Strong Association of Celiac Disease Serology with Idiopathic Autoimmune Hemolytic Anemia from Western India

Idiopathic autoimmune hemolytic anemia (AIHA) may be associated with positive autoimmune serology and some of the patients develop autoimmune disorder, malignancy on long follow up.

There are no cohort studies on AIHA from India with long follow up. As AIHA has no known etiology and different populations of the world differ in their genetic makeup, environment background, it is likely that underlying conditions associated with AIHA will also vary in different countries with different population characteristics.

Present study evaluates association of autoimmune markers along with follow up of a cohort of 21 well characterized AIHA patients from Gujarat, a western state of India.

The cohort comprises of 2 men and 19 women aged between 20-72 years (Mean 36 years), followed up for a varying period of 6 month to 25 years (Mean 4¹/₂years) after the diagnosis. AIHA was diagnosed by classical criteria of clinical presentation with severe weakness with feeling of being unwell, pallor and yellow discoloration coupled with laboratory parameters showing low hemoglobin (3.7-7.2 g/dL), high serum bilirubin level ( 2.1-3.8 mg/dl) , high reticulocyte count (5-69%) and strong direct anti human globulin(AHG) test coupled with absence of any other disease on detailed biochemical, flow cytometry (PNH, clonal disorders excluded) and other relevant imaging studies. Bone marrow examination was done in all patients. Splenomegaly of varying degree was present in 16/21 (78%) of the patients.

All patients except 3/21 (14%) received red cell transfusions following the diagnosis as the Hb levels were very low. Best cross matched red cells were provided along with high dose prednisolone (1 mg/kg body weight). One of the patients, a 32 year old lady presented with intense hemolysis, hepatosplenomegaly, lymphadenopathy and hemophagocytosis in peripheral blood and in the marrow. After their stabilization the patients were tested for several autoimmune markers e.g. ANA, Anti ds-DNA, Antiparietal Cell, Antithyroid, AntiCardiolipin, Anti-β₂glycoprotein, anti-tissue transglutaminase antibody IgA and lupus anticoagulants. 11/21 patients became AHG negative within one year, however they continued to show positive reaction by western blot test.

7/21 (34%) positive for LA screening test (3 confirmed by platelet neutralization (14%), 2/21 positive for anti-β2 glycoprotein antibody. Anticardiolipin antibody and antiparietal cell antibody was negative in all. 4/21 were positive for antithyroid antibody and one of them needed thyroxine. 7/21 (34%) were ANA positive (6/7 anti dsDNA positive), one of them went on to develop SLE. One patient with LA positivity developed DVT in left leg and portal vein thrombosis.

Most striking association in our cohort was seen with anti-transglutaminase antibody IgA, 8/21 (38%) were strongly positive for the antibody and 6/21 (28%) were in the borderline range. Hence 66% of our cohort had abnormal serology for celiac disease. AIHA in all our patients were well controlled 16/21 (78%) with steroid and azathioprine only, 4/21 underwent (18%) splenectomy. Single patient presenting with extensive hemophagocytosis and immune hemolytic anemia received weekly courses of Rituximab (375mg/m²), 4 cycles and her Hb was stabilized.

Association of Celiac disease marker with AIHA in a large majority of patients needs further exploration. Western blot can be used when AHG tests become negative during follow up.