517

Dermatologic Therapy, Vol. 17, 2004, 517522

, J

ASHIN

J. W

U

, K

ATIE

R. P

ANG

&
S

TEPHEN

K. T

YRING

*

Department of Internal Medicine, Division of Infectious Diseases, Baylor
College of Medicine, Houston, TX,

Department of Internal Medicine, Division
of Infectious Diseases, University of Texas Health Science Center, Houston, TX,

Department of Dermatology, University of California, Irvine, CA,

Department of Dermatology, Wayne State University School of Medicine,
Detroit, MI, and

Department of Dermatology, University of Texas Health
Science Center, Houston, TX and Center for Clinical Studies, Houston, TX

ABSTRACT:

Supercial fungal infections are common, especially onychomycosis, dermatophytoses,
and supercial

Candida

infections. Most supercial fungal infections are treated with topical antifungal
agents unless the infection covers an extensive area or is resistant to initial therapy. Onychomycosis
often requires systemic therapy with griseofulvin, itraconazole, or terbinane. The objective of this
review is to provide the practicing dermatologist with the recommended available therapy for the
treatment of common supercial fungal infections.

KEYWORDS:

fungi, supercial, therapy

Introduction

Supercial fungal infections, such as onycho-
mycosis, dermatophytoses, and supercial

Candida

infections, are common and can be caused by a
myriad of fungi. Many cutaneous fungal infections
may be treated with topical agents. Other fungal
dermatoses may require systemic treatment for
more serious (i.e., difcult to treat organisms,
large infected areas, maceration with secondary
infections, or in immunocompromised individuals)
and relapsing infections to ensure the adequate
presence of a therapeutic agent at the site of
infection. However, the improved cure rates of
topical agents such as azoles, reduced adverse
events prole by topical routes, decreased drug
interactions, and lower cost of these agents make
this therapy a favorable choice in the manage-
ment of supercial fungal infections.

Onychomycosis

Onychomycosis is a fungal infection of the
nger or toe nails. Onychomycosis of the toenails
(FIG. 1) is usually caused by dermatophytes such
as

Trichophyton rubrum

and

Trichophyton menta-
grophytes

. There are four types of onychomycosis:
distal subungual, proximal subungual, white super-
cial, and candidal. Proper diagnosis of the
presence of fungi is necessary prior to initiation
of therapy. Diagnostic methods include use of a
potassium hydroxide preparation, fungal culture,
and/or nail plate biopsy with periodic acid-Schiff
(PAS) stain. Approved topical treatments of ony-
chomycosis have low efcacy rates. Ciclopirox
lacquer is less effective than oral agents such as
itraconazole and terbinane. For onychomycosis
of the toenails, itraconazole may be administered
at 200 mg per day for at least three months or given

No nancial support was received for the following manuscript.
Address correspondence and reprint requests to: David B.
Huang, MD, MPH, Department of Medicine, Division of
Infectious Diseases, Baylor College of Medicine, One Baylor
Plaza, BCM 286, Room N1319, Houston, TX 77030, or
email: dhuang1@bcm.tmc.edu.
Huang et al.

518

as pulse therapy at 200 mg twice a day for one
week per month and no therapy for the remaining
three weeks and treated for three months or
longer (1). For onychomycosis of the ngernails,
itraconazole may be given at 200 mg per day for at
least two months; or at 200 mg twice a day for one
week per month and no therapy for the remaining
three weeks and treated for two months or longer.
Terbinane is also an option for onychomycosis
(1). Terbinane 250 mg per day is given for three
months for toenail infections and two months for
ngernail infections. Treatment with both itracon-
azole and terbinane for longer than one month
requires laboratory monitoring of liver function
tests pretreatment and at four- to eight-week
intervals. Both itraconazole and terbinane
are metabolized by the P-450 3A enzyme system
and may have drug interactions with other medi-
cations. Itraconazole is contraindicated with
cisapride, dofetilide, lovastatin, midazolam,
pimozide, quinidine, simvastatin, and triazolam.
Griseofulvin is also effective for onychomycosis
but must be used for at least four months for
ngernail infections and at least six months for
toenail onychomycosis.

Dermatophytoses

Tinea infections include tinea pedis (feet) (FIG. 2),
tinea barbae (beard area), tinea corporis (general
skin), tinea cruris (groin), tinea capitis (head/scalp)
(FIG. 3), and tinea manuum (limited to the hands).
Tinea infections are caused by three genera of
dermatophytes

