{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T17:50:44Z","timestamp":1772387444597,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>The axon\u2010reflex flare response is a reliable method for functional assessment of small fibers in diabetic peripheral neuropathy (DPN), but broad adoption is limited by the time requirement. The aims of this study were to (1) assess diagnostic performance and optimize time required for assessing the histamine\u2010induced flare response and (2) associate with established parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 60 participants with type 1 diabetes with (<jats:italic>n<\/jats:italic>\u2009=\u200933) or without (<jats:italic>n<\/jats:italic>\u2009=\u200927) DPN participated. The participants underwent quantitative sensory testing (QST), corneal confocal microscopy (CCM), and flare intensity and area size assessments by laser\u2010Doppler imaging (FLPI) following an epidermal skin\u2010prick application of histamine. The flare parameters were evaluated each minute for 15\u2009min, and the diagnostic performance compared to QST and CCM were assessed using area under the curve (AUC). Minimum time\u2010requirements until differentiation and to achieve results comparable with a full examination were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Flare area size had better diagnostic performance compared with CCM (AUC 0.88 vs. 0.77, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and QST (AUC 0.91 vs. 0.81, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) than mean flare intensity, and could distinguish people with and without DPN after 4\u2009min compared to after 6\u2009min (both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Flare area size achieved a diagnostic performance comparable to a full examination after 6 and 7\u2009min (CCM and QST respectively, <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05), while mean flare intensity achieved it after 5 and 8\u2009min (CCM and QST respectively, <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The flare area size can be evaluated 6\u20137\u2009min after histamine\u2010application, which increases diagnostic performance compared to mean flare intensity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27925","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T11:48:19Z","timestamp":1688039299000},"page":"308-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Optimizing examination time and diagnostic performance of the histamine\u2010induced axon\u2010reflex flare response in diabetes"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-1328","authenticated-orcid":false,"given":"Johan","family":"R\u00f8ikjer","sequence":"first","affiliation":[{"name":"Steno Diabetes Center North Denmark Aalborg University Hospital  Aalborg Denmark"},{"name":"Integrative Neuroscience Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-8962","authenticated-orcid":false,"given":"Suganthiya Santhiapillai","family":"Croosu","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Radiology Aalborg University Hospital  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-3409","authenticated-orcid":false,"given":"Mette Krabsmark","family":"Borbjerg","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark Aalborg University Hospital  Aalborg Denmark"},{"name":"Integrative Neuroscience Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6160-5519","authenticated-orcid":false,"given":"Tine Maria","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Radiology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-0070","authenticated-orcid":false,"given":"Jens Br\u00f8ndum","family":"Fr\u00f8kj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Radiology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1579","authenticated-orcid":false,"given":"Lars","family":"Arendt\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP) Aalborg University  Aalborg Denmark"},{"name":"Department of Medical Gastroenterology, Mech\u2010Sense Aalborg University Hospital  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-3403","authenticated-orcid":false,"given":"Niels","family":"Ejskjaer","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark Aalborg University Hospital  Aalborg Denmark"},{"name":"Clinical Medicine and Endocrinology Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-2028","authenticated-orcid":false,"given":"Carsten Dahl","family":"M\u00f8rch","sequence":"additional","affiliation":[{"name":"Integrative Neuroscience Aalborg University  Aalborg Denmark"},{"name":"Center for Neuroplasticity and Pain (CNAP) Aalborg University  Aalborg 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