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July 2014

855

Copyright 2014

ORIGINAL ARTICLE

VOLUME 13 ISSUE 7
Journal of Drugs in Dermatology

Can Pityriasis Versicolor Be Treated With 2%

Ketoconazole Foam?
Wendy C. Cantrell DNP CRNP and Boni E. Elewksi MD
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL

ABSTRACT

JD

BACKGROUND: Pityriasis (tinea) versicolor is a superficial fungal infection of the stratum corneum caused
by Malassezia species. The diagnosis is made clinically by its classic appearance of round or oval macules
with fine scale that may be hyperpigmented or hypopigmented. Diagnosis may also be confirmed with
microscopic evaluation of skin scrapings that reveal both short, stubby hyphae, and spores under KOH
preparation. Ketoconazole is an important treatment of pityriasis versicolor but is primarily used in cream
formulas. A foam vehicle has been shown to improve drug absorption through the stratum corneum and
distribution in the skin. This study has assessed the safety and efficacy of ketoconazole 2% foam in
treatment of pityriasis versicolor.
METHODS: Ketoconazole 2% foam was evaluated in a single-center, open-label, one-arm pilot study
which enrolled eleven subjects to gain 10 evaluable subjects aged 21 years and older with a clinical
diagnosis of tinea versicolor and positive KOH using calcofluor. The subjects came for 4 scheduled visits
(baseline, week 1, week 2, and week 4) and were instructed to apply ketoconazole 2% foam to all affected
areas twice daily for 2 weeks. At each visit, mycological and clinical assessment of a target area was done,
along with static global assessment and body surface area estimation of the disease in each subject.
Patient questionnaires were given at baseline and at week 2 to rate pruritus and satisfaction with the foam.
RESULTS: At the week 2 visit, following the treatment period, three out of ten evaluable subjects had
negative skin samples prepared with KOH/calcifluor. Of these three, one subject later showed recurrence
of fungal elements consistent with tinea versicolor at the week 4 follow-up visit. The other negative
subjects remained negative and four additional subjects tested negative at week 4. Three subjects with
positive samples at week 4 had only yeast forms without hyphae present. Investigator ratings of the target
area were averaged for each clinical feature and demonstrated improvement in scale, hyper- or
hypopigmentation, erythema, and induration throughout the study. Average pruritus score increased
slightly 1 week after the baseline visit, but then improved steadily over the remaining visits. The
investigators static global assessment rating showed improvement from mild to moderate disease at
baseline to minimal or no disease at week 4 in 7 subjects. The remaining subjects showed neither
improvement nor progression of the disease throughout the study. One out of the eleven subjects enrolled
did not complete the study. One subject noted mild skin burning sensation after application of medicine.
Post-treatment patient questionnaires indicated overall satisfaction with the foam vehicle.
LIMITATIONS: This was a single-arm, open-label, noncomparative trial.
Conclusion: Ketoconazole 2% foam improved overall clinical assessment and microscopic evidence of
pityriasis versicolor in all subjects with favorable patient feedback regarding the novel foam vehicle.

J Drugs Dermatol. 2014;13(7):855-859.

INTRODUCTION

Pityriasis versicolor, also known as tinea versicolor, is a common superficial fungal infection caused by

