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.

Cosmetovigilance for infrequent allergens in Spain using a national online registry: The example of allergic contact dermatitis caused by phenylethyl resorcinol.

BACKGROUND: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. OBJECTIVES: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. METHODS: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. RESULTS: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32-59) and their lesions were mainly in the face. CONCLUSION: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens.

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.

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.

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.

Should methyldibromo glutaronitrile continue to be used in the European baseline Series? A REIDAC national cross-sectional study.

BACKGROUND: Methyldibromo glutaronitrile (MDBGN) was one of the most frequent and relevant allergens found in patch testing at the beginning of this century. In 2008, this preservative was banned from cosmetics in Europe and ever since the prevalence of contact allergy to MDBGN has progressively decreased. Despite that gradual decline, MDBGN is still patch-tested in most baseline series. This study assessed the frequency of MDBGN sensitization, epidemiological characteristics of allergic patients, and the relevance of positive patch tests in a nationwide Spanish registry (REIDAC). PATIENTS AND METHODS: We evaluated consecutively patch-tested patients in all participating centres. Using these data, we calculated the proportion of patients with positive patch tests to MDBGN from June 2018 to June 2020 and evaluated the relevance of the positive patch tests. RESULTS: One hundred and fourteen out of 5072 (2.24 %) tested patients were sensitized to MDBGN. Clinical current relevance was confirmed in only one case. CONCLUSION: Although the frequency of contact allergy to MDBGN remains high, no clinical significance was found in most of these patients (5072 tests needed to obtain one relevant positive result). The clinical usefulness of this allergen seems weak and its continued inclusion in the European baseline series is questionable.

Trend of relevant contact allergens of the feet in Spain over a period of 10 years.

INTRODUCTION: Allergic contact dermatitis (ACD) of the feet accounts for approximately 10% of all patch tested patients. OBJECTIVE: To study the clinical profile of patients with feet dermatitis and relevant contact allergens in Spain over a 10-year period. METHODS: Retrospective observational study of patients with suspected ACD from the GEIDAC (Spanish Research Group on Contact Dermatitis and Cutaneous Allergy) baseline series from eight hospitals in Spain between 2004 and 2014. The clinical data collected from each patient were age, sex, occupation, history of atopic dermatitis, and eczema location. RESULTS: A total of 450 cases clinically presented dermatitis affecting the feet; of these, 41% of were males and 5.6% were suspected to be of occupational origin. As much as 47% were diagnosed with ACD, 20% with atopic dermatitis/dyshidrotic eczema, and 5% with psoriasis. The "feet group" included statistically significantly more females in the age range of 21 to 60 years. The most frequent relevant contact allergens were potassium dichromate, cobalt(II) chloride, p-tert-butylphenol formaldehyde resin, mercapto mix, and mercaptobenzothiazole. CONCLUSIONS: ACD is the most frequent clinical diagnosis of feet dermatitis in our series. The most frequent allergens are similar to those published in other series of foot ACD in Europe and the trend has not changed in the studied decade.

Are the Spanish baseline series markers sufficient to detect contact allergy to corticosteroids in Spain? A GEIDAC prospective study.

BACKGROUND: Corticosteroids are among the most commonly used topical drugs. Contact allergy to these exists, but can be easily missed. Corticosteroid screening markers have been included in the baseline series with the aim of detecting most of the sensitized patients. OBJECTIVES: To assess the prevalence of contact allergy to topical corticosteroids in Spain and examine the usefulness of corticosteroid markers to detect contact allergy to corticosteroids. METHODS: In total, 3699 patients referred to 20 dermatology departments across Spain for patch testing with the baseline series, including budesonide and tixocortol pivalate, were also tested with six supplementary corticosteroids (methylprednisolone aceponate, mometasone furoate, prednicarbate, clobetasol propionate, betamethasone 17-valerate, and betamethasone 17,21-dipropionate). Additionally, 2547 (68.8%) patients were tested with hydrocortisone 17-butyrate. RESULTS: Fifty-four patients showed positive reactions to at least one of all tested corticosteroids (1.46%). Thirty-nine (1.05%) reacted to at least one of the additionally tested corticosteroids; among these, 24 of 39 (61.5%) did not react to any of the corticosteroid allergy screening markers tested. CONCLUSIONS: More than half of the patients who were allergic to the additionally tested corticosteroids were not detected with the corticosteroid allergy markers. An update of the corticosteroid allergy screening markers is encouraged, with consideration of group 3 corticosteroids.

Allergic contact dermatitis caused by (meth)acrylates in long-lasting nail polish - are we facing a new epidemic in the beauty industry?

BACKGROUND: Allergic contact dermatitis (ACD) caused by (meth)acrylates has been described both in occupational and in non-occupational settings. OBJECTIVES: To evaluate the clinical patterns, the most frequent allergens and the prognosis in patients sensitized to (meth)acrylates in long-lasting nail polish. METHODS: The files of patients with ACD caused by (meth)acrylates in long-lasting nail polish diagnosed between January 2013 and June 2016 in four dermatology departments in Spain were reviewed. Patients were followed up by telephone interview. RESULTS: Overall, 2353 patients were patch tested. Forty-three (1.82%) were diagnosed with ACD caused by (meth)acrylates in long-lasting nail polish during that period; all were female, and all had hand dermatitis. Patients were mostly less than 40 years old (72.1%), non-atopic (95.4%) and had an occupational cause of their dermatitis (93%), which developed ∼10.1 months after they had started to use this technique. The most frequent positive allergens were: 2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, and tetrahydrofurfuryl methacrylate. Eight of the 22 interviewed patients were able to improve their working technique and used 4H® protective material (fingerstalls/gloves). CONCLUSIONS: Long-lasting nail polishes have become widespread, and it is a matter of concern that we may be facing a new epidemic of ACD caused by these. Policies regulating their use are urgently needed.

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.