The sesquiterpene lactone mix: A review of past, present and future aspects.

The sesquiterpene lactones (SLs) are secondary plant metabolites, which are widespread in the Compositae/Asteraceae plant family. The first SLs were detected more than 100 years ago, and allergic contact dermatitis from Compositae has been reported since the beginning of the 1900s, but it was not until the late 1960s and early 1970s that a collaboration between dermatologists, chemists and botanists led to the detection of SLs as the main allergens of Compositae plants. In the 1980s, the SL mix, consisting of equimolar amounts of alantolactone, costunolide and dehydrocostus lactone, was developed as a screening agent for Compositae sensitisation. Today, after inclusion of SL mix in the baseline series, the mean prevalence of reactions in Europe is around 1%, and in North America 0.8%. In countries outside Europe and North America, the prevalence ranges between 0% and 10.7%. The detection rate of SL mix is lower than that of some plant extracts, and ideally, SL mix should be supplemented with a mix of SLs from locally prevalent allergenic plants. The prevalence of positive reactions to SL mix suggests continued baseline testing in most European countries, North America, New Zealand, Australia and probably some Chinese centres.

Patch Testing with Propolis of Different Geographical Origins in a Baseline Series.

The chemical composition of propolis varies with geographical origin; however, it is not known whether this affects the frequency of contact allergy to propolis. In order to study the frequency of contact allergy to propolis of different geographical origins and concomitant reactions, 1,470 consecutive patients with dermatitis from Denmark, Lithuania and Spain were patch tested with propolis from China, Lithuania, North America and Sweden, and with a baseline series. Patch test reactions to any type of propolis ranged from 1.3% to 5.8%. There were no statistically significant differences in the frequency of positive reactions between the 4 types of propolis in the respective countries. Testing with a single commercially available type of propolis detects only approximately half of propolis-allergic patients. In patients allergic to propolis, concomitant reactions to Myroxylon pereirae resin, colophonium and Fragrance mix I were common, ranging from 12.5% to 50.0%.

Value of photo assessment in late patch test readings-A multicenter study from six European patch test clinics.

BACKGROUND: It is recommended that patch test readings include a day (D)7 reading. Substitution of the D7 reading with a photo may be a valid option. OBJECTIVES: To compare the sensitivity of digital photos at D7 to clinical readings, to assess the number of positive reactions appearing at D7 only (late reactions), and after D7 only (delayed reactions). METHODS: Patients patch tested in six European clinics were instructed to forward photos of the patch test reactions to the respective clinics at D7 (before attending the clinic) and at D21. Only allergens in the baseline series or TRUE Test were included in the data analysis. RESULTS: Two hundred ninety-three of 629 patients had a total of 599 positive reactions, with 6.3% occurring at D7 only. When substituting the D7 reading with a photo (90% submitted), 26.3% of late reactions were missed and nine false-positive reactions were found. Delayed reactions were detected in four patients at D21 (65.3% submitted). CONCLUSION: Our data show that if the D7 reading is not performed, 6.3% of positive reactions from the baseline series would be missed, and if substituting the D7 reading by digital photo, 26.3% late reactions would be missed. Delayed reactions seemed rare.

Compositae sensitization in Danish children and adolescents.

BACKGROUND: Compositae plant sensitization in children is relatively frequent. From 1995-2006, we found a prevalence of 1.8% sesquiterpene lactone (SL) mix/parthenolide patch test positives among consecutive eczema patients <18 years. OBJECTIVES: To report the results of patch test screening for Compositae sensitization in patients <18 years in the last 13 years. METHODS: Children and adolescents <18 years, diagnosed with Compositae sensitization between 2007 and 2019, were included. RESULTS: Among 388 children tested, 12 (3%) were Compositae-sensitized, and 11 (2.8%) had positive reactions to SL mix. Compositae mix 5% pet. elicited positive reactions in six of seven patients tested, and dandelion extract 2.5% pet. in six of 10 patients tested. The mean age of the five girls and seven boys was 9.4 years and 11.7 years, respectively. Eleven children had a personal and one a family history of atopy, and 11 children had hand eczema. Only two were mono-sensitized to Compositae. CONCLUSIONS: SL mix is a suitable screening agent among children and adolescents in our area, well supplemented with Compositae mix 5% and dandelion extract. The study emphasizes the importance of Compositae screening in children with a personal and/or family history of atopy, hand eczema or widespread airborne dermatitis, summer exacerbation, and plant exposure.

