Case Report of Pathognomonic Findings of Severe Colchicine Effect in the Esophagus, a Rarely Reported Site of Colchicine Effect

Abstract

Colchicine, a medication commonly used to treat gout, interferes with the cell cycle and can injure rapidly reproducing cells, including proliferative cells in gastrointestinal mucosa, primarily in the small bowl. Esophageal injury is rarely reported, and when reported is typically mild. A case is reported of severe injury to esophageal mucosa secondary to colchicine. A 47-year-old male with a medical history of systemic lupus erythematosus, intermittently treated with corticosteroids for 2 years, recently treated with azithromycin therapy for upper respiratory infection and hydroxychloroquine for polyarthritis, presented with dyspnea and severe substernal chest pain, exacerbated by deep inspiration, and ameliorated by leaning forward. Physical examination revealed an afebrile man with stable vital signs and no friction rub. Laboratory tests revealed Hb=12.6 g/dl, creatinine=1.33 mg/dl, CRP=3.4 mg/dl, ESR=51 mm/hr, D-Dimer=1140 ng/ml, and troponin level was within normal limits. EKG revealed PR segment depression and upwardly concave ST elevation, findings suggestive of pericarditis. Echocardiogram revealed no pericardial effusion. CT angiogram of chest was negative for pulmonary embolus, but showed prominent distal esophagus wall. Patient was admitted for acute pericarditis, likely viral versus lupus pericarditis. Patient treated with prednisone 50 mg/ day and colchicine 0.6 mg twice daily with significant symptomatic improvement. Esophagogastroduodenoscopy revealed LA grade C reflux esophagitis and nonbleeding small gastric ulcers. He was treated with an oral proton pump inhibitor and discharged home. Pathological examination of esophageal biopsies revealed mild chronic gastritis at the gastroesophageal junction, with cytotoxic colchicine effect, but no intestinal metaplasia, dysplasia, or H. pylori infection. Colchicine prevents tubulin protein polymerization, prevents mitotic spindle formation and causes mitotic arrest during metaphase. The pathognomonic histopathologic finding is ring mitoses accompanied by increased glandular cell apoptosis and epithelial pseudostratification. Small bowel is the most severely affected site in the GI tract by colchicine, but in the present case the esophagus was significantly affected, a highly uncommon finding. Colchicine toxicity typically manifests soon after therapy initiation; in the current case endoscopic biopsies were performed one day after receiving 3 doses of colchicine therapy. The irregular arrangement of nuclei, increase in mitotic figures, and hyperchromatism of nuclei are pathognomonic of colchicine, but this finding can occasionally mimic dysplasia. Nontoxic doses of colchicine do not cause mucosal changes, except in areas with increased cell proliferation, such as a hyperplastic polyp, where nontoxic levels of colchicine can cause mitotic arrest and ring figures, and mimic a sessile serrated adenoma. These pathologic findings should be assessed in conjunction with clinical presentation to avoid missing the diagnosis of colchicine toxicity.Figure: Esophagogastroduodenoscopy showing deep linear erosions in distal esophagus. The lesions are unlikely from Mallory-Wiess tear in the absence of antecedent vomiting.Figure: Medium power photomicrograph of esophageal squamous mucosa showing brisk mitotic activity involving almost the entire thickness of the epithelium. Right inset shows high power view of characteristic ring mitosis associated with colchicine effect.Figure: Medium power photomicrograph of gastric cardial epithelium at gastroesophageal junction showing brisk mitotic activity in columnar epithelial cells. Right inset shows a high power view of numerous mitotic figures.