Emerging Topical Therapies and Skin Care Management for Hidradenitis Suppurativa

Amber Fielding, BSc¹ and Lauren Lam, MD, BScH, FRCPC^2
1Department of Medicine, University of Alberta, Edmonton, AB, Canada
²Beacon Dermatology, Calgary, AB, Canada

Conflicts of Interest: Lauren Lam is a principal investigator for the following studies: Bioderma Sébium Foaming Gel, NanoTess NanoSALV, and La-Roche Posay Syndet Cleanser. In addition, Dr. Lam has disclosed relationships with AbbVie, Amgen, Arcutis, Bausch Health, Beiersdorf, Bioderma, Boehringer-Ingelheim, BMS, Celltrion, Eli-Lilly, Galderma, Incyte, Janssen, JAMP, Kenvue, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sanofi, Sun Pharma, UCB. Amber Fielding declares no conflict of interest. Funding sources: None.

ABSTRACT
Hidradenitis suppurativa (HS) is a painful, chronic inflammatory condition that forms recurring nodules and abscesses in skin folds, leading to severe scarring. While the exact pathogenesis is still being determined, it is thought to involve follicular occlusion and rupture, driven by multifactorial influences such as genetics, environment, hormones, microbiome, and immune dysregulation. The complex nature of this disease entails complicated management and has led to the development of various therapies targeting these different factors. While moderate-to-severe HS has seen growing therapeutic options in recent years, mild early-stage forms of the disease lack any approved treatments. This review examines the most recent developments in topical therapies specifically for mild HS, along with advancements in daily HS skin care and post de-roofing wound management. These emerging therapies offer the potential for more effective, personaldized care to reduce the disease burden for patients living with HS.

Keywords: Bioderma Sébium foaming gel, Lipikar syndet cleanser, ruxolitinib, roflumilast, clascoterone, Catalytic Treatment Matrix

Introduction

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by recurring painful nodules, abscesses and draining sinus tracts in intertriginous regions, such as the axilla, groin, and genital areas.¹ Over time, the persistent inflammation leads to irreversible scarring and permanent changes in the skin structure.² The primary driver of HS is thought to be a defect in the folliculopilosebaceous unit, causing follicular occlusion and eventual rupture, which mounts a large-scale inflammatory response.³ Although, the exact pathophysiology of this disease still remains unknown, it is thought to be multifactorial. HS has been shown to be influenced by genetic, environmental, hormonal, microbial and immunological factors. The greater prevalence of this disease in women illustrates the potential influence of androgens, especially testosterone, on disease formation.³ Furthermore, while HS is primarily an inflammatory condition rather than a true infection, bacterial colonization still plays a significant role in driving ongoing inflammation and treatment resistance. A major contributor is the formation of biofilms, which are extracellular polysaccharide matrices that surround colonies of bacteria such as Staphylococcus epidermidis. These biofilms shield the bacteria from the body’s immune defenses and antibiotics, leading to the highly resistant and chronic nature of HS lesions.⁴

The development of these lesions and the progression to more severe stages are driven by inflammation. This inflammation is caused by the upregulation of signaling pathways leading to the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-17 and IL-1.⁵ Although this disease presents diagnostic and management challenges due to its multifactorial nature, these same pathogenic complexities have enabled the development of targeted therapies addressing distinct mechanisms across different stages of HS. Disease severity guides current management strategies and is determined by Hurley staging: Stage I (mild) includes abscesses/nodules without tunnels or scarring; Stage II (moderate) includes recurrent abscesses with tunnels/ scarring; and Stage III (severe) shows diffuse involvement with interconnected tracts.⁶ Traditionally, HS therapies have been directed towards moderate-to-severe disease stages using a range of treatment strategies including topical, oral, biologic and surgical interventions.⁶ Currently, there are no approved treatments for patients with mild disease. Earlier intervention offers the potential to halt or slow disease progression and limit deleterious effects. The chronic pain and visibility of HS have major impacts on patients, leading to increased levels of anxiety, depression and decreased quality of life.⁷ This article focuses on emerging topical therapies in mild HS, and advancements in lesion and post-surgical care.

Emerging Topical Cleansers

HS frequently presents with exudative lesions that produce an unpleasant odour. As a result, self-care and hygiene rituals are cornerstones of a daily regime for many HS patients.⁸ Topical cleansers serve as critical first-line interventions in routine management. Despite this, there is currently limited access to safe and reliable cleansers that address the associated odour and inflammation.⁸

