Roflumilast Cream 0.3% for a Patient With Genital Psoriasis Refractory to Other Topical and Systemic Treatments: A Case Report

J Clin Aesthet Dermatol. 2025;18(1–2 Suppl 1):24–27.

by Melodie Young, MSN A/GNP-C, FSDNP

Ms. Young is with Mindful Dermatology and Modern Research Associates in Dallas, Texas.

Funding: Funding was provided by Arcutis Biotherapeutics, Inc.

Disclosures: Melodie Young has been an investigator for AbbVie, Alumis, Amgen, AnaptysBio, ASLAN Pharmaceuticals, Boehringer Ingelheim, Cara Therapeutics, Incyte, Janssen, Lilly, Novartis, Pfizer, Sanofi, Takeda, and UCB; received consulting fees from Arcutis, Dermavant, Janssen, LEO Pharma, Novartis, Sanofi, Sun Pharma, and UCB; and received honoraria for speakers bureaus from Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Janssen, LEO Pharma, Lilly, Sun Pharma, and UCB.

ABSTRACT: Genital involvement is a frequent complication of plaque psoriasis (PsO) and is associated with substantial emotional and physical burden. We report a case of a male patient with genital PsO who did not respond to multiple systemic and topical therapies but achieved complete clearance with roflumilast cream 0.3% (a potent phosphodiesterase 4 inhibitor). After 28 weeks of initial treatment with guselkumab, body surface area (BSA) affected had fallen from 42 to 8 percent; however, new genital lesions were noted. After eight months of additional topical treatment, BSA affected had fallen to 2 percent, but the patient had developed gluteal cleft lesions as well. Over the next three years, several topical and systemic treatments were tried, but his genital and gluteal cleft disease persisted and intense pruritus developed. Based on concerns about continued topical corticosteroid use, the lack of efficacy observed thus far, and the potential for rebound flare, once-daily roflumilast cream 0.3% was initiated. At Week 8, BSA affected had fallen to 1 percent, and was limited to residual scalp disease (which had not been treated with roflumilast); the genitals and gluteal cleft were clear, with slight erythema present only on the scrotum. At 16 weeks, genital and gluteal cleft disease remained well-controlled with no evidence of active disease. Overall, roflumilast cream 0.3% was well tolerated with no pruritus, folliculitis, irritation, or contact dermatitis observed. Keywords: Psoriasis, pruritus, genital, topical treatment, systemic treatment

Introduction

Over the course of their disease, at least 33 to 63 percent of patients with plaque psoriasis (PsO) will have genital involvement,^1–3 although this is likely an underestimation.^4,5 Relative to PsO that affects other body areas, PsO that affects the genitals has a greater impact on patient well-being and quality of life, including increased rates of depression and feelings of stigmatization.^3,6 Genital PsO is often classified as a type of inverse or intertriginous PsO; however, management of genital PsO should take into account the unique nature of genital disease as affecting a sensitive, private area.

Genital PsO is often resistant to treatment and difficult to treat. There are no published treatment guidelines specific to genital PsO and, among major PsO guidelines,^7–11 only the Canadian guidelines include a section dedicated to genital PsO.¹² Accordingly, published clinical data on effective treatments for genital PsO are sparse.

Low-to-mid potency topical corticosteroids (TCS) are commonly used as first-line treatment of intertriginous^13–15 and genital PsO,^15,16 and low-potency TCS are recommended as initial therapy for intertriginous PsO by the American Academy of Dermatology-National Psoriasis Foundation (AAD-NPF) guidelines.¹⁷ Following initial treatment with TCS, topical calcineurin inhibitors (TCIs) are commonly prescribed as maintenance therapy. A few small clinical trials have reported efficacy and safety data with tacrolimus in the treatment of genital PsO in adults^18–20 and with pimecrolimus in intertriginous PsO in adults.²¹ The AAD-NPF guidelines recommend TCIs for the treatment of inverse PsO in adults,¹⁷ and for the treatment of genital PsO in pediatric patients.²² However, in areas of sensitive and thin skin like the genitals, there is an increased risk of side effects and decreased local tolerability with these topical agents, especially with long-term use.²³

Although no topical treatments have been approved for genital PsO specifically, roflumilast cream 0.3% has been approved for—and is the only topical therapy to have been approved for—intertriginous PsO.²⁴ With this indication and as a water-based formulation of roflumilast (a potent phosphodiesterase 4 inhibitor) that contains no known skin irritants, roflumilast cream 0.3% could be especially well-suited to treat genital PsO. In fact, among patients with genital involvement in the pivotal Phase 3 trials (DERMIS-1 and -2), roflumilast cream 0.3% was well-tolerated and provided improvement across multiple efficacy endpoints versus vehicle cream.^25,26 Of note, all of the currently available PsO guidelines predate the approval of topical roflumilast, so there are currently no recommendations for its use.

