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Leung AKC, Barankin B, Lam JM, et al. Drugs Context. 2022;11:2022-9-2. https://doi.org/10.7573/dic.2022-9-2 1 of 20
ISSN: 1740-4398
drugsincontext.com
REVIEW
Tinea versicolor: an updated review
Alexander KC Leung1, Benjamin Barankin2, Joseph M Lam3,4 , Kin Fon Leong5, Kam Lun Hon6,7
1Department of Pediatrics, The University of Calgary, and The Alberta Children’s Hospital, Calgary,
Alberta, Canada; 2Toronto Dermatology Centre, Toronto, Ontario, Canada; 3Department of Pediatrics
and Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, BC, Canada;
4BC Children’s Hospital, Vancouver, BC, Canada; 5Pediatric Institute, Kuala Lumpur General Hospital,
Kuala Lumpur, Malaysia; 6Department of Paediatrics, CUHK Medical Centre, Hong Kong Institute of
Integrative Medicine, Hong Kong; 7Jockey Club School of Public Health and Primary Care,
The Chinese University Hong Kong, Hong Kong
Introduction
Tinea versicolor (also known as pityriasis versicolor) is
a common supercial fungal infection of the skin. Pa-
tients with tinea versicolor typically present with asymp-
tomatic hypopigmented or hyperpigmented, nely
scaled, oval or round macules/patches on the trunk
and upper arms.1 Patients occasionally report pruri-
tus, particularly when the condition is more extensive.
The term ‘versicolor’ refers to the variable colours of
the skin lesions that may occur in this disorder. Clinical
manifestations of tinea versicolor are myriad, and the
differential diagnoses are broad. This review aims to
familiarize readers with the various clinical manifesta-
tions of tinea versicolor to avoid misdiagnosis, unneces-
sary investigations and mismanagement of the disease
and will also highlight the correct management of this
disease.
Abstract
Background: Tinea versicolor is a common supercial
fungal infection of the skin with various clinical manifes-
tations. This review aims to familiarize physicians with
the clinical features, diagnosis and management of tin-
ea versicolor. Methods: A search was conducted in July
2022 in PubMed Clinical Queries using the key terms “tin-
ea versicolor” OR “pityriasis versicolor”. The search strat-
egy included all clinical trials, observational studies and
reviews published within the past 10 years. Results: Tin-
ea versicolor is caused by Malassezia species, notably
M. globosa, M. furfur and M. sympodialis. The condition
is characterized by scaly hypopigmented or hyperpig-
mented macules/patches, primarily located on the up-
per trunk, neck and upper arms. The diagnosis is usually
based on characteristic clinical features. If necessary, a
potassium hydroxide preparation test can be performed
to reveal numerous short, stubby hyphae intermixed with
clusters of spores. Most patients with tinea versicolor re-
spond to topical antifungal therapy, which has a better
safety prole (fewer adverse events, fewer drug interac-
tions) and lower cost compared to systemic treatment
and is therefore the treatment of choice. Oral antifungal
therapy is typically reserved for patients with extensive
disease, frequent recurrences or disease that is refrac-
tory to topical therapy. Advantages of oral antifungal
therapy include increased patient compliance, shorter
duration of treatment, increased convenience, less time
involved with therapy and reduced recurrence rates. On
the other hand, oral antifungal therapy is associated
with higher cost, greater adverse events and potential
drug–drug interactions and is therefore not the rst-line
treatment for tinea versicolor. Long-term intermittent
prophylactic therapy should be considered for patients
with frequent recurrence of the disease. Conclusion: Se-
lection of antifungal agents depends on several factors,
including efcacy, safety, local availability, ease of ad-
ministration, likelihood of compliance and potential drug
interactions of the antifungal agent.
Keywords: evoked scale sign, uconazole, itraconazole,
ketoconazole, Malassezia species, pityriasis versicolor,
selenium sulde, terbinane, zinc pyrithione.
Citation
Leung AKC, Barankin B, Lam JM, Leong KF, Hon KL. Tinea
versicolor: an updated review. Drugs Context. 2022;11:
2022-9-2. https://doi.org/10.7573/dic.2022-9-2
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ISSN: 1740-4398
Methods
A search was conducted in July 2022 in PubMed Clinical
Queries using the key terms “tinea versicolor” OR “pityri-
asis versicolor”. The search strategy included all clinical
trials (including open trials, non-randomized controlled
trials and randomized controlled trials), observation-
al studies and reviews (including narrative reviews and
meta-analyses) published within the past 10 years. Only
papers published in the English literature were included
in this review. The information retrieved from the search
was used in the compilation of this article.
