Gastrointestinal Imaging Pictorial Essay Vallurupalli and Coakley MDCT of Visceral ngioedema Gastrointestinal Imaging Pictorial Essay Kalyani Vallurupalli 1 Kevin J. Coakley 2 Vallurupalli K, Coakley KJ Keywords: abdominal CT, abdominal pain, CE inhibitor, angiotensin-converting enzyme inhibitor, CT, visceral angioedema DOI:10.2214/JR.10.4856 Received pril 22, 2010; accepted after revision September 20, 2010. 1 oth authors: Department of Radiology, Southern Illinois University, 701 N First St, Springfield, IL 62781. ddress correspondence to K. Vallurupalli (kalyaniv2003@yahoo.com). CME This article is available for CME credit. See www.arrs.org for more information. WE This is a Web exclusive article. JR 2011; 196:W405 W411 0361 803X/11/1964 W405 merican Roentgen Ray Society MDCT Features of ngiotensin- Converting Enzyme Inhibitor Induced Visceral ngioedema OJECTIVE. Our objectives are to describe the CT features of angiotensin-converting enzyme (CE) inhibitor induced visceral angioedema and to review other conditions that may have similar findings. CONCLUSION. CT findings in a patient taking an angiotensin-converting enzyme (CE) inhibitor help in the diagnosis and subsequent treatment of CE inhibitor induced visceral angioedema. V isceral angioedema is, as the name suggests, edema of the abdominal viscera mainly involving the small bowel with thickening of the small-bowel wall. Visceral angioedema induced by an angiotensin-converting enzyme (CE) inhibitor is a rare adverse reaction, with only 18 cases reported in the literature [1]. ll but one of the reported cases and the six cases encountered in our institute have been women with a wide age range. cute-onset or recurrent acute abdominal pain and nausea are the usual presenting features, with a common medication history of CE inhibitor. None of the patients seen in our institute had upper oropharyngeal symptoms. Imaging Characteristics Fluoroscopic studies may show mural thickening with luminal narrowing and flocculation of barium due to intraluminal fluid [2] or may show normal findings [3]. The most useful tool in the diagnosis is MDCT. The radiologic hallmark findings are circumferential small-bowel wall thickening (Figs. 1), mesenteric edema (Fig. 1), and ascites (Figs. 1 and 2). The bowel wall thickening has a stratified or target appearance [4] with low-attenuation submucosa between an enhancing mucosal layer and outer serosal layer. This finding may be difficult to see in patients who have positive oral contrast material in the involved portion of the bowel. The vasa rectae may be engorged in some patients (Fig. 3). None of the patients encountered in our institute had mesenteric lymphadenopathy or bowel obstruction. In our experience, the bowel wall thickness ranges from approximately 4 to 9 mm and the segment involved ranges from approximately 20 to 60 cm; there is no associated mesenteric lymphadenopathy or bowel obstruction. Pathophysiology CE degrades bradykinin, a peptide that causes vasodilation and increased vascular permeability. Inhibition of this action with the use of an CE inhibitor in predisposed individuals leads to the well-known adverse reaction of angioedema involving the face, tongue, and upper respiratory tract. The actual mechanism of visceral angioedema induced by CE inhibitor remains unknown. Diagnosis There is no definitive diagnostic test for CE inhibitor induced visceral angioedema. The cited studies in the literature have reported symptom onset to occur between days [5] to 9 years [6] after starting an CE inhibitor medication. Most of the CT features mentioned unfortunately are not specific for CE inhibitor induced visceral angioedema. However, these imaging findings in a patient with abdominal pain and a history of CE inhibitor intake complemented by relief of symptoms with discontinuation of the offending medication are very helpful in making the diagnosis. Symptoms usually resolve within 24 48 hours after withdrawal of the medication [5, 7]. Resolution of abnormal findings JR:196, pril 2011 W405