This case report details the successful treatment of genital PsO with roflumilast cream 0.3% in a male patient with a five-year history of severe PsO and genital involvement following failure of multiple topical and systemic therapies.

Case Report

This patient (White, male, aged 29 years at the time of this report [February 2023]) with a history of psoriasis (60% body surface area [BSA] affected) post upper respiratory infection was treated was seen in the emergency department (ED) in April 2017 (Figure 1). Lesions initially cleared with ED-prescribed systemic corticosteroids, but the patient experienced rebound flare. Ustekinumab Q12W (following loading doses at Weeks 0 and 4 and with occasional supplemental doses to improve clearance) was prescribed, and the patient experienced 100 percent lesion clearance (July 2017).

Approximately one year after initial diagnosis (April 2018), the patient presented lesions affecting 42 percent BSA after discontinuing ustekinumab (~9-month treatment gap). Ustekinumab Q12W was restarted, but proved ineffective. This patient was prescribed guselkumab Q8W (following loading doses at Weeks 0 and 4), with occasional supplemental doses to improve clearance.

Following 28 weeks of guselkumab treatment (October 2018), BSA had decreased to 8 percent, with scalp, face, ears, trunk, and penis most affected. This was the first report of genital involvement. Topical treatment (halobetasol proprionate/‌tazarotene lotion 0.01%/0.045% [body] and calcipotriene/‌betamethasone dipropionate suspension 0.005%/0.064% [scalp]) was added, and by July 2019, lesions had largely cleared (2% BSA affected). Genitals remained erythemic and pruritic and gluteal cleft lesions developed following an episode of diarrhea (managed by gastroenterology). Guselkumab Q8W was continued and halobetasol proprionate/tazarotene lotion 0.01%/0.045% was prescribed to treat lesions that, at this point, involved the scalp, ears, trunk, genitals, and gluteal cleft. Within four weeks, affected BSA decreased to 2 percent, affecting the hairline and genitals with new lesions on the scrotum. The genital lesions and intense pruritus negatively impacted the patient’s sexual intimacy and ability to work and sleep. An escalation of TCS was initiated with minimal to no response, and an elevated concern for skin atrophy, striae, secondary infection, and systemic absorption associated with continued TCS use.

Approximately four months later (December 2019), the patient experienced a disease flare with 4 percent BSA affected and new lesions on the trunk, scalp, face, ears, gluteal cleft, and genitals (scrotum and penis). Systemic treatment was changed to secukinumab Q4W, with occasional supplemental doses given to improve clearance. Within eight weeks, BSA had decreased to 1 percent affecting the scalp, ears, and genitals. Clascoterone cream was prescribed.

At his next follow-up visit over one year later (May 2020), the patient returned to the clinic with intense genital pruritus. Topical treatment with nystatin/triamcinolone applied BID to the genitals and groin creases for seven days was added. By his next visit six months later (November 2020), pruritus had intensified and BSA affected had increased to 10 percent. In the interim, the patient had seen gastroenterology 2 to 3 times for anal pruritus associated with anal PsO that developed after an episode of diarrhea. Systemic treatment was switched to risankizumab Q12W. Following the first two injections of risankizumab (April 2021), BSA affected had fallen to 5 percent. Pimecrolimus cream BID was prescribed for treatment of genital and facial PsO and clobetasol solution was prescribed for treatment of scalp PsO. There was no additional improvement following the third risankizumab injection (BSA affected remained 5%). Nystatin/triamcinolone treatment for genital PsO and pruritus restarted. One month later (June 2021), genital PsO had spread to the penis shaft and scalp erosions developed. Lesions had become infected as a consequence of excessive cleansing and continuous scratching. Doxycycline was prescribed to treat the infection. The patient was instructed to continue risankisumab Q12W, and nystatin/‌triamcinolone BID for 10 days followed by BIW was added. Affected BSA decreased to 2 percent within one month, but genital, anal, scalp, and ear locations continued to flare.

