title: Successful treatment of type B insulin resistance with rituximab.
abstract: BACKGROUND
  Type B insulin resistance is a very rare disease caused by autoantibodies against the insulin receptor. The mortality of type B insulin resistance is high (>50%), and management of this disease is not yet standardized. We report the successful treatment of a patient with type B insulin resistance with rituximab, cyclophosphamide, and prednisone.
  
  
  METHODS
  A 45-year-old woman presented with unintended weight loss of 20 kg, unusually widespread acanthosis nigricans, and glucose levels > 500 mg/dL, which could not be controlled with up to 600 IU/d of insulin. Because of the severity of the insulin resistance combined with features of insulin deficiency, type B insulin resistance was suspected. Detection of high levels of insulin receptor autoantibodies confirmed the diagnosis. Neither immunosuppressive therapy with Ig iv nor plasmapheresis had an effect on glucose levels or insulin dose. Because the patient's condition was deteriorating, we started rituximab (750 mg/m(2) in two doses 2 wk apart) together with cyclophosphamide (100 mg/d orally) and dexamethasone 40 mg/d for 4 days. Two months after initiation of rituximab therapy, fasting glucose levels ranged from 80 to 110 mg/dL and could be controlled with very low insulin doses. Glycated hemoglobin decreased from 11.8 to 6.5%. Two months later, insulin therapy was stopped, and the patient showed normal blood glucose readings.
  
  
  CONCLUSIONS
  In this patient with type B insulin resistance, Ig treatment and plasmapheresis failed to improve the condition. Finally, treatment with rituximab, cyclophosphamide, and steroids was successful in inducing a complete remission.
authors: University Duisburg-Essen (E.-D.M., D.F., L.C.M.), Department of Endocrinology and Metabolism and Division of Laboratory Research, 45147 Essen, Germany; Wellcome Trust-Medical Research Council Institute of Metabolic Science (I.I., R.K.S.), Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; and University of Maryland School of Medicine (R.M.), Division of Endocrinology, Diabetes, and Nutrition, Baltimore, Maryland 21201.
authors: Emmanouil-Dimitrios
authors: ED
authors: Manikas
authors: Iona
authors: I
authors: Isaac
authors: Robert K
authors: RK
authors: Semple
authors: Rana
authors: R
authors: Malek
authors: Dagmar
authors: D
authors: Führer
authors: Lars C
authors: LC
authors: Moeller
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000276:immunology*; D008875:Middle Aged; D010956:Plasmapheresis; D011972:Receptor, Insulin / Q000276:immunology*; D019233:Retreatment; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D011972:Receptor, Insulin