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Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry.

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.

Adult↗

Skin absorption from patch test systems.

The development of topical drug products requires testing for skin toxicology reactions. A variety of patch test systems are available with which chemicals are applied to skin. The purpose of this study was to determine the skin absorption of paraphenylenediamine (PPDA) from a variety of such systems. [14C]-PPDA (1% pet., USP) was placed in a variety of patch test systems at a concentration normalized to equal surface area (2 mg/mm2). Skin absorption was determined in the guinea pig by urinary excretion of 14C. There was a six-fold difference in the range of skin absorption (p less than 0.02). In decreasing order, % skin absorption from the systems were Hill Top Chamber (53.4 +/- 20.6) greater than Teflon Control patch (48.6 +/- 9.3) greater than Small Finn Chamber with paper disc insert (34.1 +/- 19.8) greater than Small Finn Chamber (29.8 +/- 9.0) greater than Large Finn Chamber (23.1 +/- 7.3) greater than AL-Test Chamber (8.0 +/- 0.8). Thus, the choice of patch system could produce a false negative error if the system inhibits skin absorption, with a subsequent skin toxicology reaction.

Administration, Cutaneous↗

Patch test response to house dust mites is positive in children with atopic dermatitis and in their parents.

We studied the patch test response to Dermatophagoides pteronyssinus in 79 atopic children and in their parents. The atopic children were divided into 3 groups: 1) children with atopic dermatitis (group 1); 2) children who had suffered from atopic dermatitis but the disease was cured (group 2); and 3) atopic children with asthma and without atopic dermatitis (group 3). Our data show that a significantly higher proportion of children with atopic dermatitis (groups 1 and 2) have positive patch tests to Dermatophagoides pteronyssinus in comparison to atopic children without atopic dermatitis (group 3) and the controls (p < 0.001). In addition, we have shown that a positive patch test to Dermatophagoides pteronyssinus is significantly more common in parents of children with atopic dermatitis with respect to parents of children with asthma or parents of control children.

Adolescent↗

Patch test reactions to mite antigens: a GERDA multicentre study. Groupe d'Etudes et de Recherches en Dermato-Allergie.

We performed patch tests with Dermatophagoides pteronyssinus (Dp) antigens from 2 different sources in 355 non-randomly selected patients with atopic dermatitis (AD) and 398 subjects of a control group. The study demonstrated that contact sensitization to mites occurred in an appreciable % of AD cases (20.8%), using commonly available assay products. The differences recorded between the 2 materials tested were related to the concentration of P1 antigen. Non-atopic patients rarely showed positive reactions to Dp (0.75%), when strict criteria for readings were applied and if 2 readings were performed. Patients with positive patch tests did not necessarily show positive immediate skin tests. It would be useful to carry out tests systematically in atopic patients, even if it is not yet known what modern treatment would be best for the patient. Laboratories still do not provide standardized house dust mite preparations--measuring and codifying their biological activity--for use in patch tests. It is to be hoped that the extension of this type of test will lead to the production of better test materials, in syringes with homogeneous dispersion and concentration.

Administration, Inhalation↗

Allergic patch test reactions caused by the rubber chemical cyclohexyl thiophthalimide.

Rubber chemicals are among the most common occupational contact sensitizers. The most common rubber sensitizers are thiurams, thiazoles, carbamates and paraphenylenediamine derivatives. Here we present data on a less-well-known rubber chemical, N-(cyclohexylthio)phthalimide (CTP; CAS 17796-82-6). This chemical is currently the most widely used vulcanization retarder, but data on allergic contact dermatitis caused by CTP are lacking. We conducted a survey of 310 patients who had been patch tested with 30 rubber chemicals including CTP. 11 (3.5%) showed an allergic patch test reaction provoked by CTP, and 9.0% by thiurams. 4 of the patients reacted only to CTP and not to other rubber chemicals, whereas the other 7 concomitantly reacted to other rubber chemicals. After analyzing the patch test data of these 11 patients, it was concluded that CTP probably did not cross-react with the other rubber chemicals. Therefore the patch test results may indicate independent sensitization to CTP and other rubber chemicals. Because very little data on the components of rubber chemicals in rubber products are available, the source of the putative sensitization to the rubber vulcanization retarder CTP is unknown.

