We describe the first case of drug-induced solar urticaria due to repirinast, an antiallergic drug developed and introduced into the market in Japan in 1987. The patient was a 72-year-old woman who had been on repirinast for 1 year and 8 months. She developed urticaria immediately after an irradiation with 1.5 J/ cm of UVA, and the provocation test confirmed that repirinast was responsible for the urticarial reaction. The action spectrum of the urticarial reaction was deduced to be 320–350 nm. Passive and reverse passive transfer test results were both negative. However, intradermal injection of patient serum, obtained while she was on repirinast and irradiated in vitro with UVA, demonstrated positive reactions both in the patient and in a normal volunteer. Our findings suggest that nonallergic mechanisms are involved in the reaction. However, the rarity of the phenomenon also suggests an association with some allergic mechanisms.
ABSTRACT. The melanin granules are synthesized in melanocytes in the epidermal basal layer and the hair matrix. For the effective passage of melanin granules to the adjacent keratinocytes, melanocytes utilize unique cytoplasmic delivery system in which cytoskeletal network is prominently involved. Here, we show that the t-SNARE protein syntaxin3, a member of a family of key mediators of the cytoplasmic vesicle fusion and potent modulators of cytoskeletal dynamics, dramatically affects melanocyte cell behavior. Although plasmalemmal syntaxin3 has been detected also on the melanosomes of normal human melanocytes, we noticed that mouse melanoma B16 cells had completely lost endogenous syntaxin3. In response to the forcible expression of syntaxin3, B16 cells formed well-developed dendritic filopodia and accumulated melanin granules in the cytoplasm. We found that exogenous syntaxin3 was not expressed at the plasma membrane, but rather, localized with non-fibrous F-actin and melanin-packed melanosomes in the cytoplasm, by which the assembly/ polymerization of actin was dramatically impacted and the melanosome secretion was severely suppressed. The syntaxin3-triggered phenotypic changes were also induced by a syntaxin3 mutant lacking SNARE and transmembrane domains, and they were completely reverted by the subsequent knockdown of exogenous syntaxin3. This t-SNARE protein may act as a regulator of the actin dynamics, rather than a direct vesicle fusion mediator, to determine the fundamental properties of melanocytes.
Ustekinumab is an effective drug against moderate-to-severe psoriasis, but not all patients are responders to therapy and some patients may develop adverse effects. Only two studies have evaluated the influence of pharmacogenetics in psoriatic patients treated with ustekinumab. We evaluated 121 polymorphisms to study a possible association between these SNPs and the response to ustekinumab measured by PASI75 at 4 months of treatment (N¼69). The weight was evaluated for response to treatment (PASI75) and a higher weight was obtained in nonresponders than responders (p¼0.018). In addition, the adjusted results (FDR) showed an association between 5 SNPs in TNFRSF1A, HTR2A, NFKBIA, ADAM33, and IL13 genes and poor response to ustekinumab. Furthermore, 6 SNPs in CHUK, C17orf51, ZNF816A, STAT4, SLC22A4, and Corf72 genes were associated with better response to ustekinumab. However, there was not significant association between response to ustekinumab and SNPs in HLA-C as has been recently described.
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