Hypoplastic Anemia Associated with Ulcerative Colitis in a Child

Ulcerative colitis (UC) has protean extraintestinal manifestations affecting nearly all the organ systems. Hematological abnormalities, such as iron deficiency anemia (most common), hemolytic anemia, leukocytosis, thrombocytosis, immune thrombocytopenia, and coagulation defects are known to occur in UC (1). We report an unusual case of a child with UC having associated hypoplastic anemia, since no such case has been reported. CASE REPORT A 9-year-old boy was seen at our hospital for recurrent episodes of bloody diarrhea, progressive anemia, and growth retardation, which he had experienced since the age of 5 years. On average he had five to eight stools per day, and each episode lasted 15-20 days with symptom-free periods of 1-2 months. There was no history of drug intake before this illness. Physical examination showed severe pallor, weight of 14 kg (expected 24 kg), and height of 108 cm (expected 125 cm). Examination of the abdomen, chest, and cardiovascular, nervous, and skeletal systems was normal. Family history was noncontributory. Laboratory investigations showed normocytic normochromic anemia (Table 1) with hematocrit of 22%, mean corpuscular volume of 80 fl, mean corpuscular hemoglobin of 27 pg and mean corpuscular hemoglobin concentration of 34 g/dl. Liver function tests, coagulation profile, and urea and creatinine levels were normal. Both direct and indirect Coombs tests were negative. Hepatitis B surface antigen and anti-HCV (by enzyme-linked immunosorbent assay) were negative. Stool examination was positive for red blood cells. Stool culture did not grow any enteropathogen. Radiography of the wrist confirmed a bone age of 3 to 4 years. A bone marrow trephine biopsy from the iliac crest was done outside our institution 6 months before presentation to our hospital. It showed few fatty marrow fragments with marked reduction in myeloid, erythroid, and megakaryocytic series suggestive of hypoplastic anemia. On total colonoscopic examination the lumen contained blood and mucus; the mucosa was friable and edematous with multiple ulcerations and nodularity extending from the rectum to the splenic flexure. Rectal biopsy showed crypt distortion, cryptitis, severe mucodepletion, and a mixed inflammatory cell infiltrate suggestive of UC. A small bowel contrast study was normal. The patient was given 25 mg of oral prednisolone and 400 mg of 5-aminosalicylic acid daily and required 5 u of blood. The UC went into remission after 6 weeks' therapy. Thereafter 5-aminosalicylic acid was continued as maintenance therapy. After 6 months of follow-up, significant improvement in physical growth and hematological parameters (Table 1) was seen. Bone marrow trephine biopsy from the iliac crest done during remission showed normal cellularity of myeloid, erythrocytic, and megakaryocytic series. After 1 year (18 months from presentation) the patient had a relapse of UC and also showed hematological abnormalities (Table 1) and features of hypoplastic anemia on bone marrow examination Both the UC and hypoplastic anemia responded to oral steroids. After 3 months the patient again showed signs of hypoplastic anemia without any relapse of UC and required frequent blood transfusions (10-12 u in 6 months) to maintain a normal hemoglobin. DISCUSSION The prevalence of inflammatory bowel disease (IBD) in the general population varies from 30 to 80 per 100,000, and ≈20% of affected patients show symptoms in childhood (2,3). Acquired aplastic anemia has been estimated at 3.5-5.4 cases per million population per year (4). Anemia in UC has been attributed to various factors, such as blood loss, sepsis and toxemia, bone marrow depression, myelodysplastic syndromes, pure red cell aplasia, faulty absorption, mild hemolysis, and a combination of these factors (1,5-9). An immunological link between ulcerative colitis and hematological abnormalities has been suggested by reports of Coombs-positive autoimmune hemolytic anemia (8,9). Hypoplastic anemia associated with infection and toxemia is thought to be due to bone marrow depression preventing normal development and delivery of red cells from the marrow. Pollard et al. attempted to correlate the occurrence of hypoplastic anemia with the presence of infection and toxemia. This factor was found to be particularly important in normocytic anemia, where 10 of 13 patients had a severe degree of toxemia, as indicated by highgrade fever and leukocytosis (10). In the present case of hypoplastic anemia, fever, leukocytosis, and toxemia were not features. Absence of these common factors in the present case suggests some other mechanism of bone marrow hypoplasia. Anemia with thrombocytopenia has been reported in a child with inflammatory bowel disease who had a low reticulocyte count, but megakaryocytic hyperplasia on bone marrow examination suggested increased peripheral destruction. This finding is in contrast to our patient, who had a low reticulocyte count and bone marrow hypoplasia (11). Although the association between UC and hypoplastic anemia may be coincidental, the temporal relationship between anemia and the activity of colitis suggests otherwise. A definite history of exposure to agents that may induce aplastic anemia has been reported in 50% of pediatric patients. In 30-50% of patients no cause can be found (12). Non-drug-induced hypoplastic anemia is usually caused by immunological abnormality and is known to be associated with various immunological disorders, such as thymoma, hypogammaglobulenemia, paraproteinemia, lupus erythematosus, and myasthenia gravis (13). The presence of an IgG inhibitor of erythropoiesis with either an elevated erythropoietin level or near absence of erythropoietin has been confirmed in some patients (13,14). Erythropoietin supplementation can enhance erythropoiesis in patients with low erythropoietin concentrations (15). Immune dysfunction, including impairment of T cells and natural killer cells, has been described in patients with IBD (16). In addition, chronic immune stimulation with increased endogenous release of cytokines, such as interferon, interleukin 1, and tumor necrosis factor, have been thought to be responsible for suppressing bone marrow (17). It is thus possible that immune-mediated inhibition of erythropoiesis played a part in this case.