Topical antibiotics are considered the treatment of choice in superficial skin infections and infected wounds although increased resistance of Staphylococcus aureus to topical antibiotics has been observed.

As bacterial resistance does not develop with antiseptics, it would be pertinent to extend our knowledge of the irritant/allergenic capacity of these agents. All antiseptics have an irritant capacity, particularly when applied to lesioned skin. Allergic contact dermatitis occurs less frequently and is often underdiagnosed.

Mercromina Film (Spanish tradename) is an antiseptic indicated for disinfecting small superficial wounds, cracks, burns, and grazes.1 It has been marketed in Spain since 1971 by Laboratorio Lainco SA and, according to the Anatomical Therapeutic Chemical classification, is considered a mercury product (D08AK).

Mercury derivatives can cause local and systemic allergic contact dermatitis (baboon syndrome). The standard Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) series includes 2 mercury derivatives: thiomersal and mercury metal.

The prevalence of allergic contact dermatitis is 5% to thiomersal and 3.7% to mercury metal.2 Cross-reactions occur between organic and inorganic mercury derivatives and so it is recommended to avoid mercury-based antiseptics in patients sensitized to this metal. The use of mercury-based antiseptics can also cause sensitization.

In a study from 1991, merbromin only induced an allergenic response in 1% of tests.3 Despite this finding, recent reviews still do not recommend use of mercury-based antiseptics because of their allergenic capacity and recommend replacing them with other safer antiseptics.4

Given that there are no recent studies on the allergenic capacity of merbromin, the primary objective of the present study was to determine the percentage of patients who present allergic contact dermatitis to the most common topical antiseptics: merbromin, chlorhexidine, povidone-iodine, and eosin. As secondary objectives, we compared the percentage of patients who presented with allergic contact dermatitis to these antiseptics and investigated concomitant allergies produced by the antiseptics of the study.

This was a prospective, observational, comparative safety study in patients with clinical suspicion of allergic contact dermatitis. In total, we recruited 105 consecutive patients who attended the dermatology department of the Hospital Clinic in Barcelona, Spain, for skin patch tests between March and November 2014. The inclusion criteria for the study were adult age and suspicion of allergic contact dermatitis. All participants signed the informed consent form prior to inclusion. No patient had concurrent diseases of relevance for the study. All study procedures were performed according to the Declaration of Helsinki and approved by the ethics committee of the hospital.

The standard GEIDAC battery, specific batteries selected according to the reason for the referral, and the topical antiseptics object of the study were applied to the study participants. Topical antiseptics included (Spanish tradename given): Mercromina Film (active substance: merbromin 2%), Mercromina Film without any active substance, Cristalmina (active substance: chlorhexidine digluconate 10mg/mL), Betadine dermal solution (active substance: povidone-iodine 10%), eosin 2% (magistral formula). All antiseptics were applied with occlusion for the first 48hours.

The tests were read at 48 and 96hours and the results were interpreted according to the parameters shown in Table 1. A patient was considered to have allergic contact dermatitis to an antiseptic when the result at 96hours was weakly positive, evidently positive, or intensely positive.

Assuming that 1% of the patients had allergic contact dermatitis to merbromin,3 and assuming that 10% of the patients would not be analyzable, the sample size required to give a precision of±2.8% was 105. Categoric variables were described by absolute and relative frequencies (%), while the mean and SD were calculated for continuous variables. Comparisons of patients positive for antiseptics were made using the nonparametric Mann-Whitney U test. The McNemar test was used to compare the percentage of patients with allergic contact dermatitis obtained with one antiseptic compared with another. Statistical significance was set at P≤.05. All statistical procedures were performed using the SAS version 9.3 statistical package.

Of a total of 105 participants in the study, 84 were women (80.0%) and the mean age was 49.4±16.7 years.

The results showed that 12.4% of the patients in the study had allergic contact dermatitis to Betadine dermal solution and 1.9% to Mercromina Film (Table 2). No patient presented allergic contact dermatitis to Mercromina Film without active substance, Cristalmina, or eosin.

In comparison with the presence of allergic contact dermatitis according to a antiseptic pairs, the differences found between the percentage of patients who presented allergic contact dermatitis to Betadine dermal solution with respect to other antiseptics (Table 3) was statistically significant (McNemar test, P<.05). The other comparisons were not statistically significant (McNemar; P>.05). No patient presented allergic contact dermatitis to several antiseptics at the same time.

Recent reviews of the use of topical antiseptics do not recommend the use of mercury derivatives, alluding to their allergenic capacity, and recommend replacing them with other safer antiseptics.4 However, in a study from 1991 by Romaguera et al.,3 merbromin induced an allergenic response in only 1%. Similarly, in our study, merbromin was shown to have a very low allergenic capacity (1.9% of patients). The differences between merbromin and other antiseptics were not statistically significant (except Betadine).

Of the 105 patients in the study, 6 had allergic contact dermatitis to mercury derivatives (5.7%) (Table 4). Of the 2 patients who obtained a positive reaction to merbromin, only 1 had concomitant allergy to thiomersal and mercury metal. Both these compounds are included in the standard GEIDAC battery.

Most sensitizations to mercury are caused by exposure to sanitary products (mainly disinfectants or antiseptics) or cosmetics that have mercury compounds.5,6 For the 6 cases in our study with a positive reaction to 1 or several mercury derivatives, the potential sources of sensitization analyzed are reflected in Table 5.

With regards povidone-iodine, in our study, we found 12.4% of patients with contact allergy to Betadine. These differences are statistically significant compared with other antiseptics. This percentage was much higher than expected according to the literature and might be explained by the fact that the patch tests were conducted with occlusion, as povidone-iodine has a high irritant capacity (probable false positives). Performing a repeat open application test would make it possible to differentiate between cases of irritant dermatitis and those that are truly allergic.

In conclusion, the prevalence of allergic contact dermatitis to merbromin in our study is very low—only 1.9%. The differences between merbromin and other antiseptics were not significant (except Betadine). This prevalence is lower than that described for other mercury derivatives (3.7%-5%) and similar to those reported for other antiseptics such as chlorohexidine (2%).

As is the case for all observational studies, the results of this study should be interpreted with caution. Although more studies are required with more patients to confirm the results, according to the findings of the present study, use of merbromin as an antiseptic is as safe as using other commonly used antiseptics.

The financial costs of the study were met by Lainco SA. These costs included those derived from the study conduct, and was well as fees paid to La Fundació Clínic per a la Recerca Biomèdica and Dr. Susana Baltá for enrolment and follow-up of patients who participated in this study.

The authors declare that they have no conflicts of financial or personal interest that might have an inappropriate impact on the course of this study.