Mycopathologia (2008) 166:353–367
DOI 10.1007/s11046-008-9109-0
Update in Antifungal Therapy of Dermatophytosis
Aditya K. Gupta Æ Elizabeth A. Cooper
Received: 15 October 2007 / Accepted: 30 January 2008 / Published online: 14 May 2008

Springer Science+Business Media B.V. 2008
Abstract Treatment of dermatophyte infection
involves primarily oral and/or topical formulations
of azoles or allylamines, particularly itraconazole and
terbinafine. Topical medications applied once or
twice daily are the primary treatment indicated for
tinea corporis/cruris, and tinea pedis/manuum. Use of
oral antifungals may be practical where the tinea
involvement is extensive or chronic, or where appli-
cation of a topical is not feasible. For tinea unguium
(onychomycosis) and tinea capitis, oral therapies are
the primary treatments provided. Recently, topical
amorolfine and ciclopirox formulations have been
approved for use in milder onychomycosis cases, and
their role in the treatment of the different clinical
forms of onychomycosis is currently being defined.
Relapse of infection remains a problem, particularly
with tinea pedis/unguium. Appropriate follow-up
duration and education of patients on proper foot
hygiene are also important components in providing
effective therapy.
A. K. Gupta
Division of Dermatology, Department of Medicine,
Sunnybrook Health Sciences Center, Toronto, ON,
Canada
A. K. Gupta
University of Toronto, Toronto, ON, Canada
A. K. Gupta (&)
E. A. Cooper
Mediprobe Research Incorporated, 645 Windermere
Road, London, ON, Canada N5X 2P1
e-mail: agupta@execulink.com
Introduction
Dermatophyte organisms infect humans across the
world, with widely varying frequency and epidemi-
ology. Nonetheless, treatment methods are similar
across the world, and modern antifungal medications
can provide effective treatment for most presenta-
tions of dermatophytosis.
There are few new medications available for
dermatophyte infection. Most agents, even where
new, remain within the two main antifungal drug
families, the azoles and the allylamines; a newer
class, the echinocandins, is currently used only for
systemic Candida/Aspergillus infection [1, 2]. Inno-
vation in dermatophyte treatment has involved
marketing of wide-spectrum topical agents, use of
topical agents with anti-inflammatory as well as
antifungal actions, and use of a combination of
existing oral antifungal agents, or oral/topical anti-
fungal agents, in attempts to improve on
monotherapy cure rates.
Current country-specific prescribing information
for any antifungal should be consulted prior to
providing any medication. The information provided
in this article may not reflect country-specific prac-
tices, due to the variation in antifungal formulations
and availability outside of North America. Regarding
the variety of topical antifungals available, this article
provides a general picture of topical antifungal
treatment using topical medications most frequently
cited in medical literature, and does not attempt to
123
354
provide a comprehensive listing of all topical
antifungals available.
Topical Antifungal Medications
Topical medications applied once or twice daily are
the primary treatment indicated for tinea corporis/
tinea cruris, and tinea pedis/tinea manuum (Table 1).
A wide variety of topical agents are available, in
cream, gel, lotion, and shampoo formulations [3–10].
A majority of the agents are of the ‘azole’ antifungal
family (clotrimazole, miconazole, econazole, oxicon-
azole, tioconazole, …). Terbinafine and naftifine
represent the ‘allylamine’ family of agents. Both
families of drugs are known for their high efficacy
against the dermatophytes. In addition, amorolfine
and butenafine are popular antifungals classed as
morpholine derivatives. Cure rates of tinea corporis/
tinea cruris/tinea pedis are high, with infections
resolving with 2–4 weeks of topical therapy. Safety
of therapy is less of a concern for topical medications
than oral medications, as serum absorption tends to
be minimal with topical dermatophytosis therapy.
Most adverse events following topical drug applica-
tion are skin reactions at the application site, which
are mild and transient [11].
Bacterial superinfection may be present in some
cases of dermatophytosis, particularly in tinea pedis,
thus a topical antifungal agent providing both anti-
bacterial and antifungal activity may be desired, and
many available agents have wide-spectrum effect.
Similarly, inflammation is a component of some
dermatophytoses, and there are several topical anti-
fungal agents, which provide anti-inflammatory
action as well as effective antifungal therapy.
Systemic Antifungal Medications
For tinea unguium (onychomycosis) and tinea
capitis, oral therapies are the primary treatments
provided, though there is evidence to suggest
topicals can be effective in less-severe grades of
onychomycosis infection and two topical agents,
ciclopirox and amorolfine, have been approved for
onychomycosis therapy (Table 1). Five main sys-
temic agents are available: terbinafine, itraconazole,
fluconazole, griseofulvin, and ketoconazole. Oral
123
Mycopathologia (2008) 166:353–367
formulations of itraconazole and terbinafine are the
most common drugs used for onychomycosis. Gris-
eofulvin plays a large role in tinea capitis treatment,
though its use has been superseded in other areas by
itraconazole and terbinafine. The main pharmaco-
logical and safety properties of the oral agents are
listed in Table 2.
The oral antifungal medications may be associated
with some potential for severe hepatic toxicity, rare
serious skin events such as Stevens–Johnson syn-
drome, and possible drug–drug interactions due to
metabolism through the cytochrome P-450 system
[12–17]. Current country-specific prescribing infor-
mation for any oral antifungal medication should be
consulted prior to providing any medication.
Though oral antifungals are typically not approved
for use in children, pediatric use has been docu-
mented widely in the medical literature for numerous
indications, and has typically provided safety profiles
similar to use in adults [18–20]. Oral suspensions are
available for many of the oral antifungals, providing
easier dosing for children; however, the pharmaco-
logical profiles of oral suspensions may differ from
capsule/tablet dosage.
Oral terbinafine is indicated for the treatment of
adults with dermatophyte onychomycosis of the
toenails and/or fingernails. Serum transaminase tests,
i.e., alanine transaminase (ALT) and aspartate trans-
aminase (AST) are suggested prior to beginning oral
terbinafine and periodically during therapy, as there is
some potential for liver dysfunction/damage with
terbinafine use [12]. Terbinafine is not recommended
for patients with existing liver disease [12, 21].
Terbinafine has been reported infrequently to precip-
itate or exacerbate cutaneous and systemic lupus
erythematosus, and should be discontinued in patients
showing signs of lupus erythematosus; furthermore,
physicians should consider monitoring complete
blood counts in patients with known or suspected
immunodeficiency who are administered oral terbi-
nafine for longer than 6 weeks [12]. Terbinafine is
metabolized through the CYP2D6 enzymes, and thus
may interfere with other CYP2D6 drugs. Other drug
interactions are possible, and a current country-
specific product monograph should be consulted for
complete listing of known drug interactions, warn-
ings and monitoring requirements prior to
prescribing. Terbinafine may be taken in fasted or
fed state without affecting absorption.
