Contact dermatitis (CD) is a prevalent inflammatory skin condition frequently encountered in dermatological practice. Its clinical presentation is characterized by erythematous, desquamative, and pruritic vesicles, papules, or plaques, often accompanied by lichenification, leading to a significant impact on patients' quality of life⁠.1 The CD comprises a significant proportion of occupational dermatoses and carries substantial socioeconomic implications, particularly in industrialized nations.2⁠⁠

CD can be classified into two main types: Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD arises from the direct toxic and pro-inflammatory effects of certain substances, while ACD is a delayed-type hypersensitivity reaction mediated by hapten-specific T-cells⁠⁠.1

While the diagnosis of CD primarily relies on clinical evaluation, patch testing (PT) serves as the gold standard complementary diagnostic tool for confirming this condition. PT aims to reproduce the elicitation phase of ACD by controlled exposure to suspected agents, thereby confirming the diagnosis and determining the etiology of ACD. The PT series typically consists of a standard battery of common allergens and irritants, including fragrances, preservatives, metals, rubber, and other chemicals to which patients are commonly exposed and may be associated with their clinical presentation.2,3

In Brazil, the Brazilian Group for the Study of Contact Dermatitis (GBEDC) developed a standardized battery in 2000, approved by the Brazilian Society of Dermatology (SBD), comprising 30 substances. However, there is a scarcity of Brazilian etiological and epidemiological data on ACD across different regions that could provide population representativeness. While several studies have been published by prominent Brazilian dermatological centers, they have been conducted in isolation, and no comprehensive analyses or comparisons of results have been published at the national level⁠⁠.2,3

It is well-established that the population profile and exposure to various substances can influence PT results, which are also known to evolve over time. Therefore, to address these gaps in knowledge, a systematic review was undertaken with the objective of collating and synthesizing information regarding PT results obtained using the Brazilian standard battery over the past 22-years.

Through the initial search, a total of 81 articles deemed potentially relevant were identified. Following the removal of duplicates, 55 articles remained for further evaluation. Subsequently, 37 articles were excluded based on title and abstract screening. The full texts of the remaining 18 articles were thoroughly assessed for eligibility. Ultimately, 10 studies met the predefined inclusion criteria and were included in this systematic review, as depicted in Fig. 1. Table 1 provides a summary of the selected studies and their respective characteristics.

Figure 1.

Search strategy results.

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Considering the criteria of the tool used for quality assessment, the Joanna Briggs Institute Critical Appraisal Tool, the authors found 7 articles of medium quality,2,3,6–8,11,13 3 considered to be of good quality,9,10,12 and none of the 10 articles pre-selected based on the inclusion and exclusion criteria were considered to be of low quality, with no indication for exclusion from the systematic review.

The total number of patients subjected to patch testing, considering all selected studies, was 4703. In all 10 studies, the tests were performed on patients with suspected contact dermatitis. The studies were conducted in four different states in Brazil, but only in two regions, in the South and Southeast. ⁠⁠In the South region, there was one study in the state of Santa Catarina and two studies in the state of Rio Grande do Sul.2,6,7 In the Southeast region, there were five studies in the state of São Paulo8–12 and two studies in the state of Minas Gerais.3,13⁠⁠ Regarding gender, the majority of the population included in the studies was female in all 10 studies, as shown in detail in Table 1.

As for the sites of dermatitis, the cephalic segment (face, head, and neck) was the most affected in all studies, except in Rodrigues et al.,13 where it ranked as the second most common after the hands. In Fernandes et al.9⁠⁠ the most common sites were eyelids (12.30%) and face (9.2%); in Silva et al.,12⁠⁠ the cephalic segment including the head, face, and neck accounted for 44.79% of cases; in Duarte et al.,11 the cephalic segment accounted for 45.3% of cases; in Rodrigues et al.⁠⁠,3 the face was affected in 24.8% of cases; in Artus et al.,6 the head and neck were affected in 48.9% of cases; and in Duarte et al.,8 the cephalic segment (head and neck) was the most frequently affected (81 cases, 29%). In Rodrigues et al.,13 the hands were the most affected site (44.7%), and the studies by Opperman et al.,7 GBEDC10⁠⁠, and Correa et al.2 did not provide this information.

