Nickel: the search for alternative, optimal and non-irritant patch test preparations

Background/aims: Several contact allergens including nickel are also irritants. Ideal patch test preparations should not miss cases of contact allergy and should be non-irritant. The currently used nickel preparation (5% nickel sulfate in petrolatum; 0.19 m) is a compromise. The present aim was to compare the skin-irritant potential of various nickel preparations (sulfate, chloride, nitrate in petrolatum and in water) by using the objective, noninvasive laser Doppler technique for assessment.
Methods: Preparations with various nickel concentrations and vehicle controls were applied under occlusion (Finn chambers) on the volar forearms of healthy subjects for 48 h. The test sites were examined visually and measured with a laser Doppler flowmeter before, and repeatedly after, removal of test patches. Some preparations were also used when patch testing consecutive dermatitis patients.
Results: 0.19 m nickel chloride and nickel nitrate in petrolatum caused erythema as well as increase in skin blood flow, while lower concentrations (0.10, 0.05 and 0.01 m) did not affect skin blood flow. At higher concentrations the sulfate was less reactive than the other salts. The reactivity was more pronounced with the salts in petrolatum than in water. 0.05 m nickel nitrate was equivalent to 0.19 m nickel sulfate in diagnosing contact allergy in patch testing, while 0.30 m nickel sulfate in water missed several cases.
Conclusions: The laser Doppler technique is more sensitive than the naked eye and can indicate nickel patch test preparations with marginal irritant properties. Some promising alternative candidates have been identified.     

Site variations in patch test responses on the back

To establish the existence of intra-regional variations in response to allergens on the back, we performed patch tests in 21 patients at 2 different sites on the back. Visual readings using the numerical scale established by the International Contact Dermatitis Research Group were carried out 2 days after application of the allergen. After each visual reading, the skin blood flow at the test sites was quantified by laser Doppler flowmetry. The results of laser Doppler flowmetry showed a highly significant difference between the upper and lower back. It is therefore necessary that in quantitative and comparative investigations, symmetrical sites, i.e., left versus right sides of the body, should be studied.     

UV sunlight and patch test reactions in humans

No seasonal influence of UV sunlight on patch test reactions in humans over a period of 9 years of clinical practice was found in this retrospective study of almost 8000 patients. Although the mean UV monthly dose varies seasonally, up in the summer and down in the winter, no significant differences could be identified for patch test reactions, either for the mean number of positive test reactions or for the intensity of the skin reaction or for the id-like spread reactions seen in summer or winter. Furthermore, no short-term influences of UV exposure during the weekend preceding patch testing could be demonstrated. Therefore, reliable patch-test results can be expected at any season of the year from a general population, at least in Belgian-type climates.     

A method for the analysis of milk and egg allergens for the atopy patch test

Abstract:  The patch test with food antigens (atopy patch test, APT) has been reported as a more specific method than prick or RAST for the early detection of cow's milk and/or egg sensitizations in children. Standardization of APT extracts is a major issue on the road towards full clinical exploitation of this assay. Here, we used sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) to characterize sensitivity and specificity of commercial preparations of APT for milk and egg allergies, which are expected to improve the reliability of this test, when compared with fresh food allergen sources. We found that: (i) SDS-PAGE is an appropriate technique for quality control of APT and (ii) commercial milk and egg APT are equivalent to fresh food preparations in terms of allergen content. Clinical trials aimed at characterizing sensitivity and specificity of APT in the diagnosis of food allergy in children will benefit from this technique.     

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.     

