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Oral contact allergy to carvone: with a focus on oral lichen
Malmö University, Faculty of Odontology (OD).ORCID iD: 0000-0003-3984-0210
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Avhandlingen undersöker karvon (l-karvon), ett mintsmakandearomämne, och hur kontaktallergi mot karvon yttrar sig. Karvonfinns framför allt i grönmynta/spearmint, men aromämnet kan ävenframställas ur limonen, ett citrondoftande parfymämne. Karvonär ett svagt kontaktallergen och allergiförekomsten är bara någraprocent i lapptestade populationer. Kontaktallergi mot karvon har ienstaka studier visat sig vara vanligare hos individer med lichenoidamunslemhinneförändringar som oral lichen planus. Avsikten medavhandlingen har varit att studera detta samband vidare.I studie I analyserades mängden karvon i 66 tandkrämer inköptai Sverige. Även innehållsförteckningarna studerades. Lagstiftningenoch innehållsmärkningen av karvon diskuterades. Karvonmängdeni tandkräm varierar stort, 0,35–0,00005 %, men återfinns i allatandkrämer med någon form av smak, även fruktsmak. De uppmättamängderna är under det tillåtna gränsvärdet för att inte kunna gekontaktallergi men några av tandkrämerna innehåller tillräckligtmycket karvon för att ge en reaktion hos redan kontaktallergiskaindivider.I studie II studerades journal- och databasdata från alla patienteri södra Sverige som testats positivt för kontaktallergi mot karvonmellan 1996-2016. Gruppdata jämfördes med andra lapptestadegrupper som inte var karvonallergiska, bl.a. en matchad grupp(ålder, kön, tidpunkt för test och liknande besvär). Karvonallergiskapatienter hade hög medelålder och var ofta kvinnor. De hade oftabesvär från munhålan och över hälften hade orala lichenoidaförändringar. I den matchade jämförelsen hade karvonallergiskapatienter betydligt mer orala lichenoida förändringar jämfört medpatienter utan karvonallergi.I studie III undersöktes hur allergi mot karvon i tandkräm yttrarsig. Karvonallergiska försökspersoner fick använda tandkrämmed 1 % karvon under en månads tid. Även försökspersonermed orala lichenoida förändringar och individer utan allergi ellermunslemhinneförändringar deltog. Slemhinnorna och läpparnaundersöktes vid tre tillfällen under det månadslånga användartestet.Förutom den kliniska bedömningen svarade försökspersonerna påen livskvalitetsenkät (S-OHIP-49) före och efter användartestet.Karvonallergiska individer exponerade för karvon i tandkrämreagerade med antingen eksem runt munnen eller med förvärradeorala lichenoida förändringar. Även livskvaliteten försämrades hosdessa individer.I studie IV undersöktes vävnadsprover från kind tagna påförsökspersonerna i studie III. Inflammationen och olika markörer förinflammationsceller undersöktes. Det gick inte att finna någon störreskillnad i inflammationsgrad eller i förekomst av inflammationscellermellan individer med karvonallergi och individer med oral lichenplanus förutom avseende förekomst av Langerhans celler, vilka varvanligare i vävnader från individer med oral lichen planus. Denlichenoida reaktionen som ses i de undersökta grupperna tolkasdärför som ett reaktionsmönster vilket kan ha olika orsaksursprung.För de flesta individer är karvon ett ofarligt smakämne trotslivslång exponering från tandkräm och andra mintsmakandeprodukter. Individer med orala lichenoida förändringar tycks dockha en ökad risk för karvonallergi och allergin förvärrar dessutomsymptomen från munslemhinnan. Karvonallergi kan både klinisktoch på vävnadsnivå likna oral lichen planus vilket normalt sett intekopplas samman med kontaktallergi. Karvonallergiska individerriskerar därför att inte bli diagnostiserade för sin allergi. Kliniker somhandhar patienter med oral lichen planus bör därför uppmärksammasom denna form av allergi.

