Management of Seborrheic Dermatitis
Seborrheic dermatitis is a common, chronic, recurrent inflammatory skin condition for which no definitive cause has been found. The disorder is usually confined to the scalp, nasolabial folds, external ear canal, hair-bearing areas of the face and/or presternal area of the chest.1 Scalp seborrheic dermatitis ranges from mild dandruff to dense, diffuse, adherent scale, while facial and trunk seborrheic dermatitis involves fine scale in skin folds and along the margins of the hairline.2 In adults, the condition tends to persist, undergoing periods of remission and exacerbation.1
The prevalence of seborrheic dermatitis is usually thought to range somewhere between 1% to 5% of the immunocompetent adult population, and is extremely high in the immunocompromised population, particularly AIDS patients — 30% to 83%.1,3 More prevalent in males, the disorder usually starts during puberty and is most common in adolescents and young adults, with increased incidence in adults older than 50. As a general rule, the disease seems to be influenced by seasonal variations, being worse in winter and improved by summer sunlight.3
Seborrheic dermatitis is sometimes seen in conjunction with rosacea, atopic dermatitis, blepharitis, acne vulgaris, tinea (pityriasis) versicolor and Malassezia folliculitis.3,4 One study of the epidemiology of rosacea, for example, found that seborrheic dermatitis was the third most common comorbid diagnosis made by dermatologists and primary care providers treating rosacea.5
The precise cause of seborrheic dermatitis has not yet been identified, although a number of species of the lipophilic yeast Malassezia, formerly known as Pityrosporum, have been implicated in the development of the disease, including M. furfur, M. globosa, M. restricta, and others.1,3 Most of the evidence for this observation has come from studies that showed that antifungal agents are effective in treating the disease. One suggestion regarding the pathogenesis of seborrheic dermatitis is that it represents an inflammatory response to Malassezia, which is present on all persons, but that hypothesis does not explain why some people develop the disease while others do not.
Genetic and environmental factors, including comorbid conditions, may predispose some individuals or populations to the development of the disorder. As noted above, people with AIDS are extremely likely to develop seborrheic dermatitis, as are those with central nervous system disorders such as Parkinson’s disease, cranial nerve palsies and major truncal paralyses, although it is not known exactly why these associations occur. Speculation in the case of seborrheic dermatitis associated with AIDS has focused on CD4-positive T lymphocyte counts, Malassezia spp density, and nutritional factors, while its correlation with CNS disorders has been explored as a function of sebum pooling due to immobility, which permits growth of M. furfur.2
Traditional Treatment Approaches
The overall goal of treatment of seborrheic dermatitis is to identify a safe and effective regimen that leads to improvement with low rates of recurrence, because the tendency of the disease to recur is the biggest challenge to clinicians and patients.1 To control outbreaks, patients should be encouraged to practice lifelong good hygiene.2
Pharmacologic options for treating seborrheic dermatitis include antifungal preparations that decrease colonization by lipophilic yeast, including selenium sulfide, pyrithione zinc and azole antifungals. Topical corticosteroids are also used, as are keratolytics such as salicylic acid, which are useful for the removal of scale. Examples of the available therapies used to treat seborrheic dermatitis are summarized in Table 1.
Ketoconazole and Seborrheic Dermatitis
Ketoconazole was introduced in 1979, the first imidazole known to have activity against a broad spectrum of fungi, such as dermatophytes, yeasts including Candida spp and Malassezia spp, and both dimorphic and polymorphic fungi. In addition, ketoconazole has anti-inflammatory properties as well, stemming from the inhibition of 5-lipoxygenase activity bearing on the production of leukotrienes derived from arachidonic acid.6 Of particular importance in the treatment of seborrheic dermatitis is the fact that ketoconazole is sebostatic, that is, it is able to lower the sebum content of seborrheic skin, and has antiproliferative effects demonstrated in human keratinocyte cultures, possibly achieved through inhibition of cholesterol biosynethesis.6-8
Clinical Trials for Ketoconazole Gel
Recently, ketoconazole has been formulated as 2% anhydrous gel (Xolegel).
In one phase III randomized, multi-center, double-blind study, the efficacy and safety of anhydrous ketoconazole 2% gel was studied in 459 patients with moderate to severe seborrheic dermatitis.9 Patients were randomized to receive either the gel (n=229) or vehicle (n=230) once daily for 14 days, with four assessments of their condition performed at baseline (day 0), mid-treatment (day 7), end of treatment (day 14) and follow-up (day 28). Primary efficacy measure was the proportion of patients effectively treated at day 28, while secondary efficacy measures included change from baseline in signs and symptoms (erythema, scaling, and pruritus at scalp hairline, retro-auricular area, eyebrows and bridge of nose, nasolabial folds and sternum) at day 14. Safety was assessed as incidence and severity of adverse events, with results that were similar in both test groups. Results showed that compared to vehicle, a significantly greater percentage of patients receiving ketoconazole gel had been effectively treated at day 28 — 27.2% of ketoconazole patients vs. 13.9% vehicle, P=0.0005.9 Change from baseline in scores of signs and symptoms at day 14 are shown in Figure 1.
In a report of three randomized, double-blind, vehicle-controlled, multicenter phase III trials, the efficacy and tolerability of ketoconazole gel 2% was compared with vehicle gel in more than 900 patients with moderate to severe seborrheic dermatitis who applied the treatment for 14 days and were followed for an additional 14 days. Two of the studies also compared a combination gel containing ketoconazole 2% plus desonide 0.05%, each active gel separately, and vehicle control. Treatment was considered successful if investigator global assessment (IGA) scores and observed erythema and scaling had decreased to 0 or 1 by day 28, depending on baseline scores. Pooled data from the three studies showed that the proportion of effectively treated subjects was significantly greater in the ketoconazole gel 2% group, compared to vehicle (P<0.001). As illustrated by Figure 2, ketoconazole gel alone was comparable in efficacy to the combination gel as well as to desonide gel alone, indicating that ketoconazole 2% gel is an effective treatment for seborrheic dermatitis and an alternative to the ketoconazole cream 2% formulation.8
Points to Remember
• In adults, seborrheic dermatitis tends to persist, undergoing periods of remission and exacerbation.
• The precise cause of seborrheic dermatitis has not yet been found, although the lipophilic yeast Malassezia has been implicated in the development and exacerbation of the disease
• The overall goal of treatment of seborrheic dermatitis is to identify a safe and effective regimen that leads to improvement with low rates of recurrence and a low potential for side effects.
• Non-corticosteroid options for treating seborrheic dermatitis include selenium sulfide, pyrithione zinc, azole antifungals, sodium sulfacetamide, coal tar preparations or salicylic acid.
• An anhydrous 2% gel of ketoconazole has been shown to be effective and safe in the treatment of seborrheic dermatitis in double-blind, randomized clinical trials.
• The anhydrous gel vehicle disappears rapidly into skin and may be perceived by some patients to be more cosmetically appealing than cream.