Systemic Antifungal Therapy For Tinea Capitis in Children (Review)

Systemic antifungal therapy for tinea capitis in children
(Review)
Gonzlez U, Seaton T, Bergus G, Jacobson J, Martnez-Monzn C
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2012, Issue 8
http://www.thecochranelibrary.com
Systemic antifungal therapy for tinea capitis in children (Review)

Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Terbinafine (4 weeks) versus griseofulvin (8 weeks); short treatment duration; 12 to 24 weeks
follow-up, Outcome 1 complete cure. . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.1. Comparison 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum infections; 16 weeks
Analysis 2.2. Comparison 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum infections; 16 weeks
follow-up, Outcome 2 clinical cure. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.1. Comparison 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections; 12 to 20 weeks
Analysis 3.2. Comparison 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections; 12 to 20 weeks
follow-up, Outcome 2 clinical cure. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.1. Comparison 4 Terbinafine (standard dose compared to double dose) in Microsporum infections; 20 weeks
Analysis 5.1. Comparison 5 Itraconazole (6 and 2 weeks, respectively) versus griseofulvin (6 weeks) in Trichophyton and
Microsporum infections, Outcome 1 complete cure. . . . . . . . . . . . . . . . . . . . .
Analysis 6.1. Comparison 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections, Outcome 1 complete
cure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 6.2. Comparison 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections, Outcome 2 clinical
cure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 7.1. Comparison 7 Ketoconazole (6 weeks) versus griseofulvin (8 to 12 weeks) in Trichophyton infections; 12
weeks follow-up, Outcome 1 complete cure. . . . . . . . . . . . . . . . . . . . . . . .
Analysis 8.1. Comparison 8 Fluconazole (2 and 4 weeks respectively) versus griseofulvin (6 weeks) in Trichophyton
infections; 8 -12 weeks, Outcome 1 complete cure. . . . . . . . . . . . . . . . . . . . . .
Analysis 9.1. Comparison 9 Fluconazole (2 to 3 weeks) versus terbinafine (2 to3 weeks) in Trichophyton infections; 12
Analysis 10.1. Comparison 10 Fluconazole (2 to 3 weeks) versus itraconazole (2 to 3 weeks) in Trichophyton infections; 12
Analysis 11.1. Comparison 11 Fluconazole (different doses compared: 1.5, 3 and 6 mg/kg/day) in Trichophyton infections;
4 months follow-up, Outcome 1 complete cure. . . . . . . . . . . . . . . . . . . . . . .
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1
1
2
2
3
3
5
15
18
18
19
21
47
51
52
52
53
55
57
57
58
58
59
59
60
60
61
61
69
72
73
73
73
73
74
[Intervention Review]

Urb Gonzlez1 , Terry Seaton2 , George Bergus3 , Jim Jacobson4 , Cecilia Martnez-Monzn5
1 Department
of Dermatology, Research Unit for Evidence-based Dermatology, Hospital Plat, Barcelona, Spain. 2 St. Louis College of
Pharmacy, St. Louis, Missouri, USA. 3 Department of Family Medicine, University of Iowa, Iowa City, Iowa, USA. 4 c/o Cochrane Skin
Group, University of Nottingham, Nottingham, UK. 5 Research Unit for Evidence-based Dermatology, Spanish Society of Dermatology,
Barcelona, Spain
Contact address: Urb Gonzlez, Unit of Dermatology, Clnica Go&Fer, Riera Blanca 14-16, L Hospitalet, Barcelona, 08903, Spain.
ugonzalez@goandfer.es.
Editorial group: Cochrane Skin Group.
Publication status and date: Edited (no change to conclusions), published in Issue 8, 2012.
Review content assessed as up-to-date: 22 August 2007.
Citation: Gonzlez U, Seaton T, Bergus G, Jacobson J, Martnez-Monzn C. Systemic antifungal therapy for tinea capitis in children.
Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD004685. DOI: 10.1002/14651858.CD004685.pub2.
ABSTRACT
Background
Tinea capitis is a common contagious fungal infection of the scalp in children. Systemic therapy is required for treatment and to prevent
spread.
Objectives
To assess the effects of systemic anti-fungal drugs for tinea capitis in children.
Search methods
We searched the Cochrane Skin Group Specialised Register (June 2005), the Cochrane Central Register of Controlled Trials (The
Cochrane Library Issue 2, 2005), MEDLINE (2003 to June 2005), EMBASE ( 2003 to June 2005), LILACS (1982 to July 2005),
CINAHL (1982 to July 2005), the ACP journal club (1991 to July 2005) and Healthstar (1975 to July 2005).
Selection criteria
Randomised controlled trials (RCTs) that evaluated systemic antifungal therapy in people with normal immunity under the age of 18
who had tinea capitis confirmed by microscopy or growth of dermatophytes in culture or both.
Data collection and analysis
At least two authors independently examined each retrieved trial for eligibility and quality.
Main results
We included 21 studies (1812 participants).
Infections involving Trichophyton species: Terbinafine for 4 weeks and griseofulvin for 8 weeks showed similar efficacy in 3 studies
involving 382 participants (RR 1.09; 95% CI 0.95 to 1.26). Cure rates following treatment with itraconazole and griseofulvin for
6 weeks were similar in 1 study of 35 children (RR 1.06; 95% CI 0.81 to 1.39). Another study of 100 children did not show any
significant difference in cure between itraconazole for 2 weeks compared with griseofulvin for 6 weeks (RR 0.89; 95% CI 0.76 to
1.04). There was no difference between itraconazole and terbinafine for treatment periods lasting 2 to 3 weeks in 2 studies involving
160 children (RR 0.93; 95% CI 0.72 to 1.19). Two studies that included 140 children found similar cure rates between 2 to 4 weeks
of fluconazole with 6 weeks of griseofulvin (RR 0.92; 95% CI 0.80 to 1.05).
Microsporum infections: There was no significant difference in cure between terbinafine and griseofulvin in children with Microsporum
infections in 1 small study of 29 children (RR 0.64; 95% CI 0.19 to 2.20).
Authors conclusions
The best evidence suggests that newer treatments including terbinafine, itraconazole and fluconazole may be similar to griseofulvin in
children with tinea capitis caused by Trichophyton species. Newer treatments may be preferred because shorter treatment durations may
improve treatment adherence, although they may be more expensive. There is not enough evidence on the use of systemic treatments in
children with Microsporum infections. Not all treatments for tinea capitis are available in paediatric formulations but all have reasonable
safety profiles.
PLAIN LANGUAGE SUMMARY

