Contact allergy in Swedish professional ice hockey players.

BACKGROUND: Professional ice hockey players may contract irritant and allergic contact dermatitis. AIMS: To investigate the presence of contact allergy (CA) in professional ice hockey players in Sweden. METHODS: Ten teams from the two top leagues were assessed for potential occupational exposure to sensitizers. Exactly 107 players were patch tested with an extended baseline series and a working series, in total 74 test preparations. The CA rates were compared between the ice hockey players and controls from the general population and dermatitis patients. RESULTS: One out of 4 players had at least one contact allergy. The most common sensitizers were Amerchol L 101, nickel and oxidized limonene. CA was as common in the ice hockey players as in dermatitis patients and significantly more common than in the general population. Fragrances and combined sensitizers in cosmetic products (fragrances + preservatives + emulsifier) were significantly more common in ice hockey players compared with the general population. CONCLUSION: The possible relationship between CA to fragrances and cosmetic products on the one hand and the presence of dermatitis on the other should be explored further.

Patterns of simultaneous contact allergies in patients with contact sensitization to oxidised linalool and oxidised limonene.

BACKGROUND: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. OBJECTIVES: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. METHODS: A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. RESULTS: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p-value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p-value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01-5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. CONCLUSIONS: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co-sensitization of the cosmetic allergens.

d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II.

BACKGROUND: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-ß-cyclodextrin (HßDL) during treatment with Doxo, focusing on the arrhythmic feature. METHODS: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HßDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. RESULTS: Electrocardiograms showed that administration of 10 mg/kg of HßDL prevented Doxo-induced widening of the QRS complex and QT interval. HßDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. CONCLUSION: Our results show that 10 mg/kg of ßDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation.

Patch testing hydroperoxides of limonene and linalool in consecutive patients-Results of the IVDK 2018-2020.

BACKGROUND: Hydroperoxides of limonene (Lim-OOHs) and linalool (Lin-OOHs) are potent contact sensitizers. OBJECTIVES: To investigate the prevalence of positive patch test (PT) reactions to Lim-OOHs and Lin-OOHs in consecutive patients, their demographic factors and concomitant reactions. METHODS: Between 7/2018 and 12/2020, Lim-OOHs 0.3% pet. and Lin-OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim-OOHs and Lin-OOHs. RESULTS: Positive PT results to Lim-OOHs (n = 170, 3.1%) and Lin-OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim-OOHs and Lin-OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides. CONCLUSION: The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended.

Efeitos do D-limoneno no metabolismo energético de camundongos C57/Bl6 com obesidade induzida pela dieta / Effects of D-limonene on the energy metabolism of C57/Bl6 mice with diet-induced obesity

A obesidade está associada ao desenvolvimento de doenças crônicas não transmissíveis como hipertensão, resistência insulínica, dislipidemia e esteatose hepática. O consumo de compostos bioativos impacta na manutenção da saúde e na prevenção de risco de desenvolvimento dessas doenças. Entre os compostos bioativos, os monoterpenos são pouco investigados, apesar da literatura demonstrar efeitos promissores desses compostos sobre o metabolismo. O D-limoneno, o principal monoterpeno encontrado na laranja, é caracterizado por possuir efeitos hipolipemiantes, anti-inflamatórios e anti-obesogênicos. Estudos in vitro e in vivo descrevem sua capacidade de promover a ß-oxidação de ácidos graxos em adipócitos e redução da inflamação. Este estudo teve como objetivo investigar o efeito do D-limoneno no metabolismo e inflamação em um modelo de obesidade induzida por dieta. Para isso, quarenta camundongos machos (C57/Bl6) de 11 semanas de idade, foram distribuídos em 4 grupos, sendo que um dos grupos recebeu ração normolipídica e os demais, ração hiperlipídica. O D-limoneno foi suplementado na ração de dois grupos que receberam dieta hiperlipídica nas concentrações de 0,1%, e 0,8%. Considerando-se a ingestão alimentar dos animais, a ração suplementada com 0,1% D-limoneno correspondeu à ingestão de 0,15 g/kg/dia e ração com 0,8% de D-limoneno correspondeu a 1,3 g/kg/dia. Os animais tiveram o peso e a ingestão alimentar monitorados ao longo da intervenção com duração de 7 semanas. Os camundongos que receberam D-limoneno a 0,1% apresentaram menor ganho de peso e de acúmulo de tecido adiposo, comparado com os animais sem suplementação alimentados com a dieta hiperlipídica. Além disso, o D-limoneno promoveu a diminuição da concentração plasmática de marcadores inflamatórios incluindo TNF-α, INF-γ e IL-6 nos animais dos grupos que foram suplementados com D-limoneno. Entretanto, não houve diferença nos marcadores bioquímicos e metabólicos. Uma limitação do estudo foi o fato das complicações metabólicas associadas ao modelo de obesidade não terem sido plenamente estabelecidas, dados o alojamento individual, à curta duração da exposição à ração hiperlipídica e idade dos animais no início da suplementação. Esse fato pode ter dificultado a observação dos efeitos do D-limoneno na reversão dos parâmetros que seriam normalmente deteriorados pelo desenvolvimento da obesidade. Concluímos que o D-limoneno pode interferir no metabolismo energético, com possível efeito anti-obesogênico e anti-inflamatório. Devido às limitações do modelo, são necessários mais estudos para confirmar esses resultados

