Table_1_Evidence for histamine release in chronic inducible urticaria – A systematic review.docx

BackgroundChronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU.MethodsWe systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or in vitro or ex vivo histamine release (indirect evidence) following trigger exposure.ResultsAn initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H1-antihistamines.ConclusionsHistamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.

背景慢性可诱导性荨麻疹（CIndU）包括九种不同的荨麻疹类型，患者在暴露于特定明确诱因后会出现瘙痒性风团及/或血管性水肿。据认为，由活化并脱颗粒的皮肤肥大细胞释放的组胺在CIndU的发病机制中起着关键作用，但支持这一观点的证据尚未被系统性地或详尽地审查。本研究旨在描述组胺在CIndU中的角色及其相关性。方法：我们对PubMed、Scopus和Embase三个电子数据库进行了系统检索，以寻找报道在诱因暴露后血清或皮肤组胺浓度增加（直接证据）或体外或离体组胺释放（间接证据）的研究。结果：最初检索到的3,882篇文章经过筛选，最终得到107项相关研究，其中52项关于冷性荨麻疹，19项关于胆碱能性荨麻疹，14项关于热性荨麻疹，10项关于接触性荨麻疹，各7项关于日光性荨麻疹和振动性血管性水肿，各4项关于症状性皮肤划痕症和水源性荨麻疹，以及3项关于延迟性压力性荨麻疹。我们的综述结果支持组胺在所有CIndU的发病机制中起着关键的致病作用，但并非唯一的介质，这由组胺水平与症状严重程度之间的不佳关系以及H1-抗组胺药物的变量临床疗效所证明。结论：来自皮肤肥大细胞的组胺是CIndU中症状和体征发展的关键驱动力，并且是CIndU中一种有前景的治疗靶点。