Systemic antifungal therapy for tinea capitis (also known as ringworm) in children.
Tinea capitis is a fungal infection of the scalp caused by two main species called Trichophyton and Microsporum. It is common in children.
Systemic therapy is generally required to cure the problem, and several systemic anti-fungal agents are available. The best evidence
suggests that newer treatments such as terbinafine, itraconazole and fluconazole are probably as good as griseofulvin in children with
tinea capitis caused by Trichophyton infections. Newer treatments may be preferred because they can be given for shorter treatment
durations which may in turn improve adherence to treatment. However, they may be more expensive. There is still not enough evidence
on the use of treatments in children with Microsporum infections. Not all treatments for tinea capitis are available in syrup formulations
but all appear to be reasonably safe.
BACKGROUND
Description of the condition

Tinea capitis is the medical term for an infection of the scalp (also
known as scalp ringworm) involving the skin and the hair. It is
caused by fungi (dermatophytes), mainly by Trichophyton or Microsporum species which invade the hair shaft. The clinical hallmark is a single patch, or multiple patches of hair loss, sometimes
with a black dot pattern (studded with broken-off hairs), that
may be accompanied by inflammation, scaling, pustules and itching.
Tinea capitis is uncommon in adults and is seen predominantly
in pre-teenage children. The infection is mainly seen in disadvantaged communities in low, middle and higher income nations.
During the past 30 years, a significant increase has occurred in
the reported incidence of tinea capitis. Travel and migration have
been associated with changes in epidemiology, and in distribution
of the species of fungi that are likely to cause tinea capitis (Aly
1999).
There are over eight species of dermatophytes characteristically

associated with tinea capitis. Infections due to Trichophyton predominate from Central America to the United States and in parts
of Western Europe. Cases of Microsporum infections are mainly
seen in South America, Southern and Central Europe, Africa and
the Middle East.
Tinea capitis is infectious and can be transmitted by humans,
animals or objects carrying the fungus. Carrier states also exist
where the fungus is present on the scalp but there is no clinical
infection. Although it is not life-threatening in people with normal
immunity, if left untreated there may be persistent symptoms. The
inflammatory form, kerion, can result in scarring alopecia (hair
loss), or permanent baldness (Elewski 2000).
Description of the intervention

The clinical diagnosis should be confirmed by identifying the presence of fungi within the hair shaft in hair samples viewed under
the microscope or by growing the fungus from such samples in
laboratory conditions (mycological diagnosis) or both. The main

methods of collecting samples for microbiological diagnosis involve either scraping or brushing the scalp and plucking of affected
hairs. Looking at the sample under a microscope is the fastest
way to diagnose the infection and allows treatment to commence
immediately, if positive. However, sometimes this method indicates someone does not have the condition even if they actually
do. Culturing the scrapings allows accurate identification of the
organism involved and may indicate an infection even when microscopy is negative; however, this method may take up to four
weeks to provide a result. A Woods light (filtered ultraviolet light)
can be used to detect infections that fluoresce under this type of
light (such as Microsporum canis and Microsporum audouinii) but
it is not helpful in diagnosing Trichophyton tonsurans tinea capitis
(Elewski 2000).
Why it is important to do this review

