Claudia Pirker

Further important sensitizers in patients sensitive to fragrances - II. Reactivity to essential oils

The aim of this study was to determine the frequency of responses to selected fragrance materials in consecutive patients patch tested in 6 dermatological centres in Europe. 1855 patients were evaluated with the 8% fragrance mix (FM) and 14 other frequently used well‐defined fragrance chemicals (series I). Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Reactions to FM occurred in 11.3% of the subjects. The 6 substances with the highest reactivity following FM were Lyral® (2.7%), citral (1.1%), farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of series I and not to FM. 6.6% of 1855 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 41.1%, to series I and FM in 12.0% and to series I only in 7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials of series I had any type of positive fragrance history, which was significantly higher in comparison to those with isolated reactions to series I (53.6% of 41), p = 0.04. The study identified further sensitizers relevant for patch testing of patients with contact dermatitis, of which Lyral® is the most important single chemical.

Further important sensitizers in patients sensitive to fragrances

In order to find sensitizers additional to the current fragrance mix (FM) a series of fragrance materials (series II) was evaluated in 6 dermatological centres in Europe. 11 of the test materials were essential oils, the remaining 7 being either mixtures of isomers or simple chemicals of frequent usage in the perfume industry. 1606 patients were consecutively tested with series II and 8% FM. Each patient was classified regarding a history of adverse reactions to scented products: certain, probable, questionable, none. Reactions to FM occurred most frequently in 11.4% of the subjects. The 6 materials with the highest reactivity after the FM were ylang‐ylang oil (YY) I (2.6%), YY II (2.5%), lemongrass oil (1.6%), narcissus absolute (1.3%), jasmine absolute (1.2%) and sandalwood oil (0.9%). 48 (3.0%) of the patients reacted only to materials of series II and not to FM. 6.0% of 1606 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 22.9%, to series II and FM in 15.6% and to series II only in 5.2%. 63.5% of the patients reacting to both FM and 1 of the materials of series II had some type of positive fragrance history, which was higher in comparison to those with isolated reactions to FM (46.2% of 121) or to series II, respectively, (45.8% of 48). However, this difference was not statistically significant. In conclusion, the materials of series II identified a further subset of patients with a fragrance problem, which would have been missed by the current FM as the single screening tool for patch testing.

Lyral® is an important sensitizer in patients sensitive to fragrances

Contact allergy to fragrances is a common problem world‐wide. The currently used fragrance mix (FM) for patch testing has only eight constituents and does not identify all fragrance‐allergic patients. As perfumes may contain 100 or more substances, the search for markers for allergy continues. The synthetic fragrance 4‐(4‐hydroxy‐4‐methylpentyl)‐3‐cyclohexene carboxaldehyde (Lyral®) was tested together with the FM and 11 other fragrance substances on consecutive patients in six European departments of dermatology. All patients were carefully questioned regarding a history of reactions to scented products in the past and were grouped into four categories: ‘certain’, ‘probable’, ‘questionable’ and ‘none’. Lyral® (5% in petrolatum) gave a positive reaction in 2·7% of 1855 patients (range 1·2–17%) and ranked next to 11·3% with FM allergy. Twenty‐four patients reacted to both Lyral® and FM, but 21 (1·1%) reacted positively only to Lyral®. Of 124 patients with a ‘certain’ history, 53·2% reacted to the FM and a further 7·2% to Lyral® only. If any kind of history of fragrance intolerance was given, 80% (40 of 50) of Lyral® positive patients had a ‘positive’ history while only 58·6% (123 of 210) of FM positive patients had such a history; this difference was significant at P < 0·01. Lyral® was identified by gas chromatography–mass spectrometry in some products which had caused an allergic contact dermatitis in four typical patients who showed a patch test positive to Lyral® and negative or doubtful to FM. In conclusion, we recommend the testing of 5% Lyral® (in petrolatum) in patients suspected of contact dermatitis.

Lyral has been included in the patch test standard series in Germany.

