Allergic Contact Dermatitis From Doxepin Cream

North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens

Diethylthiourea is widely used in the rubber industry, particularly in neoprene rubber, and may cause allergic contact dermatitis. However, as thiourea allergens are not part of the European baseline series, the diagnosis of allergic contact dermatitis caused by thiourea compounds depends on clinical suspicion and aimed testing. The aims of this study were to evaluate the occurrence of sensitization to diethylthiourea during a 19-year period by using data from the Allergen Bank database at the Department of Dermatology and Allergy Centre, Odense University Hospital, and to evaluate whether the yield of aimed patch tests with diethylthiourea differed between the dermatologists in practice and those working in the dermatology department. A total of 239 patients were patch tested with diethylthiourea 1% in petrolatum obtained from the Allergen Bank. The records for patients with positive reactions were evaluated retrospectively. One hundred and fifty-one patients were tested by 27 different dermatologists in private practice, and positive reactions were found in 16% (24/151) of the patients; 88 patients were tested at the dermatology department, and positive reactions were found in 15% (13/88). Thus, 15% (37/239) had positive patch test reactions to diethylthiourea, all with current clinical relevance and all strong. Clinical suspicion of neoprene rubber allergy and subsequent aimed patch testing with diethylthiourea give a high yield of clinically relevant allergic patch test reactions for both dermatologists in practice and dermatologists in the hospital department.

BACKGROUND AND OBJECTIVESContact allergy is associated with a significant morbidity all over the world. This study was performed to investigate the pattern of sensitization by contact allergens in the local population.DESIGN AND SETTINGRetrospective study to investigate patch test reactivity among patients with clinical diagnosis of contact dermatitis who were referred to the allergy clinic at the King Khalid University Hospital, Riyadh, between April 2008 and March 2010.PATIENTS AND METHODSOf the 196 patients referred to the allergy clinic over the 2-year period, 91 (46.4%) patients reacted to one or more patch test allergens, and these patients were included in this study. The study group included 82 (91.1%) of Saudi nationality and 9 (8.9%) patients of other nationalities. The patch test was performed using the T.R.U.E TEST, containing 24 allergens/allergen mixes.RESULTSOf the 91 cases who reacted positively to one or more allergens, 67 (73.6%) were females with a mean age of 37 (8.3 years) and 24 (26.4%) were males with a mean age of 34 (11.6 years). Thirty-three (36.2%) patients reacted to nickel sulfate, 14 (15.3%) to p-phenylenediamine, 13 (14.2%) to p-tert-butylphenol-formaldehyde resin, 13 (14.2%) to thimerosal, and 9 (9.8%) to colophony. Reactivity against the rest of the allergens was not remarkable. A significantly higher percentage of females reacted to nickel sulfate (84.8% vs 15.2% in males; P=.0001), p-tert-butylphenol-formaldehyde resin (92.3% vs 7.7%; P=.0001), and thimerosal (76.9% vs 23.1%; P=.03).CONCLUSIONSPatch test reactivity to nickel sulfate was high. The pattern of contact allergy observed in this study indicates the need for large-scale investigations to identify local allergens responsible for contact allergy and for formulation of policies directed towards avoidance of exposure.

Objective: Allergic contact dermatitis (ACD) is a hypersensitivity reaction which develops against substances contacting the skin. Patch tests are used for the detection the allergens that cause ACD. The most common substances that cause ACD vary based on geographic regions. In this study, detection of the most common allergens in patients who underwent patch testing with the diagnosis of ACD and comparison of the results with literature were aimed.Mateials and Methods: One hundred forty-eight patients, who underwent European standard patch test with the diagnosis of ACD in our clinic between January 2010 and June 2013, were enrolled in our study. The data about age, sex, duration of disease, occupation, the presence of atopy, localization of the lesion of the patients and patch test results were recorded retrospectively.Results: Eighty-nine females and 59 males, a total of 148 patients, were included in the study. The mean age of the patients was 35.3 ± 14.8. Positive reactions to one or more allergens were observed in forty-five (30.4%) of 148 patients who underwent patch test. The allergens that were the most common cause of positive reactions were nickel sulfate (11.5%), potassium dichromate (6.1%), cobalt chloride (4.7%), paraben mix (4.1%), thiuram mix (2.7%), neomycin sulfate (2.7%) and fragrance mix (2.7%), respectively. Conclusion: We believe that our study will contribute to the determination of contact allergens which is the most common cause of sensitization in our country

