Resorcinol 10% as a Promising Therapeutic Option for Mild Hidradenitis Suppurativa: A Prospective, Randomized, Open Study

Abstract

Introduction

Treatment of hidradenitis suppurativa (HS) is challenging, and in Hurley stage I, it is based on topical measures. Our aim was to compare the efficacy and safety of topical resorcinol 10% with topical clindamycin 1% and no therapy, in Hurley stage I HS.

Methods

In this open, prospective, randomized trial, we studied 60 Hurley stage I patients with IHS4 ≤10. Group A was treated with topical resorcinol 10%; group B with clindamycin lotion 1%; and group C received no treatment. Patients were evaluated by total lesion count, the International Hidradenitis Suppurativa Severity Score System (IHS4) and the Dermatology Life Quality Index (DLQI) at baseline, 12 and 24 weeks. Self-reported number of flares and adverse events (AEs) were recorded.

Results

A significant reduction in the mean total lesion count and DLQI scores were observed in group A, compared to group B at week 12 (p = 0.036, p < 0.001, respectively), and in the mean total lesion count, IHS4, and DLQI scores at week 24 (p = 0.034, p = 0.017, p < 0.001, respectively). Resorcinol 10% was well-tolerated with only mild AEs.

Conclusion

Resorcinol 10% may represent a useful alternative for the long-term treatment of mild HS, which is superior to topical clindamycin and has a favorable safety profile.

Introduction

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease, usually presenting after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body [1]. The worldwide prevalence ranges from 1 to 4% [1, 2]. Women are more commonly affected, with a male-to-female ratio of 1:2.7–3.3 [3]. HS negatively affects psychosocial well-being and has a strong negative impact on patients’ quality of life [1].

Treatment of HS remains challenging. It escalates, depending on Hurley staging, and involves general measures, medical and surgical interventions. Topical therapy is the mainstay of treatment for mild-to-moderate HS, but the therapeutic options are limited and moderately effective [1]. Αntibiotics remain the first-line treatment because of their anti-inflammatory properties and immunomodulatory effects [4]. Resorcinol is a self-administered, chemical peeling agent that has been used as an alternative option to topical antibiotics in the treatment of HS, due to its keratolytic and anti-inflammatory properties [5]. Furthermore, it contributes to the prevention of antibiotic resistance that emerges from the long-term antibiotic therapies for HS [5].

Recent studies have shown the efficacy and safety of 15% topical resorcinol cream [4, 6]. To the best of our knowledge, the efficacy of 10% topical resorcinol cream has not yet been studied. The aim of the present study was to evaluate the efficacy and safety of topical resorcinol 10% in patients with mild HS and compare it with standard therapy with topical clindamycin 1% or no therapy.

Materials and Methods

The study was conducted at the 2nd Department of Dermatology and Venereology of the National and Kapodistrian University of Athens, Medical School, “Attikon” General University Hospital, in Athens, Greece, during a 12-month-period (2020–2021). The design of the study was of an open, prospective, randomized study. The study was conducted according to the principles expressed in the Declaration of Helsinki. Moreover, it was approved by the Ethics Committee of the Hospital and all participants provided a signed informed consent.

Participants

Sixty consecutive patients (28 males and 32 females), aged 18–59 years, attending the HS Clinic of our Academic Department and presenting with HS Hurley stage I and IHS4 ≤10, have been recruited. The diagnosis of HS and Hurley staging was based on clinical grounds. The eligible patients were randomly assigned into three groups. Patients in group A were treated with topical resorcinol 10%, incorporated in an oil/water cream as galenic product, twice daily. Group B patients were treated with topical clindamycin 1%, a commercially available product. Patients in group C served as controls, receiving no therapy. All patients were instructed to apply the assigned topical agent to the affected areas, twice daily, for 24 weeks.

A detailed personal and family history was obtained in all cases and complete, whole-body clinical examination was performed. The demographic characteristics of the group, as well as, clinical parameters, such as the total lesion count, the International Hidradenitis Suppurativa Severity Score System (IHS4 score), the Dermatology Life Quality Index (DLQI) score, and the self-reported number of flares, have been recorded. All patients were evaluated at recruitment (week 0) and at weeks 12 and 24. During the follow-up visits, self-reported adverse events were recorded, as well.

Statistical Analysis

The parametric method of Variance Analysis was used for the variables that followed normal distribution, according to the Kolmogorov-Smirnov test, and the nonparametric Kruskal-Wallis was used for the rest of the variables. Statistical analysis was performed using the statistical software IBM SPSS version 26.0 (IBM) and the level of significance was set at 5% (p < 0.05).

