I. Stefanaki, MD and A. Katsambas, MD
Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece
Seborrheic dermatitis is a recurrent, usually mild, skin disorder with typical clinical manifestations. As it most frequently involves exposed areas, such as the face and scalp, patients seek advice from a dermatologist in order to control their disease. This article will review the available treatments for this common dermatologic problem.
antifungals, calcineurin inhibitors, corticosteroids, lithium salts, metronidazole, phototherapy, seborrheic dermatitis, zinc pyrithione
Seborrheic dermatitis is a chronic mild skin disorder that characteristically presents as sharply demarcated red patches and plaques with greasy scales in areas with increased density of sebaceous glands, namely the scalp, face, upper trunk, and flexures. It affects approximately 3-5% of the population, with a predilection in men.1 An even higher incidence can be found amongst patients with HIV infection, Parkinson’s disease, and several other medical conditions.1 There is still debate as to whether infantile seborrheic dermatitis represents a distinct dermatitis.
The pathogenesis of the disease remains controversial. The role of Malassezia spp. carriage is not clear. However, the number of yeasts decreases with antimycotic treatment, resulting in clinical improvement, and increases in periods of exacerbation.2 Despite its name, sebum excretion in patients with seborrheic dermatitis is not significantly increased when compared with controls. Malassezia metabolism alters sebum composition by consuming saturated fatty acids and releasing unsaturated fatty acids, which in turn promotes inflammation in susceptible individuals.3 It has also been proposed that Malassezia spp. induce cytokine production by keratinocytes,4 while studies on cellular immunity show contradictory results.5,6
Patients should be informed that all available therapeutic modalities alleviate symptoms temporarily until the next relapse, which is typically followed by variable periods of remission. Affected individuals should avoid causing compounding irritation to active lesions, i.e., through the mechanical removal of scales and the use of potent keratolytic preparations. Daily cleansing of the skin and the use of emollients are beneficial.
Topical therapies are the mainstay of treatment as the condition is recurrent, usually mild, and responds well to these agents.
Since the first publication in 1984 on the use of ketoconazole in seborrheic dermatitis,7 several studies have validated its efficacy utilizing various vehicles of delivery (e.g., cream, foam, gel, and shampoo).8-10 Ketoconazole shampoo 2% is superior to 1%11 and can be used once-weekly as maintenance therapy for scalp seborrheic dermatitis.10
Another topical azole, bifonazole 1% cream, is likewise effective and provides the additional advantage of once-daily application. It has also been tried successfully in combination with 40% urea for scalp seborrheic dermatitis.12 Bifonazole shampoo used 3 times weekly was significantly more beneficial than placebo in a randomized, double-blind study of 44 patients.13 Miconazole can also be used either alone or in combination with hydrocortisone.14
Ciclopirox has both antifungal and anti-inflammatory properties.15 Ciclopirox 1% cream is superior to placebo for facial seborrheic dermatitis.16 The response rates appear to be dose-dependent, with higher concentrations (1% vs. 0.1% or 0.3%) and more frequent use yielding better results.17,19 Combinations of ciclopirox 1.5% shampoo with salicylic acid 3% or zinc pyrithione 1% are also effective.19,20 Statistical non-inferiority of ciclopirox in comparison with ketoconazole has been demonstrated.21
For severe seborrheic dermatitis, low- or medium-potency topical corticosteroids can be used when beginning treatment, either alone or in combination with an antifungal agent, to limit inflammation. Prolonged and/or frequent use should be avoided due to their well known associated risks (e.g., atrophy, telangiectasias, hypertrichosis, and perioral dermatitis). In a double-blind controlled study, 70 seborrheic dermatitis patients were treated with either miconazole 2% and hydrocortisone 1% in combination, miconazole 2%, or 1% hydrocortisone. Patients in both miconazole- containing treatment arms showed significant improvement when compared with those who received hydrocortisone 1% cream as prophylactic therapy.14 Miconazole treatments also lowered the number of Malassezia spp. yeasts.14 Double- blind comparative studies have found that hydrocortisone cream is not superior to ketoconazole 2% cream in improving seborrheic dermatitis symptoms, as significantly higher reductions in the number of Malassezia spp. were observed with ketoconazole, when compared with hydrocortisone.22 Ketoconazole 2% foaming gel was found to be superior to betamethasone dipropionate 0.05% lotion in reducing symptoms and lowering the number of Malassezia spp.23
