P#59  Dandruff and seborrheic dermatitis result from oleic acid released from sebum lipids by Malassezia lipase activity

Thomas L. Dawson Jr. , Joseph R. Kaczvinsky, Yvonne DeAngelis, Roger Treadway and James R.Schwartz. The Procter & Gamble Company, Cincinnati, OH

In spite of the high global incidence of dandruff and seborrheic dermatitis, few details are known about their molecular etiology. Research in our laboratories have recently yielded a more detailed mechanism. The scalp is populated by numerous microorganisms, including both bacteria and fungi. Two pieces of data implicate fungi as the causative agents of dandruff: 1) the correlation of decreasing fungal density with dandruff amelioration and 2) the success of several different fungal-specific anti-microbials in dandruff treatment. The genus Malassezia has long been implicated due to its presence on human skin and its lipophylic nature, but the lack of a numerical correlation between the number of Malassezia and the presence and severity of dandruff has been perplexing. The reclassification of Pityrosporum ovale into Malassezia furfur and then into the genus Malassezia, including at least seven different species, have further confused identification of the causal organism. Using molecular methods we have found that M. restricta, M. globosa, and, rarely, M. sympodialis are found on human scalps, so neither M. furfur, M. obtusa, M. slooffiae, nor M. pachydermatis can be the cause of dandruff. A direct numerical correlation may well exist to one Malassezia species (or combination of species) and not to a total Malassezia count. All Malassezia are lipophylic, and use a cell-wall associated lipase to cleave sebaceous triglycerides into assimilateable free fatty acids. The Malassezia species have variable lipase activity but M. restricta, the most common and numerous inhabitant of human scalp, has little or no lipase activity. M. restricta may not contribute to dandruff genesis and therefore confuse attempts to correlate Malassezia number to dandruff. While Malassezia require saturated fatty acids for survival, human sebum consists mainly of triglycerides of oleic acid, with lower concentrations of stearic and palmitic. The Malassezia lipase is non-specific (in regards to saturation and chain length), so unsaturated fatty acids not utilized are left on the scalp. Oleic acid is a known skin irritant and we have now shown that oleic acid alone can induce dandruff-like flaking in dandruff sufferers. The oleic acid has to penetrate into the stratum corneum to induce dandruff, implicating a breach of skin barrier function. Further, non-oxidizable branched chain fatty acids induce a response similar to oleic acid, indicating that oxidization is not the predominate mechanism. Therefore, we have now built a comprehensive mechanism for dandruff etiology: Malassezia globosa on the scalp digest sebaceous triglycerides, releasing irritating oleic acid. The oleic acid penetrates the stratum corneum, breaking down skin barrier function. The resultant attempt at barrier repair causes the hyperproliferation seen in dandruff scalp, as well as inducing the secretion of more sebum, thereby feeding the Malassezia population. The role of the immune system remains to be elucidated.