Esophageal Stricture: Not Your Usual Culprit?

Abstract

Question: A 60-year-old woman with past medical history of ATTR amyloidosis and status post heart and liver transplantation presented with complaints of progressive esophageal dysphagia to solids and liquids. She was on tacrolimus, mycophenolate mofetil (MMF), and prednisone. Other pertinent medications included trimethoprim sulfamethoxazole and valganciclovir for infection prophylaxis. Physical examination and laboratory data were unremarkable. Esophagogastroduodenoscopy (EGD) with histopathologic examination of biopsies from the middle third of the esophagus showed the findings presented in Figure A and B. Despite high-dose proton pump inhibitor therapy and repeated dilations, symptoms were unchanged and little progress was made in maintaining an increase in luminal diameter. What is the most likely diagnosis? Look on page 400 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The EGD demonstrates a long, benign-appearing, intrinsic moderate stenosis with extensive fibrotic stricturing in the middle one-third of the esophagus (8 mm inner diameter × 4 cm in length) (Figure A). The stenosis was dilated with a through the scope dilator to 11 mm. Esophageal biopsies demonstrated extensive ulceration with fibrinopurulent exudate and inflamed granulation tissue (Figure B). No fungal or viral infection or malignancy was seen. The patient underwent placement of a percutaneous gastrostomy tube. Over the next year, despite continuous high-dose proton pump inhibitor therapy, she continued to experience dysphagia and required monthly dilations. After ruling out an infectious etiology, MMF was suspected as the possible culprit. Immediately upon withdrawal of MMF, the patient reported significant clinical improvement. A follow-up EGD 4 months later showed a widely patent esophageal lumen with only mild mucosal variance characterized by flattening and scarring in the mid esophagus. MMF has well-known gastrointestinal (GI) adverse effects, including nausea, vomiting and diarrhea. Although the entire GI tract is susceptible to MMF-related toxicity, the colon and, less commonly, the small bowel are the most affected areas.1Nguyen T. Park J.Y. Scudiere J.R. Montgomery E. Mycophenolic acid (CellCept and Myofortic) induced injury of the upper GI tract.Am J Surg Pathol. 2009; 33: 1355-1363Crossref PubMed Scopus (59) Google Scholar A variety of mucosal changes can be seen in the lower GI tract, ranging from inflammatory bowel disease–like changes to features akin to graft-versus-host disease. Upper GI tract toxicities of MMF have included features ranging from those compatible with nonsteroidal anti-inflammatory drug use with topical irritation and damage to ulcerative esophagitis, reactive gastropathy, and duodenal ulceration.2Panarelli N.C. Drug-induced injury in the gastrointestinal tract.Semin Diagn Pathol. 2014; 31: 165-175Crossref PubMed Scopus (24) Google Scholar MMF-related esophageal strictures are rare.3Kim J.J. Mulki R.H. Sebastian K.M. Recalcitrant esophageal stricture secondary to mycophenolate mofetil.Case Rep Gastrointest Med. 2020; 2020: 8817801PubMed Google Scholar This case highlights an uncommon cause of a refractory esophageal stricture that should be considered as a potential etiology for dysphagia, especially in a transplant recipient, when more common etiologies have been excluded or when esophagitis is refractory to proton pump inhibitor therapy.