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Vol. 115. Núm. 4.
Páginas T331-T340 (Abril 2024)
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Vol. 115. Núm. 4.
Páginas T331-T340 (Abril 2024)
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[Translated article] Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends
Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias
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F. Tous-Romeroa,
Autor para correspondencia
fatimatousro@gmail.com

Corresponding author.
, L. Borrego-Hernandob, I. García-Dovalc, P. Mercader-Garcíad, J.F. Silvester-Salvadore, A. Sánchez-Gilof, T. Sanz-Sánchezg, A.M. Giménez-Arnauh, V. Zaragoza-Nineti, J. Miquel-Miquelj, R. González Pérezk, S. Córdoba-Guijarrol, J.M. Carrascosa-Carrillom, M.E. Gática-Ortegan, I. Ruíz-Gonzálezo, E. Serra-Baldrichp, A. Pastor-Nietoq, M. Rodríguez-Sernar, J. Sánchez-Pérezs, G. Melé i Ninott..., P. Sánchez-Pedreño Guillénu, J. Ortiz-de FrutosaVer más
a Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, Spain
b Servicio de Dermatología, Hospital Universitario Insular de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
c Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, Spain
d Servicio de Dermatología, Hospital General Universitario José M. Morales Meseguer, Murcia, Spain
e Servicio de Dermatología, Hospital General de Alicante, Alicante, Spain
f Servicio de Dermatología, Hospital Rey Juan Carlos, Madrid, Spain
g Servicio de Dermatología, Hospital Universitario Infanta Sofía, Madrid, Spain
h Servicio de Dermatología, Hospital del Mar, Barcelona, Spain
i Servicio de Dermatología, Hospital Universitario de Valencia, Valencia, Spain
j Servicio de Dermatología, Hospital Universitario Arnau de Vilanova, Valencia, Spain
k Servicio de Dermatología, Hospital Universitario Araba, Vitoria, Álava, Spain
l Servicio de Dermatología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
m Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
n Servicio de Dermatología, Complejo Hospitalario Universitario de Toledo, Toledo, Spain
o Servicio de Dermatología, Complejo Asistencial Universitario de León, León, Spain
p Servicio de Dermatología, Hospital de la Santa Creu i San Pau, Barcelona, Spain
q Servicio de Dermatología, Hospital Fundación Jiménez Díaz, Madrid, Spain
r Servicio de Dermatología, Hospital Universitario La Fe, Valencia, Spain
s Servicio de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain
t Servicio de Dermatología, Hospital Sagrat Cor, Barcelona, Spain
u Servicio de Dermatología, Hospital Virgen de la Arrixaca, Murcia, Spain
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F. Tous-Romero, L. Borrego-Hernando, I. García-Doval, P. Mercader-García, J.F. Silvester-Salvador, A. Sánchez-Gilo, T. Sanz-Sánchez, A.M. Giménez-Arnau, V. Zaragoza-Ninet, J. Miquel-Miquel, R. González Pérez, S. Córdoba-Guijarro, J.M. Carrascosa-Carrillo, M.E. Gática-Ortega, I. Ruíz-González, E. Serra-Baldrich, A. Pastor-Nieto, M. Rodríguez-Serna, J. Sánchez-Pérez, G. Melé i Ninot, P. Sánchez-Pedreño Guillén, J. Ortiz-de Frutos
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Table 1. Variation of MOAHLFA index on a yearly basis.
Table 2. Positivity rates to the different allergens included in the standard GEIDAC series in all the studied patients differentiated by sex.
Table 3. Percentage of positivity for various allergens included in the standard GEIDAC series across the study years.
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Abstract
Background

The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process.

Objectives

To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022.

Methods

This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend).

Results

A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend.

Conclusions

Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Keywords:
Patch tests
Methylisothiazolinone
GEIDAC
REIDAC
Epidemiological surveillance
Trends
Resumen
Antecedentes

El Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea tiene entre sus objetivos la vigilancia epidemiológica de la dermatitis de contacto. Para ello es importante conocer si se producen alteraciones en el tiempo de las prevalencias de las positividades a los distintos alérgenos.

