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.

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.

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.

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.

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.

Contact sensitization to calocephalin, a sesquiterpene lactone of the guaianolide type from cushion bush (Leucophyta brownii, Compositae).

BACKGROUND: Cushion bush [Leucophyta brownii Cass. = Calocephalus brownii (Cass.) F. Muell.] is an Australian Compositae shrub that has been introduced into Scandinavia as a pot plant. The first case of sensitization occurred in a gardener, and the main allergen was identified as the guaianolide calocephalin. OBJECTIVE: To present the identification of the main allergen, and to assess the prevalence of sensitization to calocephalin in Compositae-allergic patients. MATERIALS AND METHODS: Calocephalin was isolated from a dichloromethane extract of aerial parts of cushion bush. Calocephalin 0.1% ethanol was included in the plant series in Malmö, Sweden, and Odense, Denmark. RESULTS: Nuclear magnetic resonance (NMR) analysis of calocephalin resulted in a revision of its chemical structure to 4α-acetoxy-1α,2α-epoxy-5α,10αH-guai-11(13)-en-12,8ß-olide. The prevalence of patch test positivity was up to 28% in aimed patch testing. Despite strongly positive patch test reactions, the relevance was unknown in the majority of cases, and only 1 person was occupationally sensitized. CONCLUSION: Calocephalin is a potent contact allergen, but, as cushion bush is a low-maintenance pot plant, primary sensitization is most likely to occur through occupational exposure. Positive reactions in Compositae-sensitive persons probably occur because of cross-reactivity, and patients should be warned about contact with cushion bush plants.

Sensitization patterns in Compositae-allergic patients with current or past atopic dermatitis.

BACKGROUND: An association between Compositae sensitization and atopic dermatitis has been suggested on the basis of case reports and clinical studies. OBJECTIVES: To describe the characteristics of sensitization in Compositae-allergic patients with current and/or past atopic dermatitis. PATIENTS/MATERIALS/METHODS: Consecutive Compositae-sensitive patients were selected for analysis if they had a history of (i) present and/or past atopic dermatitis or (ii) childhood flexural eczema or (iii) childhood eczema of any kind and a positive prick test result. RESULTS: Fifty-one persons (35 females and 16 males) were included. The mean age was lower and the percentage of males was slightly higher than in non-atopics. Testing with sesquiterpene lactone mix, parthenolide and Compositae mix 6% or 5% detected 96% of the patients. Occupational sensitization occurred in 22%. The sensitizing pattern did not differ much from that of non-atopics, except that dandelion was an important allergen in children. Cobalt allergy was the most frequent other contact allergy, occurring in 37%. CONCLUSIONS: Persons with current or past atopic dermatitis may become sensitized to Compositae at any age, both occupationally and non-occupationally. They should be screened for Compositae allergy on equal terms with non-atopics, except that dandelion extract should always be tested in children. Co-sensitization to cobalt was frequent, but probably not related to the plant allergy.

Tomato contact dermatitis.

The tomato plant (Solanum lycopersicum) is an important crop worldwide. Whereas immediate-type reactions to tomato fruits are well known, contact dermatitis caused by tomatoes or tomato plants is rarely reported. The aims of this study were to present new data on contact sensitization to tomato plants and review the literature on contact dermatitis caused by both plants and fruits. An ether extract of tomato plants made as the original oleoresin plant extracts, was used in aimed patch testing, and between 2005 and 2011. 8 of 93 patients (9%) tested positive to the oleoresin extracts. This prevalence is in accordance with the older literature that reports tomato plants as occasional sensitizers. The same applies to tomato fruits, which, in addition, may cause protein contact dermatitis. The allergens of the plant are unknown, but both heat-stable and heat-labile constituents seem to be involved. The fruit contains fragrance compounds that are also present in Myroxylon pereirae (balsam of Peru), possibly accounting for cross-reactivity. The proteins in pulp and peel may contribute to protein contact dermatitis. Until more is known about the allergens, the diagnosis of contact dermatitis caused by tomato plants and fruit may be established with the use of ether extracts and fresh fruits, respectively.

