Scientific Update No

Transcription

1 In this newsletter: 1) The detection of clinically relevant contact allergens with a standard screening tray of 28 allergens 2) A multi-center, retrospective review of patch testing for contact dermatitis in allergy practices 3) The diagnostic value of patch tests with two fragrance mix I preparations for detection of clinically relevant perfume allergy 1) The detection of clinically relevant contact allergens with a standard screening tray of 28 allergens The TRUE Test Panels 1, 2 and 3 on the market in the United States contained until recently 20 individual allergens and 8 allergen mixes.* Previous published studies had raised concern regarding the adequacy of the initial two-panel system (16 individual allergens and seven allergen mixes) in fully assessing patients with possible allergic contact dermatitis (ACD). In this retrospective study the effectiveness of all 28 allergens and allergen mixes from the three-panel TRUE test product as the sole diagnostic tool for detecting ACD has been evaluated. The study was done at the University of Kansas and at American Dermatology Associates in Shawnee, Kansas, USA. 1) * In March 2012, FDA approved the addition of more allergens to Panel 3. Background Patch testing is the gold standard for evaluating patients with suspected ACD. Several studies have analysed the reliability of a standard series (referred to as baseline series in Europe) alone in fully evaluating ACD. These studies have shown that any one standard series may be insufficient for complete and correct diagnosis. To increase the diagnostic accuracy of patch testing, physicians must use allergens beyond those present in the standard series. Study details and results The study is a retrospective study looking at a total of 2088 consecutive patients with suspected ACD. They were patch tested between 1995 and 2010 with 27 of the 28 allergens and/or mixes similar to those present in the TRUE Test product. The allergen preparations from the North American Contact Dermatitis Group (NACDG) standard series (Finn Chambers filled with petrolatum and aqueous patch test products from Chemotechnique ) were used for the patch testing. Instead of Quinoline mix, which has never been a part of the standard series of the NACDG, the patients in this study who gave a history of using Clioquinol were tested with this allergen. Page 1 of 6

2 The allergens and allergen mixes tested are shown in the following table: Tested allergens and allergen mixes corresponding to TRUE Test Panels 1, 2 and 3 in the USA (incorporated in Chemotechnique patch test products): From Panel 1: Nickel sulphate, Wool alcohols, Neomycin sulphate, Potassium dichromate, Caine mix, Fragrance mix, Colophony, Paraben mix, Peru balsam, Ethylenediamine dihydrochloride and Cobalt dichloride. From Panel 2: p-tert-butylphenol formaldehyde resin, Epoxy resin, Carba mix, Black rubber mix, Cl+Me-Isothiazolinone, Quaternium-15, Mercaptobenzothiazole, p-phenylenediamine, Formaldehyde, Mercapto mix, Thimerosal and Thiuram mix. From Panel 3: Diazolidinyl urea, Imidazolidinyl urea, Tixocortol-21-pivalate, Budesonide and Clioquinol. The patients were also tested with the remaining allergens in the NACDG standard series (in total 65 allergens and allergen mixes) together with supplementary allergens (pure chemicals, personal/work-related products, etc.). Relevance, exposure, and dermatitis site and type were recorded (66.3%) patients had at least one positive reaction to TRUE Test allergens. Among these 1385 patients, 28.5% would have had all of their known clinically relevant allergic reactions detected with the TRUE Test panels only. If only the TRUE Test allergens had been tested, 25.6% would not have had any of their clinically relevant allergens detected, and 45.9% would have been aware of only a partial list of their allergens. Expanding the panel of standard allergens to include all the 65 allergens and/or mixes from the NACDG standard series, 43.0% of the patients would have had all their potential allergic reactions detected, 13.1% would not have been aware of any of their allergens, and 43.9% would have been partially evaluated. When relevance was used, these percentages did not change materially. It is discussed that the use of standard series alone may be inadequate for accurate evaluation, as no standard series can include all allergens from the environments of all individual patients. It is concluded that when put into the perspective that over 3700 allergens are identified in the literature, the TRUE test system performs well, given its relatively small number of allergens. Finally, it is also noted that it is difficult to gauge exactly how well any given standard series performs, as the results will be affected by the number of non-standard allergens tested. Comments from SMARTPRACTICE DENMARK In March 2012 new configurations and new allergens on TRUE Test Panel 2 and Panel 3 were approved by the FDA. From now on the TRUE Test product in the USA will consist of 3 panels with 27 individual allergens and 8 allergen mixes. Page 2 of 6

