Acetylsalicylic Acid Intolerance

Twenty‐seven ASA‐intolerant individuals were investigated. Twenty‐six of them suffered from chronic bronchial asthma, one from urticaria. All reacted to the ingestion of a therapeutic dose of ASA with more or less violent signs and symptoms resembling a systemic allergic (anaphylactic) reaction of the immediate type. Seventy percent of them reacted in the same way to one or more chemically unrelated drugs. Seventeen of these patients were skin‐tested with N‐salicyloyl‐ and N‐acetylsalicyloyl‐PLL without the appearance of immediate type reactions. Furthermore, the sera of these patients were passively transferred to rhesus monkeys. The intradermally sensitized monkeys were challenged by i.v. or intradermal injection of N‐salicyloyl‐BSA or N‐acetylsalicyloyl‐PLL or by oral administration of ASAN or ASA. No positive reaction was obtained. Intracutaneous sensitization of rhesus monkeys with the sera of individuals allergic to Timothy grass pollen revealed strong reactions of the immediate type following challenge with Timothy grass pollen extract. The IgE levels and the concentrations of the other immunoglobulins of the ASA‐intolerant individuals were found to be within the normal range. Thus, homocytotropic antibodies with N‐salicyloyl or N‐acetylsalicyloyl specificity could not be detected in the ASA‐intolerant individuals. These results, the frequency of intolerance to other drugs, the familial occurrence of ASA intolerance and the demonstration of “latent” ASA intolerance in about 20% of chronic asthmatics indicate that the clinical picture of the syndrome is not a sufficient criterion of its allergic origin. In our opinion the syndrome is caused by direct (i.e. not antibody mediated) liberation of histamine and other mediators by the offending drugs, due to an “inborn error of metabolism” in intolerant individuals. The syndrome should be properly denoted as ‘drug‐induced anaphylactoid syndrome“.