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.     

The impact of meteorological conditions on patch test results with 12 standard series allergens (fragrances, biocides, topical ingredients)

Background Fluctuating irritability of the skin induced by low ambient temperature and humidity may compromise the reproducibility of patch testing. Objectives To assess the impact of temperature and absolute humidity at the time of patch testing on the occurrence of irritant or doubtful (IR/?), weak positive (+) and (strong) positive (++/+++) reactions, respectively, among 12 allergens included in the German Standard Series. Methods Analysis of clinical data collected in the surveillance network IVDK ( http://www.ivdk.org ) between January 1993 and December 2001 (n = 73 691 patients) combined with meteorological data obtained by the national services in Germany and Austria. Multinomial logistic regression analysis was used to estimate the risk associated with temperature, absolute humidity and vapour pressure, respectively, adjusted for sex, age, atopic dermatitis and duration of patch test application. Results For low temperature and humidity, a relevant increase of IR/? reaction frequency was observed in the cases of paraben mix and (chloro‐) methylisothiazolinone. Both IR/? and + reactions were significantly increased with respect to the allergens fragrance mix, oil of turpentine, methyldibromo glutaronitrile + phenoxyethanol and particularly formaldehyde, while ++/+++ reactions were hardly affected by weather conditions. Conclusions The observed increase of IR/? reactions may be due to epidermal barrier function impairment. The impact of dry/cold weather on + reactions in terms of possibly false‐positive reactions is restricted to few allergens. In the case of + reactions of unknown relevance, a re‐test under warm conditions or verification tests such as the repeated open application test or the provocative use test may be recommendable.     

Simultaneous sodium lauryl sulphate testing improves the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG)

Background There is evidence that a higher skin susceptibility may induce nonspecific erythematous or weak positive reactions to contact allergens in patch testing. Objectives To evaluate whether simultaneous application of sodium lauryl sulphate (SLS) along with diagnostic patch tests with contact allergens can provide information regarding skin irritability which may help to discriminate allergic from nonspecific irritant reactions to contact allergens. Methods Between July 2001 and June 2003, this prospective study collected patch test data of 5971 patients from 19 centres in Germany and Austria in the Information Network of Departments of Dermatology (IVDK). In addition to contact allergens (standard series and eight known ‘problematic’ allergens with a low reaction index and a high positivity ratio: 1,3‐diphenylguanidine, amerchol L‐101, benzalkonium chloride, benzoyl peroxide, cocamidopropyl betaine, octyl gallate, phenyl mercuric acetate and propylene glycol), patches with SLS 0·5% and 0·25% aq. were applied. Reactions to the allergens and to SLS were analysed at the IVDK data centre. The association between an erythematous or positive reaction to a certain allergen and an irritant reaction to SLS was assessed with logistic regression analysis, at the same time controlling for the influence of age and sex. Results Of the 29 allergens of the standard series, 23 and 21 gave a higher percentage of nonspecific erythematous reactions in patients with an irritant reaction to 0·25% and 0·5% SLS, respectively, in comparison with SLS‐negative patients. All eight ‘problematic’ allergens gave an increased percentage of nonspecific erythematous reactions. Similarly, 22 and 21 allergens of the standard series gave a higher percentage of positive allergic reactions in patients with an irritant reaction to 0·25% and 0·5% SLS, respectively, and seven of the eight ‘problematic’ allergens gave a higher percentage of positive allergic rections (exception: octyl gallate). For most allergens, the markers of skin reaction (reaction index and positivity ratio) were worse in SLS‐positive patients. Differences were more pronounced when testing with SLS 0·25% than with SLS 0·5%. Conclusions Because there is a convincing association between skin irritability (evaluated by SLS test) and the degree of skin reaction to contact allergens, the SLS test may help in deciding whether a doubtful erythematous or weakly ‘positive’ skin reaction should be interpreted as allergic or irritant.     

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.     

Citral a fragrance allergen and irritant

Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2% petrolatum and the European standard series. 28 of the patients showed a positive patch test reaction (+ to +++) to citral and 82 at least 1 IR patch test reaction and no positive patch test reaction to citral. A statistically significant association between a positive patch test reaction to citral and positive patch test reactions to other fragrances compared with IR reactions (n = 82) was established. The difference regarding fragrance history found between those with IR and positive reactions to citral was not significant. Citral could be an allergen and/or irritant, worthy of further more extensive studies.     