Lyral® 5% pet. was tested in 3245 consecutive patch test patients in 20 departments of dermatology in order (i) to check the diagnostic quality of this patch test preparation, (ii) to examine concomitant reactions to Lyral and fragrance mix (FM), and (iii) to assess the frequency of contact allergy to Lyral in an unselected patch test population of German dermatological clinics. 62 patients reacted to Lyral, i.e. 1.9%. One third of the positive reactions were + + and + + + . The reaction index was 0.27. Thus, the test preparation can be regarded a good diagnostic tool. Lyral and fragrance mix (FM) were tested in parallel in 3185 patients. Of these, 300 (9.4%) reacted to FM, and 59 (1.9%) to Lyral. In 40 patients, positive reactions to both occurred, which is 13.3% of those reacting to FM, and 67.8% of those reacting to Lyral. So the concordance of positive test reactions to Lyral and FM was only slight. Based on these results, the German Contact Dermatitis Research Group (DKG) decided to add Lyral 5% pet. to the standard series.

Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant

Several contact allergens are tested at concentrations which might cause irritant reactions. In this study we investigated whether the reactivity to a standard irritant is useful in identifying subjects with hyperreactive skin yielding a higher rate of doubtful or irritant reactions. Sodium lauryl sulfate (SLS) 0.5% (aqua) was tested in addition to the standard series routinely for 5 years in the Department of Dermatology, Dortmund. For data analysis, we compared reactions at D3 to the standard series, the vehicle/emulsifier and preservative series and benzoyl peroxide to the reactions obtained with SLS. Proportions were standardized for age and sex. The association between reactivity to a certain allergen and SLS reactivity as a dichotomous outcome, controlled for age and sex as potential confounders, was assessed with logistic regression analysis. Results showed that of the 1600 tested patients, 668 (41.8%) had an irritant reaction to SLS which exceeded 2 + in only 41 patients. Seasonal variation was statistically significant, showing reduced SLS reactivity in summer vs. winter. Patients with irritant reactions to SLS showed significantly more erythematous reactions to the following 10 allergens of the standard series: fragrance mix, cobalt chloride, balsam of Peru (Myroxylon pereirae), lanolin alcohol, 4‐phenylenediamine base (PPD), propolis, formaldehyde, N‐isopropyl‐N′‐phenyl‐p‐phenylenediamine (IPPD), benzocaine, and 4‐tert‐butylphenol‐formaldehyde resin. No significant differences regarding strong positive allergic reactions were observed. Concerning other allergens, significantly more erythematous reactions were observed in SLS‐reactive patients to benzoyl peroxide, octyl gallate, cocamidopropyl betaine, Amerchol L‐101, tert‐butylhydroquinone, and triethanolamine. In the SLS‐reactive group of patients, the reaction index was negative for 10 allergens of the standard series compared to only 5 in the SLS non‐responder group. For the first time, this study, based on a large data pool, revealed a significant association between reactivity to the irritant SLS and erythematous reactions to certain allergens. With SLS as a marker for hyperreactive skin at hand, some of these reactions can now be classified as irritant more confidently, particularly if there is no history of exposure to the allergen.

Hydroxyisohexyl 3-cyclohexene carboxaldehyde- known as Lyral : quantitative aspects and risk assessment of an important fragrance allergen

Hydroxyisohexyl 3‐cyclohexene carboxaldehyde, also known as Lyral®, is a fragrance ingredient identified as the cause of contact allergic reactions in 2–3% of eczema patients undergoing patch testing. Lyral® has been included in the standard patch test series in many clinics due to its importance as an allergen. It has been used without restrictions in cosmetic products, until now. In the present study, the dose–response relationship of Lyral® contact allergy was studied with doses relevant for normal exposure in cosmetic products. 18 eczema patients, who previously had given a positive patch test to Lyral® 5% petrolatum, were included along with 7 control subjects. All cases were tested with a serial dilution of Lyral® in ethanol 6% to 6 p.p.m and subjected to a 2‐week, repeated open application test with a low dose of Lyral® in ethanol. In the case of no reaction, this was followed by another 2 weeks of testing with a higher dose. The test was performed at the volar aspect of the forearm. In 16 of 18 cases (89%), a positive use test developed, 11 reacting to the low and 5 to the high concentration. None reacted to the vehicle control of ethanol applied to the contralateral arm. All controls were negative to both the test solutions of Lyral® and the ethanol control. The difference between the test and the control group was statistically significant (Fishers test, P < 0·001). It is concluded that Lyral® at the current usage levels is inducing sensitization in the community. The same levels were shown to elicit allergic contact dermatitis in almost all sensitized individuals. A significant reduction in usage concentrations is recommended to prevent contact allergic reactions.