Review
Aetiopathogenesis
Tinea versicolor is caused by dimorphic lipophilic and
lipid-dependent yeasts in the genus Malassezia
(formerly known as Pityrosporum) species, notably Mal-
assezia globosa (M. globose), M. furfur and M. sympodi-
alis.2–12 Other species that have been implicated include
M. restricta, M. obtuse, M. sloofae, M. pachydermatis
and M. japonica.13–16 These yeasts are normal commen-
sals on the skin surface.17,18 Skin colonization increases
with age; 25% of children and almost 100% of adults are
affected.19 Tinea versicolor occurs when the saprophytic
yeast or budding form of the organism converts to the
pathogenic hyphal or mycelial form. The fungal infection
is localized to the stratum corneum. Predisposing fac-
tors for the conversion include a hot and humid environ-
ment, hyperhidrosis, application of oily lotion or cream
to the skin, wearing of masks, excessive lipid-containing
sebaceous secretions, malnutrition, poor general health,
use of oral contraceptives, pregnancy, diabetes melli-
tus, use of topical or systemic corticosteroids, Cushing
disease, Helicobacter pylori infection, immunodeciency
and genetic predisposition.20–36 A recent study showed
oxidative stress has no role in the pathogenesis of tinea
versicolor.29
Hypopigmented lesions (more commonly noted in dark-
er skin tones) seen in tinea versicolor are thought to
result from damage to melanocytes and inhibition of ty-
rosinase by azelaic acid (a dicarboxylic acid) produced
by the Malassezia species involved, small melanosomes
and accumulation of lipid-like material in the stra-
tum corneum blocking ultraviolet light.37–40 On the other
hand, hyperpigmented lesions (more commonly not-
ed in lighter skin tones) may result from a hyperaemic
inammatory response elicited by Malassezia species,
more tonolaments in the granulosum, a thicker stratum
corneum and abnormally large melanosomes.8,38,41,42
Keratinase, produced by the Malassezia species, causes
loosening of the stratum corneum with subsequent
scale formation.43,44
Prevalence
Tinea versicolor occurs worldwide. The prevalence is
very high in hot and humid climates.35 In some tropical
countries, the prevalence is as high as 50% whereas, in
Sweden, the prevalence is as low as 0.5%.17,45,46 Tinea versi-
color is most common amongst adolescents and young
adults, presumably because of increased sebum pro-
duction in individuals of these age groups.47–55 Although
uncommon, the condition can occur in young children
and elderly individuals.47–55 Rarely, tinea versicolor has
been reported in infants including neonates.56–60 Tinea
versicolor is slightly more common in men than in wom-
en presumably due to increased sebaceous activity in
men.8,47,54 A positive family history of tinea versicolor is
present in approximately 17% of affected individuals.61,62
The incidence of tinea versicolor appears to be the same
in all races, though the change in skin pigmentation is
more visually apparent in dark-skinned individuals.8
Histopathology
Histological ndings include parakeratosis, hyperkerato-
sis, slight acanthosis and a mild supercial, perivascu-
lar inltrate in the upper dermis.63 Haematoxylin-eosin,
methenamine silver or periodic acid–Schiff staining re-
veal the presence of yeast in a ‘spaghetti and meatballs’
pattern in the stratum corneum.63–65 Hyperpigmented
lesions tend to contain more hyphae and spores than
hypopigmented lesions.62,65,66 In hypopigmented lesions,
the horny layer tends to be slightly hyperkeratotic and
there may be a decrease in melanosomes in the stra-
tum spinosum.39,45
Clinical manifestations
Tinea versicolor is characterized by mildly scaly hypop-
igmented or hyperpigmented macules/patches, most
commonly affecting areas of skin that are rich in sebum
production such as the trunk (especially the upper part),
neck, shoulders and upper arms (Figures 1–3A).19,21,24,67–69
Facial involvement is less common in adults. On the oth-
er hand, facial involvement is common in children and
may be the only site involved (Figure 3B).19,70 The fore-
head is the usual site of facial involvement.71–74 Other
sites of involvement, such as forearms and thighs, are
less common (Figure 4).75 Unusual sites of involvement
include the scalp, eyelid, axilla, areola, periareolar area,
antecubital fossae, popliteal fossa, pubis, groin, perine-
um, penile shaft and vulva.75–86
Typically, lesions arise as multiple, small, oval or round,
well-demarcated, round or oval macules.8 Smaller
macules may have a powdery appearance because
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of aking.87 Over time, the macules enlarge radially and
coalesce into patches or very supercial plaques.8 The
lesions are covered with a ne scale, which is often dif-
cult to appreciate upon clinical examination. On the oth-
er hand, the scale becomes more apparent when the
lesion is stretched or scraped (the ‘evoked scale sign’)
(Figure 5A,B).1,44,88,89 It should be noted that burned-out or
treated lesions usually lack scale.90 In patients with tinea
versicolor, when the affected skin is wiped with a piece of
wet cloth and scraped, it yields a considerable amount
of dirty brown keratin. Tinea versicolor lesions are typi-
cally asymptomatic, although some patients complain
of mild pruritus,45 which may become worse in hot and
humid conditions.
The eruption varies in colour from individual to individual,
but each individual usually has lesions of a single hue.
