{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:07:04Z","timestamp":1790078824400,"version":"4.0.1"},"reference-count":10,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Nitric oxide (NO) donors reliably provoke cluster headache attacks in susceptible individuals, supporting an important role of NO signalling in cluster headache pathophysiology. Headache following accidental nitric acid inhalation has previously been reported; however, de novo chronic cluster headache following inhalational exposure to nitric acid and nitrogen oxides has not been described. We report a case in which the close temporal relationship and clinical circumstances raise the possibility of secondary headache attribution according to the principles of the International Classification of Headache Disorders, 3rd edition (ICHD-3). Methods: We describe the clinical course of a 54-year-old man without a previous history of cluster headache or comparable recurrent headache attacks who developed a novel headache immediately following occupational inhalational exposure involving nitric acid and nitrogen oxides. Clinical characteristics, temporal evolution, diagnostic findings and treatment response were evaluated according to ICHD-3 criteria and interpreted in the context of published evidence concerning nitric acid-induced headache and NO-provoked cluster headache. Results: Following the inhalational event in September 2024, a novel headache occurred immediately and subsequently evolved into a characteristic trigeminal autonomic cephalalgia. From December 2024 onward, the patient experienced 5\u20138 daily attacks of severe to very severe, strictly left-sided periorbital\u2013temporal pain lasting 15\u201320 min, accompanied by ipsilateral lacrimation and marked restlessness. The disorder persisted without sustained remission for more than one year, fulfilling the phenotypic criteria of chronic cluster headache. Cranial magnetic resonance imaging revealed no structural cause. According to ICHD-3 attribution principles, the de novo onset in close temporal relation to an exposure capable of causing headache supports classification as secondary headache. This attribution is further supported biologically by the established ability of NO donors to provoke cluster headache attacks and activate trigeminovascular mechanisms. Conclusions: This case describes a de novo chronic cluster headache phenotype temporally associated with occupational inhalational exposure to nitric acid and nitrogen oxides. The temporal relationship and experimental evidence concerning TRPA1-mediated chemosensory activation, NO\u2013cGMP signalling, CGRP release and trigeminovascular activation provide biological plausibility for a possible exposure-related association. However, neither a toxicological causal relationship nor the proposed transition to persistent trigeminal\u2013autonomic sensitization can be established from this single case.<\/jats:p>","DOI":"10.3390\/jcm15187255","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["De Novo Chronic Cluster Headache Following Occupational Inhalational Exposure to Nitric Acid and Nitrogen Oxides: A Case Report"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4283-6936","authenticated-orcid":false,"given":"Carl H.","family":"G\u00f6bel","sequence":"first","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"},{"name":"Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, 24149 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svea","family":"Freitag","sequence":"additional","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Heinze","sequence":"additional","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Heinze-Kuhn","sequence":"additional","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8637-9637","authenticated-orcid":false,"given":"Anna","family":"Cirkel","sequence":"additional","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"},{"name":"Department of Neurology, University Hospital Schleswig-Holstein, Campus L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2163-112X","authenticated-orcid":false,"given":"Hartmut","family":"G\u00f6bel","sequence":"additional","affiliation":[{"name":"Kiel Migraine and Headache Center, Heikendorfer Weg 9-27, 24149 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Headache Classification Committee of the International Headache Society The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Arnold","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1046\/j.1468-2982.2003.00553.x","article-title":"Nitric oxide pathway and response to nitroglycerin in cluster headache patients: Plasma nitrite and citrulline levels","volume":"23","author":"Costa","year":"2003","journal-title":"Cephalalgia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1001\/archneur.1968.00480050057005","article-title":"Nitroglycerin as a provocative agent in cluster headache","volume":"19","author":"Ekbom","year":"1968","journal-title":"Arch. 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Neurol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:26:49Z","timestamp":1790076409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":10,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187255"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187255","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]}}}