Objetivos

Describir las variaciones en las tendencias temporales en positividades a alérgenos en la serie estándar del GEIDAC en el periodo comprendido entre 2018 y el 31 de diciembre de 2022.

Métodos

Estudio observacional multicéntrico de pacientes estudiados consecutivamente mediante pruebas epicutáneas dentro del estudio de un posible eczema alérgico de contacto recogidos de forma prospectiva en el seno del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. Se analizaron los datos mediante 2 pruebas estadísticas: una de homogeneidad (para ver si hay cambios en los diferentes años) y otra de tendencia (para ver si los cambios siguen una tendencia lineal).

Resultados

Se incluyeron un total de 11.327 pacientes en el periodo de estudio. Los alérgenos en los que de forma global se detectó una sensibilización mayor fueron sulfato de níquel, metilisotiazolinona, cloruro de cobalto, metilcloroisotiazolinona/metilisotiazolinona y mezcla de fragancias i. Se detectó una disminución estadísticamente significativa en el porcentaje de positividades de metilisotiazolinona a lo largo de años de estudio con una tendencia ordenada.

Conclusiones

Si bien se pueden apreciar diferentes cambios en las tendencias a sensibilizaciones a varios de los alérgenos de la batería estándar, se observa que persiste una alta sensibilización al níquel, a la metilcloroisotiazolinona/metilisotiazolinona y a la mezcla de fragancias i. Solo se aprecia una tendencia a disminuir de forma significativa en el caso de la metilisotiazolinona.

Palabras clave:
Pruebas epicutáneas
Metilisotiazolinona
GEIDAC
REIDAC
Vigilancia epidemiológica
Tendencias
Texto completo
Introduction

The Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC) has, among its objectives, the epidemiological surveillance of contact dermatitis. For this purpose, it is essential to know if there are any changes in the prevalences of sensitizations to different allergens over time.1,2

Patch tests constitute the fundamental method for detecting sensitization to contact allergens,3,4 serving as an essential tool for diagnosing allergic contact dermatitis (ACD).3,4 The evaluation of any patient with suspected ACD should include a standard national or international battery of patch tests and, optionally, one or more specific batteries, which may also include the patient's own products.3,4

The Spanish standard battery is a dynamic battery that is periodically updated by members of the Spanish Research Group on Contact Dermatitis and Skin Allergy (GEIDAC). To do this, various criteria are taken into consideration, such as the frequency of sensitization (> 0.5% to 1%), as well as other characteristics, such as whether there are emerging allergens in the dermatological medical literature available or neighboring countries, or whether they are of particular importance for a group of patients, or exposure environment.

The objective of our work is to describe the variations in temporal trends in sensitizations to allergens in the standard series of GEIDAC from 2018 through December 31, 2022.

Materials and methods

REIDAC prospectively collects the results of all consecutively patched patients in the participant centers. The data are anonymized at the source, and the registry complies with all ethical standards on informed consent and data protection legislation. In addition to the present positivities and relevancies, the registry successively collects epidemiological, clinical, and allergic variables of patients who underwent patch tests at the participant centers across this period, including the data necessary to obtain the Male, Occupational dermatitis, Atopic dermatitis, Hand dermatitis, Leg dermatitis, Facial dermatitis, Age > 40 years (MOAHLFA) index. In this study, we used data from 2018 through December 31, 2022.3

Patch tests were performed following the recommendations of the European Society of Contact Dermatitis,5 considering readings (+), (++), or (+++) as positive. Relevance was determined based on the patient's health record.