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Malassezia that affects the top layer of skin by causing well-demarcated hypo- or hyperpigmented, round or
oval macules with fine scale. The lesions may be singular or may coalesce and most likely present on trunk
and upper arms, though some cases involving scalp, face, neck, genitalia, axilla, finger webbing, and
antecubital fossa have been reported.1 Pityriasis versicolor may be found on both men and women in areas
all over the world, but in tropical climates, up to 40% of the population could be effected.2 The diagnosis is
made clinically by its classic appearance and may be confirmed by evaluating the mycology of skin scrapings
prepared with potassium hydroxide (KOH), which reveals both short, stubby hyphae and budding yeast
spores. Often described as spaghetti and meatballs for its appearance under the microscope,1,3 Malassezia
is a lipophilic organism found in the skins outermost barrier, the stratum corneum. Most species of
Malassezia are a part of normal skin flora, but as conditions become more favorable, the organism evolves
from the physiologic blastospore form into its pathologic mycelial form.2 Favorable conditions include warmer
temperatures, increased humidity, immunodeficiency or immunocompromise, elevated corticosteroids,
pregnancy,4 and malnourishment.5 These conditions generally cause increased activity of sebaceous glands,
which helps create the lipid-rich environment needed for Malassezia to thrive. This quality seems to explain
why pityriasis versicolor, is rarely found in very young or very elderly patients,2,6 but usually appears in
postpubertal and mature ages when the sebaceous glands are most active.2
Complete eradication of pityriasis versicolor may be difficult to achieve, especially knowing that the causative
agent lives on healthy skin, even after treatment.6 Assuming that exogenous and endogenous conditions
change over time and may become more or less favorable for Malassezia derived skin changes, it is easy to
see how recurrence of pityriasis versicolor is common. 2,5 Faergemann quotes up to 60% recurrence after
one year and 80% after two years post-treatment of pityriasis versicolor.
Ketoconazole is a common treatment for pityriasis versicolor,4 and well-known for its anti-Malassezia effect.
Studies have tested antifungal activity against the Malassezia species and deem ketoconazole as an
appropriate fungistatic medication.7 The oral formulation may be preferred in more severe cases of PV but
may cause undesired side effects, such as liver toxicity. 2 Since Malassezia infection only injures the
superficial stratum corneum, a topical preparation is most practical. As topical formulations were developed,
most pityriasis versicolor was treated with a ketoconazole cream. Within the past decade, however, studies
have exhibited that a novel foam vehicle has faster penetration of skin barriers, as well as higher
concentration of medication delivered to the stratum corneum, the exact site of pityriasis versicolor infection.8
Abramovits et al reviewed a 2% ketoconazole foam and determined that the epidermis retains the drug longer
when using a foam vehicle versus a cream. While approval of ketoconazole foam exists for treatment of
seborrheic dermatitis, we propose that it may also be effectively used against pityriasis versicolor, particularly
because of the shared involvement of Malassezia species.
METHODS

Subjects
Ten subjects with clinically diagnosed pityriasis versicolor were to be evaluated for the study. Subjects of
either gender were to be aged 19 years and older. In addition to clinical presentation of pityriasis versicolor,
inclusion criteria also deemed microscopic confirmation of pityriasis versicolor in each subject by scraping the
scaly border of the lesion with a #15 blade, fixing it on a slide with calcofluor KOH solution, and identifying
fungal features of short, stubby hyphae and round yeast spores under a light microscope. None of the
subjects had received any topical antifungal treatment to the affected area in the past 30 days, nor any
topical steroid treatment to the affected area in the past 14 days. Other exclusion criteria included
immunocompromising conditions, medical or psychiatric conditions that may interfere with treatment or
compliance, other dermatologic conditions in the region of treatment sites that may interfere with study
results, pregnancy, breast-feeding, or woman of child-bearing potential unwilling to use a reliable method of
contraception during the study.

Study Design
This one-arm, open-label pilot study was designed to assess the efficacy and safety of 2% ketoconazole
foam in treating pityriasis versicolor, and gain feedback about subjects satisfaction with the foam vehicle.
After obtaining written informed consent from the subjects, four visits (baseline, week 1, week 2, and week 4)

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were scheduled. At baseline visit, a target area of affected skin was selected and then assessed by the
investigator at each visit for scale, erythema, hypo-/hyperpigmentation, induration, and pruritus. The
investigator scored by visual inspection and also by asking the subject about pruritus on a 5-point scale with
values of 0=none, 1=minimal, 2=mild, 3=moderate, 4=severe. Investigator static global assessment (ISGA) of
the same features was also scored on the same scale at each visit. Body surface area (BSA) of disease was
assessed using the investigators palm as equaling 1% BSA. Photographs and specimen collection of target
area, were also done at each visit. Skin samples from target lesion were analyzed at a single, central
mycology laboratory to provide objective data. Samples were rated by the lab as follows: consistent with tinea
versicolor, yeast forms only, rare yeast forms, or negative. A patient questionnaire to assess pruritus was
given at baseline and week 2 visits, plus an additional questionnaire to rate patient satisfaction with the foam
vehicle. The study design was approved by the University of Alabama at Birmingham Institutional Review
Board.

Treatment Protocol
The study medication was a 2% ketoconazole foam dispensed to all subjects at baseline visit. Each patient
was instructed to apply the foam to all affected areas twice daily for 2 weeks. After treatment, subjects
returned for a follow-up visit at week 4. Missed doses, adverse events, and any additional concomitant
medications were assessed at week 1, week 2, and week 4.

