Improving Patch Test Efficacy

Part 1 of this article series focuses on patch test kits, choosing the right patient, selecting an adequate screen and suspect allergens, accepting test limitations, and supplemental panels.  

patch test

Allergic contact dermatitis (ACD) is a common disease that affects more than 13 million Americans each year.1 The societal impact of ACD is significant, with an estimated prevalence in the United States of almost 20% and an annual cost approaching $2 billion.1,2 ACD can also have a significant negative physical and emotional impact on patients’ quality of life. With thousands of potential allergens lurking amidst innumerable products, isolating relevant allergens can be a daunting and often frustrating task. However, with appropriate testing, education, and diligence, remission of ACD is an attainable goal. 

This 2-part series discusses improving patch test efficacy. Part 1 provides information on patch test kits, choosing the right patient, selecting an adequate screen and suspect allergens, accepting test limitations, and supplemental panels. Part 2 discusses performing the test correctly, use in pediatric populations, relevance determination, and education.

Patch Test Kits

In 1895, a man developed a blistering reaction after applying a mercurial cream to treat pediculosis pubis. After trading one pruritic groin affliction for another, he sought the professional opinion of Josef Jadassohn, a professor of dermatology and syphilology at the University of Bern. To “accustomize” the patient to mercury, Jadassohn applied a mercurial patch to the patient’s arm.3,4 However, the patient returned a few days later with blisters at the patch site. Where others might have been discouraged, Jadassohn saw potential. He described the observation as “Funktionelle Hautprüfung,” or the functional exam/patch test, and proposed that this new technique be developed as a diagnostic tool for medicament-induced reactions.3 

patch test

With the work of Jadassohn and other patch-testing leaders, such as Bruno Bloch and Marion Sulzberger, patch testing was gradually refined, eventually gaining traction within the dermatology community. However, the specific details of substrates and procedural timing were left to the discretion of the administering health care provider. Among many of Bloch’s major contributions to patch testing, he helped develop the idea of constructing a limited standard series for patch testing.3 His ideas were further expanded and refined by one of his former assistants, Paul Bonnevie, a professor of occupational medicine in Copenhagen. Based on his experiences and observations at the Finsen Institute in Copenhagen, Bonnevie published the first screening series of 21 allergens in his textbook on environmental dermatology in 1939.3 His list of allergens is considered to be the prototype of the standard series of patch tests.3 This list remained unchanged until 1955, and it is speculated that the stagnation of the series was a result of  World War II.3,5 Today, 7 allergens from his initial series remain in modern standardized screens.3 The rest were deemed to be less environmentally relevant, likely due to shifts in industrial practices.5

In the 1960s, coalitions such as the Scandinavian Committee for Standardization of Routine Patch Testing and the International Contact Dermatitis Research Group began forming to push for professionally driven standardization. Soon after, the North American Contact Dermatitis Group (NACDG) was established as a research consortium.6 

By the 1980s, the FDA called for official regulations on the sale and production of allergens in the United States due to the lack of evidence supporting the safety and efficacy of patch testing.7 In response, the early pioneers in the NACDG collaborated with the German Hermal/Trolab to develop a standardized allergen test kit in 1988.8 As a result, Hermal/Trolab produced a European-based 20-allergen patch test kit that was distributed by the American Academy of Dermatology.8 This was the first FDA-approved commercially available kit.7,9 By 1995, Howard Maibach, MD, and the Pharmacia-Upjohn Company developed a kit customized for a North American market.8 The kit was expanded to 23 allergens and distributed as the Thin-Layer Rapid Use Epicutaneous (T.R.U.E) Test (Smart Practice).8 A 1997 survey of 14% of US dermatologists revealed that 3 of 4 dermatologists who patch tested used T.R.U.E. Test, with the most common cited reason for use being ease of use.10 In 2007, 5 new allergens were added to the test11 and by 2012, T.R.U.E Test had expanded to 35 allergens and 1 vehicle control.7,9 Over the last 2 decades, the use of the T.R.U.E Test kit became widespread within the US.12 Internationally, other screening kits are regionally utilized, such as the European Baseline or Latin American Baseline, in over 100 countries.9

The 35 allergens included in the kit are believed to identify 69.7% to 75.1% of the positive reactions identified by the NACDG screening series of 70 allergens.13 Comprehensive patch testing using supplemental allergens provides a higher diagnostic value compared to the kit, as the yield of positive reactions is significantly higher. Unfortunately, unlike customized or comprehensive patch testing, it is not a simple task to update allergens in the kit annually to reflect changing allergen prevalence rates. 