The latest update of the GEIDAC standard battery dates back to January 2022, including 4 new allergens (hydroxyethyl methacrylate, textile dye mix, linalool hydroperoxides, and limonene hydroperoxides), and removing 3 (ethylene diamine dihydrochloride, methyl dibromoglutaronitrile, and hydroxyisohexyl-3-cyclohexene-carboxaldehyde), which were not included in the current study.3

A descriptive analysis of the MOAHLFA index was performed, as well as the prevalence of each allergen, and its distribution over the years was compared. The results were graphically presented. Homogeneity comparisons were drawn using the chi-square test, and the linear trend analysis was performed using the linear trend tests for scores. For trend analysis, raw P values and MOAHLFA-adjusted values were obtained. The prevalence of each allergen in the standard battery was also presented by age and sex.

All statistical analyses were performed using the STATA v.17.0 software (Stata Corp. 2021. Stata Statistical Software: Release 17). P values < .0016 (adjusted with Bonferroni correction for multiple comparisons) were considered statistically significant.

REIDAC was approved by Hospitalario Universitario Insular-Materno Infantil Research Ethics Committee (2017/964) in full compliance with the Declaration of Helsinki. All patients signed a written informed consent form for participation purposes.

Results

The total number of patients included in REIDAC during the study period was 11327 participants. The distribution by years of this population, as well as the description of the MOAHLFA index by year, are included in Table 1.

Table 1.

Variation of MOAHLFA index on a yearly basis.

MOAHLFA index per year
  Year of consultation
  20182019202020212022P 
   
Total samples  1067  100  3.436  100  1701  100  2421  100  2.702  100   
Men (M)  322  30  1063  31  476  28  750  31  839  31  .1902 
Occupational factors (O)  106  10  311  10  194  12  195  247  .0038** 
Atopic dermatitis (A)  179  17  531  16  293  17  468  19  513  19  .0005*** 
Hands (H)  320  30  977  28  529  31  748  31  885  33  .0023** 
Legs (L)  69  187  100  105  138  .0706 
Face (F)  275  26  920  27  366  22  518  21  596  22  .0000*** 
Age>40 years (A)  734  69  2463  72  1.132  67  1573  66  1790  67  .0000*** 
Any positive (P)  490  46  1595  46  769  45  1090  45  1196  44  0,5362 
**

P<.01.

***

P<.001.

Although there are statistically significant differences in some variables, conditioned by the large sample size, these are clinically less relevant, and when adjusting values for these differences, there are no changes in the trends reported.

Table 2 illustrates the total positives for different allergens in the standard series of GEIDAC in the patients studied over the study years in the overall population studied, differentiated by gender, and standardized by sex and age.

Table 2.

Positivity rates to the different allergens included in the standard GEIDAC series in all the studied patients differentiated by sex.

