PHARMACOLOGY /

COSMETOLOG Y

The treatment of dandruff

of the scalp
prof. dr hab. med. Zygmunt Adamski*/**, lek. med. Magorzata Deja*/**
*Department of Medical Mycology and Dermatology, Pozna University
of Medical Science
Director: prof. dr hab. med. Zygmunt Adamski
**Provincional Hospital in Pozna, Department of Skin Diseases
Head: prof. dr hab. med. Zygmunt Adamski

Introduction
Term dandruff pityriasis,
meaning bran-like epidermal scaling (Greek pityron: bran-like) was
introduced into dermatological vocabulary by Galen [1]. Disease constitutes a very widespread problem,
present in more than a half of population of Caucasian origin [2].
Although most commonly it is
a problem of just aesthetic nature,
chronic character of this condition
and tendency to relapse makes it
troublesome and difficult to cope
for people suffering from this condition. Two types of dandruff can
occur common (dry) or oily dandruff.
Common (dry) Dandruff (Pityriasis simplex capiliti s. sicca, furfuracea) is characterised by excessive
formation of minute scales of
whitegreyish or ashen colour, accumulating on the scalp area. These
bran-like scales are at first localised
in the middle of the scalp area and
then spread towards, parietal, frontal and occipital areas [3].
Scales visible on the scalp are separated cells of keratinised layer,
whose renewal cycle is pathologically shortened (even to 7 days, with
the norm equalling 28 days). Hair
in this type of dandruff are not

changed and no excessive hair loss

is observed.
In the epidermis of people suffering from common dandruff histopathology analysis reveals characteristic intervals of parakeratosis foci,
raised mitotic index of corneocytes
and peeling in the form of multicellular aggregates; there is no actual
inflammatory status of the proper
skin [4].
The other form of the disorder is
so called oily dandruff (Pityriasis
steatoides), being just the form of
dandruff arising on the scalp skin
with varied intensity of sebum production. It appears most often in
young men following puberty (aged
between 18 and 24). On the skin of
the scalp area inflammation of various intensity then develops, constituting the basis for fragile, oily
scales (Pityriasis oleosa) of dirty-yellow colour, which can form accumulations. These lesions can be
associated with pruritus of various
intensity [3].
The aetiology of dandruff, being
the form of seborrhoeic dermatitis,
is not unequivocally established.
Many factors are usually listed, described as endogenous and exogenous. Researchers include the following into the first group:
- immunological abnormalities,

related to humoral and cell immunity, proved by associated severe seborrhoeic dermatitis often observed
in subjects infected with HIV or
suffering from AIDS; disorder is
present in a significant proportion
of this group of patients (even 34-83%) [5];
- hormonal factors, related to
the fact, that lesions appear more
commonly in younger males (during puberty) and in young adults,
when sebum glands function is
most intensive and androgen level
increases,
- neurological
abnormalities
(during depression, also in cases of
Parkinson disease),
Cited exogenous factors include:
- lifestyle (incorrect skin care,
mikrotrauma and stress),
- diet factors (poor nutrition, alcoholism),
- environmental factors (environmental pollution and climate)
[5,11,12].
Seborrhoeic dermatitis can also
be associated with the presence of
other diseases including: pancreatitis, HVC infection, neoplasms and
also genetic abnormalities (for
example Down syndrome, Hailey-Hailey disease) [5].
Regardless of such multifactor

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49

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COSMETOLOGY

etiopathogenesis of the disease, the

greatest significance is believed to
be associated with lipophilic yeast
Malassezia furfur (Pityrosporum ovale,
Pityrosporum orbiculare) infection.
This thesis, regarding the explanation of scalp skin peeling was proposed already in 1874 by Malassez
[6]. Since that time great many
number of trials have been performed in order to confirm or negate
the thesis. It has been noted, that
increased number of this yeast-like
population present on the scalp
skin disturbs its ecosystem, enabling development of the disorder.
Lipophilic yeast-like constitute just
46% of scalp microflora in healthy
subjects, whereas in dandruff their
number increases to 74%, and in
cases of seborrhoeic dermatitis
even to 82% [7]. In studies by
Adamski, where classic mycological
methods were used, presence of
Malassezia furfur was shown in
22% of subjects in the control group, in 55% patients with scalp dandruff and 40% of patients with seborrhoeic dermatitis [8]. Additionally in patients with oily steatic
dandruff high level of serum antibodies against Pityrosporum was
found [9]. Association between
a yeast infection and disease pathogenesis was also confirmed by
improvement observed following
treatment with fungicidal drugs
[1,10,11]. While the new generation of drugs was being developed
interest in the infection with Malassezia furfur and its association with
aetiology of seborrhoeic dermatitis
flourished. It was observed, that in
patients treated with ketoconazole
apparent improvement of clinical
status was associated with the reduction of the number of Malassezia
yeasts within disease lesions. Some
authors showed, that Malassezia
fungi are more commonly found in
patients with dandruff and seborrhoeic dermatitis than in healthy
subjects [5,13]. Others however do

