BACKGROUND: Carvone (l-carvone) is a mint-tasting flavour additive that most of us is exposed to and can cause allergic contact reactions.

OBJECTIVES: To analyse the frequency and the relevance of positive carvone reactions in a dermatitis population.

METHOD: A retrospective analysis of dermatitis patients consecutively tested with carvone from 2017 to 2021. Data were retrieved from the department's patch-test database.

RESULTS: Of 3554 patients tested with carvone, 28 (0.79%) had a positive reaction. Carvone-positive patients had higher mean age, were significantly more likely female (p < 0.001) and had often an intraoral/lip involvement (p < 0.001). In the carvone-positive group, 50% (n = 14) had a relevant reaction, and in 4 of 14, the relevance was first revealed after test reading. Of the carvone-positive patients, 18 of 28 did not have a coexisting allergy to a fragrance/flavour allergen and of these 44% had a relevant allergy.

CONCLUSIONS: The study suggests that a significant fraction of relevant carvone contact allergies may be overlooked if the allergen is not tested. Furthermore, as the exposure is widespread, inclusion of carvone in the Swedish baseline series may be justified even if the contact allergy prevalence is below 1%.

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.

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.

INTRODUCTION Carvone (l‐carvone), a mint‐tasting flavour often found in toothpaste, is considered a weak contact allergen and the prevalence of positive patch tests to carvone among dermatitis patients is 1.6–2.8%. However, contact allergy to carvone is more prevalent (12%) in patients with oral lichen planus (OLP) or oral lichenoid lesions (OLL) and patients with positive patch tests to carvone often have OLP/OLL. OLP is considered an autoimmune disease but the cause/relationship to carvone contact allergy is unclear. The aim of this study was to investigate how carvone affects the oral mucosa and peri‐oral area in sensitized individuals through a use test with toothpaste containing carvone. MATERIALS AND METHODS 16 allergic subjects with a positive patch test to carvone, 18 subjects with OLP/OLL only and 3 healthy controls were patch tested one week prior to the use test. Patch test preparations comprised test toothpaste, ± 1% carvone, and 10 different dilutions of carvone in acetone, 5%–0.000158%. During the month‐long use test, subjects were instructed to use 1 ml toothpaste twice daily and they were examined fortnightly. 5 allergic subjects received non‐flavoured toothpaste and all other subject received the same non‐flavoured toothpaste with 1% carvone added. Clinical signs were assessed with a mucosal scoring system by Escudier et al. and the subjects’ quality of life (QoL) were measured before and after the use test with a 49‐item questionnaire – oral health impact profile (OHIP‐49). RESULT Positive patch tests to carvone, ranging between ‘+’ and ‘++’, were recorded in 8 allergic subjects and 2 had late reactions (day 19 and 21). Five allergic subjects reacted to toothpaste with carvone. A majority of the allergic subjects had OLP/OLL at baseline (13/16). In four allergic subjects, the use test was terminated ahead of time due to mucosal/cutaneous lesions from carvone toothpaste. Allergic subjects reacted with aggravated OLL (7/10) and two displayed peri‐oral eczema. The mucosal score was significantly worse in allergic subjects receiving carvone toothpaste compared to those receiving non‐flavoured toothpaste. Additionally, allergic subjects with OLP/OLL had a worsening of mucosal score compared to subjects with OLP/OLL only. The difference of QoL, before and after the use test, showed the same pattern as the mucosal scores. CONCLUSION When exposed to carvone, allergic individuals may react with either aggravated OLL and/or peri‐oral eczema. These lichenoid lesions mimic OLP and therefore allergic individuals are at risk of not being investigated with regard to flavour contact allergy.

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.

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.

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.

A predominant part of the Swedish population uses toothpaste daily. Besides fluoride preventing caries, toothpastes usually have flavours added to make the user feel fresh and clean. Among potential allergens in toothpastes, flavours are the most common cause of oral or perioral lesions. Flavour concentrations vary between 0.3% and 2.0%, and usually several types of mint are used; however, the true composition of the added aroma is seldom known. l‐Carvone is a mint‐tasting flavour that can act as a potential allergen. Previous findings have shown that approximately 4% of a patch‐tested selected population in southern Sweden had a positive reaction to l‐carvone and half of them had oral inflammatory lesions, notably oral lichenoid lesions. Among patients with lichenoid lesions approximately 12% have a contact allergy to l‐carvone and several other contact allergies are more common in this patient group. The concentration of l‐carvone in toothpastes available for sale on the Swedish market was investigated. Sixty‐six different toothpastes were selected from local stores and pharmacies. l‐Carvone content was extracted from toothpastes using n‐heptane. The sample extracts were separated on a silica column using straight‐phase high‐performance liquid chromatography and a diode‐array detector. Three samples of each toothpaste were analysed, and the mean concentration and relative SD were calculated. Detectable levels of l‐carvone (0.00005–0.35%) were found in 63 of the toothpastes. l‐Carvone was found in half of the toothpastes (n = 32) at a concentration of ≥ 0.01%. A higher concentration (≥ 0.1%) was found in 18% (n = 12). Of the top six toothpastes with highest l‐carvone content (0.15–0.35%), one was intended for use by children. Two of the toothpastes were stated as having fruit flavour, but there were still detectable levels of l‐carvone (0.0003% and 0.00007%, respectively). l‐Carvone was below detectable levels in three of the toothpastes, where one was stated as being without flavour. l‐Carvone is present in virtually all toothpastes on the Swedish market. It is therefore likely that l‐carvone in toothpastes is important for the induction of sensitization to l‐carvone, as contact allergy to l‐carvone is over‐represented in patch‐tested individuals with oral lichenoid reactions. However, are the concentrations demonstrated relevant for causing reactions or aggravating already existing lesions?

Background: Carvone (L-carvone) is naturally found in spearmint oil and is considered a mild skin sensitizer. It commonly serves as a flavoring agent in toothpaste and other mint tasting products. There is recent evidence that carvone may have a relationship with oral lichenoid lesions (OLL). Objectives: The aim was to study the frequency of carvone contact allergy in a Swedish patch test population at the Malmö clinic and to investigate the characteristics of the group with special reference to OLL. Methods: A 15-year retrospective study including all consecutive patients tested positive for carvone with different series containing carvone. The patients’ records were reviewed in regard to symptoms, previous diagnoses, type of referrer and contact allergy. Results: Three thousand eight hundred and twelve patients were patch tested to different series containing l-carvone, the most common being the Swedish dental series. One hundred and forty-three patients (3.7%) were positive to carvone whereof 138 patients had records available for review. Of the carvone-sensitized patients, 46.9% had suspected or previously diagnosed OLL and 8.0% had dermal or genital lichen planus. The majority of the carvone-sensitized patients had also positive reactions to several other allergens. The most common allergens were spearmint oil (39.9%), gold (35.5%) fragrance-mix (17.4%) and nickel (15.5%). The majority of the carvone-sensitized patients with allergy to gold (30/49) or allergy to mercury (16/18) also had OLL. The male-to-female ratio was 1:4.75 among the carvone-sensitized patients compared to 1:2.55 in the overall test groups. Conclusions: The frequency of patients sensitized to carvone seems to correspond with previous findings. Concomitant contact allergy to gold or mercury was often associated with OLL and these patients were often referred for suspected allergy from d ental restorations. The data together with conclusions in recent reports suggests a relationship between OLL and l-carvone contact allergy. The relationship is yet unknown and needs further investigation.