3 In this study it is discussed whether or not the addition of more allergens to the product will increase the amount of patients having all of their known clinically relevant allergic reactions detected when they are tested with the TRUE Test panels only. It is shown that an increase from 28 to 65 allergens and allergen mixes does only increase this amount to a limited extent so physicians still have to use allergens beyond those present in the standard series. TRUE Test is a screening tool and it will never be possible to implement all known allergenic substances in TRUE Test. It is desired by many patch test users that the available number of allergens and allergen mixes in TRUE Test should be higher. Long development time and costs restrict development of many allergens and therefore it has been decided that the product will encompass only the major allergens recognized by contact dermatitis research groups in the USA and Europe. Together with the high quality of the product, this decision results in a clinically effective and standardized first-line screening tool. Relevance to TRUE Test The changes in configurations and new allergens and formulations in TRUE Test approved in March 2012 for the US market are: - On Panel 2, the new allergen Methyldibromo glutaronitrile has substituted Mercaptobenzothiazole (which has been moved to Panel 3). Thimerosal (Thiomersal) has been formulated into a new vehicle. - Panel 3 consists of 11 single allergens and one allergen mix: Diazolidinyl urea, Imidazolidinyl urea, Tixocortol pivalate, Budesonide, Hydrocortisone-17-butyrate, Mercaptobenzothiazole (on the European Panel 2) and Quinoline mix (on the European Panel 1), and the new allergens Gold sodium thiosulphate, Bacitracin, Parthenolide, Disperse blue 106 and Bronopol. References 1) D Patel & D V Belsito: The detection of clinically relevant contact allergens with a standard screening tray of 28 allergens. Contact Dermatitis 2012: 66: ) A multi-center, retrospective review of patch testing for contact dermatitis in allergy practices Again in this American retrospective study it was discussed whether patch testing results using a limited panel of allergens such as in the TRUE test product compared with an extended panel will miss a significant number of positive patch tests. 1) Background The aim of this retrospective study was to determine whether the use of TRUE Test consisting of 28 allergens and allergen mixes alone, compared with an expanded panel, will miss a significant number of positive patch tests. One of the principal advantages of TRUE test is that the allergens are premeasured and preloaded on the tape requiring minimal preparation time. Disadvantages include lack of flexibility in allergen choice and the limited number of allergens available. Expanded panels available for use in the USA include the North American Contact Dermatitis (NACD) Panel, a series of 65 allergens based on the most common Page 3 of 6

