Q:

11/8/2012
We have a 40 year old female with history of 2 episodes of anaphylaxis 2 years ago. Also the patient has history of one episode of angioedema per week. We performed all work up without any findings and also administered transhexamic acid, anti histamine, prednisolon without any response. Would you please help?

A:

Thank you for your inquiry.

I am not sure that I can be of help to you, but will do my best. First of all, I think it is important for you to understand that a very large percentage of episodes of anaphylaxis in adults are idiopathic (see Webb abstract copied below). Idiopathic anaphylaxis is a difficult problem to manage, and sometimes cannot be adequately controlled.

There is an excellent review article by Dr. Paul Greenberger which goes into depth regarding potential management strategies for these patients. I have copied an abstract of this review article below.

In addition, the vast majority of causes of angioedema are also of unknown origin and do not respond adequately to therapy. I have copied several titles from our Ask the Expert website which discuss alternative therapies for angioedema including an anti-kinin drug normally reserved for treatment of the hereditary variety. You mentioned that you have employed tranexamic acid, and the use of this agent was originally derived from treatment protocols utilized for hereditary angioedema as well. These links can be accessed by typing angioedema into our search box on the "Ask the Expert" website.

In recalcitrant cases of anaphylaxis with multiple episodes you should consider a bone marrow to rule out mastocytosis or mast cell activating disorders.

Finally, there are quite a number of alternative therapies that in various hands have been reported to help prevent recurrent episodes of anaphylaxis These include methotrexate, mycophenolate mofetil, tacrolimus, and omalizumab.

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

Abstracts:
Ann Allergy Asthma Immunol. 2006 Jul;97(1):39-43. Anaphylaxis: a review of 601 cases. Webb LM, Lieberman P.
Source
Department of Internal Medicine, University of Tennessee, Germantown, Tennessee, USA.
Abstract
Background: The allergist usually sees patients with anaphylaxis after the event for the purposes of identifying the cause, establishing a prognosis, and preventing further episodes. Knowledge of the characteristics of such patients is essential to achieve these goals.
Objective: To examine the natural history, clinical manifestations, and factors that affect the patients' adherence to suggested treatment and preventive strategies of anaphylaxis.
Methods: A retrospective medical record review spanning 25 years (1978-2003) and follow-up questionnaires were used to obtain data on 601 patients who presented with anaphylaxis of unknown origin to a private university-affiliated allergy-immunology practice.
Results: Patients ranged in age from 1 to 79 years, with a mean age of 37 years. Females comprised 62% of cases. Causes of anaphylaxis were elucidated in 41% of cases. Known causes included foods in 131 patients (22%), medications in 69 cases (11%), and exercise in 31 cases (5%). Two hundred twenty-three patients (37%) were found to be atopic by history confirmed with skin prick testing. The most common manifestation was urticaria and/or angioedema, reported in 87% of patients. Systemic mastocytosis was found in 3 patients. Episodes tended to decline in frequency with time. Adherence to instructions to carry epinephrine can be improved with more effective teaching.
Conclusions: In most cases, the cause of anaphylaxis is undetermined. Women are affected more commonly than men. Systemic mastocytosis should be considered in cases of idiopathic anaphylaxis, and patients with a history of atopy are at an increased risk of developing anaphylaxis. Patients are more reliably carrying epinephrine as a result of changes in physician instructions. Finally, anaphylactic episodes tend to decrease in frequency and severity with time.

Immunol Allergy Clin North Am. 2007 May;27(2):273-93, vii-viii. Idiopathic anaphylaxis. Greenberger PA.
Source
Division of Allergy-Immunology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Suite 14018, 676 North St. Clair Street, Chicago, IL 60611, USA.
Abstract
Idiopathic anaphylaxis is a prednisone-responsive condition without external cause, but it can coexist with food-, medication-, or exercise-induced anaphylaxis. Mast cell activation may occur at night or after foods that have been eaten with impunity many times previously. Idiopathic anaphylaxis can be classified into frequent (if there are six or more episodes per year or two episodes in the last 2 months) or infrequent (if episodes occur less often). Idiopathic anaphylaxis-generalized consists of urticaria or angioedema associated with severe respiratory distress, syncope or hypotension, and gastrointestinal symptoms. Idiopathic anaphylaxis-angioedema consists of massive tongue enlargement or severe pharyngeal or laryngeal swelling with urticaria or peripheral angioedema. The differential diagnosis of idiopathic anaphylaxis is reviewed, and treatment approaches are presented.

9/4/2012 - Evaluation of a patient with recurrent episodes of anaphylaxis of unknown cause
8/14/2012 - Recalcitrant angioedema
7/3/2012 - Recalcitrant urticaria and angioedema
3/7/2012 - Recalcitrant angioedema

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology