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Current Fungal Infection Reports

https://doi.org/10.1007/s12281-018-0328-7

FUNGAL INFECTIONS OF SKIN AND SUBCUTANEOUS TISSUE (A BONIFAZ, SECTION


EDITOR)

Pityriasis Versicolor: Treatment Update


Martin Arce 1 & Daniela Gutiérrez-Mendoza 1

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review To address the latest treatments used for pityriasis versicolor and identify those that have proven to be
effective in recent publications.
Recent Findings Even though Malassezia spp. have shown resistance to antifungals, classical treatments continue to be effective,
and other novelty therapies including light therapies have shown promising results in the treatment of this condition.
Summary Pityriasis versicolor is a common superficial fungal infection of the skin. There are numerous and diverse topical and
systemic therapeutic options that are successful for the treatment and prophylaxis of this mycosis. New substances that act against
the fungus through other mechanisms of action different from those used until now are expected in the near future.

Keywords Superficial mycosis . Tropical mycosis . Pytiriasis versicolor . Tinea versicolor . Malassezia spp. . Antifungals

Introduction of the lesion, there are papular and imbricate forms, and there
is an atrophic type rarely reported in the literature [3, 6].
Pityriasis versicolor, or tinea versicolor, is a mildly inflamma- Recently, a new disseminated and recurrent variety of
torily superficial mycosis with a chronic and relapsing course. pytiriasis versicolor has been suggested based on the clinical
It is easy to recognize by its characteristic light or dark colored characteristics of extension and evolution [7].
oval or circular patches with fine and superficial desquama- Pityriasis versicolor can be found mainly in young patients,
tion, and a tendency to form groups of larger patches. The as well as children and adults, more commonly in the summer
disease affects the oily or seborrheic areas of the body such or in hot climate and high humidity environments; other
as the trunk, posterior and anterior thorax, neck, arms, and influencing factors include sun exposure, excessive sweating,
face: especially in the forehead and around the ears. It can also application of creams or oils on the skin and hair, and use of
be seen in the large skin folds, specially at hyperhidrosis sites tight clothing or synthetic fabrics [3, 4, 8]. In tropical coun-
[1–3]. tries, the disease has been found in 32% of the mycoses stud-
There are clinical varieties of the disease: (1) According to ied and can be the cause in up to 40 to 50% of individuals. It
the predominance of the color of the spots, the most frequent has also been found to have a high recurrence rate, with 60%
are the hyperpigmented variety with brown spots and the relapse after treatment before 1 year and 80% in a period of
hypopigmented variety with white spots, also referred to as 2 years [8–10].
the alba form, followed by the erythematous variety with red- The disease can be managed by various therapeutic modal-
dish spots (Fig. 1a) [1, 4, 5]. (2) In relation to the morphology ities. In general, the choice depends on the clinical variety and
the causal agent; however, the age of the individual, the sever-
ity or extension of the lesions, the recurrence of the disease,
This article is part of the Topical Collection on Fungal Infections of Skin
and Subcutaneous Tissue and other medications prescribed to the patient may influence
the type of treatment [4, 8, 11•]. When adequate treatment is
* Martin Arce employed, resistant cases are extraordinary, but if it is the case,
it may be due to inappropriate treatment or incorrect diagno-
sis. Residual spots may be observed after treatment because
1
Tijuana, Mexico pigmentation is slow to recover [12, 5].
Curr Fungal Infect Rep

Fig. 1 a Hypopigmented circular


spots and confluent, with smooth
scale. b Skin scales on transparent
adhesive tape on slides. c
Microscopic exam: yeasts and
filaments stained with
lactophenol blue

Aetiological Agent 10%–20% potassium hydroxide (KOH) (Fig. 1b, c) [8].


