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Most common scalp flaking disorders show a strong correlation with sebaceous gland (SG) activity. Early SG activity in the neonate results in microfloral colonization and cradle cap. After maternal hormonal control subsides, there is little SG activity until puberty, when the SG turns on under sex hormone control. When the SG activity increases, the present but low Malassezia population has a new food source and proliferates, resulting in the scalp itching and flaking common to greater than 50% of adults. Dry scalp flaking, dandruff, and seborrheic dermatitis are chronic scalp manifestations of similar etiology differing only in severity. The common etiology is a convergence of three factors: (1) SG secretions, (2) microfloral metabolism, and (3) individual susceptibility. Dandruff and seborrheic dermatitis (D/SD) are more than superficial stratum corneum disorders, including alteration of the epidermis with hyperproliferation, excess lipids, interdigitation of the corneal envelope, and parakeratosis. The pathogenic role of Malassezia in D/SD has recently been elucidated, and is focused on their lipid metabolism. Malassezia restricta and M. globosa require lipids. They degrade sebum, free fatty acids from triglycerides, consume specific saturated fatty acids, and leave behind the unsaturates. Penetration of the modified sebaceous secretions results in inflammation, irritation, and scalp flaking.
Human SG are found over the entire skin surface (except the palms of the hands and soles of the feet), but sebum secretion is highest on the scalp, face, chest, and back (
Histology, histochemistry, and electron microscopy of sebaceous glands in man.
in: Gans O. Steigleder G.K. Handbuch der Haut-und Geschlechtskrankheiten; Normale und Pathologische Anatomie der Haut I. Berlin,
Springer-Verlag1968: 184-223
). Sebum is produced under hormonal control, with SG active at birth under the control of maternal androgens. They quickly reduce in size and sebum production until the onset of puberty. As puberty begins the SG again activate, this time under the control of circulating androgens. The sebum secretion rate increases throughout the teens, remains steady through the 20s and 30s, then lessens with age (
). Throughout the active period of sebum secretion, the secretion rate is higher in males than in females. In males, the rate remains higher longer, into the 50s and 60s, but in females, the secretion rate drops quickly after menopause (
). Common scalp flaking disorders all show a strong temporal correlation with sebaceous activity, following the pattern of early cradle cap, low incidence until puberty, increasing incidence through the teens, second and third decades, then declining (
The primary functions of sebum have historically been controversial, but are recently being elucidated. Sebum is involved in development of epidermal structure and maintenance of the epidermal permeability barrier (
). It has also recently come to light that sebum is directly involved in skin-specific hormonal signaling, epidermal differentiation, and protection of the skin from ultraviolet irradiation (
Human skin is a steroidogenic tissue: Steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1).
When secreted human sebum is a complex mixture of triglycerides, fatty acids, wax esters, sterol esters, cholesterol, cholesterol esters, and squalene Figure 1 (
). As the sebum is secreted, it consists primarily of triglycerides and esters, which are broken down by commensal microbes into diglycerides, monoglycerides, and the constituent free fatty acids. Human sebum contains both saturated and unsaturated fatty acids, with a preponderance of unsaturates. The fatty acid chain lengths of human sebum vary considerably, but are predominantly 16 and 18 carbons (stearic, C18:0, oleic, C18:1Δ9, linoleic, C18:2Δ9Δ12, palmitic, 16:0, sapienic, 16:1Δ6, and palmitoleic, C16:1Δ9, Figure 1). The role of specific fatty acids of human sebum becomes apparent when we examine the metabolism of Malassezia.
Figure 1Relative composition of human sebum. Samples of human sebum were collected and analyzed by gas chromatography. Peaks were identified by comparison to known standards. Identifications confirmed by GC-mass spectrometry.
Early SG activity in the neonate allows initial Malassezia colonization and is likely an initiating factor for cradle cap. The Malassezia population then drops dramatically, only to re-appear as SG activity increases at the onset of puberty (
). The Malassezia lipases are non-specific and degrade any available triglycerides Figure 2. The saturated fatty acids are consumed, and the abundant unsaturates are left on the skin (Figure 2 and Figure 3).
Figure 2Triglyceride degradation and increased free fatty acids after incubation of artificial sebum by Malassezia globosa. Lipid composition analyzed as in Figure 1, but following incubation of M. globosa for 24 hours with defined lipid matrix.
Figure 3Triglyceride and fatty acid composition of sebum extracted from human scalp. Lipid profile analyzed as in Figure 1, samples collected from a dandruff sufferer with high Malassezia counts before (red, primarily free fatty acids) or after (blue, both triglycerides and free fatty acids) treatment with a commercial antifungal shampoo.