Lesions are usually evenly pigmented. In general, hyper-
pigmented lesions tend to occur in fair-skinned patients
whereas hypopigmented lesions tend to occur in dark-
skinned individuals.8,91 When hyperpigmented lesions oc-
cur in dark-skinned individuals, they are often grey-black,
dark brown or black whereas these are often tan, light
brown, red or pink in fair-skinned individuals.1,8,40 Lesions
may become more apparent following exposure to the
sun and are thus more noticeable during the summer
months. Mixed hyperpigmented and hypopigmented le-
sions may be found, especially in the axilla and groin.8,41,91
Several morphological variants have been described.
An inverse form of tinea versicolor has been described,
especially in patients who are immunocompromised.92
Some authors favour labelling this variant as ‘tinea In-
Versicolor’.92 In this variant, lesions tend to localize in the
exural areas (axilla, elbow, popliteal fossa and groin)
and isolated areas of the extremities (Figure 6).92–94
Atrophying tinea versicolor typically presents with nu-
merous, hypopigmented or erythematous/violaceous,
round to oval, scaly lesions with a typically depressed
appearance.95–98 Lesions tend to cluster and are gen-
erally uniform in size (a few millimetres to several centi-
metres) on the same patient and may have a wrinkled
surface.99 The atrophy is limited to the area affected
by tinea versicolor.100 The exact aetiology of the atro-
phy is not known. It is postulated that the atrophy may
result from prolonged use of topical corticosteroids or
delayed type IV hypersensitivity to epicutaneous anti-
gens from the Malassezia species.100–104 Folliculocentric
tinea versicolor involves the hair follicle and presents
with asymptomatic hypopigmented or hyperpigment-
ed macules located exclusively around the follicles105,106;
these macules may merge into patches.106 The disorder
Figure 1. Tinea versicolor presenting as multiple hypopigmented macules and
patches on the chest (part a) and left shoulder and upper back (part b).
a) b)
Figure 2. Multiple erythematous macules and patches
on the upper abdomen and chest.
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If necessary, a potassium hydroxide (KOH) preparation
test can be performed; examination of scrapings from
the border of the lesion soaked with 10–15% KOH reveals
numerous short, stubby hyphae intermixed with clusters
of spores (the so-called ‘spaghetti and meatballs’ ap-
pearance) (Figure 8).51 KOH helps to dissolve the keratin
and debris so that the hyphae and spores can be read-
ily visible by microscopy. The border of the lesion con-
tains the highest number of fungi. Because the standard
Figure 3. Multiple hypopigmented macules and patches on the neck and face of a
5-year-old child (part a) and on the face of a 10-year-old child (part b).
a) b)
Figure 4. Multiple hypopigmented macules and
patches on the left forearm.
is typically localized to the chest and back.106,107 A Wood
lamp examination reveals folliculocentric uorescence
in hypopigmented areas.107 Papular tinea versicolor pre-
sents with multiple, asymptomatic, monomorphic, red-
brown papules (2–3 mm), which may or may not show
the ne overlying scale.105 They are usually found on
the trunk.105 Confetti-like tinea versicolor presents with
asymptomatic confetti-like spots with slightly scaly sur-
faces (Figure 7). The spots are usually bilateral and sym-
metrically distributed. The formation of scaly, guttate
and coalescent hypopigmented patches or plaques is
unique in African Americans; this variant is colloquially
known as acid skin.108
Diagnosis
The diagnosis is usually clinical, based on the charac-
teristic features (multiple hypopigmented or hyper-
pigmented, centrally coalescing, oval to round, nely
scaling macules or patches and the ‘evoked scale sign’).35
However, the varied presentations of tinea versicolor
may be confusing to an inexperienced physician. Exam-
ination of the lesion with a Wood lamp (ltered ultravio-
let light with a peak of 365 nm) may show gold-yellow,
yellowish-green or coppery-orange uorescence, although
some lesions do not uoresce.17,56 The uorescence may
include areas surrounding clinically visible lesions, sug-
gesting that the fungal infection is spreading.17
Dermoscopy is a useful ancillary tool for the diagnosis
of tinea versicolor.109–114 Typical dermoscopic ndings in-
clude alteration in the background pigmentation, a ‘con-
trast halo’ sign (a ring of hypopigmentation surrounding
the primary lesion of increased pigmentary network in a
hyperpigmented lesion or a ring of increased pigmen-
tation surrounding the primary lesion of decreased pig-
mentary network in hypopigmented lesion), ne scale on
the involved skin, folliculocentricity and hypopigmenta-
tion of the invaded hair follicle.110–114
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KOH mount does not show a colour contrast, ink blue,
Parker blue-black ink, methylene blue, chlorazol black E,
Swartz–Lamkin, Swartz–Medrik or Chicago Sky Blue (CSB)
6B staining may be added for better visualization of the
causative organism.35,115,116 Thus far, the contrast stain
containing 1% CSB 6B has the greatest specicity and
sensitivity.115
Dierential diagnosis
The differential diagnoses are broad, especially those
with unusual presentations. The differential diagnosis
of hypopigmented lesions of tinea versicolor includes
pityriasis alba, nevus anemicus, nevus depigmentosus,
idiopathic guttate hypomelanosis, eruptive hypomela-
nosis, progressive macular hypomelanosis, leukoderma
punctate, hypomelanosis of Ito, vitiligo, ash-leaf spot in
tuberous sclerosis, corticosteroid-induced hypopigmen-
tation, arsenicosis, leprosy, hypopigmented mycosis fun-
goides and post-inammatory hypopigmentation.117–124
On the other hand, hyperpigmented lesions of tinea
versicolor should be differentiated from tinea corporis,
pityriasis rosea, pityriasis rotunda, tinea imbricata, acan-
thosis nigricans, terra rma-forme dermatosis, café
au lait macules, ephelides, solar lentigines, melasma,
erythrasma, guttate psoriasis, nummular eczema, seb-
orrheic dermatitis, contact dermatitis, post-inammatory
hyperpigmentation, type 1 (classic adult) pityriasis ru-
bra pilaris, secondary syphilis, conuent and reticulat-
ed papillomatosis (also known as Gougerot–Carteaud
syndrome), and epidermodysplasia verruciformis (also
known as Lewandowsky–Lutz dysplasia).125–138 The dis-
tinctive features of many of these conditions help to dif-
ferentiate them from tinea versicolor.
