Toward a rationalization of the sensitizing potency of substituted p-benzoquinones: reaction of nucleophiles with p-benzoquinones.

MNDO calculations have been carried out for the contact sensitizers 2,6-dimethoxy-1,4-benzoquinone (6) and 2-methoxy-6-methyl-1,4-benzoquinone (10) and for 2,5-dimethoxy-1,4-benzoquinone (7), which is nonallergenic in contrast to thymoquinone (8) (2-methyl-5-isopropyl-1,4-benzoquinone), which is a relatively strong contact allergen. Theoretical results indicate that the conformational flexibility of methoxy groups substituted at the quinone rings influences the electronic properties of these compounds, in particular their reactivity with regard to nucleophiles. According to theory, 6, 10, and 8 should possess a pronounced reactivity toward nucleophiles while 7 should resist nucleophilic attack. Hence, the allergenic capacity of a quinone seems to depend on their binding interactions with nucleophiles such as amino or thio groups of amino acids.

Allergic contact dermatitis to quinones in Paphiopedilum haynaldianum (Orchidaceae).

An eczematous eruption developed on the hands and forearms of a 68-year-old man after frequent contact with homebred specimens of the lady slipper Paphiopedilum haynaldianum. Patch tests with leaves, petals, and stems, as well as with two quinones isolated from the plant by thin-layer chromatography, gave strongly positive reactions. The results demonstrated that the recurrent skin lesions were the expression of an allergic contact dermatitis due to the quinoid constitutnets, which are the main contact allergens in this orchid species.

Allergic contact dermatitis caused by olive wood jewelry.

A case of allergic contact dermatitis to olive wood occurred. To our knowledge, this is the first such case reported. The diagnosis was confirmed by positive patch tests to scrapings from olive wood and to the quinone compound fractions isolated from an extract of olive wood by thin-layer chromatography. The sensitizing properties of olive wood were proved by experimental sensitization of two guinea pigs that reacted positively to a raw extract an to the fractionated quinone compounds from olive wood after sensitization. The chemical analysis made has shown, for the first time, that olive wood contains quinoid compounds belonging to the same group as the strong sensitizers desoxylapachol from teakwood and the dalbergiones from Brazilian and East Indian rosewood. However, compared with teakwood and rosewood, olive wood can only be considered a relatively weak sensitizer.

Orchid allergy.

A female office worker acquired contact allergy by handling Cymbidium cultivars for several years. The sensitizing properties of this ornamental orchid were demonstrated by experimental sensitization of guinea pigs. Chemical analysis of the ether extracts disclosed the presence of two quinones. The structure of the main quinone was elucidated as 2,6-dimethoxy-1,4-benzoquinone by x-ray crystallographic analysis. In the patient and in the sensitized animals, only this quinone elicited strong reactions, while tests with the second constituent were negative or gave only weak responses. Although 2,6-dimethoxy-1,4-benzoquinone is only a moderately strong sensitizer, its role as a contact allergen is emphasized, as it has been found in more than 50 different plant and wood species.

On the occurrence of the contact allergen primin and other quinoid compounds in species of the family of primulaceae.

82 different species of the Primulacea family have been investigated by a screening test. In 16 Primula species and 4 species of other genera the strong contact allergen primin could be detected by the Craven-test. Extracts of only 12 plants gave no color reaction. In the remaining species other quinoid components were detectable. From 4 species new quinoid substances were isolated. Primin itself was obtained from Primula elatior and from the petals (corollas) of Primula obconica. The results indicate that the presence of primin and other quinones is determined by their origin and seasonal variations. It is supposed that some of the detected quinones may function as allergens and therefore may be responsible for the contact dermatitis described in the literature due to several Primula species and some other species of the same family. Some indications point to the suspicion that primin occurs in the plant as a glycoside which is separated by extraction treatment to give its quinole and an unknown substance. The quinole oxidizes then to the quinhydrone and finally to primin itself.

The sensitizing capacity of Compositae plants. VI. Guinea pig sensitization experiments with ornamental plants and weeds using different methods.

Experimental studies in guinea pigs using ether extracts of 20 different species of the Compositae plant family were carried out with the open epicutaneous method (OET) and the guinea pig maximization test (GPMT). The results demonstrate that Cnicus benedictus (blessed thistle), Chrysanthemum leucanthemum (marguerite, ox-eye daisy) and Helianthus debilis (dwarf sunflower) are strong sensitizers while Helenium amarum (bitterweed), Gaillardia amblyodon (blanket flower), Artemisia ludoviciana (prairie sage), Ambrosia trifida (giant ragweed) and Solidago virgaurea (goldenrod) are medium sensitizers. Twelfe species revealed only a weak or no sensitizing capacity; among those were corn flower, wormwood, mugwort, coltsfoot and dandelion. Cross-reactivities were observed in a considerable number of the investigated plant species. The sensitizing power as well as the observed cross-reactions depend on the occurrence of sesquiterpene lactones which have an alpha-methylene group exocyclic to the lactone in common ("immunologic requisite"). As a practical consequence, patients suffering from allergic contact dermatitis due to Compositae species are strictly requested to avoid contact with the offending species and all related species to prevent recurrences of their skin lesions.

