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.

[Sensitization to tea tree oil in Germany and Austria. A multicenter study of the German Contact Dermatitis Group]. / Sensibilisierung auf Teebaumöl in Deutschland und Osterreich--Eine multizentrische Studie der Deutschen Kontaktallergiegruppe.

BACKGROUND AND AIM: Tea tree oil, a distillation product of the Australian tea tree (Melalence alternitolia) is increasingly used as an alternative remedy for various dermatological diseases. Tea tree oil contains several allergenic monoterpenes and sesquiterpenes. In this multicenter study it was evaluated, whether the increasing use of tea tree oil has lead to an increased frequency of sensitization in Germany and Austria which would justify its inclusion into the standard series. PATIENTS AND METHOD: For patch testing a standardized tea tree oil was used, dissolved 5% in diethylphtalate (DEP). Consecutive patients of 11 dermatological departments in Germany and Austria were tested. Readings were taken on day 2 and 3 according to the guidelines of the German Contact Dermatitis Research Group (DKG). RESULTS: 5% tea tree oil was positive in 36/3375 patients (1.1%). Sensitization frequencies showed great regional variations and ranged from 2.3% (Dortmund), 1.7% (Buxtehude), 1.1% (Essen), 0.7% (Graz), to 0% (Berlin, Vienna). 14/36 patients (38.9%) also showed a positive patch test reaction to oil of turpentine. CONCLUSION: Our results show that tea tree oil is an important contact allergen for some centers. It should be tested, if medical history suggests its previous use. Considering the great regional differences in frequencies of sensitization its inclusion into the standard series is not recommended yet.

The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.).

Medical remedies of plant origin have gained increasing popularity in recent years. Both anaphylactic and eczematous allergic reactions are on the rise, accordingly. Arnica and marigold, both of the Compositae family, are in widespread use, but only limited data are available on their allergenic potential. We tested 443 consecutive patients, in addition to the European standard and other series, with Compositae mix, sesquiterpene lactone mix, arnica, marigold, and propolis. 5 subjects ( approximately 1.13%) reacted to arnica, 9 ( approximately 2.03%) to marigold. The Compositae mix was positive in 18 cases ( approximately 4.06%). Among them were 3 out of 5 individuals with a sensitization to arnica, and 4 out of 9 who reacted to marigold. Sensitization to arnica and marigold was often accompanied by reactions to nickel, Myroxylon Pereirae resin, fragrance mix, propolis, and colophonium. We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.

Sensitization and cross-reaction patterns in Danish Compositae-allergic patients.

Results of aimed patch testing with constituents of sesquiterpene lactone (SL) mix, Compositae mix (CM) and other Compositae extracts and allergens in 190 Compositae-allergic patients detected in an 8-year period are presented. Feverfew of CM elicited positive reactions most frequently, followed by tansy, wild chamomile, yarrow and arnica, whereas dehydrocostus lactone of SL was the most frequent elicitor of positive reactions, followed by alantolactone and costunolide. Chrysanthemum (Dendranthema) and marguerite (Argyranthemum frutescens) were the most important suspected sensitizers in both occupationally and nonoccupationally exposed, and cross-reactions between chrysanthemum and feverfew/tansy/chamomile may partly explain the high prevalence of positive reactions to the 3 last mentioned. In the nonoccupationally sensitized group, garden plants such as feverfew, blanket flower (Gaillardia), elecampane (Inula helenium), large yellow ox-eye (Telekia speciosa) and cosmea (Cosmos) were additional important allergenic plants. The 3 last mentioned were picked up by SL mix. Most of the lettuce-sensitized persons were CM-positive. 19% of the occupationally sensitized group were negative to both SL and CM, making very aimed patch testing necessary, notably when suspecting rare sensitizers such as Gerbera and star of the veldt (Osteospermum). The significance of the weeds dandelion, dog fennel and ox-eye daisy as sensitizers is not clarified, but they are probably less important than cultivated plants.

An 8-year experience with routine SL mix patch testing supplemented with Compositae mix in Denmark.

