New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies.

Pathogenesis of dandruff/seborrhoeic dermatitis (D/SD) involves Malassezia yeasts, leading to the most widely accepted treatment strategy of topical application of antifungal agents, usually from rinse-off shampoos. The scalp spatial distribution of Malassezia must be mirrored by the distribution of the active agent to realize the full benefit of the active material. Based on observations that Malassezia yeasts reside in follicular infundibula, we sought to determine whether commercial shampoo products based on the active agent zinc pyrithione (ZPT) could deliver this material to this highly restricted, but therapeutically relevant space. Three new methods have been developed to assess ZPT active delivery to the follicular infundibulum: (i) hair plucks followed by chemical quantification of the subsurface portion; (ii) cyanoacrylate infundibular biopsies followed by chemical quantification of extracted ZPT; and (iii) confocal microscopy of infundibular spaces coupled with image analysis to yield relative quantification. Infundibular ZPT was detected, the quantity of which directly correlated with the consequent reduction of the infundibular Malassezia population. A commercial therapeutic shampoo delivered a disproportionately high level of ZPT to the infundibular spaces, suggesting an active mechanism to draw ZPT particles of optimum size to this space. Imaging of the infundibular ZPT in vivo allows an assessment of its state of aggregation, which would tend to minimize bioavailability. Effective therapeutic D/SD products must deliver the antifungal active material to the infundibulum as well as superficially on the scalp surface. This is achieved by certain therapeutic ZPT shampoos, in which the particle size of ZPT is likely to be an important factor in determining the efficiency of spatial delivery.

Schwartz JR ，Shah R ，Krigbaum H ，Sacha J ，Vogt A ，Blume-Peytavi U ... -  《-》

Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione.

Dandruff/seborrhoeic dermatitis is a common scalp condition that is characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect tissue level events that are poorly understood at the molecular level. The purpose of this work was: (i) to compare gene expression profiles in subjects with dandruff vs. those of subjects without dandruff to determine the key physiological disruptions manifest in the condition; and (ii) to determine the effect on this profile of treatment with a shampoo containing potentiated zinc pyrithione (ZPT). In study 1, scalp biopsies were taken from 16 normal subjects and from involved and uninvolved sites in 15 subjects with dandruff. In study 2, 30 subjects with dandruff were treated for 3 weeks with a commercial ZPT shampoo (n = 15) or a vehicle (n = 15), and scalp lesional biopsies were collected at baseline and end of study for transcriptomic analysis. RNA was extracted from all biopsies and Affymetrix gene chips were used to analyse transcriptomic profiles, followed by bioinformatic analysis. Analysis of study 1 biopsies revealed more than 7000 individual probes differentially regulated in dandruff lesional skin relative to normal. Enriched Gene Ontology categories included: lipid metabolism, immune response, response to stimulus, apoptosis, cell proliferation, and epidermal development. The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. Induced inflammatory genes were also enriched in dandruff uninvolved skin, suggesting the existence of predisposing factors associated with inflammation. Many genes increased in lesional skin were increased at the level of protein in stratum corneum samples (e.g. IL-1RA, S100A8, S100A9, S100A11, IL-8). Under conditions known to improve overall scalp condition, the ZPT shampoo treatment in study 2 produced a transcriptomic profile resembling that of normal scalp skin. These data provide novel insights into the nature of dandruff and the therapeutic action of potentiated ZPT-containing shampoo, and provide a basis to explore many new mechanistic questions related to these topics.

Mills KJ ，Hu P ，Henry J ，Tamura M ，Tiesman JP ，Xu J ... -  《-》

Therapeutic efficacy of anti-dandruff shampoos: a randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole.

Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti-fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti-fungal shampoos are maximizing bio-availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches - maximization of bio-availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material. The anti-fungal potency of shampoos representing each of these approaches was evaluated in vitro using a standard microbiology method. Spatial delivery of ZPT particles in the follicular infundibulum was assessed in vivo using a novel confocal microscopy methodology. Clinical efficacy was assessed in a randomized, double-blind trial involving 620 male and female subjects using scalp flaking and epidermal histamine level as endpoints. The shampoo formula with maximized ZPT bio-availability known as the Potentiated ZPT formula exhibited greater anti-fungal potency than the Dual Active shampoo containing both ZPT and climbazole. The Potentiated ZPT formula also delivered more ZPT to the lower infundibulum than the Dual Active shampoo. A 4-week treatment with the Potentiated ZPT formula resulted in superior clinical efficacy compared with the Dual Active product at all 4 weekly time points for both flaking and epidermal histamine endpoints. These results highlight the critical role that the shampoo vehicle plays in realizing full potency of active materials. By optimizing the delivery vehicle, the enhanced anti-fungal potency and the maximized spatial delivery of active materials result in greater symptomatic improvement than a product with two active materials. The therapeutic efficacy of a product based on a complex delivery vehicle such as a shampoo must be considered from a full-product perspective rather than just the active system as the non-active components of the composition will often play a significant role in the overall product pharmacology and resultant efficacy.

Schwartz JR ，Bacon RA ，Shah R ，Mizoguchi H ，Tosti A ... -  《-》

Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics.

Schwartz JR 《Journal of Drugs in Dermatology》

A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis.

Ketoconazole (KET) and zinc pyrithione (ZPT) are compounds active against the Malassezia spp. yeasts, which are believed to play a major role in dandruff and seborrheic dermatitis. We compared the efficacy and safety of KET 2% and ZPT 1% in shampoo formulations for the alleviation of severe dandruff and seborrheic dermatitis. This open randomized, parallel-group trial began with a 2-week run-in phase during which subjects applied a neutral non-antidandruff shampoo. It was followed by a 4-week randomized treatment phase and a subsequent 4-week follow-up phase without treatment. Shampooing during the treatment period was carried out twice weekly for the KET group and at least twice weekly for the ZPT group in accordance with the label instructions. A total of 343 subjects were recruited to enter the trial. Of the 331 eligible volunteers, 171 were randomized to KET 2% and 160 to ZPT 1%. Clinical assessments were performed. Beneficial effects were evidenced for both medicated shampoos, but the effect was significantly better for KET 2%, which achieved a 73% improvement in the total dandruff severity score compared with 67% for ZPT 1% at week 4 (p < 0.02). The recurrence rate of the disease was also significantly lower following KET 2% treatment than following ZPT 1% treatment. As a consequence, the overall clearing of the skin condition at the end of treatment and follow-up phase was in favor of the KET 2% formulation (p = 0.004). Side effects were minimal. It is concluded that after a 4-week treatment, KET 2% shampoo was significantly superior to ZPT 1% shampoo in the treatment of subjects with severe dandruff or seborrheic dermatitis of the scalp. It is our assumption that this difference is noticeable for the patient and as a consequence relevant. Both formulations were well tolerated.

Piérard-Franchimont C ，Goffin V ，Decroix J ，Piérard GE ... -  《-》