  AllWomenMen
  ResultResultResult
    Positivity (+/++/+++)  Positivity (+/++/+++)  Positivity (+/++/+++)
  N (%)  Statistics (95%CI)  N (%)  Statistics (95%CI)  N (%)  Statistics (95%CI) 
1. Nickel sulfate  1 1258  2604 (23.13)  17.01 (16.31-17.71)  7836  2266 (28.92)  22.96 (22.03-23.91)  3420  338 (9.88)  8.08 (7.17-9.03) 
2. Lanolin alcohols  11 241  66 (0.59)  0.46 (0.35-0.61)  7820  43 (0.55)  0.46 (0.32-0.64)  3419  23 (0.67)  0.46 (0.27-0.76) 
3. Neomycin sulfate  11 241  99 (0.88)  0.95 (0.78-1.14)  7820  69 (0.88)  0.84 (0.65-1.06)  3419  30 (0.88)  1.11 (0.79-1.53) 
4. Potassium dichromate  11 255  347 (3.08)  3.09 (2.78-3.42)  7831  186 (2.38)  2.48 (2.14-2.85)  3422  161 (4.7)  4 (3.35-4.7) 
5. Cain mix  7322  69 (0.94)  1.11 (0.88-1.38)  5141  47 (0.91)  0.84 (0.61-1.13)  2179  22 (1.01)  1.5 (1.05-2.13) 
6. Fragrance mix i  11 243  465 (4.14)  3.63 (3.29-3.99)  7821  334 (4.27)  3.77 (3.36-4.22)  3420  131 (3.83)  3.42 (2.85-4.1) 
7. Colophony  11 247  153 (1.36)  1.43 (1.23-1.68)  7825  105 (1.34)  1.5 (1.24-1.8)  3420  48 (1.4)  1.33 (0.96-1.76) 
8. Paraben mix  11 250  46 (0.41)  0.49 (0.37-0.64)  7826  22 (0.28)  0.29 (0.18-0.43)  3422  24 (0.7)  0.8 (0.52-1.15) 
10. Peru balsam  11 245  362 (3.22)  3.37 (3.04-3.72)  7824  226 (2.89)  2.93 (2.56-3.33)  3419  136 (3.98)  4.03 (3.38-4.73) 
12. Cobalt chloride  11 257  536 (4.76)  4.12 (3.76-4.51)  7833  402 (5.13)  4.56 (4.11-5.05)  3422  134 (3.92)  3.45 (2.87-4.13) 
13. P-tert-Butylphenol formaldehyde resin  11 244  173 (1.54)  1.37 (1.16-1.6)  7822  132 (1.69)  1.68 (1.41-1.99)  3420  41 (1.2)  0.9 (0.62-1.29) 
14. Epoxy resin  11 243  102 (0.91)  0.72 (0.57-0.89)  7822  54 (0.69)  0.53 (0.38-0.71)  3419  48 (1.4)  1 (0.69-1.39) 
15. Carbamix mix  11 201  187 (1.67)  1.66 (1.43-1.91)  7792  98 (1.26)  1.1 (0.89-1.37)  3407  89 (2.61)  2.49 (2-3.08) 
16. Black rubber mix/IPPD  11 243  100 (0.89)  1.18 (0.99-1.4)  7822  68 (0.87)  1.11 (0.88-1.36)  3419  32 (0.94)  1.3 (0.94-1.73) 
17. Methylchloroisothiazolinone/methylisothiazolinone  9358  420 (4.49)  4.02 (3.62-4.43)  6520  284 (4.36)  4.07 (3.6-4.58)  2836  136 (4.8)  3.93 (3.24-4.71) 
18. Quaternium-15  11 255  94 (0.84)  0.91 (0.74-1.1)  7830  73 (0.93)  0.99 (0.78-1.23)  3423  21 (0.61)  0.78 (0.52-1.15) 
20. Paraphenylenediamine  11 243  416 (3.7)  3.25 (2.92-3.59)  7821  337 (4.31)  3.67 (3.27-4.12)  3420  79 (2.31)  2.6 (2.1-3.2) 
21. Formaldehyde  9777  254 (2.6)  2.6 (2.29-2.93)  6799  181 (2.66)  2.91 (2.52-3.34)  2976  73 (2.45)  2.14 (1.64-2.71) 
22. Mercaptan mix  11 241  42 (0.37)  0.41 (0.29-0.54)  7820  22 (0.28)  0.25 (0.15-0.38)  3419  20 (0.58)  0.65 (0.4-0.98) 
24. Thiuram mix  11 240  177 (1.57)  1.34 (1.14-1.57)  7819  111 (1.42)  1.08 (0.86-1.33)  3419  65 (1.9)  1.74 (1.32-2.23) 
25. Diazolidinyl urea  11 258  49 (0.44)  0.67 (0.53-0.84)  7831  32 (0.41)  0.61 (0.44-0.8)  3425  17 (0.5)  0.75 (0.5-1.11) 
27. Tixocortol pivalate  11 245  41 (0.36)  0.45 (0.34-0.6)  7821  32 (0.41)  0.56 (0.4-0.74)  3422  9 (0.26)  0.3 (0.14-0.54) 
29. Imidazolidinyl urea  11 259  44 (0.39)  0.4 (0.29-0.53)  7832  30 (0.38)  0.37 (0.25-0.53)  3425  14 (0.41)  0.43 (0.25-0.72) 
30. Budesonide  11 247  84 (0.75)  0.79 (0.64-0.98)  7823  44 (0.56)  0.64 (0.48-0.85)  3422  40 (1.17)  1.03 (0.72-1.42) 
32. Mercaptobenzothiazole  11 241  40 (0.36)  0.41 (0.3-0.55)  7820  18 (0.23)  0.31 (0.2-0.46)  3419  22 (0.64)  0.56 (0.34-0.87) 
33. Methylisotiazolinone  10 295  729 (7.08)  6.84 (6.36-7.34)  7154  470 (6.57)  6.42 (5.86-7.01)  3139  259 (8.25)  7.47 (6.58-8.45) 
35. Fragrance mix ii  10 293  351 (3.41)  3.35 (3.01-3.71)  7150  232 (3.24)  3.03 (2.65-3.46)  3141  119 (3.79)  3.81 (3.16-4.53) 
38. 2-HEMA  6245  277 (4.44)  3.19 (2.77-3.66)  4358  265 (6.08)  5.02 (4.38-5.7)  1885  12 (0.64)  0.44 (0.18-0.84) 
39. Textile dye mix  6211  202 (3.25)  2.98 (2.57-3.43)  4290  137 (3.19)  2.92 (2.45-3.48)  1919  65 (3.39)  3.08 (2.36-3.96) 
40. Linalool hydroperoxides  6507  361 (5.55)  6.01 (5.45-6.62)  4538  265 (5.84)  6.11 (5.42-6.84)  1967  96 (4.88)  5.87 (4.87-7) 
41. Limonene hydroperoxides  6532  284 (4.35)  4.36 (3.87-4.88)  4546  216 (4.75)  4.5 (3.91-5.14)  1984  68 (3.43)  4.15 (3.31-5.13) 