There is a choice between several systemic antifungals for treating
children with tinea capitis. The authors wanted to determine the
comparative efficacy and safety profiles for these drugs. Furthermore, because of the world-wide distribution of this infection and
the responsiveness of fungal species to different drugs, the cost
implications may also be very important. Lastly, the authors were
interested in comparing different lengths of treatment. Shorter
course therapy, if effective, seemed desirable because prolonged
therapy increases the risk of adverse effects and the likelihood of
drop-outs.
OBJECTIVES
How the intervention might work
The primary aim of treatment for tinea capitis is to achieve complete clinical (signs and symptoms) and mycological cure (culture
negative) as quickly as possible with minimal adverse effects. Most
superficial fungal infections can be treated topically (treatment applied directly to the skin), but tinea capitis always requires systemic
(treatment which spreads throughout the entire body) medication
because the fungal infection is found at the root of the hair follicles, where topical agents cant reach. Topical treatments are only
used as adjuvant therapy (alongside systemic therapy).
Tinea capitis is seen mainly in children, and there are potential
problems with persuading them to take their medicine. Factors enhancing compliance include an acceptable taste and a short course
of therapy. The latter factor might also reduce the risk of adverse
effects. A further goal of therapy is to prevent the spread of the
disease to other children via the infected child, asymptomatic carriers, objects or animals (Gupta 1999).
Griseofulvin has traditionally been the most widely prescribed and
commonly used antifungal treatment for tinea capitis in clinical
practice (Bennet 2000; Friedlander 2000). The pediatric dosage
of griseofulvin often prescribed is 10 to 25 mg/kg/day for 6 to 8
weeks. It is still a relatively inexpensive drug and has been used as
the standard for evaluation of many newer agents. However, it has
a bitter, unpleasant taste and should be taken with meals for one
to two months (which may affect compliance in children). The
liquid form is no longer available in some countries.
Newer antifungal agents, such as ketoconazole, itraconazole,
terbinafine or fluconazole, are increasingly being considered for
the treatment of tinea capitis, however, some species of fungi may
respond better to other treatments. There is concern regarding the
use of these drugs in children because of the possibility of rare
but potentially serious side-effects, such as liver toxicity or drug
interaction (Blumer 1999). These newer agents also are expensive,
which is an important consideration given that tinea capitis is endemic in some of the poorest communities in the world.
To assess the effects of systemic antifungal drugs for tinea capitis

in children.
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs). We did not consider internally controlled trials, such as those with cross-over and withinparticipant designs because they are inappropriate designs for systemic treatment.
Types of participants
Children with normal immunity under the age of 18 with tinea
capitis confirmed by microscopy or growth of dermatophytes in
culture or both.
Types of interventions
We considered all regimens of any systemic antifungal drug interventions for tinea capitis such as:
any systemic treatment versus no treatment or placebo;
comparison of two or more systemic therapies;
comparison of different doses and regimens of the same
systemic therapy;
comparison of systemic versus topical therapies.
It was anticipated that some systemic antifungal agents, such as
amphotericin B, flucytosine, capsofungin, or miconazole, would
not be studied for tinea capitis because of either lack of antifungal
spectrum of activity or lack of acceptable toxicity in this population.

Types of outcome measures
Primary outcomes
(a) The proportion of participants with complete cure i.e. clinical

and mycological cure.
(i) Complete clinical cure was defined as resolution of itching and
clinical signs, such as redness, scaling, and oedema;
(ii) Complete mycological cure, defined as negative results on microscopy or no growth in culture or both.
(b) The frequency and type of adverse effects.
Secondary outcomes
(a) The proportion of participants with clinical cure only.

(b) Measurement of recurrence of the condition after the end of
the intervention period.
(c) Percentage of drop-outs as a surrogate for participant compliance.
(d) The time taken to cure.
Search methods for identification of studies
Unpublished literature
We obtained unpublished, on-going trials and grey literature via

correspondence with authors of published studies and pharmaceutical companies. We consulted the Ringworm Committee of
the European Confederation of Medical Mycology about other
unpublished data and we also searched the meta Register of Controlled Trials (www.controlled-trials.com) in July 2005 for possible ongoing trials.
Conference Proceedings
We stated in the protocol that we would search the conference

proceedings from major dermatology and mycology meetings. We
were unable to search proceedings from mycology meetings but
we now understand the major dermatology meetings are being
searched by the Cochrane Skin Group. We will search mycology
meeting abstracts for an update of this review.
Adverse effects
We asked pharmaceutical companies for surveillance data on adverse events.

