Doxycycline-induced espohageal ulceration in the U.S. military service

Military Medicine, Apr 2000 by Morris, Todd J

U.S. military forces are frequently deployed with little warning to regions of the world where chloroquine-resistant malaria is endemic. Doxycycline is often used for malaria chemoprophylaxis in these environments. The use of doxycycline can be complicated by esophageal injury. Two cases of esophageal ulceration will be discussed, followed by a review of the literature. Doxycycline causes esophageal injury through a combination of drug-specific factors, the circumstances of drug administration, and individual patient conditions. Patients with dysphagia attributable to esophageal ulceration are managed by intravenous fluid support and control of gastric acid reflux until their symptoms resolve over 5 to 7 days. The risk of esophageal injury can be minimized by use of fresh capsules, drug administration in the upright position well before lying down to sleep, and drinking at least 100 ml of water after swallowing the medication.

Introduction

The changing role of U.S. military forces in recent years has led to the deployment of personnel to smaller regional conflicts around the world, including those in central Africa and southwest Asia. Many of these areas have provided significant preventive medicine challenges. The nature of these modern deployments often calls for rapid insertion of personnel with little warning. Consequently, prophylactic medicines that require longer-term pretreatment have lost some of their utility. As a result of deployments into areas of endemic malaria and the increasing prevalence of chloroquine-resistant malaria, doxycycline has been used as a prophylactic agent for deploying U.S. military members. Recently, two patients with doxycycline-induced esophageal ulceration presented to the General Surgery Department at the U.S. Naval Hospital (USNH) in Naples, Italy. This article will describe these cases and review the literature to bring further awareness of this condition to medical personnel involved with deploying units.

Case Reports

Case 1

A 20-year-old female who had recently returned from a deployment in Africa presented complaining of sharp substernal chest pain and dysphagia. She was taking doxycycline as malaria prophylaxis. Six days before presentation, she reported taking her evening doxycycline capsule just before going to bed. She awoke hours later and had the sensation of the capsule being lodged in her lower esophagus. She swallowed several times, and the sensation eventually passed. During the ensuing 4 days, she noted progressively worsening pain with wet or dry swallowing. On presentation, she was unable to swallow solids, liquids, or even her own saliva. She reported no previous medical problems and was taking no other medications. Physical examination was unremarkable. She required 4 L of fluid resuscitation to correct her volume deficit. Esophagogastroduodenoscopy identified a small esophageal ulceration at 27 cm and a large ulceration at 30 cm that encompassed approximately 20% of the esophageal lumen. She was given nothing by mouth and treated with ranitidine and sucralfate slurry for the next 48 hours until her pain improved. She then resumed eating a regular diet without difficulty. A barium swallow 6 weeks later showed no evidence of persistent ulceration or esophageal stricture.

Case 2

A 27-year-old male presented with an 8-day history of dysphagia and sharp substernal chest pain. His pain had increased in intensity during the first 5 days, and he was evacuated to USNH Naples. He was initially unable to swallow any solid food, but during the 24 hours before arrival at USNH Naples he was able to tolerate liquids and soft food. He reported no previous medical problems. He was taking doxycycline as malaria prophylaxis after a deployment to northern Africa, and occasionally he used terfenadine for seasonal allergic rhinitis. He did not specifically recall having trouble swallowing his doxycycline capsule. Physical examination was unremarkable. During esophagogastroduodenoscopy, he was found to have a 1-cm esophageal ulcer covered with a yellow film at 35 cm. He was treated with parenteral ranitidine, and during the next 2 days his symptoms improved. He was advanced to a regular diet, which he tolerated well.

Discussion

Malaria remains endemic in most of Central and South America, sub-Saharan Africa, southern Asia, and the Middle East. Resistance of Plasmodium falciparum to chloroquine is widespread except in Central America and the Middle East, making alternative drug therapy necessary for effective prophylaxis.' At present, mefloquine, primaquine, hydrochloroquine sulfate, proguanil, and doxycycline are in common use. Mefloquine 250 mg once a day is currently the drug of choice for malaria prophylaxis, with fairly good (70%-80%) long-term compliance and efficacy.1,2 However, emerging resistance, especially in southeast Asia and Africa, and neuropsychiatric side effects may limit its use.1,3 Malaria prophylaxis begins 1 to 2 weeks before exposure with the exception of doxycycline, which can begin on the day before exposure.1