JEADV (2005) 19, 172175

DOI: 10.1111/j.1468-3083.2005.01090.x
OR IG INAL AR T ICLE

Oral itraconazole for the treatment of seborrhoeic dermatitis:

Blackwell Publishing, Ltd.

an open, noncomparative trial

O Kose,* H Erbil, AR Gur
School of Medicine, Department of Dermatology, 06018 Ankara, Turkey. *Corresponding author, Gulhane Military Medical Academy, School of Medicine,
Department of Dermatology, 06018 Ankara, Turkey. Current address: Queen Mary School of Medicine, Cutaneous Research Centre, 2nd Floor, 2 Newark
Street, Whitechapel, London E1 2AT, UK, E-mail: okose@gata.edu.tr

ABSTRAC T
Background Seborrhoeic dermatitis is an inflammatory cutaneous disorder in which the colonization of
the affected area by Malassezia has been proved to play a key role.
Objective To perform a noncomparative open clinical study with oral itraconazole capsule (200 mg/
day 7 days) and consecutive usage 200 mg/day for the first 2 days of the following 2 months in patients
with seborrhoeic dermatitis.
Methods Twenty-nine patients were enrolled to determine the efficacy and safety of oral itraconazole. The
patients were evaluated according to itching, burning, erythema, desquamation and seborrhoea, each
scored on a 0 4 scale on days 15 (T15), 30 (T30), 60 (T 60) and 90 (T90). Itraconazole capsule 100 mg was
given twice a day for 1 week and then, after a 3-week interval, patients used itraconazole capsule 200 mg/
day for the first 2 days of the following 2 months. The clinical response was graded as markedly effective,
effective, moderate or ineffective.
Results A clinical improvement (evaluated as markedly effective or effective) was observed in 23
patients (83%) at T15, 21 (76%) at T30, 20 (72%) at T60 and 17 (61%) at T90. At baseline, the mean SD
total clinical scores were 10.44 2.45, 1.98 0.5, 2.97 1.12, 3.15 1.74 and 3.30 1.90 at T0, T15, T30,
T60 and T90, respectively. Compared with baseline values, itraconazole capsule significantly reduced the
mean SD total score as well as individual erythema and desquamation (Wilcoxons signed test-two tailed)
(P < 0.0001). No drug-related systemic adverse event was observed during the study.
Conclusions Seborrhoeic dermatitis shows marked reduction in inflammation when treated with itra-
conazole. The anti-inflammatory activity of oral itraconazole and efficacy on Malessezia suggests that itra-
conazole capsule will be first oral treatment option in future in severe seborrhoeic dermatitis.
Key words: intermittent therapy, itraconazole, pityrosporum ovale, seborrhoeic dermatitis

Received 10 December 2003; accepted 4 March 2004

Seborrhoeic dermatitis (SD) is a common chronic inflammatory
disease of the skin characterized by scaly, reddish lesions in
regions rich in sebaceous glands. It shows periods of remission
and exacerbation. Topical steroid creams and antifungal agents
are commonly used for seborrhoeic dermatitis but there is no
curative therapy.1,2 The lipophilic Malassezia yeasts form part
of the normal human cutaneous flora. However, under the influ-
ence of certain predisposing factors they become pathogenic
and yield seborrhoeic dermatitis.3,4 Itraconazole is a highly
keratophilic and lipophilic triazole. Secretion in sebum is a
major route by which the drug reaches the stratum corneum.5,6
The aim of this study was to determine the efficacy and safety of
oral itraconazole capsule 100 mg given twice in a day for 7 days
and consecutive usage in the treatment of severe SD.
Materials and methods
Study design and population
The study was an open, noncomparative clinical trial, in which
33 eligible patients were evaluated. Four patients were excluded
from the study for personal reasons leaving 29 patients with

172 2005 European Academy of Dermatology and Venereology

 Itraconazole in seborrhoeic dermatitis 173

severe SD who were enrolled in the trial. Written informed Table I Effects (mean SD) on clinical signs of seborrhoeic dermatitis
consent was obtained from each patient before entering the
Symptoms T0 T15 T30 T60 T90
study. Patients were evaluated according to the following items:
itching, burning, erythema, desquamation (scale) and seborrhoea. Erythema 2.6 0.7 0.5 0.1 0.8 0.5 0.7 0.5 0.7 0.5
For each parameter a four-point score was used; 0, absent; 1, Desquamation 2.5 0.5 0.3 0.1 0.6 0.2 0.7 0.5 0.7 0.4
mild; 2, moderate; 3, severe. To be included patients were Seborrhoea 2.2 0.4 0.3 0.1 0.5 0.2 0.4 0.1 0.5 0.1
required to have a sum equal to at least 5 but with an erythema Itching 1.6 0.3 0.5 0.2 0.6 0.2 0.6 0.2 0.6 0.3
Burning 1.4 0.3 0.4 0.2 0.4 0.1 0.6 0.2 0.6 0.2
score not greater than 2. The clinical efficacy parameter was the
proportion of patients who achieved complete or partial P < 0.001, Wilcoxon signed tests.
disappearance according to the four-point total score; markedly
effective (sum 0), effective (sum 1 or 2), moderate (sum 3 or 4)
and ineffective (sum > 5). Patients who had taken systemic Table 2 Efficacy of the treatment
antibiotics or used topical corticosteroids, topical antifungals,
selenium or zinc pyrithione within 15 days prior to study entry, Clinical response T15 T30 T60 T90