Cross Reactions↗

Delayed patch test reactions at days 7 and 9.

403 consecutive patients were examined on days 2, 4, 7, and 9 following application of patch tests. Late positive reactions, i.e., those which manifested after day 4, were seen in 29 patients (7.2%). The allergens which most commonly produced late positive reactions were neomycin (7), potassium dichromate (4), and cobalt (3). Paired patch test readings on days 4 and 7 were more reliable than those on days 2 and 4. If only 1 patch test reading were performed, a single reading on day 4 would have been most useful. The reading on day 9 proved to be of limited value. Of 11 patients who were retested after an interval of more than 6 months, 7 showed earlier eliciting reactions, which may have been due to active sensitization.

Dermatitis, Contact↗

Sodium lauryl sulfate irritant patch tests. II. Variations of test responses among subjects and comparison to variations of allergic responses elicited by Toxicodendron extract.

Inflammation was induced on the forearms of volunteers by twenty-four closed patch tests to either the irritant 10% sodium lauryl sulfate (SLS) or Toxicodendron extract. Each chemical was tested at eight sites on the ventral forearms of each volunteer in order to assess the variability of response among test sites in individual subjects. Inflammation was assessed about 10 minutes after patch tests were removed. The degree of inflammation elicited by both Toxicodendron and SLS was variable among subjects, but variation among individual test sites was much more marked in subjects tested with SLS (p less than 0.002). The marked variability of responses to irritation that occur in any single subject may explain why irritant patch test responses do not reliably identify the irritation-prone individual.

Adolescent↗

Can pre-employment patch testing help to prevent occupational contact allergy?

175 subjects (157 female, 18 male) were patch tested with a standard series of allergens (Epipharm Allergy Service, GmbH, Linz, Austria), during pre-employment examinations in the pharmaceutical industry, considered an industry at risk for the development of contact sensitization. None of those examined had contact dermatitis prior to testing and none gave a positive history of hand ecczema. Patch testing was positive in 12 (7%) subjects, of whom 7 showed a positive reaction to only 1 contact allergen and 5 reacted to several contact allergens. 5 subjects (2.9%) reacted positively to metal salts (nickel, cobalt, chromium), 5 (2.9%) had a positive skin reaction to mixtures of rubber additives, and the remaining 2 to other allergens.

Adult↗

Quantification of allergic and irritant patch test reactions using laser-Doppler flowmetry and erythema index.

The laser-Doppler blood flow and erythema index were assessed in 16 patch test reactions caused by irritants (1% aq. sodium lauryl sulphate and 1% aq. benzalkonium chloride) and in 13 varied allergic reactions, at 2 or 4 days. Both irritant and allergic responses produced statistically significant increases in laser-Doppler flow index and erythema index compared to control sites (p less than 0.05 or less, using the Wilcoxon rank-sum test). A disproportionately greater increase in erythema index than in laser-Doppler flow was seen in mild irritant reactions, compared to allergic, though the two could not be reliably distinguished by these tests. 2 non-allergic nickel sulphate sites produced an increase in both blood flow and erythema without any clinical change. Petrolatum alone produced no significant change in either measurement. The laser-Doppler flow showed an overall correlation with the erythema index (product moment method; r = 0.55, p less than 0.001), but there was little correlation between these indices and patch test reactivity as judged clinically by conventional scoring. Generally, allergic and irritant patch test reactions could not be differentiated on the basis of laser-Doppler flow or erythema index. However, the disproportionate increase in erythema index over laser-Doppler flow index for mild irritant responses warrants further study in other irritant models.

Allergens↗

The outcome of an additional patch-test reading on days 6 or 7.

