Inter-rater variability in patch test readings and final interpretation using store-forward teledermatology.

BACKGROUND: Data regarding teledermatology for patch testing are limited. OBJECTIVES: Compare patch test readings and final interpretation by two in-person dermatologists (IPDs) with eight teledermatologists (TDs). METHODS: Patch tested patients had photographs taken of 70 screening series of allergens at 48 hours and second readings. Eight TDs reviewed photos and graded reactions (negative, irritant, doubtful, +, ++, +++) at 48 hours and second readings; in addition, they coded a final interpretation (allergic, indeterminant, irritant, negative) for each reaction. TDs rated overall image quality and confidence level for each patient and patch test reaction, respectively. Percentage of TD-IPD agreement based on clinical significance (success, indeterminate, and failure) was calculated. Primary outcome was agreement at the second reading. RESULTS: Data were available for 99, 101, and 66 participants at 48 hours, second reading, and final interpretation, respectively. Pooled failure (+/++/+++ vs negative) at second reading was 13.6% (range 7.9%-20.4%). Pooled failure at 48 hours and final interpretation was 5.4% (range 2.9%-6.8%) and 24.6% (range 10.2%-36.8%), respectively. Confidence in readings was statistically correlated with quality of images and disagreement. CONCLUSION: For patch testing, teledermatology has significant limitations including clinically significant pooled failure percentages of 13.6% for second readings and 24.6% for final interpretation.

Developing a cosmetic series: Results from the ESSCA network, 2009-2018.

BACKGROUND: There is considerable variability across European patch test centres as to which allergens are included in local and national cosmetics series. OBJECTIVES: To propose a standardized, evidence-based cosmetic series for Europe based on up-to-date analysis of relevant contact allergens. METHODS: We collated data from the European Surveillance System on Contact Allergies (ESSCA) from 2009 to 2018 to determine which cosmetic allergens produce a high yield of contact allergy. Contact allergens with a prevalence of >0.3% that were considered relevant were included. Rare contact allergens were excluded if deemed no longer relevant or added to a supplemental cosmetic series for further analysis. RESULTS: Sensitization prevalences of 39 cosmetic contact allergens were tabulated. Thirty of these allergens yielded >0.3% positive reactions and are therefore included in our proposed European cosmetic series. Six were considered no longer relevant and therefore excluded. Three were included in a supplementary European cosmetic series. An additional nine allergens were included in either the core or supplemental European cosmetic series following literature review. CONCLUSION: We have derived a potential European cosmetic series based upon the above methods. This will require ongoing investigation based upon the changing exposure profiles of cosmetic allergens as well as new and evolving substances.

Quantification of aluminium release from Finn chambers under different in vitro test conditions of relevance for patch testing.

BACKGROUND: Contact allergy to aluminium (Al) might pose a risk of false-positive readings of patch-test results when testing with Finn chambers. OBJECTIVES: To quantify the release of Al from empty Al Finn chambers, covered Finn Aqua chambers, and Al Finn chambers containing different baseline patch-test substances. METHODS: Al Finn chambers of different conditions and with different patch-test substances were tested in artificial sweat and their Al release was analyzed by atomic absorption spectroscopy and inductively coupled plasma sector field mass spectrometry. RESULTS: The amount of Al released from empty Finn chambers corresponded to a skin dose of 0.03%-0.5% Al chloride hexahydrate applied in plastic chambers. Although most patch-test substances reduced the release of Al from the Finn chambers due to covering the surface, some substances significantly increased the release of Al from the Finn chambers, most notable for Caine mix II 10% pet., Myroxylon pereirae 25% pet., and sodium tetrachloropalladate hydrate 3.0% pet. CONCLUSIONS: The release of Al from Finn chambers corresponds in some cases to clinically relevant concentrations of Al for Al-sensitized individuals.

A seven-year retrospective analysis of patch test data in a cohort of patients with contact dermatitis in Sri Lanka.