 Table 1 Treatment options available for dermatophytoses
Terbinafine Itraconazole Fluconazole Ketaconazole Griseofulvin Topicals

Tinea pedis/ Creamb: apply twice Oral: 200 mg Oral: 150 mg once 2% Creamb: apply Microsizeb Ciclopiroxb Clotrimazoleb
manuuma daily 9 1–4 weeks bid for 1 week weekly for once daily for 1 g/day 0.77% Miconazoleb
b 2–6 weeks 6 weeks cream and
1% Solution : apply Ultramicrosize 660 Butenafineb
twice daily for Oralb: 200–400 or 750 mg/day gel twice
daily for Econazoleb
1 week mg/day for [4 for 4–8 weeks
weeks 4 weeks Naftifineb
Mycopathologia (2008) 166:353–367

Oral: 250 mg/day

2 weeks Antifungal Oxiconazoleb
powder for
prevention
Tinea corporis/ Creamb: apply twice Oral: 200 mg/day Oral: 150–300 mg 2% Creamb: apply Microsizeb Ciclopiroxb Clotrimazoleb
cruris daily 9 1–4 weeks for 1 week once weekly for once daily for 500 mg/day 0.77% Miconazoleb
b 2–4 weeks 2 weeks cream and
1% Solution : apply Ultramicrosize Butenafineb
twice daily for Oralb: 200–400 mg/ 330–375 mg/day gel twice
daily for 4 Econazoleb
1 week day for 4 weeks for 2–4 weeks
Naftifineb
Oral: 250 mg/day for
2–4 weeks Oxiconazoleb
Tinea capitis See Table 3: Pediatric See Table 3: See Table 3: Pediatric Only effective against See Table 3: Selenium Corticosteroid
dosing Pediatric dosing dosing Trichophyton Pediatric Dosing sulfide adjunct
2% shampoo used as shampoo therapy for
adjunct therapy 1% as severe
adjunct inflammatory
therapy varieties
Onychomycosis Oral: 250 mg/day Oral: Pulse therapy: Oral: 150 or 300 mg Oral: 200–400 mg/Microfine preparation: Amorolfine Ciclopiroxb 8%
Toenail: 12–16 weeks 200 mg bid for once weekly for day 9 6 months 500 mg daily 5% lacquer lacquer once
1 week, followed 6–12 months Not recommended due for 6–12 months daily for
Fingernail: 6 weeks
by 3 itraconazole- (Toenail: approx. to hepatotoxicity (FDA approved: 48 weeks
free weeks 9–15 months; risk Microsize 1 g/day
Toenails: 3 pulses Fingernail: Ultramicrosize 660
Fingernails only: approx. 4–9 months) or 750 mg/day
2 pulses for 4–12 months)
a
There are no approved treatments specifically for tinea manuum; treatments shown are for tinea pedis which are effective in the treatment of tinea manuum
b
FDA approved indication
355

123

Table 2 Summary of systemic antifungal agent properties
Terbinafine [12]
123
Chemistry Allylamine
Available as tablet
Inhibits squalene
epoxidase = ergosterol
deficiency (fungistatic) and
accumulation of squalene
(fungicidal)
Lipophilic; Binds strongly
([99%) and nonspecifically
to plasma proteins
Extensively metabolized in
liver
Metabolism Reported to inhibit CYP 2D6
in vitro: use with caution in
patients with concomitant 2D6
substrates such as tricyclic
antidepressants
Contraindications None
Cautions Monitor CYP2D6-metabolized
drug concentration for
increases (tricyclic
antidepressants, selective
serotonin reuptake inhibitors,
beta-blockers and monoamine
oxidase inhibitors type B)
356
Itraconazole [13] Fluconazole [14] Griseofulvin [15, 16] Ketoconazole [17]
Triazole Bis-triazole Spiro-benzo[b]furan Imidazole
Available as capsule, oral Available as tablet, oral Available as tablet or oral Available as tablet
solution or IV formulation suspension or IV formulation suspension Inhibition of C14 demethylation
Inhibits fungal lanosterol Inhibits fungal lanosterol 14-aDisruption of fungal cell mitotic of cell membrane sterols (e.g.
14-a demethlyase = ergosterol demethylase = ergosterol spindle, arresting cell division lanosterol); fungistatic;
deficiency (fungistatic) deficiency (fungistatic) (fungistatic) Concentrated in fungicidal at high
Lipophilic; binds strongly More hydrophilic than other azoles skin, hair, nails, liver, fat and concentrations;
to plasma proteins ([99%) skeletal muscles; deposited in 84–99% bound to plasma
Protein binding of 11–12% keratin precursor cells, and proteins
Extensively metabolized in the
No significant first-pass bound to new keratin Partially metabolized in liver
liver predominantly by CYP3A4 hepatic metabolism
Oxidative demethylation
principally in liver
Potential for itraconazole Potent inhibitor of CYP2C9, Induces hepatic enzymes— May inhibit synthesis of
metabolism alteration where and CYP2C19; weaker potential for adverse events, adrenal steroids, testosterone
CYP3A4 is altered by other inhibition of CYP3A drug interactions Potent inhibitor of CYP3A
medications group—potential for drug group—possible drug
interactions interactions
Patients with evidence of Severe liver disease; Use with Patients with porphyria or Cisapride
ventricular dysfunction such as caution in patients sensitive hepatocellular failure Triazolam
congestive heart failure (CHF) or to other azoles
a history of CHF; Cisapride, Terfenadine, Astemizole
Cisapride
Midazolam (oral), Triazolam,
Terfenadine, Astemizole, Terfenadine
Pimozide, Quinidine, Dofetilide,
Levacetylmethadol
(levamethadyl) HMG CoA-
reductase inhibitors: lovastatin,
simvastatin, ...; Ergot alkaloids
metabolized by CYP3A4:
dihydroergotamine, ergometrine
(ergonovine), ergotamine,
methlergometrine
(methylergovovine)
Use is strongly discouraged for Discontinue in patients Use with caution in patients with Close monitoring of hepatic
patients with elevated or showing signs/symptoms penicillin sensitivity function required;
abnormal liver enzymes or active of liver disease Female patients should be aware Discontinue in patients
liver disease, or who have Use with caution in patients that there is a possibility of showing signs/symptoms of
experienced liver with potential proarrhythmic decreased oral contraceptive liver disease
toxicity with other drugs conditions efficacy with griseofulvin use Recommended dosage should
be followed closely to avoid
depression of adrenocortical
function and serum
testosterone
Mycopathologia (2008) 166:353–367
 Table 2 continued
Terbinafine [12]
Not recommended for patients with Baseline LFTs for all patients;
chronic or active liver disease; Discontinue in patients showing
baseline LFTs for all patients
Not recommended for
patients with renal impairment
(creatinine clearance
B50 ml/min)
Discontinue in patients with
clinical signs or symptoms
of lupus erythematosus
Monitor complete blood counts
in patients with known or
suspected immunodeficiencies
(terbinafine used [6 weeks),
for decrease in lymphocyte
counts, neutrophil counts
Adverse events GI: Diarrhea (5.6%), dyspepsia
(4.3%), nausea (2.6%),
abdominal pain (2.4%),
flatulence (2.2%), taste
disturbance (2.8%) Cutaneous:
Rash (5.6%), pruritis (2.8%),
urticaria (1.1%) CNS: Headache Cutaneous: Rash (4%)
(12.9%) Hepatic/Renal: Liver
enzyme abnormalities (C29
upper limit of normal) (3.3%)
Other: Visual disturbance (1.1%)
123
Itraconazole [13] Fluconazole [14] Griseofulvin [15, 16] Ketoconazole [17]
Monitor patients developing rashes Patients using oral
closely for signs of exfoliative hypoglycemics should
signs/symptoms of liver disease skin disorders closely monitor blood sugar;
Use with caution in patients Patients using oral hypoglycemics may need to adjust
sensitive to other azoles should closely monitor blood hypoglycemic dosing
Advise patients with risk factors sugar; may need to adjust
for CHF (ischemic and valvular hypoglycemic dosing
disease, significant pulmonary
disease, renal failure or other
edematous disorders) to watch
Mycopathologia (2008) 166:353–367
for signs and symptoms of CHF
Discontinue if signs of neuropathy
develop
Patients using oral hypoglycemics
