Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis but also various other disorders. The use of methotrexate has been somewhat limited by concerns regarding its adverse effects, including its potential for hepatotoxicity. The purpose of this article is to provide an overview of methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and recommendations for monitoring it by US, UK and European guidelines, as well as providing a brief overview of its mechanism of action and of high-dose methotrexate.

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INTRODUCTION: Acute esophageal necrosis (AEN) is a rare clinical entity characterized by diffuse, circumferential, black-appearing distal esophageal mucosa on EGD typically limited to the gastroesophageal junction. In this case, we discuss AEN in a chronically ill female precipitated by an acute low perfusion state in the setting of her preexisting vasculopathy. CASE DESCRIPTION/METHODS: A 76-year-old female with past medical history of severe coronary artery disease, high-grade distal aortic stenosis, gastroesophageal reflux disease, history of ischemic colitis presents with two-day history of melena. Patient initially presented at an outside hospital for symptomatic anemia and was transfused packed red blood cells. She was transferred to our institution and was found to have a systolic blood pressure in the 80s. Physical exam was notable for pallor and a delayed capillary refill time. Labs revealed a hemoglobin of 10.8 g/dL, white blood count of 17 uL, procalcitonin of 1.8 ng/mL, creatinine of 1.2 mg/dL, INR of 2.7, and albumin of 2.5 g/dL. CT of the chest and abdomen revealed a right lower lobe lung consolidation and a very decompressed IVC concerning for a low volume state. Patient was adequately fluid resuscitated, kept NPO and was placed on a pantoprazole (PPI) infusion. An EGD was performed which revealed diffuse severe mucosal changes characterized by ulceration with necrotizing black mucosa in the lower third of the esophagus, and non-bleeding cratered and superficial duodenal ulcers. One week later, a repeat EGD demonstrated significant esophageal mucosal healing with esophagitis and distal esophageal ulcerations. Esophageal biopsies revealed denuded submucosa, marked acute inflammation with negative HSV, CMV and fungal cultures. Given the significant improvement in symptoms and findings, her diet was advanced. She was discharged on oral PPI and sucralfate with a plan for repeat EGD in three months. DISCUSSION: The incidence of AEN ranges from 0.2% to 0.28%, however, true prevalence is underestimated given the transient nature of the insult and early tissue healing. Distal esophagus and duodenal injury are common given their similar supply from the celiac artery. This case highlights a rare disease entity with increasing prevalence owing to the increased number of comorbid conditions attributed to the disease process. It emphasizes the potential causes of the disease and timely diagnosis warranting physicians to have an understanding and awareness on potentially fatal but reversible clinical syndrome.