Vallurupalli and Coakley was documented in two patients in our institute on follow-up imaging (Fig. 4). Primary differential diagnostic considerations for CE inhibitor induced visceral angioedema include vasculitis, intramural hemorrhage, and ischemia [4, 8]. dditional considerations include nephrotic syndrome [8] with hypoproteinemia, Crohn disease, infectious enteritis, radiation enteritis, lymphoproliferative disease, and hereditary and acquired C1 esterase deficiency. Vasculitis may result in segmental bowel wall involvement identical to that seen with visceral angioedema. Helpful clinical clues may include cutaneous manifestations of vasculitis or a known predisposing condition such as systemic lupus erythematosus or Henoch- Schönlein purpura (Fig. 5). Intramural hemorrhage may appear very similar to CE inhibitor induced visceral angioedema on contrast-enhanced CT, with the relatively low-density submucosa. Unenhanced CT will often show increased density in the bowel wall [9] (Fig. 6). Furthermore, intramural hemorrhage usually occurs in patients taking warfarin who have an elevated prothrombin time and international normalized ratio. In patients with bowel ischemia, arterial or venous occlusion may be seen (Fig. 7); in addition, patients may have a history of mesenteric insufficiency. Crohn disease may be associated with circumferential or eccentric bowel wall involvement and may result in either a striated or a homogeneous appearance of the bowel wall. In addition, mesenteric findings including fistulas, creeping fat, and reactive adenopathy may be seen with Crohn disease (Fig. 8). Lymphoma of the small bowel may result in segmental wall thickening, but the involved wall will have a homogeneous density rather than a striated appearance as would be seen with visceral angioedema (Fig. 9). Lymphoma is also typically associated with lymphadenopathy and is often associated with involvement of other abdominal structures. Medication history will help to differentiate CE inhibitor induced visceral angioedema from hereditary (Fig. 10) and idiopathic angioedema. Last, but not the least, radiation enteritis may be differentiated from visceral angioedema by history of irradiation and mural thickening of bowel in a stratified manner in the area of previous irradiation (Fig. 11). Conclusion CE inhibitor induced visceral angioedema is a rare cause of abdominal pain. However, a timely and correct diagnosis of this entity is important in terms of not only bringing quick relief of symptoms but also avoiding unnecessary procedures. cknowledgment We thank K. Gupta for help with the images. References 1. Marmery H, Mirvis SE. ngiotensin-converting enzyme inhibitor-induced visceral angioedema. Clin Radiol 2006; 61:979 982 2. Jardine DL, nderson JC, McClintock D. Delayed diagnosis of recurrent visceral angio-edema secondary to CE inhibitor therapy. ust N Z J Med 1999; 29:377 378 3. yrne TJ, Douglas DD, Landis ME, Heppell JP. Isolated visceral angioedema: an underdiagnosed complication of CE inhibitors? Mayo Clin Proc 2000; 75:1201 1204 4. Macari M, Megibow J, althazar EJ. pattern approach to the abnormal small bowel: observations at MDCT and CT enterography. JR 2007; 188:1344 1355 5. Rosenberg EI, Mishra G, bdelmalek MF. ngiotensin-converting enzyme inhibitor-induced isolated visceral angioedema in a liver transplant recipient. Transplantation 2003; 75:730 732 6. Orr KK, Myers JR. Intermittent visceral edema induced by long-term enalapril administration. nn Pharmacother 2004; 38:825 827 7. bdelmalek MF, Douglas DD. Lisinopril-induced isolated visceral angioedema: review of CE-inhibitor-induced small bowel angioedema. Dig Dis Sci 1997; 42:847 850 8. De acker I, De Schepper M, Vandevenne JE, Schoeters P, Michielsen P, Stevens WJ. CT of angioedema of the small bowel. JR 2001; 176:649 652 9. Macari M, althazar EJ. CT of bowel wall thickening: significance and pitfalls of interpretation. JR 2001; 176:1105 1116 Fig. 1 Contrast-enhanced abdominopelvic 64-MDCT (Definition, Siemens Healthcare) of 22-year-old woman with acute-onset abdominal pain started on angiotensinconverting enzyme inhibitor 1 day before presentation., xial image shows circumferential mural thickening of duodenum and jejunum with stratified appearance., xial image shows mesenteric (arrow) edema and ascites. W406 JR:196, pril 2011