Associations between variables

Regarding the associations tested between the percentage of positive tests and the variables of sex, age, and region in Brazil, the results are described in Table 3. Values with p < 0.1 were considered statistically significant.

Table 3.

Associations identified with sex, age, and region from the period of 2000 to 2022.

Blue: As the proportion of the variable increases, the proportion of positive tests decreases. Pink: As the proportion of the variable increases, the proportion of positive tests increases. Yellow: Statistically significant associations.

a Southeast region considered as the reference.

Sex

A higher proportion of females in the sample was associated with a lower proportion of positive tests for the following substances: anthraquinone, potassium dichromate, carbamix, colophony, epoxy resin, hydroquinone, nitrofurazone, paraben mix, paraphenylenediamine, propylene glycol, quaternium 15, quinoline mix, and turpentine (p < 0.1).

For the substances ethylenediamine, formaldehyde, lanolin, mercapto mix, neomycin, nickel sulfate, thimerosal, and thiuram mix, a higher proportion of females in the sample was associated with a higher proportion of positive tests (p < 0.1).

Age

A higher average age in the study was associated with a lower proportion of positive tests for the substance’s potassium dichromate, carbamix, cobalt chloride, colophony, nitrofurazone, paraphenylenediamine, PPD mix, propylene glycol, p-tertiary butylphenol, and turpentine (p < 0.1).

Conversely, only for nickel sulfate, a higher average age in the study was associated with a higher proportion of positive tests (p < 0.1).

Brazilian regions of the studies: The substances formaldehyde, lanolin, quaternium 15, quinoline mix, and thimerosal appeared in a lower proportion of positive tests in the southern region, but without a statistically significant direct association (p > 0.1).

On the other hand, the substances anthraquinone, balsam of Peru, benzocaine, carbamix, colophony, epoxy resin, hydroquinone, triclosan, Kathon CG, paraben mix, perfume mix, paraphenylenediamine, PPD mix, propylene glycol, promethazine, quaternium 15, quinoline mix, p-tertiary butylphenol, and turpentine showed a higher proportion of positive tests in the studies conducted in the southeastern region (p < 0.1). The same suggestion is made for potassium dichromate, cobalt chloride, neomycin, nitrofurazone, and nickel sulfate, although no statistically significant significance was observed (p > 0.1).

No trends or associations were observed for the remaining substances.

The primary objective of this study was to compile and compare the results of patch tests conducted on the Brazilian population, specifically focusing on patients suspected of contact dermatitis, from 2000 to 2022.

Consistent with global literature, nickel was identified as the main sensitizing agent across all studies. The positivity rates found in the Brazilian population in this study (31.8%) were higher compared to more recent reports in the European population, where nickel sensitization was found in approximately 13%‒17% of adults, around 10% of adolescents, and 7%‒9% of children.14⁠⁠

Metals emerged as significant sensitizers in most studies and are among the primary allergens causing contact dermatitis. Apart from nickel, cobalt and chromium were notable sensitizers, likely due to the high prevalence of metal-containing products to which the Brazilian population is exposed, such as jewelry, piercings, cleaning products, eyewear, watches, buttons on clothing, and gold-plated items, along with the presence of metals in occupational dermatoses.15⁠

According to Spiewak et al.,14 the most common sensitizers in the European population, in addition to nickel sulfate, are thimerosal and fragrances. Similarly, in the systematic review, thimerosal ranked among the top 10 most frequent sensitizers in all articles. The authors emphasize its presence in medications, vaccine preservatives, contact lens solutions, and tattoo inks, which may contribute to the high prevalence of sensitization to this substance⁠⁠.2⁠

Regarding substances with a lower prevalence of positive reactions in patch tests, this study identified triclosan, p-tert-butylphenol, and anthraquinone, with average prevalence percentages of up to 1%. Considering the very low frequency of positive tests for these substances, the authors can question their real importance in the etiology of allergic contact dermatitis in the Brazilian population over the past two decades and the need to include them in the standard Brazilian patch test panel.