IPPD, N-isopropyl-n-phenyl-phenylenediamine; 2-HEMA, hydroxyethyl methacrylate; Statistics (95%CI): age and sex standardized percentage (95% confidence interval)

As can be seen, the allergens that showed a higher overall sensitization frequency across the study period were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and fragrance mix i. Some gender differences were seen while for women, the most frequently positive allergens were nickel sulfate, methylisothiazolinone, cobalt chloride, MCI/MI, fragrance mix i, and paraphenylenediamine (PPD), for men, they were nickel sulfate, MCI/MI, and potassium dichromate, with lower sensitization to PPD in men compared to in women (2.31 vs 3.31), and higher sensitization to potassium dichromate (4.7 vs 2.38), among other differences. The sensitization frequency to the allergens added in January 2022 in the studied patients was 4.44% for hydroxyethyl methacrylate, 2.58% for textile dye mix, 4.59% for linalool hydroperoxides, and 3.92% for limonene hydroperoxides.

Table 3 shows the percentage of positives for different allergens included in the standard GEIDAC series across different study years. The allergens recently included in the GEIDAC standard battery are included at the end of this table; since they were not systematically patched in the early years and, therefore, were studied in a much smaller number of patients, their data prior to their inclusion in 2022 are not included in the trend study.

Table 3.

Percentage of positivity for various allergens included in the standard GEIDAC series across the study years.

