Urticaria

DOI: 10.1111/j.1468-3083.2011.04017.x

JEADV

SHORT REPORT

Cholinergic urticaria: pathogenesis-based categorization and its treatment options
S. Nakamizo, G. Egawa,* Y. Miyachi, K. Kabashima
Department of Dermatology, Kyoto University, Kyoto, Japan *Correspondence: G. Egawa. E-mail: gyohei@kuhp.kyoto-u.ac.jp

Abstract
Background Cholinergic urticaria (CU) has well-describedcharacteristic clinical presentations, yet the precise pathological mechanism remains incompletely understood. A variety of pathogeneses has been proposed, which suggests that there exists several clinical subtypes. Conclusions In this review, we categorize CU into four subtypes: (i) CU with poral occlusion; (ii) CU with acquired generalized hypohidrosis; (iii) CU with sweat allergy; and (iv) idiopathic CU,and discuss diagnostic and treatment options. Received: 16 November 2010; Accepted: 28 January 2011

Conflict of interest
None declared.

Funding sources
None.

Introduction
Cholinergic urticaria (CU) is one of the physical urticaria characterized by small and pruritic weals which follow sweating events, including elevation of body temperature, physical exercise, intake of spicy foods andemotional strains. To make the diagnosis of CU is generally not difficult because of its characteristic clinical manifestations. However, the underlying pathological mechanism remains incompletely understood. CU is sometimes accompanied by acquired generalized hypohidrosis (AGH), suggesting that the sweat itself is not essential for the initiation of CU. Recently, we and others have revealed thatthe disturbance of muscarinic cholinergic receptors (CHRMs) expression is involved in the development of CU associated with AGH. In this review, we will present an overview of the current range of our knowledge on the pathological mechanisms of CU and its treatment options, and propose a simple categorization based on its pathogenesis.

injection of cholinergic agents induce sweating and thedevelopment of numerous pin-point hives in patients with CU, and that the symptoms of CU are inhibited by prior atropinization of the skin.1 In addition, recent studies have shown that not only sweat glands but also mast cells express muscarinic cholinergic receptor 3 (CHRM3), which is a responsible cholinergic receptor for sweating.2 In fact, acetylcholine triggers degranulation of rat mast cells.3Although it remains unknown whether this is applicable even in human,3 acetylcholine seems to play an essential role in the development of CU.

The minor role of histamine in the pathogenesis of cholinergic urticaria
Previous studies have reported that serum histamine levels are elevated in the presence of weals and are further increased by hard exercise in some patients with CU.4 These findingssuggest that histamine plays at least some roles in the pathogenesis of CU. However, serum histamine levels are not elevated in all CU patients and are not correlated with the severity of symptoms.5 In addition, in contrast to conventional urticaria, the effect of antihistamine drugs is rather limited in most cases of CU, suggesting that histamine plays only a minor role in the pathogenesis ofCU. The potential involvement of additional mediators apart from histamine, such as serotonin, bradykinin and eosinophil chemotactic agents has been postulated.4,6

The essential role of acetylcholine in the development of cholinergic urticaria
The sweat glands receive sympathetic innervations but express muscarinic acetylcholine receptors, which are normally expressed on parasympathetic nervoussystems; therefore, acetylcholine is considered to be a central signal mediator for the secretion of sweat. Previous reports have demonstrated that subcutaneous

JEADV 2012, 26, 114–116

ª 2011 The Authors Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology

Categorization of Cholinergic urticaria

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Cholinergic...