These results align with published data reporting infrequent contact sensitization to triclosan. The Swiss Contact Dermatitis Research Group reported a triclosan sensitization prevalence of 0.8% in a large study involving 2,295 patients.16⁠ Schena et al.17⁠ confirmed a low incidence of triclosan sensitization, mainly associated with the use of deodorants containing this substance in their study.

Due to reported potential risks ranging from allergies to endocrine disruption, triclosan was banned by the FDA in September 2016 in soaps (liquid, gel, foam, bar), while the European Union (EU) prohibited its use in all biocidal products for human hygiene starting in January 2017, which may explain the reduction in positive tests for triclosan.18⁠

A study by Fransway et al.19⁠ from the North American Contact Dermatitis Group in 2013 also reported a decreased prevalence of positive reactions to p-tert-butylphenol, a substance commonly used in adhesives, including shoe production, among other substances, when compared to rates observed in the previous ten years.

Regarding anthraquinones, they have industrial applications in the production of hydrogen peroxide, paints, and medications such as laxatives and cathartics. They are also present in plants like Senna, Cascara sagrada, Rhubarb, and Aloe⁠.20,21⁠ Anthraquinone is not included in the standard American and European patch test panels, with limited published data on its prevalence of positive reactions in patch tests.

A tendency towards a higher proportion of positive tests in women was found for a number of substances, possibly related to the greater frequency of exposure occurring in this group. Among these are ethylenediamine, primarily used in topical medications such as antifungals, antibacterial, and corticosteroids; formaldehyde, utilized in the formulation of cosmetics, personal hygiene products, and nail polishes; lanolin, a cutaneous emollient used in the cosmetics industry; mercapto mix, employed in the rubber industry and found in gloves, condoms, toys, shoes, among other items; thimerosal, utilized as a preservative in vaccines; thiuram mix, used in the rubber industry for fungicides and pesticides, as well as repellents; neomycin, an over-the-counter antibacterial medication in Brazil; and nickel sulfate, found in jewelry, earrings, watches, bracelets, denim buttons, needles, zippers, coins, keys, buckles, eyeglass frames, orthodontic and orthopedic appliances, foods, among others.

Additionally, the authors found a higher tendency of positive test proportions for a multitude of substances in the southeastern region compared to the southern region (anthraquinone, balsam of Peru, benzocaine, carbamix, colophony, epoxy resin, hydroquinone, triclosan, Kathon CG, paraben mix, perfume mix, paraphenylenediamine, PPD mix, propylene glycol, promethazine, quaternium 15, quinoline mix, p-tertiary butylphenol, and turpentine). This finding may be justified by the greater number of studies conducted in the southeastern region (7 out of 10 studies) included in the analysis.

Moreover, a higher average age in the study population, encompassing children, adults, and the elderly, was associated with a lower proportion of positive tests for substances such as potassium dichromate, carbamix, cobalt chloride, colophony, nitrofurazone, paraphenylenediamine, PPD mix, propylene glycol, p-tertiary butylphenol, and turpentine. A possible explanation lies in the association of these substances with occupational activities such as construction work and industries like rubber, leather, and metals, which tend to be less common in older age groups.

