HEMOLYTIC ANEMIA IN RHEUMATOID ARTHRITIS: A RARE CASE REPORT Durgesh Srivastava*, Pooja Dhaon**, Urmila Dhakad***, Saumya Ranjan Tripathy*, Danveer Bhadu*, Siddharth Das**** *Senior Resident, **Senior Research Associate, ** *Assistant Professor, *** Professor, Department of Rheumatology, King George’s Medical University, Lucknow, India Most chronic inflammatory rheumatic diseases are complicated by hematologic abnormalities, including anemia; disorders of leukocytes, platelets, and the coagulation system; and hematologic malignancies1. Rheumatoid arthritis (RA) is one of the most common inflammatory arthritides. It is associated with multiple systemic features, including hematological manifestations such as anemia, neutropenia and thrombocytopenia. However, immune hemolytic anemia is extremely rare with very few reports, and one of them being due to methotrexate toxicity. We hereby report a 40 years old lady; a known case of seropositive RA for past 3 years who presented to us with history of recurrent anemia and jaundice. Her hand radiographs did not show any erosions but bone scan was suggestive of active arthritis in both knees, elbows, shoulders and ankles. The patient fulfilled 2010 criteria for RA and she did not have any feature of any other disease. She had initially responded to prednisolone 0.5mg/kg and azathioprine150 mg daily. Due to relapse of anemia, azathioprine was switched to mycophenolate mofetil (dose increased upto 1.5g twice daily) and steroid was gradually tapered. After 3 months she again relapsed. There was no splenomegaly, and leukocyte and platelet counts were normal ruling out hypersplenism. She was restarted on low dose prednisolone and MMF was continued. Her DAS-28 had improved with treatment and clinical remission had been achieved within 1 year of starting treatment, but her anemia continued independent of her joint disease. Currently her arthritis is in remission and her Hb is 11.3, and it has been stable for the last 6 months of follow up and steroid is being tapered. With no clear evidence of immune mediated hemolysis or hemoglobinopathy, the possibility of hemolytic anemia was considered. As the anemia persisted despite remission of joint activity, the possibility of anemia being a direct consequence of RA is unlikely. It could be a co-existence of the two disorders in a same patient. Introduction Table 1. Details of the case reports in literature on the association of AIH with RA. Case report Age/ sex Duration of RA at the time of diagnosis of AIH Clinical presentation Coombs test Treatment/ outcome Chapman AH. (1972) 56/F 1year Anemia Not performed Steroids Maharaj D. (1986) 82/F 5 year Parosysmal nocturnal hemoglibinuria Positive Transfusion of washed red blood cells Ryumachi et al. (2000) 57/F 1 year Severe anemia (Methotrexate induced) positive Steroids. Souza RAS et al. (2003) 69/F 30 years Not discussed. Kaur et al. (2006) 38/F 5 months Jaundice (Cold antibody type) Not discussed. Patient expired Garcia et al. (2011) 27/M Simultaneously Transfusion of washed red blood cells, Methotrexate, steroids Present case 40/F 2 years negative Steroids, Mycophenolate mofetil. Case INVESTIGATIONS Hemoglobin 8g/dl Mean Corpuscular volume 104 fl White blood cells 5500/ cumm Platelets 163000 C-Reactive protein 19 nmol/l Rheumaroid Factor Positive (1259 IU.ml Anti CCP Antibody Positive (198 IU) Serum Bilirubin Total- 3.18 mg/dl, Indirect- 2.67 mg/dl Serum Lactate Dehydrogenase 259 IU/L (>240) Reticulocyte count 10% Serum Ferritin 342ng / dl Serum Iron 126 Microgram/dl Coomb’s Test Negative Anti Nuclear Antibody (Hep-2) 1+ at 1:100 titre Complements levels Normal Anti double stranded DNA G-6-Phosphate Dehydrogenase activity Hemoglobin Electrophoresis Bone marrow examination Normal hematopoiesis HIV/ HBSAg/ Anti HCV Even though Coombs test is the mainstay for serological diagnosis of AIH, it can be negative in some situations as low levels of antibodies on red blood cell (RBC) membranes, low sensitivity of the conventional test and presence of other auto- antibodies like IgA and IgM2. RBC- IgG levels should be measured by immunoradiometric assay to confirm the diagnosis patients in such situations which was not done in this case due to unavailability of the test. Coombs negative AIH is usually mild and responds equally well to steroids in comparison to Coombs positive AIH. The association of AIH with RA is very rare. Only 6 cases have been reported till date (table 1). All except one patient were females aged between 30 – 80 years. 3 patients presented with jaundice, 2 with anemia and 1 patient with paroxysmal nocturnal hemoglobinuria.. Only 1 patient had cold antibody type AIH. In only 1 patient, the etiology was attributed to Methotrexate Probably the pathogenesis in other patients can be attributed to the immune dysregulation in RA, which leads to the development of multiple auto reactive clones. This is the first report with Coombs negative AIH in RA which responded to steroids and mycophenolate mofetil. Still more evidence is required in regards to this association, to come to conclusion regarding the pathogenesis and the exact association of AIH in RA. 1. Hamilton PJ. The haematology laboratory and the rheumatologist. Clin Rheum Dis 1983; 9:69. 2. Hansen OP, Hansen TM, Jans H, Hippe E. Red blood cell membrane-bound IgG: demonstration of antibodies in patients with autoimmune haemolytic anaemia and immune complexes in patients with rheumatic diseases. Clin Lab Haematol 1984; 6:341. References Discussion