should closely monitor blood
sugar; may need to adjust
hypoglycemic dosing
Drug (capsules) should be taken
after a full meal or with an 8oz
cola beverage
GI: Diarrhea (4%), dyspepsia (4%), GI: Nausea (3.7%), vomiting GI: Epigastric distress; nausea, GI: Nausea and/or vomiting
flatulence (4%), abdominal pain (1.7%), abdominal pain (1.7%), vomiting, excessive thirst; (3–10%); 1% or less of
(4%), nausea (3%), appetite diarrhea (1.5%) flatulence; diarrhea; oral thrush patients: Abdominal pain,
increase (2%), constipation Cutaneous: Skin rash (1.8%) Cutaneous: Hypersensitivity constipation flatulence, GI
(2%), gastritis (2%), reactions including rash, and bleeding, diarrhea
gastroenteritis (2%) urticaria CNS: Headache, Cutaneous: Pruritis (2%)
fatigue, dizziness, insomnia
Less than 1%: Rash, dermatitis,
purpura, urticaria
357
 Table 2 continued
Terbinafine [12]
123
Rare events based on worldwide
experience with terbinafine
tablets:
Idiosyncratic and symptomatic
hepatic injury and cases of liver
failure, some leading to death or
liver transplant; Serious skin
reaction (Stevens–Johnson
syndrome, toxic epidermal
necrolysis); Changes in ocular
lens and retina; Agranulocytosis;
Thrombocytopenia, angioedema
and allergic reactions (including
anaphylaxis); Transient
decreases in absolute
lymphocyte count; cases of
severe neutropenia; Precipitation Rare cases of serious hepatotoxicity
and exacerbation of cutaneous
and systemic lupus
erythematosus; malaise; fatigue;
vomiting; arthralgia; myalgia;
hair loss;
Itraconazole [13]
CNS: Headache (10%), dizziness
(4%), abnormal dreaming (2%)
Hepatic/Renal: Liver function
abnormality (3%), liver enzyme
abnormalities (C2x upper limit
of normal) (4%), urinary tract
infection (3%)
Other: Rhinitis (9%), upper
respiratory tract infection (8%),
sinusitis (7%), cystitis (3%),
myalgia (3%), asthenia (2%),
fever (2%), pain (2%), tremor
(2%), herpes zoster (2%),
pharyngitis (2%)
Post-marketing experiences (rare):
including liver failure and death;
Vomiting; Peripheral edema,
congestive heart failure,
pulmonary edema; Peripheral
neuropathy; Menstrual disorders;
Reversible increases in hepatic
enzymes, hepatitis, liver failure;
Hypokalemia,
kypertriglyceridemia; Alopecia;
Allergic reactions (pruritis, rash,
urticaria, angioedema,
anaphlaxis); Stevens–Johnson
syndrome; Anaphylactic,
anaphlactoid and allergic
reactions; Photosensitivity;
Neutropenia; Congenital
abnormality including skeletal,
genitourinary tract,
cardiovascular and ophthalmic
malformations as well as
chromosomal and multiple
malformations (causal relation to
itraconazole not established)
Fluconazole [14]
CNS: Headache (1.9%)
Post-marketing experiences (rare):
Rare cases of serious hepatic
reactions ranging from mild
transient elevations in
transaminases to clinical
hepatitis, jaundice, cholestasis,
and fulminant hepatic failure,
including fatalities; Rare cases
of anaphlyaxis (including
angioedema, face edema and
pruritis); QT prolongation,
torsade de pointes; Seizures;
Dizziness; Alopecia; Exfoliative
skin disorders including
Stevens–Johnson syndrome
and toxic epidermal necrolysis;
Leucopenia, including
neutropenia and agranulocytosis;
Thrombocytopenia;
Hypercholesterolemia,
hypertriglyceridemia,
hypokalemia; Dyspepsia,
vomiting, and taste perversion
Griseofulvin [15, 16]
Post-marketing experiences (rare):
Paresthesia of hands and feet;
Mental confusion, impairment
of performance of routine
activities and psychotic
symptoms with large doses; GI
bleeding; Angioedema;
Erythema multiformae-like
reaction, serum-sickness-like
reaction; Photosensitivity;
Lupus erythematosus, lupus-
like syndrome or exacerbation
of preexisiting lupus
erythematosus; Toxic
epidermal necrolysis;
Proteinuria, nephrosis;
Hepatotoxicity; Menstrual
irregularity, amenorrhea;
Estrogen-like effects in
children; Transient diminution
of hearing; Reversible
leucopenia; Elevated
concentrations of porphyrins in
feces and erythrocytes;
Tachycardia, flushing when
concomitant with alcohol, and
potentiation of alcohol effects
358
Ketoconazole [17]
CNS: Less than 1%: Headache,
dizziness, somnolence,
lethargy, asthenia,
nervousness, insomnia,
abnormal dreaming,
photophobia, paresthesia
Hepatic/Renal: Transient
increases in serum
AST(SGOT), ALT (SGPT)
and alkaline phosphatase
Other: Less than 1%:
Arthralgia, fever and chills,
dyspnea, tinnitus, impotence,
changes in sweat patterns,
alopecia, signs of increased
intracranial pressure,
hemolytic anemia,
thrombocytopenia,
leucopenia
Post-marketing experiences
(rare):
Hepatotoxicity (hepatocellular,
cholestatic or mixed pattern),
typically reversible, death
rarely; Bilateral
gynecomastia with breast
tenderness in some men;
Adrenocorticol insufficiency;
Transient decrease in serum
cholesterol, alterations in
serum triglyceride
concentrations; Anaphylactic
reactions after first dose;
Neuropsychiatric
disturbances including
suicidal tendencies, severe
depression; Hypertension in
several subjects receiving
400 mg every 6–8 h for
metastatic prostate
carcinoma; Disulfiram
reactions (flushing, rash,
peripheral edema, nausea,
headache) when ingesting
alcohol
Mycopathologia (2008) 166:353–367
Mycopathologia (2008) 166:353–367
Oral itraconazole is indicated for the treatment of
adults with dermatophyte onychomycosis of the
toenails and/or fingernails, and for systemic mycoses
such as blastomycosis, histoplasmosis, and aspergil-
losis. Liver function monitoring should be considered
for any subject, and testing is required for any subject
with pre-existing hepatic function abnormalities or
previous experience of liver toxicity with other
medications [13]. Itraconazole is metabolized
through the CYP3A4 pathway and thus has potential
for numerous drug interactions, limiting its use in
some patients. Itraconazole is prohibited in patients
showing ventricular dysfunction such as current or
past congestive heart failure [13]. A current country-
specific product monograph should be consulted for
complete listing of known drug interactions, warn-
ings and monitoring requirements prior to
prescribing. Capsules must be taken with a meal, or
cola beverage to ensure adequate absorption [13, 21].
Oral fluconazole is indicated for the treatment of
(1) vaginal candidiasis (vaginal yeast infections due
to Candida species), (2) oropharyngeal and esopha-
geal candidiasis, and (3) cryptococcal meningitis
[14, 22]. Though not specifically indicated for
dermatophyte infection, fluconazole has been docu-
mented in the medical literature as a successful agent
for all types of superficial dermatophytoses, particu-
larly tinea capitis. When fluconazole and cyclo-
sporine are given concomitantly, careful monitoring
of cyclosporine concentration and serum creatinine
concentration is recommended [14]. Similarly, blood
glucose levels should be closely monitored when
using oral hypoglycemics concomitantly with fluco-
nazole, and prothrombin time should be monitored
for patients receiving coumarin-type anticoagulants
concomitantly with fluconazole.
Oral griseofulvin is indicated for the treatment of
tinea infections of the skin, hair, and nails [15, 16].
As with other oral antifungal agents, the use of
griseofulvin is not justified for the treatment of tinea
infections that would be expected to respond satis-
factorily to topical antifungals. During prolonged
griseofulvin therapy, periodic assessment of renal,
hepatic, and hematopoietic functions should be
performed [15, 16].
