1

THE USED OF ZINC PYRITHIONE (ZPT)

IN SEBORRHEIC DERMATITIS

INTRODUCTION

Seborrheic dermatitis is a common chronic inflammatory skin condition,

characterized by scaling and poorly defined erythematous patches with a
predilection for areas rich in sebaceous glands. It may be associated with pruritus,
and it primarily affects sebum-rich areas, such as the scalp, face, upper chest, and
back.

The reported prevalence of seborrheic dermatitis in the overall adult population

ranges from 1 to 5 percent, and the disorder can affect any ethnicity. There is a
transient infantile form of seborrheic dermatitis that presents and resolves within
the first 3 to 4 months of life; however, some cases may be more persistent with
recurrences over several months. Infantile seborrheic dermatitis may be limited to
scalp involvement (cradle cap) or may be more diffuse. The adult form of
seborrheic dermatitis, which is far more common than infantile seborrheic
dermatitis and appears to affect men more than women, may present first around
puberty, correlating with the increase in cutaneous lipids resulting from androgen-
driven sebaceous gland development and sebum secretion. The course of adult
seborrheic dermatitis in affected individuals is variable throughout adulthood with
some noting only occasional periods of exacerbation and others experiencing
greater chronicity with more frequent recurrences. The common presence of
seborrheic dermatitis after the age of 50 years has been noted. In patients with
acquired immunodeficiency syndrome (AIDS), the incidence of seborrheic
dermatitis increases markedly, affecting from 30 to 80 percent of individuals.1

Several modalities may be effective in the treatment of seborrheic dermatitis. The

mechanism of action of the most common treatments includes inhibition of skin
yeast colonization, reduction of pruritus and erythema, loosening of the crusts and
scales, and reduction of inflammation. These therapies consist of antifungal
agents, corticosteroids, immunomodulators, and keratolytics. However, some of
these modalities have multiple characteristics, such as the anti-inflammatory
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properties inherent in many of the antifungal agents as well as the keratolytic

properties of selenium, zinc, and tar preparations. 2

SEBORRHEIC DERMATITIS

Seborrheic dermatitis is a common chronic inflammatory skin condition,

characterized by scaling and poorly defined erythematous patches with a
predilection for areas rich in sebaceous glands. It may be associated with pruritus,
and it primarily affects sebum-rich areas, such as the scalp, face, upper chest, and
back. A milder variant is dandruff, which is manifested by dry, flaking scales on
the scalp. Seborrheic dermatitis of the scalp commonly presents as dandruff, a
milder eruption, characterized by smaller dry, flaking scales.

Although its pathogenesis is not completely understood, some postulate that the
condition results from colonization of the skin of affected individuals with species
of the genus Malassezia (formerly, Pityrosporum). The pathogenesis of seborrheic
dermatitis is not completely understood, but there seems to be a strong association
with skin colonization with yeasts of the genus Malassezia. These yeasts are
present on the skin of affected individuals, and antifungal therapy that decreases
the number of Malassezia organisms present has been shown to be effective in the
treatment of seborrheic dermatitis.

Another theory is that the lipid layer of the fungus leads to keratinocyte
production of proinflammatory cytokines, causing inflammation and the skin
eruption. No genetic predisposition has been identified with seborrheic
dermatitis.2

CLINICAL FEATURE

Seborrheic dermatitis is considered one of the most frequent skin disorders,

although estimates of prevalence are limited by the lack of validated criteria for
diagnosis or grading of severity. Seborrheic dermatitis is characterized by the
development of pruritic, erythematous patches with easily detachable, greasy
large scales and poorly defined erythematous patches, with large variations in
extent and morphologic characteristics depending on the area of skin involved.
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Although it may appear in various anatomical locations, it tends to occur in areas

that contain numerous sebaceous glands, such as the scalp, face, upper chest, and
back.2 An infantile form, which usually involves the scalp (cradle cap), the face,
and the diaper area, is particularly common.3

Seborrheic dermatitis of the scalp commonly presents as dandruff, a milder

eruption, characterized by smaller dry, flaking scales.2 Dandruff is mediated by
Malassezia metabolites, specifically irritating free fatty acids released from
sebaceous triglycerides. Investigation of the toxic Malassezia free fatty acid
metabolites (represented by oleic acid) reveals the component of individual
susceptibility. Malassezia metabolism results in increased levels of scalp free fatty
acids. Of the three etiologic factors implicated in dandruff, Malassezia, sebaceous
triglycerides, and individual susceptibility, Malassezia are the easiest to control.
Pyrithione zinc kills Malassezia and all other fungi, and is highly effective against
the Malassezia species actually found on scalp. Reduction in fungi reduces free
fatty acids, thereby reducing scalp flaking and itch.4

ZINC PYRITHIONE IN SEBORRHEIC DERMATITIS

Some antimicrobial agents that inhibit Malassezia spp. yeasts are selenium
disulfide, zinc pyrithione (ZPT), piroctone olamine, ketoconazole, and ciclopirox
olamine;

ZPT has some synonyms: bis[1-hydroxy2 (1H)-pyridine-thianato] zinc, ZP,

ZnPT, ZnPTO, zinc bis(2-pyridylthio)-N- oxide, Zinc 2-pyridinethione-1-oxide.5
ZPT which known also as zinc omadine atau vancidine is a biocide whose rational
development in the 1950s was based on aspergillic acid, the natural antibiotic
from Aspergillums. ZPT was included in the evaluation of over 1,000 candidates
for controlling the yeast of the genus Malassezia relevant in dandruff etiology.