Results

Sixty patients with HS had been recruited and were randomly assigned into the three groups. Data for weeks 0, 12, and 24 were collected and analyzed.

Mean IHS4 scores were significantly reduced in the resorcinol treatment group compared to the no treatment group at both week 12 (p < 0.001) and week 24 (p < 0.001); there was also significantly greater reduction of IHS4 score for the resorcinol group, compared to the clindamycin group at week 24 (p = 0.017). Moreover, the mean number of lesions in the resorcinol group was also significantly lower compared to the no treatment group at both week 12 (p < 0.001) and week 24 (p < 0.001), as expected. In addition, a significantly greater reduction in the mean number of lesions was observed for resorcinol group, compared to the clindamycin group at week 12 (p = 0.036) and week 24 (p = 0.034). The mean DLQI scores also showed a significant reduction for the resorcinol group compared to the clindamycin and the no treatment groups both at week 12 (p < 0.001 for both) and at week 24 (p < 0.001 and p = 0.018, respectively). It is of interest that clindamycin appears to provide effective control of HS during the initial 12 weeks of treatment, but its efficacy wanes over time, up to week 24, as depicted by the values of the total lesion count, as well as the IHS4 and the DLQI scores. Our results are presented in Figures 1–3.

Fig. 1.

Mean IHS4 scores in the different treatment groups.

Fig. 3.

Mean DLQI scores in the different treatment groups.

Fig. 2.

Mean number of lesions in the different treatment groups.

Lastly, a progressive decline in flares was reported by the patients in both groups with active treatment (A, B). Statistically significant differences were documented for the mean number of flares at week 24 between the active treatment groups (A, B) and the control group (p < 0.001).

The most commonly reported resorcinol-associated adverse events were desquamation, irritation, and reversible brown discoloration of the skin, in 37%, 25%, and 11% of the participants, respectively. The symptoms were transient, reversible, and resolved spontaneously. None of the participants discontinued treatment for any reason.

Discussion

As our results indicate, topical resorcinol 10% had a positive impact on the treatment outcome of patients with Hurley stage I HS, and this outcome was significantly better than treatment with topical clindamycin, or no therapy. Furthermore, it was demonstrated that although clindamycin is effective in controlling HS during the initial 12-week period, its efficacy decreases over time with continued use. This is in accordance with the view that long-term use of topical antibiotics in HS produces unsatisfactory clinical outcomes, highlighting the need for non-antibiotic therapeutic modalities.

As the aetiopathogenesis of HS is complex and multifactorial, treatment is often unsatisfactory. On the other hand, the chronic, recurrent, suppurative, and scarring nature of the disease necessitates early and effective therapeutic interventions, in the context of what has been described as “the window of opportunity” [7, 8].

According to the European S1 Guidelines for the treatment of HS, topical therapy is used in all stages, and it is the mainstay of treatment in Hurley stage I HS. Topical therapeutic approaches include topical antibiotics and exfoliants [1].

Clindamycin 1%, applied twice daily, is the only antibiotic that has been studied in mild-to-moderate HS (Hurley Stage I or II). In a double-blinded randomized trial of 27 patients with stage I or mild stage II HS, there was a significant improvement (p < 0.01%) in superficial lesions (nodules, follicular papules/pustules) for those treated with topical clindamycin, compared to placebo [9]. The standard duration of treatment is 12 weeks to prevent the emergence of resistant microbial strains [1, 9].

Resorcinol is an organic phenol derivate, used mainly because of its keratolytic properties at the level of the follicular infundibulum [5]. Given the pivotal role of follicular occlusion in the pathogenesis of HS, resorcinol has emerged as an important, nonantibiotic topical therapy for HS [5, 6]. In the literature, topical resorcinol 15% has been used in patients with Hurley stage I or II HS [4, 5]. Resorcinol exhibits anti-inflammatory, antimicrobial, and immunomodulatory properties, by promoting prostaglandin E2 production [10]. The peeling effect initiates at a concentration of 10% or higher, by disrupting the weak keratin hydrogen bonds of the skin [11].

Topical resorcinol 15% has been shown to have a satisfactory clinical efficacy with a favorable safety profile [4, 5, 12]. In a small retrospective study, Boer and Jemec [12] described topical resorcinol 15% as an effective treatment for managing acute flares by reducing pain and the duration of clinical manifestations. However, resorcinol had no influence on scarring, fibrosis, or deep-seated lesions, as sinus tracts [12]. In a prospective study of 32 patients, topical application of resorcinol 15%, twice daily, was associated with significant reduction in pain and size of inflammatory nodules and abscesses (fistulous tracts were excluded) [13]. Interestingly, Molinelli et al. [4] observed similar efficacy of topical resorcinol 15%, not only in acute, but also in long-standing non-fistulous and fistulous HS lesions. More recently, a study established the efficacy of topical resorcinol as sustained treatment in HS manifestations, compared to traditional topical clindamycin 1% [5].