BACKGROUND: Patch testing with a baseline series is a common tool employed when the sensitizing agent in contact dermatitis is unclear. However, for Asian countries, there are no locally validated baseline series to utilize in screening. METHODS: We completed a retrospective analysis of all patients that had undergone patch testing with the European Baseline series, Shoe Series or Comprehensive International Baseline series, over 7 years from 2012 to 2018 in a tertiary care reference dermatology clinic in Sri Lanka to evaluate the suitability of these investigations to identify causes for contact dermatitis in the local study population. RESULTS: Out of 438 patients tested, 239 (54.8%) reacted to at least one substance in the series. The Shoe Series was significantly more likely to yield a positive result than the European Baseline Series (70.2% vs 46.9%, p < 0.05). The top three sensitizers identified by all series were nickel sulfate (16%, 70/438), p-phenylenediamine (12.3%, 54/438) and 2-mercaptobenzothiazole or mercapto mix (10.5%, 46/438). CONCLUSION: Shoe series has a comparatively high yield in the local population compared to European Baseline series. Since little less than half of the study population did not have any reactivity to any of the allergens tested it is important to develop or modify and validate a locally relevant, more suitable baseline series which is based on the Shoe Series in Sri Lanka. This is further evidence for the continuously changing nature of allergens in the environment and the need to modify existing patch testing standards accordingly.

Patch testing with the European baseline series fragrance markers: a 2016 update.

BACKGROUND: Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. OBJECTIVES: To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. METHODS: We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. RESULTS: Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. CONCLUSIONS: Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.

A proposal to create an extension to the European baseline series.

BACKGROUND: The current European baseline series consists of 30 allergens, and was last updated in 2015. OBJECTIVES: To use data from the European Surveillance System on Contact Allergies (ESSCA) to propose an extension to the European baseline series in response to changes in environmental exposures. METHODS: Data from departmental and national extensions to the baseline series, together with some temporary additions from departments contributing to the ESSCA, were collated during 2013-2014. RESULTS: In total, 31689 patients were patch tested in 46 European departments. Many departments and national groups already consider the current European baseline series to be a suboptimal screen, and use their own extensions to it. The haptens tested are heterogeneous, although there are some consistent themes. Potential haptens to include in an extension to the European baseline series comprise sodium metabisulfite, formaldehyde-releasing preservatives, additional markers of fragrance allergy, propolis, Compositae mix, and 2-hydroxyethyl methacrylate. CONCLUSION: In combination with other published work from the ESSCA, changes to the current European baseline series are proposed for discussion. As well as addition of the allergens listed above, it is suggested that primin and clioquinol should be deleted from the series, owing to reduced environmental exposure.

National survey of patch testing in the United Kingdom and Republic of Ireland: what proportion of the population is and should be tested?

BACKGROUND: An initial study of patch testing practices across Wales, United Kingdom, showed wide variation in practice against a standardized set of guidelines and best practice recommendations. OBJECTIVES: To evaluate (i) current patch testing practice on a national level in the United Kingdom and Republic of Ireland (ROI), (ii) compliance with the current published guidelines, and (iii) the proportion of the catchment population tested by patch testing centres. METHODS: In consultation with the British Association of Dermatologists and British Society for Cutaneous Allergy, proformas addressing clinical guidelines and best practice recommendations were sent to all dermatology units in the United Kingdom and ROI. RESULTS: Ninety one of 325 centres (28%) performed patch testing. The optimum proportion of annual tests was not being achieved in the United Kingdom and ROI. The range tested varied between 1:1200 and 1:1600. CONCLUSIONS: Most centres achieved a high level of best practice outcomes. Shortcomings were found in the recording of minimum data, benchmarking, and attendance at meetings. We suggest that the findings of this study should be used as evidence to help improve services locally.

Pilot study on a new concept of documenting the clinical relevance of patch test results in contact dermatitis patients.

BACKGROUND: Assessment of the clinical relevance of patch test reactions is an essential part of the diagnostic work-up of patients with (occupational) contact dermatitis. However, final diagnostic information, particularly the clinical relevance of allergic patch test reactions, has hitherto been ill-represented in clinical documentation systems (patch test software) and surveillance registries based on these. OBJECTIVES: To develop, implement as a pilot study, and analyse concerning feasibility and contents a new concept of representing the full scope of diagnostic information utilized in the diagnosis of patients with (occupational) contact dermatitis. METHODS: On the basis of a European working group discussion on items to document and catalogue lists to use for this purpose, an online documentation system to collect data was set up, followed by pilot use involving 9 dermatology departments across Europe. RESULTS: Data on 176 patients with suspected occupational hand dermatitis were included; among these, work-relatedness was confirmed in 150, and in 53 non-occupational aetiology was the sole or a contributory cause. Data were further analysed with regard to occupations, product categories, substances (haptens), source of information on which the evaluation was based, and various combinations of these factors, to illustrate the usefulness of the proposed data representation. CONCLUSIONS: An improved method of data collection is presented that more accurately links allergen to exposure and to clinical disease and patient history, and thus better represents clinical relevance. This enables more precise analysis of the causation of contact dermatitis, occupational or non-occupational, and thereby better targeting of prevention. The development of future databases should incorporate the above considerations to record the results of investigation.

