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An unusual gastrointestinal manifestation of non‐steroidal anti‐inflammatory drugs

To the Editor, Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for decades to relieve pain, inflammation and fever. NSAIDs are associated with several side-effects. Hypersensitive reaction to NSAIDs is a well-known and frequent cause of skin reactions. NSAIDs have been found to cause damage to the mucosa of the digestive tract primarily in the stomach and upper intestine. This damage can result in an ulcer or intestinal bleeding. We report here a case of a hypersensitive skin reaction, similar to mucosal reaction, in the duodenum caused by NSAIDs. A 51-year-old man was admitted to hospital complaining of ache and swelling in his right knee after falling down. His medical history was unremarkable. He was treated by the physical treatment department and rehabilitation and resting were advised. An NSAID, naproxen, was prescribed. One week later the patient was readmitted to hospital with the same complaints. Laboratory findings including blood count, biochemical tests and rheumatological markers were unremarkable. Knee effusion was evacuated and a sample was analyzed showing pure polymorphonuclear cells without any microorganisms. Sample culture was also negative. He was advised to continue taking the NSAID and to rest.Three days later, skin eruptions appeared all over his body. He denied taking any medications or herbal medicine other than the NSAIDs (naproxen and indomethacin). He was diagnosed as having drug-related eruptions and he underwent upper gastrointestinal endoscopy because of the dyspeptic symptoms. Endoscopic examination of the esophagus, stomach and duodenal bulbus was normal other than antral erosions. Diffuse rashes in the duodenum are seen in Fig. 1. A proton pump inhibitor was prescribed and NSAIDs were stopped. One month later, control endoscopy was performed showing antral erosions and completely normal duodenum. Skin lesions waned and disappeared over the following 15 days. NSAIDs are the most widely used medications in the world. Although NSAIDs are clinically effective antipyretic, analgesic, and anti-inflammatory agents, they may be associated with several side-effects. The most common side-effects are nausea, vomiting, diarrhea, constipation, decreased appetite, rash, dizziness, headache, and drowsiness. Adverse effects of NSAIDs in the upper and lower gastrointestinal tract are well known. Serious complications of NSAID use that are less commonly recognized include pill esophagitis, small-bowel ulceration, small-bowel strictures, colonic strictures, diverticular disease, and exacerbations of inflammatory bowel disease. Clearly, the major effects of NSAIDs in the digestive tract are in the upper gastrointestinal tract. NSAID-induced gastroduodenal mucosal injury is superficial and self-limited in the majority of patients. However, peptic ulcers develop in some patients, and they may lead to gastroduodenal hemorrhage, perforation, and death. Because of the broad and non-specific definitions of gastrointestinal disorders caused by the use of NSAIDs, as well as differences in patient populations, drugs, dosages, and periods of use, estimates of the prevalence of adverse effects vary greatly. In the present case, gastric erosions secondary to NSAIDs were evident. Interestingly esophagus, stomach and the first part of the duodenum were free of rashes and the remaining duodenum was involved separately. NSAIDs sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. The hypersensitivity reactions that are induced by NSAIDs are introduced frequently in medical practise. Hypersensitivity to NSAIDs manifesting in the airways or in the skin is the second most frequent untoward allergic reaction to drugs. The skin eruption in our patient was very similar to the skin rash occasionally observed in patients treated with NSAIDs. NSAIDs were stopped and duodenum and skin lesions waned and disappeared after a while. Skin rashes improved later than the gastrointestinal tract lesions. In conclusion, NSAIDs-induced allergic lesions may occur simultaneously on both skin and in the gastrointestinal tract. Allergic rashes may appear in any part of the tract and can be present solely in the duodenum. Gastrointestinal rashes disappear earlier than skin lesions following discontinuation of the NSAIDs. Conflict of interest: There are no conflicts of interest to disclose for any of the authors.