Zinc pyrithione 1% shampoo in comparison with ketoconazole 2% shampoo has produced inferior results, whereas selenium sulphide exhibited similar efficacy.24,25
Topical metronidazole 0.75% gel for seborrheic dermatitis has been evaluated in only a limited number of double-blind studies with contradictory results. In two trials, metronidazole showed greater efficacy over placebo26 and was equally effective as ketoconazole 2% cream,27 while in two other studies it was not superior to placebo.28,29
Both lithium succinate and lithium gluconate have demonstrated effectiveness in treating seborrheic dermatitis, probably due to their anti-inflammatory effects. Lithium succinate 8% ointment was investigated twice-daily (for a total of 8 weeks) and showed significantly greater efficacy than placebo.30 It has also been used successfully in HIV patients with facial seborrheic dermatitis.31 Lithium gluconate 8% ointment used twice-daily was tested in a multicenter, randomized, double-blind, placebo-controlled clinical trial in 129 patients.32 After 8 weeks, 29.1% in the lithium group and 3.8% in the placebo group had experienced complete remission. Lithium gluconate 8% ointment used twice-daily was 22% more effective than ketoconazole 2% emulsion used twice-weekly in a randomized study of 288 patients.33
In a randomized, double-blind, vehicle-controlled 4-week efficacy trial of twice-daily pimecrolimus 1% cream in 96 patients, topical calcineurin inhibitor (TCI) therapy was effective and well tolerated for the treatment of facial seborrheic dermatitis.34 In two randomized clinical trials,35,36 pimecrolimus 1% proved to be equally effective as topical corticosteroids (hydrocortisone acetate 1% cream or betamethasone 17-valerate 0.1% cream). Furthermore, pimecrolimus demonstrated additional benefits, such as longer periods of remission and milder relapses, when compared with betamethasone.35 This TCI has also been tested against ketoconazole 2% cream in an open randomized study that showed comparable efficacy, but more frequent side-effects were reported with pimecrolimus treatment.37 Topical tacrolimus 0.1% ointment was tried in an open-label 4-week randomized study against betamethasone 17-valerate lotion and zinc pyrithione 1% shampoo in 83 patients with seborrheic dermatitis of the scalp.38 Tacrolimus ointment demonstrated greater prolonged efficacy than topical steroids, but exhibited shorter durability of improvement than zinc pyrithione shampoo. Due to the increased viscosity of the tacrolimus ointment, treatment was inconvenient to use on the scalp.
Coal Tar Shampoos
The beneficial effects of tar in seborrheic dermatitis may be attributed to its anti-proliferative and anti-inflammatory properties, antifungal action, and inhibition of sebum secretion.39 In a randomized, double-blind parallel-group trial, treatment with 4% coal tar shampoo resulted in a significantly greater reduction in scalp seborrheic dermatitis, when compared with placebo, and the result was further enhanced when coal tar was combined with ciclopirox olamine.40
In a randomized double-blind trial, selenium sulfide 2.5% was tested against ketoconazole 2% and placebo in 246 patients with moderate to severe dandruff.41 Both ketoconazole and selenium sulfide shampoos were effective, but ketoconazole was better tolerated.
Other Topical Treatments
There are scarce reports of successful treatment with benzoyl peroxide,42 azelaic acid,43 1a-24 (R)-dihydroxycholecalciferol (tacalcitol) cream,44 and MAS064D cream (a non-steroidal preparation containing multiple active ingredients that include emollients, anti-inflammatories, keratolytics, and an antimycotic).45
Ultraviolet B (UVB)
Patients often experience improvement during the summer. The direct inhibitive effect of UVA and UVB light on Malassezia yeasts cultured from the skin has been experimentally confirmed.46 In an open prospective study, 18 patients with severe seborrheic dermatitis were treated with narrow-band UVB 3 times per week until clearance or upon completing 2 months of therapy.47 The median number of treatment sessions was 23 and the median cumulative UVB dose was 9.8 J/cm-2. All patients responded well to therapy, especially those with widespread disease. The major limitations of UVB irradiation for seborrheic dermatitis are the frequent visits to a phototherapy unit, the rapid disease relapse appearing 2-6 weeks after treatment, and the risks associated with exceeding the maximum lifetime allowable cumulative dose.
