Patch test results to the Spanish baseline patch test series according to age groups: A multicentric prospective study from 2019 to 2023.

INTRODUCTION: Patch test results may be influenced by age-related factors. However, there is still discordant evidence between age and patch test results. OBJECTIVES: We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group. METHODS: Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre-defined as children (0- to 11-years), adolescents (12- to 18-years), young adults (19- to 30-years), middle-aged adults (31- to 65-years) and older adults (≥66-years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression. RESULTS: A total of 13 368 patients were patch-tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle-aged adults. Age-related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2-hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31-65 (OR: 1.41, 95% CI: 1.26-1.58) and above 66-years (OR: 1.15, 95% CI: 1.01-1.32) with a higher proportion of positive results, compared with young adults. CONCLUSIONS: Positive patch test results vary according to age, with the highest occurrence in middle-aged adults. Most haptens did not present age-related differences, reinforcing the use of baseline series regardless of age.

An emerging epidemic of allergic contact dermatitis due to phytonadione epoxide (oxidised vitamin K1).

BACKGROUND: Reports of allergic contact dermatitis (ACD) to phytonadione epoxide (PE) in cosmetics suggest that PE is as powerful a sensitiser as its parent compound phytonadione. OBJECTIVE: To evaluate a case series of ACD to PE in Spain. METHODS: We reviewed the records of 20 patients with ACD to cosmetics containing PE diagnosed across Spain between January 2019 and June 2023. RESULTS: All 20 patients developed patch test (PT) or repeated open application test (ROAT) reactions to cosmetics containing PE. All involved women with eyelid eczema. PT or ROAT with PE preparations were positive in 17/20 (85%). PE at 1%, 5%, 10% and 20% in pet. was patch-tested in 8/17, 14/17, 11/17 and 8/17 patients; being positive in 6/8 (75%), 13/14 (92.85%), 11/11 (100%) and 8/8 (100%), respectively. CONCLUSION: Regulators should, not only ban the specific dangerous cosmetic ingredients, but also consider to ban or keep under close surveillance those closely related products or derivatives that might potentially cause similar harmful effects. PTs with PE are suggested to be performed at a 5% concentration in pet. Higher concentrations (10% pet.) should be tested whenever PTs with 5% pet. PE are negative.

A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019-2022 prospective study with cluster and network analysis.

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.

2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.

Patch Testing in Patients With Severe Atopic Dermatitis Treated With Dupilumab: A Multicentric Approach in Spain.

Background: Persistent localized dermatitis (PLD) or eczema flare-ups (EF) may occur in atopic dermatitis (AD) patients treated with dupilumab. They may reflect concomitant allergic contact dermatitis (ACD) exposed by the inhibition of the Th2 pathway by dupilumab in some cases. Objective: To evaluate the prevalence and etiology of these events and the impact of dupilumab on patch test outcome. Methods: We performed patch tests on 54 AD patients treated with dupilumab and evaluated the prevalence and final diagnosis of EF and PLD as well as the patch test results. Results: The patch test results were positive in 20/54 (37.0%). 21/54 patients (38.9%) had PLD and 12/54 (22.2%) had EF. Ten of 54 (18.5%) had both conditions and 11/54 (20.4%) had neither PLD nor EF. 64.5% of PLD involved the face. 83.9% patients with PLD and 90.9% patients with EF were diagnosed with inadequately controlled AD. 9.7% patients with PLD and 4.5% patients with EF were finally diagnosed with ACD. Nine of 21 (42.9%) patients patch tested twice were positive either before and/or during dupilumab. Patch tests results changed over time in all of them. Conclusions: Patch testing assisted us to exclude ACD as the cause of PLD/EF in AD patients treated with dupilumab. Most PLD and EF were, however, diagnosed as poorly controlled AD. Dupilumab appeared to impact the patch test outcomes.

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019-2021 epidemiological situation.

BACKGROUND: Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. OBJECTIVES: To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. MATERIALS AND METHODS: We analysed all 2019-2021 consecutive patients patch-tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). RESULTS: A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI-positive patients were positive to BIT, whereas one in five BIT-positive patients were positive to MI. CONCLUSIONS: Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon.

Nonoccupational Allergic Contact Dermatitis to 4-Acryloylmorpholine in Smartwatch Screen Protectors Glue.