Patch testing with components of water-based metalworking fluids: results of a multicentre study with a second series

BACKGROUND: Although many allergens in metalworking fluids (MWF) are identified, there are still some MWF components, which are not sufficiently investigated concerning their sensitizing properties. OBJECTIVES: To investigate sensitization to 10 frequently used MWF components, which are not part of the established MWF test series, in metalworkers with suspected occupational dermatitis due to MWF. PATIENTS/METHODS: Oleyl alcohol, myristyl alcohol, dimethylolurea, 4,4'-methylenebis morpholine, imazalil, 1-amino-2-propanol (monoisopropanolamine; MIPA), 2-amino-2-ethyl-1,3-propanediol (AEPD), 2,5-bis(n-octyldithio)-1,3,4-thiadiazole, zinc alkyl dithiophosphate and dibenzyl disulfide have been patch tested in 144 patients. RESULTS: 7 patients reacted positively to the formaldehyde releaser 4,4'-methylenebis morpholine, and 6 of these patients also reacted to formaldehyde and/or other formaldehyde releasers. 4 patients reacted positively to myristyl alcohol tested at 10% petrolatum (pet.). Additionally, 20 doubtful or irritant reactions occurred. 1 patient each reacted positively to oleyl alcohol, MIPA, and AEPD. None of the other test substances mentioned above elicited any clear-cut positive reaction. Patch testing with well-known MWF allergens showed proportions of positive reactions, which were comparable to those from other studies, e.g. 11% to monoethanolamine, 8% to colophonium and 3%-5% to various preservatives. CONCLUSIONS: 4,4'-methylenebis morpholine may be an important MWF allergen, although clinical relevance could not be stated definitely in every case. Myristyl alcohol should not be patch tested at 10% pet., but at a lesser concentration, due to irritant properties.     

Comparative multi-center study with TRUE Test and Finn Chamber Patch Test methods in eight Swedish hospitals

292 individuals were patch tested with twelve allergens, using a new patch test technique, TRUE Test (TT). As controls, the same allergens in standard concentrations in petrolatum were applied using the Finn Chamber technique (FC). The allergen doses used in TT were chosen according to results from a previous serial dilution patch test study. There were reactors to all twelve allergens. The concordance of positive reactions between TT and FC was 78%. 10% were indicated only with TT and 12% FC only. Irritant reactions occurred in the same order of magnitude for the two tests. Weak positive, uncertain, and irritant reactions observed with the different test methods used, indicate minor errors of allergen dosage in both. The investigation indicates that the TRUE Test method is simple to handle, is well standardized and gives good accuracy with the 12 allergens investigated.     

A multicenter study of patch test reactions with dental screening series.

Background: Dental products contain many allergens, and may cause problems both for patients undergoing dental treatment and for dental personnel because of occupational exposure. Individual patch test clinics may not study sufficient numbers of patients to collect reliable data on uncommon allergens. Objective: To collect information on dental allergens based on a multicenter study. Materials and Methods: The Finnish Contact Dermatitis Group tested more than 4,000 patients (for most allergens, 2,300 to 2,600 patients) with dental screening series. Conventional patch testing was performed. The total number and percentage of irritant (scored as irritant [IR] or doubtful [?]) and allergic (scored as +, ++, or +++) patch test reactions, respectively, were calculated, as well as the highest and lowest percentage of allergic patch test reactions recorded by the different patch test clinics. A reaction index (RI) was calculated, giving information on the irritancy of the patch test substances. Results: The most frequent allergic patch test reactions were caused by nickel (14.6%), ammoniated mercury (13%), mercury (10.3%), gold (7.7%), benzoic acid (4.3%), palladium (4.2%) and cobalt (4.1%). 2-hydroxyethyl methacrylate (2.8%) provoked most of the reactions caused by (meth)acrylates. Menthol, peppermint oil, ammonium tetrachloroplatinate, and amalgam alloying metals provoked no (neither allergic nor irritant) patch test reactions. Conclusion: Patch testing with allergens in the dental screening series, including (meth)acrylates and mercury, needs to be performed to detect contact allergy to dental products.     