4 relevant allergens. Supplementary allergens can also be used for patch testing such as personal products. Study details and results Between 2005 and 2010, 427 patients suspected of having allergic contact dermatitis (ACD) were evaluated by 5 allergists in 3 separate Allergy and Immunology offices in the USA. The patients were patch tested with a combination of limited (TRUE Test), expanded (NACD panel), and supplementary allergens (cosmetics, corticosteroids, or personal products). The 9 most common positive patch test allergens were Nickel, Fragrance mix, Cobalt, p-phenylenediamine (PPD), Thimerosal (Thiomersal), Neomycin, Balsam of Peru, Thiuram mix and Glutaraldehyde. Within TRUE Test allergens alone, the most common positives were Nickel, Fragrance mix and PPD. 57% of the patients were positive to at least one TRUE Test allergen, 26% would have been partially evaluated, and 12.5% would have been completely missed if patch tested with TRUE test allergens alone. Supported by these findings and compared with previous studies, the TRUE Test product appears to be a sufficient screening tool, but expanded panels may be necessary to adequately assess patients with ACD. Comments from SMARTPRACTICE DENMARK The results from this study support the results presented in the study from Patel & Belsito discussed above: Again it can be concluded that TRUE Test is a sufficient screening tool, but expanded panels may be necessary to adequately assess patients with ACD. The advantages of TRUE test are highlighted in this study: The allergens are premeasured and preloaded on the tape requiring minimal preparation time. Compared to other patch test systems, where risk of variation in the amount of allergens used highly exists, TRUE Test is also a more reliable and standardized product. Relevance to TRUE Test TRUE Test consists of 3 panels with a total of 35 allergens and allergen mixes. On some European markets only 29 allergens and allergen mixes are available. References 1) M Camacho-Halili et al: A multi-center, retrospective review of patch testing for contact dermatitis in allergy practices. Ann Allergy Asthma Immunol. 2011: 107: Page 4 of 6

5 3) The diagnostic value of patch tests with two fragrance mix I preparations for detection of clinically relevant perfume allergy In this article two different Fragrance mix I test preparations are evaluated for their ability to detect perfume contact allergy in consecutively tested eczema patients. 1) Fragrance mix from TRUE Test is one of the preparations. Background Sensitization to fragrances is common, with an estimated prevalence of approx %. Since the late 1970s, Fragrance mix I (FM I) has been used as a screening tool for fragrance contact allergy. Studies suggest that FM I detects 70-80% of patients who are allergic to fragrances. The aim of this retrospective study was to evaluate two different FM I test preparations for their ability to detect perfume contact allergy in consecutively tested eczema patients. And in order to compare the diagnostic value of the two fragrance mixes, a gold standard for the diagnosis of fragrance contact allergy was defined on the basis of questionnaire responses as a certain history of adverse reaction to fragrances. Study details and results This study includes a total of 949 patients. The patients were patch tested from 2000 to 2002 at Odense University Hospital, Denmark. 70 patients had a certain history of adverse reaction to fragrances, 92 patients had a probable history, 122 had a possible history and 665 patients had no history of adverse reactions to fragrances. The patients were patch tested with two FM I preparations: The Fragrance mix I patch (430 µg/cm²) from the TRUE test product and the Fragrance mix I preparation (8% in petrolatum) from Trolab. A positive reaction to FM I from TRUE Test was found in 43 patients (4.5%), and a positive reaction to FM I in Trolab was found in 80 patients (8.4%). In total, 89 patients (9.4%) reacted to one or both of the patch test preparations and 34 reacted to both. Based on the histories of possible perfume allergy by the patients the diagnostic value of the two preparations was assessed and compared. Statistical calculations showed that it is advantageous to test with both preparations. But the low sensitivity rates for both preparations strongly support the use of additional fragrance allergens, such as patch testing with patients own products. Comments from SMARTPRACTICE DENMARK Regarding TRUE test and Fragrance mix, it has been discussed over the years if the Fragrance mix patch is too low in dosage, which could be one of the causes for the low sensitivity rate. Another problem is that Fragrance mix only contains 8 fragrance substances and as the composition of perfumes and fragranced products changes and new allergenic fragrance substances are detected, it will never be possible to cover all allergenic substances in one TRUE Test formulation. Page 5 of 6

6 Nevertheless Fragrance mix is still a valuable screening tool and it has been decided to improve the TRUE Test product by developing a patch with a higher content of Fragrance mix. Relevance to TRUE Test Fragrance mix I is included on Panel 1. References 1) L Schollhammer, K E Andersen & C G Mortz: The diagnostic value of patch tests with two fragrance mix I preparations for detection of clinically relevant perfume allergy. Contact Dermatitis 2012: 66: Page 6 of 6