Oral ketoconazole is indicated for the treatment of
patients with severe recalcitrant cutaneous dermato-
phyte infections who have not responded to topical
therapy or oral griseofulvin, or who are unable to take
359
griseofulvin, as ketoconazole has been associated
with a potential for liver damage [17]. Patients using
oral ketoconazole should be tested for signs of liver
dysfunction prior to initiating therapy. While on
therapy, patients should be closely monitored for
signs of hepatotoxicity, both clinically and biochem-
ically, using liver function tests, including serum
AST, ALT, alkaline phosphatase, gamma-glutamyl-
transferase, and bilirubin (e.g., biweekly during the
first 2 months of therapy; monthly or bimonthly
afterwards) [17]. Patients should be instructed to
report any symptoms of liver dysfunction such as
persistent nausea, anorexia, fatigue, vomiting, right
upper abdominal pain or jaundice, dark urine or pale
stools.
Treatment of Tinea Pedis/Tinea Manuum
Topical formulations of terbinafine, butenafine, mico-
nazole, econazole, ketoconazole, clotrimazole,
oxiconazole, and ciclopirox are the most frequently
used topical preparations for tinea pedis/tinea man-
uum [23–25] (Table 1). Topical formulations may be
used for milder, limited presentations. Many topical
agents (e.g., miconazole nitrate 1%, ciclopirox ola-
mine 1%, naftifine hydrochloride 1%, sulconazole
nitrate 1%) provide antibacterial activity and may be
preferred where bacterial superinfection is suspected.
Formulations allowing once-daily application rather
than twice-daily (e.g., naftifine 1% cream, bifonazole
1%, ketoconazole cream 2%) may aid patient com-
pliance and subsequent efficacy. There are no
approved treatments specifically for tinea manuum;
treatments for tinea pedis are effectively used to treat
tinea manuum.
Chronic infection may warrant the use of oral
antifungals, particularly if previous topical regimens
have failed. Off-label use of oral itraconazole,
terbinafine, or fluconazole may be practical where
the tinea involvement is extensive and application of
a topical is not feasible [26]. Studies have shown that
oral terbinafine and itraconazole may be the most
effective treatments, and a higher cure rate has been
shown with topical allylamines than with topical
azoles [23, 27]. Terbinafine 250 mg/day has been
used for tinea pedis with a duration of 2–6 weeks
[11, 28]. Itraconazole regimens of 100 mg/day for
30 days or 4 weeks, 400 mg daily for 1 week, and
123
360
200 mg/day for 2–4 weeks have been reported [11,
26, 29]. The dose of fluconazole for tinea pedis most
frequently reported is 150 mg once weekly adminis-
tered for 2–6 weeks [30–37].
Though oral griseofulvin is approved for treatment
of tinea infections that are not expected to respond
satisfactorily to topical antifungals, griseofulvin has
lower efficacy than the newer antifungals, poor
keratin adherence, and narrow-spectrum activity
(dermatophytes only) which may be a limitation
where superimposed bacterial infection is present
[11]. Where griseofulvin dosing is used, the sug-
gested dosage for tinea pedis is 660 or 750 mg daily
for 4–8 weeks [11]. Similarly, use of ketoconazole
tablets has been discouraged due to the potential for
hepatic side effects; however ketoconazole dosing of
200–400 mg daily for 4–8 weeks has been used for
the treatment of tinea pedis infection [11, 17, 22, 28].
Prevention of reinfection is important, and educa-
tion of the patient on proper foot hygiene is essential.
Patients should avoid walking barefoot in communal
areas such as bathrooms, showers or swimming areas,
and ensure that feet are dried thoroughly after
bathing, showering, or swimming [38]. Occlusive
footwear should be avoided, or shoes should be
alternated every 2–3 days, with frequent sock
changes to reduce the moisture in the foot environ-
ment [38].
Treatment of Tinea Corporis/Tinea Cruris
Topical therapies for treatment of tinea corporis/tinea
cruris include terbinafine, butenafine, econazole,
miconazole, ketoconazole, clotrimazole, and ciclopi-
rox [39] (Table 1). Topical formulations may
eradicate smaller areas of infection, but oral therapy
may be required where larger areas are involved or
where infection is chronic or recurrent [28].
Off-label use of oral antifungals may be practical
where the tinea involvement is extensive and appli-
cation of a topical is not feasible [26]. Oral
itraconazole, terbinafine, and fluconazole have been
used successfully in the treatment of tinea corporis/
tinea cruris. Terbinafine 250 mg/day has been used in
this clinical context with a regimen generally of
2–4 weeks [28]. A continuous itraconazole regimen
of 200 mg/day for 1 week is recommended, though a
regimen of 100 mg/day for 2 weeks has also been
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Mycopathologia (2008) 166:353–367
reported to be effective [28, 40, 41]. The dose of
fluconazole suggested for tinea corporis/tinea cruris
is 150–300 mg once weekly administered for
2–4 weeks [28]. These oral agents are preferred over
ketoconazole, due to the potential for hepatic side
effects with ketoconazole use, and griseofulvin is not
recommended as it does not adequately bind the
keratin in the stratum corneum, reducing efficacy
[28]. Where griseofulvin is used for these indications,
the suggested dosage is 250 mg twice daily until cure
is reached [28]. Similarly, where the decision is made
to provide ketoconazole, the suggested dosage is
200–400 mg daily for 4–8 weeks [28].
Treatment of Tinea Capitis
Unlike most dermatophytoses, topical monotherapy is
not recommended for tinea capitis. Oral therapy is
required to adequately treat tinea capitis, as they are
able to penetrate the infected hair shaft where topical
therapies cannot (Table 1). Topical antifungals such
as antifungal shampoos (ketoconazole, selenium
sulfide, povidone iodine, zinc pyrithione) may be
used as adjunct therapy with or without oral antifun-
gals to prevent reinfection or to treat asymptomatic
carriers [38, 42, 43].
Griseofulvin is the only oral antifungal treatment
approved for use in tinea capitis in North America;
however use of terbinafine, itraconazole, and fluco-
nazole for tinea capitis are also reported extensively
in the medical literature. The efficacies and safety
profiles of terbinafine, itraconazole, and fluconazole
are similar to griseofulvin, and may be used where
griseofulvin therapy has failed. Itraconazole, terbina-
fine, and fluconazole have the advantage of shorter
treatment durations compared to griseofulvin [42].
Dosages are typically given on a weight-based scale,
and infections with Microsporum may require higher
dosing than infections with Trichophyton, or longer
therapy durations [42, 44]. Oral suspensions are
available for griseofulvin, itraconazole, and fluco-
nazole to aid pediatric dosing (Table 3). Terbinafine
and griseofulvin tablets can be crushed, and itraco-
nazole capsules can be opened, and added to a fatty
food such as peanut butter [45, 46].
