{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:23:10Z","timestamp":1790270590180,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cholinergic urticaria (CholU), a frequent form of chronic inducible urticaria, is characterized by itchy wheals and angioedema in response to sweating. As of now, the rate and pathophysiological relevance of impaired sweating in patients with CholU are ill-defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess in CholU patients the rate and extent of impaired sweating and its links to clinical and pathophysiological features of CholU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>We assessed sweating in patients with CholU (<jats:italic>n<\/jats:italic> = 13) subjected to pulse-controlled ergometry (PCE) provocation testing. Pre- and post-PCE biopsies of lesional (L) and non-lesional (NL) skin were analyzed for the expression of acetylcholine receptor M3 (CHRM3) and acetylcholine esterase (ACh-E) by quantitative histomorphometry and compared to those of healthy control subjects (HCs). CholU patients were assessed for disease duration and severity as well as other clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 13 patients with CholU, 10 showed reduced sweating in response to PCE provocation, and 3 had severely reduced sweating. Reduced sweating was linked to long disease duration and high disease severity. CholU patients with impaired sweating responses showed reduced sweat gland epithelial expression of CHRM3 and ACh-E.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduced sweating is common in CholU patients, especially in those with long-standing and severe disease, and it can be severe. Reduced expression of CHRM3 and ACh-E may be the cause or consequence of CholU in patients with impaired sweating, and this should be explored by further studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.955161","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T13:13:14Z","timestamp":1659100394000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Impaired sweating in patients with cholinergic urticaria is linked to low expression of acetylcholine receptor CHRM3 and acetylcholine esterase in sweat glands"],"prefix":"10.3389","volume":"13","author":[{"given":"Yiyu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Scheffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Ayala","family":"Vera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"G\u00fcnzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Terhorst-Molawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Altrichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/all.12884","article-title":"The definition, diagnostic testing, and management of chronic inducible urticarias - the EAACI\/GA(2) LEN\/EDF\/UNEV consensus recommendations 2016 update and revision","volume":"71","author":"Magerl","year":"2016","journal-title":"Allergy"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(94)70267-5","article-title":"Prevalence of cholinergic urticaria in young adults","volume":"31","author":"Zuberbier","year":"1994","journal-title":"J Am Acad Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13023","article-title":"Cholinergic urticaria patients of different age groups have distinct features","volume":"47","author":"Asady","year":"2017","journal-title":"Clin Exp Allergy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00502986","article-title":"[On the pathogenesis of cholinergic urticaria. i. clinical observations and histological studies]","volume":"229","author":"Illig","year":"1967","journal-title":"Arch Klin Exp Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1365-2133.1978.tb07332.x","article-title":"Tests to establish the diagnosis in cholinergic urticaria","volume":"98","author":"Commens","year":"1978","journal-title":"Br J Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1987.01660280064024","article-title":"Cholinergic urticaria. a clinical and histologic study","volume":"123","author":"Hirschmann","year":"1987","journal-title":"Arch Dermatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-009-0038-x","article-title":"New concepts of hive formation in cholinergic urticaria","volume":"9","author":"Horikawa","year":"2009","journal-title":"Curr Allergy Asthma Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.12-RAI-0485","article-title":"Pathogenesis of cholinergic urticaria in relation to sweating","volume":"61","author":"Bito","year":"2012","journal-title":"Allergol Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1000","article-title":"Cholinergic urticaria associated with acquired hypohidrosis: an ultrastructural study","volume":"91","author":"Chinuki","year":"2011","journal-title":"Acta Derm Venereol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2332\/allergolint.13-OA-0611","article-title":"Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria","volume":"63","author":"Hiragun","year":"2014","journal-title":"Allergol Int"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/all.13494","article-title":"Updosing of bilastine is effective in moderate to severe chronic spontaneous urticaria: A real-life study","volume":"73","author":"Weller","year":"2018","journal-title":"Allergy"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.jaip.2018.10.013","article-title":"Angioedema frequently occurs in cholinergic urticaria","volume":"7","author":"Mellerowicz","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.jaip.2018.12.025","article-title":"Efficacy and safety of omalizumab (Xolair) for cholinergic urticaria in patients unresponsive to a double dose of antihistamines: A randomized mixed double-blind and open-label placebo-controlled clinical trial","volume":"7","author":"Gastaminza","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1159\/000057877","article-title":"Cholinergic urticaria, a new pathogenic concept: hypohidrosis due to interference with the delivery of sweat to the skin surface","volume":"204","author":"Kobayashi","year":"2002","journal-title":"Dermatology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000096205","article-title":"Cholinergic urticaria and hypohidrosis: a clinical reappraisal","volume":"213","author":"Rho","year":"2006","journal-title":"Dermatology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000142036.54112.57","article-title":"Idiopathic pure sudomotor failure: anhidrosis due to deficits in cholinergic transmission","volume":"63","author":"Nakazato","year":"2004","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2011.04015.x","article-title":"A case of cholinergic urticaria associated with acquired generalized hypohidrosis and reduced acetylcholine receptors: cause and effect","volume":"36","author":"Nakamizo","year":"2011","journal-title":"Clin Exp Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.244","article-title":"Decreased expression of acetylcholine esterase in cholinergic urticaria with hypohidrosis or anhidrosis","volume":"134","author":"Sawada","year":"2014","journal-title":"J