5,8-dihydroxyflavone (primetin) the contact sensitizer of Primula mistassinica Michaux.

5,8-Dihydroxyflavone (primetin) has been shown to be the sensitizer in Primula mistassinica Michaux and probably the source of allergic contact dermatitis in four milkers. Its sensitizing properties as determined in guinea-pigs, are strong. As far as is known this is the first experimental demonstration of the sensitizing potency of a flavone. Presumably the flavone, with its uncommon 5,8-arrangement of hydroxy groups, is oxidized in the skin to the corresponding quinone (primetinquinone). Quinone was prepared from primetin and used for experimental sensitization of guinea-pigs. It also revealed strong sensitizing properties. Cross-reactions were obtained not only with the synthetic quinone in the flavone-sensitive animals but also with primetin in primetinquinone-sensitive guinea-pigs. Preliminary sensitization tests with other flavones have demonstrated that the whole group of flavonoid components should be taken into consideration as potential sensitizers.

The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones.

Experimental studies on the sensitizing capacity of naturally occurring benzoquinones, isolated from plants and woods have been carried out in guinea pigs of the Pirbright white strain. Seven compounds were available: primin, three dalbergiones, mansonia quinone (mansonone A), 2,6-dimethoxybenzoquinone and rapanone. With five of these substances (primin, mansonone A, three dalbergiones) guinea pigs could be sensitized. Primin, the allergen of Primula obconica Hance (primrose) proved to be the most effective one of all quinones tested in this and the preceding studies. As a similar but weaker sensitizer R-3, 4-dimethoxydalbergione from Machaerium scleroxylon Tul. (Pao ferro, Caviuna vermelha) could be identified. The results obtained with mansonone A, a sesquiterpenoid quinone from Mansonia altissima A. Chev. demonstrate that even naturally occurring orthoquinones are capable of inducing contact allergy. Allergic cross reactions could be obtained between all chemically related mansonones A-F. The results are in good accordance with the view that the sensitizing capacity of naturally occurring quinones depends on the fundamental quinoid structure and the length, position and configuration of the aliphatic side-chain.

[Contact allergy for Alstrumeria (inca lily)]. / Contactallergie voor Alstroemeria (incalelie).

We report 6 patients with occupational contact allergy to Alstroemeria cultivars. Four of them presented with the clinical picture of 'tulip fingers'. They all reacted to parts of fresh plants and to tuliposide A. The literature on Alstroemeria allergy is reviewed.

[Toxic contact dermatitis from poison ivy in a private garden in Germany]. / Toxische Kontaktdermatitis auf Poison Ivy in einem Privatgarten in Deutschland.

A couple suffered for 5 years from recurrent eruptions with vesicles and bullae after contact with an unknown "climbing weed" in their private garden in Germany. After this plant was identified as poison ivy and eradicated, their skin problems were solved. This is the first report of poison ivy in this setting. Urushiols in poison ivy are not only strong allergens but also potent irritants. Negative patch tests in the husband suggest that the bullous dermatitis was a toxic reaction.

Contact vitiligo following a strong patch test reaction to triglycidyl-p-aminophenol in an aircraft industry worker: case report and review of the literature.

Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he had started working in aircraft construction. Patch tests showed positive reactions at day 3 to nickel sulfate, epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-aminophenol (TGPAP) applied at 1% and 0.1% induced the strongest (+++ positive) reaction. About 4 months after the patch test with TGPAP, the patient presented with 2 circular depigmented spots in the former TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis of contact vitiligo.

Absence of contact sensitization to Aloe vera (L.) Burm. f.

Aloe vera has been used as a cosmetic and medical remedy since ancient times and has gained increasing popularity in recent years. Despite its widespread use, reports of allergic reactions are rare. We patch tested 702 consecutive patients with an oily extract from the leaves, Aloe pulvis from the entire plant and concentrated Aloe vera gel. A specially designed questionnaire was used for the use of Aloe vera, reasons and location of application, adverse reactions, occupation, hobbies and atopy. None of the subjects showed any reaction to one of the preparations. 2 components of the plant have to be distinguished: the bark of the leaves contains anthrachinones with pro-peristaltic and potential antibiotic and anticancer properties. Constraints have been imposed due to their considerable toxic potential. Today, mostly the Aloe gel from the center of the leaves is processed. It almost exclusively consists of carbohydrates to which also many medical effects have been attributed. Carbohydrates are not likely to induce contact sensitization, which might explain the outcome of our study. However, this does not justify unrestrained promotion of Aloe products, as scientific studies investigating the claims on its constitutional effects are few in number, and the majority of them have been unable to diminish the intuitive scepticism against miracle cures, like Aloe seems to be.

