the association between primary immune thrombocytopenia ( itp ) and autoimmune hemolytic anemia ( aiha ) was first reported by evans et al . in 1951 . since this first report , there have been many reports of evans syndrome in association with other autoimmune diseases . hashimoto 's disease is one of the most common autoimmune diseases and is often associated with other non - endocrine autoimmune diseases . evans syndrome is a non - endocrine autoimmune disease and can present with anti - thyroid auto - antibodies . although it is assumed that autoimmune thyroiditis and evans syndrome have overlapping immunological mechanisms , to date , there has been little evidence to support this assumption . here , we present a 50-year - old female patient who was diagnosed with hashimoto 's disease , aiha , and itp over a 16-year period . the patient was diagnosed with hashimoto 's disease and overt hypothyroidism in may 1994 and aiha in october 2006 . subsequently , after 22 months , in september 2009 , she developed itp and was diagnosed with evans syndrome ( the combination of aiha and itp ) . treatment options for evans syndrome include corticosteroids ; intravenous immunoglobulin ; immunosuppressive drugs such as danazol and rituximab ; splenectomy ; and stem cell transplantation . recently , the use of rituximab has shown promising results [ 2 , 3 ] . several cases of combined evans syndrome and thyroid endocrine dysfunction ( hyperthyroidism or hypothyroidism ) have been reported [ 1 , 4 , 5 ] . however , to the best of our knowledge , this is the first korean report that describes a case with the sequential development of autoimmune thyroiditis , aiha , and itp , and was successfully treated with rituximab . a 51-year - old female patient visited the outpatient clinic of the department of hematology for regular follow - up visit for her aiha in september 2009 . she was diagnosed with hashimoto 's thyroiditis and had been taking synthetic thyroid hormone for hypothyroidism since 1994 . in 2001 , her anti - microsomal antibody level increased to 1:6,400 , but we did not have data about her thyroid autoantibody level at diagnosis . in september 2006 , she was admitted to the hospital due to dizziness and jaundice , and was subsequently diagnosed with aiha . serologic testing showed elevations in anti - microsomal antibody ( 49 u / ml ) and thyroglobulin antibody . the tests for human immunodeficiency virus ( hiv ) antibody , hepatitis b surface ( hbs ) antigen , hbs antibody , hepatitis c virus ( hcv ) antibody , and igm hepatitis a virus ( hav ) antibody were all negative . after this diagnosis , her hemoglobin level waxed and waned between 6 g / dl and 11 g / dl based on the dose of prednisolone being taken at the time . during this time , she refused to undergo a splenectomy . abrupt thrombocytopenia ( 6810/l ) was detected during a regular follow - up on september 1 , 2009 . during that visit , she also complained of weight gain of 10 kg that had occurred during the past 3 years . on physical examination the abdomen was soft and flat , and the liver and spleen were not palpable . the patient had persistent thrombocytopenia ( 2110/l to 3010/l ) for the subsequent 3 months while she was taking prednisolone ( 2.5 mg / day ) . on the other hand , her hemoglobin level remained stable ( 10 g / dl to 13 g / dl ) during the 3-month period . no abnormal findings were observed on bone marrow biopsy , and bone marrow cellularity was normal ( 40% ) . normal levels of erythropoiesis and granulopoiesis were observed , and the number of megakaryocytes was slightly high . on the basis of these results of bone marrow biopsy , she was diagnosed as having itp . serologic testing showed elevations in anti - thyroglobulin antibody ( > 2,000 u / ml ) and anti - microsomal antibody ( 80.3 u / ml ) , and the serum was positive for the anti - nuclear antibody test ( 1:640 , cytoplasmic pattern ) . after the diagnosis of itp , the dose of prednisolone was increased to 1 mg / kg ( 60 mg ) . while prednisolone was being tapered back down over a period of 4 months , the platelet count decreased to 710/l . rituximab ( 375 mg / m ) was administered once a week for 4 weeks along with 1 mg / kg prednisolone from may 20 , 2010 till june 10 , 2010 . rituximab was well tolerated , and the platelet count rapidly increased to 9210/l by 2 weeks after the completion of the fourth dose of rituximab . azathioprine 100 mg was added from june 17 till