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AESTHETIC DERMATOLOGY /NO. 2 /2006

The treatment of dandruff

of the scalp
SUMMARY
Key words: dandruff of the scalp, dermatitis seborrhoica, clinical trials, treatment of dandruff, zinc pyrithione, imidazole agents, tar, octopirox, salicylic
acic, urea, sulfur
Dandruff of the scalp is a very common problem in aesthetic dermatology. The
pathogenesis of dandruff is connected with an infection with a yeast-like fungus
Malassezia furfur and with shortend proliferation cycle of keratinocytes which
causes abundant epidermis desquamation on the skin. There are two forms of
dandruff sicca or steatoides.
The aim of this article is to present dandruff treatment methods with a special
emphasis on modern antidandruff products which are devided into three
groups due to their mechanism of activity (antifungal agents, keratolytic agents
and cytostatic agents). The comparison of efficiency of these products based
on results of worldwide clinical trials is presented to propose physicians the
best possible therapy.
The most efficient drugs and thus mainly used are shampoos including antimycotic agents that eliminate Malassezia furfur from the scalp. The most widely
antimycotic shampoos used in dandruff therapy are products with ketoconazole and zinc pirythione. However, the risk of developing yeast species resistent
to imidazole agents has to be taken under consideration while treatment.
Antidandruff products such as keratolitic and cytostatic agents work only symptomatically, and often recurrence of dandruff after stopping treatment
is observed. It is a reason why these groups of agents are recommended
in politherapy of dandruff of the scalp. Octopirox is efficient, antidandruff cytostatic agent with additional antibacterial and antimycotic activity.
The important role of proper skin treatment, prophylactic and metaphylactic
methods should always be remember in dandruff treatment.

not find differences in the content

of Malassezia furfur in disease lesions as compared to healthy skin
[14]. It is clearly visible then, that
the problem of etiopathogenesis of
seborrhoeic dermatitis and dandruff is till causing a lot of controversy and is vividly discussed.
In severe cases of seborrhoeic
dermatitis differential diagnosis
should consider other diseases such
as, scalp psoriasis, fungal infection,
some forms of ichthyosis, and also
asbestos dandruff (Pityriasis amiantacea) [3].
Considering the fact, that scalp
dandruff is a chronic and relapsing
condition, the question of proper
treatment has been widely analysed. Effective pharmacological formulas were sought, also therapeutic
use of herbal substances was tried,
for example nettle leaves (Folium
Urticae), camomile pellets (Anth.

Chamomillae), soapwort roots (Rad.

Saponariae) or burdock roots (Succ.
Bardanae). Herbal treatment involves also use of complex formulas
such as Betulan (birch leaves, camomile capitules, yarrow herb, Pot
Marigold pellets and lavender pellets) or Seboren (parsnip fruits, nettle roots, burdock roots and sweet
flag rhizome) [15].
The rules of pharmacological
treatment of dandruff were summarised and codified in Consensus of
the expert group of Polish Dermatological Society Mycological Section on dandruff therapy. According to the mechanism of action
the recommended formulas were
classified into three groups:
1) fungicidal substances (zinc
pirythioniate, imidazole formulas
for example ketoconazole),
2) cytostatic substances (tar, selenium sulphide, octopirox),

PHARMACOLOGY /
3) keratolytic substances (tar,
salicylic acid, urea, sulphur compounds).