We conducted a separate search for severe adverse effects combined
with the intervention terms in MEDLINE (OVID) (1966 to June
2005) using the search strategy in additional Appendix 6.
Electronic searches
We searched the Cochrane Skin Group Specialized Register in
June 2005 using the terms in Appendix 1.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005) using the strategy in
Appendix 2.
We searched MEDLINE (OVID) (2003 to June 2005) using the
search strategy in Appendix 3.
We searched EMBASE (OVID) (2003 to June 2005) using the
search strategy in Appendix 4.
We searched the database LILACS (www.bireme.br) (1982 to July
2005) using the search strategies in Appendix 5.
We searched the Database of Abstracts of Reviews of Effects (The
Cochrane Library Issue 2, 2005) using the strategy in Appendix 2.
We searched the ACP journal club (1991 to July 2005), Healthstar
(1975 to July 2005) and CINAHL (to July 2005) using the terms
tinea capitis and ringworm.
Language restrictions
We imposed no language restrictions.
Data collection and analysis
Selection of studies
Searching other resources
Two authors (GB and UG) checked titles and abstracts identified from the searches. We excluded publications that were not
randomised controlled trials of tinea capitis. If study design was
not clear from the abstract, then two authors (GB and UG) independently reviewed the full text of the study. The authors also
decided which trials met the inclusion criteria and resolved any
disagreement by discussion between the authors or referred to a
third author (JT) when necessary. We listed the excluded studies
and reasons for exclusion in the Table Characteristics of excluded
studies.
References from published studies
Data extraction and management
We searched the bibliographies of all papers identified by these

strategies for reference to other clinical trials.
At least two authors (TS and UG) extracted data independently

using a pre-designed data extraction form. We extracted reported

data for cure rates for all evaluated drugs paying attention particularly to the doses and therapy frequencies (including pulsed regimens: administering the drug in waves with drug-free intervals).
We resolved disagreements by discussion and we obtained missing
information from authors whenever possible.
We recorded the information in a table of quality criteria (Table

1) and provided a description of the quality of each study based
on these components.
Data synthesis
Assessment of risk of bias in included studies
Assessment of methodological quality of included studies
In order to assess the quality of each included study we evaluated

the following components, since there is some evidence that these
were associated with biased estimates of treatment effect (Juni
2001).
(a) Randomisation (method of generation of allocation
sequence)
(i) Adequate: if sequences were suitable to prevent selection bias
and the method used was described. Adequate methods included
random numbers generated by computer or table of random numbers or other methods of allocation that appear to be unbiased.
(ii) Inadequate: if sequences could have been related to prognosis.
(iii) Unclear: stated but method not described
(b) Allocation concealment
Adequate if participants and investigators could not foresee intervention assignment. Appropriate methods included: a priori third
party numbered or coded drug containers of identical appearance;
central randomisation; sequentially numbered, opaque, sealed envelopes; or other description that contained convincing elements
of concealment.
(c) Blinded assessment
Who was blinded/not blinded (participants, clinicians or outcome
assessors or both).
(d) Loss to follow up
How many participants were lost to follow up in each arm (split
into post-randomisation exclusions and later losses if possible),
and whether participants were analysed in the groups to which
they were originally randomised (intention to treat principle).
In addition, we considered other factors like:
(e) sample size calculation declared;
(f ) inclusion and exclusion criteria defined;
(g) reporting of type of fungi involved;
(h) baseline comparability of severity of infection, age, sex and
duration of complaint;
(i) conflict of interest.
To estimate differences between treatments, we pooled trials that

evaluated similar interventions using meta-analysis based on a random-effect models (DerSimonian and Laird model), if possible,
to calculate a weighted treatment effect across trials. The results
are expressed as risk ratios (RR) and 95% confidence intervals
(CI) for dichotomous outcomes (e.g. complete and clinical cure,
drop-outs). For each trial we calculated the cure rates at follow up
based on the reported mycological and clinical results. Although
we failed to specify the acceptable window for the timing in the
primary outcome assessment in the original protocol, we decided
during the course of the review to combine studies that recorded
primary outcomes at between 12 to 20 weeks on the basis that
these are the range of time periods that best reflect clinical decision
making in practice. When necessary, we categorised the duration
of treatment into short-term (closest to 2 weeks, but between 1
and 4 weeks), medium-term (closest to 6 weeks, but between 6
and 8 weeks), and long-term (closest to 12 weeks, but between
10 and 14 weeks).
Subgroup analysis and investigation of heterogeneity

To explore reasons for heterogeneity, we performed subgroup analysis where adequate information was given based on dermatophyte species variation. Previous investigations have demonstrated
that this factor may play an important role in the response, e.g.
Microsporum infections usually have a poorer response and can
need longer regimens of treatment (Gonzlez 2003). We assessed
heterogeneity for primary outcome measures using I2 . Quasi-randomised and non-randomised controlled studies are not discussed
further and we described studies relating to adverse effects qualitatively.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
Results of the search

We initially identified 24 trials of systemic treatments for tinea
capitis.