september 16 ( for 3 months ) and danazol 300 mg was added from june 29 to august 31 . considering median time to response ( usually few months ) of these drugs , elevation of platelet count hemoglobin levels , platelet counts , doses of prednisolone , and the timing of medications are illustrated in fig . currently , she is not taking any medication for itp or aiha and appears to be in complete remission , except for a slightly decreased platelet count ( > 11010/l ) for about 10 months . interestingly , the intermittent peaking of tsh in this patient was greatly reduced after the use of high - dose prednisolone and rituximab in combination with a low dose of l - thyroxine ( 0.1 mg ) . before the initiation of rituximab miu / l and 19.7 miu / l , even though she was taking a higher dose of l - thyroxine ( 0.15 mg ) . the doses of l - thyroxine , prednisolone , and rituximab , and the tsh levels are presented in fig . 2 . we could not follow up the autoantibody level after rituximab therapy , because the patient was transferred to another hospital . her last serologic test at our institution showed reduction in the titer of anti - nuclear antibody test ( 1:80,cytoplasmic pattern ) . evans syndrome is a rare hematological abnormality characterized by coombs - positive aiha and itp without any known underlying cause first - line therapy is immunosuppression , while second - line therapy includes danazol and splenectomy [ 2 , 3 ] . various immunosuppressive therapies , including vinca alkaloids , androgens , corticosteroids , intravenous immunoglobulin , and splenectomy , have been used to treat evans syndrome . however , both medical and surgical treatments have been rather unsuccessful in treating refractory cases of evans syndrome . response rates to conventional agents are variable , and some patients require lifelong immunosuppression to keep the disease in remission . rituximab is a chimeric human / mouse monoclonal antibody that targets cd20 on b lymphocytes   and is increasingly used for a variety of autoimmune disorders , including evans syndrome [ 2 , 3 , 8 ] . previously , many researchers have reported the successful use of rituximab for the treatment of patients with corticosteroids - refractory evans syndrome [ 3 , 7 , 10 , 11 ] . there have been several reports of the co - existence of evans syndrome and thyroid endocrine dysfunction [ 1 , 4 , 5 ] . recently , there have been reports of the use of rituximab for the treatment of autoimmune thyroid diseases [ 12 - 14 ] . b cell depletion resulted in diminished b cell and t cell infiltration in the thyroid , thereby inhibiting the development of spontaneous autoimmune thyroiditis . although we could not determine the thyroid autoantibody level after rituximab therapy , thyroid functions were normalized gradually despite taking a small dosage of l - thyroxine . our results suggest that rituximab therapy may be beneficial for patients with hashimoto 's thyroiditis . to our knowledge , our report is the first to describe the stabilization of both autoimmune thyroiditis and evans syndrome by the administration of rituximab . although the causes of these diseases remain uncertain , this case suggests a common immunological mechanism may play an important role in the pathogenesis of these diseases and supports the use of rituximab in patients with these 3 disorders ( hashimoto 's thyroiditis , aiha , and itp ) .
we report a case of a 51-year - old woman with evans syndrome ( autoimmune hemolytic anemia and primary immune thrombocytopenia ) and hypothyroidism . 
 she was previously diagnosed with hashimoto 's thyroiditis in 1994 ( age , 35 ) and autoimmune hemolytic anemia ( aiha ) 3 years ago . 
 she was treated with oral prednisolone . after a period , in which the anemia waxed and waned , there was an abrupt development of thrombocytopenia ( nadir 15109/l ) that coincided with the tapering off of prednisolone after 3 years of administration . because her thrombocytopenia was refractory to prednisolone , we administered rituximab ( 375 mg / m2 weekly ) for 4 weeks . 
 two weeks after the completion of the rituximab treatment , her platelet count was up to 92109/l . 
 no intermittent peaking of thyroid stimulating hormone occurred after rituximab treatment was initiated . 
 evans syndrome and autoimmune thyroiditis might share common pathophysiological mechanisms . 
 this notion supports the use of rituximab in a patient suffering from these disorders .