Fungicidal substances
Considering confirmed influence
of Malassezia yeasts on development
of dandruff, fungicidal formulas are
widely used in therapy of this condition and are characterised by
great therapeutic effectiveness. It
can even be said, that introduction
of fungicidal drugs, for example imidazole derivatives ketoconazole,
econazole etc., zinc pirythioniate
and selenium sulphide constituted
a break-through in the therapy of
dandruff. These compounds are
a group of drugs with etiological action, inhibiting the growth of Malassezia furfur.
Ketoconazole is an imidazole
derivative of wide fungicidal spectrum, which mechanism of action
involves inhibition of biosynthesis
of ergosterole (P-450 cytochrome)
within the fungal cell wall, causing
its altered permeability and consequently death of a cell. Ketoconazole displays also anti-inflammatory
action through inhibition of 5-lipooxygenase and leukotriene B4 production, as well as antiandrogen action. Used topically also relieves
prurigo and decreases intensity of
skin lesions present in the course of
seborrhoeic dermatitis, common
dandruff and pityriasis versicolor.
Numerous clinical trials confirmed
therapeutic effectiveness of ketoconazole in these diseases.
In a randomized trial including
66 subjects effectiveness of application of shampoos containing 1%
and 2% ketoconazole in treatment
of severe dandruff and scalp seborrhoeic dermatitis was weighed. The
trial included a few stages: period of
2 weeks before treatment, period of
4 weeks of using shampoos with 2%

or 1% ketoconazole and further period of consecutive 4 weeks without

therapy. Effectiveness of therapy
was assessed on the basis of clinical
picture, mycological tests, showing
presence of Malassezia spp. and peeling measurements (scales measurements). Following 4 weeks of treatment shampoo containing 2% of
ketoconazole proved to more efficacious than shampoo with 1% concentration. Lesser tendency to experience disorder relapses was also noted during the period of use of 2%
shampoo [16].
A multicentre, randomized trial
with double blind placebo controlled outlay including 575 patients
has been organised, in which effectiveness of introducing a shampoo
with 2% ketoconazole in therapy
and prophylaxis of moderate and
severe dandruff was assessed. Very
good therapeutic results were achieved in 88% of patients. Prophylactic phase fo the trial lasting for 6
months revealed disease relapse in
only 23% of patients using ketoconazole, while relapse occurred in
47% of patients in the placebo
group. Results proved effectiveness
of using shampoo with ketoconazole 2% in the treatment and prophylaxis of relapsing dandruff [17].
Also in Polish studies performed
by Adamski, effectiveness of therapy of scalp oily dandruff in 40 patients applying 2% ketoconazol was
assessed. Following 4 weeks of treatment the number of positive mycological tests decreased from 55% to
7%. In further tests still greater reduction of clinical symptoms and
signs in the form of prurigo, peeling
and erythema was observed. Therapy efficiency reached 75%. Achieved results confirmed the important
role of Malassezia furfur in scalp dandruff etiopathogenesis and effectiveness of fungicidal therapy of
this condition [8].
Numerous clinical trials were
performed comparing application of

COSMETOLOG Y

ketoconazole and other antidandruff substances. Multicentre, randomised trial by Pierard-Franchimont et al., evaluating use of
a shampoo containing 2% ketoconazole or 1% zinc pirythioniate in
a group of patients with severe scalp
dandruff can serve as an example.
The results of the trial confirmed
the effectiveness of both shampoos,
however better therapeutic effect
was noted in the group applying
2% ketoconazole (improvement of
73%) as compared with the group
applying 1% zinc pirythioniate (improvement of 67%). The percentage
of disease relapses was also lower
in the group using 2% ketoconazole [18].
In another randomised trial with
blind setting efficiency of using two
shampoos was assessed: one containing 2% ketoconazole and the
second one, containing 1.5% cyclopiroxolamine and 3% salicylic acid,
in the course of treatment of scalp
seborrhoeic dermatitis. This study
confirmed effectiveness and safety
of therapy employing any of tested
shampoos [19].
Danby et al. completed randomised double blind placebo controlled
clinical trial involving 246 patients,
in whom effectiveness of a shampoo
with 2% ketoconazole was compared with shampoo containing 2.5%
selenium sulphide in treatment and
prophylaxis of moderate and severe
dandruff. This study showed therapeutic effectiveness of both tested
shampoos disclosing at the same
time, that shampoo with 2% ketoconazole was better tolerated by patients [20].
In the therapy of dandruff employment of other, apart from ketoconazole, imidazole derivatives (for
example flutrimazole, econazole, bifonazole, clotrimazole) is possible.
A randomised double blind clinical
trial was performed comparing effectiveness of 1% flutrimazole in the
form of a cream with 2% ketocona-