Griseofulvin suggested dosing is 20–25 mg/kg/day
using the microsize formulation, for 6–12 weeks [43]
(Table 3). Where the ultramicrosize formulation is
 Table 3 Tinea capitis dosing in childrena
Regimen Duration Weight (kg)
10–20 21–30 31–40 41–50 [50
Mycopathologia (2008) 166:353–367

Terbinafine (continuous) 5 mg/kg/day 2–4 weeks 62.5 mg qd 125 mg qd 125 mg qd 250 mg qd 250 mg qd
Itraconazole (continuous) 5 mg/kg/day 2–4 weeks 100 mg qd, every 100 mg qd 100 mg qd/bid on 200 mg qd 200 mg qd
second day alternate days
Itraconazole (pulse)b Capsules: 5 mg/kg/day 1–3 pulses 100 mg qd, every 100 mg qd 100 mg qd/bid on 200 mg qd 200 mg bidc
second day alternate days
Oral suspension: 3 mg/kg/day 1–3 pulses
Fluconazole (continuous) Oral suspension:6 mg/kg/day 20 days
Fluconazole (pulse)d Oral suspension:6 mg/kg/day 8–12 weeks
Griseofulvin (continuous) Microsize: 20–25 mg/kg/day 6–12 weeks
Ultramicrosize: 10–15 mg/kg/day 6–12 weeks
Oral suspension: 15–25 mg/kg/daye 6–12 weeks
a
Durations of treatment are for Trichophyton tonsurans infection. Longer durations are needed for Microsporum canis infections. Dosing based on US FDA regulations—consult
country-specific prescribing information prior to providing dosages. qd: once daily; and bid: twice daily
b
Itraconazole pulses are given for 1 week, with 3 weeks ‘‘off’’ before starting the next pulse
c
No standard has been established in clinical trials for tinea capitis for children[50 kg, and use varies from once-daily as with continuous regimen to twice-daily 200 mg dosing
d
Fluconazole pulses are 1 day on, 6 days off, before beginning next pulse
e
Dosing based on Grifulvin V suspension 125 mg/5 ml
361

123
362
used, a dose of 10–15 mg/kg/day is suggested, as it is
more rapidly absorbed than the microsize form [43].
The oral suspension (microsize griseofulvin) contains
125 mg per 5 ml. Treatment should be continued for
2 weeks after the resolution of clinical symptoms.
Mycological cure rates and effective therapy rates are
generally high, being in the range of 80–95% and
88–100%, respectively [26, 43].
The standard terbinafine dosing regimen for tinea
capitis daily dosing is based on weight (less than
20 kg = 62.5 mg; 20–40 kg = 125 mg; greater than
40 kg = 250 mg per day) (Table 3). The duration of
therapy is generally 4 weeks, though pulse dosing
regimens and shorter durations have also been
reported to be effective [43, 47, 48]. Higher dosages
or longer duration of therapy may be required for
M. canis infection [43]. Limited studies suggested
that doses greater than 4.5 mg/kg/day might increase
cure rates in both Trichophyton and Microsporum
infections, with duration of therapy being less
important [49, 50].
Both continuous and pulse regimens of itraconaz-
ole have been used to treat tinea capitis. The
continuous regimen is 5 mg/kg/day for 4 weeks,
and the pulse therapy regimen is 5 mg/kg/day for
1 week a month, given for 2–4 months [43]
(Table 3). Where the oral solution is used, dosage
is reduced to 3 mg/kg/day, whether used as contin-
uous or pulse therapy [43, 51].
A limited number of studies have shown that
therapy with fluconazole 6 mg/kg/day lasting 2–
3 weeks can effectively treat tinea capitis [42, 43]
(Table 3). A comparative study of 5 mg/kg/day for
4 weeks showed similar efficacy to griseofulvin
6 mg/kg/day for 6 weeks [52]. Once weekly therapy
with fluconazole for tinea capitis has also been found
to be effective [53, 54].
Transmission of infection from patients and from
symptom-free carriers has been a concern for clini-
cians treating tinea capitis. Adjunct therapies can be
provided to the patient and family members to control
transmission. Infection frequently may initiate from
contact with animals, and treatment of pets may be
required. Patients and family members should be
counseled to avoid sharing items such as caps, combs,
and toys [42, 43]. Hats, combs, pillows, blankets,
scissors, etc, may be disinfected with bleach [38].
Most clinicians agree that infected children do not
need to be kept out of school once treatment is
123
Mycopathologia (2008) 166:353–367
initiated, particularly children in higher grades where
little physical contact between students is expected
[38, 43].
Tinea Unguium (Onychomycosis)
Distal-lateral subungual onychomycosis is difficult to
cure and has a high rate of recurrence [24, 55].
Fingernails may show higher treatment success rates
than toenails due to faster rates of outgrowth, and
suggested dosing regimens are shorter for fingernail
infection than toenail infection [56].
Where the nail has been injured or shows other
abnormal growth patterns, nail outgrowth may be
slow, and the nail may never regain a normal
appearance though the infection may be eradicated.
Furthermore, relapse of infection is frequently noted.
Nail growth should be assessed, and patient expec-
tations should be discussed, so the patient
understands that successful treatment is unlikely to
occur quickly, that long-term follow-up is necessary
to catch any relapses in the early stages, and that the
nail may not return to a normal appearance even
though the infection may clear.
Routine nail debridement may be complementary
for subjects using oral therapy as well as topical
therapy, particularly where the nail is thickened, or
where the infection presents as a dermatophytoma,
spike or lateral infection. A recent clinical trial
(IRON-CLAD) demonstrated that elderly subjects
receiving aggressive debridement in conjunction with
a 12-week course of oral terbinafine showed higher
rates of clinical improvement than that of subjects
who did not receive debridement [57]. Subjects
receiving debridement also showed higher rates of
treatment satisfaction [58]. Caution must be taken not
to damage the underlying skin during debridement,
particularly in subjects who are vulnerable to severe
lower limb complications, such as diabetics or
individuals with reduced lower limb profusion.
Nail avulsion is one of the traditional options
available to manage onychomycosis. Atraumatic nail
removal with urea or bifonazole compounds is
preferred to surgical removal, as surgical removal
has some potential to permanently alter the nail bed,
and may also be painful for the subject to undergo
[59–61]. Removing the infected nail plate eliminates
most of the invading fungi and allows the underlying
Mycopathologia (2008) 166:353–367
surface to be treated with conventional topical
antifungal agents [62]. Partial nail plate avulsion
may be appropriate in cases of superficial white
onychomycosis and early distal subungual onycho-
mycosis, although these management options have
not been examined in large randomized, controlled
trials [59, 63]. The utility of topical agents as
adjunctive therapy following nail avulsion also has
not been conclusively established, though some cases
may benefit [64, 65].
As with tinea pedis, proper foot and nail hygiene
may help prevent reinfection. Patients should avoid
walking barefoot in communal areas such as bath-
rooms, showers, or swimming areas, and ensure that
feet are dried thoroughly after bathing, showering or
swimming [38]. Nails should be kept short and clean.
Shoes should fit properly and socks should be made
from absorbent material such as cotton. Disinfection
of socks and shoes should be performed, and
laundering of socks in 60C water with an all-
purpose detergent may also aid in destruction of
fungal elements [61].
Topical Therapy
Topical therapy may be indicated for cases of mild to
moderate infection (B50% of distal end affected)
where the matrix is not involved, and few (3–4) nails
are affected [2]. Few adverse events are expected
with topical therapy compared to oral therapy [2].
Two topical medications formulated as lacquers
provide good penetration of the nail unit and are
approved for use in onychomycosis as monothera-
pies: ciclopirox and amorolfine [2, 65]. The lacquer
formulations may be superior to other topical formu-
lations, as the volatile vehicles leave an occlusive
film of concentrated drug on the nail, providing a
fixed drug gradient, and increasing hydration of the
nail which further aids diffusion into the underlying
nail structures [65]. However, while it is practical to
use nail lacquers in situations where few nails are
involved, an oral antifungal agent should be consid-
ered when a greater number of nails are involved,
greater areas are involved, or infection includes the
matrix region.
Ciclopirox nail lacquer 8% solution is approved
for the management of mild to moderate onychomy-
cosis without lunula involvement caused by
T. rubrum and should be applied once daily for
363
48 weeks, though some trials showed success with
less frequent use (e.g., 3 times per week) [65, 66].