Complications
Skin discolouration can be cosmetically unsightly and
socially embarrassing especially if it occurs in exposed
areas of the body. This may have an adverse effect on
quality of life. The discolouration of the skin (without
Figure 5. Hyperpigmented macules with minimal desquamation on the upper back
(part a) and with prominent desquamation on the upper back after the skin lesion was
scrapped (the evoked scale sign, part b).
b)a)
Figure 6. Hyperpigmented macules in the axillary
region of a 17-year-old male with tinea InVersicolor.
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overlying scaling) may persist for weeks to months even
after completion of successful therapy. The disappear-
ance of the scale is evidence that the hyphal yeast has
been eradicated.44 A preliminary study showed that top-
ical application of cycloserine, a transaminase 1 inhib-
itor, to the hyperpigmented lesions of tinea versicolor
twice a day for 5 days resulted in complete clearing of
the hyperpigmentation.139 Well-designed, large-scale,
multicentre, randomized, placebo-controlled trials are
needed to conrm or refute this nding.
Hair thinning and/or hair loss within the tinea versicolor
lesions has been reported.140 In a study of 39 patients with
tinea versicolor, hair thinning and/or hair loss within the
tinea versicolor lesions occurred in 24 (61.5%) patients.140
Hair thinning and/or hair loss occurred most commonly
on the forearms, abdomen, neck and, in men, the beard
area.
Prognosis
The prognosis is good. Mycological cure is usually
achieved soon after antifungal treatment. Tinea versi-
color tends to persist for years if left untreated.141–143 The
disorder has a high recurrence rate, especially in patients
with a positive family history of tinea versicolor.51,63,144,145
Framil et al. followed 102 patients with clinical and lab-
oratory diagnosis of tinea versicolor for one year.145 After
appropriate treatment, 33 (33.35%) patients did not have
any relapsing episodes, 54 (52.94%) patients had one to
four relapsing episodes and 15 (14.7%) patients had more
than four relapsing episodes.145 Patients with a positive
family history of tinea versicolor also have a longer du-
ration of the disease.51 Relapse rates as high as 80% fol-
lowing treatment have been reported.146
Management
Most patients with tinea versicolor respond to topical
antifungal therapy (Box 1). Additionally, topical anti-
fungal therapy has a better safety prole (fewer ad-
verse events, fewer drug interactions) and lower cost
compared to systemic treatment and is therefore the
treatment of choice. Oral antifungal therapy is typical-
ly reserved for patients with extensive disease, frequent
recurrences or disease that is refractory to topical ther-
apy (Box 1). For resistant or stubborn cases, combining
oral and topical therapies may be considered. Alterna-
tive and complementary therapies are still used in many
parts of the world.141,142
Topical antifungals
Many topical antifungals have proved to be effective
in the treatment of tinea versicolor. Various antifungal
preparations are available, including shampoos, foams,
gels, lotions and creams and are usually applied once
to twice daily.1 Shampoo is preferred when a large per-
centage of the body surface area is involved. Treatment
regimens range from a few days to 4 weeks.1,147 A sys-
tematic review of 93 controlled trials (n=8327) showed
that most topical antifungal medications used to treat
tinea versicolor are effective compared to placebo, with
numbers needed to treat of 1–3.147 Additionally, greater
cure rates can be achieved with higher concentrations
of active ingredients in the topical antifungal medica-
tions and longer duration of treatment.147,148 The most
common side-effects of topical antifungal agents are
skin irritation and contact allergy.35
Azoles
Topical azole drugs (for example, ketoconazole, econa-
zole, eberconazole, enaconazole, bifonazole, luliconazole,
Figure 8. KOH preparation of tinea versicolor showing
numerous short, stubby, hyphae intermixed with
clusters of spores (the so-called ‘spaghetti and
meatballs’ appearance).