Psoralen plus Ultraviolet A (PUVA)
Five HIV patients who were administered PUVA treatment (30 to 262 J/cm2 every 2-4 weeks) exhibited clearance of skin lesions, including seborrheic dermatitis.48 This finding contradicts the report of 28 new cases of facial seborrheic dermatitis appearing during PUVA therapy in 347 patients with psoriasis.49
Controlled studies of systemic antifungal therapy are limited. In a randomized, double-blind, placebo-controlled study, 174 patients with seborrheic dermatitis received either 250mg of terbinafine or placebo for 6 weeks.50 Patients with facial lesions did not benefit from terbinafine, while patients with lesions in non-exposed areas receiving terbinafine showed significant improvement. Another placebo-controlled trial showed that terbinafine 250mg daily for 4 weeks was more effective than placebo.51 In a double-blind, placebo- controlled study of 63 patients receiving either oral fluconazole 300mg in a weekly single dose or placebo for 2 weeks, no statistically significant improvement was seen between treatment groups.52 Ketoconazole 200mg daily for 4 weeks was tried in 19 patients in a randomized, double- blind, placebo-controlled study; active treatment resulted in significant improvement.53 Itraconazole given at an initial dose of 200mg daily for 1 week, followed by a maintenance single dose of 200mg every 2 weeks, was beneficial in an open non-comparative study of 60 patients with moderate to severe seborrheic dermatitis.54
Topical antifungal therapy has proved to be effective in many studies, offering more frequent and sustained relapse-free periods, as compared with corticosteroids and without their untoward side-effects. Therefore, antimycotic agents may be considered first-line treatment for seborrheic dermatitis. Other topical agents with established efficacy can be used as complimentary therapy. UVB phototherapy should only be considered for severe and/or recalcitrant disease. Oral administration of antifungals is highly questionable, as treatment carries the potential risk of serious side-effects from repetitive use.
- Naldi L, Rebora A. Clinical practice. Seborrheic dermatitis. N Engl J Med 360(4):387-96 (2009 Jan).
- Crespo EV, Delgado FV. Malassezia species in skin disease. Curr Opin Infect Dis 15(2):133-42 (2002 Apr).
- Ro BI, Dawson TL. The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff. J Investig Dermatol Symp Proc 10(3):194-7 (2005 Dec).
- Watanabe S, Kano R, Sato H, et al. The effect of Malassezia yeasts on cytokine production by human keratinocytes. J Invest Dermatol 116(5):769-73 (2001 May).
- Neuber K, Kröger S, Gruseck E, et al. Effects of Pityrosporum ovale on proliferation, immunoglobulin (IgA, G, M) synthesis and cytokine (IL-2, IL-10, IFN gamma) production of peripheral blood mononuclear cells from patients with seborrhoeic dermatitis. Arch Dermatol Res 288(9):532-6 (1996 Aug).
- Parry ME, Sharpe GR. Seborrheic dermatitis is not caused by an altered immune response to Malassezia yeast. Br J Dermatol 139(2):254-63 (1998 Aug).
- Farr PM, Shuster S. Treatment of seborrheic dermatitis with topical ketoconazole. Lancet 2(8414):1271-2 (1984 Dec). 8. Elewski B, Ling MR, Phillips TJ. Efficacy and safety of a new
- once-daily ketoconazole 2% gel in the treatment of seborrheic dermatitis: a phase III trial. J Drugs Dermatol 5(7):646-50 (2006 Jul-Aug).
- Elewski BE, Abramovits W, Kempers S, et al. A novel foam formulation of ketoconazole 2% for the treatment of seborrheic dermatitis on multiple body regions. J Drugs Dermatol 6(10):1001-8 (2007 Oct).
- Peter RU, Richarz-Barthauer U. Successful treatment and prophylaxis of scalp seborrhoeic dermatitis and dandruff with 2% ketoconazole shampoo: results of a multicentre, double- blind, placebo-controlled trial. Br J Dermatol 132(3):441-5 (1995 Mar).
- Piérard-Franchimont C, Piérard GE, Arrese JE, et al. Effect of ketoconazole 1% and 2% shampoos on severe dandruff and seborrhoeic dermatitis: clinical, squamometric and mycological assessments. Dermatology 202(2):171-6 (2001).
- Shemer A, Nathansohn N, Kaplan B, et al. Treatment of scalp seborrheic dermatitis and psoriasis with an ointment of 40% urea and 1% bifonazole. Int J Dermatol 39(7):532-4 (2000 Jul).
- Segal R, David M, Ingber A, et al. Treatment with bifonazole shampoo for seborrhea and seborrheic dermatitis: a randomized, double-blind study. Acta Derm Venereol 72(6):454-5 (1992 Nov).
- Faergemann J. Seborrhoeic dermatitis and Pityrosporum orbiculare: treatment of seborrhoeic dermatitis of the scalp with miconazole-hydrocortisone (Daktacort), miconazole and hydrocortisone. Br J Dermatol 114(6):695-700 (1986 Jun).
