We are reporting the case of a 33 years old Iraqi female Sanaa Ghazi Faisal who presented with history of recurrent episodes of hematuria (blood in urine) for last 6 years associated with extreme fatigue and tender, swollen and stiff joints of both hands, wrists and knees for 1 month. Her physical examination was remarkable for the presence of pallor, bipedal edema, multiple oral aphthous ulcers and tender, swollen bilateral proximal interphalangeal, metacarpophalangeal and wrist joints. She was initially investigated in Iraq but the etiology of anemia and hematuria remained elusive.

Her blood investigations revealed low hemoglobin of 8.1 g/dl, MCV – 93.7 fl, RDW – 26.7, MCH – 30.1, MCHC – 32, reticulocyte count of 3.5%, TLC – 8700 cells/µl, platelet count – 138000 cells/µl, blood urea – 59, creatinine – 0.65, Na+ – 136.8, K+ – 4.6, SGOT – 249, SGPT–180, alkaline phosphatase-233, serum protein-8.5 and serum albumin-4.0. Peripheral blood film showed marked anisopoikilocytosis with presence of microcytic hypochromic red cells, few macrocytes, macro-ovalocytes and micro-spherocytes mixed with occasional fragmented cells, nucleated red cells and hypersegmented neutrophils with no atypical cells. Her serum LDH was 4610 (high) and serum haptoglobin levels were low. She had no haemoglobinuria or hemosiderinuria but had mild proteinuria. The iron profile showed serum iron- 26, TIBC – 205, ferritin-624.85 and transferrin saturation of 19.38% and her vitamin-B12 level was more than 1000 pg/ml. Her Coomb’s test (direct and indirect) were strongly positive. Her bone marrow examination showed erythroid hyperplasia without any evidence of granuloma or malignancy. The upper GI endoscopy did not show any source of gastrointestinal bleed but duodenal biopsy revealed lymphocytic enteritis (Marsh grade I). Further workup for symmetrical polyarthritis showed immunologic markers to be strongly positive with RA factor-365, ESR-128, CRP-104 and anti-ccp antibodies-67.70. She was further worked up for other auto-immune diseases but ANA, anti-ds DNA, anti-scl 70, anti-centromeric antibodies, p-ANCA, c-ANCA, anti-TTG antibodies were all negative. Haemoglobin electrophoresis, uric acid, thyroid profile, HBsAg, anti-HCV IgM, HIV antibody, abdominal ultrasonography and lower limb venous doppler were also unremarkable. Her HRCT chest was done to rule out underlying ILD or lymphoma but showed only some post infective changes.

Based on that she was started on oral steroids (prednisolone – 60 mg OD) and on hydroxychloroquine. Later as her liver functions improved she was started on methotrexate. Meanwhile as she had episodes of nocturnal hematuria, her flow cytometry was done which returned as positive for PNH with 21.76% of CD59 negative red cells.

She was diagnosed as a case of autoimmune hemolytic anaemia with paroxysmal nocturnal haemoglobinuria with rheumatoid arthritis with celiac disease and was planned for eclizumab therapy for PNH. In her follow up she had shown drastic improvement in all her symptoms. Her hemoglobin improved to 11g/dl and polyarthritis also subsided. She had no further episodes of hematuria. She is now maintained on a 10 mg/day dose of prednisolone.

There are only few cases reported in literature where such an association between autoimmune hemolytic anemia, rheumatoid arthritis and PNH was found possibly reflecting an immunologic basis underlying all these entities.