Contact sensitization to florists' chrysanthemums and marguerite daisies in Denmark: A 21-year experience.

BACKGROUND: Both florists' chrysanthemums (Chrysanthemum cultivars) and marguerite daisies (Argyranthemum frutescens [L.] Sch.Bip. and its varieties and cultivars) are popular ornamental plants in Denmark. OBJECTIVES: To present results of aimed patch testing with chrysanthemum and marguerite daisy extracts in Danish patients with Compositae sensitization. METHODS: The results of patch testing with chrysanthemum extract 3% petrolatum (pet.) and marguerite daisy extract 3% pet. (and possibly 1% pet.) from 1998 to 2019 were analyzed. RESULTS: Altogether, 111/191 (58%) patients tested positive to chrysanthemum extract and 104/179 (58%) tested positive to marguerite daisy. The majority was recreationally exposed, and most reactions were considered relevant. Feverfew extract 1% pet., Compositae mix 5% or 6% pet., or parthenolide 0.1% pet. may cross-react with chrysanthemum; Compositae mix seems to be best at detecting sensitization to marguerite daisy. CONCLUSIONS: In areas where exposure to chrysanthemum or marguerite daisies is prevalent, it is suggested to include extracts of these plants in the plant series to improve diagnosis of, and advice to, Compositae-allergic patients.

Fragrant and sticky allergens from the pinewood: Cohabiting and coreacting.

BACKGROUND: Tree moss (Pseudevernia furfuracea [L.] Zopf.), a lichen growing on conifers, is a frequent fragrance sensitizer. Previous studies have shown two subgroups of tree moss-allergic patients: a group sensitized to common allergens of tree and oak moss (Evernia prunastri), and another group sensitized to colophonium-derived allergens, which may contaminate tree moss extract. OBJECTIVES: To report the results of including tree moss extract in the baseline series and discuss the clinical implications. METHODS: Tree moss extract was included in the baseline series and sensitized patients were assessed for concomitant allergy to colophonium and oak moss, and the relevance of these reactions was analyzed. RESULTS: Altogether, 22 of 632 patients (3.5%) had positive reactions to tree moss. Eight patients were sensitized to tree moss only (among fragrance allergens) and 75% had relevant reactions to colophonium. Fourteen patients were sensitized to other fragrance allergens as well and 28.5% had relevant colophonium reactions. CONCLUSIONS: The prevalence of positive tree moss reactions is high enough to justify its inclusion in the baseline series. If tree moss is not included, patients with positive colophonium reactions should be informed of possible (false) cross-reactivity to tree moss to avoid this labeled fragrance allergen.

Screening for Compositae contact sensitization with sesquiterpene lactones and Compositae mix 2.5% pet.

BACKGROUND: Compositae contact sensitization may be difficult to diagnose, because of a lack of reliable screening allergens. OBJECTIVES: To assess the suitability of Compositae mix II 2.5% pet. (CM2.5) as a screening mix in the baseline series combined with sesquiterpene lactone (SL) mix and parthenolide (PTH). METHODS: CM2.5 was added to the baseline series, which included SL mix and PTH 0.1% pet., in January 2015, and PTH was included in TRUE Test Panel 3 in October 2015. All Compositae-sensitive patients diagnosed or tested in the next 4 years were assessed. RESULTS: Altogether, 57 patients (2.7%) presented with Compositae allergy. On primary testing in 53 newly diagnosed patients, SL mix elicited positive reactions most frequently (53% positive), followed by CM2.5 (47% positive), and PTH (45% positive). CM2.5 and PTH pet. elicited a few irritant reactions. Three patients had late reactions. Altogether, 16 patients (28%) were not detected by any of the three screening agents. CONCLUSIONS: SL mix is an indispensable, although insufficient, screening mixture in Denmark. It may be relatively safely supplemented with CM2.5 and PTH in the TRUE Test system for screening, but, when Compositae sensitization is suspected, further extracts should be tested on the basis of the history.