Thoughts on how to improve the quality of multicentre patch test studies.

Multicentre patch test studies (MPTSs) can contribute useful information for diagnostic and preventive measures. The aim of the present paper is to propose how to perform high-quality MPTSs. To this end, factors of significance for the patch test result are discussed with regard to the standardization and calibration of high-quality MPTSs. The 16 factors discussed are scored 0, 1, 2, or 3, depending on the relative importance of a particular factor for the patch test result. The total score of an MPTS allows it to be ranked as having doubtful, acceptable, high or excellent quality. A total score of 30 is possible. Depending on the total score the MPTSs are grouped into those with a doubtful, acceptable, high, and excellent quality. In conclusion, high-quality MPTSs can be performed and are facilitated if a guideline and check list are followed when the study is being planned. The scoring enables the calculation of a total score, which can be used for quality ranking.

Quality in epidemiological surveillance of contact allergy.

The reporting of scientific results (in the field of contact dermatitis/allergy) should include a description of the methods used, including, but not limited to, standardized patch testing. Several aspects always need to be reported, such as duration of exposure, reading times, vehicle, and concentration of allergens. However, concerning other aspects, explicit compliance with international patch testing guidelines, notably the European Society of Contact Dermatitis guideline, which covers all relevant general aspects, is deemed to be a sufficient description of methods, supplemented by study-specific information, including partial non-compliance with the guideline, as indicated. Besides technical aspects, the quality of reporting of scientific results has several other dimensions, including epidemiological and biostatistical aspects discussed in this article. Prospectively, when a study is planned, performed, and reported, issues such as selection of patients and sample size and their impact on power and precision, the role of misclassification and potential conflicts of interests need to be addressed and discussed, respectively. Retrospectively, when a study is read and analysed, all relevant aspects of quality should be considered when the weight of evidence that a study publication provides is evaluated. Employing rigid 'quality criteria' may have the detrimental effect of relevant, if slightly imperfect, evidence being deliberately excluded.

The Spanish standard patch test series: 2016 update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la serie estándar española de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC) para 2016.

The Spanish standard patch test series, as recommended by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC), has been updated for 2016. The new series replaces the 2012 version and contains the minimum set of allergens recommended for routine investigation of contact allergy in Spain from 2016 onwards. Four haptens -clioquinol, thimerosal, mercury, and primin- have been eliminated owing to a low frequency of relevant allergic reactions, while 3 new allergens -methylisothiazolinone, diazolidinyl urea, and imidazolidinyl urea- have been added. GEIDAC has also modified the recommended aqueous solution concentrations for the 2 classic, major haptens methylchloroisothiazolinone and methylisothiazolinone, which are now to be tested at 200ppm in aqueous solution, and formaldehyde, which is now to be tested in a 2% aqueous solution. Updating the Spanish standard series is one of the functions of GEIDAC, which is responsible for ensuring that the standard series is suited to the country's epidemiological profile and pattern of contact sensitization.

Strip patch testing does not affect reaction profiles of standard allergens.

BACKGROUND: It has been hypothesized that positive reactions in the strip patch test are irritant rather than allergic. OBJECTIVE: To study reaction profiles of the baseline series patch test substances applied routinely on tape-stripped skin according to the reaction index (RI) and the positivity ratio (PR). PATIENTS AND METHODS: One thousand two hundred and twenty-eight consecutive patients were routinely strip patch tested with the baseline series between January 2011 and June 2013 (intervention group). On the basis of test reactions at D3/D4, the RI, and the PR, 25 standard allergens were analysed, and the results were compared with those obtained in 1161 patients patch tested conventionally from July 2008 to December 2010 (historical control group). RESULTS: Nickel sulfate, fragrance mix I, cobalt chloride, Myroxylon pereirae (balsam of Peru) and colophonium showed the highest frequencies of positive reactions in both groups, without any significant differences. Of 25 patch test substances of the baseline series, 18 showed good reaction profiles in the intervention group, and 16 in the historical control group. CONCLUSIONS: Reaction profiles of baseline series patch test substances remained largely unaffected by tape stripping the skin prior to patch testing. Thus, if conventional patch test results are presumed to be false-negative, performance of the strip patch test can be recommended independently of the standard allergen.