In vivo cytokine profiles in allergic and irritant contact dermatitis

Local cytokine profiles in skin biopsies from allergic and irritant patch test reactions were determined by in vivo immunohistochemistry to differentiate between these 2 clinically identical afflictions especially at the time of final reading in diagnostic patch testing. Biopsies were taken from established allergic persons after specific allergic patch test.-, to epoxy resin (1%) and formaldehyde (1%) and from non-allergic individuals with irritant patch tests to sodium lauryl sulfate (10%) and formaldehyde (8%). At 72 h after application of the agents, significantly enhanced frequencies of dermal infiltrating cells, producing IL-1α, TNF-α. IL-2. and IFN-γ per 100 infiltrating cells in the dermis. were observed in allergic as well us irritant patch test reactions, as compared to normal skin. Significantly higher frequencies of IL- Iα-producing cells were observed in biopsies from epoxy resin (1%) allergen-affected and sodium lauryl sulfate (10%) irritant-affected skin as compared to formaldehyde (1%) allergen-affected skin. In addition, significantly higher frequencies of TNF -α reproducing cells were observed in epoxy resin allergen-affected skin us compared to Formaldehyde (1%) allergen-affected and formaldehyde (8%) irritant affected skin. The allergic and irritant patch test reactions showed similar levels of expression of the Thl cytokines IL-2 and IFN-γ in the dermis. confirmed by probe based detection of IL-2 mRNA and IFN-γ- mRNA, In conclusion, the described similarity shows that allergens and irritants can induce the same profile of IL-la. TNF-α. IL-2. and IFN-γ production, resulting in the near impossibility of discriminating between allergic and irritant contact dermal is at the lime of patch test reading.     

More positive patch test reactions with larger test chambers?

Test chambers of various sizes are commercially available for patch testing. Therefore, we asked the question whether the size of patch test chambers may affect allergic patch test reactions. A total of 495 patients were doubletested synchronously with small and large Finn Chambers containing standard preparations of fragrance mix, wool wax alcohols. Kathon CG and formaldehyde, Double tests in 217 patients who had reacted with at least 1 allergic, questionable, or irritant reaction to 1 of these allergens were statistically evaluated. For each of the 4 allergens, a significantly higher number of stronger reactions was seen with the large chambers as compared to the small ones. It is concluded that large test chambers may be useful for detection of weak sensitizations to particular contact allergens.     

Occupational contact allergy to glyoxal

Glyoxal is a dialdehyde that is used as a disinfectant in health care and dentistry work. Allergic contact dermatitis from glyoxal has been described in these occupations. We analysed our patient data from 1998 to 2004 for allergic reactions to glyoxal. 20 patients had allergic reactions to glyoxal on patch testing. 5 of these patients worked in dentistry and 4 of them had present exposure to glyoxal. 9 patients were machinists without obvious exposure to glyoxal. A grinder with work-related facial dermatitis is described in detail. The chemical analysis of air samples from his workplace revealed 9.4-21 microg/m3 glyoxal. Glyoxal was also present in the used metal-working fluid, and apparently it had been formed during grinding. The remaining 6 patients worked in miscellaneous occupations and had no present exposure to glyoxal. Glyoxal is irritant on patch testing. Especially, solitary reactions to glyoxal 10% in aq. may be false-positive irritant reactions. 9 (45%) of our patients reacted to formaldehyde or glutaraldehyde. Glyoxal is an important allergen in dentistry and medical care, and we recommend it to be added to the antimicrobial patch test series. It also seems to be a 'hidden' allergen in the metal industry.     

Relationship of occupation to contact dermatitis: Evaluation in patients tested from 1998 to 2000

BACKGROUND: Both irritant and allergic contact dermatitis can be influenced by occupational and nonoccupational environmental exposures. OBJECTIVE: The aim of this study is to compare the occupations and allergens of occupational contact dermatitis cases with nonoccupational contact dermatitis cases. METHODS: Diagnostic patch testing was conducted with the 50 screening allergens of the North American Contact Dermatitis Group and occupational coding by the Surveillance Branch of the National Institute of Occupational Safety and Health. RESULTS: Of the 5,839 patients patch tested for contact dermatitis, 1,097 (19%) were deemed to be occupationally related. Of the occupational cases, 60% were of allergic and 32% were of irritant origin. The hands were the primary body part affected in 64% of allergic occupational cases and 80% of irritant occupational cases. Epoxy resin was the only allergen tested that was associated more with an occupational exposure than nonoccupational exposure. The allergens encountered most frequently in the occupational cases were carba mix, thiuram mix, epoxy resin, formaldehyde, and nickel. The medical field is overrepresented in the data compared with other occupations. CONCLUSIONS: Occupational contact dermatitis frequently was found to be multifactorial and associated with several specific allergens and occupations.     