The isolation of the yeasts that require lipids can be done
Malassezia genus is the predominant commensal of the skin in enriched media such as Dixon Agar (DA), modified
microbiota of healthy adults in the back and specific areas of Dixon (mDA), Leeming and Notman Agar (LNA), or
the head and face, occiput, external auditory canal, glabella, Sabouraud Agar with olive oil. Analytical and molecular
and atrial fold, as well as sternal manubrium and inguinal methods like real-time PCR that do not require culture can
crease; however, it can be found as a yeast and symbiont in also be employed. The histopathological study may be per-
practically all the cutaneous surface [13, 14]. The former rep- formed for academic or research reasons, but it is not re-
resent seborrheic areas; these anatomic sites are preferred by quired for the diagnosis of the disease [21–23, 25].
Malassezia spp. because it utilizes the fatty acids as exoge-
nous sources of lipids for nutritional requirements. Enzymes
such as lipases and phospholipases are necessary to assimilate
the lipids of the host’s sebum [2, 15]. Treatment
The genus Malassezia has been reclassified within the
class Malasseziomycetes, in Ustilaginomyco tina Non-specific Topical Treatments
(Basidiomycota, fungi) and new species have been identi-
fied. Almost all of them are obligatory lipophilic yeasts. At Topical treatments with keratolytic and antimicrobial ac-
this moment, 17 species of the genus are recognized tivity, without specific antifungal activity against
[15–17, 18••, 19••]. Malassezia globosa, M. simpodialis, Malassezia spp., have been used for a long time. They
and M. furfur are most frequently isolated in Pityriasis have proved to be an effective treatment for pityriasis
versicolor [2, 20–23]. M. pachydermatis, the only species versicolor and continue to be considered as first line of
not dependent on lipids, has rarely been reported as caus- treatment. These therapies include made to order formula-
ative of the disease [15, 24]. tions and over the counter medications that encompass
various presentations such as tinctures, ointments, creams
or lotions, soaps, and shampoos. The main substances
Diagnosis used are sulfur, salicylic acid, benzoic acid, propylene gly-
col, and benzoyl peroxide, at different concentrations, ei-
The diagnosis of pityriasis versicolor is done by clinical ther alone or combined with other products [4, 26]. This
observation of the characteristic lesions; a green-yellow group includes retinoid drugs such as tretinoin (retinoic
fluorescence in the depigmented macules on Wood’s light acid) and adapalene 0.1%. They act as keratolytics in pit-
examination can help corroborate the diagnosis. yriasis versicolor by increasing the exfoliation of the stra-
Laboratory analysis of the scales under the light micro- tum corneum, where the fungus is found [27]. Physical
scope will show the dimorphism of the fungus with short treatments with mechanical keratolytic effects such as ex-
and thick filaments and yeast cells. A smear is easily ob- foliation of the skin with loofah during the bath are also
tained from the surface of the skin by scraping scales with mentioned as effective [28]. Miscellaneous topical drugs
adhesive tape and stained with Alibert’ solution or such as diclofenac 1%, a non-steroidal anti-inflammatory
Lactophenol cotton blue and methylene blue, or with drug, have been tested in pityriasis versicolor [29].
Curr Fungal Infect Rep

Specific Topical Treatments The first, itraconazole, is highly lipophilic with affinity to
keratinized tissue. Pramiconazole is also broad-spectrum an-
Antifungal drugs have traditionally been used in pityriasis tifungal and more effective than ketoconazole against derma-
versicolor. These include haloprogin, thiocarbamates such as tophytes and yeasts such as Candida spp. and Malassezia spp.
tolnaftate and tolciclate, as well as cyclopirox olamine 1%, The three agents are well tolerated, with mild side effects such
zinc pyrithione 1%, and various imidazoles 1–2%, for exam- as headache, and most commonly gastrointestinal complaints;
ple, clotrimazole and miconazole, and recently the triazole these adverse effects are the same as in those observed with
fluconazole 2% in shampoo [8, 30, 31]. In the last years, the ketoconazole, but without its hepatotoxicity and more impor-
antifungal mechanism of zinc pyrithione has been described. tantly they are most active against Malassezia spp. [37, 38•].
It acts as an ionophore, apparently increasing cellular copper The recommended dosage is as follows: itraconazole
levels and inhibiting the growth of the fungus [32, 33]. 200 mg per day for 5 to 7 days, fluconazole 300 mg weekly
Currently, topical medications such as ketoconazole and for 2 weeks, or a single dose of 450 mg, and pramiconazole
terbinafine are considered first-line treatments that can be ap- 200 mg daily for 2 days. Oral terbinafine is not useful in
plied directly on the skin in cream, gel, foam, or shampoo pityriasis versicolor [31, 34•, 11•].
formulations. Ketoconazole 2%, cream or foam, including
shampoo, is used one to two times a day for 14 days, while Mechanism of Fungal Resistance to Azoles
terbinafine 1% cream, emulsion or solution, twice a day, 1 or
2 weeks [11•, 28, 31, 34•]. Azole antifungals act directly on the cell membrane of the
Topical treatments are effective, accessible, and less expen- fungus, affecting its integrity and growth, by inhibiting the
sive. They have some disadvantages compared to oral treat- cytochrome p450 14α-lanosterol demethylase enzymatic
ments. They may be relatively difficult to self-apply and in function. Mechanisms of azole resistance have been de-
some cases cause skin irritation. In cases of pityriasis scribed, such as increased drug efflux, target mutations such
versicolor with extensive lesions, frequent relapses, resistant as decreased affinity, dysregulation of target expression, and
lesions, or lack of adherence to topical treatment, systemic alterations in ergosterol biosynthesis [39, 40, 41]. It has been
therapy is recommended. It has the disadvantage of probable observed that species such as M. pachydermatis and M. furfur
adverse effects or interactions with other drugs [35, 36, 8, 31, can depend on cellular efflux pumps to resist the action of
11•]. azoles [42••].