Included studies
We found no other studies about systemic antifungal therapy for
tinea capitis in children, either in-progress or in pre-publishing
phases. We therefore included 21 studies that randomised 1812
participants (Characteristics of included studies). We found no
other trials which compared an active treatment to placebo. The
trials compared different active treatments: either different drugs
or the different regimens of the same drug.
Included studies
with griseofulvin, one with terbinafine, one with itraconazole and

one by itself with varying doses.
Outcomes
All but three studies (Martnez-Roig 1988; Rademaker 1998; Tanz
1985) reported the proportion of participants with complete cure.
Most of the studies reported complete cure at 12 to 16 weeks but
2 reported at 8 weeks (Dastghaib 2005; Gan 1987), and 2 at 20
to 24 weeks (Fuller 2001; Ungpakorn 2004). Three studies fail to
report adverse events (Gan 1987; Kullavanijaya 1997; Solomon
1997). Eleven studies reported mycological cure as an outcome.
Setting
The studies included in this review were conducted throughout
many parts of the world.
Six were performed in Asia: three in Pakistan (Haroon 1995;
Haroon 1996; Jahangir 1998); two in Thailand (Kullavanijaya
1997; Ungpakorn 2004); and one in Iran (Dastghaib 2005).
Five studies were carried out in Europe: one in Germany (Hamm
1999); one in Turkey (Memisoglu 1999); two in Spain (LpezGmez 1994; Martnez-Roig 1988); and one in the UK (Fuller
2001).
Two studies were from South America (Cceres-Ros 2000;
Talarico Filho 1998) and five were completed in the North America (Friedlander 2002; Gan 1987; Solomon 1997; Tanz 1985; Tanz
1988). One study took place in New Zealand (Rademaker 1998).
Two of the trials included participants from two different locations, such as the United States and South Africa (Gupta 2001),
and Europe and South America (Lipozencic 2002).
Excluded studies
We excluded 3 of the initial 24 trials of systemic treatments for
tinea capitis, because they evaluated the therapy for the inflammatory component (kerion) caused by tinea capitis infection,
(Ginsburg 1987; Honig 1994; Hussain 1999). Details of the studies are provided in the Characteristics of excluded studies table.
Risk of bias in included studies
Allocation
Randomisation
Follow up
The follow-up period ranged from 6 weeks (Martnez-Roig 1988;
Tanz 1985) to 26 weeks (Gan 1987). Although most studies had
a 12-week follow-up period, 5 trials had longer follow-up periods
ranging from 16 to 24 weeks (Fuller 2001; Kullavanijaya 1997;
Lipozencic 2002; Solomon 1997; Ungpakorn 2004).
All included studies stated or implied that treatment allocation

was randomised; however, there were only four studies that reported an adequate generation method of randomisation; two
with a computer-generated random number table (Fuller 2001;
Martnez-Roig 1988) and two with a table of random numbers
(Gan 1987; Ginsburg 1987).
Interventions
Allocation concealment
In total, we studied five different antifungal agents: griseofulvin,

terbinafine, itraconazole, fluconazole and ketoconazole. We evaluated a variety of regimens, including between-drug and amongdrug comparisons. We considered griseofulvin to be the standard
because it is the oldest agent and it was used as control in 13 studies. Terbinafine was compared with griseofulvin in 7 studies with
itraconazole in 2, with fluconazole in 2, in different treatment duration regimens in 5 studies, and comparing different doses in 1,
with a total of 14 trials. Five studies compared itraconazole with
other antifungals: two with griseofulvin, two more with terbinafine
and one with fluconazole. Ketoconazole was compared with griseofulvin in four trials. Fluconazole was studied in three RCTs; two
None of the included studies had adequate reporting of allocation

concealment.
Blinding
Eleven of the 21 RCTs included in this review were doubleblinded, 5 were single-blinded (Dastghaib 2005; Gupta 2001;
Kullavanijaya 1997; Solomon 1997; Talarico Filho 1998), and 4
did not use any blinding at all (Fuller 2001; Gan 1987; Haroon
1995; Rademaker 1998). One RCT (Lipozencic 2002) blinded
the participants, clinicians and outcome assessors, except for the
arm taking griseofulvin, which was open.

