Pharmacology and Treatment
Received: September 3, 2001
Dermatology 2004;208:55–59
DOI: 10.1159/000075047
Single-Dose Fluconazole versus
Itraconazole in Pityriasis versicolor
R. Partap a I. Kaur a A. Chakrabarti b B. Kumar a
Departments of a Dermatology, Venereology and Leprology and b Medical Microbiology, Postgraduate Institute of
Medical Education and Research, Chandigarh, India
Key Words
Itraconazole, single-dose W Fluconazole, single-dose
Pityriasis versicolor
Abstract
Background: The new antifungal triazoles itraconazole
and fluconazole have revolutionized the treatment of
pityriasis versicolor. Both drugs have shown promising
results in different dose schedules. Objective: To com-
pare the efficacy and safety of single oral dose treatment
with fluconazole versus itraconazole in patients with
pityriasis versicolor. Methods: A total of 40 patients with
pityriasis versicolor were allocated randomly to group A
and group B. A single dose of fluconazole (400 mg) or
itraconazole (400 mg) was given orally to group A or
group B patients, respectively. Patients were assessed
mycologically by KOH and culture. Culture was done
from lesional and perilesional skin to quantify growth
and to observe the effect of these drugs and the persis-
tence/reappearance of the fungus in relation to relapse at
2 and 8 weeks. Relapse was defined as reappearance or
worsening of clinical signs and symptoms or positive
KOH/culture after initial improvement. Results: Thirteen
(65%) patients in the fluconazole group and 4 (20%)
patients in the itraconazole group became culture nega-
© 2004 S. Karger AG, Basel
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Accepted: August 14, 2003
tive at the end of 8 weeks. Relapse was found to be high-
W er in the itraconazole group compared to the fluconazole
group (60 vs. 35%). A direct correlation was found
between the relapse rate and positivity of perilesional
skin for Malassezia furfur. Conclusion: In the same dos-
ing, fluconazole was found to be more effective than itra-
conazole; however, both drugs were found to be safe.
Copyright © 2004 S. Karger AG, Basel
Pityriasis versicolor caused by Malassezia furfur is the
most common superficial mycotic disease with worldwide
distribution; however, M. globosa and M. sympodialis
have also been occasionally isolated. Most of the time,
treatment is sought only for cosmetic reasons. As sponta-
neous improvement is uncommon, the majority of pa-
tients require treatment. Treatment is simple but relapse
is a common problem. Topical therapy ranging from sele-
nium sulphide to imidazoles has been used effectively in
managing pityriasis versicolor, but this treatment is time
consuming, messy and inadequate especially for large
areas. Ketoconazole was the first oral antifungal used in
pityriasis versicolor, but its use is limited by the risk,
albeit low, of hepatic toxicity and possible endocrine
effects. Newer triazoles like itraconazole and fluconazole
have revolutionized the treatment of pityriasis versicolor.
Dr. Inderjeet Kaur, Additional Professor
Department of Dermatology, Venereology and Leprology
PGIMER
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Chandigarh 160 012 (India)
Fax +91 0172 744 401, 745 078, E-Mail kaur_inderjeet@yahoo.com
University of Hong Kong
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The advantage is their safety, better cure rates and infre- Table 1. Clinical details of patients with pityriasis versicolor
quent relapses. Many clinical trials with both fluconazole
Group A Group B
and itraconazole in different dosage regimens reported
(n = 20) (n = 20)
cure rates ranging from 75 to 94% [1–5]. Itraconazole has
been tried in various regimens with varying dosage and Mean age, years 26.7B11 26.35B11.8
durations. As the drug achieves higher concentrations in Sex ratio M:F 4:1 3:2
the stratum corneum and persists for 3–4 weeks after dis- Age of onset, years 23.15B10 20B5
continuation of therapy, single-dose regimens are likely to Mean duration, years 3.55B4.3 7.05B9.2
Extent of involvement
be effective [6]. Fluconazole also achieves more than 10 ! 20% 1 1
times the concentration of plasma in the stratum corneum 21–30% 16 17