Obesity is associated with the development of chronic non-communicable diseases such as hypertension, insulin resistance, dyslipidemia, and hepatic steatosis. The intake of dietary bioactive compounds is associated with the maintenance of health and the prevention of chronic diseases. Among the group of bioactive compounds, monoterpenes are poorly investigated, in spite of several reports of their promising effects on metabolism. D-limonene is the main monoterpene found in oranges, known for its hypolipemic, anti-inflammatory, and anti-obesogenic effects. in vitro and in vivo studies associate D-limonene to increased ß-oxidation of fatty acids in adipocytes and reduced inflammation. This study aimed at investigating the effects of D-limonene on metabolism and inflammation in a diet-induced obesity model. For this purpose, forty male mice (C57/Bl6) were distributed in 4 groups, with one group receiving a normolipidic diet and the others, a high-fat diet. D-limonene was supplemented in the diets of two groups that received high-fat diet at the concentrations of 0.1% and 0.8%. Considering the feed intake, mice receiving D-limonene supplementation at 0.1% ingested in average 0.15 g/kg/day, while the mice receiving the supplemmentation at 0.8%, ingested approximately 1.3 g of D-limonene /kg/day. The animals had their weight and food intake monitored throughout the intervention. Mice that received Dlimonene supplementation at 0.1% showed reduced weight gain and accumulation of adipose tissue compared to the non-supplemented mice fed the high-fat diet. In addition, D-limonene promoted a decrease in hepatic inflammatory markers including TNF-α, INF-γ, and IL-6. However, there was no difference in biochemical and metabolic markers. A limitation of the study was that the metabolic complications associated with the obesity model were not fully established, probably due to the age at the start of the protocol (11 weeks), individual housing and short duration of the exposure to the high-fat feed. This fact may have prevented the observation of the positive effects of D-limonene in reversing parameters that would normally be impaired by the development of obesity. We conclude that D-limonene may interfere in energy metabolism, with a possible anti-obesogenic and anti-inflammatory effect. Due to the limitations of the model, further studies are needed to confirm these findings

Limonene and linalool hydroperoxides review: Pros and cons for routine patch testing.

Limonene and linalool are among the most common fragrance terpenes used in everyday products. They are pre-haptens, forming hydroperoxides (Lim-OOHs, Lin-OOHs) upon oxidation and inducing frequent positive patch test reactions in patients with dermatitis, and yet they are not routinely tested in Europe. This review evaluates current patch testing with Lim-OOHs and Lin-OOHs by asking whether hydroperoxide patch testing is warranted, examining the difficulties or challenges related to reading and interpreting hydroperoxide patch test results with currently available material, and assessing their relevance. Studies are increasingly pointing to high percentages of positive reactions in patients consecutively patch tested with these oxidized products. An association between a positive clinical history and a strong patch test reaction has been described, but problems with doubtful/irritant reactions have also been reported. Considering the high frequency of relevant positive reactions, the incorporation of Lim-OOHs 0.3% and Lin-OOHs 1% in the baseline series may be justified. Since exposure, sensitization, and elicitation limits of Lim-OOHs and Lin-OOHs in the products still need to be better determined, an assessment of previous exposure, possible sensitizations, and reactions may help to improve the clinical assessment.

