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Background Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise- induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. Methods The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. Results Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl- phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. Conclusions Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Background Regulated on activation, normal T expressed and secreted (RANTES) has been known to be deeply involved in the pathophysiology of atopic dermatitis (AD). To examine whether a –401A/G polymorphism in the RANTES promoter gene is associated with the susceptibility to AD in Japanese, we determined the genotypes of the polymorphism in 145 Japanese students and 65 patients with AD. Methods DNA was isolated from the mononuclear cells by using SepaGene (Sanko) and analyzed by the polymerase chain reaction (PCR) technique. Results The frequency of –401A allele was 0.39 in the healthy subjects without AD. This was not significantly different from that in the patients with AD (0.41). We also failed to show association between the polymorphism in the RANTES promoter gene and the production of IgE. Conclusions These results suggest that the –401A/G polymorphism in the RANTES promoter gene does not determine the susceptibility to AD in Japanese, although larger studies could explore the exact role of the polymorphisms in AD, or Japanese might have other susceptibility genes more potent than the RANTES promoter gene.

Background: Challenge testing with wheat plus exercise and or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA. Methods: Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations―Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable―were given according to the results of wheat plus exercise and or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and or dietary management in Group II and III. Results: Positive results for wheat plus exercise and or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes. Conclusions: Our study revealed that serum gliadin monitoring during challenge testing is useful.