In a retrospective study (period 1997-1998), the usefulness of an additional patch-test reading on day (D) 6 or 7 was investigated. In 62 out of 760 patients (8.2%), 77 late-positive reactions, those manifest after D3, were seen. 4 late reactions of allergens of which a related allergen reacted earlier (at D2 or D3) in the same patient were not incorporated in the study as late-positive. Allergens most involved in producing late-positive reactions were nickel sulfate (20 reactions), neomycin sulfate (7), tixocortol-21-pivalate (5), p.t. butylphenol formaldehyde resin (5) and Cl+ Me isothiazolinone (5). Special attention is paid to ?+ reactions at D6 or D7, because these reactions could add extra information to the outcome of patch-test readings, considering that this might be a group of allergens that has been positive between D3 and D6/7 or become positive later on. When this group is included, the total number of late-positive reactions is 105 in 88 out of 760 patients (11.6%). By doing D3 readings in combination with D6 or D7 readings only, one would miss 24 positive reactions. However, we concluded that it was preferable to have a reading on D2 and D3. An extra reading on D6 or D7 is very useful as it gives additional information in 8.2% of patch-tested patients.

Adolescent↗

Allergic and irritant patch test reactions and atopic disease.

This study presents a profile of patients with chronic recalcitrant eczematous disease referred by dermatologists for contact allergy evaluation. Allergic contact dermatitis (ACD) and irritant responses were carefully defined, as was the presence or absence of atopy obtained by history. Of 410 patients studied, 44% had no history of atopic disease and 46% were classed as definitely atopic. Among relevant ACD patch test reactors (n = 198), 51.5% had atopy, compared with 40.9% with no atopy but this difference was not significant. Likewise, among atopics (n = 189), 54% had definite, relevant ACD patch test responses while 33.9% had negative ACD (again not significant). Significance was seen in the higher mean number of positive allergic patch tests in the atopic group (2.7 versus 2.0, p = 0.0223). Irritant patch tests were highest among patients with both ACD and atopy (p = 0.0308) and the proportion of irritant responses correlated with increasing numbers of positive ACD tests. We conclude that atopics are at least as likely to have ACD as are non-atopics. Irritancy is increased in these patients with chronic dermatitis and the frequency of irritant reactions correlates with both greater numbers of ACD responses and with presence of atopy.

Adolescent↗

Patch test responses to rockwool of different diameters evaluated by cutaneous blood flow measurement.

Rockwool is a man-made mineral fiber used mainly for insulation, which can cause mechanical skin irritation. This study was performed to evaluate the irritant potential of rockwools of different diameters and to compare the change of blood flow, measured by laser Doppler flowmetry, at different patch test occlusion times with rockwools. Rockwool A (mean diameter 4.20 +/- 1.96 mu) was more irritating than rockwool B (mean diameter 3.20 +/- 1.5 mu). The difference was more clearly observed in a 48-h patch test than in an 8-h or 24-h test. We concluded that laser Doppler blood flow measurement was a useful experimental tool for the evaluation of irritant patch test responses to mechanical irritants like rockwool, and that 48 h or more of occlusion time was necessary to produce irritant patch test responses to certain types of rockwool.

Construction Materials↗

Comparison of patch test contact sensitivity to acetone and aqueous extracts of Parthenium hysterophorus in patients with airborne contact dermatitis.

Our aim was to compare the degree of patch test positivity to acetone and aqueous extracts of Parthenium hysterophorus in patients with airborne contact dermatitis. We performed patch testing with the Indian standard series (which includes aqueous extracts of parthenium, xanthium and chrysanthemum), and with 1 : 100 and 1 : 200 dilutions of an acetone extract of parthenium in 72 patients with airborne contact dermatitis. All patients showed contact sensitivity to the 1 : 100 dilution and 67 patients had positive allergic reactions to the 1 : 200 dilution of the acetone extract, whereas only 45 patients showed a positive reaction to the aqueous extract of P. hysterophorus. Our results confirm that parthenium allergens are more soluble in acetone than in water, and that the acetone extract is significantly better in detecting contact sensitivity to parthenium in patients with suspected plant dermatitis. Hence, the acetone extract is recommended for routine patch testing.

Acetone↗

[Determination of alkali resistance by skin patch testing].

298 patients suffering from eczema were tested for alkali-resistance by means of the method according to Burckhardt-Locher (ARBL) as well as patch-testing. If ARBL revealed decreased alkali-resistance, there was a high correlation with the outcome of the patch-test of alkalis. If ARBL showed normal values, however, additional patch-testing detected reduced alkali-resistance in 42.9% of the cases. In order to make a well-founded diagnosis of alkali-resistance, we suggest to combine both methods and/or to include a control of ARBL after 24 hours as proposed by Burckhardt.