Sébium Foaming Gel

To address the limited options in HS-specific cleansers, a recent prospective, observational study was conducted evaluating Sébium foaming gel cleanser (Bioderma) in Hurley stage I patients.⁸ The foaming gel is formulated with copper and zinc sulfate to provide antibacterial and anti-inflammatory properties. The primary objective of the study was to evaluate tolerance in patients with Hurley stage I disease. The secondary objective was to assess the efficacy and cosmetic qualities of the cleanser. The trial included 50 adults (aged >21 years; 82% female, 18% male; 71 enrolled, 21 discontinued before follow-up) who completed a 21-day twice-daily regimen.⁸ Assessments were taken at baseline and day 21, using a 5-point scale (strongly disagree, somewhat disagree, neither agree nor disagree, somewhat agree, totally agree). At day 21, participants reported strong agreement with statements indicating the cleanser provided effective cleansing (90%), soothing effects (73%), and improved comfort (73%). Patients also reported greater symptom relief, including reduced lesion inflammation (53%) and decreased pain (51%).⁸ Only 1 subject (2%) reported a mild adverse event, in which the skin felt pruritic, but resolved upon discontinuation. The Sébium foaming gel was well tolerated by 98% of participants. The efficacy and cosmetic properties of the cleanser were assessed using the same scale. The cosmetic properties of the cleanser scored very highly with the following feedback: pleasant appearance (100%), texture (98%), ease of use (92%), and scent (90%).⁸ Overall product satisfaction reached 90% with 84% indicating intent to continue use. The findings from this study demonstrate a promising advancement in daily hygiene options by providing an effective, well-tolerated, gentle cleanser for early-stage mild HS lesions.⁸

Lipikar Syndet Cleanser

A current clinical study is underway to evaluate the role of a syndet cleanser on biofilm reduction in HS lesions, utilizing its inclusion of the probiotic aqua posae filiformis (Vitreoscilla filiformis) to prevent biofilm formation rather than broad-acting bactericidal washes that can cause stinging.

Emerging Topical Anti-Inflammatory Therapies

Despite the expansion of treatment options in recent years for moderate-to-severe HS, there remains a scarcity of approved options for patients with mild, early stages of the disease. First-line therapy for mild HS is limited to topical or oral antibiotics, which are frequently inadequate and associated with low patient satisfaction.⁹ Patients with milder, Hurley stage I/II disease, are often excluded from clinical trials, leading to no approved treatments and only low-level evidence guiding physicians on the use of off-label therapies.⁹ Early intervention provides an opportunity to slow disease progression, reduce painful flares and ultimately limit the physical and emotional impact that patients with HS often face.

Ruxolitinib

A topical Janus kinase (JAK) inhibitor, ruxolitinib cream, has recently been investigated as a topical treatment for mild HS. The JAK signaling pathway serves as a phosphorylation cascade, driving the transcription of genes responsible for creating pro-inflammatory cytokines. Dysregulation of this JAK pathway has been shown to be implicated in HS disease. Ruxolitinib cream serves as a potent JAK1/ JAK2 inhibitor to downregulate this pathway and limit the production of the inflammatory cytokines driving disease development.⁹ In a randomized, double-blind, vehicle-controlled phase 2 trial (n=69 adults with Hurley stage I/II HS and baseline abscess and inflammatory nodule [AN] count of 3-10), patients applied a 1.5% ruxolitinib cream or vehicle treatment twice-daily for 16 weeks.⁹ After 16 weeks, the cream use was extended on an as-needed basis and benefits were seen to continue to week 32 with fewer flares noted. At week 16, the primary endpoint of change from baseline in AN count was significantly greater in patients using the ruxolitinib cream compared to the vehicle treatment (least squares mean -3.61 vs. -2.41; P=0.0215).⁹ The study reported a greater proportion of patients achieved clinically meaningful responses using ruxolitinib cream versus the vehicle – hidradenitis suppurativa clinical response (HiSCR) 50, defined as a ≥50% reduction in inflammatory lesion count, (79.2% vs. 50.0%); AN50 (79.2% vs. 56.3%); AN75 (54.2% vs. 25.0%); and AN90/100 (20.8% vs. 12.5%).⁹ The trial reported the cream was well tolerated, with no grade ≥3 treatment-emergent adverse events reported. While this trial is confined by its modest sample size, number of discontinuations and racial imbalance limiting generalizability, the results overall support the use of ruxolitinib cream, as a promising new topical therapy for patients with milder HS.⁹

Roflumilast

Additionally, a prospective case series was recently published on the use of a new topical roflumilast 0.3% cream on 3 patients with mild Hurley stage I HS.¹⁰ Roflumilast serves as a phosphodiesterase-4 (PDE4) inhibitor, inhibiting the reduction of cyclic adenosine monophosphate (cAMP) to AMP. Intracellular cAMP serves to upregulate pro-inflammatory cytokines that lead to the downstream inflammatory reactions observed in HS lesions. PDE4 inhibitors, like roflumilast, serve to downregulate the production of cAMP which inhibits the protein kinase A-nuclear factor Kappa B (PKA-NF-κB) signaling pathway from producing the pro-inflammatory cytokines T helper 1 (Th1) and Th17.¹⁰ In this study, the cream was applied once daily to affected sites and continued even after lesion closure. These patients were evaluated at baseline, Day 30, and Day 60, at which the absolute AN counts and patient-reported intensity of pain, itch, odour and drainage were reported.¹⁰ In this prospective study, there was a notable reduction in AN count and patients reported symptoms after 1 month, along with sustained improvement after 2 months.¹⁰ Limitations of this study include the small size, absence of a control group and limited baseline lesions. However, the promising results of this study highlight the potential use of roflumilast as a topical treatment option for patients with mild HS. Recently, a phase II clinical trial assessed the effectiveness of roflumilast cream in mild/ moderate HS and showed potential to progress to phase III clinical trials.