Diagnosis of allergic contact dermatitis to epoxy can be challenging especially in the occupational context. We present a second case of allergic contact dermatitis (ACD) to benzyl alcohol in an epoxy floor paint.1 A 45-year-old Caucasian male with a past history of psoriasis was referred for hand and wrist eczema. (Figure 1). He had been working in industrial paving for 20 years. In his work he used several products such as cement, sealants and epoxy floor paints. His eczema was considerably worsened at work and improved on holidays. Patch tests were performed with the European Baseline Series and cosmetic, rubber, plastic/glue, epoxy and acrylates series using test preparations from SmartPractice Europe, (Greven, Germany), using IQ ultra chambers® from Chemotechnique MB Diagnostics AB (Vellinge, Sweden) according to ESCD guidelines with an occlusion time of 48 h. We routinely patch test benzyl alcohol along with baseline series as additional GERDA series (french group of dermato-allergology study and research). Positive results were found for benzyl alcohol 10% in softisan 649 (++), diglycidyl ether of bisphenol A (DGEBA) 1% pet (++), 1,6 hexanediol diglycidyl ether 0.25% pet (++), 1,4 butanediol diglycidyl ether 0.25% pet (++), diaminodiphenylméthane 0.5% pet (++) at D3 and D10 (Table 1). A second series of patch tests were performed to isocyanate series which remained negative. The safety data sheets of the floor paints used at work, clearly mentioned the presence of benzyl alcohol in various products confirming current definite relevance of this test. (Table 1). He was advised to avoid the exposure to these products at his workplace, and his hand dermatitis considerably improved. Benzyl alcohol (CAS no. 100-51-6) is a well-known allergen in antiseptic products. Multiple cases of sensitizations in antiseptics have been described by the French network REVIDAL-GERDA.2 It can also be used as a fragrance component, preservative, solvent, food additive and excipient in medicinal products.3 Its presence is not so well known in the construction sector, particularly in epoxy systems. It is generally used as a thinner in epoxy resins (an additive to regulate viscosity) and can be found in the epoxy resin part (A) or the hardening part (B). Benzyl alcohol was not present in any of the patient's personal cosmetic products. The patient's work related eczema could be explained by ACD to benzyl alcohol as well as ACD to several other epoxy compounds. Occupational ACD to benzyl alcohol in epoxy systems has recently been reported in another patient working with similar products for the repair and coating of concrete floors.1 Regular occupational exposure to epoxy products with benzyl alcohol, with an altered skin barrier could explain the sensitization to this allergen. Furthermore, a positive patch test reaction to diaminodiphenylmethane (MDA) may indicate ACD to isocyanates. The safety data sheet of one of his products, a polyurethane sealant, mentioned the presence of diisocyanate de 4,4′ methylenediphenyle, but it was not tested and our patient had negative isocyanate series (with toluene 2,4 diisocyanate [TDI] 2%, diphenylmethane 4,4′ diisocyanate [MDI] 0.5%, isophorone diisocyanate [IPDI] 1%, hexamethylene diisocyanate [HDI] 0.1% and polymeric diphenylmethane diisocyanate [PDMI] 2%). A positive reaction to MDA could also indicate ACD to hydrogenated formaldehyde-benzamine polymer (FBAP, CAS no. 135108-88-2) as described by Suomela, due to structural resemblance or a possible cross allergy.4 The safety data sheet of one of our patient's epoxy products mentioned the presence FBAP, as well as BA, but we could not test it separately to confirm this allergy. In conclusion, this is the second case of hand ACD associated with benzyl alcohol in an epoxy system, and can be considered an emerging allergen of relevance in occupational ACD to epoxy system in the construction sector. Marion Menanteau: Investigation; writing – original draft; writing – review and editing. Lynda Bensefa-Colas: Writing – review and editing. Marie-Noëlle Crepy: Writing – review and editing; supervision. We thank Sylvain Caillol PhD Research Director, CNRS (National Centre for Scientific Research) for his contribution to the discussion. The authors declare that they do not have any conflicts of interest regarding this study. The patient in this manuscript has given informed consent to publication of their case details and photographs.

It is tacitly assumed that a positive patch test reaction is not affected by adjacent negative tests. However, despite its fundamental importance for the interpretation of test reactions this assumption has not been proven. To test this assumption, special TRUE-test strips were prepared containing placebo, nickel sulphate and fragrance mix as the only allergens, separated by distances of 1 cm and 7 cm and blinded to the investigators. Patients were synchronously tested with two strips. Out of 493 patients tested in 6 centres, the 93 with positive reactions to nickel sulphate only were evaluated. No relevant difference was found between positive nickel reactions in the two different distances to a negative fragrance patch test. We conclude that a positive patch test reaction is not affected by adjacent negative patch tests, which therefore can be neglected for the interpretation of positive reactions.

