Topical ruxolitinib in the treatment of refractory facial seborrheic dermatitis

Abstract

IntroductionSeborrheic dermatitis (SD) is a chronic, inflammatory skin condition that affects sebum-rich areas of the body.1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar,2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar It is one of the most common skin diseases, with a prevalence of 14.3% in the middle-aged and elderly population.3Sanders M.G.H. Pardo L.M. Franco O.H. Ginger R.S. Nijsten T. Prevalence and determinants of seborrhoeic dermatitis in a middle-aged and elderly population: the Rotterdam Study.Br J Dermatol. 2018; 178: 148-153https://doi.org/10.1111/bjd.15908Crossref PubMed Scopus (40) Google Scholar SD follows a relapsing and remitting course, worsening with stress and during the winter months.1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar Importantly, SD has been reported to have a negative effect on quality of life.2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The underlying mechanism of SD is poorly understood; a combination of Malassezia species colonization, immune system activation, and genetic predisposition, among various other endogenous and exogenous factors, likely contribute to its pathogenesis.4Adalsteinsson J.A. Kaushik S. Muzumdar S. Guttman-Yassky E. Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis.Exp Dermatol. 2020; 29: 481-489https://doi.org/10.1111/exd.14091Crossref PubMed Scopus (34) Google Scholar The clinical presentation ranges from simple dandruff to a fulminant rash.4Adalsteinsson J.A. Kaushik S. Muzumdar S. Guttman-Yassky E. Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis.Exp Dermatol. 2020; 29: 481-489https://doi.org/10.1111/exd.14091Crossref PubMed Scopus (34) Google Scholar The diagnosis is made clinically by the presence of greasy yellow scales overlying well-demarcated erythematous patches or plaques affecting the face, scalp, and upper portion of the chest in a symmetric distribution; the hairline, eyebrows, glabella, and nasolabial folds are particularly involved. Facial SD is frequently associated with rosacea. The goal of therapy is to clear visible signs of disease and reduce associated symptoms and must be maintained long-term to prevent recurrence.2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar Since the underlying mechanism involves, at least in part, Malassezia proliferation and inflammation, common treatments include antifungal and anti-inflammatory therapy.5Borda L.J. Perper M. Keri J.E. Treatment of seborrheic dermatitis: a comprehensive review.J Dermatolog Treat. 2019; 30: 158-169https://doi.org/10.1080/09546634.2018.1473554Crossref PubMed Scopus (41) Google Scholar First-line therapy includes topical antifungals (eg, ketoconazole 2% cream) in combination with a mild topical corticosteroid (eg, hydrocortisone 2.5% or desonide 0.05% creams) or topical calcineurin inhibitor (eg, tacrolimus 0.1% ointment).1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar With concomitant rosacea, metronidazole 1% gel or cream has been reported to help both conditions.6McFalda W.L. Roebuck H.L. Rational management of papulopustular rosacea with concomitant facial seborrheic dermatitis: a case report.J Clin Aesthet Dermatol. 2011; 4: 40-42PubMed Google ScholarCase reportHere, we present the case of a 74-year-old man with an unremarkable medical history, who presented to our clinic with a chief complaint of redness and scaling on the nasolabial folds. He had no relief of his symptoms in the past with topical ketoconazole, desonide, and hydrocortisone creams. On examination, there were several red plaques with overlying greasy scale over the nasolabial folds and periorally, without pustules or papules (Fig 1). Additionally, we could appreciate the presence of significant erythema and telangiectasias localized in the central face, for which he had been prescribed metronidazole 1% gel and doxycycline 100 mg daily without improvement. Clinically, we made a diagnosis of rosacea, with a marked presence of SD, for which we prescribed ruxolitinib 1.5% cream to be applied twice daily; we also discontinued the metronidazole and doxycycline. At his follow-up visit only 2 weeks later, he had achieved complete resolution of the SD (Fig 1), with a partial decrease of the erythema of rosacea.DiscussionSD is a chronic and common inflammatory skin disease associated with reduced quality of life. When first-line treatments fail, additional therapies are necessary to manage symptoms and prevent recurrences. Topical ruxolitinib cream was approved by the Food and Drug Administration in late 2021 for the short-term and noncontinuous treatment of mild-to-moderate atopic dermatitis in nonimmunocompromised patients aged 12 and up. Ruxolitinib is a Janus kinase (JAK) inhibitor, which selectively targets JAK1 and JAK2.7Papp K. Szepietowski J.C. Kircik L. et al.Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies.J Am Acad Dermatol. 2021; 85: 863-872https://doi.org/10.1016/j.jaad.2021.04.085Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar In atopic dermatitis, inflammation is driven by type 2 cytokines, which are modulated by JAKs.7Papp K. Szepietowski J.C. Kircik L. et al.Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies.J Am Acad Dermatol. 2021; 85: 863-872https://doi.org/10.1016/j.jaad.2021.04.085Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar In clinical trials, patients with AD experienced rapid and sustained skin improvement with the use of topical ruxolitinib, which provided potent antipruritic and anti-inflammatory effects.7Papp K. Szepietowski J.C. Kircik L. et al.Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies.J Am Acad Dermatol. 