Reproducibility of irritant patch test reactions to sodium lauryl sulfate in a double-blind placebo-controlled randomized study using clinical scoring

Reading of doubtful patch test reactions can be improved by comparing them to dened negative, allergic and irritant controls. For the latter, an irritant patch test is needed that gives sufficiently reproducible results. In our double-blind, placebo-controlled, randomized study, we have analysed the synchronous reproducibility of patch tests with 0%, 0.0625%, 0.125%, 0.25%, 0.5% and 1.0% sodium lauryl sulfate (SLS). Tests and readings were done according to ESCD guidelines. 139 patients (75 women, 64 men) 18 to 77 years old were tested. The % of positive patients as well as the % of reproducible positive reactions increased with rising concentrations of SLS to a maximum of approximately 90% and 85%, respectively, with 1 % SLS. Time courses of reactions were also related to the concentration of SLS: with 1 % SLS, plateau-type time courses were most common (65%), followed by decrescendo- (23%) and crescendo-type reactions (12%). With 1% SLS, very similar mild to moderate reactions were obtained on days 2 and 3. The reaction threshold and reproducibility of tests were not related to age and sex of patients or to their own assessment of skin irritability. We conclude that 1% SLS is appropriate for an irritant patch test that gives sufficiently reproducible results.     

Patch test reactions at D4, D5 and D6

In this retrospective study, patch test reactions in 3 groups of patients were analysed, in order to obtain information on the best day for the 2nd patch-test reading after day 2 (D2), on the usefulness of additional readings after D3, and on the dependence of patch-test reactions at D4, D5, or D6 on allergen and/or patient characteristics. In the years 1990 to 1995, patch tests were routinely read at D3 and D4 in 1096 patients, at D3 and D5 in 1243 patients, and at D3 and D6 in 1136 patients. In all of the 3 groups, significantly more positive reactions diminished than appeared de novo from D3 to the later reading. Virtually identical results were observed in subgroups of patients formed by sex, age or atopy. However, men might possibly react more slowly than women on patch testing, showing more increasing than diminishing reactions in the D3/D4- and the D3/D5-comparison. Reactions to individual allergens showed wide differences in this connection. Neomycin sulfate, cobalt salts, and p-phenylenediamine can be characterized as slow allergens, with more reactions increasing than diminishing from D3 to the later readings. With fragrance mix and balsam of Peru, the opposite pattern occurred. In all subgroups of patients, and with most allergens, the gain in positive reactions was biggest when an additional reading was performed at D5. We conclude that for a single 2nd patch test reading after D2, D3 is the best day, and especially better than D4. If a 3rd reading is performed, it should be done at D5 to get the maximum information out of patch testing. However, this extends the test procedure to at least 1 day of the weekend.     

Allergic contact dermatitis due to phenylephrine hydrochloride, with an unusual patch test reaction

2-day (2-D) closed patch tests are often used in daily clinical practice and useful for evaluating the cause of allergic contact dermatitis. However, even when 2-D closed patch tests at appropriate concentrations are performed for suspected allergic contact dermatitis based on clinical findings, positive reactions are not always obtained. Therefore, although the use of the allergen again induces similar symptoms, a definite diagnosis cannot be made in some cases. We report a case of allergic contact dermatitis due to phenylephrine hydrochloride in eyedrops, with an unusual patch test reaction. Although the results of the routine 2-D closed patch test were negative, a definite diagnosis could be made by closed scratch-patch test. In addition, long-lasting allergic patch test reactions were observed at the positive scratch-patch test site for about 3 months. We speculated that these unusual results on patch testing in our case were associated with the degree of percutaneous absorption of causative agents. Therefore, even when 2-D closed patch tests are negative, scratch-patch tests may be indicated for patients in whom clinical symptoms continue strongly to suggest contact dermatitis.     

Ring-shaped positive allergic patch test reactions to allergens in liquid vehicles

In recent years, we have observed several "ring-shaped" positive allergic patch test reactions to allergens dissolved in a liquid vehicle, a more intense response at the periphery of the site of application than in the central part. The occurrence of such reactions was evaluated for formaldehyde, Kathon CG, hydrocortisone and hexamidine diisethionate. Possible explanations for such reactions include pressure and/or a capillary effect.     

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients

BACKGROUND: The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). OBJECTIVES: To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. METHODS: In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). RESULTS: Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. CONCLUSIONS: These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.