Clinical patterns of Compositae dermatitis in Danish monosensitized patients.

BACKGROUND: Compositae dermatitis was originally described as airborne contact dermatitis. More recent studies have reported a wider clinical spectrum, but often in polysensitized patients. OBJECTIVE: To evaluate the clinical features of patients sensitized to Compositae only. PATIENTS/METHODS: Consecutive Compositae-sensitive eczema patients, tested between 1990 and 2015, who, at the patch testing session diagnosing their Compositae allergy, were found to be sensitized only to the plant family, were included. RESULTS: Altogether, 529 of 13 139 patients tested (4.0%) were sensitized to Compositae, and 95 (18% of these) were monosensitized. The majority had hand eczema, and 39 (44%) had a vesicular volar pattern. Eighty-one patients were classified into one of three groups of similar size: localized eczema, eczema of exposed skin, and localized eczema turning into widespread eczema. CONCLUSIONS: The prevalence of Compositae sensitization is continuously high in consecutive eczema patients. Sensitization may occur at any age. Clinical features in monosensitized patients vary, but, with continuing exposure, the patients may develop more widespread dermatitis similar to classic Compositae dermatitis. Avoidance may clear the exogenous part, but not endogenous aetiological factors such as vesicular hand eczema or possible photosensitivity. Thorough clinical assessment and patient education are important in reducing the impact of Compositae contact allergy.

Parthenolide in Danish biodynamic and organic milk: A new source of exposure to an allergenic sesquiterpene lactone.

BACKGROUND: The sunflower family of plants (Compositae = Asteraceae) is currently the most allergenic plant family worldwide, according to the number of sensitizing species. Secondary plant metabolites, including the allergenic sesquiterpene lactones present in Compositae plants, may occur in food items either through their presence in, or through contamination of, plant-based raw materials, or through their occurrence in products of non-plant origin. OBJECTIVE: To analyse biodynamic, organic and conventional milk for the presence of the sesquiterpene lactone parthenolide. METHODS: The content of parthenolide in the milk samples was investigated in dichloromethane extracts obtained by liquid-liquid extraction, followed by gas chromatography-mass spectrometry analyses. RESULTS: The concentration of parthenolide was 0.07 ±0.004 ppm in biodynamic milk, 0.05 ±0.002 ppm in organic milk, and not detectable (<0.002 ppm) in conventional milk. CONCLUSIONS: This is the first report of a potent contact allergen in milk. There seems to be an association between the time that the dairy cattle spend grazing and the amount of parthenolide detected. Although the concentration is low, it is estimated to be high enough to elicit dermatitis in the most sensitive persons by direct contact with the milk.

Allergic contact dermatitis caused by nail acrylates in Europe. An EECDRG study.

BACKGROUND: Allergic contact dermatitis (ACD) caused by nail acrylates, also including methacrylates and cyanoacrylates here, is being increasingly reported. METHODS: A retrospective study in 11 European Environmental Contact Dermatitis Research Group (EECDRG) clinics collected information on cases of ACD caused by nail acrylates diagnosed by aimed testing between 2013 and 2015. RESULTS: Among 18 228 studied patients, 136 had ACD caused by nail acrylates (0.75%; 95%CI: 0.60-0.90), representing 67.3% (95%CI: 60.4-73.7) of ACD cases caused by acrylates. There were 135 females and 1 male, with a mean age ± standard deviation of 36.7 ± 12.2 years; 59 (43.4%) were exposed as consumers, and 77 (56.6%) were occupationally exposed. Occupational cases were more frequent in southern Europe (83.7%), and were younger (mean age of 33.4 ± 8.9 years); most developed ACD during the first year at work (65.0%), and at least 11.7% had to leave their jobs. Skin lesions involved the hands in 121 patients (88.9%) and the face in 50 (36.8%), with the face being the only affected site in 14 (10.3%). Most patients reacted to two or more acrylates on patch testing, mainly to 2-hydroxyethyl methacrylate (HEMA) (92.5%), 2-hydroxypropyl methacrylate (88.6%), ethylene glycol dimethacrylate (69.2%), and ethyl cyanoacrylate (9.9%). CONCLUSIONS: Nail cosmetics were responsible for the majority of ACD cases caused by acrylates, affecting nail beauticians and consumers, and therefore calling for stricter regulation and preventive measures. As HEMA detects most cases, and isolated facial lesions may be overlooked, inclusion of this allergen in the baseline series may be warranted.

