Pill-Induced Gastric Injury

Alex Sherman, M.D., and Edmund J. Bini, M.D.Division of Gastroenterology, New York University Medical Center and Department of Veterans Affairs Medical Center, New York,

New York

Pill-induced esophageal injury is a well described clin-ical entity. In contrast, pill-induced gastric injury hasnot been well characterized. In this report, we describetwo patients with acute gastric ulcers due to pill inges-tion and review the available literature on pill-inducedgastric injury. The first patient presented with uppergastrointestinal hemorrhage and was found to have alarge gastric ulcer with multiple potassium chloride pillsin the ulcer crater. The second patient presented withodynophagia and endoscopy revealed doxycycline-in-duced esophageal and gastric injury. To our knowledge,this is the first case report of doxycycline-induced gastriculcer. (Am J Gastroenterol 1999;94:511–513. © 1999 byAm. Coll. of Gastroenterology)

INTRODUCTION

Pill-induced esophageal injury is a well described clinicalentity (1–9). In contrast, pill-induced gastric injury has notbeen well characterized. In this report, we describe twopatients with acute gastric injury due to pill ingestion andreview the available literature. We believe that pill-inducedgastric injury is a distinct clinical entity that can be distin-guished from the more commonly encountered antral le-sions due to aspirin and nonsteroidal anti-inflammatorydrugs (NSAIDs).

CASE REPORTS

Patient 1

An 88-yr-old woman presented to the emergency roomwith 1 day of melena and nausea. Examination revealed athin, pale woman with a blood pressure of 90/50 mm Hg anda pulse of 110 beats/min. Orthostatic changes were present.On abdominal examination, mild epigastric tenderness todeep palpation was noted. Rectal examination revealed me-lena.

Her past medical history was remarkable for hyperten-sion, coronary artery disease, congestive heart failure, hy-pothyroidism, and left hemiparesis secondary to a stroke.The patient had chronic dementia and was bed-bound. Shedid not have a prior history of gastrointestinal disease.

Medications included levothyroxine, furosemide, potassiumchloride, digoxin, and transdermal nitroglycerin. She did nottake aspirin or NSAIDs.

Initial laboratory results revealed a hematocrit of 26%.She was given 2 L of normal saline intravenously andtransfused with 2 U of packed red blood cells. Upper gas-trointestinal endoscopy showed a 3-cm-deep ulcer crater inthe fundus of the stomach without active bleeding. Withinthe ulcer, several large, white pills were noted (Fig. 1). Abiopsy forceps was used to extract multiple intact pills fromthe ulcer crater. Other than mild gastritis and duodenitis, noother endoscopic abnormalities were observed. Biopsiesobtained from the gastric ulcer were negative for malig-nancy andHelicobacter pylori. The pills were subsequentlyidentified as potassium chloride (K-Dur). Potassium supple-mentation was discontinued, and she was treated with ome-prazole. No further bleeding was noted, and the patient wasdischarged on the third hospital day.

During follow-up, the patient had no recurrent melenaand her hematocrit remained stable. Repeat upper gastroin-testinal endoscopy 6 wk later demonstrated that consider-able ulcer healing had taken place. Repeat biopsies werenegative for malignancy. No further evidence of gastroin-testinal bleeding was noted on follow-up. A third endoscopy10 wk later showed complete healing of the gastric ulcer.

Patient 2

A 25-yr-old woman was referred for gastroenterologyconsultation to evaluate a 10-day history of odynophagiaand epigastric pain. Previously, she was well with no sig-nificant past medical history. Three weeks before consulta-tion, she had a tick bite and developed a rash suspicious forearly Lyme disease. A 3-wk course of doxycycline 100 mgb.i.d. was prescribed. Approximately 10 days after begin-ning doxycycline, the patient experienced odynophagia andepigastric pain. The pain became progressively more severeover the next several days. She was prescribed omeprazole40 mg/day and referred for endoscopic evaluation.

Closer questioning revealed that she took her second doseof doxycycline at bedtime with a small sip of water, justbefore lying down. She was a nonsmoker and used alcoholrarely. She denied aspirin or NSAID use. There was noprevious gastrointestinal history.

An upper gastrointestinal endoscopy was performed. InReceived Apr. 3, 1998; accepted July 28, 1998.

THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 2, 1999Copyright © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00Published by Elsevier Science Inc. PII S0002-9270(98)00767-9

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the mid-esophagus, a focal area of denuded mucosa wasencountered. The proximal and distal esophagus was nor-mal. In the gastric cardia, multiple linear ulcerations, withabundant overlying adherent exudate, were seen. The ulcerswere oriented longitudinally, extending approximately twocentimeters distally from the gastroesophageal junction.Pathologic examination of the esophageal biopsies revealedacute erosive esophagitis with granulation tissue. Specimensfrom the ulcers in the gastric cardia showed acute erosivegastritis with ulcerations. There was no evidence ofHeli-cobacter pylori, fungi, or tumor in any of the pathologicspecimens.