Ciclopirox lacquer should be used with routine nail
debridement to provide effective delivery of drug to
the infected area and to reduce the burden of fungal
material [66]. The mycological cure rate at week 48
was 33% in the pivotal US clinical trials; other trials
which were mostly open-label showed mycological
cure rates of 47–67% [65, 66]. Though mycological
cure rates are reasonable, overall success rates may
be quite lower [65]. Its use is not associated with any
of the potential adverse effects that might occur with
oral antifungals, for example hepatotoxicity and
cutaneous reactions [66].
Amorolfine 5% nail lacquer is approved for
monotherapy of mild onychomycosis with no matrix
involvement. Application is typically once or twice
weekly, for 6–12 months. Pivotal trials indicated that
amorolfine 5% provided mycological cure rates of
60–76% with once or twice weekly use, and very few
adverse events were associated with its use, with all
events being minor and confined to the application
site [2, 56, 65, 67]. Though mycological cure rates
are reasonable, overall success rates may be quite
lower [65].
Topical medications such as terbinafine may be
useful as an adjunctive therapy for severe infections
being treated with oral terbinafine, or where paro-
nychia is present [2]. Topical monotherapy with
terbinafine or azoles would not be expected to
provide effective therapy in more severe cases of
infection, particularly where the matrix is involved.
Use of topical azoles or allylamines as prophylactic
therapy has rarely been reported; limited reports with
miconazole powder did not show successful prophy-
laxis of infection [68].
Tinea pedis is frequently seen in conjunction with
toenail onychomycosis, and onychomycosis infection
can spread to other parts of the body as well, such as
in the two feet-one hand syndrome [69]. Topical
adjunctive therapy may be warranted for such cases
to clear up and prevent further spread of infection.
Oral Therapy
Though griseofulvin is approved for tinea infection of
the nails, its affinity for keratin is low and long-term
therapy is required [21]. Efficacy in the treatment of
onychomycosis is also low, and the newer azole and
123
364
allylamine agents have largely replaced griseofulvin
for this indication [21]. Ketoconazole is not recom-
mended for therapy of onychomycosis due to the
potential for hepatotoxicity (blocking human CYP-
dependent demethylation of ergosterol at higher
concentrations), and to the availability of alternative
oral treatments [21]. Fluconazole has shown high
efficacy, low relapse rates, and usefulness with yeast
coinfection; however, there have been few studies on
this treatment method [39, 56].
The oral therapy regimens for onychomycosis are
as follows: terbinafine 250 mg/day for 12 weeks
(toenails) or 6 weeks (fingernails only); and itraco-
nazole 200 mg twice daily as pulse therapy (one pulse:
1 week of itraconazole followed by 3 weeks without
itraconazole) using 2–3 pulses (two pulses: fingernails;
three pulses: toenails) [21, 61]. In countries where
fluconazole is approved for the treatment of onycho-
mycosis, the most frequently used schedule is
fluconazole 150–300 mg once weekly given until the
abnormal-appearing nail has grown out (fingernails:
approx. 3–6 months; toenails: approx. 9–12 months)
[21].
Use of pulsed terbinafine regimens has been
suggested as a method to improve the safety profile
of oral terbinafine; however, unlike itraconazole, the
efficacy of pulsed terbinafine has not been conclusively
established compared to continuous regimens [70].
Combination Therapies
The cure rates for onychomycosis are lower than
desirable, and it has been recognized that there is a
high rate of relapse following successful treatment
[61, 71]. Efforts to improve the cure rates have most
recently involved various combinations of antifungal
therapies. It has been suggested that oral antifungals
with differing mechanisms of action may provide
synergistic effects leading to increased fungicidal
activity (i.e., terbinafine/itraconazole combination
therapy) [65, 72, 73]. Use of a topical medication
(amorolfine, ciclopirox nail lacquer, …) in combina-
tion with an oral antifungal may improve the efficacy
by providing increased routes of drug penetration,
and increase efficacy may also improve cost-benefit
rates for severe onychomycosis treatment [26, 65, 72,
74–77]. These combination methods require further
study to determine efficacy, and are not currently
accepted treatment methods.
123
Mycopathologia (2008) 166:353–367
Discussion
Oral therapy may be considered over topical therapy
for patients with large areas of infection extent, where
infection presents with unusual severity or persis-
tence, or where patients may have problems
complying with daily topical application. Similarly,
patients who are immunocompromised may be pro-
vided with oral treatment where prompt, thorough
resolution of infection is mandatory.
Topical corticosteroid use is not recommended for
dermatophytosis, as it may lead to suppression of
physical signs of infection, with lack of symptoms
being wrongly associated with clearance of infection,
leading to treatment relapse [28].
Relapse of therapy has been noted with most types
of dermatophyte infection. Infection transmission
from symptom-free carriers like family members
and pets may need to be controlled with adjunct
therapies and techniques; fomites such as hats and
combs must also be treated. Patients must be
encouraged to complete a full treatment cycle, as
infection can be present without visible symptoms.
Microscopic examination and culture are required
to confirm elimination of the pathogen; however, there
are limitations with basing ‘cure’ on negative culture
findings as well. There is a high false negative culture
rate, and thus there is a question of whether new
episodes of infection are new infections, or relapses of
previous infection. Limitations of standard microscopy
and culture methods have been recognized for years,
but until recently no other reliable methods of fungus
identification have been available. Reports on the use
of molecular biology methods to identify fungal DNA
are increasing [78–82]. These molecular methods
provide fast identification relative to the standard
microscopy/culture methods. It remains to be seen
what impact such analysis may have on fungal
treatment. Greater use of such analyses can be expected
in future, particularly if it can be conclusively demon-
strated that such methods can provide an analysis of
viable fungus present in nails with higher reliability
than standard microscopy/culture methods. Reassess-
ment of oral antifungal efficacy measures, particularly
in onychomycosis, may be called for if more reliable
identification methods become accepted in general
dermatology treatment.
Though there is concern over the high relapse/
reinfection rates in onychomycosis, prophylactic
Mycopathologia (2008) 166:353–367
regimens for onychomycosis have not been developed.
Use of miconazole powder 2% biweekly for 2 years in
shoes and on feet did not show any significant effects in
prevention of reinfection at the conclusion of a double-
blind trial, but these conclusions may be limited by the
small sample size (n = 45) [68]. Use of amorolfine 5%
nail lacquer twice monthly has been suggested as
prophylaxis for onychomycosis, but efficacy of such a
treatment has not been reported [65]. Future efforts
need to focus on this issue, as it remains a significant
obstacle for those combating onychomycosis.
References
1. Loo DS. Systemic antifungal agents: an update of estab-
lished and new therapies. Adv Dermatol. 2006;22:101–24.
2. Lecha M, Effendy I, Feuilhade de Chauvin M, Di Chiac-
chio N, Baran R. Treatment options—development of
consensus guidelines. J Eur Acad Dermatol Venereol.
2005;19(Suppl 1):25–33.
3. TARO Pharmaceuticals Inc. Clotrimazole cream USP, 1%.
Prescribing information. Bramalea, Ontario, Canada, June
1996.
4. TARO Pharmaceuticals Inc. Econazole nitrate cream 1%.
Prescribing information. Brampton, Ontario, Canada,
September 2001.
5. Merz Pharmaceuticals. Naftin Naftifine HCl 1% gel/
cream. Prescribing information. Greensboro, NC, USA,
May 2007.
6. McNeil Consumer & Specialty Pharmaceuticals. Nizoral
(ketoconazole) 2% shampoo. Prescribing information. Fort
Washington, PA, USA, October 2003.
7. TARO Pharmaceuticals Inc. Ciclopirox olamine cream
USP, 0.77%. Prescribing information. Brampton, Ontario,
Canada, March 2005.