Incomplete outcome data
Follow up and exclusions
The drop-outs were categorised into groups according to percentage of evaluable losses to follow up. Overall, of the 1812 patients
randomised, 322 patients (18%) were lost after randomisation.
Seven studies did not mention any drop-out or later loss-to-followup rate (Hamm 1999; Haroon 1995; Haroon 1996; Jahangir
1998; Martnez-Roig 1988; Rademaker 1998; Ungpakorn 2004);
4 studies reported a drop-out rate of less than 10% (Cceres-Ros
2000; Gupta 2001; Kullavanijaya 1997; Lpez-Gmez 1994) but
only 2 of these 4 trials reported exact losses; 5 studies mentioned
losses greater than 10% but less than a 25% (Friedlander 2002;
Gan 1987; Lipozencic 2002; Memisoglu 1999; Talarico Filho
1998); there were 2 trials that reported losing more than 25% but
less than 40% (Tanz 1985; Tanz 1988); 2 studies registered more
than 50% of losses (Fuller 2001; Solomon 1997); concerning the
losses to follow up, it was not always possible to determine from
which intervention group the losses occurred.
Other potential sources of bias

Eight of the 21 studies failed to mention potential conflict of interests for the investigators. The remaining trials were supported
by Sandoz (Haroon 1995; Haroon 1996; Kullavanijaya 1997;
Talarico Filho 1998), Janssen (Lpez-Gmez 1994; Tanz 1985;
Tanz 1988), Novartis (Fuller 2001; Hamm 1999; Lipozencic
2002; Ungpakorn 2004) and Laboratories Dr. Esteve (MartnezRoig 1988).
Other factors
Sample size
Regarding the sample size, we divided the studies into three distinct
groups:
small (< 50 participants) with 9 studies (Cceres-Ros 2000;
Dastghaib 2005; Hamm 1999; Lpez-Gmez 1994;
Martnez-Roig 1988; Rademaker 1998; Solomon 1997; Tanz
1985; Ungpakorn 2004);
medium (51 to 150 participants) with 6 studies (Gan 1987;
Jahangir 1998; Kullavanijaya 1997; Memisoglu 1999; Talarico
Filho 1998; Tanz 1988);
large (>150 participants), with 6 studies (Friedlander 2002;
Fuller 2001; Gupta 2001; Haroon 1995; Haroon 1996;
Lipozencic 2002).
Only two studies reported sample size calculation (Fuller 2001,
Lipozencic 2002).
Participant age
With regard to age, most of the participants enrolled into the
studies included in this review were older than two years. Two
studies (Cceres-Ros 2000; Talarico Filho 1998) included participants as young as one year old. Another study involved participants as young as six months of age, (Gupta 2001). The upper age limit in the majority of the trials was 16 years, although
1 trial (Haroon 1995) included participants ranging in age from
2 to 65 years. Ninety-four of the 105 participants were younger
than age 12, so in this case, we assumed all the participants in this
study were younger than 16 years old and, therefore, the whole
population was analysed. Three other studies reported a total of
four adults in their samples (Kullavanijaya 1997; Lipozencic 2002;
Lpez-Gmez 1994).
Fungal type
Each of the 21 studies reported the types of fungi cultured; some
provided general percentages, and reported exact proportions of
the types of fungi within each arm. Trichophyton species predominated over Microsporum species. T. tonsurans and M. canis were
responsible for causing infection in the highest proportion of participants. T. tonsurans was the most commonly identified fungus in
seven studies (Cceres-Ros 2000; Friedlander 2002; Fuller 2001;
Gan 1987; Ginsburg 1987; Solomon 1997; Tanz 1985; Tanz
1988); T. violaceum was the predominant fungus in three studies (Haroon 1995; Haroon 1996; Jahangir 1998); In one study,
the proportion of M. canis and T. tonsurans was the same (Hamm
1999); M. canis was the main fungus in five trials (Lipozencic
2002; Lpez-Gmez 1994; Memisoglu 1999; Rademaker 1998;
Talarico Filho 1998). In three trials, the causative fungi were identified, but their relative frequencies were not provided so it was
impossible to determine the frequencies: T. tonsurans and M. ferrugineum were identified in one study (Kullavanijaya 1997), T.
tonsurans and T. violaceum in another (Gupta 2001), and T. mentagrophytes and M. canis in a third study (Martnez-Roig 1988).
Three other studies failed to classify the causative species of fungi
(Gan 1987; Memisoglu 1999; Tanz 1985).
Other
Some of the studies did not report the comparability between arms
or provide detailed information on the baseline characteristics of
sex, age, infection severity, and symptom/sign duration. One study
did not compare the baseline characteristics at all (Rademaker
1998) and two trials did not report the information on comparability (Martnez-Roig 1988; Solomon 1997). Finally, only three
trials reported information about the severity of the infection
(Cceres-Ros 2000; Gupta 2001; Tanz 1985). For the 20 studies,
the most common reason for excluding a participant from the trial
was treatment with any antifungal agent within one month prior
to entering the trial.