All            Corrected P value  .0016   
  Percentage of pos. per year of consultation     
  2018  2019  2020  2021  2022       
            P value homogeneity  P value trend  P value adjusted trend 
1. Nickel sulfate  24.93  23.23  23.65  22.87  22.20  .4592  .1031  .2061 
2. Lanolin alcohols  0.75  0.44  0.65  0.67  0.60  .7052  .7065  .6004 
3. Neomycin sulfate  1.03  1.14  0.77  0.83  0.60  .2239  .0331  .0445 
4. Potassium dichromate  3.10  3.66  3.19  2.54  2.76  .1255  .0397  .0212 
5. Cain mix  0.44  0.84  1.31  0.74  1.14  .2882  .1862  .3812 
6. Fragrance mix i  3.95  4.57  3.67  4.29  3.82  .4853  .3973  .5267 
7. Colophony  1.41  1.67  1.30  1.17  1.16  .4114  .1016  .0513 
8. Paraben mix  0.47  0.56  0.41  0.25  0.34  .4428  .1242  .9651 
9. Peru balsam  3.01  3.19  3.08  3.04  3.59  .7880  .4008  .3678 
10. Cobalt chloride  4.05  4.59  4.91  4.87  5.07  .7139  .1870  .8976 
11. P-tert-Butylphenol formaldehyde resin  1.98  1.76  1.30  1.17  1.57  .2624  .1736  .6070 
12. Epoxy resin  0.75  1.00  1.18  0.58  0.97  .2943  .7691  .4718 
13. Carbamix mix  2.45  1.43  1.72  1.60  1.70  .2699  .6302  .6766 
14. Black rubber mix/IPPD  1.60  1.00  0.47  0.58  1.01  .0121  .1440  .8857 
15. Methylchloroisothiazolinone/methylisothiazolinone  5.08  4.30  5.34  5.07  3.57  .0488  .1470  .6301 
16. Quaternium-15  0.66  1.11  0.77  0.67  0.75  .3200  .2687  .1568 
17. Paraphenylenediamine  4.33  3.78  3.66  3.92  3.18  .4711  .1544  .4577 
18. Formaldehyde  2.58  2.93  2.55  2.52  2.33  .7384  .2623  .1630 
19. Mercaptan mix  0.56  0.35  0.41  0.33  0.34  .8510  .4745  .5352 
20. Thiuram mix  1.79  1.46  2.13  1.46  1.39  .3130  .4415  .5161 
21. Diazolidinyl urea  0.38  0.50  0.30  0.46  0.45  .8810  .9628  .4792 
22. Tixocortol pivalate  0.85  0.29  0.35  0.33  0.30  .1045  .1622  .3815 
23. Imidazolidinyl urea  0.00  0.44  0.30  0.50  0.45  .2207  .1631  .3252 
24. Budesonide  0.75  0.88  0.77  0.92  0.41  .2176  .1340  .1648 
25. Mercaptobenzothiazole  0.66  0.29  0.65  0.29  0.19  .0458  .0806  .4879 
26. Methylisotiazolinone  8.55  8.00  7.82  6.79  5.21  .0002  .0000  .0232 
27. Fragrance mix ii  2.62  4.08  2.83  3.46  3.20  .0957  .5608  .9768 
28. 2-HEMA          4.73       
29. Textile dye mix          2.58       
30. Linalool hydroperoxides          4.59       
31. Limonene hydroperoxides          3.92       

IPPD, N-isopropyl-n-phenyl-phenylenediamine; 2-HEMA, hydroxyethyl methacrylate; Pos.: positivity

Data with statistically significant differences highlighted in bold.

We can see how the percentage of positives for methylisothiazolinone decreases over time, with an orderly trend.

The figures below represent the variation in the percentage of positives for different allergens across the study years, both globally and differentiated by gender.

Figure 1 includes allergens with sensitization rates > 4% (nickel sulfate, methylisothiazolinone, cobalt chloride, MCI/MI, and fragrance mix I).

Figure 1.

Variation across time for allergens with overall sensitization rates in the study years > 4%, both for the ovefrall population and broken down by gender.

(0,3MB).

The allergens that showed sensitization frequencys ranging from 1% to 4% during the study period were PPD, fragrance mix II, balsam of Peru, potassium dichromate, formaldehyde, carbamate mix, thiuram mix, p-tert-butylphenol-formaldehyde resin, and rosin, as shown in Figure 2.

Figure 2.

Variation across time for allergens with overall sensitization rates in the study years from 1% to 4%, both for the overall population and broken down by gender.

(0,37MB).