Trichophyton

,

Microsporum

and

Epidermophyton

(2). Supercial skin infections
can also be caused by nondermatophytes such
as

Candida

spp. and

Malassezia furfur

in tinea
versicolor. The majority of dermatophytoses are
caused by

T. rubrum.

Most dermatophytes con-
ned to supercial keratinized tissue can be
treated with topical antifungal therapy with a cure
rate greater than 80% (3,4). Topical antifungals
do not penetrate hair or nails so dermatophytes
involving the hair or nails generally need to be
treated with systemic antifungal therapy (5,6). In
addition, systemic antifungal therapy should be
given consideration when lesions involving a large
body surface area fail to clear with repeated treat-
ment using different topical agents (6).
Table 1 lists the indications, formulation, and
frequency of application for common antifungals
used for treatment of dermatophyte infections.
There are limited numbers of studies comparing
the individual agents available. The formulation is
important, as creams or solutions are preferred
for ssured or inamed intertriginous areas and
powders conned to mild lesions of the same
areas. Generally, for tinea corporis and tinea cruris,
topical agents are applied on affected areas and
2 cm beyond once to twice daily for two weeks.
Topical treatment should be given for at least one
week after signs and symptoms resolve.
FIG. 1. Onychomycosis of the toenails.
FIG. 2. Tinea pedis.
Therapy of common supercial fungal infections

519

Combination therapy with antifungals and
corticosteroids may be considered when inam-
mation such as erythema, pruritus, and burning
exist. Clotrimazole-betamethasone (Lotrisone) is
a combination antifungal/steroid agent indicated
for the treatment of dermatophytosis. This ther-
apy has been shown to be efcacious for tinea
cruris and tinea corporis in two randomized con-
trolled studies (7,8). The rst study examined the
efcacy of 1% clotrimazole/0.05% betamethasone
dipropionate versus each of the individual com-
ponents in the treatment of patients with tinea
cruris. The combination antifungal/steroid ther-
apy was found to be more efcacious than either
of the components alone in the clearance of tinea
cruris. The second study examined the efcacy
and safety of 1% clotrimazole/0.05% betametha-
sone dipropionate versus each of its individual
components in patients with tinea cruris or tinea
corporis (8). Each of the three groups received
treatment twice a day for two weeks. At the end
of two weeks, patients in the group receiving
combination antifungal/steroid therapy had an
increased resolution of signs and symptoms asso-
ciated with tinea infection compared to each of its
individual components. All three treatment groups
were found to be safe and there were no reports of
adverse events. Physicians should, however, be
cautious with the long-term use (> two weeks) of
betamethasone (i.e., burning at the area of
application, dryness, itching, thinning of skin,
and striae), especially in the groin area.
Griseofulvin is also used to treat tinea infections.
Griseofulvin is considered the drug of choice for
tinea capitis by some authorities, however, there
are concerns with resistance and toxicities with
this antifungal agent. Griseofulvin is available as
a tablet, a capsule, and in liquid formulation. It is
usually taken once a day or can be taken two to
four times a day. Griseofulvin is usually taken
for two to six weeks for skin infections, four to
eight weeks for hair and scalp infections and four
to eight weeks for foot infections.

Supercial

Candida

infections

Onychomycosis caused by

Candida

spp. may be
treated with itraconazole or terbinane as described
above. For other supercial

Candida

infections
such as cutaneous (FIG. 4) including intertrigo
in skin folds, vaginal or penile lesions, topical
treatment with polyenes (e.g., clotrimazole, micon-
azole, and nystatin), or azoles or systemic treatment
with azoles (i.e., ketoconazole, uconazole, or vori-
conazole) usually are very efcacious (Table 1) (9).

Candida

spp. often affect mucous membranes,
such as oral candidiasis, in immunocompetent and
especially among immunocompromised individ-
uals (FIG. 5). In immunocompetent individuals,
nystatin oral suspension, topical azoles, ucon-
azole single dose orally, or amphotericin B oral
suspension may be used. Among immunocompro-
mised individuals, systematic therapy is preferred
because topical agents are associated with a high
relapse rate (10). Oral therapy with uconazole
(100200 mg/day for two weeks) has a clinical
cure of 84% and mycological cure of 48% in HIV
patients and is likely higher in immunocompetent
individuals (11). With increasing use of uconazole,
uconazole-resistant candidiasis (dened as a MIC

24

g/mL) has been more frequently reported
(12). A gradual increase in minimal inhibitory
concentration (MIC) for

Candida albicans

occurred
in patients who received repeated uconazole
therapy for recurring oropharyngeal candidiasis.
FIG. 3. Tinea capitis with diffuse scaly patches on
the scalp.
Huang et al.

520

Thirteen of 65 (20%) HIV-infected patients devel-
oped in vitro uconazole-resistant

C. albicans

isolates after the repeated use of uconazole for
the treatment of oropharyngeal candidiasis (12).
Itraconazole (200 mg per day for two to four weeks)
may be useful for patients with uconazole-
refractory oral candidiasis (12). Fluconazole and
itraconazole swish and swallow solutions are avail-
able and effective as antifungal therapy for oroph-
aryngeal and supercial

Candida

skin infections.
Itraconazole has a clinical cure of 74% and myco-
logical cure of 40% in HIV patients. In the capsule
formulation, unlike uconazole, itraconazole must
not be taken in patients with hypochlorhydria. The
oral solution of itraconazole has a reliable absorp-
tion and greater bioavailability than the capsule
formulation with a clinical cure of 97% and a
mycological cure of 88% in immunocompromised
Table 1. Antifungal agents available for the treatment of common supercial fungal infections