and those who had taken retinoids within 30 days, were excluded
Markedly effective 18 (65%) 16 (58%) 15 (54%) 14 (51%)
from the study. The study population was composed of patients Effective 5 (18%) 5 (18%) 5 (18%) 3 (10%)
over 18 years of age with severe SD of the nasolabial folds (11 Moderate 3 (10%) 4 (14%) 4 (14%) 6 (21%)
patients), face (15 patients) and sternal area (two patients). Ineffective 2 (7%) 3 (10%) 4 (14%) 5 (18%)

Conduct of study
In the treatment protocol, itraconazole capsule (Itraspor,
Jansen, Turkey) 100 mg twice a day was given for 1 week, then after
a 3-week interval, patients used itraconazole capsule 100 mg
capsule twice a day for the first 2 days of the following months
for 2 months. This study was carried out in the winter and early
spring, seasons in which seborrhoeic dermatitis is normally
exacerbated.
Study parameters
Study evaluation visits were performed at baseline, and on
days 15 (T15), 30 (T30), 60 (T60) and 90 (T90). The total scores,
that is the sum of the gradings on itching, burning, erythema,
desquamation and seborrhoea, were assessed at each visit. A
global evaluation of tolerance and ease of use was also reported
by the subjects themselves at the end of the study. On days 15,
30, 60 and 90, clinical response was classified as markedly
effective, effective, moderate and ineffective by measuring the
total score. Complete blood count, liver and renal function tests
were checked before and after treatment. Mycological
examination was carried out in all patients at T0, T15 and T90.
patients (20 males, nine females, mean age 31.2 years) with
SD unresponsive to conventional therapies were evaluated
after giving their informed consent. Clinical improvement
was evaluated (as markedly effective and effective) and was
observed in 23 patients (83%) at T15, 21 (76%) at T30,
20 (72%) at T60 and 17 (61%) at T90. The efficacy of the
treatment is shown in Table 1. In the patients who could
be evaluated, the average global clinical score varied from
10.44 2.45 at T0, to 1.98 0.65 at T15, 2.97 1.12 at T30,
3.15 174 at T60, and 3.30 1.90 at T90. There were
statistically significant results between T0 and T15, T0 and T30,
T0 and T60, and T0 and T90 (Wilcoxon signed two-tailed tests,
significance for P-values < 0.0001). The effects on clinical signs
of SD with oral itraconazole are shown on Table 2. Burning and
itching were self-evaluated by the patients. There were no
problems with compliance on using the drug. Mycological
examinations were positive in all cases at T0 and negative in all
cases at T15. At the end of the study (T90), four patients with a
positive mycological examination were treated with topical
antifungal drugs. The excellent results in one patient are shown
in fig. 1.

Statistical analysis
Statistical analysis was performed using Friedmann varians
analyses and Wilcoxons signed rank test. Lesional scores and
global evaluation were compared using Wilcoxons two-tailed test.
Results
Thirty-three patients were enrolled in the study. Four patients
were excluded from the study for personal reason and 29
Discussion
Seborrhoeic dermatitis is characterized by inflammation and
desquamation in areas with a rich supply of sebaceous glands.1 3
Malassezia has been implicated in the development of this
condition. It has been suggested that SD is an inflammatory
response to this organism, but this remains to be proved.
Malassezia may play an important role in the pathogenesis of
SD, stimulating cytokine production by keratinocytes.4 Many
studies show that antimycotics are effective in clearing lesions,
with reduction in the number of the Malassezia yeasts and

