A 13-year-old girl from Tamil Nadu, India, has had progressive pallor since 14 months of age. Haemoglobinopathies were ruled out. The parents later noted black stools from age 3, initially attributed to oral iron therapy. At 4 years of age, she was getting recurrent pain in the abdomen, intermittent abdominal distension, along with chronic watery diarrhoea. An esophagogastroduodenoscopy and ileocolonoscopy were normal, and biopsies from the corresponding areas ruled out inflammatory bowel disease (IBD). A genetic analysis performed at that time identified a homozygous mutation in the SLCO2A1 gene (Exon 10, c1406C>G), which is known to cause primary hypertrophic osteoarthropathy (PHOA). She was being managed with monthly parenteral iron therapy at the time of referral to us. She was first seen at our centre at 13 years of age. Her height was 128 cm (Z-score 24 h) in the transverse and descending colon, suggestive of accumulated blood from a proximal source, most likely the small bowel. She responded dramatically to oral prednisolone (1 mg/kg) followed by Azathioprine (1 mg/kg/day). At 12 months of follow-up, she has a generalised well-being, with improved appetite and no gastrointestinal symptoms. She had a weight gain of 4 kg and required parenteral iron therapy only once thereafter. She also gained 10 cm in height during this period. Melena resolved completely after starting oral tranexamic acid. The plan is to taper steroids and continue Azathioprine maintenance. CEAS is an extremely rare autosomal recessive disorder caused by mutations in the SLCO2A1 gene 1. It is characterised by the formation of non-specific ulcers in the small intestine, which leads to chronic enteropathy and blood loss. Patients usually present with abdominal pain, diarrhoea, oedema, along with general fatigue due to chronic anaemia, and hence it is an important disorder mimicking Crohn's disease or CMUSE, with the latter being caused by a defect in the PLA2G4A gene 1, 2. The same genetic defect can involve the skeletal system and cause PHOA 2. The diagnosis of CEAS is confirmed by genetic analysis along with supportive findings from abdominal imaging, like CECT. Patients with CEAS have a defect in OATP-mediated degradation of prostaglandin E2 (PGE2) 2, 3. Failure of this transporter to clear extracellular PGE2 triggers immune cells and disrupts the intestinal lining, leading to the characteristic multiple ulcers and also leads to fibrogenesis in the long run. Strictures and dilatations in the small bowel occur as sequelae of this uncontrolled fibrogenesis. The mucosa and submucosa show significant infiltration by plasma cells and neutrophils, with superficial ulceration, but no evidence of vasculitis. CEAS can mimic IBD in children, especially Crohn's disease (CD) 2. The disease predominantly involves the mid to distal ileum, characteristically sparing the terminal ileum, which helps distinguish it from Crohn's disease 4, 5. In contrast to patients with CD, the superficial ulcers of CEAS are not of a geographic pattern, and they never progress to fistulae or cobblestoning. These ulcers are usually multiple and are an important source of chronic GI blood loss 4. Strikingly, patients with CEAS have no features of systemic inflammation, which is common in CD 5. The commonest clinical presentation in patients with CEAS includes intestinal obstruction, obscure GI bleeding and protein-losing enteropathy 6, 7. In the largest series on CEAS by Umeno et al., the ileum was universally involved but with sparing of its terminal segment, and 60% of patients had undergone bowel surgery 5. The youngest age of presentation was at 1 year. A diagnostic criterion for this disorder has also been proposed, which includes the presence of the SLCO2A1 mutation 5. CECT of the abdomen in these patients shows multifocal strictures with intervening areas of dilatation and diffuse smoothing of the small bowel's luminal folds, providing a diagnostic clue to this disorder 5. Small bowel enteroscopy can be used to demonstrate ileal ulcers and is usually performed for therapeutic dilatation of narrowed segments. Anaemia can occur secondary to malabsorption, chronic blood loss and bacterial overgrowth. The latter can also contribute to chronic diarrhoea in these patients 4. Treatment of CEAS is predominantly with corticosteroids, and the majority would remain steroid-dependent in follow-up 2, 3. Patients not responding to steroids are known to have poorer outcomes. Azathioprine and other immunomodulators have also been used to treat patients with CEAS. The mechanism of action of Azathioprine in these patients is unknown, and treatment responses have been variable 8. Tranexamic acid was used in our patient in view of its antifibrinolytic and endothelial-stabilising effects, which likely resolved her gut-related bleed. Enteroscopic balloon dilatation can be attempted in cases of resistant strictures in the small bowel, and surgical resection has to be kept as a last resort to prevent short gut syndrome. Post-surgical recurrence of the disease is also known. Our patient had the onset of her gastrointestinal symptoms at 14 months of age, along with extremely severe anaemia, and was diagnosed to have CEAS, a rare disorder mimicking Crohn's disease in children. The absence of terminal ileal involvement was a diagnostic clue in favour of CEAS in our patient, as this finding is rarely seen in Crohn's disease. Although our patient has shown a significant response to Azathioprine, it has to be remembered that the majority of these patients respond poorly to this agent, in contrast with those suffering from CD. Tranexamic acid was helpful in our case for controlling her gastrointestinal bleeding. The role of small bowel transplantation and stem cell transplantation in patients with treatment-refractory CEAS remains unknown. H.S., J.M. and R.R. compiled the manuscript; J.M., S.S. and N.S. did the proofreading. The authors have nothing to report. The authors have nothing to report. The authors declare that the research presented in this manuscript adheres to the ethical principles outlined by the review board of Bharath Institute of Higher Education & Research (BIHER). All procedures involving human participants were conducted in accordance with the ethical standards of the institution, university or country and the Declaration of Helsinki (1964), as revised in 2013. No experiments involving humans were included in this report. Parents of the child gave consent for publishing this report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Seetharaman et al. (Thu,) studied this question.