Indications Antifungal (trade name) Formulation Frequency
Onychomycosis Ketaconazole (Nizoral) Oral 200 mg per day for 23 months
Terbinane (Lamsil) Oral 250 mg per day for 6 weeks for
ngernails and 12 weeks for toenails
Tinea infections Butenane (Mentax) 1% Cream Once or twice daily
Ciclopirox (Loprox, Penlac) 1% Lacquer, lotion, cream Twice daily
Clotrimazole (Lotrimin) 1% Solution, lotion, cream Twice daily
Econazole (Spectazole) 1% Cream Once daily
Griseofulvin (Fulvicin,
Grifulvin, Gris-PEG,
Grisactin, Gristatin)
Oral 500 mg per day for 46 weeks in adults
for tinea capitis, corporis, cruris,
or pedis; and 1020 mg/kg per day
for 68 weeks in children for tinea
capitis, 24 weeks for corporis, and
48 weeks for pedis
Haloprogin (Halotex) Solution, cream Twice daily
Ketaconazole (Nizoral) 2% Shampoo, 1% Cream Twice weekly, once daily
Miconazole (Micatin) 2% Solution, lotion,
cream, powder
Twice daily
Naftine (Naftin) 1% Cream, 1% Gel Once daily
Oxiconazole (Oxistat) 1% Lotion, cream Once or twice daily
Sulconazole (Exelderm) 1% Lotion, cream Once or twice daily
Terbinane (Lamsil) 1% Solution, 1% Cream Once or twice daily
Tonaftate (Tinactin) 1% Solution, lotion,
cream or powder
Twice daily
Oral Candidiasis Nystatin (Mycostatin) Solution 46 ml swish and swallow solution
four times daily for 2 weeks
Amphotericin B (Fungizone) Solution 1 ml oral suspension swish and swallow
four times daily for 2 weeks
Anidulafungin
(LY303366, VER-002)
Intravenous Unknown
Fluconazole (Diucan) Oral In non-AIDS patients, 200 mg single
dose
Itraconazole (Sporanox) Oral In AIDS patients, 200 mg the rst day,
then 100 mg for 2 weeks 200 mg
per day for 2 weeks 50 mg per day
for 10 days
Micafungin (FK463) Intravenous
Voriconazole (Vfend) Oral or intravenous IV: Loading dose 6 mg/kg every
12 hours for 1 day, then maintenance
dose at 4 mg/kg every 12 hours
Oral: > 40 kg body weight: 400 mg orally
every 12 hours for 1 day, then 200 mg
orally every 12 hours; < 40 kg body
weight: 200 mg orally every 12 hours
for 1 day, then 100 mg orally every
12 hours
Therapy of common supercial fungal infections

521

patients (13). Voriconazole is a relatively new anti-
fungal that should be a useful addition to the avail-
able therapies for supercial

Candida

infections
such as oral candidiasis.
Echinocandins are antifungal agents that inhibit
glucan synthesis, a major component of the
fungal cell wall of which Caspofungin (Cancidas) is
the most well known. Echinocandins are effective
against uconazole-resistant strains, have excel-
lent clinical efcacy, and provide improved safety
proles in individuals with supercial

Candida

infections. Two phase III studies are currently
underway to examine the clinical efcacy of anidula-
fungin (LY303366, VER-002) compared to ucon-
azole for the treatment of invasive candidiasis.
Micafungin (FK463), also a member of the echino-
candin class of antifungals, is being developed
for intravenous use and is currently in Phase II
trials (14). Both anidulafungin and micafungin have
a broad spectrum activity against

Candida

spp.,
including azole resistant

C. albicans

and some molds
such as

Aspergillus

spp. (1416).

Severe supercial skin/systemic
fungal infections

Severe supercial and systemic fungal infections
involving the skin often require systemic anti-
fungal therapy in the presence or absence of
topical antifungals. A dedicated section is included
in this issue discussing the available therapy for
severe supercial and systemic fungal infections.

Prevention

In addition to treatment, preventive measures
of fungal infections such as tinea infections
include practicing good personal hygiene; keep-
ing the skin dry and cool at all times; wearing
loose-tting garments made of cotton or synthetic
material; and avoiding sharing towels, clothing, or
hair accessories with infected individuals.

Summary

Supercial fungal infections are common espe-
cially with the involvement of the nails, skin, and
mucous membranes. Onychomycosis accounts
for a great majority of nail disorders. Tinea infec-
tions are the most common fungal infection
worldwide. Ubiquitous candidal organisms are
found in the oral ora of many healthy persons
and result in infection in the presence of certain
host factors or immunodeciency disorders. A
number of antifungals are currently available and
in development for the treatment of supercial
fungal infections. Thus, it is important that both
dermatologists and primary care physicians are
familiar with the many cutaneous fungal infec-
tions and their differential diagnosis to ensure
that appropriate therapy is selected.

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