She was diagnosed with AIE based on her symptomatology, affirmative histopathologic findings, and exclusion of related conditions. Her treatment consisted of temporary total parenteral nutrition and 40 mg IV methylprednisolone daily for 5 days, followed by a prolonged oral prednisone taper at the time of discharge. At her 2-month follow-up, she was transitioned from low-dose prednisone to budesonide, had gained back 10 pounds, and had complete resolution of her nausea, vomiting, and diarrhea. She discontinued corticosteroid treatment at 3 months, and 6 months later, she was still in remission.
AIE is an emerging diagnosis in the adult population and should be included in the differential diagnosis for patients with intractable diarrhea. A diagnostic criterion includes malabsorptive diarrhea for more than 6 weeks that does not improve with dietary changes and characteristic histological findings. Small bowel histology shows partial or complete blunting of the villi, deep crypt lymphocytosis, increased crypt apoptosis, and minimal intraepithelial lymphocytosis. Diagnosis is supported by positive antienterocyte antibodies in approximately 80% of cases. Differential diagnosis includes celiac disease, common variable immune deficiency (CVID), refractory sprue, small bowel lymphoma, and medication-related enteropathy most notably from olmesartan. These related conditions should be excluded before making a diagnosis of AIE. Celiac disease, unlike AIE, typically responds to a gluten-free diet. Refractory celiac disease does not respond to dietary changes but more often has histological findings of increased intraepithelial lymphocytes (>40 per 100 epithelial cells) compared with patients with AIE.4 Furthermore, AIE can be distinguished from CVID because the latter would have serum studies showing 2 or more immunoglobulin deficiencies, and most patients (83%) with CVID do not have plasma cells on histology.
Once a diagnosis has been performed, consider any potential polyendocrinopathy syndromes, such as immunodysregulation polyendocrinopathy, enteropathy X-linked syndrome and autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy, given their known association with AIE. This patient did not have any of the features of these or other polyendocrinopathies such as psoriasis, anemia, nephritis, pneumonitis, candidiasis, hypoparathyroidism, or Addison disease. Furthermore, these endocrinopathies are generally pediatric diseases, and it would be highly unlikely to make a new diagnosis in an adult. However, our patient had a history of RA, and a rare association between AIE and RA has been reported in the literature.5
Treatment of AIE usually starts with corticosteroids, and then, patients with refractory symptoms may advance to other immunosuppressive medications on a trial and error basis. Previous case studies have documented the use of cyclosporine, tacrolimus, azathioprine, sirolimus, 6-mercaptopurine, rituximab, infliximab, adalimumab, and vedolizumab. Generally, patients require total parenteral nutrition as well for their caloric needs. Our patient had a complete response after 8 weeks of prednisone and stopped treatment after 12 weeks without return of symptoms. Approximately 60% of patients have symptom resolution after 1–8 weeks of steroids with or without additional immunosuppression, whereas 20% of patients achieve partial response and 20% do not respond.1 Prognosis varies widely based on the severity of symptoms and extent of histological lesions, and more research is needed to better understand the natural history and treatment for this emerging condition.
This case is unique in that the patient had an initial nondiagnostic EGD and small intestinal histopathology despite having chronic malabsorptive diarrhea and weight loss for at least 2 months duration. The fact that her initial EGD sampling was histopathologically normal but her repeat EGD 9 weeks later had villous blunting on direct visualization and histopathology raises the possibility of sampling error because of patchy villous blunting or a slowly evolving small intestinal inflammatory process, whereby the characteristic histologic features of AIE may be missed if sampled too early in the disease process. This case highlights the importance of maintaining a broad differential diagnosis for patients with chronic diarrhea. It also emphasizes the utility of repeat EGD and biopsy in patients with unexplained diarrhea with an initial nondiagnostic EGD and persistent symptoms because villous blunting may be patchy and chronic inflammatory changes of AIE may evolve over time.
Author contributions: MD Lundholm wrote the manuscript. X. Ding provided the images and interpreted histopathology. AT Abegunde, K. Wanta, and L. Palmer revised the manuscript. AT Abegunde is the article guarantor.
Financial disclosure: None to report.
Previous presentation: The abstract was presented at the American College of Gastroenterology Annual Scientific Meeting; October 25–30, 2019; San Antonio, Texas.
Informed consent was obtained for this case report.
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© 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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