A presumptive diagnosis of pill esophagitis and pill-induced gastric injury was made. Doxycycline was discon-tinued. Sucralfate slurry 1 g four times/day was added to herregimen. Her symptoms of odynophagia and epigastric paindiminished rapidly, and within several days she was asymp-tomatic. Endoscopic follow-up 1 month after the initialexamination showed complete resolution of the patient’sesophageal and gastric lesions.

DISCUSSION

In contrast to the abundant literature on pill-inducedesophageal injury, gastric damage due to pills other thanaspirin and NSAIDs has received only scant attention. In aseries of reports in the 1970s and 1980s, potassium chloridepreparations have been documented to cause gastric lesionsranging from minor inflammation to gastric ulcerations(10–19). Although several reports (11, 13, 16) document theincreased potential of slow-release wax matrix potassiumchloride (Slow-K), as opposed to micro-encapsulated prep-arations (Micro-K), to cause gastric injury, another studydisputes this (14). One report describes the ability of adispersal agent to prevent gastric injury (17). The majorityof the studies used glycopyrrolate, an anticholinergic drug,to decrease gastric motility, perhaps enhancing the potentialof potassium chloride preparations to induce mucosal injury.Interestingly, one report implicated glycopyrrolate itself asthe cause of gastric injury (15). Corrosive damage to thestomach was reviewed in 1979 by Loweet al. (20). Theauthors presented five cases of corrosive gastric injury that

primarily involved the gastric antrum; three of these weredue to sulfuric acid, and one each to Clinitest (copper sulfatereagent) and potassium hydroxide.

Our two cases demonstrate a potentially wide range ofclinical presentation in pill-induced gastric injury. In patient1, a deep gastric ulcer producing upper gastrointestinalhemorrhage was encountered in the fundus. The etiology ofthe ulceration was made self-evident by the fact that mul-tiple intact pills were extracted from the deep ulcer crater.This elderly patient was taking several medications and mayhave been unable to complain of gastrointestinal symptomsbecause of chronic dementia, accounting for the severity ofher gastric lesion. In contrast, patient 2 was a healthy youngwoman with odynophagia, epigastric pain, and uncompli-cated doxycycline-induced esophageal and gastric injury.To our knowledge, this report describes the first case ofdoxycycline-induced gastric injury in the medical literature.

The severity of the gastric lesions in the two cases variedsignificantly. In patient 1, the gastric ulceration was largeand deep and led to the complication of gastrointestinalbleeding. In contrast, the gastric injury in patient 2 wassuperficial and was unlikely to have resulted in complica-tions. Similar to reported cases of medication-inducedesophageal injury (9), our patients ingested their pills atbedtime with little or no water.

We propose that pill-induced gastric injury is a distinctclinical entity, to be distinguished from the more commonlyencountered gastric antral lesions of aspirin and NSAIDs.Damage is proximal, perhaps occurring in the location towhich the pill gravitates in a dependent manner after tra-versing the lower esophageal sphincter. Gastric damage mayoccur in association with, or independent of, esophagealinjury. The pathophysiology of gastric injury is likely mul-tifactorial. In the case of potassium chloride, a high localconcentration of this salt is thought to produce mucosalulcerations (18). Doxycycline, which is acidic in solution,causes mucosal injury by its caustic nature (8). In both ofour cases, discontinuation of the implicated medication ledto the rapid disappearance of the gastric lesion. The use ofadjunctive therapy, such as H2 receptor antagonists, protonpump inhibitors, or the mucosal coating agent sucralfate,may result in more rapid healing. Recommendations toavoid taking pills at bedtime before lying down and to ingestpills with sufficient water may prevent pill-induced gastricand esophageal injury. These considerations are especiallyimportant in elderly, debilitated, bed-bound, or dementedpatients and in those taking multiple medications. Patientswith gastric motility disturbances, such as diabetic gastro-paresis, may also be at risk.

In conclusion, pill-induced gastric injury is a distinctclinical entity that may be more common than currentlyappreciated. As a result of the popularity of doxycycline forthe treatment of Lyme disease, along with the continuednecessity for potassium supplementation in patients takingdiuretics, clinicians should be aware of the potential of thesemedications to cause both gastric and esophageal injury.

FIG. 1. Upper endoscopy showing a large, deep ulcer in the fundus of thestomach. Potassium chloride (K-Dur) pills are seen within the ulcer crater.

512 SHERMAN AND BINI AJG – Vol. 94, No. 2, 1999

Reprint requests and correspondence: Edmund J. Bini, M.D., Divisionof Gastroenterology (111D), Department of Veterans Affairs Medical Cen-ter, 423 East 23rd Street, New York, NY 10010.

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