Systemic allergic dermatitis caused by sesquiterpene lactones.

Patients with Compositae sensitization are routinely warned against the ingestion of vegetables, spices, teas and herbal remedies from this family of plants. The evidence for the occurrence of systemic allergic dermatitis caused by sesquiterpene lactone-containing plants is mostly anecdotal and based on statements from patients rather than scientific data. However, a few clinical reports on accidental sensitization and exposure and oral challenge prove the existence of this kind of reaction, most convincingly for strong contact allergens such as costunolide in bay leaves, and less so for weak allergens such as those of lettuce. Other Compositae species suspected of causing systemic reactions are artichoke, mugwort, yarrow, dandelion, feverfew, and elecampane. Some Compositae vegetables and teas, such as lettuce and chamomile tea, may induce systemic reactions through both humoral and cell-mediated mechanisms. It is difficult to disentangle the contribution of these reactions to both local and systemic symptoms of skin and mucous membranes in, for example, lettuce contact allergy. Further studies are needed to assess the prevalence of systemic allergic dermatitis caused by sesquiterpene lactones, and to clarify the pathogenesis for individual haptens.

Allergenic sesquiterpene lactones from cushion bush (Leucophyta brownii Cass.): new and old sensitizers in a shrub-turned-a-pot plant.

BACKGROUND: The Australian cushion bush (Leucophyta brownii) of the Compositae family of plants has become a popular pot and container plant. The plant produces the sesquiterpene lactone allergen calocephalin. OBJECTIVES: To assess the sensitizing potential of sesquiterpene lactones from cushion bush. PATIENTS/MATERIALS/METHODS: Eleven Compositae-sensitive patients were patch tested with seven sesquiterpene lactones isolated from cushion bush. RESULTS: Six of seven sesquiterpene lactones elicited positive reactions in 4 of 11 patients. CONCLUSIONS: The well-known sesquiterpene lactone pseudoivalin and its derivative pseudoivalin acetate, as well as calocephalin and tomentosin, were confirmed to be sensitizers, whereas leucophytalin A and 4α-hydroxy-5αH,10αH-1,11(13)-guaidien-8ß,12-olide were shown to be allergenic for the first time. The patch test reaction patterns seem to follow the chemical patterns, which may eventually make it possible to trace primary sensitizers and advise patients more precisely.

The epidemic of methylisothiazolinone: a European prospective study.

BACKGROUND: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. OBJECTIVES: To describe demographics and MI exposures for European patients with MI contact allergy. METHODS: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.). RESULTS: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. CONCLUSION: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.

Lettuce contact allergy.

Lettuce (Lactuca sativa L.) and its varieties are important vegetable crops worldwide. They are also well-known, rarely reported, causes of contact allergy. As lettuce allergens and extracts are not commercially available, the allergy may be underdiagnosed. The aims of this article are to present new data on lettuce contact allergy and review the literature. Lettuce is weakly allergenic, and occupational cases are mainly reported. Using aimed patch testing in Compositae-allergic patients, two recent Danish studies showed prevalence rates of positive lettuce reactions of 11% and 22%. The majority of cases are non-occupational, and may partly be caused by cross-reactivity. The sesquiterpene lactone mix seems to be a poor screening agent for lettuce contact allergy, as the prevalence of positive reactions is significantly higher in non-occupationally sensitized patients. Because of the easy degradability of lettuce allergens, it is recommended to patch test with freshly cut lettuce stem and supplement this with Compositae mix. As contact urticaria and protein contact dermatitis may present as dermatitis, it is important to perform prick-to-prick tests, and possibly scratch patch tests as well. Any person who is occupationally exposed to lettuce for longer periods, especially atopics, amateur gardeners, and persons keeping lettuce-eating pets, is potentially at risk of developing lettuce contact allergy.