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COSMETOLOGY

zole for treatment of Candida spp.

and dermatophytic infections,
which proved, that these formulas
are at least equally effective. Additionally flutrimazole displays also
anti-inflammatory action, which
makes it more useful in cases of bacterial infection associated with inflammatory reaction [21,22].
It must be however remembered,
that widespread use of imidazole
derivatives can in a long term cause
increased resistance of Malassezia
yeasts to the formulas used and make therapy of not only dandruff, but
also more severe fungal skin infections more difficult.
Zinc pirythioniate is a further
substance displaying fungicidal activity, useful in eliminating Malassezia
furfur. Mechanism of action of this
substance involves inhibition of cell
wall transport in the fungal cell
(probably by inhibiting proton
pomp), what in effect leads to lysis
of fungal cells. It has been shown,
that apart from described fungicidal
action, this formula influences ultrastructure of epidermal layer cells,
enabling its normalization [23,24].
It should also be stressed, that zinc
pirythioniate is characterised by its
significant lipid solubility, dissolves
in sebum, thus the period when
effective concentration of the formula is maintained in keratinized
epidermal layer is prolonged achieving increased fungicidal activity.
Azole substances on the other hand,
contrary to zinc pirythioniate, are
hydrophilic compounds and do not
accumulate in lipophilic environment of Malassezia furfur, what
explains required prolonged period
of treatment if azole based drugs are
employed [15].
Numerous clinical trials were
performed evaluating effectiveness
of shampoos containing zinc pirythioniate and comparing it with
other formulas. An example of such
trials was multicentre evaluation of

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shampoos incorporating 2% ketoconazole and 1% zinc pirythioniate

versus placebo. The above listed formulas were used in 364 patients
with moderate and severe dandruff
through the period of 4-6 weeks.
The trial has proven comparable
therapeutic effectiveness of both
formulas [25].
Samplea et al. organised a study
involving 236 patients with moderate and severe dandruff, in whom
a shampoo with ketoconazole 2%
and zinc pirythioniate 1% was used
for a period of 4 weeks. The results
included significant improvement
of the skin status, disease symptoms
reduction of even 90%, comprising
receding of prurigo and erythema.
Shampoo with ketoconazole 2%
and zinc pirythioniate 1% turned
out to be safe and efficient way of
treating dandruff [26].
The test of popular antidandruff
shampoo was performed showing,
that formula with 1% ketoconazole
is 10-times more efficient than
other competing shampoos (assessed versus Head & Shoulders, Pantene Blue, Gard Violet, Selsun
Blue), while shampoo with 2% ketoconazole is 10-times more efficient
than the one containing 1% [27].
While discussing fungicidal substances recommended for treatment
of dandruff, attention must be paid
to new formulas currently at the stadium of clinical research; these include: rilopirox, climbazole and lithium succinate [12]. The above listed formulas for local use arise
wide interest as a new therapeutic
options. There are also trials currently running evaluating effectiveness
of the above substances in the elimination of Malassezia furfur.
In the study by Harady et al. assessing in vitro antifungal activity of
rilopirox it was shown that the new
formula displays a wide range of
fungicidal activity, comparable with
cyclopiroxolamine spectrum [28].

Effectiveness and therapy safety

associated with climbazole use was
confirmed by the study prepared
by Wigger-Alberti et al., which
involved testing shampoo containing 0.65% climbazole in a group
of 30 people with mild and moderate scalp seborrhoeic dermatitis.
Following 4 weeks of treatment reduction of dandruff was observed,
receding of the erythema and prurigo was confirmed in 80% of tested
subjects, in the remaining 20% improvement of the skin status was
noted [29].