DKG statement on the use of metal alloy discs for patch testing in suspected intolerance to metal implants.

Intolerance reactions to metal implants may be caused by metal allergy. However, prior to implantation, 'prophetic'/prophylactic patch testing should not be performed. Pre-implant patch testing should only be done to verify or exclude metal allergy in patients with a corresponding history. In case of implant-related complications - in particular following replacement arthroplasty - such as pain, effusion, skin lesions, reduced range of motion or implant loosening, orthopedic causes should be ruled out first. Workup of suspected metal implant allergy should then be done using the DKG standard series, which includes nickel, cobalt, and chromium preparations. Various studies assessing the usefulness of metal alloy discs for patch testing have shown this particular approach to be ineffective with respect to providing reliable information on metal allergy. Any positive reaction in such tests cannot be assigned to a specific metal contained within the alloy. Furthermore, there is a risk of broad and indiscriminate use of these readily available discs. Accordingly, given the lack of additional benefit compared to patch testing with standardized metal salt preparations, we do not recommend patch testing with metal alloy discs.

Trends in patch-test results and allergen changes in the standard series: a Mayo Clinic 5-year retrospective review (January 1, 2006, to December 31, 2010).

BACKGROUND: Patch testing is essential for identification of culprits causing allergic contact dermatitis. OBJECTIVE: We sought to identify trends and allergen changes in our standard series during 2006 to 2010, compared with our previous report (2001-2005). METHODS: We conducted a retrospective review of patch-test results. RESULTS: A total of 3115 patients were tested with a mean of 73.0 allergens. Since our prior report, 8 allergens were added to the standard series; 14 were deleted. Significantly higher rates of allergic positive reaction were documented for carba mix, 3%, and Disperse Orange 3, 1%. Rates were lower for 10 allergens: neomycin sulfate, 20%; gold sodium thiosulfate, 0.5%; hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, 1%; disperse blue 124, 1%; disperse blue 106, 1%; diazolidinyl urea, 1%; hexylresorcinol, 0.25%; diazolidinyl urea, 1% aqueous; 2-bromo-2-nitropropane-1,3-diol, 0.25%; and lidocaine, 5%. Many final patch-test readings for many allergens were categorized as mild reactions (erythema only). Overall allergenicity and irritancy rates declined significantly since our prior report. Results were generally comparable with those in a North American Contact Dermatitis Group report from 2005 to 2006. LIMITATIONS: This was a retrospective study; there is a lack of long-term follow-up. CONCLUSIONS: Since our previous report, our standard series composition has changed, and overall rates of allergenicity and irritancy have decreased. Notably, many final patch-test readings showed mild reactions.

Utility of patch testing for patients with drug eruption.

BACKGROUND: Patch testing is less dangerous than oral provocation testing for identification of the causative drug for patients with drug eruption; however, its usefulness for such identification is controversial. AIM: To clarify the rates of positive patch testing for patients with drug eruption, classified by causative drugs and clinical features. METHODS: We analysed results during the period 1990-2010 for 444 patients (151 men, 293 women; mean ± SD age 49.9 ± 18.6 years) who were tested for drug eruption. In the patient group, there were 309 people (69.1%) with maculopapular eruption and 31 (6.9%) with severe drug eruption. The test materials were applied to the back and left for 2 days under occlusion, then results were assessed by the International Contact Dermatitis Research Group (ICDRG) scoring system 3 days after application. Reactions of + to +++ were regarded as positive. RESULTS: Of the 444 patients, 100 (22.4%) had a positive patch test result to a suspected drug. Positive rates were 23.6% and 20.0% for maculopapular eruption and fixed drug eruption, respectively. The class of materials to which most patients reacted positively was contrast medium (n = 53; 41.1%), followed by drugs acting on the central nervous system (n = 18; 28.6%). In the latter group, 16 of the 18 patients were positive to antiepileptics. CONCLUSIONS: Positive rates depend on the causative drug rather than the clinical features of the drug eruption. Patch testing is useful when contrast medium or antiepileptics are suspected to be the causative drugs. However, standardization of patch test materials and method of reading is needed, as well as guidelines regarding when testing should be performed. Although patch testing for drug eruption has significant potential, it requires further validation.

