Pityriasis versicolor
Definition
This is a mild, chronic infection of
the skin caused by Malassezia, lipophilic dimorphic yeasts, and
characterized by discrete or confluent, scaly, discolored areas, mainly on the
upper trunk.
Malassezia furfur, dimorphic
lipophilic yeast, is part of the normal flora of human skin
that normally
resides in the keratin of skin and hair follicles of individuals at puberty and
beyond. An opportunistic organism, causing pityriasis versicolor (TV) and Malassezia
folliculitis; it is also implicated in the pathogenesis of seborrheic
dermatitis. Malassezia infections are not contagious.
The
typical patient is a young adult, but people of any age may develop the
disease. Interestingly, Malassezia requires oil to grow, accounting for
the increased incidence in adolescents and preference for sebum-rich areas of
the skin.
Pathogenesis
M.
furfur
normally lives on human skin in amounts so minute as to be undetectable on
potassium hydroxide (KOH) examination of stratum corneum. Pityriasis versicolor
occurs when the round saprophytic yeast form transforms to the predominantly
parasitic mycelial form under the
influence of predisposing factors. Factors predisposing to mycelial transition
include a warm, humid environment, hyperhidrosis, oily skin, oral
contraceptive, and systemic corticosteroid use, immunosuppression, and a
malnourished state. Application
of lipids such as cocoa butter predisposes young children. Because this yeast
is lipophilic, use of bath oils and skin lubricants may increase the risk of
disease.
Biofilm formation represents one of the main mechanisms by
which microorganisms maintain viability in hostile environments and this
biofilm formation is potentially responsible for both the pathogenesis and the
chronicity of this infection. This gives rationale to biofilm-dispersing
agents, such as selenium sulfide, as important components in the standard P.
versicolor treatment regimen. Periodic use of such agents would conceivably
prevent reinfection.
While
M. furfur had long been identified as the fungus causing tinea versicolor, M.
globosa is now thought to be the predominant species involved in its
pathogenesis.
Pathology
The infecting
organism is usually present in the upper layers of the stratum corneum, and on
electron microscopy may be seen to invade not only between but within the
keratinized cells. While the yeast may be identified with
hematoxylin and eosin staining alone, visualization is enhanced through PAS
stain. Microscopic examination reveals clusters of oval budding yeast cells
with short, septate, and occasionally branching hyphae inhabiting the stratum
corneum.
Causative
organisms
Tinea
versicolor is usually caused by M. globosa and possibly M.
sympodialis and M. furfur.
Clinical
features
Patients usually present with multiple oval-to-round macules,
patches or thin plaques with mild, fine scale. The
primary lesion is a sharply demarcated macule, characterized essentially by
fine scaling. Typically,
the eruption shows large confluent areas, scattered oval patches and outlying
macules. The scale is characteristically described as dust-like or furfuraceous.
Where scaling is minimal, demonstration of this associated
scale may require scratching or stretching the skin surface or with a sticky
tape strip. Treated
or resolved lesions lack scale. Patches may have a wrinkled surface
appearance and this feature serves as a useful clinical pearl for the
diagnosis. In time,
individual lesions may enlarge and merge, forming extensive geographic areas.
Seborrheic regions, in particular the upper trunk are most commonly
affected, but there is often spread to the shoulders, upper arms, the
neck and the abdomen. Facial and scalp lesions occur in persons applying creams or
ointments or topical glucocorticoid preparations, and
occasional cases in which only these areas are affected are seen. Lesions on the face are also seen in children.
Involvement of flexural areas such as axillae, groins, antecubital fossae and sub mammary region is sometimes
referred to as “inverse” pityriasis versicolor. Lesions on the thighs and
genitalia can occur, and extension down the forearms on to the backs of the
hands, and into the popliteal fossae is also seen.
The most common colors are brown
(hyper pigmented) and whitish-tan (hypo pigmented); occasionally there is mild
inflammation leading to a pink color. Decreased pigmentation may be secondary
to dicarboxylic
(Azelaic) acid formed by enzymatic ( via lipase enzyme is present in M.
furfur) oxidation of fatty acids in skin surface lipids that inhibits
tyrosinase in epidermal melanocytes
and perhaps a direct cytotoxic effect on hyperactive melanocytes lead to hypomelanosis; or decreased tanning, due to the ability of the fungus to
filter sunlight. However, such acids had no effect on normal melanocytes. The explanation for
the hyperpigmentation is due to presence of abnormally large melanosomes in hyper
pigmented lesions. In general,
pityriasis versicolor is asymptomatic and the major concern is about dyspigmentation.