Cytostatic substances
Substances from this group act
through regulation of the excessive
speed of epidermal cells division inhibiting exaggerated peeling of the
scalp area, thus eliminating the
scales, being the basic feature of
dandruff. The above mentioned
group includes: tars, selenium sulphide and piroktolamine (octopirox). These substances action is however restricted only to the period
of actual use, meaning that after
cessation of treatment relapses of
the disease are quite often noticed.
It can be explained by symptomatic
only action of these formulas and
lack of aetiological effect associated
with insignificant influence on the
population of Malassezia furfur [15].
Formulas containing selenium
sulphide are also recommended in
the treatment of the form of dandruff (pityriasis versicolor). Selenium sulphide has a cytostatic effect on epidermal and hair follicles
cells, inhibiting excessive peeling,
redness and prurigo. It also exhibits
antifungal activity inhibits development of dermatophytes, which
cause proper mycoses of epidermis,
hair and nails. However, it must be
remembered, that regular use of formulas containing selenium sulphide
can give rise to excessive produc-

PHARMACOLOGY /
tion of sebum and oily hair [30].
Octopirox is a pyrydinone derivative of a proven effectiveness in
dandruff treatment, used since
1977. In recommended therapeutic
shampoos preferred concentration
of this substance ranges from 0.5%
to 1.0%. A wide range of antibacterial and antifungal action of octopirox has been shown in in vitro studies. Its effectiveness and safety of
therapy was confirmed in the clinical studies: in over 200 volunteers
using formulas containing octopirox
no signs or symptoms of irritation,
allergy or other toxic reactions were
observed. Octopirox formulas of
0.5% concentration are also effective in prophylaxis [31].
In the trial by Futterer effectiveness of the formula containing octopirox in the concentration of 0.75%
was compared with placebo. After

six weeks of therapy reduction of

dandruff symptoms by 54.5% was
achieved in subjects using octopirox
and by 9.9% in subjects applying
placebo [32]. A comparative effectiveness study was performed involving shampoo containing piroktolamine 0.75% in association with 2%
salicylic acid versus shampoo containing 1% zinc pirythione. Both
shampoos displayed high effectiveness against dandruff, however
shampoo containing both ingredients seemed to be more efficient
in eradicating symptoms of dandruff [33].
A very interesting formula introduced for therapy of dandruff is
a therapeutic shampoo Mediket
Plus. This product contains two therapeutic substances: ketoconazole
1% characterised by antifungal action and octopirox 1% restricting

Table 1
Examples of the products used in the treatment of dundruff

Imidazole
formulas

ketoconazole 2% (Nizoral, Nizoxin)

ketoconazole 1% (Nizorelle, Mediket, Mediket Plus)
clotrimazole (Triazol)
flutrimazole (Micetal gel)
econazole (Pevaryl)
bifonazole (Mycospor)

Zinc
pirythione

therapeutic shampoos: firmy Head & Shoulders, Polytar AF,

Ocerin PTZ, Squa-med, Freederm, Zinc Shampoo, Satinique

Cytostatic
formulas

tars (Polytar Liquid, Neutrogena T-Gel, Freederm)

selenium sulphide (Selsun Blue)
piroktolamine (Octopirox, Dercos, Ocerin OPX)
1.5% cyclopiroxolamine (Stieprox)

Keratolytic
substances

Cocois: tar, precipitated sulphur, salicylic acid, coconut oil

Provictiol: urea and salicylic acid

Complex
formulas

Ocerin PTZ: urea, undecenoic acid derivative and zinc

pirythioniate
Ocerin OPX: urea, undecenoic acid derivative and octopirox
Saliker: i.a. salicylic acid and piroktolamine
Mediket Plus: contains ketoconazole 1% i octopirox 1%
Kerium

COSMETOLOG Y

development of yeasts and bacterial

skin flora. For treatment of dandruff use of the shampoo 2-3 times
a week for a period of 4-6 weeks is
recommended, followed by prophylactic routine, meaning use of the
formula containing ketoconazole
1% only.
At present use of a shampoo containing 1.5% cyclopiroxolamine is
recommended in the treatment of
dandruff along with pyrydinone
derivative, which shows fungicidal
and fungostatic action (towards dermatophytes, yeast-like fungi, mould
and dimorphic fungi), antibacterial
(Gram positive, Gram negative bacteria) and anti-inflammatory action
(greater than 2.5% hydrocortisone)
[23]. Mechanism of antifungal
action of the formula is different
from the mechanism of action of
imidazole derivatives drug accumulates in the fungal cells, binds to
its organellae, thus causing increased permeability of the cell membrane, escape of nutrients and
blocking of enzymatic processes. All
the above leads finally to death of
fungal cells [34].
Gullon et al. performed tests
comparing effectiveness of anti-dandruff therapy using two shampoos:
with 1.5% cyclopiroxolamine and
2% ketoconazole. Study results showed stronger action of anti-dandruff
shampoo with 1.5% cyclopiroxolamine [33]. It has been proved
that, shampoo with 1.5% cyclopiroxolamine is a modern, effective formula well tolerated by patients
[34].
Study by Lee et al. involved comparison of effectiveness of the shampoo containing 1.5% cyclopiroxolamine with shampoo containing 2%
ketoconazole in treatment of mild
and moderate dandruff. Study included 64 patients. It was observed
that dandruff intensity decreased
during use of both formulas. Only
a mild degree of increased perceived
scalp itching was observed in III

