Doxycycline-Induced Gastrointestinal Injury for Potential Lyme Disease Exposure

Authors: Sapana R. Gupta, Ryan Liu, Lindsey Channen, Syed Quadri, Amanda Pressman

Abstract

Doxycycline is an antibiotic frequently used to treat tick-borne diseases. It is known to cause esophageal injury, although gastric injury is less often described. Few cases have been reported of gastrointestinal bleeding secondary to biopsy-proven doxycycline use. In the setting of widespread doxycycline use, it is important to recognize this drug-specific pattern of injury to guide appropriate patient management. This case demonstrates doxycycline-induced gastrointestinal injury and highlights characteristic histological findings.

INTRODUCTION

Several medications, such as nonsteroidal anti-inflammatory drugs, bisphosphonates, and antibiotics (including tetracyclines), are known to induce gastrointestinal injury. Esophagitis is commonly seen, although pill-induced gastric injury is less well characterized. On endoscopy, these medications present with mild inflammatory changes to ulcerations or perforations.^1^ In this report, we describe a case of gastrointestinal bleeding from biopsy-proven doxycycline-induced gastric injury.

CASE REPORT

The patient was a 69-year-old man from India with no medical history who presented to the emergency department (ED) with 1 week of fever. He had traveled to Greece, Egypt, and Israel 4 months prior but had been at his baseline health status since then. He cut tall grass around his property 3 weeks earlier but checked for ticks afterward. He complained of headaches, body aches, skin hyperpigmentation, and lightheadedness, although he denied shortness of breath, cough, nausea, or diarrhea. Upon outpatient evaluation, he was started on levofloxacin and chloroquine for concern of malaria.

In the ED, the patient had a fever of 39.8°C, heart rate of 82, blood pressure of 108/61, and oxygen saturation of 97% on room air. He denied alcohol, tobacco, or illicit drug use. A physical examination revealed scleral icterus. The abdomen was soft, nontender, and without palpable organomegaly. The skin was free of rash. Laboratory data were significant for creatinine 1.78 mg/dL (unknown baseline), aspartate aminotransferase 186 IU/L, alanine aminotransferase (ALT) 130 IU/L, total bilirubin 7.7 mg/dL, direct bilirubin 4.6 mg/dL, lactic acid 2.9 mEq/L, white blood cell count 7.9 ×10^9^/L, hemoglobin 10.9 g/dL, hematocrit 31.6%, and platelet of 76 ×10^9^/L. A blood smear showed intraerythrocytic parasitic ring forms and a tetrad, favoring the diagnosis of Babesiosis without excluding Plasmodium falciparum due to recent travel history. The patient was started on atovaquone and azithromycin, with the addition of doxycycline for potential Lyme exposure. Although serological testing for Lyme disease was performed upon ED presentation and returned negative, the infectious disease consult advised continuing doxycycline for the full treatment course due to the patient's high risk of exposure.

Daily blood counts demonstrated down-trending hemoglobin, which was thought to be due to parasitic hemolysis. Otherwise, the patient's symptoms and lab values were improving. However, 4 days after initiation of doxycycline treatment, hemoglobin decreased to 6.7 g/dL in the setting of a melenic stool. One unit of packed red blood cells was administered, and gastroenterology was consulted. Upper endoscopy revealed Grade A esophagitis without bleeding, gastritis with linear erosions and friability, and multiple, nonbleeding, clean-based duodenal ulcers, as shown in Figure 1. Histology of random gastric biopsies revealed antral mucosa with erosive gastropathology and fibrinoid deposits within lamina propria capillary walls, consistent with doxycycline-induced gastric injury, as shown in Figure 2. Figure 2 also highlights microthrombi using a black arrow, a feature associated with doxycycline toxicity. Differential diagnoses of pathology results included but were not limited to ischemic gastropathy, small-vessel vasculitis, and infectious gastritis. Staining for Helicobacter pylori (H. pylori) was negative. Repeat hemoglobin improved to 7.7 g/dL with a hematocrit of 22.0% at discharge. The patient remained hemodynamically stable and was discharged on a proton pump inhibitor 40 mg twice daily for at least 30 days pending outpatient evaluation of clinical symptoms. In addition, he completed a 10-day course of antibiotics including atovaquone, azithromycin, and doxycycline. The pathology report resulted 3 days after biopsy collection, by which time the patient had completed the antibiotic course of doxycycline. Follow-up endoscopy was not performed after discharge, as the patient's symptoms resolved after the initiation of proton pump inhibitor therapy.

DISCUSSION

Doxycycline is a tetracycline antibiotic that is used to treat tick-borne and other infections. Doxycycline-induced esophageal injury is well studied, but gastric mucosal injury is not. This case report demonstrates a pattern of doxycycline-induced gastric injury supported by clinical, endoscopic, and histological features in the literature.

Several case reports have documented doxycycline-associated gastric injury. Endoscopy in these case reports often revealed superficial erosions, ulcerations, or white and yellow adherent plaques on the gastric mucosa.^2–6^ In addition, they reported a recurring histological pattern of lamina propria fibrosis, capillary degeneration, and fibrinoid deposits within superficial vessels. These features were also seen in our patient's gastric biopsies.^4–6^ Some cases reported microthrombi and reactive epithelial changes, which are consistent with the microvascular damage in our case.^6^ These repeated findings across different case reports support our association. In addition, many cases reported resolving symptoms after discontinuing doxycycline, either confirmed on follow-up endoscopy or assessed based on clinical improvement.^4,5,7^

Some proposed mechanisms for injury are doxycycline's caustic effect on mucosal surfaces because of its acidity, as well as impaired clearance or prolonged mucosal contact time, especially in patients with delayed gastric emptying or inadequate fluid intake.^3,8^ Also, doxycycline has been shown to inhibit matrix metalloproteinase-9, which may impair angiogenesis and contribute to the vascular injury and fibrinoid necrosis seen in histological samples.^9,10^

In our patient, the association between starting doxycycline and the onset of gastrointestinal bleeding, along with the endoscopic and histologic findings consistent with previously reported cases, provides evidence that doxycycline was likely the cause. Even after completing the doxycycline course, the patient's bleeding did not worsen, likely due to the superficial nature of the doxycycline-induced injury and the early initiation of proton pump inhibitor therapy promoting mucosal healing.^4–6^ Recognizing this pattern is important, especially in patients with new-onset gastrointestinal symptoms or bleeding soon after starting doxycycline. Discontinuing the drug and supportive therapy may prevent further mucosal damage in these cases.^4–6^

In summary, recognition of doxycycline as a causative agent for gastric injury can guide patient management to minimize further injury. Alternative antibiotics may be considered in patients at high risk for gastrointestinal bleeding. For those unable to select another antibiotic, there may be a role for protein pump inhibitor use as a protective mechanism.

DISCLOSURES

Author S. Gupta wrote the article and reviewed the present literature. R. Liu also contributed to article writing. L. Channen and A. Pressman revised the article for intellectual content and formatting. S. Quadri provided histologic images. S. Gupta is the article guarantor.

Previous This case has been presented as a poster at the American College of Gastroenterology's 2024 Annual Scientific Meeting & Postgraduate Course held from October 25-30, 2024, in Philadelphia, PA.

Financial None to report.

Informed consent was obtained for this case report.