Over the next three months (October 2021), the patient continued risankizumab Q12W, but found that his disease began to flare at approximately Week 10. Based on this, risankizumab frequency was increased to Q10W. By January 2022, BSA affected had again fallen to 1 percent, but his scrotum remained erythemic and pruritic. This risankizumab Q10W + topical nystatin/‌triamcinolone BIW regimen maintained affected BSA at 1 percent through his next follow-up visit in March 2022. However, in May 2022, the patient retuned to the clinic complaining of “unbearable” pruritus and erythema. Nystatin/‌triamcinolone increased to BID for 10 to 14 days, and clobetasol solution (scalp) was added. The patient experienced modest improvement within two weeks, but pruritus remained intense (Figure 2). Risankizumab Q10W + nystatin/‌triamcinolone BIW regimen continued.

By August 2022, BSA affected had increased to 2 percent, scalp and facial lesions were present, and gluteal cleft and genital pruritus remained. Risankizumab Q10W was maintained, but due to concerns about continued TCS use, the lack of efficacy observed thus far, and a fear of rebound flare, topical treatment for gluteal cleft and genitals was changed to roflumilast cream 0.3% QD (which had just been approved for PsO, including intertriginous areas, in July 2022).²⁷ After eight weeks, BSA affected had decreased to 1 percent, limited to residual scalp disease (which had not been treated with roflumilast). Genital (groin creases, penis) and anal areas appeared clear, with only slight erythema present on the scrotum.

After 16 weeks, disease remains well controlled with no evidence of active genital disease. A maintenance plan of continued once-daily roflumilast cream 0.3% applied to the gluteal cleft and genitals, even in the absence of disease, was initiated and risankizumab Q10W was maintained. Roflumilast cream 0.3% was well tolerated with no pruritus, folliculitis, irritation, or contact dermatitis. Following clearance on this regimen (October 2022), the patient discontinued roflumilast cream 0.3%. At a follow-up visit four months later, the scrotum remained clear (Figure 3). Risankizumab frequency was reduced to Q12W, and the patient was instructed to apply roflumilast cream 0.3% QD as needed to pruritic or erythemic areas (including the scalp [patient has very short hair]). Upon follow-up in 2024, the patient remained without complaint and has not had a medication change. Upon follow-up in 2025, the patient had seen another provider within the clinic and remained stable on the same biologic and occasional clobetasol foam to treat scalp psoriasis. The exam documentation stated he had scrotal erythema but no active plaque psoriasis or pruritus, except for on the scalp.

Discussion

This case illustrates the utility of roflumilast cream 0.3% to clear refractory genital PsO after failing other topical treatment classes and several systemic treatments. It further demonstrates that genital PsO could be resistant to biologic and systemic treatments that are effective for the patient in other body surface areas. It also provides insight into the burden of genital disease symptoms and management of the patient.

In the absence of controlled clinical evidence and specific treatment recommendations, clinicians should choose genital PsO treatments based on their expert experience and/or published efficacy and safety information, taking into account patient goals and preferences for genital wellness. This process should include discussions regarding route of administration, impact on family planning, timeframe for improvement, and the safety and tolerability profiles of prescribed products. Such shared decision-making fosters personal accountability for the patient and can improve treatment adherence.

Recent and forthcoming clinical data regarding systemic and topical treatment of genital PsO should also be considered. Ixekizumab is currently the only biologic therapy with published, controlled clinical data supporting its use in genital PsO,²⁸ and emerging real-world data might provide support for use of additional systemic and topical therapies in this arena.²⁹ Ixekizumab was not used for treatment because the patient was being worked up for chronic diarrhea and was awaiting confirmation that he did not have ulcerative colitis or Crohn’s disease before trying another IL-17 inhibitor.

Conclusion

We report successful use of roflumilast cream 0.3%, in combination with a biologic agent, for the clearance of refractory genital PsO. Prior to treatment with roflumilast cream 0.3%, the patient’s quality of life and genital PsO symptoms had been worsening over three years of trials with multiple systemic and topical treatments. As of this report, the patient’s disease remains well-controlled overall, and no evidence of active genital disease, with continued risankizumab use and roflumilast cream 0.3% applied as needed pruritic or erythemic areas. The patient was to use only roflumilast cream 0.3% in the intertriginous areas and to only use clobetasol on the scalp, and if he had flares, we could consider changing to bimekizumab or ixekizumab. The author was reminded to continually assess the topicals patients have at home and remind them how to use them if flares occured. Left over corticosteroids are easily accessed, and patients might not realize the danger of misusing topical corticosteroids if not instructed properly.

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