2021; 85: 863-872https://doi.org/10.1016/j.jaad.2021.04.085Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Similarly, due to reports (albeit preliminary) that the inflammation in SD is driven by interleukin 4 and interleukin 17,4Adalsteinsson J.A. Kaushik S. Muzumdar S. Guttman-Yassky E. Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis.Exp Dermatol. 2020; 29: 481-489https://doi.org/10.1111/exd.14091Crossref PubMed Scopus (34) Google Scholar similar mechanisms of action could explain the effect of ruxolitinib in ameliorating both spongiotic diseases. Topical ruxolitinib has also been reported as an effective new therapy for vitiligo and lichen planus—diseases driven by elevated levels of interferon gamma, an upstream effector of JAKs.8Rothstein B. Joshipura D. Saraiya A. et al.Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.J Am Acad Dermatol. 2017; 76: 1054-1060.e1https://doi.org/10.1016/j.jaad.2017.02.049Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar,9Brumfiel C.M. Patel M.H. Severson K.J. et al.Ruxolitinib cream in the treatment of cutaneous lichen planus: a prospective, open-label study.J Invest Dermatol. 2022; (2022:S0022-202X(22)00083-5.)https://doi.org/10.1016/j.jid.2022.01.015Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar In these reports, ruxolitinib 1.5% cream provided significant repigmentation8Rothstein B. Joshipura D. Saraiya A. et al.Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.J Am Acad Dermatol. 2017; 76: 1054-1060.e1https://doi.org/10.1016/j.jaad.2017.02.049Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar and rapid improvement9Brumfiel C.M. Patel M.H. Severson K.J. et al.Ruxolitinib cream in the treatment of cutaneous lichen planus: a prospective, open-label study.J Invest Dermatol. 2022; (2022:S0022-202X(22)00083-5.)https://doi.org/10.1016/j.jid.2022.01.015Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar of facial vitiligo and cutaneous lichen planus, respectively. To our knowledge, this is the first report describing the excellent efficacy of ruxolitinib in a patient with significant SD and concomitant rosacea. This case highlights the promising role of topical ruxolitinib cream in the treatment of facial SD. IntroductionSeborrheic dermatitis (SD) is a chronic, inflammatory skin condition that affects sebum-rich areas of the body.1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar,2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar It is one of the most common skin diseases, with a prevalence of 14.3% in the middle-aged and elderly population.3Sanders M.G.H. Pardo L.M. Franco O.H. Ginger R.S. Nijsten T. Prevalence and determinants of seborrhoeic dermatitis in a middle-aged and elderly population: the Rotterdam Study.Br J Dermatol. 2018; 178: 148-153https://doi.org/10.1111/bjd.15908Crossref PubMed Scopus (40) Google Scholar SD follows a relapsing and remitting course, worsening with stress and during the winter months.1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar Importantly, SD has been reported to have a negative effect on quality of life.2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The underlying mechanism of SD is poorly understood; a combination of Malassezia species colonization, immune system activation, and genetic predisposition, among various other endogenous and exogenous factors, likely contribute to its pathogenesis.4Adalsteinsson J.A. Kaushik S. Muzumdar S. Guttman-Yassky E. Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis.Exp Dermatol. 2020; 29: 481-489https://doi.org/10.1111/exd.14091Crossref PubMed Scopus (34) Google Scholar The clinical presentation ranges from simple dandruff to a fulminant rash.4Adalsteinsson J.A. Kaushik S. Muzumdar S. Guttman-Yassky E. Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis.Exp Dermatol. 2020; 29: 481-489https://doi.org/10.1111/exd.14091Crossref PubMed Scopus (34) Google Scholar The diagnosis is made clinically by the presence of greasy yellow scales overlying well-demarcated erythematous patches or plaques affecting the face, scalp, and upper portion of the chest in a symmetric distribution; the hairline, eyebrows, glabella, and nasolabial folds are particularly involved. Facial SD is frequently associated with rosacea. The goal of therapy is to clear visible signs of disease and reduce associated symptoms and must be maintained long-term to prevent recurrence.2Dessinioti C. Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies.Clin Dermatol. 2013; 31: 343-351https://doi.org/10.1016/j.clindermatol.2013.01.001Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar Since the underlying mechanism involves, at least in part, Malassezia proliferation and inflammation, common treatments include antifungal and anti-inflammatory therapy.5Borda L.J. Perper M. Keri J.E. Treatment of seborrheic dermatitis: a comprehensive review.J Dermatolog Treat. 2019; 30: 158-169https://doi.org/10.1080/09546634.2018.1473554Crossref PubMed Scopus (41) Google Scholar First-line therapy includes topical antifungals (eg, ketoconazole 2% cream) in combination with a mild topical corticosteroid (eg, hydrocortisone 2.5% or desonide 0.05% creams) or topical calcineurin inhibitor (eg, tacrolimus 0.1% ointment).1Clark G.W. Pope S.M. Jaboori K.A. Diagnosis and treatment of seborrheic dermatitis.Am Fam Physician. 2015; 91: 185-190PubMed Google Scholar With concomitant rosacea, metronidazole 1% gel or cream has been reported to help both conditions.6McFalda W.L. Roebuck H.L. Rational management of papulopustular rosacea with concomitant facial seborrheic dermatitis: a case report.J Clin Aesthet Dermatol. 2011; 4: 40-42PubMed Google Scholar

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