Recently, novel molecular methods have overcome the difficulties presented by culture of Malassezia, and the specific Malassezia species present on human scalp have been elucidated (
Fast, noninvasive method for molecular detection and differentiation of Malassezia yeast species on human skin and application for the method to dandruff microbiology.
Sequence Diversity of the intergenic spacer region of the rRNA gene of Malassezia globosa colonizing the skin of patients with atopic dermatitis and healthy individuals.
). Malassezia nomenclature has evolved over the last century, but the genus now consists of 10 distinct species: M. globosa, M. restricta, M. furfur, M. sympodialis, M. slooffiae, M. obtusa, M. nana, M. dermatis, M. japonica, and the sole non-lipid-dependent species, M. pachydermatis. All except M. pachydermatis can be found on human skin, but the most common species on human scalp are M. restricta and M. globosa (
Fast, noninvasive method for molecular detection and differentiation of Malassezia yeast species on human skin and application for the method to dandruff microbiology.
). Further molecular investigation will undoubtedly produce more distinct genetic entities, but detailed biochemical and physiological experiments will be needed to define the actual species.
Etiologic Mechanism of Dandruff and Seborrheic Dermatitis (D/SD)
D/SD are chronic clinical scalp conditions affecting greater than 50% of the population, the primary symptom of which is visibly excessive scalp scaling. Seborrheic dermatitis is a more severe disorder which can include increased desquamation of facial areas other than the scalp and visible inflammation. Although dandruff is not a life-threatening disease, its presence can lead to loss of self-esteem and a negative social image (
). D/SD are more than just superficial disorders of the stratum corneum, including alteration of the epidermis with hyperproliferation, excess intercellular and intracellular lipids, interdigitation of the corneal envelope, and parakeratosis (
). This evidence includes the effectiveness of multiple chemical entities whose sole common mechanism of action is antifungal activity, as well as the very distinct numerical correlation of reduction in severity with reduction of Malassezia numbers (
). Combination of several recent lines of investigation points out a novel mechanism for the etiology of D/SD. M. restrica and M. globosa require lipids as food source (
), and are perfectly adapted for life on the human scalp. The Malassezia degrade sebum, freeing multiple fatty acids from triglycerides Figure 2. They consume the very specific saturated fatty acids necessary for their proliferation, leaving behind the unsaturated fatty acids Figure 3. Experimentally, it can be shown that the changes in sebum composition over time are a direct result of Malassezia metabolism. Table I illustrates the effect of removing scalp microflora with an antimicrobial shampoo (removal of microorganisms verified by molecular analysis, data not shown). The sebum composition changes back to near normal levels of triglyercides and free fatty acids.
Penetration of the modified sebaceous secretions into the stratum corneum breaks down the skin barrier function, resulting in inflammation, irritation, and the resultant scalp flaking. Recent data shows that the penetration and inflammation response to the fatty acids are different between dandruff and non-dandruff sufferers.
DeAngelis Y, Leland M, Gemmer C, et al: The three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, sebaceous lipids, and individual sensitivity. Intercontinental Meeting of Hair Research Societies, Conference poster, 2004.
Additionally, immunodeficiency, such as AIDS, allows excess Malassezia proliferation, resulting in severe D/SD. Physical factors, nutritional disorders, drugs, and neurotransmitter abnormalities are additional aggravating factors.
Conclusion
The common etiology of D/SD is therefore a convergence of three factors: (1) SG secretions, which provide the substrate for Malassezia growth; (2) Malassezia metabolism of the sebaceous secretions, releasing irritating unsaturated fatty acids; and (3) individual susceptibility to the penetration of the fatty acids and the resultant inflammation.
ACKNOWLEDGMENTS
The authors would like to thank Christina Gemmer, Yvonne DeAngelis, and Meredith Leland for their expertise in handling, growing, and detecting Malassezia; Shane Whitaker and Joe Kaczvinsky for their analytic expertise; and Aditya Gupta and Teun Boekhout for their expertise in Malassezia clinical implications and phylogeny/physiology, respectively.
References
Dawber R.
Diseases of the Hair and Scalp. London,
Blackwell Science1997: 499-504
Fast, noninvasive method for molecular detection and differentiation of Malassezia yeast species on human skin and application for the method to dandruff microbiology.
Histology, histochemistry, and electron microscopy of sebaceous glands in man.
in: Gans O. Steigleder G.K. Handbuch der Haut-und Geschlechtskrankheiten; Normale und Pathologische Anatomie der Haut I. Berlin,
Springer-Verlag1968: 184-223
Sequence Diversity of the intergenic spacer region of the rRNA gene of Malassezia globosa colonizing the skin of patients with atopic dermatitis and healthy individuals.
Human skin is a steroidogenic tissue: Steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1).