Abstract [en]

This thesis examines carvone (l-carvone), a mint flavour, andcontact allergy to carvone with a focus on oral lichen. Carvone isa constituent of spearmint oil and is used to flavour toothpaste andfood. Like many flavours and fragrances, carvone may cause contactallergy, but the prevalence is low, between 1.6 and 2.8%. Affectedpatients often have perioral or oral signs. A couple of studies haveshown that patients with oral lichen planus or oral lichenoid lesionsoften have contact allergy to carvone but it is not known if theselichenoid lesions are a manifestation of contact allergy or part of theauto-immune disease, oral lichen planus.In paper I, the amount of carvone was measured in 66 toothpastesand the ingredient lists were studied. Carvone was detected in alltoothpastes with flavour, even fruit flavoured toothpaste, in up to0.35%. The measured concentrations were all within the safe use levelestimated to not induce contact allergy, but carvone concentrationsover 0.1% are high enough to elicit a reaction in already allergicindividuals. The regulation of carvone as a constituent in toothpastewas discussed.Registry data (age, sex, referring information and patch testsresults) on patients with a positive patch test reaction to carvonewas studied in paper II. Data was retrieved from 1996 to 2016 andwas compared with other patch tested groups not allergic to carvone.A matched comparison was also made between carvone-positive andcarvone-negative patients tested with the same test series. Patientswith contact allergy to carvone had a high mean age and were oftenwomen. According to the referrals, they often had oral signs and 57% had oral lichenoid lesions. In the matched comparison, oral(lichenoid) lesions were more common in carvone-positive patients.A provocation test (or use test) with carvone in toothpaste wasperformed in contact allergic subjects in paper III. Subjects with apositive patch test to carvone used toothpaste with 1 % carvoneduring a month. Subject with oral lichen and healthy controls alsoparticipated in the study. The oral mucosa and the perioral area wereexamined three times during the test. The subjects’ oral health-relatedquality of life was also assessed with a questionnaire (S-OHIP-49)before and after the use test. Carvone allergic patients exposedto toothpaste with carvone reacted with perioral eczema and/orincreased oral lichenoid lesions. They also had reduced quality of liferatings after the use test. It is concluded that the clinical appearance ofcontact allergy to flavour ingredients may mimic oral lichen planus.In paper IV, mucosal tissue samples from the subjects in paperIII were investigated with. The inflammatory pattern and immuneexpression were analysed in allergic subjects and subject with orallichen planus. No major differences were found between the groups;only Langerhans cells were more prevalent in oral lichen planus.For most of us, carvone is a harmless flavour despite the life-longexposure from toothpaste. However, for individuals with oral lichenthere is an increased risk to acquire contact allergy to carvone. Patientswith oral lichen and contact allergy to carvone may get aggravatedsymptoms when exposed to carvone. Contact allergic reactions tocarvone may imitate the clinical features of oral lichen planus andaffected patients are potentially left undiagnosed with contact allergyto carvone. Clinicians treating patients with OLP should be madeaware of this contact allergen and other soluble allergens.

Place, publisher, year, edition, pages
Malmö university. Faculty of Odontology , 2018. , p. 76
Series
Doctoral Dissertation in Odontology
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:mau:diva-7728DOI: 10.24834/978-91-7104-966-7Local ID: 26008ISBN: 978-91-7104-966-7 (print)ISBN: 978-91-7104-965-0 (print)OAI: oai:DiVA.org:mau-7728DiVA, id: diva2:1404668
Note

Paper III as manuscript in theses.

Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2023-06-21Bibliographically approved
List of papers
1. Quantification of l-carvone in toothpastes available on the Swedish market.
Open this publication in new window or tab >>Quantification of l-carvone in toothpastes available on the Swedish market.
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2017 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 77, no 4, p. 224-230Article in journal (Refereed)
Abstract [en]

BACKGROUND: Toothpastes have widespread use in the population, and contain flavours used to give a pleasant and often minty aroma. Flavours are prevalent allergens in toothpastes, and adverse reactions often present as perioral dermatitis or stomatitis. l-Carvone, a mint flavour found in spearmint oil, is one of these allergens. There are few studies on contact allergy to l-carvone, and some of them have indicated a positive relationship with oral lichenoid lesions. OBJECTIVES: To qualitatively and quantitatively investigate the presence of l-carvone in commercially available toothpastes on the Swedish market. METHODS: l-Carvone in 66 toothpastes was analysed with straight-phase high-performance liquid chromatography. The product labels were studied with regard to limonene. RESULTS: l-Carvone was found in 64 of 66 toothpastes (concentration: 0.00005-0.35%). In 10 of these, the concentration exceeded 0.1%. Higher concentrations of l-carvone were found if limonene was listed on the label. CONCLUSION: The majority of toothpastes on the Swedish market contain l-carvone, but the concentration hardly relates to the advertised flavour or labelled ingredients. It is hitherto unknown whether the found concentrations are sufficient for induction of contact allergy in individuals with healthy oral mucosa or in those with oral lichenoid lesions or other mucosal disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
contact allergy, contact dermatitis, high-performanceliquid chromatography, L-carvone, limonene, oral lichen planus, oral lichenoid lesions, toothpastes
National Category
Dentistry
Identifiers
urn:nbn:se:mau:diva-15837 (URN)10.1111/cod.12803 (DOI)000409110100005 ()28524256 (PubMedID)2-s2.0-85028733948 (Scopus ID)23457 (Local ID)23457 (Archive number)23457 (OAI)
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2024-06-18Bibliographically approved
2. Carvone Contact Allergy in Southern Sweden: A 21-year Retrospective Study.
Open this publication in new window or tab >>Carvone Contact Allergy in Southern Sweden: A 21-year Retrospective Study.
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2018 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 98, no 10, p. 938-942Article in journal (Refereed)
Abstract [en]

