Off-Label Case Series: Topical Roflumilast for Mild HS

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that typically affects areas such as the axillae, groin, and inframammary folds. In recent years, treatment options for moderate to severe HS have expanded with the approval of biologic therapies. At the same time, increased awareness of HS has led to earlier diagnosis, and clinicians are now seeing more patients with mild disease (Hurley stage I). Despite these advances, there are currently no targeted, FDA-approved therapies for mild HS, and management continues to rely on approaches with well-recognized drawbacks.¹

Standard treatments for mild HS include topical or injected corticosteroids, topical or oral antibiotics, antiseptic washes, and, in selected patients, hormonal therapies such as anti-androgens. While these strategies may reduce symptoms, repeated use of corticosteroids in skin folds raises concerns about local side effects, and frequent antibiotic courses contribute to resistance. As a result, there is growing interest in topical anti-inflammatory medications that could address inflammation without these risks.

Roflumilast is a phosphodiesterase-4 (PDE4) inhibitor that is approved as a topical 0.3% cream for plaque psoriasis. PDE4 inhibition increases intracellular cyclic adenosine monophosphate (cAMP), which in turn reduces inflammatory signaling.² This process leads to lower production of inflammatory cytokines that are known to play a role in HS, including tumor necrosis factor alpha and several interleukins involved in immune activation. Oral roflumilast has previously been used off-label in patients with severe, treatment-resistant HS, suggesting that this pathway may be relevant in HS across disease severities. Based on this rationale, authors behind a recent publication evaluated whether topical roflumilast could be beneficial in mild HS.³

The publication describes a small prospective case series involving 3 women with Hurley stage I HS. Patients were evaluated at baseline and again after 30 and 60 days of treatment. Eligibility criteria were similar to those used in a prior exploratory trial of topical ruxolitinib in HS. Patients were allowed to remain on stable biologic or anti-androgen therapy if dosing had been unchanged for at least 6 months. Other medicated topical treatments and corticosteroids were stopped at least 4 weeks before the study and were not used during the study period. All patients used chlorhexidine wash every other day.

Topical roflumilast 0.3% cream was applied once daily to affected areas, including periods without active flares. At each visit, clinicians recorded the number of nodules and abscesses. Patients also reported symptom severity, pain, itch, odor, and drainage, using the HS Symptom Questionnaire, reflecting their experience over the prior week.

Two patients achieved complete resolution of nodules and symptoms by 1 month, with improvement maintained at 2 months. The third patient, who had the highest baseline lesion count and symptom burden, showed improvement at 1 month and complete clearance by 2 months. All patients reported improvement in itch within the first month, including the patient with the highest initial itch score. No new lesions were reported during the study period.

One patient initiated spironolactone during the study due to higher baseline disease activity. Because clinical improvement with spironolactone typically takes several months, the authors felt this was unlikely to explain the changes observed within the 60-day timeframe. Importantly, topical roflumilast was well tolerated. None of the patients reported local irritation, burning, stinging, or systemic side effects, even when applying the cream to multiple skin folds.

The authors note several important limitations. The study included only 3 patients, lacked a control group, and involved patients with relatively mild disease, which can improve spontaneously. In addition, background therapies were not completely uniform. These factors limit the ability to draw firm conclusions about efficacy.

Overall, this case series suggests that topical roflumilast 0.3% cream may reduce lesions and symptoms in patients with mild HS and appears to be well tolerated. While the findings are preliminary, they highlight a potential role for topical PDE4 inhibition as a non-antibiotic, steroid-sparing option in early HS. Larger, controlled studies will be needed to better define its effectiveness and place in HS treatment algorithms.

References

1. Virone M, Zappia E, Di Caro A, et al. Hidradenitis suppurativa: state-of-the-art review and update. Dermatol Reports. Published online August 27, 2025. doi:10.4081/dr.2025.10328
2. Gupta S. Roflumilast in dermatology: Revolutionizing inflammatory skin treatment. Indian J Pharmacol. 2025;57(6):421-422. doi:10.4103/ijp.ijp_161_25
3. Adusumilli N, Zarabian N, Farah M, Murphy E, Friedman A. Topical roflumilast 0.3% cream for mild hidradenitis suppurativa: a prospective case series. JAAD Case Reports. 2025. doi: 10.1016/j.jdcr.2025.12.016.