and persists there for about 2 weeks. So it is expected to be 31–40% 1 0
effective in a similar fashion with a single dose as has been 1 40% 2 2
reported [4, 5]. Influenced by these observations we Complaints
undertook this study to compare the efficacy and safety of Cosmetic 12 (60) 10 (50)
a single-dose regimen of oral fluconazole versus itracona- Itching 8(40) 9(45)
zole in the treatment of pityriasis versicolor. We did a Lesions 1
quantitative culture from lesional and normal-looking Hypopigmented 13 (65) 7 (25)
perilesional skin to assess the presence of M. furfur and Hyperpigmented 3 (15) 2 (10)
Hyper- + hypopigmented 4 (20) 11 (55)
the effect of treatment on the presence of fungus and its Erythematous 2 (10) 3 (15)
relationship to relapse.
Culture grade before therapy
+++ 13 11
++ 7 7
Patients and Methods + 0 2
Family history 4 (20) 3 (15)
Forty consecutive patients with pityriasis versicolor were re-
cruited for this study from the Dermatology Department of the Post- Figures in parentheses are percentages.
1 Many patients had more than one type of colour change.
graduate Institute of Medical Education and Research, Chandigarh,
India. Patients included in the study were above 16 years of age with
skin surface area involvement of more than 15%. The patients had
not received any topical or systemic antifungal therapy for at least 3
weeks prior to this study. Exclusion criteria were: very sick patients
(those on multiple therapies for more than one disease) or those with
systemic mycoses, pregnant and lactating mothers and patients on Patients were asked to report for follow-up at 2 weeks and then at
systemic steroids, antimitotic or immunosuppressive drugs. 8 weeks. Skin scrapings/strippings for KOH examination and culture
Patients were allocated randomly (T table method) to groups A were done initially and then at each follow-up at 2 and 8 weeks in all
and B. In group A, 16 were males and 4 females. The mean age was patients.
26.7 B 11 years (range 17–55 years). In group B, there were 12 male Routine investigations including haemogram, liver and renal
and 8 female patients. The mean age in this group was 26.35 B 11.8 function tests were done in all patients at baseline and repeated only
years (range 16–60 years). The mean duration of the disease was 3.55 at 2 weeks after treatment. Parameters for clinical evaluation were
B 4.3 years in group A and 7.05 B 9.2 years in group B. Other char- itching, scaling and pigmentation. Side effects, if any, were noted.
acteristics of patients before treatment are listed in table 1. A detailed Patients who became KOH and culture negative were considered to
history was taken, and clinical examination was done in all patients be cured irrespective of residual dyschromia.
initially and at each follow-up at 2 and 8 weeks. Skin scrapings for Relapse was defined as reappearance or worsening of clinical
KOH (10%) examination were taken from the lesional and perile- signs and symptoms (vide supra) or positive KOH/culture after ini-
sional (normal-looking) skin 3 cm away from the margins of the tial improvement.
lesion. Skin strippings from lesional and perilesional skin were also The statistical method used was the ¯2 test. The ∑ coefficient
taken by applying Scotch tape of 1 square inch. These strippings were dichotomous variable was used to find the degree of correlation
cultured in Dixon medium modified by Midgley [7]. Culture grading between the perilesional skin positivity and relapse rate.
from both lesional and perilesional skin was done by counting the A higher grade of culture positivity in patients of both groups
number of colonies as follows: + = ^10; ++ = 11–39; +++ = 1 40 after treatment was considered as manifestation of mycological
colonies/square inch of Scotch tape. relapse.
No further species identification was done and all isolates were Written informed consent was obtained from all patients. The
labelled as M. furfur. Patients were administered a single dose of flu- study was approved by an institutional review board and was not
conazole (400 mg) or itraconazole (400 mg) after breakfast. sponsored.

