Lymphocytic Esophagitis in Crohn’s Disease: Understanding the Significance

Abstract

Introduction: Lymphocytic esophagitis (LE) is a rare, recently described entity of undetermined etiology or significance. We report an adult man with Crohns disease (CD) controlled with anti-TNF therapy but with refractory nausea and vomiting attributed to LE. A 49-year-old man with a 23-year history of CD reports persistent nausea, vomiting, and diarrhea for several years. He has peripheral arthritis that is worse with CD flares, GERD treated with omeprazole, and recently quit smoking. He had 2 prior surgeries 15 years apart, first for enterovesical fistula and later ileocecal resection. Three years ago, evaluation of symptoms and weight loss with colonoscopy and EGD showed active ileitis on biopsy, no UGI CD, and a transient ringed esophagus, but was negative for eosinophilic esophagitis or LE. He is currently on adalimumab 40mg weekly, which has improved pain, diarrhea, and weight; nausea and vomiting persist. He had not responded to mesalamine, 6MP, or a lower dose of adalimumab, had a partial response to steroids with severe side effects, and a delayed hypersensitivity reaction to infliximab. One year ago, MR enterography and colonoscopy revealed no evidence of active CD. Two months ago, upper and lower endoscopy were grossly normal. However, biopsies revealed esophageal LE at 35cm and increased lymphocytes in the duodenum. Despite swallowed Flovent for 2 months, nausea and vomiting persist. LE was first described in 2006 by Rubio et al as increased intraepithelial lymphocytes near the peripapillary fields without increased granulocytes. The less than 10 published studies to date have noted few associations without a dominant theory to its clinical significance. Data suggest an association of LE to pediatric CD, but 4 separate studies have found no association in adult CD. Dysphagia, the most common presenting complaint, is present in about half of LE cases. Interestingly, patients with LE may be half as likely to have GERD than patients without LE. Another reported association has been esophageal rings, as in our patient. In one large retrospective review, the esophageal mucosa was visually normal in as many as 91% of cases. Thus, clinicians with a degree of suspicion should consider performing blind esophageal biopsies to look for LE. Our patient has severe CD tried on multiple therapies. His current regimen has improved weight, diarrhea and abdominal pain. Recent endoscopic evaluation was negative for active CD. His refractory nausea and vomiting is puzzling; our hypothesis is that LE is contributing. Further studies, including prospective observational studies and additional retrospective reviews of esophageal biopsies, are needed to characterize the significance, natural history and management of LE.