The profile of patch test reactions to common contact allergens is related to sex

Background:  Women are more often patch tested than men, and the reactivity to patch test allergens is dependent on sex. However, it is unclear whether the profiles of test reactions are also sex-related.
Objective:  To compare the profiles of patch test reactions of men and women.
Methods:  Sex-related reaction profiles of 16 common patch test allergens were analysed based on data of 47 626 patients filed by the Information Network of Departments of Dermatology in Germany. The proportions of weak positive reactions and of questionable and irritant reactions were evaluated by calculating the positivity ratio (PR) and the reaction index (RI) separately for men and women for each allergen.
Results:  Of the 16 allergens evaluated, 8 had a higher PR and a higher RI in women than in men. 4 allergens had a lower PR and another 4 had a lower RI in women than in men. For allergens with similar sensitization prevalence in men and women, female sex was associated with a higher PR and RI ( P  < 0.01).
Conclusions:  There is a marginal disparity in the reactivity of men and women to patch test allergens that is probably not of clinical relevance but constitutes a scientific challenge.     

Immunopathological and ultrastructural findings in human allergic and irritant contact dermatitis

The histopathological features of allergic contact dermatitis were compared with those of irritant contact dermatitis in a group of 17 subjects. Each patient received simultaneous patch tests of a known allergen and a standardized irritant (benzalkonium chloride). The cellular changes occurring between 3 h and 7 days after patch test application were studied by light and electron microscopy and immunocytochemistry. No differences were observed between the induced allergic contact dermatitis (ACD) and the irritant contact dermatitis (ICD), either in the responding cell types or the sequence of cellular events. Both reactions showed a predominantly T lymphocyte infiltrate with no polymorphonuclear leukocyte involvement. Apposition of Langerhans cells to lymphocytes in the epidermis was seen in both types of response. Considerable variability in the intensity of reaction to irritant and allergen occurred within individuals. There was no statistically significant difference between the intensity of the reactions to the irritant and the allergen.     

Allergic contact dermatitis from formaldehyde

Formaldehyde is a common contact allergen. The prognosis of formaldehyde-sensitive patients is generally considered to be bad because of widespread exposure to formaldehyde. 11 patients with eczema and a positive patch test to formaldehyde were interviewed by a dermatologist and a toxicologist/chemist and instructed to fill in a questionnaire on exposure to chemical products. The content of formaldehyde and formaldehyde releasers in such products was examined using the database of the Danish Product Register (PROBAS) and by supplemental inquiries of manufacturers or importers. All the patients used one or more products containing formaldehyde or formaldehyde releasers. Sources of exposure were cosmetics and personal care products, dishwashing liquids, water-based paints, photographic products, etc. Patients were advised to use alternatives to those products containing formaldehyde or formaldehyde releasers. The status of 10 out of the 11 patients' eczema at follow-up was about 1/3 healed, 1/3 improved and in 1/3 no change. When the relevance of positive patch test reactions to formaldehyde was based on information obtained on exposure, a very high rate of current relevance was found. Computerized data on product composition allows the screening of products for contact allergens and also generates lists of contact allergens indicated for patch testing, based on the patients' own products.     

The reproducibility of patch tests

There is conflicting evidence regarding the reproducibility of patch testing. Discordant results have been reported in up to 44% of cases. The clinical relevance of these discordant patch tests has not been previously assessed. We studied 383 consecutive patients receiving simultaneous duplicate patch testing on opposite sides of the upper back with 10 allergens from the European standard series. Completely discordant patch tests-a negative test on one side with a positive test on the opposite side-were recorded in 30 (8%) patients. Two patients had discordant tests to two of the allergens; 28 had discordant reactions to one allergen. Completely discordant tests were recorded for nickel in 10 (3%) patients, balsam of Peru in two (0.5%), thiomersal in one (0.3%), cobalt in four (1%), paraphenylenediamine in three (0.8%), fragrance mix in two (0.5%), formaldehyde in four (1%), potassium dichromate in two (0.5%), lanolin in three (0.8%) and Kathon CG in one (0.3%). Of those patients with completely discordant patch tests, the allergen was deemed to be a true positive in 11 (3% of total) cases and of possible relevance in a further three. The allergen was felt to be relevant to the presenting complaint in seven (2% of total) patients.     

