The Three Major Facets of Seborrheic Dermatitis and their Treatment

  Aditya K. Gupta, MD, Ph.D.1; Yvonne M. DeAngelis, CVT2; Christina M. Gemmer,B.S.2; Meredith Leland, B.A.2; Shane Whitaker, B.S.2;

James R. Schwartz, Ph.D.2; and Thomas L. Dawson, Jr., Ph.D.2 ;

1 MediProbe Labs, London, Ontario, Canada and the University of Toronto, Toronto, Canada 2 The Procter & Gamble Company, Cincinnati, Ohio.

Introduction

Dandruff is a chronic scalp condition characterized by visible flakes induced by rapid turnover of scalp cells. Seborrheic dermatitis is a more severe form of dandruff, resulting from the same etiologic events. Dandruff and seborrheic dermatitis (D/SD) have been shown to be more than just superficial disorders of the stratum corneum, including significant alteration of the epidermis with hyperproliferation

An abnormally high rate of cell division, which occurs in the scalp epidermis with dandruff/seborrheic dermatitis. The normal epidermal maturation rate increases from 28 days for a healthy scalp to 7-21 days for an unhealthy scalp.

, excess intercellular and intracellular lipids, interdigitation of the corneal envelope, and parakeratosis1, 2. This study reveals an individual susceptibility to unsaturated fatty acids and highlights that dandruff and seborrheic dermatitis are caused by a convergence of three factors: 1) sebum, 2) microbial effects (primarily by Malassezia yeasts), and 3) aggravating factors associated with individual susceptibility.

 

Methods

Scalp Lipid Assay - Human scalps were swabbed with a paper swab and the lipids extracted with hexane/methanol. Derivatized samples were analyzed by gas chromatography.

Lipase Assay - Cultured Malassezia were washed into dPBS and assayed by the release of p-nitrophenol from pnitrophenyl oleate. Samples were normalized for protein content based on Pierce commassie protein detection.

tFLP (terminal fragment length polymorphism)3 - DNA was extracted from scalp swabs collected from subjects in the US and China. The fungal ribosomal gene cluster ITS I and ITS II regions were amplified and fragment size analysis used to differentiate Malassezia species. Samples were compared to standards from CBS, Utrecht; The Netherlands.

Oleic Acid Flake Induction - 20 dandruff sufferers were selected after a two week washout with a commercial nonantidandruff shampoo. All subjects then used a commercial PtZ -containing shampoo for two weeks and throughout the study to eliminate microbial background (no changes were seen). Subjects were dosed with both 150l of 7.5% oleic acid or vehicle control on a 5cm2 area every other day for 5 days.

 

Results

human scalp sebum after removal of Malassezia. After Malassezia removal by a commercial anti-fungal shampoo, human sebum consists of primarily triglycerides and wax esters, with low levels of free fatty acid.

Figure 1b. Fatty acid and triglyceride composition of human scalp sebum with active Malassezia. When active Malassezia are present, triglycerides are degraded by lipase activity into irritating free fatty acids.

Figure 2a. Presence of Malassezia on human scalps. Malassezia globosa a n d Malassezia restricta are the predominant fungal species found on human scalp3.

Figure 2b. Lipase activity of Malassezia species. Of the Malassezia species found on human scalp, M. globosa has the highest lipase activity and thus the greatest ability to induce production of irritating free fatty acids.

 

Figure 3a. Oleic acid induces dandruff-like flaking in dandruff subjects. Oleic acid induced flaking in subjects who had been identified as having dandruff (p0.1 at days 5, 7, and 8).

Figure 3b. Oleic acid, at the same dose, does not induce flaking in non-dandruff subjects. Subjects predetermined to not suffer from dandruff do not have increased flaking when challenged with oleic acid. Oleic acid induced dandruff was ultrastructually identical to normal dandruff (data not shown).

 

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Conclusions

Dandruff has now been shown to be the result of three etiologic factors: Sebum, Malassezia fungi, and Individual susceptibility. Of these etiologic three factors, only fungal density can be easily controlled. The treatment of dandruff is therefore primarily composed of antifungal agents,

such as pyrithione zinc ( PtZ), ketoconazole, ciclopiroxolamine and selenium-sulfide 4. Shampoos containing zinc pyrithione also reduce the ultrastructural abnormalities, including excessive

intercellular lipid level, parakeratosis, corneocyte lipid inclusions and Malassezia numbers, thereby returning the scalp to a more healthy "normal" state5.

 

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References

1. Gupta, AK, et al. Skin diseases associated with Malassezia species. JAAD; 51:785-98

2004.

2. Gupta, AK, et al. Seborrheic dermatitis. Derm Clin 21:401-412, 2003

3. Gemmer, C, et al. Fast, noninvasive method for molecular detection and differentiation

of Malassezia yeast species on human skin and application of the method to dandruff

microbiology. JCM 40:3350-3357, 2002.

4. Shuster, S: The aetiology of dandruff and the mode of action of therapeutic agents. Brit

J Dermatol 111:235-242, 1984

5. Warner, R, et al. Dandruff has an altered stratum corneum ultrastructure that is

improved with zinc pyrithione shampoo. JAAD 45:897-903, 2001

 

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