ZPT has many properties which make it especially useful to deliver in the
complex vehicle of a shampoo; it is:

only sparingly water-soluble, allowing efficient scalp retention after rinsing;

affordable for regular usage;

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and it allows galenic formulations due to lack of color and odor impact on
product cosmetics.6

Recently, ZPT is known as a substance that can be used as antibacterial and anti
fungal especially for yeast cell. It has demonstrate a strong antidandruff effect
with a low potential for irritation or sensitization. Clinical studies have shown it to
be superior to coal tar, selenium disulfide, and piroctone olamine.

Widely, ZPT used to control the dandruff in seborrheic dermatitis and psoriasis.
For the management of dandruff in seborrheic dermatitis, ZPT can decrease the
turn over rate of epidermis cells. Mechanism of action of ZPT still unknown, but
it is believed that ZPT has the mechanism as anti proliferatin which involved the
regulations of DNA transcriptions factors contained zinc finger binding
domains.5

These attributes have led to ZPT becoming the most common material used for
dandruff treatment globally. Antidandruff efficacy and safety were demonstrated
in the early 1960s, which served as the basis for acceptance by the US Food and
Drug Administration. Until recently there has been little known of the antifungal
mechanism of action. Ermolayeva and Sanders and Chandler and Segel showed
that ZPT can depolarize membranes and prevent membrane transport, although
the ZPT concentrations used (> 100 M) are much higher than required to inhibit
fungal growth. More recently, Yasokawa et al. used microarray analysis to show
that ZPT induces iron starvation, suggesting the antifungal mechanism is due to
iron starvation. Recently, Reeder et al. demonstrated a new hypothesis on the
mechanism of action of ZPT, namely that ZPT inhibits S.cerevisiae growth
through copper influx. The data supporting this conclusion are 1) an increase in
cellular copper content, 2) gene expression responses indicative of excess
intercellular copper, 3) a requirement for environmental copper for ZPT activity,
and 4) the observation that mutant cells more sensitive to copper are likewise
more sensitive to ZPT. The molecular mechanism of ZPT-mediated inhibition of
S. cerevisiae is copper-mediated loss of function of iron-sulfur proteins.4 The
results of yeast deletions indicated that ZPT inhibits growth through increased
levels of copper but not zinc. From these data, it seems possible that ZPTs
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primary effects on cells are due to an imbalance of copper, zinc, and iron.6

The effectiveness of ZPT could be significantly improved with the use of

micronized ingredients, especially given the legal maximum of 1 %.

The combination of ZPT with zinc carbonate leads to reduced dissociation of the
active ingredients into zinc and pyrithione, which alone have a lower anti-
dandruff effect.7

CONCLUSION

Seborrheic dermatitis is considered one of the most frequent skin disorders,

although estimates of prevalence are limited by the lack of validated criteria for
diagnosis or grading of severity. Seborrheic dermatitis of the scalp commonly
presents as dandruff, a milder eruption, characterized by smaller dry, flaking
scales. Of the three etiologic factors implicated in dandruff, Malassezia, sebaceous
triglycerides, and individual susceptibility, Malassezia are the easiest to control.
Some antimicrobial agents that inhibit Malassezia spp. yeasts are selenium
disulfide, zinc pyrithione (ZPT), piroctone olamine, ketoconazole, and ciclopirox
olamine.

Pyrithione zinc kills Malassezia is highly effective against the Malassezia species
actually found on scalp. Widely, ZPT used to control the dandruff in seborrheic
dermatitis and psoriasis. For the management of dandruff in seborrheic
dermatitis, ZPT can decrese the turn over rate of epidermis cells. The
effectiveness of ZPT could be significantly improved with the use of micronized
ingredients, especially given the legal maximum of 1 %.
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REFERENCES

1. James Q. Del Rosso, Do. Adult Seborrheic Dermatitis, A Status Report On

Practical Topical Management. The Journal of Clinical Aestetic
Dermaologies, 2011: 32-38
2. Thomas Berk, MD, and Noah Scheinfeld, MD. Seborrheic Dermatitis.
P&T , June 2010: 35 No. 6: 348-352
3. Luigi Naldi, M.D., and Alfredo Rebora, M.D. Seborrheic Dermatitis. The
new england journal of medicine. 2009;360:387-96.
4. Yvonne M. DeAngelis, Christina M. Gemmer, Joseph R. Kaczvinsky,
Dianna C. Kenneally, James R. Schwartz, and Thomas L. Dawson, Jr.
Three Etiologic Facets of Dandruff and Seborrheic Dermatitis: Malassezia
Fungi, Sebaceous Lipids, and Individual Sensitivity. J Investig Dermatol
Symp Proc 10:295297, 2005
5. Charles, Crutchfield, lewis EJ, Zelickson BD. The highly effective use of
topical zinc pyrithione in the treatment of psoriasis. [Online]. [access
2012 January 18] ; Available at : URL :
http//www.dermatology.cdlib.org/DOJvol3num1/zinc/zinc.html.
6. Nancy L. Reeder, Jerry Kaplan, Jun Xu, R. Scott Youngquist, Jared
Wallace, Ping Hu, Kenton D. Juhlin, James R. Schwartz, Raymond A.
Grant, Angela Fieno et all. Zinc Pyrithione Inhibits Yeast Growth through
Copper Influx and Inactivation of Iron-Sulfur Proteins. Antimicrobial
Agents And Chemotherapy, Dec. 2011, p. 57535760
7. Ralph M. Treb. Review article: Shampoos: Ingredients, efficacy and
adverse effects. JDDG; 2007 5:356365