Irritant contact dermatitis to glyceryl monothioglycolate

Glyceryl monothioglycolate has recently been implicated as an allergen. A case of a hairdresser who used this material is presented. He appeared to have an irritant contact dermatitis on his fingertips. Patch testing the patient and extensive patch testing in a group of fifty-four volunteers showed a very high incidence of irritant positive patch tests. No instance of allergy could be demonstrated in the reading of the patch tests or in biopsies of several individuals. Differentiation between allergens and irritants is difficult at times, but is necessary to avoid mislabeling of chemicals.     

Patch testing with components of water-based metalworking fluids

Water-based metalworking fluids (MWFs) may cause both irritant and allergic contact dermatitis. Several well-known MWF allergens are available for patch testing, but considering the wide variety of possible components used in MWF, our diagnostic arsenal covers only a small part of potential allergens. We therefore selected 13 frequently used MWF components that might be sensitizers and had not yet been tested routinely. In 5 centres, 233 dermatitis patients with present or past occupational exposure to MWF were patch tested with this and other panels. Only 7 patients showed positive reactions to the study panel. Allergic reactions to the emulsifier diglycolamine [syn. 2-(2-aminoethoxy) ethanol] were seen in 5 patients, and 1 patient each reacted positively to 2-amino-2-ethyl-1,3-propanediol (AEPD) and methyldiethanolamine (MDEA). Clinical relevance of the reactions to diglycolamine was unequivocally proven by its presence in the MWF from the patients' workplace in 3 cases. Diglycolamine seems to be an important MWF allergen, independently from monoethanolamine and diethanolamine. A test concentration of 1% petrolatum (pet.) appears to be appropriate. The importance of AEPD and MDEA as MWF allergens still remains to be established. The lack of positive test reactions to the other MWF components tested may be due to their low-sensitizing potential or too low a patch test concentration being used.     

Thermographic assessment of patch-test responses

Infra-red thermography was used to quantify, at patch test sites, the allergic responses to experimental preparations of nickel sulphate and primary irritant responses to sodium lauryl sulphate in small groups of volunteers. The technique was also used to assess the patch-test responses in a much larger group of patients who had undergone routine patch testing for contact allergy with a wide range of test substances and among which there were large numbers of allergic, irritant and equivocal reactions. Thermographically, when compared to the surrounding normal skin surface, the sites of allergic reactions appeared as hot areas, the temperature and area of which were apparently dependent on the severity of the response. For allergic responses, there was a good correlation between the clinical assessment and either of two thermographic parameters, temperature and area of involvement. Compared with an aqueous solution of nickel sulphate, 'poor' formulations of the allergen, such as a suspension in soft paraffin base, elicited smaller and cooler reactions. Irritant reaction sites were not 'hot' and the temperature at such sites was no different from that of the surrounding normal skin. Infra-red thermography is a convenient non-invasive technique which apparently can be used to discriminate between irritant and allergic responses and to quantify the latter type of response.     

Angry back or the excited skin syndrome. A prospective study

Allergens eliciting weak positive reactions were retested to ascertain their reproducibility. Weak positive patch test reactions, concomitant to other weak or strong positive reactions, were retested after 3 weeks in 61 patients. 79 reactions were retested; 35 (44.3%) were negative. Allergens which are marginal irritants, e.g., formaldehyde, often gave weak positive reactions which were lost at retesting. In patients without dermatitis but with several strong positive reactions, lost reactions were frequently encountered, suggesting that strong reactions induced a state of hyperirritability. False positive reactions were often found in the proximity of strong reactions. We attempted to develop a nonspecific irritant (sodium lauryl sulfate) as a hyperirritability marker. A correlation between the score of this test and false positive reactions was not found. It is concluded that weak positive reactions should not be accepted as a proof of sensitization. The allergens eliciting these reactions should be retested at a later date.