- Gupta AK, Bluhm R. Ciclopirox (Loprox) gel for superficial fungal infections. Skin Therapy Lett 9(7):4-5, 9 (2004 Aug-Sep). 16. Dupuy P, Maurette C, Amoric JC, et al. Study Investigator Group. Randomized, placebo-controlled, double-blind study on clinical efficacy of ciclopiroxolamine 1% cream in facial seborrhoeic dermatitis. Br J Dermatol 144(5):1033-7 (2001 May).
- Altmeyer P, Hoffmann K, Loprox Shampoo Dosing Concentration Study Group. Efficacy of different concentrations of ciclopirox shampoo for the treatment of seborrheic dermatitis of the scalp: results of a randomized, double-blind, vehicle-controlled trial. Int J Dermatol 43(Suppl 1):9-12 (2004 Jul).
- Abeck D, Loprox Shampoo Dosing Study Group. Rationale of frequency of use of ciclopirox 1% shampoo in the treatment of seborrheic dermatitis: results of a double-blind, placebo- controlled study comparing the efficacy of once, twice, and three-time weekly usage. Int J Dermatol 43(Suppl 1):13-6 (2004 Jul).
- Squire RA, Goode K. A randomised, single-blind, single- centre clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5%) and salicylic acid (3%), or ketoconazole (2%, Nizoral) for the treatment of dandruff/seborrhoeic dermatitis. J Dermatolog Treat 13(2):51-60 (2002 Jun).
- Lorette G, Ermosilla V. Clinical efficacy of a new ciclopiroxolamine/zinc pyrithione shampoo in scalp seborrheic dermatitis treatment. Eur J Dermatol 16(5):558-64 (2006 Sep-Oct).
- Ratnavel RC, Squire RA, Boorman GC. Clinical efficacies of shampoos containing ciclopirox olamine (1.5%) and ketoconazole (2.0%) in the treatment of seborrhoeic dermatitis. J Dermatolog Treat 18(2):88-96 (2007).
- Katsambas A, Antoniou C, Frangouli E, et al. A double-blind trial of treatment of seborrhoeic dermatitis with 2% ketoconazole cream compared with 1% hydrocortisone cream. Br J Dermatol 121(3):353-7 (1989 Sep).
- Ortonne J-P, Lacour J-P, Vitetta A et al. Comparative study of ketoconazole 2% foaming gel and betamethasone dipropionate 0.05% lotion in the treatment of seborrheic dermatitis in adults. Dermatology 184(4):275-80 (1992).
- Piérard-Franchimont C, Goffin V, Decroix J, et al. A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol 15(6):434-41 (2002 Nov-Dec).
- Fredriksson T. Controlled comparison of Clinitar shampoo and Selsun shampoo in the treatment of seborrheic dermatitis. Br J Clin Pract 39(1):25-28 (1985 Jan).
- Parsad D, Pandhi R, Negi KS, et al. Topical metronidazole in seborrheic dermatitis–a double-blind study. Dermatology 202(1):35-7 (2001).
- Seckin D, Gurbuz O, Akin O. Metronidazole 0.75% gel vs. ketoconazole 2% cream in the treatment of facial seborrheic dermatitis: a randomized, double-blind study. J Eur Acad Dermatol Venereol 21(3):345-50 (2007 Mar).
- Koca R, Altinyazar HC, Eºtürk E. Is topical metronidazole effective in seborrheic dermatitis? A double-blind study. Int J Dermatol 42(8):632-5 (2003 Aug).
- Ozcan H, Seyhan M, Yologlu S. Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study. Eur J Dermatol 17(4):313-6 (2007 Jun).
- Gould DJ, Mortimer PS, Proby C, et al. A double-blind, placebo-controlled, multicenter trial of lithium succinate ointment in the treatment of seborrheic dermatitis. Efalith Multicenter Trial Group. J Am Acad Dermatol 26(3 Pt 2):452-7 (1992 Mar).
- Langtry JA, Rowland Payne CM, Staughton RC, et al. Topical lithium succinate ointment (Efalith) in the treatment of AIDS-related seborrheoic dermatitis. Clin Exp Dermatol 22(5):216-9 (1997 Sep).
- Dreno B, Moyse D. Lithium gluconate in the treatment of seborrhoeic dermatitis: a multicenter, randomised, doubleblind study versus placebo. Eur J Dermatol 12(6):549-52 (2002 Nov-Dec).
- Dreno B, Chosidow O, Revuz J, et al. Lithium gluconate 8% vs ketoconazole 2% in the treatment of seborrhoeic dermatitis: a multicentre, randomized study. Br J Dermatol 148(6):1230-6 (2003 Jun).
- Warshaw EM, Wohlhuter RJ, Liu A, et al. Results of a randomized, double-blind, vehicle-controlled efficacy trial of pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic dermatitis. J Am Acad Dermatol 57(2):257-64 (2007 Aug).