Routine patch testing with sesquiterpene lactone (SL) mix, supplemented with Compositae mix (CM) and other Compositae extracts and allergens where appropriate, was evaluated over an 8-year period. 190 of 4386 patients tested (4.3%) were Compositae-sensitive, 143 females (mean age 51.5 years) and 47 males (mean age 55 years), and 83% of reactions considered clinically relevant. 22% were suspected of occupational sensitization/dermatitis. 62% had a contact allergy to 2 or more compounds, most often to nickel, fragrance and colophonium. SL mix detected 65%, CM 87% of Compositae-allergic patients, and the overall detection rate with both mixes was 93%. Few irritant reactions and no cases of clear-cut active sensitization were recorded with the mixes, but our results emphasize the importance of differentiating late-appearing reactivation reactions from patch test sensitization. The weakly positive CM reactions could reflect some irritancy, but as they were associated with fragrance and/or colophonium allergy to a higher degree than weakly positive SL mix reactions, they probably represented cross-reactions. In conclusion, the detection rate with SL mix was high enough to support its continued use as a screening mix and it was very well and rather safely supplemented by aimed testing with CM.

Sensitizing capacity of azole derivatives: Part III. Investigations with anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump inhibitors.

BACKGROUND: More than hundred azole derivatives are used today for different purposes. The majority possess antimycotic, antibacterial, anthelmintic, and antiprotozoal properties. They are used as agricultural fungicides; topical antimycotics, and, for example, in antidandruff cosmetics. More recently the antithyroid and antiulcerative activity of certain imimidazoles and benzimidazoles also has been proven, which led to the introduction of proton pump inhibitors and antithyroid drugs to the market. OBJECTIVE: Case reports from the literature and experimental studies suggest that some of the azole derivatives possess a distinct sensitizing potency. Occupational exposure either in the pharmaceutical manufacture or in the pesticide's application by farmers caused allergic contact dermatitis (ACD). However, experimental studies in guinea pigs to determine their sensitizing capacity have been performed only sporadically. METHOD: Guinea pigs were sensitized by a modified Freund's complete adjuvant (FCA) method, with 35 azoles used as agricultural fungicides, proton pump inhibitors, antimycotics, antithyroid agents, antiprotozoals, antimicrobials, anthelmintics, and wood preservatives. RESULTS: Four azoles exhibited a strong sensitizing capacity, 3 a moderate, and 11 a weak sensitizing capacity. Seventeen derivatives remained negative. Among the strong sensitizers were the 3 proton pump inhibitors omeprazole, pantoprazole, and rabeprazole, as well as the antithyroid drug carbimazole. The latter displayed the highest sensitizing power (mean response = 2.50) of all 62 azole derivatives investigated in the present and the 2 previous experimental studies. CONCLUSION: As long as the strong sensitizing azoles are used only systemically the risk of acquiring contact hypersensitivity is low. However, if the idea should arise to use them topically, for example in ointments, tinctures, or lotions against fungal infections, skin problems will probably be observed abundantly.

Degradation products of monoterpenes are the sensitizing agents in tea tree oil.

BACKGROUND: Patients using tea tree oil (TTO) topically may become sensitized to this natural remedy. More than 30 cases have been documented in the literature since 1991. OBJECTIVE: Freshly distilled, as well as oxidized TTO, some fractions, and single constituents were used for experimental sensitization in guinea pigs. TTO was stored on a window sill to study the influence of light, oxygen, and warmth. The oxidized oil and different fractions were devoted to experimental sensitization in guinea pigs to determine their sensitizing potency. Fifteen constituents were patch tested in TTO-sensitive patients to find how many may play a role as contact allergens. METHODS: Guinea pigs were sensitized by a modified FCA-method (Freund's complete adjuvant) with freshly distilled TTO, oxidized TTO, the monoterpene and sesquiterpene fraction, and 1, 8-cineole. TTO-sensitive patients were tested with 15 typical constituents and degradation products. Gas chromatographic analysis was used to detect degradation products of the deteriorated TTO. RESULTS: Fresh TTO was revealed to be a very weak sensitizing material whereas oxidized TTO was 3 times stronger. The monoterpene fraction showed to be a stronger sensitizer than the sesquiterpene fraction. All 11 patients reacted mostly with a ++-plus or even a -plus reaction to alpha-terpinene, terpinolene and ascaridol. alpha-Phellandrene became positive in four patients, myrcene in only two. Gas chromatographic analyses showed that the formation of peroxides increased within 4 days from less than 50 to more than 500 ppm. Peroxides, epoxides and endoperoxides were formed. Deterioration products of alpha-terpinene were found to be mainly p-cymene, ascaridol, isoascaridol, a ketoperoxide, and colorless crystals that likely were 1,2,4-trihydroxy menthane. The p-cymene content increased dramatically from 2% to 11.5%. alpha- and gamma-terpinene, as well as terpinolene, were reduced to one half of their former concentration. Ascaridol and isoascaridol have never before been found in TTO. CONCLUSION: Tea tree oil kept in open and closed bottles or other containers undergoes photooxidation within a few days to several months, leading to the creation of degradation products that are moderate to strong sensitizers. Peroxides, epoxides and endoperoxides, like ascaridol and 1,2,4-trihydroxy menthane, are formed. These must be considered responsible for the development of allergic contact dermatitis seen in individuals treating themselves with the oil. A test series with 15 characteristic constituents is recommended for patch testing.