8. MEDICIS, The Dermatology Company. Loprox Gel
(ciclopirox) 0.77%. Prescribing information. Scottsdale,
AZ, USA, July 2005.
9. BERTEK Pharmaceuticals Inc. Mentax-TC (butenafine
HCl) cream, 1%. Prescribing information. Research Tri-
angle Park, NC, USA, October 2002.
10. GlaxoSmithKline Consumer Healthcare LP. Oxistat
(oxiconazole nitrate cream) cream 1%; Oxistat (oxicon-
azole nitrate lotion) lotion 1%. Prescribing information.
Pittsburgh, PA, USA, January 2004.
11. Gupta AK, Chow M, Daniel CR, Aly R. Treatments of
tinea pedis. Dermatol Clin. 2003;21:431–62.
12. Lamisil (terbinafine hydrochloride tablets) Prescribing
information. Novartis Pharmaceuticals Corporation. East
Hanover, NJ, November 2005.
13. Sporanox (itraconazole) Capsules prescribing informa-
tion (Ortho-McNeil Inc). Janssen Pharmaceutica Products,
L.P. Titusville, NJ, June 2006.
14. Diflucan (fluconazole tablets) (fluconazole injection—for
intravenous infusion only) (fluconazole for oral suspen-
sion) Prescribing information. Pfizer Inc, August 2004.
365
15. Griseofulvin (Systemic). In: Drug information for the
health care professional, USP DI, The United States
Pharmacopeial Convention, Inc., ed 24, Taunton MA,
2004, Micromedex, p. 1493–6.
16. Miscellaneous Antifungals—Griseofulvin. In: AHFS Drug
Information 2005. Bethesda, MD, 2005, American Soci-
ety of Health-System Pharmacists, Inc., p. 535–7.
17. Azoles—Ketoconazole. In: AHFS Drug Information
2005. Bethesda, MD, 2005, American Society of Health-
System Pharmacists, Inc., p. 510–6.
18. Gupta AK, Cooper EA, Montero-Gei F. The use of fluco-
nazole to treat superficial fungal infections in children.
Dermatol Clin. 2003;21:537–42.
19. Gupta AK, Cooper EA, Ginter G. Efficacy and safety of itr-
aconazole use in children. Dermatol Clin. 2003;21:521–35.
20. Gupta AK, Cooper EA, Lynde CW. The efficacy and safety
of terbinafine in children. Dermatol Clin. 2003;21:511–20.
21. Gupta AK, Ryder JE. The use of oral antifungal agents to
treat onychomycosis. Dermatol Clin. 2003;21:469–79.
22. Antifungals, Azole (Systemic). In: Drug information for
the health care professional, USP DI, The United States
Pharmacopeial Convention, Inc., ed 24, Taunton MA,
2004, Micromedex. p. 315–23.
23. Padhye AA, Weitzman I. The dermatophytes. In: Collier L,
Balows A, Sussman M, Ajello L, Hay RJ, editors. Topley
and Wilson’s medical mycology. New York: Oxford Uni-
versity Press; 1998. p. 215–36.
24. Noble SL, Forbes RC, Stamm PL. Diagnosis and man-
agement of common tinea infections. Am Fam Physician.
1998;58:163–8.
25. Crawford F, Hollis S. Topical treatments for fungal
infections of the skin and nails of the foot. Cochrane
Database Syst Rev. 2007 Jul 18;(3):CD001434.
26. Gupta AK, Cooper EA, Ryder JE, et al. Optimal man-
agement of fungal infections of the skin, hair, and nails.
Am J Clin Dermatol. 2004;5:225–37.
27. Crawford F. Athlete’s foot. In: Williams H, Bigby M, Diepgen
T, Herxheimer A, Naldi L, Rzany B, editors. Evidence based
dermatology. London: BMJ Books; 2003. p. 436–40.
28. Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea
cruris, tinea nigra, and piedra. Dermatol Clin. 2003;21:
395–400.
29. Gupta AK, De Doncker P, Heremans A, et al. Itraconazole
for the treatment of tinea pedis: a dose of 400 mg/day
given for 1 week is similar in efficacy to 100 or 200 mg/
day given for 2 to 4 weeks. J Am Acad Dermatol.
1997;36:789–92.
30. Faergemann J, Mork NJ, Haglund A, et al. A multicentre
(double-blind) comparative study to assess the safety and
efficacy of fluconazole and griseofulvin in the treatment of
tinea corporis and tinea cruris. Br J Dermatol. 1997;
136:575–7.
31. Stary A, Sarnow E. Fluconazole in the treatment of tinea
corporis and tinea cruris. Dermatology. 1998;196:237–41.
32. Suchil P, Montero Gei F, Robles M, et al. Once-weekly
oral doses of fluconazole 150 mg in the treatment of tinea
corporis/cruris and cutaneous candidiasis. Clin Exp Der-
matol. 1992;17:397–401.
33. Haroon TS, Asghar HA, Aman S, et al. An open, non-
comparative study for the evaluation of oral fluconazole in
the treatment of tinea corporis. Specialist. 1997;13:417–23.
123
366
34. Papini M, Difonzo EM, Cilli P, et al. Itraconazole versus
fluconazole, a double-blind comparison in tinea corporis.
J Mycol Méd. 1997;7:77–80.
35. Kotogyan A, Harmanyeri Y, Tahsin Gunes A, et al.
Efficacy and safety of oral fluconazole in the treatment of
patients with tinea corporis, cruris or pedis or cutaneous
candidiasis. A multicentre, open, non-comparative study.
Clin Drug Investig. 1996;12:59–66.
36. Gomez M, Arenas R, Salazar JJ, et al. Tinea pedis. A
multicentre trial to evaluate the efficacy and tolerance of a
weekly dose of fluconazole. Dermatol Rev Mex.
1996;40:251–5 (Spanish).
37. Del Aguila R, Montero Gei F, Robles M, et al. Once-
weekly oral doses of fluconazole 150 mg in the treatment
of tinea pedis. Clin Exp Dermatol. 1992;17:402–6.
38. Gupta AK, Ryder JE, Chow M, Cooper EA. Dermato-
phytosis: the management of fungal infections. Skinmed.
2005;4:305–10.
39. Trent JT, Federman D, Kirsner RS. Common viral and fungal
skin infections. Ostomy Wound Manage. 2001;47:28–34.
40. De Doncker P, Gupta AK, Marynissen G, et al. Itraconazole
pulse therapy for onychomycosis and dermatomycoses: an
overview. J Am Acad Dermatol. 1997;37:969–74.
41. Parent D, Decroix J, Heenen M. Clinical experience with short
schedules of itraconazole in the treatment of tinea corporis and/
or tinea cruris. Dermatology. 1994;189:378–81.
42. Gupta AK, Summerbell RC. Tinea capitis. Med Mycol.
2000;38:255–87.
43. Roberts BJ, Friedlander SF. Tinea capitis: a treatment
update. Pediatr Ann. 2005;34:191–200.
44. Lipozencic J, Skerlev M, Orofino-Costa R, et al. A ran-
domized, double-blind, parallel-group, duration-finding
study of oral terbinafine and open-label, high-dose gris-
eofulvin in children with tinea capitis due to Microsporum
species. Br J Dermatol. 2002;146:816–23.
45. Gupta AK, Skinner AR. Onychomycosis in children: a
brief overview with treatment strategies. Pediatr Dermatol.
2004;21:74–9.
46. Tosti A, Piraccini BM, Iorizzo M. Management of ony-
chomycosis in children. Dermatol Clin. 2003;21:507–9.
47. Chan Y, Friedlander SF. New treatments for tinea capitis.
Curr Opin Infect Dis. 2004;17:97–103.
