INTRODUCTION
Seborrheic dermatitis (SD) is a common, chronic, and relapsing inflammatory skin disorder. It is characterized by pruritic, erythematous plaques with overlying greasy scale, typically distributed in areas rich in sebaceous glands, such as the scalp, face, ears, and upper torso.1,2 Until recently, the pathogenesis of SD has been poorly understood.3,4 A recent transcriptomic study examined the cutaneous molecular profile of patients with SD. It demonstrated that SD is an inflammatory skin disease driven by immune dysregulation and skin barrier dysfunction with Malassezia as a commensal contributor.4 The immune and barrier dysregulation seen in patients with SD may make them susceptible to Malassezia colonization. This colonization can result in the characteristic erythema, pruritus, and barrier disruption seen in SD.4 A comprehensive meta-analysis estimated the global pooled prevalence of SD at 4.38%, with South Africa (8.82%) and the United States (5.86%) reporting the highest rates.5
In darker skin tones (Fitzpatrick skin types IV-VI), persistent dyschromia can occur with variable post-inflammatory pigmentary changes (hyperpigmentation or hypopigmentation).6,7 Post-inflammatory hypopigmentation (PIH) is a particularly common and prominently acquired pigmentary disorder in patients with skin of color (SOC).8 It manifests as multiple, ill-defined, round or oval hypopigmented macules and patches with fine scale, often due to cutaneous inflammation, sequelae of inflammatory or infectious dermatoses, or dermatologic procedures. PIH can persist as long-term sequelae well after the active inflammatory disease has resolved.8
The pathophysiology of hypopigmentation involves decreased melanin production, impaired transfer of melanosomes to keratinocytes, and melanocyte destruction or dysfunction.8 These dyschromias present a significant cosmetic concern, especially in SOC populations where the visual contrast against unaffected skin is stark. Disorders of pigmentation are the third most common reason for patients with SOC to seek dermatologic care.9 Between 1993 and 2010, an estimated 24.7 million visits were related to dyschromia.9,10 These conditions can profoundly negatively impact psychosocial functioning, quality of life, self-esteem, and workplace productivity.8-11
Despite its high prevalence, treating dyschromia remains challenging due to a lack of targeted therapies.8 Management is highly individualized based on skin type and the specific pigmentary disorder. Hydroquinone remains the gold standard for hyperpigmentation, while sun protection and limitation of sun exposure are the most common strategies employed for both hyperpigmentation and hypopigmentation.8 Other agents utilized for pigmentation disorders include topical corticosteroids, tretinoin, non-hydroquinone agents, chemical peels, and laser therapy.9,10
Historically, common therapies for SD included topical antifungal agents such as ketoconazole and anti-inflammatory agents, including topical steroids and off-label use of topical calcineurin inhibitors.4,12 Topical steroids can cause local side effects like skin atrophy, telangiectasia, acne, and rosacea, and there is a known risk of severe systemic effects with prolonged use; they should only be used for a short duration to treat flares that are not controlled with other therapies.3,12 Nonpharmacologic alternatives, including prescription nonsteroidal medical "device creams," can also be used to help alleviate symptoms associated with seborrheic dermatitis, particularly pruritus, erythema, scaling, and pain.13 As an inflammatory condition, treating only the Malassezia does not address the core issue driving SD, which is dysregulation in the inflammatory pathways. Reliance on antifungal therapies can contribute to antifungal overuse and resistance.4 To effectively manage SD and practice good antifungal stewardship, therapy must directly target the underlying inflammation. Furthermore, a significant unmet need exists in the SOC population for therapies that effectively treat the resulting dyspigmentation.
A particular mechanism of interest to both SD and dyschromia is phosphodiesterase-4 (PDE4) inhibition. PDE4 inhibitors act intracellularly to prevent the degradation of cyclic adenosine monophosphate (cAMP), thereby increasing its concentration. This elevated cAMP level downregulates pro-inflammatory mediators and promotes anti-inflammatory signaling.14,15
Topical roflumilast is a selective, highly potent PDE4 inhibitor that is indicated for the treatment of several inflammatory dermatoses, such as seborrheic dermatitis, plaque psoriasis,
In darker skin tones (Fitzpatrick skin types IV-VI), persistent dyschromia can occur with variable post-inflammatory pigmentary changes (hyperpigmentation or hypopigmentation).6,7 Post-inflammatory hypopigmentation (PIH) is a particularly common and prominently acquired pigmentary disorder in patients with skin of color (SOC).8 It manifests as multiple, ill-defined, round or oval hypopigmented macules and patches with fine scale, often due to cutaneous inflammation, sequelae of inflammatory or infectious dermatoses, or dermatologic procedures. PIH can persist as long-term sequelae well after the active inflammatory disease has resolved.8
The pathophysiology of hypopigmentation involves decreased melanin production, impaired transfer of melanosomes to keratinocytes, and melanocyte destruction or dysfunction.8 These dyschromias present a significant cosmetic concern, especially in SOC populations where the visual contrast against unaffected skin is stark. Disorders of pigmentation are the third most common reason for patients with SOC to seek dermatologic care.9 Between 1993 and 2010, an estimated 24.7 million visits were related to dyschromia.9,10 These conditions can profoundly negatively impact psychosocial functioning, quality of life, self-esteem, and workplace productivity.8-11
Despite its high prevalence, treating dyschromia remains challenging due to a lack of targeted therapies.8 Management is highly individualized based on skin type and the specific pigmentary disorder. Hydroquinone remains the gold standard for hyperpigmentation, while sun protection and limitation of sun exposure are the most common strategies employed for both hyperpigmentation and hypopigmentation.8 Other agents utilized for pigmentation disorders include topical corticosteroids, tretinoin, non-hydroquinone agents, chemical peels, and laser therapy.9,10
Historically, common therapies for SD included topical antifungal agents such as ketoconazole and anti-inflammatory agents, including topical steroids and off-label use of topical calcineurin inhibitors.4,12 Topical steroids can cause local side effects like skin atrophy, telangiectasia, acne, and rosacea, and there is a known risk of severe systemic effects with prolonged use; they should only be used for a short duration to treat flares that are not controlled with other therapies.3,12 Nonpharmacologic alternatives, including prescription nonsteroidal medical "device creams," can also be used to help alleviate symptoms associated with seborrheic dermatitis, particularly pruritus, erythema, scaling, and pain.13 As an inflammatory condition, treating only the Malassezia does not address the core issue driving SD, which is dysregulation in the inflammatory pathways. Reliance on antifungal therapies can contribute to antifungal overuse and resistance.4 To effectively manage SD and practice good antifungal stewardship, therapy must directly target the underlying inflammation. Furthermore, a significant unmet need exists in the SOC population for therapies that effectively treat the resulting dyspigmentation.
A particular mechanism of interest to both SD and dyschromia is phosphodiesterase-4 (PDE4) inhibition. PDE4 inhibitors act intracellularly to prevent the degradation of cyclic adenosine monophosphate (cAMP), thereby increasing its concentration. This elevated cAMP level downregulates pro-inflammatory mediators and promotes anti-inflammatory signaling.14,15
Topical roflumilast is a selective, highly potent PDE4 inhibitor that is indicated for the treatment of several inflammatory dermatoses, such as seborrheic dermatitis, plaque psoriasis,
