Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
JAMA Dermatol. 2015 Mar;151(3):311-5. doi: 10.1001/jamadermatol.2014.3002.
Acute generalized exanthematous pustulosis (AGEP) is a rare and severe type of drug eruption. Dihydrocodeine phosphate is a semisynthetic opioid analgesic. Recently, recessive mutations in IL36RN have been identified in generalized pustular psoriasis (GPP). To date, 4 cases of AGEP and IL36RN mutation without previous history of psoriasis vulgaris (PV) have been reported.
A woman in her 60s with PV presented with diffuse erythema, nonfollicular pustules, and fever. She had been treated with dextromethorphan hydrobromide hydrate, amoxicillin hydrate, clarithromycin, dihydrocodeine phosphate, tipepidine hibenzate, and tulobuterol tape for a cough and common cold. Based on histopathologic results and a positive result in a drug provocation test with dihydrocodeine phosphate, she was diagnosed with AGEP. A heterozygous IL36RN mutation c.28C>T (p.Arg10X) was also confirmed by mutation analysis.
This is the first report of dihydrocodeine phosphate-induced AGEP. In this case, helper T cells, type 17, might have been activated because of morphine and underlying PV, followed by increased production of interleukin (IL) 36. However, because of the IL36RN mutation, IL-36 signaling was uncontrolled, which might have resulted in the occurrence of AGEP. An IL36RN mutation might underlie several different pustular skin eruptions, including AGEP and GPP, and further accumulation of patient data is required.
急性泛发性发疹性脓疱病（AGEP）是一种罕见且严重的药物性皮疹。二氢可待因磷酸盐是一种半合成阿片类镇痛药。最近，在全身性脓疱性银屑病（GPP）中发现了 IL36RN 的隐性突变。迄今为止，已有 4 例无先前寻常型银屑病（PV）病史的 AGEP 和 IL36RN 突变病例报告。
一位 60 多岁的女性患有 PV，表现为弥漫性红斑、非滤泡性脓疱和发热。她曾接受右美沙芬氢溴酸盐、阿莫西林水合物、克拉霉素、二氢可待因磷酸盐、替皮啶盐酸盐和妥洛特罗贴剂治疗咳嗽和普通感冒。根据组织病理学结果和二氢可待因磷酸盐药物激发试验的阳性结果，她被诊断为 AGEP。突变分析还证实了杂合 IL36RN 突变 c.28C>T（p.Arg10X）。
这是首例二氢可待因磷酸盐诱导的 AGEP 报告。在这种情况下，辅助性 T 细胞 17 型可能因吗啡和潜在的 PV 而被激活，随后白细胞介素（IL）36 的产生增加。然而，由于 IL36RN 突变，IL-36 信号不受控制，这可能导致 AGEP 的发生。IL36RN 突变可能是几种不同的脓疱性皮肤疹的基础，包括 AGEP 和 GPP，需要进一步积累患者数据。