[Laurel allergy. Cause, effect and sequelae of the external application of a so-called nature remedy]. / Lorbeer-Allergie. Ursache, Wirkung und Folgen der äusserlichen Anwendung eines sogenannten Naturheilmittels.

Self-medication of rheumatic complaints in the upper arm, by one woman, and of a lipoma on the thigh, by another, with pure laurel oil caused within two weeks severe contact dermatitis and swellings far from the point of application. Sesquiterpene lactone, contained within laurel oil, proved to be the cause of the induced contact allergy. Since the acquired specific hypersensitivity of the eczema type is directed primarily against the alpha-methylene group of the lactone, cross-reactions were observed against a large number of other plans which are botanically unrelated but contain substances of a similar class. Those allergic to laurel oil should therefore avoid many cosmetics, articles of hygiene, foods, drinks and medicinal preparations which contain herbs, as well as gardening, certain cut flowers and perfumes, especially those of the family Compositae. The present trend "back to nature" makes further sensitizations against laurel oil likely. This would seem to justify the inclusion of these substances among the group of potentially harmful environmental and occupational products.

[Toothpaste allergy]. / Zahnpasta-Allergie.

Cheilitis was observed in a 74-year-old patient after use of a new toothpaste which occurred after several weeks despite withdrawal of the paste. Positive patch testing with the toothpaste confirmed suspect contact sensitization. The cause was the main component of the flavour additive i. e. the terpene ketone L-carvone. Due to the characteristic flavour it is contained in many mint and peppermint oils. In this case it also caused the recurrences by sucking of refreshment lozenges. L-Carvone is also contained in most chewing gums and should thus be considered aetiologically in cases of cheilitis and stomatitis.

[Gaillardia allergy]. / Kokardenblumen-Allergie.

Allergic contact dermatitis of the face and hands occurring in a 37-year-old savings-bank employee was found to be due to non-occupational handling of Gaillardia cultivars. Additional self treatment with a body lotion containing extracts of Arnica worsened the skin lesions. Epicutaneous tests with different Gaillardia sesquiterpene lactones revealed spathulin to be the responsible sensitizer. Cross reactions were obtained with telekin, alantolactone, parthenolide, isoalantolactone and carabrone.

Allergic contact dermatitis from a wooden necklace.

A 36-year-old female kitchenworker twice developed eczematous lesions corresponding exactly to the area around her neck where she had worn a wooden necklace. Contact dermatitis lasted longer than 1 week. The necklace consisted of 42 brown wooden beads and 63 other wooden parts, 0.5 to 3 cm diameter. Most parts could be identified as Cocobolo wood, Brazilian and East Indian rosewood, and teak. Patch tests with the pure constituents gave +3-reactions to three dalbergions and obtusaquinone, which are known to be the sensitizers of Cocobolo and the above-mentioned rosewoods. Because of these test results, the identification of the species by eye examination could be corroborated. Further detailed questioning revealed that the patient had played a recorder, probably made from Cocobolo (Dalbergia retusa), when a child, to which she unknowingly became allergic.

Sensitizing capacity of naturally occurring quinones. V. 2.6-dimethoxy-p-benzoquinone: occurrence and significance as a contact allergen.

2.6-dimethoxy-1,4-benzoquinone has already been discovered in more than 25 different plants and woods. Several authors have shown its strong bacteriostatic activity against micro-organisms. In 1972 a positive skin reaction to 2.6-dimethoxybenzoquinone was obtained in a patient allergic to Sucupira wood (Bowdichia nitida Benth.). This compound could be isolated from the wood. During the chemical investigations of other commercial woods which have been described as the cause of allergic contact dermatitis, 2.6-dimethoxybenzoquinone could be isolated from an additional 21 different species. In the case of Australian blackwood Acacia melanoxylan R.BR., its structure was elucidated by x-ray analysis. Sensitization of guinea pigs revealed that 2.6-dimethoxybenzoquinone is a relatively good sensitizer. In some of the woods investigated, quinones have never been discovered before, for example in Makoré, Australian blackwood, Wengé, White wood, Afrormosia and Afzelia. In 10 of them only this quinone was detectable. Besides its allergenic properties, 2.6-dimethoxybenzoquinone may be responsible for the high termite resistance of these woods. In all cases of contact dermatitis from these wood species in which quinoid allergens other than 2,6-dimethoxybenzoquinone could be detected, this quinone should be used for patch tests.

The sensitizing capacity of Compositae plants. III. Test results and cross-reactions in Compositae-sensitive patients.

25 patients known or suspected to be allergic to different Compositae plants were tested epicutaneously with ether extracts of different Compositae species. 14 persons revealed a chrysanthemum hypersensitivity, 2 were allergic to arnica and 2 to camomile. In 1 patient a positive reaction to tansy was obtained. In the case of the chrysanthemum allergy, this was induced occupationally. All other patients had sensitized themselves by non-occupational contact. Cross-reactions were seen to tansy [14], yarrow [11], camomile [10], arnica and sunflower [5]. The components which are responsible for the sensitization as well as for the crossreactions are sesquiterpene lactones.