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Reaction pattern to histamine and codeine in a human intradermal skin test model


Prof. Dr. med. Andreas J. Bircher
Allergology Unit
Department of Dermatology,
Petersgraben 4,
4031 Basel, Switzerland.


Background Skin prick and intradermal skin tests (IDT) are useful tools in evaluating IgE-mediated allergic disorders. In the literature, many variations of the techniques used are described. No general agreement exists on test procedures and reading of test results.

Objective To analyse test conditions for IDT to facilitate comparability between different study protocols.

Methods We tested 24 healthy volunteers with three concentrations of histamine and codeine each on the upper back, lateral upper arm and volar forearm, with/without addition of ethylene diamine tetra-acetic acid. Reading of the resulting weal was performed by taking a digital image of the weal, later outlining the weal perimeter in triplicate and calculating the weal area using the NIH Image J software version 1.3.

Results Weal size was dose dependent for both substances, generally larger on the upper back than on the forearm and upper arm, and larger after codeine than after histamine. Addition of the Ca2+-chelator ethylene diamine tetra-acetic acid did not significantly affect weal size. Weal size induced by histamine showed better consistency than that induced by codeine.

Conclusions The results and our technique provide valuable tools for the daily routine as well as for the ability to compare information of intradermal tests from different studies or clinical reports. When assessing skin reactivity, we recommend the use of 1 mg/mL codeine as well as 0.1 mg/mL histamine to reflect aspects of mast-cell releasability and of vascular reactivity. The involvement of local factors influencing the vascular reactivity or differences in opiate receptor density on mast cells surfaces needs to be addressed in future studies.