Figure 3 illustrates the variation in the percentage of positive results over the years for the remaining allergens, each of which had an overall sensitization frequency < 1%.

Figure 3.

Variation across time for allergens with overall sensitization rates in the study years < 1%, both for the overall population and broken down by gender.

(0,45MB).
Discussion

Epidemiological surveillance in contact dermatitis is key to understand the variations in sensitizations to different allergens over the years, thereby enabling the implementation of proper measures for their prevention at both individual and community levels. In Spain, such surveillance is one of the objectives of REIDAC

In 1977, the first national epidemiological study of this kind was published, including 2806 patients studied through patch tests.2 The most frequently positive allergens at that time were nickel, potassium dichromate, tetramethylthiuram disulfide, PPD, a mixture of mercaptans, and wood tar extracts. Since then, various changes in exposure have led to modifications in the allergens studied (with several changes made to the GEIDAC standard series),3,4 and differences in sensitization frequencies. However, some of the allergens that were already common in those years continue to be so today. In 2011, another publication of 1161 patients from 5 national centers1 claimed that the most frequently positive allergens were nickel sulfate (25.88%), potassium dichromate (5.31%), cobalt (5.10%), a mixture of fragrances (4.64%), and balsam of Peru (4.44%). Also, there is a recent publication from our region on a specific population from Gran Canaria, Canary Islands, Spain which identified nickel sulfate, MCI/MI, methylisothiazolinone, PPD, and potassium dichromate as the most frequent allergens, even at higher frequencies than those reported at national level.6

In the international scientific medical literature available, there are other publications that attempt to capture changes in the percentage of sensitization to different allergens over the years in a similar way. In most of these series, the changes seen across years are not systematically recorded, and they are not always collected prospectively. Some series pertain to other populations,7 some of which, despite spanning across many more years, include fewer patients.8 Additionally, there are several European publications9–15 that either focus on data from years prior to ours or, in addition to that, focus on specific groups of allergic contact eczemas, such as those associated with occupational exposure,14 or due to specific allergens.15

With the current technology, a real-time approach to the most common allergens in Spain is possible.16

Among the results obtained, the persistence of high sensitization to nickel sulfate stands out, as mentioned earlier. In fact, it was already documented the early studies conducted in Spain (25.88),12 as well as in other European studies (23.98%).17 Nickel is a metal found in alloys, being nickel salts responsible for dermatitis, promoting their release and penetration into the skin primarily facilitated by sweating. In 1994, European regulations were passed to control the release of nickel in jewelry, but they did not become effective until 2021. Despite the ongoing high sensitization, many of the positive cases detected today do not seem to be relevant today.

PPD continues to exhibit high sensitization in our environment, especially among women, as mentioned earlier. In a recent publication on PPD sensitization across various Spanish centers,18 it remained fairly stable at nearly 4% of all patch-tested patients from 2004 through 2014, and no significant changes reported despite the regulation implemented in 2009 regarding hair dyes (reducing its maximum concentration from 6% down to 2%). Several hypotheses have been proposed for the persistence of this sensitization, such as the maintenance of the habit of getting temporary henna tattoos, which are often adulterated with PPD, whose concentration has not yet been regulated,19 or lifestyle changes leading to more and more patients using cosmetics containing PPD at younger ages.

In our study, sensitization to fragrance mix I also persists at a high level, despite regulatory changes introduced in the mandatory labeling of certain fragrances. Also, it remains at levels similar to those reported in previous national series (4.99%),1 and recent European studies (3.4%).17

High sensitization to isothiazolinones, both MCI/MI (which remains high throughout across the study years) and methylisothiazolinone should also be mentioned here. In the case of the latter, although sensitization remains high, there is a drop in sensitization frequency across the years, both in raw values and when adjusted for sex and age being the only allergen with statistically significant changes reported.