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phase in people using 1.5% cyclopiroxolamine. Conclusions: cyclopiroxolamine is an effective, safe and
easy to use substance in the treatment of mild and moderate dandruff [35].

Keratolytic formulas
Keratolytic formulas, whose action relies on removal of scales of
epidermal keratinised layer include:
salicylic acid, urea, tars, and sulphur
derivatives. The last ones are recommended as part of combined
therapy, for example with anti-fungal substances, because of their
short-lived, symptomatic-only therapeutic effect.
There are also a number of formulas containing tar (commonly
together with salicylic acid). Older
tar formulas were recognisable by
their unpleasant smell and dark colour. Modern, presently used formulas do not feature those unpleasant characteristics, because fractions of aromatic hydrocarbons, responsible for the negative features
of the discussed above formulas
were eliminated.
There are no sufficient number
of trials assessing effectiveness of
anti-dandruff treatment shampoos
containing tar. One of the trials
comparing effects of the products
containing tar (0.5%) and shampoo, which did not list tar as ingredients (ingredients included: 2% sa-

licylic acid, 0.75% piroctolamine

and 0.5% elubiol), showed lack of
statistically valid differences of the
relevant formulas effectiveness.
Both drug groups were assessed as
formulas achievement high percentage of improvement, of even 70%
and more. Shampoo containing salicylic acid, piroctolamine and elubiol appeared to be more efficient
in achieving reduction of a population of Malassezia spp. [36].

Summary
In the modern world much
attention is paid to the way other
people look (external features),
which quite often helps or hampers
realisation of their plans or projects.
A very fast development of aesthetic medicine or cosmetic dermatology is an adequate response to
the social need to improve ones
appearance enabling also better selfassessment.
Problem of dandruff, sometimes
underestimated by medical professionals constitutes a problem for
a large chunk of society. The aspects
of treatment presented in the article herein, therapeutic novelties and
results of numerous comparative clinical studies prove, that dandruff
treatment is not as simple an issue
as would at first appear. Regardless
of the existence and widespread use
of numerous therapeutic substances
disease relapses are common.

Shampoos with anti-fungal action, listing ingredients such as ketoconazole and zinc pirythione are
believed to be the most effective
and their effectiveness tested in numerous clinical trials seems to be
comparable. Whereas action of keratolytic and cytotoxic formulas is
only symptomatic, relying on elimination of visible scales from scalp
skin. Thus, after cessation of treatment with these formulas the relapse of disease is quite commonly observed. Keratolytic and cytotoxic
drugs are ingredients of complex
formulas and are mainly recommended for use in complex therapy of
scalp dandruff.
Considering chronic and relapsing character of the disease, proper
care of the scalp and prophylaxis
cannot be forgotten, as they are of
immense significance in the eventual success of therapeutic process,
thus also in achieving patient satisfaction.
Numerous formulas recommended for dandruff treatment are
currently available on the market,
however therapeutic result achieved
is strongly associated with adequate
patient comprehension of an actual
problem and disease aetiology. The
actual task of the physician is to
make patient aware of the necessity
of regular use of recommended therapy and of the need to continue it
even after external symptoms of the
disease have disappeared.

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Address for correspondence:

Zygmunt Adamski
Oddzia Chorb Skry z Zespoem Pomocy Doranej
Szpital Wojewdzki
ul. Juraszw 7/19, 60-479 Pozna (Poland)
Phone: 048 61 821 23 08, 048 61 821 22 52
E-mail: adamskiz@poczta.onet.pl

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a tar and a non-tar shampoo. Dermatology, 2000, 200(2):
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