Figure 7. Confetti-like spots on the left arm, left lateral
upper chest and armpit of a child with confetti-like
tinea versicolor.
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clotrimazole, miconazole, sertaconazole, sulconazole,
oxiconazole, fenticonazole, tioconazole, uconazole and
dapaconazole) have become an important treatment
class for tinea versicolor.149–165 This group of antifun-
gal agents are fungistatic and works by inhibiting the
P-450-dependent enzyme lanosterol 14-α-demethylase,
which is involved in the biosynthesis of ergosterol.166,167
Ergosterol is an important structural component of fun-
gal cell membranes.62,166 Impairment of biosynthesis of
ergosterol may limit cell function and cell growth.62,166
Randomized clinical trials have supported the efcacy
of various topical azole antifungal agents.149–165 Of the
topical azole antifungal agents, ketoconazole has been
most studied for the treatment of tinea versicolor. In ad-
dition to its ability to block the synthesis of ergosterol,
ketoconazole also has sebum-lowering effects by in-
hibiting androgenesis, anti-inammatory effects by in-
hibiting 5-lipoxygenase and barrier-restoring effects by
inhibiting hyperproliferation of keratinocytes.166,168–170 As
ketoconazole is highly lipophilic, it concentrates at sites
of tinea versicolor, thereby further increasing its efca-
cy.166 A 2019 systematic view of 40 randomized controlled
trials (n=4566) focusing on the use of topical ketocona-
zole for the treatment of Malassezia-related condi-
tions, such as tinea versicolor, showed that the efcacy
rate of topical ketoconazole for the treatment of tinea
versicolor was 71–89%.166 Topical azole drugs have a fa-
vourable safety. Adverse events are usually mild and
uncommon and include skin dryness, irritation, pruritus,
burning sensation and erythema.147 Rarely, allergic con-
tact dermatitis may occur.166
Studies have shown that combination therapies using
2% ketoconazole cream and 1% adapalene gel are more
efcacious in the treatment of tinea versicolor than
ketoconazole cream alone.171,172 To further improve the
efcacy of topical ketoconazole, future drug develop-
ment should focus on improving topical delivery to allow
better permeation of drugs into skin by using nanostruc-
tured lipid carriers, nanoparticles, microemulsions, co-
polymeric micelles, niosomes and microemulsions.156,173–176
In this regard, the development of topical gels contain-
ing uconazole-loaded solid lipid nanoparticles allows
uconazole to be used topically as the product exhib-
its skin penetration as a result of large particle surface
area and lm formation, enhancing contact between
uconazole and skin.156 Recently, it has been shown that
itraconazole-loaded aspasomal cream has a high-
er efcacy in the treatment of tinea versicolor than
non-formulated itraconazole cream alone.177
Terbinane
Terbinane, an allylamine antifungal, works by inhibit-
ing squalene epoxidase, thereby blocking the biosyn-
thesis of ergosterol.87,163,178 The accumulation of squalene
accounts for its fungicidal activity whilst ergosterol de-
ciency accounts for its fungistatic activity.163 The ef-
fectiveness of topical terbinane in the treatment of
tinea versicolor has been demonstrated in many double-
blind, randomized, placebo-controlled studies.178–181
There are very few good quality studies comparing the
efcacy of topical terbinane with topical azole drugs for
the treatment of tinea versicolor. Most trials are under-
powered to detect clinically meaningful differences. In an
open clinical trial, 60 adults with tinea versicolor were ran-
domized to receive either eberconazole 1% cream or terbi-
nane 1% cream once daily for 2 weeks.163 At the end of the
treatment period, there was a signicant improvement
in all the clinical parameters in both groups. Clinical
cure was present in 80% of patients in the eberconazole
group versus 63% of patients in the terbinane group.
Box 1. Treatment options for tinea versicolor.