- Rigopoulos D, Ioannides D, Kalogeromitros D, et al. Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrhoeic dermatitis: a randomized open-label clinical trial. Br J Dermatol 151(5):1071-5 (2004 Nov).
- Firooz A, Solhpour A, Gorouhi F, et al. Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial. Arch Dermatol 142(8):1066-7 (2006 Aug).
- Koc E, Arca E, Kose O, et al. An open, randomized, prospective, comparative study of topical pimecrolimus 1% cream and topical ketoconazole 2% cream in the treatment of seborrheic dermatitis. J Dermatolog Treat 20(1):4-9 (2009).
- Shin H, Kwon OS, Won CH, et al. Clinical efficacies of topical agents for the treatment of seborrheic dermatitis of the scalp: a comparative study. J Dermatol 36(3):131-7 (2009 Mar).
- Paghdal KV, Schwartz RA. Topical tar: back to the future. J Am Acad Dermatol 61(2):294-302 (2009 Aug).
- Davies DB, Boorman GC, Shuttleworth D. Comparative efficacy of shampoos containing coal tar (4.0% w/w; Tarmed™), coal tar (4.0% w/w) plus ciclopirox olamine (1.0% w/w; Tarmed™ AF) and ketoconazole (2.0% w/w; Nizoral™) for the treatment of dandruff/seborrhoeic dermatitis. J Dermatolog Treat 10(3):177-83 (1999 Jan).
- Danby FW, Maddin WS, Margesson LJ, et al. A randomized, double-blind, placebo controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff. J Am Acad Dermatol 29(6):1008-12 (1993 Dec).
- Bonnetblanc JM, Bernard P. Benzoyl peroxide in seborrheic dermatitis. Arch Dermatol 122(7):752 (1986 Jul).
- Bikowski J. Facial seborrheic dermatitis: a report on current status and therapeutic horizons. J Drugs Dermatol 8(2):125-33 (2009 Feb).
- Nakayama J. Four cases of sebopsoriasis or seborrheic dermatitis of the face and scalp successfully treated with 1a-24 (R)-dihydroxycholecalciferol (tacalcitol) cream. Eur J Dermatol 10(7):528-32 (2000 Oct-Nov).
- Veraldi S, Menter A, Innocenti M. Treatment of mild to moderate seborrhoeic dermatitis with MAS064D (Sebclair), a novel topical medical device: results of a pilot, randomized, double-blind, controlled trial. J Eur Acad Dermatol Venereol 22(3):290-6 (2008 Mar).
- Wikler JR, Janssen N, Bruynzeel DP, et al. The effect of UV-light on Pityrosporum yeasts: ultrastructural changes and inhibition of growth. Acta Derm Venereol 70(1):69-71 (1990).
- Pirkhammer D, Seeber A, Hönigsmann H, et al. Narrow-band ultraviolet B (ATL-01) phototherapy is an effective and safe treatment option for patients with severe seborrhoeic dermatitis. Br J Dermatol 143(5):964-8 (2000 Nov).
- Ranki A, Puska P, Mattinen S, et al. Effect of PUVA on immunologic and virologic findings in HIV-infected patients. J Am Acad Dermatol 24(3):404-10 (1991 Mar).
- Tegner E. Seborrhoeic dermatitis of the face induced by PUVA treatment. Acta Derm Venereol 63(4):335-9 (1983).
- Vena GA, Micali G, Santoianni P, et al. Oral terbinafine in the treatment of multi-site seborrhoic dermatitis: a multicenter, double-blind placebo-controlled study. Int J Immunopathol Pharmacol 18(4):745-53 (2005 Oct-Dec).
- Scaparro E, Quadri G, Virno G, et al. Evaluation of the efficacy and tolerability of oral terbinafine (Daskil) in patients with seborrhoeic dermatitis. A multicentre, randomized, investigator-blinded, placebo-controlled trial. Br J Dermatol 144(4):854-7 (2001 Apr).
- Cömert A, Bekiroglu N, Gürbüz O, et al. Efficacy of oral fluconazole in the treatment of seborrheic dermatitis: a placebo-controlled study. Am J Clin Dermatol 8(4):235-8 (2007).
- Ford GP, Farr PM, Ive FA, et al. The response of seborrheic dermatitis to ketoconazole. Br J Dermatol 111(5):603-7 (1984 Nov).
- Shemer A, Kaplan B, Nathansohn N, et al. Treatment of moderate to severe facial seborrheic dermatitis with itraconazole: an open non-comparative study. Isr Med Assoc J 10(6):417-8 (2008 Jun).