Garlic-related dermatoses: case report and review of the literature.

BACKGROUND: Garlic is widely appreciated as a spice and as a vegetable as well as an over-the-counter phytotherapeutic. From a dermato-allergological standpoint, several garlic-related adverse reactions have to be distinguished. OBJECTIVE: The corresponding literature is reviewed briefly, with regard to our present observation of a cook, who contracted garlic-induced contact dermatitis being analyzed for its complex pathomechanism. METHODS: The patient showed a positive type-IV patch test reaction for diallyl disulfide, a low molecular weight garlic ingredient; and strong, non-irritant reactions after 20 min and 24 hrs in the scratch chamber test with fresh total garlic. RESULTS: Thus, in this case of an occupational dermatosis, protein contact dermatitis had to be considered, as well as allergic type-IV contact dermatitis as a co-existing pathomechanism. CONCLUSIONS: The spectrum of garlic-related adverse reactions comprises irritant contact dermatitis, with the rare variant of zosteriform dermatitis; induction of pemphigus, allergic asthma and rhinitis; contact urticaria; protein contact dermatitis; allergic contact dermatitis, including the hematogenic variant; as well as combinations thereof, as evidenced by our present case observation.

The sensitizing capacity of ginkgolic acids in guinea pigs.

BACKGROUND: Ginkgo biloba possesses fruits that have caused numerous cases of allergic contact dermatitis. Low amounts of the ginkgolic acids occur in the leaves as well. OBJECTIVE: Leaf extracts are used to treat cerebrovascular and peripheral vascular disorders. The question arises whether skin hypersensitivity reactions may be adverse effects because the pharmaceutical preparations contain low amounts of ginkgolic acids. METHODS: Guinea pigs were sensitized experimentally with pure ginkgolic acids as well as with leaf extracts containing approximately 1,000 ppm of ginkgolic acids. RESULTS: The guinea pigs could be sensitized successfully with the pure ginkgolic acids. The animals could not be sensitized with the leaf extract. CONCLUSION: Leaf extracts of Ginkgo biloba taken orally or given by infusion to treat diffuse cerebral disturbances can be considered safe, even when they might contain up to 1,000 ppm of the sensitizing ginkgolic acids.

Occupational allergic contact dermatitis from carnosol, a naturally-occurring compound present in rosemary.

A 56-year-old man, working in a food processing factory, developed contact dermatitis of his hands, forearms, and face after the introduction of a new herb extract (Rosmanox) made from the leaves of rosemary (Rosmarinus officinalis). He reacted to carnosol, the main constituent of Rosmanox. 226 controls were negative. To our knowledge, this is the 1st reported case of contact dermatitis from carnosol.

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.

Allergenic sesquiterpene lactones from Eupatorium cannabinum L. and Kaunia rufescens (Lund ex de Candolle).

From Eupatorium cannabinum L., a hitherto unknown alpha-methylene-gamma-butyrolactone, 3 beta-peroxyeucannabinolide, was isolated. This compound and eupatoriopicrin from the same plant showed a weak sensitizing capacity in guinea pigs. 2-oxoludartin and dehydroleucodin, isolated from Kaunia rufescens (syn. Eupatorium rufescens), were strong sensitizers in the same sensitizarian procedure.

A 6-year experience with compositae mix.