A. Topical antifungals
1. Azoles (for example, ketoconazole, econazole, eberconazole, enaconazole, bifonazole, luliconazole,
clotrimazole, miconazole, sertaconazole, sulconazole, oxiconazole, fenticonazole, tioconazole, u-
conazole and dapaconazole)
2. Terbinane
3. Naftine
4. Butenane
5. Ciclopirox olamine
6. Non-specic topical antifungal agents (for example, selenium sulde, zinc pyrithione, propylene
glycol, Whiteld ointment, sulfur plus salicylic acid and benzoyl peroxide)
B. Oral antifungals
1. Itraconazole
2. Fluconazole
C. Laser and photodynamic therapies
D. Alternative therapies
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Mycological cure was achieved in 100% of patients in the
eberconazole group versus 97% of patients in the terbi-
nane group. No adverse events were noted. No relapse
was seen in patients treated with eberconazole but one
patient treated with terbinane had a relapse at the end
of 8 weeks. The authors concluded that both terbinane
and eberconazole were efcacious and safe in the treat-
ment of tinea versicolor but better response was ob-
served in patients treated with eberconazole. In another
study, 110 patients (≥14 years of age) with a clinical diag-
nosis of tinea versicolor conrmed by KOH microscopy
were randomized to receive either terbinane 1% cream
(n=55) or ketoconazole 2% cream (n=55) twice daily.182
Patients with negative mycological examination either
with clearance of skin lesions or presence of mild resid-
ual skin lesions were considered cure. Cure rates at the
end of the second, fourth and eighth weeks of treatment
were 72% and 64.3%, 81.2% and 69%, and 70.8% and 61.9%
for the terbinane group and the ketoconazole groups,
respectively. The authors concluded that there were no
signicant statistical differences between the terbinaf-
ine group and the ketoconazole group with regard to
the cure and recurrence rates. However, the numbers
of patients were higher and the recurrent cases were
lower in those treated with topical terbinane. Chopra
et al. randomized 50 patients with tinea versicolor con-
rmed by KOH microscopy to receive either terbinane
1% cream (n=25) or ketoconazole 2% cream (n=25) once
daily for 2 weeks.183 At the end of treatment, the clinical
and mycological cure rate was 96% for patients treated
with topical terbinane and 88% for patients treated with
topical ketoconazole; no adverse events were reported.
At 3 months of follow-up, the relapse rate was 8.33% in
patients treated with topical terbinane and 13.53% in
patients treated with topical ketoconazole.
Naftine
Naftine is a synthetic allylamine derivative with
broad-spectrum antifungal activity.184 The medication
works by blocking the biosynthesis of ergosterol via in-
hibition of squalene epoxidase, with resulting accumu-
lation of squalene, increase in fungal cell membrane
fragility and permeability, and inhibition of fungal cell
growth.184 As naftine is highly lipophilic, it can penetrate
efciently into the epidermis when applied topically.184
Open studies have shown that topical naftine is safe
and efcacious in the treatment of tinea versicolor.185–187
Well-designed, large-scale, randomized, double-blind
and placebo-controlled studies are necessary to further
elucidate its clinical efcacy and safety.
Butenane
Butenane, a synthetic benzylamine antifungal agent
with fungicidal activity, has also been used topically
for the treatment of tinea versicolor.188 The medication
inhibits squalene epoxidation with resultant blockage of
ergosterol biosynthesis. Small randomized controlled tri-
als have shown the clinical efcacy of topical butenane
in the treatment of tinea versicolor.189–190 In a randomized,
double-blind, parallel-group trial, the rate of mycolog-
ical cure in patients with tinea versicolor treated with
topical butenane and topical bifonazole was 87.5% and
83.3%, respectively, after 2 weeks of treatment.189 The rate
of effective clinical response in patients with tinea versi-
color treated with butenane and bifonazole was 91.7%
and 83.3%, respectively. There was no signicant statisti-
cal difference in terms of mycological cure and effective
clinical response between treatment with topical buten-
ane and topical bifonazole. Well-designed, large-scale,
randomized, double-blind and placebo-controlled
studies are necessary to determine the safety and ef-
cacy of topical butenane in treating tinea versicolor.
Ciclopirox olamine
Ciclopirox olamine is a hydroxypyridone with
broad-spectrum antifungal activity.62,191 The medica-
tion works by inhibiting the transport of essential el-
ements, which is required for the synthesis of the fun-
gal cell membrane.63 Ciclopirox olamine also interferes
with the synthesis of DNA, RNA and protein. Ciclopirox
olamine has been shown to be safe and effective for
the treatment of tinea versicolor in several studies.191–193
The safety and efcacy of topical ciclopirox olamine
in the treatment of tinea versicolor need to be sub-
stantiated by well-designed, large-scale, randomized,
double-blind and placebo-controlled studies.
Non-specic topical antifungal agents
Non-specic topical antifungal agents for the treatment
of tinea versicolor include selenium sulde, zinc pyrithione,
propylene glycol, Whiteld ointment, sulfur plus salicylic
acid and benzoyl peroxide. These topical agents do not
act specically against Malassezia species. Their mode
of action is to remove dead, infected stratum corneum
either physically and/or chemically.194
Selenium sulde, available as a shampoo, lotion and
cream in 1–2.5% concentrations, is safe and effective
in the treatment of tinea versicolor.147,195–197 Studies have
shown that the success rate of selenium sulde sham-
poo in the treatment of tinea versicolor is comparable to
that of topical bifonazole and econazole.198,199 Advantages
of selenium sulde include over-the-counter availability,
low cost and convenient application. Disadvantages in-
clude irritation of the skin, unpleasant odour, staining of
clothes and bedding, and a high relapse rate.195,196
The efcacy of zinc pyrithione 1% shampoo versus its ve-
hicle in the treatment of tinea versicolor has been shown
in an open trial200 as well as in a double-blind controlled
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trial.201 In the latter, 20 patients with tinea versicolor were
treated with either zinc pyrithione 1% shampoo or the
shampoo base for 5 minutes per day for 2 weeks.201 At
the end of the study, all 20 patients treated with zinc py-
rithione 1% shampoo had clearing of the tinea versicolor
lesions compared to none of the patients in the sham-
poo base group.