Histopathological
differences between hypo- and hyper-pigmented P. versicolor
Theories of hypopigmentation
Theories of hyperpigmentation
KOH preparation
KOH examination of
associated scale is typically diagnostic. In pityriasis versicolor, both round yeast and elongated
pseudohyphal forms
are seen; although likened to “spaghetti and meatballs” or ‘bananas and
grapes’, the findings more closely resemble “ziti and meatballs”. Visualization
of fungal elements may be enhanced by the addition of methylene blue stain to the KOH
preparation.
Wood's Lamp
Yellow-green
fluorescence of scales thought
to be due to the presence of pteridine, may be negative in individuals who have showered
recently because the fluorescent chemical is water soluble.
Course
In
ordinary cases that settle spontaneously or as a result of treatment, the
residual hypopigmentation may remain for many months without any scaling. Infection persists for years if
predisposing conditions persist. Tinea versicolor tends to recur in warmer
months of the year.
Differential
diagnosis
Vitiligo
and chloasma are normally distinguishable by their complete absence of scaling. Seborrheic dermatitis, pityriasis rosea, secondary syphilis, pinta and tinea corporis
show more inflammatory change than pityriasis versicolor, and none of these
ever has the even, fine scale of the latter condition. Erythrasma may closely
mimic pityriasis versicolor with pigmentary change and scaling, but satellite
lesions are less common, and pink fluorescence under the Wood's lamp is often
present. Erythrasma and pityriasis versicolor may occasionally coexist.
Treatment
Relapse is unfortunately very
common, whatever the primary treatment. In all cases it is probably simplest to
re‐treat each
episode rather than resort to long‐term suppressive therapy. Patients should be warned that
repigmentation may take several months, as otherwise they will often report
treatment failure, even when the organisms have been destroyed, simply because
the hypopigmentation persists.
First line
The first line treatment is topical
antifungal therapy. The topical azole antifungals work well in pityriasis versicolor,
and there is no significant difference in results achieved by different
compounds. The usual time to recovery is 2–3 weeks. However, there is
increasing evidence that shorter application periods using appropriate
formulations may work after only one or two applications.
A
widely used and inexpensive protocol involves using selenium sulfide lotion 2.5%, which
is applied liberally to affected areas for 10 minutes prior to rinsing. While
daily use may be considered for extensive cases, application 3–4 times per week
is adequate, and this frequency may be tapered further to once or twice monthly
and used as a maintenance regimen to prevent recurrences. Alternatively, ketoconazole shampoo 2% is
lathered on to affected areas and left for 5 minutes prior to rinsing; this
treatment is repeated for three consecutive days. Terbinafine solution 1% applied
twice daily to affected areas for 7 days has yielded cure rates of more than
80%.
Second line
Although topical therapy is ideal for localized or mild
infections, systemic treatment may be necessary for patients with extensive
disease, frequent recurrences, or for whom topical agents have failed. Fluconazole,
and itraconazole are
the preferred oral agents, and various dosing regimens are effective. Itraconazole is active against
pityriasis versicolor in a total dosage of 800–1000 mg, usually given over 5
days. A
single dose of oral itraconazole 400 mg has been shown to be more than 75%
effective, and in one study, just as effective as itraconazole given for 1
week. Fluconazole is also effective when administered as a single oral dose of
400 mg. Oral terbinafine, an
allylamine, is not recommended in the treatment of Malassezia related
disorders, since the drug is not delivered efficiently to the skin's surface.
The potential for drug toxicity and interactions via the influence of azoles on
cytochrome p450 isoenzyme activity should be addressed when considering the use
of oral azole agents to treat tinea versicolor.
Therapeutic ladder
First line
·
Topical azoles twice daily for 2–3
weeks
·
Terbinafine 1% cream twice daily for
2–3 weeks
·
Ketoconazole shampoo twice weekly
for 2–3 weeks
Second line
·
Itraconazole 200 mg daily for 5 days
Prevention
Recurrence is common and regular maintenance application
of any of the topical agents helps to reduce high rates of recurrence. While
the condition does not leave any permanent scar or pigmentary changes, skin
tone may take several months to return to normal. Prevention of recurrences is
helpful in limiting long-lasting dyschromia. A regimen of 400 mg fluconazole or
400 mg of itraconazole once a month for 6 months has
been used successfully to prevent recurrences.
