1. 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 mg/dl, Indirect 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