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Concept: Cholinergic urticaria


Cholinergic urticaria (CU) has clinically characteristic features, and has been frequently described in the literature. However, despite its comparatively old history, the pathogenesis and classification remains to be clarified. CU patients are occasionally complicated by anhidrosis and/or hypohidrosis. This reduced-sweat type should be included in the classification because the therapeutic approaches are different from the ordinary CU. It is also well-known that autologous sweat is involved in the occurrence of CU. More than half of CU patients may have sweat hypersensitivity. We attempt to classify CU and address the underlying mechanisms of CU based on the published data and our findings. The first step for classification of CU seems to discriminate the presence or absence of hypersensitivity to autologous sweat. The second step is proposed to determine whether the patients can sweat normally or not. With these data, the patients could be categorized into three subtypes: (1) CU with sweat hypersensitivity; (2) CU with acquired anhidrosis and/or hypohidrosis; (3) idiopathic CU. The pathogenesis of each subtype is also discussed in this review.

Concepts: Perspiration, Subtype polymorphism, Polymorphism in object-oriented programming, Type theory, Hyperhidrosis, Cholinergic urticaria, Medical terms


Several guidelines for urticaria and angioedema have been published in Europe and United States since 1997. General principles for diagnosis and treatments of them are similar. However, each guideline has its own characteristics and shows differences in areas such as the coverage of urticaria subtypes, nomenclatures, and hierarchy of the medications. In Japan, the Japanese Dermatological Association (JDA) published its first guideline for urticaria and angioedema in 2005. It established a new classification of urticaria and angioedema together with the definition of each subtype. It emphasized the importance of discriminating idiopathic urticaria, consisting of acute urticaria and chronic urticaria from inducible urticaria, such as allergic urticaria, physical urticaria and cholinergic urticaria. It contains several unique algorithms for diagnosis and treatment of urticaria from a view point of clinical practices, and was further enforced by a style of EBM in 2011. Nevertheless, these guidelines have not been recognized outside of Japan, because of a language barrier. In this article, the outline of the newest guidelines by JDA are introduced and compared with the guidelines in other countries published in English.

Concepts: Angioedema, Cholinergic urticaria, Urticaria and angioedema, Urticaria


We previously identified MGL_1304 secreted by Malassezia globosa as a sweat antigen for patients with atopic dermatitis (AD) and cholinergic urticaria (ChU). However, purifying native MGL_1304 from human sweat or culture supernatant of M. globosa (sup-MGL_1304) is costly and time-consuming. Moreover, recombinant MGL_1304 expressed by using Escherichia coli (TF-rMGL_1304) needs a large chaperon protein and lacks the original glycosylation of yeasts. Thus, we generated a recombinant MGL_1304 by Pichia pastoris (P-rMGL_1304) and investigated its characteristic features.

Concepts: Fungus, Atopy, Cholinergic urticaria, Gut flora, Endoplasmic reticulum, Yeasts, Protein, Escherichia coli


Idiopathic pure sudomotor failure (IPSF) is a subgroup of acquired idiopathic generalized anhidrosis, which is characterized by early age of onset, acute or sudden onset, concomitant sharp pain or cholinergic urticaria over the entire body, absence of autonomic dysfunction other than generalized anhidrosis, raised serum IgE level, and marked response to steroid. The aetiology of IPSF is still not well understood, but is thought to be caused by interference in cholinergic transmission in the eccrine glands of skin. IPSF after viral infection has rarely been reported in the literature. We describe a patient who developed generalized anhidrosis and cholinergic urticaria accompanied by heat intolerance after infectious mononucleosis infection. This is the first such case, to our knowledge, and the patient was successfully treated with steroid pulse therapy.

Concepts: Infectious disease, Cholinergic urticaria, Immunoglobulin E, Medical terms, Infection, Malaise


A 43 year old caucasion gentleman had been receiving Botulinum toxin type A injections (BOTOX(®) , Allergan) for his axillary hyperhidrosis since 2004 with good effect. In June 2009 he gave an 18 month history of developing small prutitic wheals on his chest, arms and to a lesser extent his legs and back.. The lesions lasted between 5 and 120mins. There was no dermographism. Triggers included anxiety, physical exercise and hot showers.