Evaluation of Efficacy and Safety

While no minimum disease activity was required to participate in the study, all subjects demonstrated 2=mild
to 3=moderate ratings on ISGA at baseline, therefore, improvement to 1=minimal or 0=none on ISGA at or
before week 4 visit was considered effective treatment with ketoconazole 2% foam. The fungal lab reports for
each skin sample were also used in assessing treatment efficacy. Successful microscopic treatment of the
subjects pityriasis versicolor was defined as having negative skin samples at or before week 4. Adverse side
effects were assessed at each visit by asking the patient for details of any adverse event experienced, as well
as by examining the areas where medication was applied.
RESULTS

Patient Population
Eleven adult subjects with clinical and microscopic diagnosis of pityriasis versicolor were recruited and
consented for the study in order to have ten evaluable subjects. One subject was lost to follow-up after the
baseline visit. Actual age range of subjects was between 21 and 55 years old. Eight female and 3 male

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subjects participated in the study. The subjects pityriasis versicolor infection was located on the back (n=4),
chest (n=3), abdomen (n=2), neck (n=1), and antecubital fossa (n=1). One patient declared herself African
American or black and the other ten declared themselves Caucasian. (Table 1)

Efficacy
By the end of treatment (week 2 visit), three subjects had negative skin samples, confirming microscopic
clearing of disease. By the week 4 follow-up visit, an additional four subjects were found to have negative
skin samples prepared with KOH/calcifluor, though one subject with microscopic clearing at week 2 relapsed.
Two out of the three negative subjects from week 2 remained negative at week 4 follow-up. Overall, a total of
seven subjects out of eleven achieved negative microscopic results after treatment with one recurrence at
the week 4 follow- up visit. Among the remaining subjects, two skin samples yielded only yeast forms without
hyphae and one subjects skin had rare yeast only at final visit.
Investigator ratings scored as 0=none, 1=minimal, 2=mild, 3=moderate, 4=severe for each clinical feature of
the target area were averaged and demonstrated in Table 2.
Improvement in scale, hyper- or hypopigmentation, erythema, and induration was recorded throughout the
study. Though the average pruritus score increased slightly at 1 week after the baseline visit, it improved
steadily over the remaining visits. Although there was no disease activity margin as inclusion criteria, a
majority of subjects began the study with moderate disease activity (investigator score of 3) in pigmentation
(n=9)

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and mild to moderate activity (investigator score 2 or higher) in scale (n=9) and erythema (n=9). Fewer
subjects exhibited similar ratings in induration (n=4), and pruritus (n=4). By week 4, many subjects achieved
disease ratings of 0=none or 1=minimal in the categories scale (n=8), erythema (n=7), induration (n=9), and
pruritus (n=9), but far less in pigmentation (n=4).
The ISGA at week 4 rated 7 subjects as 1=minimal or 0=none with remaining subjects showing neither

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improvement nor progression of disease throughout trial. Overall body surface area (BSA) of disease
averaged 4.5% at baseline and 3.0% at the week 4 follow-up visit. Six subjects exhibited a lower BSA at
week 4 than at baseline. Interestingly, seven subjects presented clinical improvement on ISGA, and although
all of these seven were not mycologically cleared, two additional subjects demonstrated objective clearing
with negative skin samples.

Safety
One participant reported mild skin burning sensation during the treatment period, which was considered to be
likely related to study medication. Another patient reported a strep throat infection, which was treated with
antibiotics and considered not related to study drug.

Patient Assessment
Subjects graded their degree of pruritus before and after treatment with the study medication by circling a
number 0-10 on a linear scale where 0=no itching and 10=severe itching. The data is presented in Table 3.
Evaluation of the foam vehicle was also done by subjects in a questionnaire given at week 2 visit. Each
statement regarding the foam was scored as follows: 5-Strongly Agree, 4-Agree, 3-Neutral (neither agree nor
disagree), 2-Disagree, 1-Strongly Disagree. As noted, all average scores were greater than 3.6 out of 5,
indicating overall satisfaction with the foam. The statements and average ratings are shown in Table 4.
DISCUSSION
In this pilot study, we demonstrated the efficacy and safety of 2% ketoconazole foam in the treatment of
pityriasis versicolor in a small study population. Subjects applied the study medication twice daily for two
weeks to areas of clinically and mycologically diagnosed pityriasis versicolor lesions. Sixty percent of those
who completed therapy experienced successful treatment as measured by negative microscopy of skin
samples and 70% ended the trial with minimal or no clinical features of the disease as demonstrated by ISGA
score of 1 or less. This response is comparable to that claimed by Kyle and Dahl after 2 weeks of daily or