Oral ketoconazole is no longer indicated
for treatment of superficial fungal infections due to risks of severe
hepatotoxicity, QT prolongation, and serious drug interactions.
|
TREATMENT OF TINEA
(PITYRIASIS) VERSICOLOR |
|
|
Initial therapy (often combination) |
Topical* Antifungal shampoo
applied as a body cleanser for 10–15 minutes before rinsing, twice weekly for
2–4 weeks ·
Selenium
sulfide shampoo, 2.5% ·
Ketoconazole
shampoo, 2% ·
Zinc
pyrithione shampoo ·
Ciclopirox olamine
shampoo, 1% Antifungal cream
applied several hand-widths beyond clinically visible lesions, daily to twice
daily for 2 weeks ·
Imidazole,
e.g. ketoconazole 2% cream ·
Ciclopirox olamine
0.77% cream, gel, or lotion
· Fluconazole: 200 mg po daily × 5–7 days†; 200–300 mg weekly × 2–3 weeks; or 400 mg once · Itraconazole: 200 mg po daily × 5–7 days |
|
Maintenance therapy to prevent
recurrence |
·
Treat
previously affected sites with topical imidazole daily for 2 weeks prior to
anticipated sun exposure ·
Apply
antifungal shampoo 1–2 times weekly |
* Treatment of all the skin from the neck down to the
knees may lead to higher success rates.
** Although there are few comparative studies of oral
antifungal medications, cure rates of 98–100% have been reported in several
randomized controlled trials of itraconazole 200 mg daily × 5 days and an
open-label study of fluconazole 300 mg weekly × 2 weeks.
Malassezia folliculitis
Definition
This
is a clinically distinct form of folliculitis on the back and upper trunk
associated with Malassezia yeasts.
Epidemiology
Malassezia organisms are observed as skin flora in
75%–98% of healthy people. Colonization by M. furfur begins soon after birth
and peaks during adolescence and young adulthood, concomitant with an increase
in sebaceous gland activity. Those living in warm and humid climates have
higher incidences of Malassezia folliculitis.
Etiology and
Pathogenesis
Malassezia yeasts are classified as superficial mycoses
that by definition do not invade past the cornified epithelium. However, in
Pityrosporum folliculitis, follicular ostia, and central and deep segments of
the hair follicle are involved by Malassezia, most commonly M furfur.
Predisposing factors
Risk factors for Pityrosporum
folliculitis include pregnancy, diabetes mellitus, and therapy with oral
antibiotics, corticosteroids and/or immunosuppressants. Other contributing
factors include warm,
humid environment; hyperhidrosis and local occlusion of the skin and hair
follicles with cosmetics, lotions, sunscreens, emollients, olive oil, or
clothing. It is due to excessive growth of M. furfur and M. globosa
within the hair follicle, with resulting inflammation due to yeast products as
well as free fatty acids generated by fungal lipase.
Patients
often report the development of lesions following a holiday in the sun or it
may be found in patients who are acutely ill, for example in an intensive care
unit.
Pathology
Malassezia organisms are noted in dilated follicular
units, which may show keratin plugging and cellular debris. Staining with PAS or methenamine
silver will reveal the oval single-budding yeast. When follicular walls
rupture, there is a resulting mixed inflammatory infiltrate of lymphocytes,
histiocytes, and neutrophils surrounding follicles. Microscopic examination of
pustules usually shows budding yeast forms and spores, not hyphae.
Clinical
features
This condition is most commonly seen in young
women and is characterized by numerous itchy, monomorphic 2-4mm follicular
papules and pustules with perifollicular erythema diffusely scattered on the
upper trunk, neck, shoulders and upper arms. The
itching and distribution distinguish them from acne vulgaris.
As in the case of pityriasis versicolor, recurrence of
Malassezia folliculitis is common.
In
KOH examination of expressed follicular contents, only yeast
forms are seen, i.e. no hyphal forms as in pityriasis versicolor. KOH
examination or culture may be required to distinguish this infection from the
more common bacterial folliculitis.
Diagnosis
Diagnosis of Malassezia folliculitis is made on clinical
grounds, and confirmed by KOH examination. Skin biopsy is rarely necessary to
make the diagnosis.
Treatment and
Prognosis
Both topical and oral antifungal agents are effective
agents in the treatment of Malassezia folliculitis and are commonly combined to
hasten resolution and maintain clearance. Topical regimens include daily use of
ketoconazole
shampoo 2%, selenium sulfide
lotion 2.5%, and ciclopirox olamine
cream 0.77%. There are limited data on the use of systemic agents in treating
Malassezia folliculitis. Commonly used regimens include fluconazole 150
mg weekly for 2–4 weeks, and itraconazole 200
mg daily for 2 weeks. Oral terbinafine is
not recommended in the treatment of Malassezia related disorders, since the
drug is not delivered efficiently to the skin's surface.
Recurrence is common. Because relapses almost always
occur after treatment is complete, topical agents are continued indefinitely at
reduced frequency as a preventative measure. Topical protocols used in the
prevention of Malassezia folliculitis include selenium sulfide
2.5% lotion once weekly, ketoconazole 2%
cream once weekly, and ketoconazole 2% shampoo 2–3 times weekly. Maintenance
therapies with systemic agents include oral itraconazole 400
mg once monthly and oral fluconazole 200
mg once monthly.