According to Curt Hamann, MD, the president and chief executive officer of SmartHealth, Inc. the current manufacturer of the kit, “to change an allergen in the current T.R.U.E Test, the new allergen must meet the preclinical and clinical requirements mandated by the FDA’s Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health. In addition, 2-year stability data must be collected substantiating that the introduction of the new allergen has not influenced the dose of the 11 other allergens on the same panel over the shelf-life label of the product. Therefore, to replace an allergen on the existing product could take between 7 and 9 years.” 

He added, “The cost of preclinical pharmaceutical development, validated analytical method development, and stability studies followed by meeting clinical trial requirements of dose response and safety and efficacy also takes between 5 to 7 years.” 

Optimization strategies are discussed below to increase patch test efficacy.

Selecting the Right Patient

Testing should be considered (1) when pruritic dermatitis persists greater than 2 months and is recalcitrant to the standard of care treatment, or (2) when there is only improvement with systemic immunosuppressant medications or increased dosing of high-potency topical corticosteroids. Certain distributions are suggestive of ACD, such as eyelid, facial, dorsal hand, dorsal foot, perineal, unilateral, or of widespread distribution. The course of the disease may be indicative of ACD, such as dermatitis with frequent recurrent flares or a notable temporal pattern, such as exacerbation of symptoms associated with occupational hours and improvement during time off.  

Selecting an Adequate Screen and Suspect Allergens

table 1The T.R.U.E Test is the only FDA approved commercially available “ready-to-use” allergen patch test system “kit” in the United States. The kit consists of 3 standardized panels pre-impregnated with 35 allergens and allergen mixes in a hydrophilic gel delivery system (Table 1).14 By selectively testing many of the most common allergens, the kit provides a good baseline screen. Beyond the baseline screen, consideration of the patient’s avocation, occupation, age, and gender favors certain allergens to emerge as likelier culprits. Selection criteria based on probabilities must be used as there is no comprehensive set list of allergens that is specifically tailored to suit all persons. Notably, the American Contact Dermatitis Society (ACDS) has designed and updated a core 80 screening panel containing 8 groups of clinically relevant allergens ranked in decreasing order of prevalence.15 The ACDS Core 80 series is routinely updated. Table 2 presents a suggested supplemental allergen tray that highlights the allergens at the top of that list, based on known prevalence rates. 
table 2

 

Limits of the Test

To compare the difference in reactivity between comprehensive individually loaded haptens applied to Finn Chambers and the T.R.U.E Test, a study of 167 patients found that T.R.U.E Test diagnosed roughly 25% more reactions to nickel, neomycin, and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), while the Finn Chambers detected almost twice the number of reactions to fragrance mix, balsam of Peru (BOP), and thiuram mix.16 The study also revealed that carba mix and formaldehyde allergies were difficult to diagnose with both the T.R.U.E Test kit and the Finn Chambers.16 Volatile substances such as formaldehyde and acrylates require loading into the chambers immediately prior to application onto the patient. 

The limited literature available suggests that the sensitivity for the screening patch test series (specifically the European Contact Dermatitis Research Group and the NACDG screening series) is roughly 70%.17,18 Evidence supports that expanded patch testing with high suspect supplemental allergens has a direct impact on the sensitivity and yield of positive reactions of the test.19,20 It is important to remain cognizant that the testing concentration of the substrates is chosen based on evidence to yield the highest numbers of true-positive reactions and the lowest numbers of irritant reactions and active sensitizations.21 

False-negative reactions may occur if the concentration of the testing substance is too low, there is insufficient contact time with the hapten, there is failure to perform a delayed reading beyond 72 hours, or if the patient has utilized an immunomodulator (such as corticosteroids or exposure to UV radiation) in the patch test period.

Supplemental Panels

Since 2012, the ACDS has published the ACDS Core 80, a screening series that was evidence- and experienced-based with allergens listed in order of descending prevalence.22 As clinically indicated, providers may also test other expanded supplemental series, in addition to the ACDS Core 80. Available series include Bakery, Cosmetics, Cutaneous Adverse Drug Reaction Series, Corticosteroids, Dental, Fragrances, Hairdressing, Leg Ulcer, Medicament, Photopatch testing, Rubber additives, Shoe, Sunscreen, and Textile trays.23 

One query often posed on the provider assistance board of the Dermatitis Academy is “what can I do to supplement my basic screening panel to increase the efficacy of my patch testing practice in the context of a busy private practice?”  

The first 12 high yield allergens from the ACDS Core 80 which are included in the base supplemental hapten tray are listed here and continue on line with descriptions.  Prevalence rates of the ACDS Core Allergen Series 2017 are presented in Table 3.22-59  

Table 3 located on page 2



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