MDCT of Visceral ngioedema Fig. 2 bdominopelvic 64-MDCT (Definition, Siemens Healthcare) of 70-yearold woman with abdominal pain and nausea of several weeks duration on angiotensin-converting enzyme inhibitor for unknown period of time. Image shows mural thickening of distal small bowel, ascites, and mesenteric edema. Fig. 3 bdominopelvic MDCT (quilion 64, Toshiba) of 22-year-old woman with acute-onset abdominal pain 2 days after starting angiotensin-converting enzyme inhibitor. Coronal reformation image shows long segment circumferential mural thickening of jejunum and ileum with target sign or stratified appearance, which is better appreciated because nonopacified fluid is present within involved small bowel (short arrow) and engorged vasa rectae (long arrow). Fig. 4 Contrast-enhanced abdominopelvic 64-MDCT (Definition, Siemens Healthcare) of 40-year-old woman with recurrent episodes of abdominal pain on angiotensinconverting enzyme (CE) inhibitor for unknown period of time., xial image shows circumferential mural thickening involving proximal jejunum., xial image obtained after withdrawal of CE inhibitor shows appearance of bowel wall is now normal. JR:196, pril 2011 W407
Vallurupalli and Coakley Fig. 5 bdominopelvic CT of 58-year-old woman with abdominal pain and history of Henoch-Schönlein purpura., Coronal reformation image shows circumferential mural thickening of relatively long segment of small bowel with mural stratification, mesenteric edema, mild ascites, and engorgement of vasa rectae., Image shows stratified appearance of small-bowel wall (i.e., increased attenuation of serosa compared with submucosa) with mild ascites. Fig. 6 bdominopelvic CT of 85-year-old woman with abdominal pain and distention on warfarin and international normalized ratio of more than 9.35., Image shows thickening and high-density bowel wall secondary to intramural bleed., Image shows increased attenuation of free fluid (short arrow) compared with that in urinary bladder (long arrow) secondary to hemoperitoneum. W408 JR:196, pril 2011
MDCT of Visceral ngioedema Fig. 7 bdominopelvic CT of 61-year-old man with increasing abdominal pain for previous 5 days and history of hypertension and polycythemia.., Image shows mural thickening of bowel without definite stratification due to venous ischemia., Image shows thrombus in superior mesenteric vein (arrow). Fig. 8 bdominopelvic CT of Crohn disease., 40-year-old man with history of Crohn disease and right lower quadrant abdominal pain. Image shows mural thickening of terminal ileum with mucosal enhancement and stricture formation causing obstruction and distention of proximal small-bowel loop., 59-year-old woman with Crohn disease and right lower quadrant pain. Coronal reformation image shows abscess in right lower quadrant of abdomen, thickened terminal ileum with enhancing mucosa, and fistulous communication of terminal ileum with abscess. JR:196, pril 2011 W409
Vallurupalli and Coakley Fig. 9 70-year-old man with lymphoma. CT image of abdomen shows bowel wall thickening without stratification (arrow) and with adjacent adenopathy. Fig. 10 Contrast-enhanced abdominopelvic CT of 35-year-old woman with history of hereditary angioedema and recurrent episodes of abdominal pain., Image shows circumferential mural thickening of stomach, proximal duodenum, and jejunum., Coronal reconstruction image shows mesenteric edema and ascites. W410 JR:196, pril 2011
MDCT of Visceral ngioedema Fig. 11 CT image of 68-year-old woman with radiation enteritis shows stratified appearance of thickened bowel wall involving distal small bowel in pelvis in prior radiation field. FOR YOUR INFORMTION This article is available for CME credit. See www.arrs.org for more information. JR:196, pril 2011 W411