2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 172175
174 Kose et al.
fig. 1 Patient (a) before treatment, (b) on day 15 and (c) on day 30.
recolonization on withdrawal of treatment leading to a
recurrence of SD. Itraconazole is anti-inflammatory, primarily
because of its inhibiting effect on the synthesis of 5-
hypooxygenase metabolites, which are involved in several
inflammatory diseases such as SD. The fact that SD responds to
antifungal medication is strongly suggestive of the role of yeast
in this disorder.5 Itraconazole is a highly lipophilic drug that can
2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 172175
be accumulated in the adipose tissue, skin and nail. It can be
detected in the tissue 24 h after administration of 200 mg and
elimination by sebum. The effective sebum concentration can
be detected in the third and fourth weeks after 4 days of
treatment.6 Itraconazole is not the only effective therapeutic
agent for SD, but it is also highly active in vitro against
Malassezia.7 Previous open clinical trials suggested that oral
itraconazole capsule could be effective in SD.811 In one study,
Masataro treated 30 patients with SD of the head and face, who
used 150 or 200 mg once per week for 23 months. Sixty-seven
per cent of the patients showed a marked or effective response.9
In an open trial, Faergemann evaluated 10 patients with
sebopsoriasis of the scalp and face. Patients were started on
itraconazole 50 mg /day for 2 weeks; if this dosage was well
tolerated, the itraconazole was increased to 100 mg /day for an
additional 4 weeks. Four patients were cured of scalp lesions
and one other patient was cured overall.10 Caputo et al. have
reported the largest study to date: 160 patients with SD treated
with itraconazole 200 mg /day for 7 days in autumn, then
200 mg/day for the first 2 days of the following months for
8 months until summer. After an interval of 3 months in
summer they reassessed the clinical picture in autumn again.
Patients were evaluated at baseline, and on days 7 and 37. At

day 37, clinical improvement was evaluated as excellent
(34%), good (40%) and moderate (18%). They claimed that
itraconazole not only induced a marked reduction in signs and
symptoms of the disease but also permitted, in many cases,
control of relapse.11 In our study, patients were offered
itraconazole 200 mg/day for 2 days a month according the
above pharmacological characteristics of the drug. Oral
itraconazole capsule 200 mg/day for 7 days is efficacious and
well tolerated in patients with SD. By day 15 (T15), the
treatment was judged to be effective in 23 (82%) patients with
overall improvements seen as markedly effective in 18 (65%),
effective in five (17%), moderate in three (11%) and ineffective
in two (7%) patients. We observed all patients 6 months after
the end of the treatment for exacerbations. During this period
we observed no recurrences. The use of oral itraconazole
capsule clearly diminished the symptoms (especially erythema
and desquamation) of the disease. The clinical outcome of
the treatment of the second (T60) and the third months (T90)
was low with respect to the previous months. Patients also
complained of burning and itching in this period. Oral
administration of itraconazole as an antifungal drug is
preferred because of its ease of usage and efficacy. As shown in
Table 2, the mean variation at T60 and T90 is greater than T30
and T0. For this reason, it will be more effective to change the
pozology of the drug to an interval of 3 weeks instead of a
1-month interval. On mycological examination, the results
were positive at T0 and negative at T15 in all patients. At T90 only
four patients were negative but the mycological results do not
reflect the clinical condition. There was no correlation between
the state of the clinical picture and the mycological results.
The anti-inflammatory activity of oral itraconazole and its
efficacy on Malassezia yeasts suggests that itraconazole may be
effective and safe in the treatment of SD, particularly that
2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 172175
The author has requested enhancement of the downloaded file. All in-text references underlined in blue are linked to publications on ResearchGate.
Itraconazole in seborrhoeic dermatitis 175
present on the face. Intermittent usage of this drug will also be
helpful for exacerbations, although it is evident that future
research is needed about the efficacy and safety of this drug in a
comparative or placebo-controlled clinical trial.
References
1 Faergemann J. Management of seborrheic dermatitis and pityriasis
versicolor. Am J Clin Dermatol 2000; 1: 75 80.
2 Faergemann J, Bergbrabt IM, Dohse M et al. Seborrheic dermatitis
and Pityrosporum (Malessezia) folliculitis: characterization of
inflammatory cells and mediators in the skin by immunochemistry.
Br J Dermatol 2001; 144: 54 556.
3 Bergbrabt IM. Seborrheic dermatitis and Pityrosporum ovale:
cultural, immunological, and clinical studies. Acta Derm Venereol
(Stockh) 1991; 167: 136.
4 Faergemann J. Pityrosporum species as a cause of allergy and
infections. Allergy 1999; 54: 413 419.
5 Rosen T, Schell BJ, Orengo I. Anti-inflammatory activity of
antifungal preparations. Int J Dermatol 1997; 36: 788 792.
6 Elewski BE. Mechanism of action of systemic antifungal agents.
J Am Acad Dermatol 1993; 28: 28 34.
7 Gupta AK, Kohli Y, Li A, Faergemann J. In vitro susceptibility of the
seven Malassezia species to ketoconazole, variconazole,
itraconazole and terbinafine. Br J Dermatol 2000; 142: 758 765.
8 Gupta AK, Bluhm R. Itraconazole for seborrheic dermatitis. Skin
Ther Lett 2002; 7: 46.
9 Masataro H. Treatment of seborrheic dermatitis with antifungal
drugs. J Clin Exp Med 1995; 173: 1026 1027.
10 Faergemann J. Treatment of sebopsoriasis with itraconazole.
Mykosen 1985; 28: 612 618.
11 Caputo R, Barbareschi M. Itraconazole: new horizons. G Ital Derm
Venereol 2002; 137: 17.