A Compositae plant mixture consisting of short ether extracts of arnica, German chamomile, feverfew, tansy, and yarrow has been included in the standard series for several years (1985 to 1990) to study the frequency of allergic reactions to Compositae (Asteraceae) species. One hundred eighteen of 3,851 tested individuals gave a positive response (3.1%). Further tests with the single species of the mixture and some additionally tested extracts of chrysanthemums and laurel oil (bay leaf; Lauraceae) revealed a high percentage of reactions to feverfew (70.1%) and lower responses to chrysanthemums (63.6%), tansy (60.8%), chamomile (56.5%), arnica (51.8%), yarrow (51.8%), and the cross-reacting laurel oil (50.5%). Ten of 85 reacted to arnica alone. The results show that it is important to test Compositae extracts in patients with allergic contact dermatitis because these contain (in contrast to a mixture of pure sesquiterpene lactones) other constituents (e.g., polyacetylenes, thiophenes) that may also contribute to the acquired hypersensitivity. Unrevealed sources of hand and face eczema (including airborne contact dermatitis) might be diagnosed more frequently.

1,2,3-Trithiane-5-carboxylic acid, a first contact allergen from Asparagus officinalis (Liliaceae).

BACKGROUND: Although hundreds of cases of allergic contact dermatitis caused by asparagus have been described in the literature, the responsible allergens are still unknown. OBJECTIVE: Fresh asparagus shoots were purchased in early April. Juice and ether extracts were prepared and stored in a deep freezer until chemical investigations and patch tests could be performed. Known constituents were obtained from investigators who have isolated asparagus components. METHODS: Asparagus-sensitive patients were patch tested with the juice or fresh parts of asparagus and four constituents. One of the compounds was synthesized to get greater amounts for experimental sensitization in guinea pigs. RESULTS: All patients gave positive results with the fresh asparagus and 1,2,3-trithiane-5-carboxylic acid, one of its constituents. Experimental sensitization showed that asparagus has a weak to moderate sensitizing capacity. 1,2,3-Trithiane-5-carboxylic acid showed a similar sensitizing power in the experiments. 1,2,3-Trithiane-5-carboxylic acid is a plant growth inhibitor occurring in asparagus mainly in the early phase of the season. CONCLUSION: For the first time, a sulfur-containing growth inhibitor could be determined as a contact sensitizer in an edible plant. A second sensitizing constituent was detected, of which the structure could not yet be elucidated completely.

Melaleuca oil (tea tree oil) dermatitis.

BACKGROUND: Melaleuca oil (tea tree oil) is the essential oil distilled from the leaves of Melaleuca alternifolia Cheel. Tea tree oil is popular for treating various cutaneous maladies. OBJECTIVE: Our purpose was to determine which constituent compounds of Melaleuca oil are responsible for allergic contact eczema in seven patients who became sensitized. METHODS: The seven patients were patch tested with Finn Chambers to a 1% solution (vol/vol) of melaleuca oil and 1% solutions (vol/vol) of 11 constituent compounds. RESULTS: Of seven patients reactive to the 1% melaleuca oil solution, six patients also reacted to limonene, five to alpha-terpinene and aromadendrene, 2 to terpinen-4-ol, and one each to p-cymene and alpha-phellandrene. d-Carvone, an autooxidative derivative of limonene, caused no reactions among the seven patients. CONCLUSION: d-Limonene was the most common allergen causing allergic contact eczema in our patients. Clinicians are likely to see more contact eczema caused by the increasing use of this popular nostrum.

Contact allergy due to colophony. (IX). Sensitization studies with further products isolated after oxidative degradation of resin acids and colophony.

Degradation of abietic, levopimaric and dehydroabietic acids after exposure to air and light over a period of one to several months, as well as examination of degraded French tall oil rosin and Portuguese colophony, led to the isolation of numerous oxidation products. These compounds were synthesized and consigned to experimental sensitization in guinea pigs. From 20 substances studied as acids or as their methyl esters, in the present and preceding paper, at least 2 can be named: 8,12-peroxydo-delta 13(14)-dihydroabietic acid and 12 alpha-hydroxyabietic acid, that contribute a great deal to colophony allergy by both their sensitizing capacity and their determined concentration in the mixture of degradation products. We recommend the preparation of a new mixture of colophony oxidation products for patch testing in the diagnosis of contact allergy to colophony.