Emerging Topical Anti-Androgen Therapy

Clascoterone

HS is a complex multifactorial disease that requires different management strategies. Currently, many off-label treatments are being trialed in patients. A 2023 case report illustrated the use of clascoterone cream 1%, an anti-androgen topical cream, which was used as an off-label treatment in an HS case.¹¹ Clascoterone serves to competitively inhibit the binding of dihydrotestosterone (DHT) to androgen receptors, preventing the elicited hormonal response.

This case study evaluated the use of the topical treatment in a 23 year-old female Hurley stage I HS patient with painful lesions in inguinal folds and buttocks, appearing in her perimenstrual period.¹¹ Given the linkage to the menstrual cycle, clascoterone was utilized as an anti-androgen topical treatment. The patient reported significant improvement in the control of her HS through applying clascoterone cream 1% monotherapy once daily. Prior to the treatment, the patient would develop 5-6 lesions prior to onset of menstruation with a pain rating of 7/10. While using the cream, the patient only developed 2-3 new lesions which she rated a 3/10 on the pain scale.¹¹ This case study illustrates the potential benefit of clascoterone topical use in patients with a hormonal component involved in HS.¹¹ Currently, small investigator trials are ongoing to determine the potential of topical clascoterone as a treatment option for HS. This poses the potential for a new topical treatment option to be offered for HS patients with a hormonal factor.

Emerging Topical Adjuncts in Post-Deroofing Care

Patients with moderate-to-severe HS often resort to surgical intervention when medical therapies are ineffective. Procedures range from minimally invasive to wide excision, with deroofing being the most common procedure for Hurley stage II and III lesions.¹² Deroofing involves removing the overlying skin (roof) of the abscesses and sinus tracts while preserving the wound base.¹² Recovery from surgical intervention is often long and painful. The current first-line post-deroofing care includes the use of petroleum jelly to maintain moisture during the healing process, however, this approach has been linked to increased biofilm formation and prolonged recovery.¹³

Catalytic Treatment Matrix Post-deroofing Therapy

A recent quality improvement study evaluated the effectiveness of the current standard of care (SOC), petroleum jelly, compared with a novel Catalytic Treatment Matrix (CTM) technology, known as NanoSALV, in post-deroofing wound care.¹³ The study evaluated 47 wounds from 34 patients (mean baseline 13.3 cm²; 59 total wounds, 12 wounds excluded due to loss of follow-up), measuring wound progression in both SOC and the CTM technology.¹³ Smaller wounds were assessed after 21-28 days and larger wounds after 35 days. The study revealed that 57% of wounds achieved 100% while 43% achieved 70-99% reduction in surface area using the CTM technology by Day 35. No complications were reported. Furthermore, with the CTM technology treatment, average follow-up appointments decreased to 1.02 compared to 2 for SOC.¹³ Qualitative analysis of the wounds noted faster granulation tissue formation, reduced biofilm development and less hypergranulation tissue utilizing the CTM technology as the aftercare treatment. Patients also reported increased comfort, high satisfaction and tolerability along with greater clinical efficiency with the CTM technology.¹³ These study results highlight the CTM technology as an effective alternative postsurgical treatment with optimal healing results compared to the current SOC, petroleum jelly. This proposes the potential use of this CTM technology to enhance patient experience and optimize wound healing after surgical deroofing (Figure 1).

Figure 1:

Conclusion

While the range of treatments for HS has expanded considerably in recent years, new therapies have often focused on treating moderate-to- severe stages of the disease. This has left patients with milder Hurley stage I HS without any approved treatment options.

This review explored emerging treatments developed specifically for mild-stage HS, including topical anti-inflammatory agents, ruxolitinib and roflumilast. Both topical agents showed promising results in clinical trials, potentially offering patients with mild HS directed treatment options. Additionally, therapeutic advancements targeting the hormonal component involved in some HS patients may benefit from the topical anti-androgen, clascoterone, which demonstrated encouraging results in a case study, however, further investigation is still needed. Innovative adjunctive skin care options were also reviewed, showing major promise for the incorporation of new cleansers and post-deroofing wound-healing technology for HS. As research continues to advance and new therapeutic options emerge, the landscape of HS management is poised to offer new first-line treatments. As we continue to evaluate new therapeutic options, we move closer to providing every HS patient with personalized care that addresses their specific needs and hopefully decreases the physical and mental toll of this disease.