Q:

10/29/2013
I have been asked to consult on a challenging case of what is thought to be intestinal angioedema. The patient is a 43yo white male with a 2yo history of gradually worsening chronic abdominal pain, vomiting, diarrhea, fatigue, night sweats, and weight loss (a total of 100 pounds over 2 years). There is some degree of memory impairment, though this is thought to be partially due to opioids that have been used to treat his pain. He has a 60pyh of smoking, but was otherwise previously healthy.

He has had an extensive work-up at a university-based center over this time, including CT abdomen, CT chest with subsequent biopsy of what ended up being reactive lymph nodes, EUS, video capsule endoscopy. All of these were essentially unremarkable. Recently, a DOTA radionuclide scan (looking for malignancy) showed significant angioedema of the small intestine. This was followed by labwork showing normal C4 (26) and C1 esterase studies (C1 esterase inh of 39, at the upper limits of normal, and C1 esterase function of 117, clearly within the normal range). However, the C1q was low at 77 (normal 109-242).

The patient has no other history of angioedema, nor of urticaria. There is no family history of angioedema. Upon my review of the literature, it seems that most cases of intestinal angioedema are either hereditary or acquired, and are associated with decreased C1 esterase levels/function, which is not the case in this gentleman. I would appreciate any assistance in further work-up and management.

A:

Thank you for your inquiry.

Intestinal angioedema, to my knowledge, has a very limited differential diagnosis. Outside of C1 esterase inhibitor deficiency syndromes, ACE inhibitors, and classical IgE-mediated (histaminergic) angioedema, I am not personally aware of any other common cause. Thus, I think you have already done due diligence from the standpoint of an allergist-immunologist, and from my personal standpoint, I cannot offer any further suggestions as far as an evaluation is concerned.

However, I am going to forward your inquiry to Dr. Ugo Nzeako, who has published extensively in this area (a link to his review article of intestinal angioedema is copied for you below). As soon as we receive Dr. Nzeako’s response, we will forward it to you.

Thank you again for your inquiry.

World J Gastroenterol. 2010 October 21; 16(39): 4913–4921.
Published online 2010 October 21. doi: 10.3748/wjg.v16.i39.4913
PMCID: PMC2957599
Diagnosis and management of angioedema with abdominal involvement: A gastroenterology perspect.
Ugochukwu C Nzeako

AJR Am J Roentgenol. 2011 Aug;197(2):393-8. doi: 10.2214/AJR.10.4451.
Angiotensin-converting enzyme inhibitor-induced small-bowel angioedema: clinical and imaging findings in 20 patients.
Scheirey CD, Scholz FJ, Shortsleeve MJ, Katz DS.
Source
Department of Radiology, Lahey Clinic, 41 Mall Rd, Burlington, MA 01805, USA. Abstract
Objective: The purpose of this article is to retrospectively review the radiologic and clinical findings in patients with angiotensin-converting enzyme inhibitor (ACEI)-induced small-bowel angioedema, with an emphasis on CT findings.
Materials and Methods: Imaging findings, with an emphasis on CT, and clinical characteristics of 20 patients (23 presentations) presenting to two institutions' emergency departments from 1996 through 2010 with ACEI-induced small-bowel angioedema were retrospectively reviewed by two abdominal radiologists who were aware of the diagnosis. Examinations were reviewed in consensus to determine common radiographic findings.
Results: Patient age range was 23-83 years (mean, 56 years). Sixteen of the 20 patients were women, and 15 of 20 were obese. All had acute onset of severe abdominal pain. The date of the initial episode prompting CT evaluation ranged from 2 days to 10 years after the start of ACEI therapy (average, 3.3 years). All patients underwent abdominal CT examinations while symptomatic; five patients also underwent a small-bowel series. Three patients underwent urgent surgery for presumed small-bowel ischemia. All patients had resolution of symptoms within 4 days of hospitalization. CT findings included ascites in all patients, small-bowel wall thickening (mean, 1.3 cm), mild dilatation (mean, 2.9 cm), and straightening. There was no small-bowel obstruction.
Conclusion: ACEI-induced small-bowel angioedema should be included in the differential diagnosis when patients receiving ACEI therapy present with abdominal complaints and the following combination of findings on CT examination: ascites, small-bowel wall thickening, dilatation without obstruction, and straightening.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Nzeako. Thank you again.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Nzeako:
After reviewing the brief history provided, I must agree with you that the test findings are not typical for hereditary or acquired angioedema.

Several questions are raised: Was the abdominal CT scan done with IV and oral contrast? What organ did the EUS examine, and what abnormality prompted the EUS? Does patient have risk factors for chronic pancreatitis? Has stool been checked for fat malabsorption?

Other helpful tests may include: LDH (high would suggest possibility of a lymphoma). RPR (syphilis), since this can cause some of these symptoms as well as neurologic ones that may be mistaken for opioid adverse effect. Porphyrin screen, since some can cause similar symptoms.

Also, radionuclide scanning may not be the best method for distinguishing between angioedema, and bowel wall thickening/swelling from other causes. True small bowel angioedema should be obvious on a good contrast enhanced CT scan of the abdomen.

My suggestion would be to do the above tests, repeat some of those already done to ensure nothing was missed, and have patient seen at a center with a gastroenterology department capable of performing a Double Balloon Enteroscopy to reach, examine, and biopsy, the area of small bowel noted to be abnormal on the scan. Laparoscopy may also be helpful in the appropriate setting, if full thickness biopsy of an abnormal area of bowel becomes necessary to rule out lymphoma and infiltrative disorders which can affect the bowel also.

Sincerely,
Ugo Nzeako, MD, MPH

AAAAI - American Academy of Allergy Asthma & Immunology