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twice daily applications of azole topical therapies. Despite literature advising prophylactic therapy to prevent
recurrence of pityriasis versicolor as anticipated in 50% of successfully treated subjects, 5 our study
prescribed no therapy during the two weeks following treatment period and only had one subject return with
mycologic evidence of fungal elements consistent with tinea versicolor in week 4. This prolonged antifungal
action may in fact be due to the foam vehicle delivering a higher concentration of medication to the site of
disease.
In a study recorded by Elewski et al, which assessed the safety and efficacy of 2% ketoconazole foam in
treatment of seborrheic dermatitis, the most common side effects listed were mild and transient burning,
stinging, and itching at application site. Many studies also include ketoconazole foam as therapy for
seborrheic dermatitis, however, our literature search for treatment of pityriasis versicolor only revealed one
study in France with a 2% ketoconazole foaming lotion, which yielded favorable results. The French study
recorded two subjects who experienced tingling of the skin after application of the foam.14 Another review
noted that 10% of subjects using either an active or placebo foam vehicle experienced burning at the
application site.12 The incidence of post-treatment mild burning effect reported in our study was similar, and
the adverse event was not severe enough for the patient to discontinue treatment.
The results from our study should be confirmed through additional trials of larger subject groups. In addition,
no conclusion may be made about the long-term effectiveness or safety of ketoconazole foam in treatment of
pityriasis versicolor. Although this study population was predominately Caucasian and does not represent the
worldwide distribution of pityriasis versicolor, the age range of subjects and sites of disease are comparable
to typical pityriasis versicolor patients.1,2,4,6
Equal efficacy of ketoconazole cream and gel formulations in destruction of Malassezia has been
suggested,15 but recently proven benefits of a novel foam vehicle, particularly in skin areas most frequently
affected by pityriasis versicolor, such as back and abdomen,8 suggest that ketoconazole foam could be a
new, preferred therapy for pityriasis versicolor. As denoted in Table 5, our subjects rated the cosmetic appeal
of the foam vehicle favorably in all categories.
As patient satisfaction is increased with medication aesthetics and vehicle, we believe patient compliance will
also improve. As mentioned during an evaluation of 2% ketoconazole foam in the treatment of seborrheic
dermatitis on multiple body regions, 13 the possibility of using one versatile therapy such as 2%
ketoconazole foam for the variety of body sites that may be affected by pityriasis versicolor, could help
decrease cost, maximize benefits, minimize adverse reactions, and improve patient compliance during
treatment of pityriasis versicolor.
ACKNOWLEDGMENTS
We would like to recognize Judy Warner of Fungal Reference Lab at University of Alabama at Birmingham for
her assistance in mycologic evaluation of skin samples. This study was supported by Stiefel Laboratories, a
GSK company, via funding and provision of study drug.
DISCLOSURES
The authors have not declared any relevant conflicts.
REFERENCES
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(16): 19-33.
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2000 Mar-Apr; 1(2): 75-80.
3. Levin NA. Beyond Spaghetti and Meatballs: Skin Diseases Associated with the Malassezia Yeasts.
Dermatol Nurs. 2009 Jan-Feb; 21(1): 7-13, 51.
4. Mellen LA, Vallee J, Feldman SR, Fleischer, Jr, AB. Treatment of pityriasis versicolor in the United

Journal of Drugs in Dermatology. All Rights Reserved. No reproduction or use of any portion of the contents of
these materials may be made without the express written consent of JDD. If you feel you have obtained this
copy illegally, please contact JDD immediately. Licensed to khalidariekas@gmail.com.

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States. J Dermatol Treat. 2004; (15): 189-192.

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13. Elewski BE, Abramovits W, Kempers S, Schlessinger J, Rosen T, Gupta AK, et al. A Novel Foam
Formulation of Ketoconazole 2% for the Treament of Seborrheic Dermatitis on Multiple Body Regions.
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14. Rekacewicz I, Guillaume JC, Benkhraba F, Archimbaud A, Baspeyras M, Boitier F et al. [A doubleblind placebo-controlled study of a 2 percent foaming lotion of ketoconazole in a single application in
the treatment of pityriasis versicolor]. Ann Dermatol Venereol. 1990; 117(10): 709-11. French.
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AUTHOR CORRESPONDENCE

Wendy C. Cantrell DNP CRNP

E-mail: wcantrell@uabmc.edu

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