Invest Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1956.tb12819.x","article-title":"Cholinesterase levels in the skin in cholinogenic urticaria and pruritus","volume":"68","author":"Magnus","year":"1956","journal-title":"Br J Dermatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03845.x","article-title":"Cholinergic urticaria associated with acquired generalized hypohidrosis: report of a case and review of the literature","volume":"143","author":"Itakura","year":"2000","journal-title":"Br J Dermatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04017.x","article-title":"Cholinergic urticaria: pathogenesis-based categorization and its treatment options","volume":"26","author":"Nakamizo","year":"2012","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-017-0418-6","article-title":"Cholinergic urticaria: epidemiology, physiopathology, new categorization, and management","volume":"28","author":"Fukunaga","year":"2018","journal-title":"Clin Auton Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/all.12901","article-title":"Definition, aims, and implementation of GA(2) LEN urticaria centers of reference and excellence","volume":"71","author":"Maurer","year":"2016","journal-title":"Allergy"},{"key":"B24","article-title":"Evaluation and relevance of atopic basic and minor features in patients with atopic dermatitis and in the general population","volume":"144","author":"Diepgen","year":"1989","journal-title":"Acta Derm Venereol Suppl (Stockh)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jdermsci.2014.04.007","article-title":"Development of a standardized pulse-controlled ergometry test for diagnosing and investigating cholinergic urticaria","volume":"75","author":"Altrichter","year":"2014","journal-title":"J Dermatol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1016\/j.jaci.2016.05.026","article-title":"Antihistamine updosing reduces disease activity in patients with difficult-to-treat cholinergic urticaria","volume":"138","author":"Koch","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1994.tb01167.x","article-title":"Dermatology life quality index (DLQI)\u2013a simple practical measure for routine clinical use","volume":"19","author":"Finlay","year":"1994","journal-title":"Clin Exp Dermatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13102","article-title":"Development and validation of the cholinergic urticaria quality-of-Life questionnaire (CholU-QoL)","volume":"48","author":"Ruft","year":"2018","journal-title":"Clin Exp Allergy"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/j.jaci.2013.12.1076","article-title":"Development and validation of the urticaria control test: a patient-reported outcome instrument for assessing urticaria control","volume":"133","author":"Weller","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2009.01364.x","article-title":"Recommendations for performing and evaluating the results of the minor test according to a sweating intensity visual scale","volume":"36","author":"Hexsel","year":"2010","journal-title":"Dermatol Surg"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.188","article-title":"Cholinergic urticaria: studies on the muscarinic cholinergic receptor M3 in anhidrotic and hypohidrotic skin","volume":"130","author":"Sawada","year":"2010","journal-title":"J Invest Dermatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24899","article-title":"Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma","volume":"116","author":"Hino","year":"2010","journal-title":"Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/dth.13647","article-title":"Regular sweating activities for the treatment of cholinergic urticaria with or without acquired idiopathic generalized anhidrosis","volume":"33","author":"Minowa","year":"2020","journal-title":"Dermatol Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.jaci.2018.08.050","article-title":"Real-life treatment of cholinergic urticaria with omalizumab","volume":"143","author":"Altrichter","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15808","article-title":"Neural control of sweat secretion: a review","volume":"178","author":"Hu","year":"2018","journal-title":"Br J Dermatol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1986.tb05166.x","article-title":"Effects of locally administered anticholinesterase agents on the secretory response of human eccrine sweat glands to acetylcholine and carbachol","volume":"21","author":"Longmore","year":"1986","journal-title":"Br J Clin Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2021.05.001","article-title":"Acetylcholine-induced whealing in cholinergic urticaria - what does it tell us","volume":"103","author":"Altrichter","year":"2021","journal-title":"J Dermatol Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/273473a0","article-title":"Release of histamine from rat mast cells by acetylcholine","volume":"273","author":"Fantozzi","year":"1978","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013205","article-title":"Characteristics of histamine release evoked by acetylcholine in isolated rat mast cells","volume":"301","author":"Blandina","year":"1980","journal-title":"J Physiol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1016\/j.celrep.2018.07.082","article-title":"Muscarinic acetylcholine receptors Chrm1 and Chrm3 are essential for REM sleep","volume":"24","author":"Niwa","year":"2018","journal-title":"Cell Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s00429-011-0376-z","article-title":"Hippocampal microRNA-132 mediates stress-inducible cognitive deficits through its acetylcholinesterase target","volume":"218","author":"Shaltiel","year":"2013","journal-title":"Brain Struct Funct"},{"key":"B42","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neubiorev.2021.04.031","article-title":"Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis","volume":"127","author":"Zheng","year":"2021","journal-title":"Neurosci Biobehav Rev"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.3390\/ijms18061316","article-title":"Drug hypersensitivity and desensitizations: Mechanisms and new approaches","volume":"18","author":"de Las Vecillas Sanchez","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.10-OA-0269","article-title":"Rapid desensitization with autologous sweat in cholinergic urticaria","volume":"60","author":"Kozaru","year":"2011","journal-title":"Allergol Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.12.772","article-title":"An open-label, proof-of-Concept study of lirentelimab for antihistamine-resistant chronic spontaneous and inducible urticaria","volume":"149","author":"Altrichter","year":"2021","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.955161\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T13:13:18Z","timestamp":1659100398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.955161\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2022.955161"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.955161","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]},"article-number":"955161"}}