BACKGROUND: We recently identified an outbreak of occupational allergic contact dermatitis (ACD) involving workers of a Spanish company selling smartphone protective cases from a glue product. A chemical analysis of one glue sample revealed the presence of 4-acryloylmorpholine among other allergens.The same glue is also used to attach tempered glass protective cases to Apple smartwatches. OBJECTIVE: Our objective was to describe a case series of nonoccupational consumer ACD from the previously mentioned Apple smartwatch protective case glue. METHODS: We evaluated epidemiological and clinical data, as well as patch tests results. RESULTS: Three women were diagnosed with nonoccupational ACD from the adhesive. An annular vesicular inflammatory plaque involving the dorsal aspect of the wrist was initially observed in all. Two of the 3 patients were patch tested with 4-acryloylmorpholine 0.5% with positive strong reactions. Both also strongly reacted to a sample of the glue semiopen tested in a drop of petrolatum. One of them was also positive for various acrylates. CONCLUSIONS: 4-Acryloylmorpholine has been identified in an adhesive used to attach protective cases to smartwatches. Nonoccupational ACD have been described to involve consumers of smartwatches. A UV-curable adhesive used to attach protective cases to smartwatches has been considered to be the culprit.

Outbreak of occupational allergic contact dermatitis from a smartphone screen protector glue.

BACKGROUND: Sensitization to acrylates is a concern in the occupational/environmental dermatology field. OBJECTIVE: To describe an occupational allergic contact dermatitis (ACD) outbreak from a smartphone screen protector glue. METHODS: Thirteen affected workers of a chain store selling phone screen protectors were investigated in five Spanish dermatology departments. The glue datasheet and label were assessed. A chemical analysis of the glue was performed. Based on this, some patients underwent additional testing. RESULTS: All patients (all female, mean age: 25) had severe fingertip dermatitis. The datasheet/label indicated that the glue contained isobornyl acrylate (IBOA), a "photoinitiator" and polyurethane oligomer. The company informed us that the ingredients were polyurethane acrylate, "methacrylate" (unspecified), acrylic acid, hydroxyethyl methacrylate, propylmethoxy siloxane, and photoinitiator 184. Isobornyl acrylate (or IBOA) and N,N-dimethylacrylamide (DMAA) were patch tested in eight and two cases, respectively, with negative results. A chemical analysis revealed 4-acryloylmorpholine (ACMO); isobornyl methacrylate (IBMA), and lauryl acrylate in one glue sample. Seven patients were patch tested with dilutions of the identified substances and six of seven were positive for ACMO 0.5% pet. CONCLUSION: An outbreak of occupational ACD, likely from ACMO in a glue is described. Further investigations are needed to corroborate the role played by each compound identified in the chemical analyses.

Candidate Allergens for Inclusion in the Spanish Standard Series Based on Data from the Spanish Contact Dermatitis Registry. / Alérgenos candidatos para ser incluidos en la serie estándar española a partir de los datos del Registro Español de Dermatitis de Contacto.

BACKGROUND: Standard patch test series must be updated using objective data on allergen sensitization. The Spanish standard series was last updated in 2016 and the European series in 2019, and the inclusion of several emerging allergens needs to be evaluated. MATERIAL AND METHODS: We conducted a prospective, observational, multicenter study of consecutive patients from the registry of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) who were patch tested in 2019 and 2020 with linalool hydroperoxide, limonene hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, octylisothiazolinone, textile dye mix (TDM), sodium metabisulfite, propolis, bronopol, Compositae mix II, diazolidinyl urea, imidazolidinyl urea, decyl glucoside, and lauryl glucoside. RESULTS: We analyzed data for 4654 patients tested with diazolidinyl urea, imidazolidinyl urea, and bronopol, and 1890 tested with the other allergens. The values for the MOAHLFA index components were 30% for male, 18% for occupational dermatitis, 15% for atopic dermatitis, 29% for hand, 6.5% for leg, 23% for face, and 68% for age > 40 years. Sensitization rates above 1% were observed for 7 allergens: linalool hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, limonene hydroperoxide, TDM, sodium metabisulfite, and propolis. Three allergens had a current relevance rate of over 1%: linalool hydroperoxide, 2-hydroxyethyl-methacrylat, and limonene hydroperoxide. Benzisothiazolinone and TDM had a relevance rate of between 0.9% and 1%. CONCLUSIONS: Our results indicate that 7 new allergens should be considered when extending the Spanish standard patch test series. The data from our series could be helpful for guiding the next extension of the European baseline series.