Patch testing with constituents of Compositae mixes.

BACKGROUND: The development of mixes containing Compositae plant extracts has improved the diagnosis of Compositae contact allergy, but none of them has fulfilled the criteria for an ideal European plant mix. OBJECTIVE: To evaluate which constituents of two commercial Compositae mixes were most useful as screening agents. PATIENTS: These comprised 76 patients testing positive to Compositae mix 6% in petrolatum and 29 patients testing positive to Compositae mix 5% pet., all of whom were tested with constituents of the respective mixes. RESULTS: The majority of patients tested positive to parthenolide or parthenolide-containing extracts, followed by German chamomile, yarrow, and arnica. As German chamomile is a weak sensitizer, the results suggest cross-reactions or reactions to unknown allergens. No one was positive to Roman chamomile. CONCLUSIONS: Even though parthenolide seems to be a suitable supplement to the baseline series, the results emphasize that it is important to patch test with extracts of native or locally grown plants, not only because of the geographical variation, but also because of the potential unknown allergens contained in short ether preparations and the variability in the individual patient's exposure and cross-reaction patterns.

Screening for Compositae sensitization with pure allergens: implications of molecular structure, strength of reaction, and time of testing.

BACKGROUND: The sesquiterpene lactone (SL) mix is the only commercial Compositae allergy screening agent that consists of pure allergens; its detection rate is lower than that of Compositae plant extracts. OBJECTIVE(S): To report a 15-year experience with routine screening with SL mix and another allergen, parthenolide, the optimal reading times when testing with SL mix constituents, and the advantages and drawbacks of using pure allergens. MATERIALS AND METHODS: The SL mix 0.1% and parthenolide 0.1% petrolatum were included in the baseline series. RESULTS: Of individuals undergoing routine testing, 157/7163 (2.19%) tested positive to SL mix, 161/7162 (2.25%) to parthenolide, and 141 to both in the 15-year period. The overall detection rate between the two was 177 persons, and 10% would have been missed without parthenolide testing. Two cases of possible active sensitization to parthenolide were recorded. Costunolide elicited positive reactions most frequently, followed by dehydrocostus lactone, and alantolactone. An important observation was that the prevalence of positive reactions to SL mix constituents was lower if they were applied 3-5 days after application of SL mix in those with 1+ or 2+ reactions. CONCLUSIONS: The benefit of detecting 10% more Compositae-sensitive patients with parthenolide in the baseline series must be weighed against a small risk of active sensitization, which may be reduced by lowering the test concentration.

Patch test reactivity to feverfew-containing creams in feverfew-allergic patients.

BACKGROUND: The Compositae plant feverfew (Tanacetum parthenium) has long been recognized as an important sensitizer in European Compositae-allergic patients, mainly because of its content of the sesquiterpene lactone parthenolide. Recently, a parthenolide-depleted feverfew extract with claimed anti-inflammatory properties has been developed for use in cosmetics. OBJECTIVE: The aim of the study was to test, on the basis of patch test reactions, whether persons with contact allergy to feverfew could tolerate creams containing this feverfew extract. PATIENTS/MATERIALS/METHODS: Seven patients with feverfew contact allergy were patch tested with two creams containing the feverfew extract. Subsequently, the creams were analysed by liquid chromatography with tandem mass spectrometry to detect parthenolide. RESULTS: Four of the patients tested positive to one of the creams; reactivity was associated with simultaneous positive reactions to parthenolide. This cream was analysed about 2 years later, and no parthenolide was detected, probably because of degradation of the compound. CONCLUSIONS: Topical products containing parthenolide-depleted feverfew extracts may elicit positive patch test reactions in feverfew-sensitive patients. The reactivity may be enhanced by simultaneous testing with parthenolide, but the reactivity is lost over time, probably because of degradation of parthenolide.