Allergic contact dermatitis caused by topical ophthalmic medications (OftACD) is frequently difficult to confirm with patch testing and, therefore, it is considered uncommon. We collected retrospective data from a cohort of 65 patients with suspected OftACD patch tested in our Dermatology Unit (2005-2021) according to ESCD guidelines, using a series of topical drugs and excipients (Chemotechnique Diagnostics), including betaxolol and timolol 5% pet. kindly supplied by the pharmaceutical industry. Also, frequently used ophthalmic medications as well as patient's own products were also patch tested 'as is' in most patients. Positive patch tests to ophthalmic medications occurred in 44 patients (67.7%) (38F/6M; mean age 63.1 years), with 102 positive reactions. Most positive reactions were associated with active ingredients (n=56), especially aminoglycoside antibiotics (n=27), followed by excipients (n=24) such as sodium metabisulfite (n=7). There were also positive reactions to topical products tested 'as is' (n=22), mostly containing beta-blockers, but only five of these reacted to the active ingredient. This study reinforces previous findings in OftACD, such as older age of onset, and the importance of antibiotics, contrasting with the progressively lower prevalence of excipients. In addition, it helps raising awareness for the sensitization to beta-blockers, which is probably underestimated. Patch test preparations for the diagnosis of OftACD may require protocol optimization.

Natural ingredients have variable compositions, so their allergenic potencies may differ. To retrospectively analyse subjects reacting to herbal remedies over the past 27 years, with the aim of (i) evaluating demographic characteristics and lesion locations, (ii) describing the frequencies of positive patch test reactions, (iii) identifing sensitization sources, and (iv) studying concomitant sensitivity. In total, 15980 patients were patch tested between 1990 and 2016 with the European baseline series and/or other series, product(s) used, and, whenever possible, the respective ingredients. Altogether, 8942 (56%) of 15 980 patients presented with at least one positive reaction. Reactions to topical herbal medicines, most often applied to treat an eczematous condition, leg ulcers, or other wounds, were seen in 125 (0.8%), that is, 1.4% of the contact-allergic subjects. Hands, legs and feet were the most frequently affected body sites. Twenty-one botanical allergens were identified, the commonest being Myroxylon pereirae (balsam of Peru), Compositae plants, and tincture of benzoin. Many patients presented with multiple positive test reactions, and some did not react to the commercial allergens but only to the products used. Topical herbal remedies should not be applied on damaged skin, as multiple sensitization may develop. Moreover, patch testing with the culprit products is important for the diagnosis.

In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P < 0·001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. The algorithm used in this study was not substantiated in this ROAT set-up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic? To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add? This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT. What are the clinical implications of this work? Further refinement of the questions is required in order to diagnose allergic contact dermatitis from fragrances based on a questionnaire.

Existing literature on the prevalence of positive reactions to allergens is largely derived from dermatologists who practice at large academic centers. Data from other providers, including allergists who practice in various other settings, is important to assess a more representative and accurate prevalence of contact allergy. To determine the prevalence of contact allergy among individuals with at least one positive patch test result by comparing data for positive patch test reaction rates of common contact allergens from 3 groups based in different practice settings, 2 of which are academic. We retrospectively analyzed patch test results of an academic center (January 1, 2011, to December 4, 2015) and a national contact allergen database (March 1, 2015, to September 1, 2016). Data from a third, academic-based group was obtained separately from the published literature. Logistic regression analysis was used to compare positive reaction rates of the widely available, patch test allergens among the 3 groups. The positive reaction rates for 10 of 36 compared allergens (28%) were significantly higher (p < 0.05) for the national contact allergen database compared with both the academic groups. Positive reaction rates to common allergens used in patch testing may be underreported in the literature. Limitations of our study included the retrospective nature of the study, different date ranges among the three groups, and the absence of all allergens tested by the national contact allergen database.

Patch testing: Facts and controversies

Impact of Anxiety on Patch Testing Results for Allergic Contact Dermatitis.

Introduction. Occupational Allergic Contact Dermatitis is a very common occupational disease and epoxy resins are among its main causes. The aim of this study was to characterize patients with positive patch test reactions to epoxy resin detected in the Coimbra Hospital and University Center between 2012 and 2018 and compare with the results of patients patch tested between 1999 and 2008 at the same Institution.&#x0D; Method and Materials. Within aretrospective analysis of the files of patients with positive patch test reactions (1+ or more intense) to epoxy resin of bisfenol A tested at 1% pet. within the Baseline Series between 2012 and 2018, we characterized demographic and clinical data of reactive patients, evaluated the relevance of the reaction, sources of exposure to epoxy resin with particular attention to occupational exposures, other positive reactions and the impact of the results of the tests in the work conditions of these patients. Lastly, we compared these results with a previous study performed in the same Hospital between 1999 and 2008.&#x0D; Results. Among 2363 patch tested patients during the study period we found 23 patients (0.97%), 17 males and 6 females, who developed contact allergy to epoxy resins. In 22 cases we identified a relevant occupational exposure: 9 from construction industry; 9 workers from wind-mill turbines factory for Eolic energy; 2 from fiberglass factories; 1 from a chemical factory and 1 from a Wastewater Treatment Plant. In 1 patient (a teacher) no relevance was found. Of these 22 workers, 9 (39.1%) had both hand and airborne lesions, while 8 (34.8%) had lesions exclusively on the hands and 5 (21.7%) had predominately airborne dermatitis. Four of the 23 (17.4%) reacted exclusively to the epoxy resin, and 11 of 18 (61.1%) also reacted to 0.25% hexanediol diglycidyl ether. Avoidance resulted in a significant improvement of symptoms. Compared to the previous period (1999-2008), there are no significative changes apart from a slight increase in the frequency of the allergic reactions to epoxy resins and its main source of exposure.&#x0D; Conclusions. The prevalence of allergic contact dermatitis to epoxy resin has slightly increased in this Portuguese Center mostly due to workers from wind-mill turbines factory for Eolic energy, a recent industry implanted in this region. This allergen still causes almost exclusively occupational dermatitis, either hand, airborne, or both.

Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations at patch tests. The present multi-center study investigated the epidemiological, occupational and temporal pattern of sensitization to Thimerosal in North-Eastern Italy during 1997–2023 and associated factors. Methods: Due to variability in patch testing and positive reactions by the centers, this study was broken down by three periods: 1997–2004 (including all centers but Trieste); 1997–2015 (considering only Padua and Pordenone); and 2010–2023 (considering only Trieste and Pordenone). Multiple logistic regression was used to investigate prevalence of sensitization to Thimerosal and associated factors. Results were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (95%CI). Results: Prevalence of positive patch test reactions to Thimerosal decreased from (8.13%) in 1997 to 0.95% in 2023 across all centers combined. Prevalence of positivity to Thimerosal was 9.49% during 1997–2004 (in all centers yet excluding Trieste), 8.41% during 1997–2015 (considering only Padua and Pordenone) and 4.01% during 2010–2023 (considering only Trieste and Pordenone). A significantly decreasing trend of Thimerosal sensitization was observed during 1997–2015 (aOR = 0.94; 95%CI: 0.92; 0.95). Regardless of the study period, sensitization to Thimerosal was consistently and significantly higher among health care workers (HCWs) and in patients born during 1981–1990. Conclusions: The significantly decreasing prevalence of sensitization to Thimerosal over time likely reflected removal policies from vaccines and medications after 1999. Likewise, the higher prevalence of patch test reactions in patients born during 1981–1990 may mirror the widespread presence of this hapten in vaccines and medications in the 1980ies. Moreover, the increased prevalence of patch test reactions positive to Thimerosal in HCWs probably reflected higher influenza vaccination uptake in this group compared to other occupational categories. Positive patch test reactions to Thimerosal after 2000 were likely clinically irrelevant though.

To verify if the counter-ion Cl- permits the same interactions between nickel and divalent metals with physicochemical similarities as the counter-ion SO4- does, 50 sensitive subjects to nickel sulfate 5% pet. who previously gave positive patch test reactions either to 8 mu 1 of aq. nickel sulfate 0.1 M or to 8 mu 1 of aq. nickel chloride 0.1 M, or to both, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M and aq. nickel chloride 0.1 M, and to 8 mu 1 of aq. mixed solutions containing, respectively, nickel chloride 0.1 M+magnesium chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.5 M, nickel chloride 0.1 M+manganese chloride 0.3 M, and nickel chloride 0.1 M+manganese chloride O.5 M. Whilst 4 subjects gave a positive patch test response to only nickel sulphate, 8 gave a positive response to nickel chloride alone and the remaining 38 gave a concomitant positive response to both. In all subjects who gave positive responses to nickel chloride, the chlorides of divalent metals were not able to inhibit or reduce the positive reaction. 25 healthy subjects patch tested to both single salts and mixed solutions, and all gave negative responses. 9 of the 50 subjects, 4 who previously gave positive reactions to only nickel chloride 0.1 M, and 5 with concomitant reactions of equal intensity to both nickel chloride and nickel sulfate 0.1 M, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M, aq. nickel chloride 0.1 M and aq. mixed solutions containing nickel sulfate (0.1 M) mixed with sulfates (0.3 M) and nickel chloride (0.1 M) mixed with chlorides of Mg, Zn, Mn (0.3 M). Whilst the mixed sulfate solutions were able to reduce nickel sulfate, 0.1 M patch test positive reactions, those containing chlorides, at all concentrations tested, did not inhibit the nickel chloride reactions in any of the subjects. The results of the tests to chlorides, compared to those reached on testing to sulfates of the same metals, lead us to hypothesize that the anion probably affects the uptake and local tissue distribution of the metal, modulating in this way, together with the individual cutaneous ligands, its effects.