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Q:

23 yo male w/ 5 yr h/o recurrent, severe mid-epigastric abdominal pain associated w/ spontaneous emesis; describes a "pulsing / burning" type pain always localized to the same area (above umbilicus); no constipation or diarrhea. Lasts up to 10 hrs. Average = once per week; may have isolated symptom free periods of up to 2 mos (not common). Multiple ER visits for pain management. Hospitalized for up to 5 days for extensive workup. No angioedema (visible); no airway obstructive symptoms. Most often occurs during the night; rapid acceleration in intensity of pain. Never triggered by exercise. Negative FH of angioedema. Cousins, aunts, uncles with SLE & Crohn's. No h/o resp or food allergies. Comprehensive GI eval = normal (IBD markers, colonoscopy, endoscopy, Barium studies, routine labs). Referred here for a "low" C1estINH (19 w/ lower end of normal @ 21). Repeat levels (quant [26] & functional [99]) were normal; C4 (23) and ESR = normal; CBC w/ slight elevation of eos (8%). Food skin test battery: low level response to barley (56 foods tested). IgE requested but not done.

 

Questions:
1. Considering possible diagnosis of type 3 angioedema. Are there any other tests you would do before establishing this diagnosis?

 

2. The symptoms have had a profound effect on his life style; multiple ER visits; does not want to be reliant on pain medications; tremendous source of anxiety. Wanted to try patient on Kalbitor (have it available in the local ER when symptoms are present). Do you agree with a trial of Kalbitor? And if it works, can we be confident of the diagnosis of type 3 AE and what would you then recommend for prophylaxis?

 

3. If it is not effective, do you have any other recommendations / suggestions?

 

Thanks so much for your input.

A:

Thank you for your recent inquiry.

This is certainly a difficult problem, and one which does not allow a definitive opinion. However, I do not think that we have established a diagnosis of angioedema at this time (unless there is information that I have not seen), and therefore would be a little reluctant to institute a trial of ecallantide.

Certainly abdominal angioedema can produce this type of severe abdominal pain, and is to be considered in the differential diagnosis, but one should be able to demonstrate bowel angioedema at the time of the pain by obtaining a CT scan. Unless this has been demonstrated, I would be hesitant to accept this diagnosis.

What I would suggest first would be to obtain a CT scan during another episode, and see if small bowel edema can be detected. If he does demonstrate small bowel edema, then an empiric trial of either icatibant or ecallantide might be indicated.

There is unfortunately no test for "type III" angioedema. A response to either ecallantide or icatibant would imply that activation of the contact system was responsible for the event. It would then become a matter of semantics whether one would label him with a diagnosis of type III angioedema. From a pathophysiologic standpoint, however, the important issue would be that drugs blocking the effect of activation of the contact system would be helpful in treatment. If you have found on CT scan small bowel edema, then I would certainly feel an empiric trial of either icatibant or ecallantide would be worthwhile. I might favor the recently approved icatibant simply because it can be given quite easily at home by subcutaneous injection. It is supplied by specialty pharmacies. There would probably be enough justification to obtain it if small bowel angioedema is demonstrated during the occurrence of these episodes.

Unfortunately, I do not have any other recommendations should there be no small bowel edema demonstrable.

In summary, I do not think there would be any harm in using either icatibant or ecallantide empirically, but they are quite expensive and of course there is a risk of anaphylaxis to ecallantide. Therefore my first choice would be to document the presence of small bowel angioedema by CT scan during an episode if it has not yet been done before initiating either of these two drugs. However, I would not be critical should you choose to go ahead and start either drug without documentation.

I would tend to favor, because of the fact that it can be easily given at home, icatibant, but either drug would serve the same purpose.

In the absence of any beneficial effect of these agents, I unfortunately have no further suggestions for workup or treatment.

Thank you again for your inquiry and we hope this response is helpful to you. We would greatly appreciate a follow-up if you do use either of the two aforementioned agents.

Sincerely,
Phil Lieberman, M.D.

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