Effects of interventions
Griseofulvin
Efficacy
Griseofulvin has been used as the standard antifungal against

which we compare the other antifungals for the analyses. Of the
21 included studies, 13 compared griseofulvin with terbinafine,
itraconazole, ketoconazole or fluconazole. The standard dose for
griseofulvin used in trials is generally 10 to 20 mg/kg/day or 125
mg/day in participants weighing from 10 to 20 kg; 250 mg/day
from 20 to 40 kg and 500 mg/day over 40 kg.
Adverse effects
Griseofulvin was associated with a small number of adverse effects

in the trials. We did not find any reports or warnings of frequent
severe adverse effects in the separate search for adverse effects.
Comparative efficacy of griseofulvin is described in its comparison
with the other treatments as follows:
Terbinafine
Efficacy
Unless otherwise stated, the standard dosing for terbinafine in the

following studies was 62.5 mg/day in participants weighing from
10 to 20 kg; 125 mg/day from 20 to 40 kg, and 250 mg/day over
40 kg.
Short-term use of terbinafine versus griseofulvin (six studies)
(1) Primary outcomes

(a) The proportion of participants with complete cure, that is,
clinical and mycological cure
Six studies assessed the efficacy of terbinafine used for four weeks as
compared to griseofulvin (Cceres-Ros 2000; Fuller 2001; Gupta
2001; Haroon 1995; Memisoglu 1999; Rademaker 1998).
One open study (Rademaker 1998) was excluded from the pooled
analyses because it did not provide data about cure rates for each
arm of the study. This study compared 24 participants, 29% of
whom had T. verrucosum and 71% had M. canis, treated with
either terbinafine for 4 weeks or griseofulvin 10 mg/kg/day for 8
weeks.
Three studies included patients with Trichophyton infections. One
RCT (Haroon 1995) comparing terbinafine for 4 weeks and 10
mg/kg/day of griseofulvin for 8 weeks in 105 participants, of whom

87.6% had T. violaceum tinea capitis showed a cure rate at week 12
of 93% (52/56) in the terbinafine group and 80% (39/49) in the
griseofulvin group (RR 1.17, 95% CI 0.99 to 1.37; Analysis 1.1).
In a large open study but with losses of follow-up of more than
50% in both groups (Fuller 2001), T. tonsurans accounted for 77%
of the terbinafine group and 88% of the griseofulvin group and
Microsporum species accounted for 14% of both groups. Unknown
fungi were reported in 1.3% of terbinafine group and 2.9% of the
griseofulvin group. The study only reported type of fungus for 77
participants in the terbinafine group and 70 in the griseofulvin
group. We assume that the same percentage of fungus type applies
to the missing participants as well (65/76 = 86% for terbinafine
and 58/68 = 85% for griseofulvin) giving in the intention to treat
analysis at 24 weeks, complete cure rates for Trichophyton of 36%
(32/88) versus 29% (26/89) respectively (RR 1.24, 95% CI 0.81
to 1.90; Analysis 1.1). Another trial (Gupta 2001) compared 50
participants in each treatment group with infections caused by T.
tonsurans and T. violaceum. In this trial terbinafine given for 2 to 3
weeks was compared with microsized griseofulvin 20 mg/kg given
for 6 weeks. The complete cure rate at week 12 was 94% (47/50)
for the terbinafine group and 92% (46/50) for the griseofulvin
treated group (RR 1.02, 95% CI 0.92 to 1.14; Analysis 1.1). In
the pooled analysis, terbinafine for 4 weeks and griseofulvin for
8 weeks showed similar efficacy in the 3 studies involving 382
participants (RR 1.09 95% CI 0.95 to 1.26; Analysis 1.1). In
the study of Fuller 2001, the corresponding cure rates for the 29
children with Microsporum infections were 21% (3/14) and 33%
(5/15) respectively (RR 0.64, 95% CI 0.19 to 2.20; Analysis 1.1).
Two studies included patients with Trichophyton and Microsporum
infections and they do not provide separate results for each type of
infection. In a study (Memisoglu 1999) the complete cure rate at
the final follow-up visit (week 12) was 39% (15/39) for the group
treated with 4 weeks of terbinafine compared with 44% (17/39)
in the group treated with 8 weeks of ultra microsized griseofulvin
(RR 0.88, 95% CI 0.52 to 1.50; Analysis 1.1). There were similar
cure rates within the subgroups infected with M. canis (48% of
cases) and Trichophyton species according to the authors. The other
study (Cceres-Ros 2000) found a significant increase in the cure
rate of terbinafine (76%;19/25) as compared to griseofulvin (44%;
11/25) measured at 12 weeks of follow-up (RR 1.73, 95% CI
1.05 to 2.83; Analysis 1.1). This double blind RCT evaluated
terbinafine for 4 weeks versus microsized griseofulvin for 8 weeks
in 50 participants from Peru. The causative organisms were T.
tonsurans and M. canis in 74% and 26%, respectively. A pooled
analysis of the two studies showed no significant difference (RR
1.24, 95% CI 0.64 to 2.42; Analysis 1.1).
A pooled analysis of the five trials found that the difference in
the cure rates between four weeks of terbinafine and eight weeks
griseofulvin was not statistically significant (RR 1.11, 95% CI
0.96 to 1.29; Analysis 1.1).
(b) Adverse effects