48. Haroon TS, Hussain I, Aman S, et al. A randomized
double-blind comparative study of terbinafine for 1, 2
and 4 weeks in tinea capitis. Br J Dermatol. 1996;135:
86–8.
49. Friedlander SF, Aly R, Krafchik B, et al. Terbinafine in the
treatment of Trichophyton tinea capitis: a randomized,
double-blind, parallel-group, duration-finding study. Pedi-
atrics. 2002;109:602–7.
50. Lipozencic J, Skerlev M, Orofino-Costa R, et al. A ran-
domized, double-blind, parallel-group, duration-finding
study of oral terbinafine and open-label, high-dose gris-
eofulvin in children with tinea capitis due to Microsporum
species. Br J Dermatol. 2002;146:816–23.
51. Gupta AK, Solomon RS, Adam P. Itraconazole oral solu-
tion for the treatment of tinea capitis. Br J Dermatol.
1998;139:104–6.
52. Dastghaib L, Azizzadeh M, Jafari P. Therapeutic options
for the treatment of tinea capitis: griseofulvin versus
fluconazole. J Dermatolog Treat. 2005;16:43–6.
123
Mycopathologia (2008) 166:353–367
53. Montero Gei F. Fluconazole in the treatment of tinea
capitis. Int J Dermatol. 1998;37:870–1.
54. Gupta AK, Dlova N, Taborda P, et al. Once weekly fluco-
nazole is effective in the treatment of tinea capitis: a
prospective, multicentre study. Br J Dermatol. 2000;142:
965–8.
55. Gupta AK, Scher RK. Management of onychomycosis: a
North American perspective. Dermatol Ther. 1997;3:58–65.
56. Gupta AK, Ryder J, Bluhm R. Onychomycosis. In: Wil-
liams H, Bigby M, Diepgen T, Herxheimer A, Naldi L,
Rzany B, editors. Evidence based dermatology. London:
BMJ Books; 2003. p. 441–68.
57. Tavakkol A, Fellman S, Kianifard F. Safety and efficacy of
oral terbinafine in the treatment of onychomycosis: anal-
ysis of the elderly subgroup in Improving Results in
Onychomycosis-Concomitant Lamisil and Debridement
(IRONCLAD), an open-label, randomized trial. Am J
Geriatr Pharmacother. 2006;4:1–13.
58. Potter LP, Mathias SD, Raut M, et al. The impact of aggressive
debridement used as an adjunct therapy with terbinafine on
perceptions of patients undergoing treatment for toenail ony-
chomycosis. J Dermatolog Treat. 2007;18:46–52.
59. Daniel CR III. Traditional management of onychomycosis.
J Am Acad Dermatol. 1996;35:S21–5.
60. King B. Pain at first dressing change after toenail avulsion:
the experience of nurses, patients and an observer: 1.
J Wound Care. 2003;12:5–10.
61. Seebacher C, Brasch D, Abeck O, et al. Onychomycosis.
Mycoses. 2007;50:321–7.
62. Baran R, Hay RJ, Haneke E, Tosti A. Review of current
antifungal treatment. Onychomycosis: the current approach
to diagnosis and therapy. London: Martin Dunitz Ltd.;
1999. p. 44–69.
63. Hay RJ, Baran R, Haneke E. Fungal (onychomycosis) and
other infections involving the nail apparatus. In: Baran R,
Dawber RPR, de Berker DAR, Haneke E, Tosti A, editors.
Baran and Dawber’s diseases of the nails and their man-
agement. Osney Mead, Oxford: Blackwell Science Ltd.;
2001. p. 129–71.
64. Grover C, Bansal S, Nanda S, et al. Combination of sur-
gical avulsion and topical therapy for single nail
onychomycosis: a randomized controlled trial. Br J Der-
matol. 2007;157:364–8.
65. Baran R, Kaoukhov A. Topical antifungal drugs for the
treatment of onychomycosis: an overview of current
strategies for monotherapy and combination therapy. J Eur
Acad Dermatol Venereol. 2005;19:21–9.
66. Penlac Nail Lacquer (ciclopirox) Topical Solution, 8%
Prescribing information. Dermik Laboratories (a division
of Sanofi-Aventis). Bridgewater, NJ, July 2006.
67. Gupta AK, Ryder JE, Skinner AR. Treatment of onycho-
mycosis: pros and cons of antifungal agents. J Cutan Med
Surg. 2004;8:25–30.
68. Warshaw EM, St Clair KR. Prevention of onychomycosis
reinfection for patients with complete cure of all 10 toe-
nails: results of a double-blind, placebo-controlled, pilot
study of prophylactic miconazole powder 2%. J Am Acad
Dermatol. 2005;53:717–20.
69. Daniel CR, Gupta AK, Daniel MP, Daniel CM. Two feet-
one hand syndrome: a retrospective multicenter survey. Int
J Dermatol. 1997;36:658–60.
Mycopathologia (2008) 166:353–367
70. Sigurgeirsson B, Elewski BE, Rich PA, et al. Intermittent
versus continuous terbinafine in the treatment of toenail
onychomycosis: a randomized, double-blind comparison.
J Dermatolog Treat. 2006;17:38–44.
71. Finch JJ, Warshaw EM. Toenail onychomycosis: current
and future treatment options. Dermatol Ther. 2007;20:
31–46.
72. Olafsson JH, Sigurgeirsson B, Baran R. Combination
therapy for onychomycosis. Br J Dermatol. 2003;
149(Suppl 65):15–8.
73. Evans EGV. Drug synergies and the potential for combi-
nation therapy in onychomycosis. Br J Dermatol. 2003;
149(Suppl 65):11–3.
74. Nandedkar-Thomas MA, Scher RK. An update on disor-
ders of the nails. J Am Acad Dermatol. 2005;52:877–87.
75. Gupta AK, Onychomycosis Combination Therapy Study
Group. Ciclopirox topical solution, 8% combined with oral
terbinafine to treat onychomycosis: a randomized, evalua-
tor-blinded study. J Drugs Dermatol. 2005;4:481–5.
76. Baran R. Topical amorolfine for 15 months combined with
12 weeks of oral terbinafine, a cost-effective treatment for
onychomycosis. Br J Dermatol. 2001;145(Suppl 60):15–9.
77. Lecha M. Amorolfine and itraconazole combination for
severe toenail onychomycosis: results of an open
367
randomized trial in Spain. Br J Dermatol. 2001;145(Suppl
60):21–6.
78. Binstock JM. Molecular biology techniques for identifying
dermatophytes and their possible use in diagnosing ony-
chomycosis in human toenails. J Am Podiatr Med Assoc.
2007;97:134–44.
79. de Assis Santos D, de Carvalho Araujo RA, Kohler LM,
et al. Molecular typing and antifungal susceptibility of
Trichophyton rubrum isolates from patients with onycho-
mycosis pre- and post-treatment. Int J Antimicrob Agents.
2007;29:563–9.
80. Brillowska-Dabrowska A, Saunte DM, Arendrup MC.
Five-hour diagnosis of dermatophyte nail infections with
specific detection of Trichophyton rubrum. J Clin Micro-
biol. 2007;45:1200–4.
81. Savin C, Huck S, Rolland C, et al. Multicenter evaluation of
a commercial PCR-enzyme-linked immunosorbent assay
diagnostic kit (Onychodiag) for diagnosis of dermatophytic
onychomycosis. J Clin Microbiol. 2007;45:1205–10.
82. Gupta AK, Zaman M, Singh J. Fast and sensitive detection
of Trichophyton rubrum DNA from the nail samples of
patients with onychomycosis by a double-round polymerase
chain reaction-based assay. Br J Dermatol. 2007;157:
698–703.
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