Methylisothiazolinone is a derivative of isothiazolinones, and is widely used as a preservative in rinse-off cosmetics, household detergents, water-based paints, and industrial products. Sensitization to it occurs both in the domestic environment—mainly due to exposure to cosmetics and household detergents—and in the workplace, especially among cleaning workers.

The epidemic of sensitization to methylisothiazolinone at the beginning of the 21st century is well known.20–22 As a result, after recognizing the problem, the use of methylisothiazolinone was ill-advised in rinse-off cosmetics by the European cosmetic industry at the end of 2013. At the same time, the Scientific Committee on Consumer Safety reevaluated the risk, which lead to the recommendation to ban the use of methylisothiazolinone in rinse-off cosmetics and keep the maximum allowable level to 15ppm in leave-on cosmetics. Although it took time for this recommendation to translate into an actual regulation, and the regulation again allowed for transition periods, a change in sensitization trends could be expected as confirmed by our most recent data.

In the United States, according to the most recent data from the North American Contact Dermatitis Group, the highest prevalence of sensitization to isothiazolinones occurred later than it did in Europe.23 While in Europe, sensitization to MCI/MI from 2013 through 2014 reached levels of 5.4% to 7.6%, before dropping in 2017-2018 down to 3.2%-4.4%,24,25 in the United States, positivity to MCI/MI increased from 2.5% in 2009-2010 up to 10.8% in 2017-2018. The same thing happened for methylisothiazolinone, where reactions decreased in Europe down to 3.4%-5.5% compared to 15% in the North American Contact Dermatitis Group during 2017-2018. This is likely due to the lack of regulations on the use of isothiazolinones in cosmetics across the United States.

According to recent data published by REIDAC,22 sensitization to both MI and MCI/MI is associated with being an active worker, hand dermatitis, the use of detergents, and being older than 40 years.

Some other changes in sensitization trends can be seen, but none of them are significant. For example, in the case of neomycin, there is a downward trend since data collection began, although it is not significant, possibly indicating reduced use of topical drugs including combinations of antibiotics and other agents (corticosteroids, antifungals, etc.). In Spain, prescriptions for topical products combining corticosteroids and antibiotics have not been funded for years.

Similarly, we can see also non-significant downward trend in sensitization to potassium dichromate. The most common sources of exposure to potassium dichromate are wet cement and chromium-tanned leather products. Since 2005, the use of cements with > 2ppm of hexavalent chromium has been restricted, and a decrease in sensitization has been detected based on historical data and in certain regions.6,26 The decrease in sensitization is likely related to this regulation, and with the improved preventive measures implemented by construction workers. Additionally, a probable decrease in the use of leather footwear in recent years may have also contributed to its decline, although there is not enough data to confirm this hypothesis to date.

Our study included data on allergens that have been more recently added to the standard GEIDAC panel, and a high overall level of sensitization to all of them can be observed (hydroxyethyl methacrylate, textile dye mix, linalool hydroperoxides, and limonene hydroperoxides).

For a specific population, changes in sensitization to different allergens often depend on the chemical characteristics of these allergens (which, overall, do not change), and the degree of exposure to them. Therefore, assuming that the characteristics of our population have remained fairly consistent across the years (no significant differences in the MOAHLFA data across the years can be seen, as shown in Table 1, except perhaps for the face, where a decrease was seen in the 2020-2022 compared to previous years, possibly influenced by the use of masks during the COVID pandemic years), the differences detected in sensitization should be attributed to changes in various exposures.

Conclusions

According to the data obtained in our study, the persistence of high sensitization to allergens such as nickel, MCI/MI, and fragrance mix I is noteworthy. Only a significant downward trend for methylisothiazolinone was found.

We want to emphasize the importance of multicenter registries, which allow us to gather data on a large scale and thereby detect trends. This enables us to observe potential increases in sensitization to certain allergens, prompting us to consider the need for measures to reduce this. Additionally, as is the case with methylisothiazolinone, it helps us verify the effectiveness of the measures taken to reduce sensitization.

Funding

None declared.

Conflicts of interest

None declared.

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