56 Dermatology 2004;208:55–59 Partap/Kaur/Chakrabarti/Kumar

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Table 2. Clinical and mycological
Group A Group B
parameters
2 weeks 8 weeks 2 weeks 8 weeks

Clinical parameters
Disappearance of scaling 8 (40) 13 (65) 1 (5) 7 (35)
Residual pigmentation 20 (100) 16 (80) 20 (100) 19 (95)
Mycological results
KOH negativity 6 (30) 12 (60) 3 (15) 5 (25)
Culture negativity 2 (10) 13 (65) 1 (5) 4 (20)

Figures in parentheses are percentages.

Results
At the end of 2 weeks, scaling had disappeared in 8
(40%) cases in group A and in only 1 (5%) patient in group
B, and this difference between the two groups was statisti-
cally significant (p ! 0.05). Pruritus was relieved in all
patients in both groups. There was not much change in
colour of the skin at the end of 2 weeks in either of the
groups. At the end of 8 weeks, scaling was absent in 13
(65%) patients in group A and in only 7 (35%) patients in
group B. Pigmentation disappeared completely in 4 (20%)
patients in group A and only in 1 (5%) patient in group B.
Erythematous and hyperpigmented scaly lesions disap-
peared earlier than hypopigmented lesions. Residual mild
hypochromia was present in 16 (80%) patients in group A
and 19 (95%) patients in group B at the end of 8 weeks.
The differences in the clinical parameters, i.e. scaling and
pigmentation, were not statistically significant at 8 weeks
between the two groups. Details of the grade of initial cul-
ture positivity in both groups are given in table 1.
Mycological assessment at the end of 2 weeks revealed
negative KOH in 6 (30%) and negative culture in 2 (10%)
patients in group A. In group B, KOH examination was
negative in 3 (15%) patients, and culture was negative in
only 1 (5%) patient (table 2).
At the end of 8 weeks, 12 (60%) patients were negative
by KOH examination and 13 (65%) by culture in group A.
Of the 7 patients who had positive culture at 8 weeks, 6
patients showed positive culture of a higher grade than at
2 weeks and 1 showed positivity of the same grade. All
these 7 patients had clinical relapse in the form of appear-
ance of new lesions, scaling or increased hypopigmenta-
tion.
In group B, at 8 weeks, 5 (25%) patients attained nega-
tive results by KOH examination but culture became neg-
ative in only 4 (20%) patients. The patient who had
Table 3. Comparisons between the two groups at the end of therapy
(8 weeks)
Clinical cure Mycological Clinical and Relapse
cure mycological cure rate
Group A 4 (20) 13 (65) 4 (20) 7 (35)
Group B 1 (5) 4 (20) 1 (5) 12 (60)
Figures in parentheses are percentages.
become culture negative at 2 weeks remained culture neg-
ative at 8 weeks. Out of the 16 (80%) patients with posi-
tive cultures, 10 showed culture positivity of a higher
grade than at 2 weeks. Six patients showed positivity eith-
er of the same or of a lower grade. Clinical relapse in the
form of appearance of new lesions, scaling or increased
hypopigmentation was seen in 12/16 of these patients
with positive culture. In all the patients who relapsed, the
grade of culture positivity had gone up to ++ or +++. The
differences in the two groups for the occurrence of relapse
were statistically significant (p ! 0.05).
Perilesional skin in group A showed positive culture in
10/20 (50%) patients. It was of grade + in 9 and grade ++
in 1, throughout the period of study. There was not much
effect of treatment on the perilesional skin culture positiv-
ity and only 2 patients –1 each at weeks 2 and 8 – became
culture negative. In 7 of the 8 culture-positive patients,
the culture grade remained + throughout. Out of these 8
patients who remained culture positive throughout, clini-
cal relapse was seen in 5. There was a positive correlation
between perilesional skin positivity and relapse rate (∑
coefficient = 0.47; ¯2 = 4.43, p ! 0.05).

