Acute Esophageal Necrosis Complicated by Severe Upper Gastroentestinal Bleeding in Association with Bosutinib Treatment for Chronic Myelogenous Leukemia

Abstract

Acute Esophageal Necrosis (AEN), also known as “Black Esophagus”, is a rare life threatening condition with unknown cause. We present a case of AEN in a patient on tyrosine kinase inhibitor (TKI) for Chronic Myelogenous Leukemia (CML). TKIs have various gastrointestinal adverse effects though this is the first known case of an association with AEN. An 82 year-old male with hypertension, gastroesophageal reflux disease and chronic phase CML presented with hematemesis and melena followed by a syncope episode. Two weeks prior to presentation, bosutinib was started to manage his CML. On presentation, he was hemodynamically unstable with a reduction in his hemoglobin by a 13 g/dL from a known baseline. Esophagogastroduodenoscopy revealed pan-esophageal necrosis characterized by confluent black mucosa with a distinct transition point to normal mucosa at the gastroesophageal junction. As is often the cease with this condition, the exact etiology of AEN is unknown in our patient. Hypotension was commonly found amongst those with AEN. It has been hypothesized that acute circulatory compromise may contribute to the esophageal ischemic necrosis. However, it is difficult differentiate whether it is the cause, or effect from the bleeding. We propose a two-hit hypothesis whereby bosutinib, the first “hit”, predisposes the esophageal mucosa to ischemic compromise via an unknown mechanism. Thereafter, the second “hit”, acute hypotension, precipitates the esophageal necrosis. Given the recent start of the TKI, bosutinib, and the absence of other significant potential causes, it seemed reasonable to implicate the drug in this case of AEN.Gastrointestinal adverse effects are known to be more common in bosutinib compared to other TKIs. EGFR tyrosine kinase, the targets of bosutinib are found in gastrointestinal stromal tumors (GIST), esophageal cancers, and normal esophageal mucosal cells. Interestingly, in a mouse model of Candida esophagitis, EGFR has been implicated in mucosal defense. Another TKI, Crizotinib has been well associated with esophagitis, although this drug acts on the ALK kinase, in contrast to bosutinib, which inhibits the EGFR tyrosine kinase.To the best of our knowledge, this is the first reported case of AEN attributable to a TKI, specifically bosutinib.Figure 1