Propylene glycol is a keratolytic agent. Faergemann et
al. treated 20 patients with tinea versicolor with propyl-
ene glycol 50% in water daily for 2 weeks.202 At the end of
treatment, all 20 patients were cured.
Whiteld ointment consists of 3% salicylic acid and 6%
benzoic acid in an emulsifying ointment.153,203 Salicylic
acid is keratolytic whereas benzoic acid is fungistatic.17
Whiteld ointment has been shown to be effective in
the treatment of tinea versicolor in a limited number of
studies.153,203
A combination of sulfur and salicylic acid has been
shown to be effective in the treatment of tinea versicolor
in a small number of studies.204,205 The combination can
be in the form of 2% micropulverized sulfur and 2% sal-
icylic acid in a shampoo base.204,205 The formulation is
cosmetically pleasant and safe.204
Benzoyl peroxide has been used with success in the treat-
ment of tinea versicolor.206–208 In three studies, the vehicle
for benzoyl peroxide was propylene glycol, which by itself
is effective in the treatment of tinea versicolor.206–208 As
such, it is not certain whether the benecial effect is due
to benzoyl peroxide or propylene glycol. It is possible that
benzoyl peroxide and propylene glycol may have a syn-
ergistic effect in the treatment of tinea versicolor.
Oral antifungals
Oral antifungals are usually reserved for treating severe,
widespread, recalcitrant or recurrent tinea versicolor.17
Advantages of oral antifungal therapy include increased
patient compliance, shorter duration of treatment, in-
creased convenience, less time involved with treatment
and reduced recurrence rates.17,209 On the other hand,
oral antifungal therapy is associated with higher cost,
greater adverse events, and potential drug–drug inter-
actions and is therefore not the rst-line treatment of
tinea versicolor, especially in children.1 Oral azole anti-
fungals, such as itraconazole and uconazole, are the
preferred systemic agents.210,211 Adverse events asso-
ciated with the use of oral antifungals include fatigue,
malaise, headache, cutaneous eruption, pruritus, dys-
pepsia, nausea, vomiting, abdominal pain, diarrhoea,
hypertension, congestive cardiac failure, thrombocyto-
penia, hypokalaemia, albuminuria, hypertriglyceridemia
and abnormal liver function.147,212,213
Oral itraconazole
Oral itraconazole, a triazole derivative with strong ker-
atophilic and lipophilic properties, is highly effective for
the treatment of tinea versicolor143,210,214; the absorption of
itraconazole is enhanced by food.17,215 The recommend-
ed dose is 200 mg per day for 5–7 days.1,63,141,142 Adverse
events are uncommon.216 Rarely, congestive heart fail-
ure and hepatotoxicity have been reported.35 Oral itra-
conazole should therefore be avoided in patients with
a history of congestive heart failure or in patients with
active hepatic disease.35 As itraconazole inhibits the en-
zyme cytochrome P450-dependent system, the medi-
cation may cause drug–drug interactions. As such, oral
itraconazole should not be given to patients who are on
astemizole or cisapride for fear of cardiovascular ad-
verse events.35
Oral uconazole
Oral uconazole, a triazole antifungal, is also highly ef-
fective for the treatment of tinea versicolor through the
inhibition of cytochrome P450-dependent ergosterol
synthesis.217–219 When administered orally, uconazole can
persist in the stratum corneum for approximately 2 weeks
following administration.219 The recommended dose
is 300 mg once weekly for 2–4 weeks.1,63,211 Because u-
conazole has little afnity for mammalian cytochromes,
the antifungal has low toxicity. Serious adverse events
are rare.35 As uconazole inhibits the cytochrome P450-
dependent system, the medication should likewise be
avoided in patients treated with astemizole or cisapride
for fear of cardiovascular adverse events.35
Oral ketoconazole
Oral ketoconazole at a dose of 200 mg daily for 10 days
is also effective for the treatment of tinea versicolor.147
The risk of hepatotoxic adverse events associated with
oral ketoconazole is about 1 in 500 and therefore out-
weighs its potential benets.220,221 Because of the risk of
hepatotoxicity, adrenal insufciency and multiple drug–
drug interactions, oral ketoconazole should no longer be
prescribed.1,35,87
Oral terbinane
Oral terbinane is not effective in the treatment of tinea
versicolor.87 Terbinane is not excreted in sweat and fun-
gicidal levels of terbinane cannot be achieved in the
stratum corneum with oral administration of the med-
ication.87
Oral griseofulvin
Oral griseofulvin is not effective for the treatment of tin-
ea versicolor.17,43
Laser and photodynamic therapies
A limited number of studies reported the successful
treatment of tinea versicolor with 308-nm excimer
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laser, narrow-band ultraviolet (UV)-B phototherapy, 5-
aminolevulinic acid photodynamic therapy and meth-
ylene blue photodynamic therapy.222–225 Well-designed,
large-scale, multicentre, randomized, placebo-controlled
trials are needed to conrm or refute these ndings.
