.lastname: Alpa
authors.forename: Franca
authors.initials: F
authors.lastname: Napoli
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Sena
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D002986:Clinical Trials as Topic; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab