A 4 years 7 months old boy presented in clinic with history of abdominal pain and diarrhea on and off for 1 year. There was also history of failure to thrive and pallor. He received treatment from many local doctor but symptoms did not improve. He also complained of body aches and distended abdomen for last 2 months. He was born full term with no postnatal issue. He was breastfed for first 6 months only followed by formula. Weaning was started at 6 months. He is partially vaccinated and developmentally normal. He has 2 other siblings who are healthy. His parents had a non-consanguineous marriage and there was no history of tuberculosis, malabsorption, or celiac disease in family.
On examination, he was hemodynamically stable, pale, and malnourished with distended abdomen. Height was 91 cm and weight was 12 kg (both less than fifth centile). There was no visceromegaly. Fluid thrill and shifting dullness were negative. Rest of systematic examination was also unremarkable.
Initial labs showed hemoglobin (Hb) 8.8 g/dl, white cell count (WBC) 9940/ul, platelets 551 000/ul, MCV 53.9, MCH 13.6, Ferritin 20.1, ESR 34, alanine aminotransferase (ALT) was 18 U/L. Electrolyte, renal, liver function test, stool examination, and culture were normal. He was investigated for CD, Anti TTG IgA <0.1 (positive >10), Anti TTG Ig G 13 (positive >10) and was also positive for deaminated gliadin peptide (DGP) IgA. To confirm the diagnosis esophagogastroduodenoscopy (EGD) was done which was consistent with diagnosis of Celiac disease (MARSH Type 3a) showing distorted villous architecture, increased intraepithelial lymphocytes (Figure 1a). He was advised to follow a gluten free diet along with iron supplements. HLA testing was not done due to non-affordability of patient.
Later, after 2 weeks he presented with jaundice, fever, anorexia, dark colored urine, and irritability. He was deeply jaundice and had marked pallor on examination, his abdomen was soft with mild hepatomegaly but no splenomegaly. He was admitted for fulminant hepatic failure and investigations for anemia. Initial investigation showed hemoglobin 7.2 g/dl, WBC 10 260, platelet 186 000, total bilirubin 7.76 mg/dl, direct bilirubin 5.40 mg/dl, (ALT) 236, aspartate transaminase AST 439, gamma GT (GGT) 226, alkaline phosphatase ALP 387, serum ammonia 141, PT 12.50, INR 1.68 (0.8-1.3) APTT 45 seconds (24.8-36.2). Viral serology for hepatitis A and E were negative. Workup for Wilson disease was normal including serum ceruloplasmin 20.2 mg/dl (15-30 mg/dl), 24 hours urinary copper excretion was 16 ug/day (normal <60 ug/day), KF rings were not seen. Serial liver function tests are shown in Table 1. Further workup for anemia showed reticulocyte count 7.1, LDH 423, direct and indirect coombs test was positive suggestive of autoimmune hemolytic anemia for which steroids were started. Ultrasound abdomen showed mild hepatomegaly.
Autoimmune liver profile showed ANA+ and was negative for AMA, ASMA, GPC, and LKM. However, patient had hyper immunoglobulin Ig G was 44.1 g/l (Normal for this age 5.04-14.65). Liver biopsy showed moderate portal inflammation with foci of interface hepatitis, parenchymal cholestasis, and giant cell changes along with fibrous portal expansion with short fibrous septae, all favoring autoimmune hepatitis type I (Figure 1b).
Prednisolone (2 mg/kg/day) and Azathioprine (2 mg/kg/day) were started. Steroids were gradually tapered over 4 weeks. Two months follow-up showed normalization of LFTs. His hemoglobin improved from 7.2 to 8.8 g/dl on follow-up. Gluten free diet is re-emphasized on each visit.
Pediatric hematologist, gastroenterologist, and dietician were involved and final diagnosis of celiac disease with autoimmune hemolytic anemia and giant cell autoimmune hepatitis was made. Written informed consent was taken from the parents.