Carvone (l-carvone), a mint flavour in spearmint oil, is considered a mild skin sensitizer. Carvone-sensitization may be linked to oral/perioral signs and oral lichen planus, but studies are sparse. The prevalence of patch test reactions to carvone and relevant findings from the positive group were investigated. Records for patch-tested patients at the Malmö clinic, for the period 1996 to 2016, were studied. Carvone-positive and carvone-negative patients were compared regarding patch test data from baseline series and dental series. Dental series-tested carvone-positive patients were also compared with a matched group. A total of 147 out of 4,221 referred patients had a positive patch test to carvone. Sensitized patients had higher mean age and were primarily women; 73% had oral signs and 57% had oral lichen. Concomitant patch test reactions to gold, nickel and mercury were common. In the matched group-comparison carvone-positive patients had a higher frequency of oral lichen, but no difference was found in sensitization to gold and mercury.

Place, publisher, year, edition, pages
European Society of Dermatology and Psychiatry (ESDaP), 2018
Keywords
l-carvone, spearmint, patch test, allergens, contact allergy, oral lichen planus, oral lichenoid lesions
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:mau:diva-15301 (URN)10.2340/00015555-3009 (DOI)000447740400004 ()30085320 (PubMedID)2-s2.0-85056285172 (Scopus ID)26732 (Local ID)26732 (Archive number)26732 (OAI)
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2024-06-17Bibliographically approved
3. Use test with l-carvone in toothpaste on sensitized individuals.
Open this publication in new window or tab >>Use test with l-carvone in toothpaste on sensitized individuals.
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2023 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 88, no 6, p. 463-471Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The mint flavour carvone (l-carvone) is considered a weak contact allergen. However, contact allergy to carvone is more prevalent in patients with oral lichen planus or oral lichenoid lesions (OLP/OLL).

OBJECTIVE: Our aim was to investigate how carvone affects sensitized individuals through a use test with toothpaste containing carvone. Non-flavoured toothpaste served as control.

METHODS: Subjects were patch tested prior to the use test-14 subjects allergic to carvone (11 with OLP/OLL), 20 subjects with OLP/OLL and 3 healthy controls. The month-long use test comprised of using toothpaste twice daily. Subjects were examined fortnightly. Clinical signs were assessed with a mucosal scoring system. The subjects' oral health-related quality of life was measured with the oral health impact profile (OHIP-49).

RESULTS: Local reactions to the carvone toothpaste presented as aggravated OLL (7/10) and peri-oral eczema (2/10) in allergic subjects. They also had significantly higher mucosal and OHIP scores compared with those receiving non-flavoured toothpaste.

CONCLUSION: In sensitized individuals, oral exposure to carvone gives aggravated oral lesions and/or peri-oral eczema. The lesions mimic OLP and allergic individuals are therefore at risk of not being assessed with regard to flavour contact allergy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
OHIP-49, contact cheilitis, contact stomatitis, l-carvone, mucosal score, oral lichen planus, oral lichenoid lesion, toothpaste, use test
National Category
Dentistry
Identifiers
urn:nbn:se:mau:diva-58816 (URN)10.1111/cod.14302 (DOI)000952966100001 ()36929649 (PubMedID)2-s2.0-85150807683 (Scopus ID)
Available from: 2023-03-27 Created: 2023-03-27 Last updated: 2023-06-21Bibliographically approved
4. Molecular profiling of oral contact reactions to l-carvone and oral lichenoid reactions
Open this publication in new window or tab >>Molecular profiling of oral contact reactions to l-carvone and oral lichenoid reactions
2018 (English)Manuscript (preprint) (Other academic)
National Category
Dentistry
Identifiers
urn:nbn:se:mau:diva-17783 (URN)
Available from: 2020-07-14 Created: 2020-07-14 Last updated: 2022-06-27Bibliographically approved

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