Adolescent↗

Patch testing: a retrospective analysis of 103 patients with emphasis on practical aspects for the clinician.

BACKGROUND: Allergic contact dermatitis is a common dermatologic disorder caused by small chemical molecules that can penetrate the skin barrier. Thousands of chemicals capable of inducing allergic contact dermatitis have been identified. To cure allergic contact dermatitis, the allergen should be identified and eliminated from the environment of the patient. Patch testing, utilizing a variety of standard panels of the most frequent allergens, is used to identify the allergen in question. Patch testing is still the gold standard tool used to identify one or more substances that may contribute to the etiology of allergic contact dermatitis. OBJECTIVE: To determine the frequency of patch test positivity and to identify the most common allergens in patients with suspected allergic contact dermatitis. METHODS: A retrospective analysis of files of 103 patients who have been clinically diagnosed to have allergic contact dermatitis and have been patch tested using a standard technique with a Northern American Contact Dermatitis Group series. RESULTS: Sixty-two patients (60.2%) showed positive reactions to one or more substance. The most common allergens were nickel sulfate, fragrance mix, and neomycin sulfate. There was an increased frequency of positive reactions to fragrance mix and a significant decrease of frequency of thimerosal positive reactions. CONCLUSIONS: Increased awareness of allergens and their potential sources may help to limit the usage of these chemicals in manufacturing consumer products. This may have contributed to decreased prevalence rates of certain allergens such as thimerosal and paraphenylenediamine.

Adolescent↗

Interlaboratory evaluation of a human patch test for the identification of skin irritation potential/hazard.

The human 4 hr patch test provides an opportunity to identify substances with significant skin irritation potential without recourse to the use of animals. To demonstrate the validity of the method it must be relevant and reliable. It is self-evident that the method is relevant to the identification of skin irritation hazards to humans. However, it is essential that the results be reproducible. This paper presents data on a number of substances tested by different laboratories. Eight substances were tested by two or more laboratories and the data compared with a standard positive control, 20% sodium dodecyl sulfate. In almost all cases, the outcome of this comparison was identical. Thus, despite the fact that there is known variability among human subjects in terms of skin reactivity to irritants, this simple method showed good reproducibility for the classification of acute skin irritation potential. Therefore, it is argued that this human 4-hr patch test is a valid alternative to the equivalent rabbit test for the assessment of skin irritation hazard to humans.

Adult↗

[Allergic contact dermatitis due to eye drops. Their clinical features and the patch test results].

We studied the clinical manifestations and causative agents in cases with allergic contact dermatitis due to eye drops who consulted the Department of Dermatology, Nippon Medical School during the period of 9 years between January, 1987 and December, 1995. Among 66,165 cases who visited the department during the studied period, 3,903 were suspected as contact dermatitis or drug eruption and underwent patch test. 141 of 3,903 cases (3.6%) were patch tested with eye drops and 49 cases (34.8%) reacted positively and were diagnosed as allergic contact dermatitis. Allergic ingredients were tested in 36 cases by the patch test with every ingredient. The 49 cases diagnosed as allergic contact dermatitis by eye drops, included 17 males and 32 females. 81.6% of the patients were aged over 40 years. The most frequent ages were between 60 and 69 years. The period from onset to the first visit to us was less than two weeks in 54.1% of the cases, but 3 cases consulted us after more than six months. The determined allergens are noted in order of frequency as follows: 1) fradiomycin sulfate in 14 cases, 2) ketotifen fumarate in 6 cases, 3) dibekacin sulfate in 3 cases, 4) befunolol hydrochloride in 3 cases, 5) phenylephrine hydrochloride in 3 cases and 6) benzalkonium chloride, the preservative of eye drops in 3 cases. Fradiomycin sulfate showed cross reactions to other aminoglycosides in the present cases. Every ingredient should be tested as much as possible, because there is a possibility that a preservative or a vehicle ingredient may be the allergen, though the incidence is low.

Adolescent↗