The article by Duarte et al.11⁠ evaluated the variation in positivity rates for substances included in the standard Brazilian patch test panel recommended by the Brazilian Group of Contact Dermatitis Studies between 2006 and 2011. Three substances showed a statistically significant decrease in sensitization rates over the studied years: lanolin (p = 0.01), neomycin (p = 0.01), and anthraquinone (p = 0.04). The systematic review, with more robust strength, also found a decreasing percentage, every five years on average, for lanolin; however, it observed an increasing percentage for neomycin and anthraquinone. Historically, exposure to certain allergens shows variation according to geographical areas, such as neomycin, which remains more common in North America than in Europe.22⁠ The overall prevalence of neomycin sensitization has decreased in several countries in recent years, possibly due to its restricted availability in some locations⁠.23⁠ In Brazil, neomycin is still present in over-the-counter topical medications with high consumption by the Brazilian population, which may explain the observed increase in percentage in this study.

The findings of this review regarding the frequency of common allergens in the pediatric and adolescent population are consistent with global literature.10 However, the present study was limited by the small number of articles including this age group. Nickel sulfate was the most frequently positive allergen in patch tests conducted on the pediatric population in Brazil, which aligns with a previous systematic review⁠.24⁠ In the same review, lanolin was considered one of the top 10 most frequently positive substances, unlike the results of this study, where the authors did not observe any positive reactions to this allergen in the pediatric and adolescent population.

Despite the rigorous methodology employed in this systematic review, several limitations must be acknowledged. One significant limitation is the small number of studies included in the analysis. Eight articles had to be excluded after initial eligibility, according to exclusion criteria described in the methodology: six for not presenting patch test results25–30 and two for partially presenting patch test results.31,32 The limited number of eligible articles restricts the generalizability of the findings. This scarcity of studies likely reflects the early stage of research in this domain within Brazil, pointing to opportunities for further investigation and expansion.

In the most recent review of the relevant literature, the authors found, after 2022, only one article that would be possible to integrate into this systematic review, which was carried out retrospectively to investigate hand contact dermatitis. This study found in a total of 173 patients, 61.8% of irritant dermatitis and only 23.1% of allergic dermatitis and 5.2% of atopic dermatitis. The most frequent allergens were kathon cg (42%), nickel sulfate (33%) and thiuram-mix 18%.33 The profile is compatible with the data observed in the 2000‒2022 historical series current in this systematic review.

Another critical limitation pertains to the overall quality of the included studies. While the majority of the selected articles were of average methodological quality, which may increase the risk of bias, it is noteworthy that high-quality studies were also included, and no low-quality studies were admitted into the review.

The most frequently identified allergens in patch tests in this SR were nickel sulfate, thimerosal and cobalt. Triclosan, tertiary P-butyphenol and anthraquinone were the three least prevalent substances. A trend has been demonstrated for test positivity to increase every 5-years on average for kathon CG, neomycin, and nickel sulfate.

This systematic review offers valuable insights, despite some limitations. Although the number of included studies is small, this highlights the potential for further exploration in this research area. The compilation of these data will enable healthcare professionals working with dermatological allergies to gain a more concrete understanding of the prevalence of positive contact test reactions to each substance present in the Brazilian standard battery. These findings, in addition to their clinical relevance, may serve as a foundation for recommending useful and appropriate series of contact tests, allowing for a more comprehensive and accurate evaluation of patients suspected of allergic contact dermatitis in Brazil in the future.

None declared.

Ana Laura Andrade Bueno: Study conception and planning; data collection, analysis and interpretation; statistical analysis; intellectual participation in propaedeutic and/or therapeutic management of studied cases; preparation and writing of the manuscript; effective participation in research orientation; manuscript critical review; approval of the final version of the manuscript.

Nathalia Hoffmann Guarda Aguzzoli: Study conception and planning; data collection, analysis and interpretation; statistical analysis; intellectual participation in propaedeutic and/or therapeutic management of studied cases; approval of the final version of the manuscript.

Renan Rangel Bonamigo: Study conception and planning; data collection, analysis and interpretation; statistical analysis; intellectual participation in propaedeutic and/or therapeutic management of studied cases; preparation and writing of the manuscript; effective participation in research orientation; critical literature review; approval of the final version of the manuscript.