WP 3.2 - Microdialysis in skin during oral challenge in patients with anaphylaxis to foods and drugs

Background:

Patients with allergen-specific IgE to foods, drugs or insects develop reactions ranging from local symptoms in the mouth (oral itching) or the skin (urticaria), whereas others develop life-threatening systemic anaphylaxis. While drug allergy in general and allergic reactions in patients with mastocytosis can be non-IgE mediated, the progression and symptoms of the reaction remains the same regardless of the presence of specific IgE. The severity of the reaction is often unpredictable and independent of the level of IgE, and the patophysiological background for the different reactions, local or systemic, remains obscure.

 

Hypothesis:

There are three parts of an allergic reaction:

 

 

In PART C we wish to investigate how mast cell mediators and neurogenic mechanisms derived from the initial site of allergen exposure can affect mast cells in distant target organs. The focus of the work package will be on skin reactions, since more than 90 % of patients experiencing a systemic reaction develop acute generalized urticaria. 

 

Methods:

Cutaneous microdialysis, a technique for measuring extracellular substances in the skin, will be performed to estimate levels of histamine, cytokines, leukotrienes, prostaglandins, PAF, and bradykinin released from skin mast cells during oral challenge with foods or drugs. This will be performed in patients routinely undergoing challenge with foods or drugs for diagnostic purposes. Levels of the different mediators will be compared to the development of symptoms and objective findings during oral challenge, with special focus on the kinectics of the different mediators released. Differences in mediator release elicited by different stimulators (e.g. peanut (IgE-mediated), penicillin (unknown mechanism) and Aspirin (COX-inhibition)) will be compared.

 

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