Systemic Treatment Antifungal Susceptibility

Ketoconazole, itraconazole, and fluconazole are well known The antifungal susceptibility for Malassezia spp. has been
oral azole broad-spectrum antifungals for superficial and deep demonstrated in vitro against azoles such as itraconazole,
mycoses. Ketoconazole is one of the main oral imidazole voriconazole, ketoconazole, and fluconazole [43–45]. To de-
medications used in pityriasis versicolor; its effectiveness in termine this antifungal susceptibility in vitro of Malassezia
the treatment and prophylaxis of the disease has solid evi- spp., methods adapted to the strict growth requirements of
dence during decades of clinical use. The posology of ketoco- these yeasts are needed. They are made in culture media such
nazole for the treatment of the disease is 200 mg per day as agar and broth. Currently, there are few tests implemented
during 10 days and for prophylaxis 200 mg day during 3 days. and are not practiced routinely since they are complex and are
Ketoconazole has excellent activity against M. furfur at con- only done in highly specialized laboratories [45–47].
centrations of 0.8 μg/mL, but at concentrations higher than
100 μg/mL, it has toxic effects. Adverse effects are mostly Diverse Compounds in the Treatment Infections
mild and affect the gastrointestinal tract, while serious adverse by Malassezia spp.
effects are rare and include hypersensitivity reactions, anaphy-
laxis and liver toxicity, the latter previously estimated at Phytotherapy has been reported in the treatment of pityriasis
1:500,000 patients taking 10 days of oral treatment. In recent versicolor with numerous medicinal plants, which contain var-
years, the risk of hepatotoxicity by oral ketoconazole in 1:500 ious compounds such as phenols, flavonoids, tannins, antho-
has been calculated and this use has been banned, specifically cyanins, as substances with antifungal properties against
in Europe and the USA, but its use continues in other regions Malassezia spp. [48, 49]. Recently, alternative and novel treat-
[37, 28, 31, 11•]. ments different from classical azole antifungals in Malassezia
Itraconazole, fluconazole, and the newer pramiconazole are spp. have been reviewed, and some of them could be useful in
triazole compounds, with high cure rates in pityriasis pityriasis versicolor; inhibitors and activators of carbonic
versicolor. They are administered orally since there are no anhydrase of M. globosa, inhibitors of lipase of M. globosa,
formulations for topical use, except for fluconazole shampoo. silver nanoparticles combined with other antifungals, and
Curr Fungal Infect Rep

inhibitors of calcineurin phosphatase, pimecrolimus, and ta- ecological niche; under certain exogenous and endogenous
crolimus, which also prohibits the growth of Malassezia spp. conditions, they produce pityriasis versicolor. This condition
[38•, 34, 33]. The mechanism of action of tacrolimus has been has a benign nature but nevertheless requires treatment be-
investigated in M. furfur and M. sympodialis; this drug binds cause it negatively affects the quality of life of the subjects
to an immunophilin (FKBP12), and inhibits fungal calcine- who suffer from it.
urin, which is involved in fungal growth and susceptibility- The drugs currently available for the treatment of pityriasis
resistance to antifungal drugs [50]. In one study of clinical versicolor are effective and safe. Topical and systemic azole
efficacy, tacrolimus was similar to clotrimazole [51]. medications continue to be the main basis of their treatment,
among multiple options and promising compounds. The
Phototherapy and Other Light Treatments choice of treatment depends basically on the extent or severity
of the lesions and recurrence of the disease, as well as the
Nowadays, the use of technology with different sources of availability and cost of the therapy and the physician’s
light energy in superficial fungal infections such as pityriasis experience.
versicolor is increasingly frequent [52–54]. Photodynamic
therapy with methyl 5 aminolevulinate has been used against Compliance with Ethical Standards
infection by Malassezia spp. [55–57]. Recently, narrow-band
ultra violet B (NB-UVB) light has been used as a safe and Conflict of Interest The authors declare that they have no conflict of
interests.
effective alternative treatment in pityriasis versicolor, al-
though it does not prevent relapses [58]. UV light has also
Human and Animal Rights and Informed Consent There was no exper-
been used to accelerate the recovery of discoloration once iment done on human or animal subjects by any of the authors for the
the fungus has been eliminated; although the repigmentation publication of this article.
of residual hypopigmented spots of pityriasis versicolor re-
solves naturally in 2 to 3 months or longer after the end of
treatment, it is recommended to begin therapy as soon as pos-
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