Angioedema and dysphagia caused by contact allergy to inhaled budesonide

Inhaled corticosteroids may cause various adverse effects ranging from irritation to severe anaphylactic reactions and systemic contact dermatitis. We report a 43‐year‐old woman who developed sore throat, swelling of the lips and oral cavity and dysphagia, 2 weeks after the use of budesonide spray (Budefat®) for treatment of bronchial asthma. The symptoms occurred with a delay of 3–4 h after the treatment ×2 daily. There were no immediate reactions on prick and intracutaneous testing with the commercial product used by the patient. However, marked pruritic infiltration developed within 24 h, progressing to coalescing eczematous lesions over the following 2 days. In addition, severe oedema of the right upper eyelid was observed. On patch testing, budesonide was strongly positive at day 2 and 3 in a concentration ranging from 1% to 10 p.p.m. (in petrolatum). Other corticosteroids of group A, B, C and D were completely negative. Repeated open application tests with amcinonide and triamcinolone acetonide cream on the ventral aspect of the upper arm were negative. Bronchial exposure to alternative sprays containing beclomethasone dipropionate (group D), fluticasone‐17‐ propionate (D) and dexamethasone‐21‐isonicotinate (C) was well tolerated. In conclusion, this case is instructive, because the symptoms which developed after a short period of corticosteroid inhalation suggested a type I allergy. Testing proved a severe type IV contact allergy restricted to budesonide (group B), without cross‐reactions to major corticosteroids of other groups.

Tetrazepam drug sensitivity − usefulness of the patch test

The muscle relaxant tetrazepam may cause severe cutaneous adverse effects. We report 4 cases of varying intensity: Stevens–Johnson syndrome, erythema–multiforme‐like exanthema, maculopapular and maculo‐urticarial exanthema. Patch testing with tetrazepam (10% in petrolatum) was strongly positive in the 2 patients with severe skin eruptions and weakly positive in the other 2. Oral rechallenge with tetrazepam was positive in 3 patients (1 not done). Diazepam, with a similar chemical structure to tetrazepam, was negative on patch testing and on oral challenge testing in 2 patients. Although the optimal patch test concentration of tetrazepam has still to be determined, it is a useful diagnostic tool to confirm sensitization, particularly in patients with severe bullous eruptions.

Sensibilisierung auf Teebaumöl in Deutschland und Österreich – Eine multizentrische Studie der Deutschen Kontaktallergiegruppe

Hintergrund und Fragestellung: Teebaumöl, ein Destillationsprodukt der Blätter des australischen Teebaumes Melaleuca alternifolia, erfreut sich zunehmender Beliebtheit als Alternativheilmittel für die Behandlung diverser Hauterkrankungen. Das Öl ist ein Gemisch aus zahlreichen allergologisch relevanten Substanzen wie Monoterpenen und Sesquiterpenen. In dieser multizentrischen Studie sollte evaluiert werden, ob die Zunahme des Verbrauches von Teebaumöl zu einer Sensibilisierungshäufigkeit in Deutschland und Österreich geführt hat, die die Aufnahme in die Standardreihe rechtfertigen würden.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 association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens.

To support the decision as to whether erythematous patch test reactions to allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0·5% in water) has been added to the standard patch tests since July 1996 in the Dortmund Department of Dermatology. Data on 1600 patients patch tested up until June 2001, as well as standardized data on ambient temperature and humidity obtained by the German Meteorological Service, were included in a logistic regression analysis taking age, sex and atopy as potential confounders into account. The pattern of association was heterogeneous: while doubtful reactions to nickel sulfate were significantly associated with dry/cold weather conditions, but not with SLS reactivity, the opposite was observed for lanolin alcohol, benzocaine and Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens, namely formaldehyde, fragrance mix or p‐phenylenediamine, were associated with both factors. For several other allergens of the standard series, no distinct, significant pattern could be discerned. In conclusion, meteorological conditions and SLS reactivity independently contribute information on individual irritability at the time of patch testing, and both should be considered.