To the best of our knowledge, there is no previous published experience with the use of lower than 15% concentration of resorcinol. In the present study, we observed significantly superior clinical efficacy of resorcinol 10%, compared to clindamycin 1% and no treatment, in patients with HS Hurley stage I. Resorcinol 10% was well-tolerated, with mild irritation, desquamation, and reversible brown discoloration of the skin being the most common self-reported adverse events.

Strengths of the study include its prospective randomized design; the presence of a non-treatment control group; the use of resorcinol in lower concentrations (10%), and the longer duration of follow-up (24 weeks), compared to previous studies [4, 5, 13]. The main limitations are the small sample size and the absence of any imaging modality, such as ultrasonography, to assist clinical assessment [13].

In conclusion, resorcinol 10% may represent a useful alternative for the long-term treatment of mild HS, given the risk for antibiotic resistance in HS patients and the limited efficacy of topical clindamycin. Resorcinol 10% appears to be as effective as resorcinol 15%, with a more favorable safety profile. By using a concentration of 10%, the risk of adverse events can be minimized while still achieving the desired therapeutic effect. In addition, it can be used in patients with sensitive skin or those who had previously experienced adverse events with higher concentrations of resorcinol. Larger randomized, blinded, and head-to-head studies with other concentrations of resorcinol are necessary to clarify the best concentration of resorcinol, in terms of long-term efficacy and safety, for the treatment of mild-to-moderate HS.

Statement of Ethics

The study was conducted according to the principles expressed in the Declaration of Helsinki. This study protocol was reviewed and approved by the Scientific Committee of “Attikon” General University Hospital (approval number: 162/09-03-2023). All participants provided a signed informed consent.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors have no funding sources to declare relevant to this work. A. Katoulis has received honoraria from AbbVie, Leo Pharma, and UCB for participation on advisory boards, honoraria, and travel grants from AbbVie, Janssen, L’OREAL, Pierre-Fabre, Pharmaserv-Lilly, Pfizer, Leo Pharma, Sanofi. O. Efthymiou has received travel grants from Abbvie, Leo Pharma, Faran and Enorasis. A. Liakou has received travel grants from Amgen, Pharmex, Pierre-Fabre and honorarium from Novartis for participation on advisory boards. G. Pappa has received travel grants from Faran and Cross Pharmaceuticals. A. Kanelleas has received honoraria and travel grants from Abbvie, Janssen, Genesis, UCB, Novartis, Pharmaserv-Lilly, Galenica. D. Sgouros has received honoraria as a speaker from Pfizer, Leo Pharma, AbbVie, L’OREAL, Pierre-Fabre, Pharmaserv-Lilly and Sanofi.

Author Contributions

Conceptualization: Alexander Katoulis; methodology: Ourania Efthymiou; project administration: Alexander Katoulis and Dimitrios Sgouros; validation: Antonios Kanelleas and Dimitra Koumaki; investigation and data curation: Ourania Efthymiou and Georgia Pappa; supervision: Alexander Katoulis; validation: Evangelia Bozi; visualization: Dimitrios Sgouros; writing – original draft: Georgia Pappa, Aikaterini Liakou, and Alexander Katoulis; writing – review and editing: Georgia Pappa and Alexander Katoulis; supervision: Alexander Katoulis. All authors have read and agreed to the published version of the manuscript.

Funding Statement

The authors have no funding sources to declare relevant to this work. A. Katoulis has received honoraria from AbbVie, Leo Pharma, and UCB for participation on advisory boards, honoraria, and travel grants from AbbVie, Janssen, L’OREAL, Pierre-Fabre, Pharmaserv-Lilly, Pfizer, Leo Pharma, Sanofi. O. Efthymiou has received travel grants from Abbvie, Leo Pharma, Faran and Enorasis. A. Liakou has received travel grants from Amgen, Pharmex, Pierre-Fabre and honorarium from Novartis for participation on advisory boards. G. Pappa has received travel grants from Faran and Cross Pharmaceuticals. A. Kanelleas has received honoraria and travel grants from Abbvie, Janssen, Genesis, UCB, Novartis, Pharmaserv-Lilly, Galenica. D. Sgouros has received honoraria as a speaker from Pfizer, Leo Pharma, AbbVie, L’OREAL, Pierre-Fabre, Pharmaserv-Lilly and Sanofi.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author, Prof. Alexander Katoulis.