Proton Pump Inhibitors and Lymphocytic Esophagitis: A Novel Association?

Abstract

Purpose: Lymphocytic esophagitis was first described by Rubio et al. as an entity in 2006; however, in 2008 Purdy et al. reviewed 42 cases of lymphocytic esophagitis and dismissed it as a non-specific response of uncertain relevance. We recently reviewed the histopathology and clinical correlations of 42 patients with dense lymphocytic infiltrates in the esophageal mucosa and concluded that lymphocytic esophagitis is a specific type of inflammatory disorder of the esophagus. Methods: Using a nationwide database of gastrointestinal biopsy specimens from community-based endoscopy centers, we extracted all cases diagnosed with increased esophageal intraepithelial lymphocytes from Jan 2007 to march 2010. Pertinent demographic, clinical and laboratory data may be extracted from the database. In addition, gastroenterologists who performed the EGD were contacted by telephone and clinical, therapeutic, and endoscopic information was obtained. Histopathologic slides from all cases were reviewed blindly by the authors. Results: A total of 42 patients (median age 52 years, range 20-84; 26 women and 16 men) were included. Histologically, the lymphocyte count in all cases was higher than 30 lymphocytes per high-power field in the squamous mucosa, with a great prevalence of CD3-positive T lymphocytes. Lymphocytes were mostly concentrated within and around the papillae, where there was consistently severe spongiosis. Reasons for undergoing an EGD included: dysphagia (30 patients, 71.42 %); GERD (11 patients, 26.1%); and non-cardiac chest pain (1 patient, 2.3%). Interestingly 41 patients were on proton-pump inhibitor (PPI) therapy at the time of EGD; the remaining patient was on H2 receptor blocker therapy. Conclusion: Lymphocytic esophagitis (defined as dense lymphocytic infiltrates in the squamous epithelium of the esophagus accompanied by severe spongiosis, particularly in the peripapillary areas) is a rare condition. Dysphagia seems to be the most common presenting symptom, and nearly all patients in our series were on PPI therapy prior to onset of dysphagia. This class of drugs has been associated with intraepithelial lymphocytes in other regions of the gastrointestinal tract, particularly with lymphocytic and collagenous colitis. It is tempting to speculate that this rare condition may be the result of an unusual immune response to these drugs. The widespread use of PPIs make the investigation of their causal relationship particularly arduous. However, assessment of the symptoms and the evaluation of esophageal biopsies after discontinuation of PPIs in patients with lymphocytic esophagitis might provide useful clues as to the etiologic role of these medications.