Q:

10/31/2012
We saw a 17year old male with idiopathic angioedema. His angioedema started about 5 years again. He will develop episodes of primarily lip swelling several times a year. There are no identified triggers, but profuse rhinorrhea is noted just prior to the lip swelling. These episodes will last for several days to weeks. He is already on Allegra 180mg 1-2 times a day, and then when these episodes occur, he will use Benadryl 50mg 1-3 times a day. He has had a few episodes where he was seen in the ER due to reported tongue and/or throat swelling. According to the mother, in the ER he will receive prednisone, Epinephrine and more benadryl. His mother reports that the swelling will resolve in a few hours after this combination of drugs, but usually will return soon after. The family does not believe that antihistamines are helpful. Prior to Allegra, he had been on Zyrtec and hydroxyzine. Epipinephrine is of questionable relief because the family has used their Epipen at home, and did not see any marked improvement. The family believes Prednisone is helpful, but after completing a 3-5 day course the swelling returns. Previous lab testing showed normal IgM, IgG and IgA, but an elevated IgE of 234. Negative for HAE screening labs. Sensitivity to johnson, bermuda and timothy grass, as well as weed and tree mixes.

A:

Thank you for your inquiry.

The case you described is puzzling. I think part of the problem may be that we need to revisit the diagnosis. There are two features of the history that bear comment. The first, I cannot explain. That is the fact that he develops diffuse rhinorrhea with episodes. I know of no syndrome where angioedema is associated with rhinorrhea, and could find no reference to this with a literature search.

The most important feature, however, is the fact that you state that “These episodes will last for several days to weeks.” Actually, angioedema does not persist for more than two or three days except in rare instances, usually related to the administration of an angiotensin converting enzyme inhibitor. The fact that these episodes persist so long gives pause and suggests perhaps another diagnosis.

There are several case reports of Melkersson-Rosenthal syndrome mimicking angioedema. For your convenience, I have copied two abstracts from these reports below. I believe consideration should be given to this syndrome. The behavior of his symptoms would be in great part explained by this diagnosis.

I do not believe, except for a biopsy of the lip to determine whether or not he has Melkersson-Rosenthal syndrome, that any further workup would be helpful to you. And if indeed this simply is recalcitrant angioedema, I am afraid there is no consistently effective therapy to deal with this problem.

Alternative therapies for recalcitrant cases of angioedema have been suggested in the past. We have a number of different entries on the Academy Ask the Expert website that discuss these alternative therapies including anti-bradykinin therapy and other drugs. These entries, in terms of potential management strategies, would be of interest to you if indeed he is having angioedema events. In order to access them, you simply need to go to the Ask the Expert website and type “angioedema” into the search box. There are potentially helpful entries as follows:

1. On 11/1/2012 - “Recurrent episodes of angioedema without known cause” - This gives a reference to the use of anti-bradykinin therapy.
2. There is an entry on 8/14/2012 regarding recalcitrant angioedema.
3. On 7/3/2012, there is an entry entitled, “Recalcitrant urticaria and angioedema” which gives two references that discuss alternative therapies for urticaria in detail. These therapies can also be used to treat recalcitrant angioedema patients as well.

However, as mentioned, I doubt that this is the case.

Thank you again for your inquiry and we hope this response is helpful to you.

J Allergy Clin Immunol. 1987 Jul;80(1):64-7. Melkersson-Rosenthal syndrome. Minor MW, Fox RW, Bukantz SC, Lockey RF.
Abstract
Two patients were referred to the University of South Florida College of Medicine Allergy and Immunology Clinic for evaluation of "angioedema." Patient 1 presented with intermittent severe lip edema, and patient 2 presented with lip and facial swelling together with facial palsy. Multiple symptomatic treatments had been ineffective. Both patients were ultimately found to have Melkersson-Rosenthal syndrome, a rare granulomatous disorder of undetermined cause that must be considered in a differential diagnosis of facial edema. The patients are presented in detail to call attention to the diagnosis of the condition in order that unnecessary treatment, with attendant side effects, may be avoided.

Ann Allergy Asthma Immunol. 2007 Aug;99(2):185-9. Melkersson-Rosenthal syndrome: a form of pseudoangioedema. Kakimoto C, Sparks C, White AA.
Source
Department of Dermatology, Naval Medical Center San Diego, San Diego, California, USA.
Abstract
Background: Melkersson-Rosenthal syndrome is an unusual cause of facial swelling that can be confused with angioedema.
Objective: To describe a young woman with facial swelling initially considered to be angioedema.
Methods: A biopsy specimen of the eyelid demonstrated findings consistent with Melkersson-Rosenthal syndrome.
Results: After reviewing the differential diagnosis of pseudoangioedema, a presumptive diagnosis of Melkersson-Rosenthal syndrome was made. The patient was successfully treated with infliximab for Melkersson-Rosenthal syndrome. Owing to medication adverse effects, infliximab treatment was discontinued. Treatment was then continued with adalimumab, with good effect and without adverse events.
Conclusions: We report the case of a patient with Melkersson-Rosenthal syndrome presenting as angioedema. Furthermore, we report the first successful treatment of Melkersson-Rosenthal syndrome with adalimumab.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology