Visceral angioedema due to angiotensin-converting enzyme inhibitor therapy
ABSTRACTVisceral angioedema is an uncommon but serious complication of therapy with angiotensin-converting enzyme (ACE) inhibitors. We report a case, review the literature, and discuss the incidence, features, and clinical recognition of this condition.
KEY POINTS
- Visceral angioedema due to ACE-inhibitor therapy can easily be diagnosed by clinical suspicion and abdominal computed tomography (CT).
- Many physicians are not aware of this condition and so may subject patients to unnecessary invasive procedures, including surgery and endoscopy.
- If a middle-aged woman taking an ACE inhibitor presents with abdominal pain and emesis, the differential diagnosis should include visceral angioedema, and CT should be strongly considered.
ON IMAGING, A THICKENED BOWEL WALL
Computed tomography can reveal bowel edema and ascites more reliably than plain radiography or barium studies. Edema thickens the bowel wall, with increased contrast enhancement that makes mesenteric vessels show up on the study. In some instances edema is so significant that edematous submucosa can be differentiated from the serosa due to impressive thickening of the mucosal wall.15,16 Oral contrast can be seen in the middle of the lumen, giving it a target-sign appearance. Edema of the small bowel and ascites can lead to fluid sequestration in the abdomen, resulting in a presentation with shock.67
Magnetic resonance imaging can be even more useful in identifying gastrointestinal angioedema, but it would not be cost-effective, and based on our study, CT and ultrasonography of the abdomen were diagnostic in most cases.
AVOIDING UNNECESSARY TESTING
Hemodynamic instability and abdominal pain usually trigger a surgical consult and a more extensive workup, but with a good clinical approach, unnecessary testing and invasive diagnostic procedures can be avoided under the right circumstances.
Numerous surgical procedures have been reported in patients presenting with visceral angioedema secondary to ACE inhibitors.67 Although a thorough history and physical examination can give us a clue in the diagnosis of drug-induced gastrointestinal angioedema, CT is extremely helpful, as it shows dilated loops, thickened mucosal folds, perihepatic fluid, ascites, mesenteric edema, and a “doughnut” or “stacked coin” appearance.17,68
So far, there have been only two reports of angioedema of the stomach (the case reported by Shahzad et al10 and the current report). Angioedema can affect any visceral organ, but we usually see involvement of the jejunum followed by the ileum and duodenum.40
FINDINGS ON ENDOSCOPY
Usually, endoscopic examination of the upper and lower gastrointestinal tract does not reveal any specific pathology, but endoscopy and biopsy can rule out other causes of abdominal pain, such as Crohn disease, ulcerative colitis, infection, malignancy, granuloma, and vasculitis. Also, hereditary or acquired C1-esterase deficiency and other autoimmune disorders should be considered in the workup.18,69 In the reported cases, endoscopy revealed petechial bleeding with generalized edema.19
Biopsy often demonstrates an expanded edematous submucosal layer with inflammatory cell infiltration and protrusion of the proper muscular layer into the submucosal layer.15 A proper muscular layer and an edematous submucosal layer can produce edema so severe as to obstruct the intestine.15
Ultrasonography or CT provides essential information as to location, structure, and size, and it rules out other diagnoses. Therefore, consideration should be given to noninvasive imaging studies and laboratory testing (C1-esterase inhibitor, complement, antinuclear antibody, complete metabolic panel, complete blood cell count) before resorting to endoscopy or exploratory laparotomy.20,70 In three case reports,29,30,32 abdominal ultrasonography did not show any thickening of the small-bowel wall. Several cases have been diagnosed with the help of endoscopy.
Symptoms usually resolve when the ACE inhibitor is stopped
There is no standard treatment for ACE-inhibitor-induced visceral angioedema. In most patients, stopping the drug, giving nothing by mouth, and giving intravenous fluids to prevent dehydration are sufficient. Symptoms usually resolve within 48 hours.
In several case reports, fresh-frozen plasma was used to increase the levels of kininase II, which can degrade high levels of bradykinin.51,71,72 However, no randomized controlled trial of fresh-frozen plasma for ACE-inhibitor-induced angioedema has been published.
Drugs for hereditary angioedema—eg, recombinant C1-INH, the kallikrein inhibitor ecallantide (Kalbitor), and the BKR-2-antagonist icatibant (Firazyr)73—have not been prospectively studied in gastrointestinal angioedema associated with ACE inhibitors. Icatibant has been shown to be effective in the treatment of hereditary angioedema and could be promising in treating angioedema secondary to ACE inhibitors.8 Rosenberg et al21 described a patient who was on prednisone when she developed intestinal angioedema, thus calling into question the efficacy of steroids in the treatment of visceral angioedema.
RAISING AWARENESS
More than 40 million patients are currently taking ACE inhibitors or ARBs.9 Therefore, we suggest that patients with a known history of angioedema in response to these drugs should wear an identification bracelet to increase awareness and to prevent recurrence of angioedema.