Allergic contact dermatitis from ("hypoallergenic") adhesives containing D-limonene.

BACKGROUND: Besides being a potential component of (some species of) colophonium, D-limonene is also used as a tackifier in the production of adhesives. Hydroperoxides of limonene are well-known skin sensitizers. OBJECTIVES: To show that D-limonene may be present in colophonium-containing but also colophonium-free ("hypoallergenic") adhesives, and that patients suffering from allergic contact dermatitis (ACD) from both types of adhesives might display positive patch test reactions to limonene hydroperoxides in this regard. METHODS: Five patients with suspected ACD from adhesives were patch tested to the baseline series (containing limonene hydroperoxides 0.3 and 0.2% pet.), additional series and, if available, to the culprit adhesives. The adhesives labelled as containing colophonium (n = 3) or free from it (n = 2) were analysed with gas chromatography - mass spectrometry (GC-MS) for the presence of D-limonene. RESULTS: All five patients sensitised to adhesives had (strong) positive patch test reactions to limonene hydroperoxides. The presence of D-limonene, and/or related components, could be demonstrated in all three colophonium-containing and, surprisingly, also in two colophonium-free ("hypoallergenic") tapes. CONCLUSIONS: D-limonene may be present in both regular and "hypoallergenic" adhesives, with limonene hydroperoxides potentially contributing to ACD from such medical devices. The use of fragrance chemicals in adhesives deserves further research.

What Is New in Occupational Allergic Contact Dermatitis in the Year of the COVID Pandemic?

PURPOSE OF REVIEW: This article aims to summarize some recent trends in occupational allergic contact dermatitis (ACD), including dermatitis related to pandemic-level personal protective equipment in healthcare workers, hazards patients may experience when working from home, and occupational perspectives on the recent American Contact Dermatitis Society (ACDS) allergens of the year and ACDS Core Allergen Series updates. RECENT FINDINGS: Recent ACDS Allergens of the Year may be particularly relevant to healthcare workers, including isobornyl acrylate, which is present in glucose sensors and propylene glycol present in hand cleansers and disinfectants. Lavender, limonene, and linalool, all of which are new additions to the ACDS Core Allergen Series, have been reported as causes for occupational ACD in massage therapists and aromatherapists. Isothiazolinone allergy continues to rise in both consumer and occupational settings. Finally, the COVID-19 pandemic has resulted in a wave of occupational ACD in healthcare workers to personal protective equipment, and revealed new potential allergens for individuals working from home. Occupational allergic contact dermatitis continues to exert a significant occupational disease burden. Remaining aware of the current trends in allergens may allow for earlier recognition, diagnosis, and treatment, subsequently helping our patients to work in healthier and safer environments.

Allergic Contact Dermatitis-Induced Stereospecificity.

Frequent allergens are known, but not whether allergens are enantiomer specific. Chemicals were tested on guinea pigs and humans to answer this question. Frullanoides showed evident allergic enantiospecificity, whereas the conclusion was shaded for α-methylene-γ-butyrolactone. A link between this chemical and chronic actinic dermatitis was proposed. No clear tendency to enantio-stereospecificity in inducing allergic contact dermatitis was ascertained. Future studies using contemporary analytical chemistry and new immunologic knowledge have to be undertaken to provide clearer mechanistic insights. This information may aid in attempts to decrease product allergenicity.

Fragrances: Contact Allergy and Other Adverse Effects.

This article gives an overview of fragrance allergy. The following subjects are discussed: composition of perfumes, contact with fragrances, diagnosing fragrance allergy, frequency of allergy, clinical picture of allergic contact dermatitis, culprit products, occupational contact dermatitis, and other adverse effects of fragrances. For diagnosing fragrance sensitization, personal products and a fragrance series may need to be tested in addition to the baseline series. In the general adult population, up to 4.5% may be allergic to fragrance materials, and in consecutive patients patch tested for suspected contact dermatitis, the frequency may reach 20% to 25%. More than 150 fragrances have caused contact allergy. The most frequent sensitizers are linalool and limonene hydroperoxides, hydroxyisohexyl 3-cyclohexene carboxaldehyde, treemoss and oakmoss absolute, isoeugenol, cinnamyl alcohol, and cinnamal. Culprit products for induction of sensitization are often deodorants, fine fragrances, and aftershaves. Occupational contact dermatitis from fragrances is seen occasionally. Other adverse effects are all discussed but occur infrequently.