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 In group B, 12/20 (60%) patients showed positive cul-
ture from perilesional skin. Colony count was grade + in
11 patients and 1 showed a positivity of +++. At 2 weeks,
only 1 became culture negative and at 8 weeks 1 more
became culture negative. Ten patients showed the same or
a higher grade of culture positivity at the end of 8 weeks.
Out of the 10 patients who were persistently culture posi-
tive from the perilesional skin, 9 developed a clinical
relapse at the end of therapy. There was a positive correla-
tion between perilesional skin positivity and relapse rate
(∑ coefficient = 0.61; ¯2 = 7.5, p ! 0.01; table 3).
Haematological and biochemical parameters remained
normal. Side-effects with both drugs were negligible. Only
1 patient in group A complained of headache and loose
stools which persisted for only 1 day and were thought to
be unrelated to the drugs.
Discussion
Pityriasis versicolor is a benign superficial fungal infec-
tion more commonly caused by M. furfur. In the revised
taxonomy, 6 species (M. globosa, M. obtusa, M. restricta,
M. sympodialis, M. slooffiae and M. pachydermatitis) oth-
er than M. furfur have been identified from humans and
animals. In some studies, M. globosa and M. sympodialis
were the most common isolates from patients with pity-
riasis versicolor [8]. Pityriasis versicolor can be effectively
treated by many topical medications but has a very high
propensity for recurrence. Systemic therapy has a definite
role in such cases [9]. Itraconazole and fluconazole have
been successfully used in the treatment of extensive and
recurrent pityriasis versicolor. Both these drugs have been
tried in different dosages for varying periods. By most
authors itraconazole has been recommended in a dose of
200 mg/day for 7 days [10]. Recently a single dose of flu-
conazole (400 mg) has been tried in many studies, and it
has been found to be as effective as any other treatment
given for a longer duration. Since itraconazole is known to
achieve higher concentrations in the stratum corneum
which persist for 3–4 weeks even after discontinuation of
drug, it is likely to be effective in a single dose.
The most distressing symptoms in patients with pity-
riasis versicolor are cosmetically unacceptable pigmenta-
tion (mostly hypopigmentation), scaling and itching. Itch-
ing was the first symptom to disappear in our study. Next
to be controlled was scaling which cleared earlier and in a
higher number of patients after fluconazole than itracona-
zole (40 vs. 5%). Erythematous and hyperpigmented scaly
lesions also disappeared earlier, as has been reported
58 Dermatology 2004;208:55–59
before [11–13]. Residual dyschromia even after successful
treatment is a well-known problem [13, 14]. In our study
complete normalization of the colour was observed in
only 4 (20%) patients in the fluconazole group. Other
studies with single-dose fluconazole have reported a very
high clinical cure rate of 74 and 100% at the end of 3 and
6 weeks, respectively [4, 5].
In the itraconazole group, only 1 patient achieved a
complete clinical cure. Three of the 4 culture-negative
patients still had residual hypopigmentation. The differ-
ence between the response to the two drugs for most of the
clinical parameters was not statistically significant except
that scaling cleared earlier in patients on fluconazole.
Fluconazole was found to be significantly better than
itraconazole as regards the mycological cure (65 vs. 20%).
Our results of 65% negativity by KOH at 8 weeks are
comparable to a study done previously from this region
which reported mycological cure in 63.4% patients, 4
weeks after treatment with fluconazole [14]. Rao and
Rajashekhar [5] achieved mycological cure in 92% of
their patients as observed by KOH examination at 6
weeks after fluconazole therapy. In the itraconazole
group, we observed mycological cure in only 4 patients.
Culture negativity did not correlate with the clinical
cure in our study. Clinical cure was found in only 4 of the
13 culture-negative patients in the fluconazole group.
Conversely in the study by Faergemann [4], clinical cure
was achieved in 12/17 (74%) patients, even when culture
was still positive. It was stated that persistence of culture
positivity was likely to end up in clinical relapse after a
variable period [4, 5].
In our study, the relapse rate was 35% in the flucona-
zole group and 60% in the itraconazole group at the end of
8 weeks of follow-up. The differences are statistically sig-
nificant. Rao and Rajashekhar [5] found a relapse rate of
only 8% in their patients at 8 weeks after a single dose of
fluconazole. There was no relapse after 6 weeks of follow-
up in the pilot study of Faergemann using single-dose flu-
conazole [4].
The safety of both these drugs is well documented in
the literature [10, 15, 16]. Most common side-effects
noted with both these drugs are mild gastro-intestinal dis-
turbances [10, 16]. In our study, only 1 patient in the flu-
conazole group complained of headache and loose stools
persisting for a day. It could be a chance occurrence.
Our results showed that fluconazole (400 mg) given as
a single dose for the treatment of pityriasis versicolor is
more effective as compared to a single dose of itracona-
zole in terms of reduction of scaling, change in the colour
of the affected skin and relapse rates.
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 Relapse after treatment is a common problem in pity-
riasis versicolor [16]. We found a direct correlation be-
tween the culture positivity and relapse. The presence of
M. furfur in the perilesional skin was more important in
the causation of relapse in both groups. From these obser-
vations, it can be hypothesized that complete elimination
of M. furfur which is part of the resident flora with anti-
fungals is not a likely possibility. The drugs only reduce
the colony counts to a level where it is unlikely to produce
the disease. It is well known that the mere presence of M.
furfur in an area may not lead to appearance of lesions.
Only when – because of external factors like heat, humidi-
ty or occlusion – overgrowth of the organism occurs
beyond a ‘critical level’ do the lesions appear. There is a
theoretical possibility that the disposed individuals with
frequent relapses might benefit from the additional topi-
cal therapy and/or more frequent administration of oral
drugs. Quantitative culture from the lesional and perile-
sional skin helped us to understand the relation between
positivity for M. furfur and response/relapse and the effect
of drugs on the colony count more precisely.
More studies on a higher number of patients under
variable external conditions may help us to understand
the relapses better.

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