Esophageal abnormalities in chronic graft-versus-host disease in humans

Disabling esophageal symptoms ((dysphagia, painful swallowing, and severe restrosternal pain) developed in 8 of 63 patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation. At endoscopy 7 patients had characteristic desquamation of the upper esophagus; 2 of these also had distal esophagitis; and 3 had distinctive upper esophageal webs. No infectious pathogens were detected in esophageal biopsies or brushings. Abnormalities of esophageal motility were seen in 5 of 7 patients studied including 3 with aperistalsis. Retrosternal pain in 3 patients resulted from acid reflux. Esophageal histology from 5 autopsied patients showed no muscle or neuronal abnormalities by silver stain or conventional light microscopy. There was increased submucosal fibrosis associated with mucosal esophagitis and ulceration. Blind microscopic review of histology clearly distinguished the esophagus of chronic graft-versus-host disease from that of progressive systemic sclerosis. We conclude that esophageal epithelium, like skin and mucous membranes, is a target organ in chronic graft-versus-host disease. This immunologic disease results in desquamative esophagitis with web formation. Peptic esophagitis, a cause of severe pain and perhaps distal esophageal strictures in these patients, may be related to poor acid clearing from the esophagus. Diagnostic endoscopy and disruption of webs should be performed carefully to avoid perforation. Treatment should be directed toward suppressing the underlying immunologic disorder and at preventing acid-peptic reflux.