Non-irritant concentrations and amounts of active ingredient in drug patch tests.

BACKGROUND: Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests. OBJECTIVES: The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. METHODS: From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. RESULTS: Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of < 2%, and 25% had an AI concentration of > 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). CONCLUSION: These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods.

Current trends in patch testing - new data from the German Contact Dermatitis Research Group (DKG) and the Information Network of Departments of Dermatology (IVDK).

BACKGROUND AND OBJECTIVES: The relevance of contact allergens is subject to constant change due to changing exposures according to consumers' preferences and legal requirements. The objective of this paper is to present trends in contact sensitization from the DKG and IVDK patch test clinics, which have led to changes in the DKG standard series (as of 1.1.2014), as well as the current legal framework which has influenced these trends and the way patch testing is performed. PATIENTS AND METHODS: The patients from 56 DKG and IVDK patch test clinics from 2010 (n = 13,117), 2011 (n = 13,320) and 2012 (n = 12,529) were analyzed with regard to frequencies of sensitization (hit list) to contact allergens as well as the location of allergic contact dermatitis. RESULTS: With a sensitization rate of 15 % nickel is still the most frequently recognized contact allergen. An increase can be observed for fragrance mix I (9.1 %), the preservative composition of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (4.5 %) and methylisothiazolinone (MI) alone (6.8 %). A decline is present for potassium dichromate from above 6 % (2007) to 3 % (2012) and for bufexamac (currently at 0.6 %). Backgrounds, legal requirements and resulting changes to the DKG standard series are illustrated. CONCLUSIONS: The indicated trends demonstrate the relevance of clinical epidemiology and the "sentinel function" of DKG and IVDK with regard to public health and prevention of contact allergies.

Update on allergic contact dermatitis due to methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone.

The combination of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) is widely used as a preservative in cosmetics, household, and industrial products. Furthermore, MI at a concentration of 100 ppm has been permitted in cosmetic products since 2005. Recently, a considerable increase in cases of contact dermatitis to both MCI and MI have been noted, and this warrants closer monitoring by relevant authorities and, probably, stricter legislation. In fact, MI at a test concentration of 2000 ppm was recently included in the European baseline patch test series. The clinical manifestations of allergy to MCI/MI and MI are highly variable and diagnosis is often missed. In the standard patch test series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC), MCI/MI is tested at 100 ppm, but at this concentration, up to 50% of cases might go undetected. Furthermore, our data indicate that MCI/MI at 200 ppm would make it possible to diagnose more cases of contact allergy to MI. To improve the diagnosis of contact allergy to MCI/MI and MI, we believe that the test concentration of MCI/MI should be increased to 200 ppm in the GEIDAC standard series and that MI should be added in the GEIDAC standard series.

Investigation of the homogeneity of methacrylate allergens in commercially available patch test preparations.

BACKGROUND: The homogeneity of methacrylates in commercial patch test preparations has not yet been investigated. Inhomogeneous patch test preparations may give rise to false-negative or false-positive patch test results in patients suspected of having methacrylate allergy. OBJECTIVES: To investigate the homogeneity of methacrylates in commercial patch test preparations. METHODS: Fresh commercial patch test preparations of methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (2-HEMA) from three test material suppliers in Europe were analysed quantitatively by means of normal-phase high-performance liquid chromatography. RESULTS: The initial concentration of MMA in all six patch test preparations was lower than stated on the label, whereas four of six patch test preparations of 2-HEMA were in accordance with the stated concentrations. The concentration of MMA increased markedly from the top segment close to the tip of the syringe to the bottom segment adjacent to the piston in four syringes (3-6). In contrast, syringes with 2-HEMA maintained a constant concentration throughout the test preparation, apart from two syringes (11 and 12). CONCLUSION: Variations in concentration and heterogeneous distribution of MMA and 2-HEMA in patch test preparations may be an additional cause of variation in patch test results, besides other technical details and reading.