Concepts: Physical exercise, Insomnia, Microbial toxins, Allergan, Cholinergic urticaria, Urticaria, Hyperhidrosis, Botulinum toxin


Adrenergic urticaria (AU) is a rare type of stress-induced physical urticaria characterized by widespread pruritic urticarial papules. Diagnosis can be made by i.d. injection of adrenaline or noradrenaline, which produces the characteristic rash. Although the lesions of AU typically respond to beta-blockers such as propranolol, the therapeutic options for AU are limited. Here, we report a case of AU that was resistant to beta-blockers and successfully treated with clotiazepam. The clinical picture of AU resembles that of cholinergic urticaria (CU), however, positive noradrenaline test and negative acetylcholine skin test were useful for the differential diagnosis of AU and CU. Although his symptoms were resistant to several therapeutic methods including olopatadine (H1 antagonist), lafutidine (H2 antagonist) and propranolol, the severity and frequency of his attacks and his subjective symptoms were reduced by oral clotiazepam, an anxiolytic benzodiazepine. Dermatologists should be aware that anxiolytic benzodiazepines may be a therapeutic option in AU.

Concepts: Pruritic urticarial papules and plaques of pregnancy, Differential diagnosis, Norepinephrine, Beta blocker, Neurotransmitter, Cholinergic urticaria, Urticaria, Adrenergic receptor


Heat urticaria is a rare type of physical inducible urticaria, characterized by itchy erythema and well-demarcated wheals appearing short after heat-exposure. Most cases occur in female patients aged 20 to 45 years. Both localized and generalized forms exist, depending on the limitation of the reaction to the skin area directly exposed to the physical stimulus or the involvement of distant sites, respectively. In most cases, heat urticaria is an immediate reaction, but delayed forms (most familial) have been described. Heat urticaria is a long-lasting disease with overall duration at diagnosis of approximately 2 years. In about half of cases it is associated with systemic symptoms such as weakness, wheezing, headache, flushing, nausea, vomiting, diarrhoea, tachycardia, even dyspnoea or syncope. The main differential diagnosis includes cholinergic urticaria, exercise induced anaphylaxis and solar urticaria. The diagnosis of heat urticaria is established by provocation testing, which is also helpful to evaluate the critical temperature threshold. The mean threshold temperature is about 44°C. Heat desensitization program can be an effective treatment. Non-sedating H1 anti-histamines administered at licensed doses are the mainstay of symptomatic therapy in nearly 60% of patients, but only in a minority of them a full symptom relief is achieved. Omalizumab has proven effective in recent case reports. This article is protected by copyright. All rights reserved.

Concepts: Urticaria, Differential diagnosis, Copyright, Symptomatic treatment, Cholinergic urticaria, Symptom, Symptoms, Medical terms


Physical urticarias are a unique subgroup of chronic urticaria in which urticarial responses can be reproducibly induced by different specific physical stimuli acting on the skin. These conditions include urticaria factitia/symptomatic dermographism, delayed pressure urticaria, cold contact urticaria, heat contact urticaria, solar urticaria, and vibratory urticaria/angioedema. Physical urticarias and cholinergic urticarias are diagnosed based on the patients' history and provocation tests including trigger threshold testing where possible. Treatment is mainly symptomatic. Many patients benefit from avoiding eliciting triggers, and desensitization to these triggers can be helpful in some physical urticarias and in cholinergic urticaria.

Concepts: Cholinergic urticaria, Solar urticaria, Urticaria and angioedema, Urticaria


Cholinergic urticaria (CholU), a common form of chronic inducible urticaria, is characterized by itchy wheals that occur in response to physical exercise or passive warming. CholU patients frequently exhibit a high burden of disease. As of yet, no specific instrument is available to assess their disease-related quality of life (QoL) impairment.

Concepts: Physical exercise, Quality of life, Exercise, Stretching, Strength training, Cholinergic urticaria, Human Development Index, Quality


Cholinergic Urticaria (CholU) is a common skin disease characterized by the development of pinpoint sized wheals and severe itch upon physical exercise. Little is known about the epidemiology of CholU. CholU can occur at any age and has the highest prevalence among young adults. As of now, it is unclear if patients of different age show differences in the clinical manifestation of CholU, duration of disease, comorbidities or response to treatment.

Concepts: Demography, Death, Disease, Cholinergic urticaria, Epidemiology