Be aware that ACEIs can occasionally cause small-bowel angioedema

Angiotensin-converting enzyme inhibitors (ACEIs) are used as antihypertensive medications by millions of people globally. Dry cough, dizziness and hypotension are some of the most common side effects of ACEIs. Angioedema, specifically visceral angioedema, is a lesser known side effect occurring in 0.1% to 0.7% of patients. This rare, often overlooked clinical condition, maybe challenging to diagnose. Gastrointestinal symptoms associated with ACEI-induced mesenteric angioedema are nonspecific and can resemble other abdominal disorders. It is crucial to identify the signs of ACEI-induced mesenteric angioedema through appropriate clinical, laboratory and imaging evaluations.Three recently reported cases are summarized below:A 43-year-old woman presented with watery diarrhea for the past month. She had two or three episodes of watery diarrhea daily beginning a few days after starting ramipril for newly diagnosed hypertension. She had no history of recent travel, dietary changes, sick contacts or other medication changes. Ramipril was stopped and the patient was prescribed losartan for hypertension. Diarrhea ceased four to five days after stopping ramipril.A 76-year-old woman with a history of hypertension and ischemic heart disease presented with diarrhea symptoms for the past year. Since starting ramipril one year ago, she experienced two loose watery stools daily and lost 13.6 kg in body weight. She had not started any new medications, changed medication doses or had any dietary changes. After extensive investigations, ramipril was stopped and she was prescribed candesartan. Diarrhea improved a few days after stopping ramipril and at a one-month follow-up she had regained 0.9 kg in weight.A 73-year-woman with hypertension and ischemic heart disease presented with watery diarrhea and chronic cough for the past seven to eight months. Her symptoms began a few days after starting ramipril. She experienced three to six episodes of watery stool over a one-hour period every morning, with no other bowel movements throughout the day. Ramipril was changed to candesartan to alleviate her chronic cough. The patient reported improvement in cough and diarrhea a few days after stopping ramipril.ACEIs block the activity of angiotensin-converting enzymes (ACEs), preventing the conversion of angiotensin I to angiotensin II, which leads to a reduction in systemic blood pressure. ACE, also known as kininase II, is responsible for breaking down bradykinin. Bradykinin influences vascular permeability and promotes the release of substance P, a peptide that induces vasodilation and fluid leakage into tissues. Inhibition of bradykinin degradation is thought to be a key factor in the development of ACEI-induced angioedema.ACEI-induced angioedema typically presents as swelling of the face, tongue and lips. In rare cases, isolated gastrointestinal (visceral) angioedema can occur. This situation is often missed and leads patients to undergo unnecessary tests, procedures and surgeries.ACEI-induced visceral angioedema usually presents as an insidious episode lasting two to five days and generally resolves on its own. The time between starting ACEI therapy and the onset of symptoms can range from weeks to years. Abdominal pain is one of the initial complaints in nearly all cases. Patients with small-bowel angioedema typically present with nausea and vomiting. Less frequent symptoms include diarrhea or ascites. The condition is most common in women (particularly Black women) between 40–70 years of age. Diagnosis is usually made through imaging (computed tomography scan). Findings may include segmental thickening of the small bowel, straightening or elongation of bowel loops, prominent mesenteric vessels, mesenteric edema with or without ascites, thickened omentum, normal appearance of pericolic fat, and the absence of vascular compromise or lymphadenopathy. These findings can help exclude other diagnoses such as inflammatory bowel disease, vasculitis, small bowel lymphoma, obstruction and mesenteric ischemia.Management of ACEI-induced visceral angioedema involves stopping the medication and providing supportive care, including hydration and bowel rest. Symptoms typically improve within 24–48 hours after the ACEI is discontinued.A thorough drug history should be taken in patients on ACEIs who develop nonspecific abdominal pain and loose bowel movements. Early consideration of ACEI-induced mesenteric angioedema in the differential diagnosis can lead to appropriate testing and prompt diagnosis. In two of the three cases summarized above, diarrhea had been present for longer than six months. A higher index of suspicion for ACEI-induced mesenteric angioedema in these patients, with discontinuation of the ACEI, could have led to avoidance of unnecessary testing, quicker resolution of symptoms and reduced psychological burden for the patients.ReferenceEkram R, Pereira M, Saif M, et al. Diarrhea induced by angiotensin-converting enzyme inhibitors. Can Fam Physician 2026;72:104-5. (accessed February 17, 2025)

Be aware that ACEIs can occasionally cause small-bowel angioedema

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