Alternative therapies
A wide variety of alternative medicines have been shown
to have some therapeutic effects on tinea versicolor. In
some cultures, alternative therapies are popular for the
treatment of tinea versicolor. These include topical ap-
plication of beeswax and honey,226 essential oils of Cym-
bopogon citratus,227 quince seed mucilage hydrogel
decorated with essential oils of Nigella sativa, Citrus sin-
ensis and Cinnamon verum,228 polyherbal Unani formu-
lation,229 Pentas longiora leaf extract,230 Acalypha wil-
kesiana leaf extract,231 Artemisia sieberi shrub extract,182
nitric oxide-liberating cream232 and irradiated human
amniotic membrane in combination with tea tree oil.233
None of these treatments have yet been subjected to
rigorous studies nor randomized clinical trials.
Prophylactic treatment
The relapse rate is high because Malassezia species are
normal commensals on the skin surface.87 Good per-
sonal hygiene may limit recurrences to a certain extent.
Long-term intermittent prophylactic therapy should
be considered for patients with frequent recurrence of
the disease who desire treatment, especially during the
warmer months of the year.87 Unfortunately, research
studies evaluating the efcacy of prophylactic antifun-
gal treatment are scarce. Prophylactic administration
of topical ketoconazole 2%, clotrimazole 1% or selenium
sulde 2.5% shampoo applied to the whole body for
10 minutes once a month may lead to decreased
relapse rate of tinea versicolor.166 An alternative is to
prophylactically administer an oral antifungal agent
such as itraconazole, especially if topical antifungal
prophylaxis is not successful. Oral itraconazole is easy
to administer and less time-consuming and thereby has
better compliance.63 The recommended dose of itra-
conazole for prophylaxis is 200 mg twice a day once per
month.1,216
Conclusion
Tinea versicolor is a common supercial fungal infection
of the skin caused by Malassezia species. Because the
clinical manifestations of tinea versicolor are myriad, clin-
ical acumen is essential to make the correct diagnosis. As
tinea versicolor is often a chronic and recurrent disease,
repetitive treatment courses are often necessary. A wide
range of antifungal agents are effective in the treatment
of tinea versicolor. In general, topical antifungal agents
are the rst-line treatment of tinea versicolor as there
are fewer adverse events associated with their use. Oral
antifungal agents are usually reserved for severe, wide-
spread, recalcitrant or recurrent disease. Apart from con-
sidering the severity and extensiveness of tinea versicolor,
patient age, and patient and physician preferences, the
selection of antifungal agents depends on a number of
factors, including the efcacy, safety, local availability,
ease of administration, likelihood of compliance and po-
tential drug interactions of the antifungal agent. In clinical
practice, it is often the patient preferences and the physi-
cian experience that dictate the selected treatment.
Contributions: AKCL is the principal author. BB, JML, KFL and KLH are coauthors who contributed and helped with the
drafting of this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE)
criteria for authorship for this article, take responsibility for the integrity of the work and have given their approval for
this version to be published. All named authors meet the International Committee of Medical Journal Editors (ICMJE)
criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their
approval for this version to be published.
Disclosure and potential conicts of interest: AKCL and KLH are associate editors of Drugs in Context and conrm
that this article has no other conicts of interest otherwise. This manuscript was sent out for independent peer review.
The International Committee of Medical Journal Editors (ICMJE) Potential Conicts of Interests form for the authors is
available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/10/dic.2022-9-2-COI.pdf
Acknowledgements: None.
Funding declaration: There was no funding associated with the preparation of this article.
Copyright: Copyright © 2022 Leung AKC, Barankin B, Lam JM, Leong KF, Hon KL. Published by Drugs in Context under
Creative Commons License Deed CC BY NC ND 4.0, which allows anyone to copy, distribute and transmit the article
provided it is properly attributed in the manner specied below. No commercial use without permission.
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Correct attribution: Copyright © 2022 Leung AKC, Barankin B, Lam JM, Leong KF, Hon KL. https://doi.org/10.7573/
dic.2022-9-2. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.
Article URL: https://www.drugsincontext.com/tinea-versicolor-an-updated-review
Correspondence: Alexander KC Leung, The University of Calgary, The Alberta Children’s Hospital, #200, 233 – 16th Av-
enue NW, Calgary, Alberta, Canada T2M 0H5. Email: aleung@ucalgary.ca
Provenance: Invited; externally peer reviewed.
Submitted: 9 September 2022; Accepted: 4 October 2022; Published: 14 November 2022.
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