Limonene Hydroperoxides.

Limonene is a fragrance widely used in cosmetics and household products. Until recently, contact allergy to limonene was considered rare because positive patch tests to it were infrequently observed. In recent years, however, it has been demonstrated that exposure of limonene to oxygen (air) results in the formation of a number of oxidation products, of which the hydroperoxides have a far stronger sensitizing potency than the pure compound. By routine testing of patients suspected of contact dermatitis with hydroperoxides of limonene, high frequencies of positive reactions were found, indicating that these chemicals are important fragrance allergens. It should be realized, however, that a number of "positive" reactions may well be false-positive, irritant responses.

Contact sensitization to hydroperoxides of limonene and linalool: Results of consecutive patch testing and clinical relevance.

BACKGROUND: Hydroperoxides of limonene and linalool are potent sensitizers. OBJECTIVES: To investigate the prevalence of contact allergy to both hydroperoxides of limonene and hydroperoxides of linalool, to report clinical relevance, and to investigate patient demographics. METHODS: A total of 821 patients (35.6% male, mean age 42.4 years ± 17.8 years) were consecutively patch tested with our departmental baseline series and our fragrance series, including hydroperoxides of limonene 0.3% pet. and hydroperoxides of linalool 1.0% pet. The clinical relevance was assessed for all positive reactions. RESULTS: Positive patch test reactions to hydroperoxides of limonene and to hydroperoxides of linalool were observed in 77 patients (9.4%, 95% confidence interval [CI]: 7.4%-11.4%) and in 96 patients (11.7%, 95%CI: 9.5%-13.9%), respectively; 38 of these patients (4.6%, 95%CI: 3.2%-6.0%) reacted to both. Most reactions were considered to be possibly or probably clinically relevant (66.3% and 68.8%, respectively), and a small proportion were deemed to be of certain clinical relevance (18.2% and 19.8%, respectively). CONCLUSION: As compared with previous studies, high numbers of positive reactions to both hydroperoxides of limonene and hydroperoxides of linalool were observed, the majority of which were clinically relevant, supporting their inclusion in the European baseline series.

Recommendation to test limonene hydroperoxides 0·3% and linalool hydroperoxides 1·0% in the British baseline patch test series.

BACKGROUND: There is a significant rate of sensitization worldwide to the oxidized fragrance terpenes limonene and linalool. Patch testing to oxidized terpenes is not routinely carried out; the ideal patch test concentration is unknown. OBJECTIVES: To determine the best test concentrations for limonene and linalool hydroperoxides, added to the British baseline patch test series, to optimize detection of true allergy and to minimize irritant reactions. METHODS: During 2013-2014, 4563 consecutive patients in 12 U.K. centres were tested to hydroperoxides of limonene in petrolatum (pet.) 0·3%, 0·2% and 0·1%, and hydroperoxides of linalool 1·0%, 0·5% and 0·25% pet. Irritant reactions were recorded separately from doubtful reactions. Concomitant reactions to other fragrance markers and clinical relevance were documented. RESULTS: Limonene hydroperoxide 0·3% gave positive reactions in 241 (5·3%) patients, irritant reactions in 93 (2·0%) and doubtful reactions in 110 (2·4%). Linalool hydroperoxide 1·0% gave positive reactions in 352 (7·7%), irritant reactions in 178 (3·9%) and doubtful reactions in 132 (2·9%). A total of 119 patients with crescendo reactions to 0·3% limonene would have been missed if only tested with 0·1% and 131 patients with crescendo reactions to 1·0% linalool would have been missed if only tested with 0·25%. In almost two-thirds of patients with positive patch tests to limonene and linalool the reaction was clinically relevant. The majority of patients did not react to any fragrance marker in the baseline series. CONCLUSIONS: We recommend that limonene hydroperoxides be tested at 0·3% and linalool hydroperoxides at 1·0% in the British baseline patch test series.