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Therapeutic Update on Seborrheic Dermatitis

I. Stefanaki, MD and A. Katsambas, MD
Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece

ABSTRACT

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.

Key Words: 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

Topical therapies are the mainstay of treatment as the condition is recurrent, usually mild, and responds well to these agents.

Antifungals

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

Corticosteroids

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

Zinc pyrithione 1% shampoo in comparison with ketoconazole 2% shampoo has produced inferior results, whereas selenium sulphide exhibited similar efficacy.24,25

Metronidazole

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

Lithium Salts

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

Calcineurin Inhibitors

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

Selenium Sulphide

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

Phototherapy

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

Systemic Therapies

Oral Antifungals

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

Conclusion

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.

References
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In this issue:

  1. Therapeutic Update on Seborrheic Dermatitis
  2. Current Management of Actinic Keratoses
  3. Update on Drugs and Drug News - May 2010