No participants reported intolerance to either griseofulvin or

terbinafine in the open study carried out in New Zealand
(Rademaker 1998). In some studies, tolerability was reported for
terbinafine as good, or as no or few adverse effects of uncertain or
no relationship (Cceres-Ros 2000; Haroon 1995). Other studies
reported cases of tonsillitis, cutaneous infestations, raised hepatic
enzymes, raised triglycerides and eosinophilia (Haroon 1995), and
mild elevated triglycerides (Memisoglu 1999) of uncertain drug
relationship. The following adverse events were reported less commonly and may not have been caused by griseofulvin: skin infections, skin infestations, elevated hepatic enzymes, elevated serum
triglycerides, elevated serum uric acid, anaemia, eosinophilia, leucocytosis and granulocytopenia (Haroon 1995; Memisoglu 1999).
Another trial (Gupta 2001) reported three gastric problems and
three cases of nausea in the griseofulvin group. One of the participants who experienced nausea dropped out of the study. In
the largest open study (Fuller 2001), 57 adverse events (pruritus,
urticaria, skin scaling) were reported by 36 participants in the
terbinafine group, and 4 participants withdrew from the study due
to adverse events (vomiting, dizziness, urticaria and weight loss).
A total of 52 adverse events, predominantly abdominal discomfort
and vomiting, were detected in 27 participants in the griseofulvin group, and one participant withdrew from the study due to
abdominal pain, headache and vomiting. We did not find any reports or warnings of frequent severe adverse effects in the separate
search.
(2) Secondary outcomes

(a) The proportion of participants with clinical cure only
Only two studies did not report or mention the proportion of patients with clinical cure only (Fuller 2001; Haroon 1995). In one
study, (Cceres-Ros 2000), terbinafine for 4 weeks showed better
clinical scores when compared with griseofulvin at week 12. In
another study (Memisoglu 1999) mean total sum of scores (erythema, desquamation and pruritus) was not statistically significant
at week 12 when terbinafine for 2 to 3 weeks was compared with
griseofulvin. In another trial (Gupta 2001), the proportion of participants with clinical cure was determined at the end of treatment
(week four for terbinafine and week six for griseofulvin) showing
better results in the griseofulvin group.
the intervention period
None of the studies reported measurements of recurrence of the
condition after the end of the intervention period.
(c) Percentage of drop-outs as a surrogate for participant compliance
Only one study did not report any percentage of drop-outs
(Haroon 1995). One drop-out was reported in a clinical trial
(Cceres-Ros 2000), albeit the drop-outs by group were not reported. In the other studies the percentage of drop-outs was 10.2%
(4/39) vs 18% (7/39) (Memisoglu 1999), 35.9% (37/103) vs
24.2% (26/107) (Fuller 2001) and 4% (2/50) vs 8% (4/50) (Gupta

2001) in the terbinafine and griseofulvin group respectively.
(d) The time taken to cure
None of these studies reported the time taken to cure.
Medium to long-term use of terbinafine versus griseofulvin

(one study)

Only one open study (Lipozencic 2002) assessed medium to longterm treatment regimens of terbinafine versus griseofulvin. In this
study 98.5% of the 165 included participants were infected with
M. canis and the remainder were infected with M. audouini. Participants were treated with terbinafine for 6, 8, 10, or 12 weeks,
followed by placebo to complete 12 weeks of treatment in a double-blinded regimen, or griseofulvin for 12 weeks using an unblinded regimen. Pooling the data for medium-term treatment
(six or eight weeks) resulted in a trend towards an increase in the
complete cure rate for the griseofulvin group as compared to the
terbinafine group at four weeks after the end of treatment (RR
0.73, 95% CI 0.53 to 1.02; Analysis 2.1). However, long-term
duration treatment (10 or 12 weeks) resulted in the complete cure
rates being significantly higher in the griseofulvin group (70%
(21/30)) as compared to the terbinafine group (51% (36/70)) at 4
weeks after the end of treatment (RR 0.51, 95% CI 0.34 to 0.76;
Analysis 2.1).
(b) Adverse effects
This open study (Lipozencic 2002), reported adverse effects from
18.4% to 42.4% for terbinafine treatment groups and 16.7% for
the griseofulvin group. The most common adverse effects, accounted for approximately 5% in any group, were fever, pharyngitis, infections (parasitic, viral and upper respiratory tract) and influenza-like symptoms. Terbinafine was well tolerated in all treatment groups, although premature discontinuation of treatment
occurred in 2 patients, 1 in the terbinafine 6-week group due to
urticaria, and the other in the terbinafine 10-week group due to
asymptomatic, reversible, neutropenia reported as a serious adverse effect according to the protocol. Both events resolved without sequelae. Somnolence and gastrointestinal disorders were also
reported. We did not find any reports or warnings of frequent severe adverse effects in the separate search.


The proportion of participants with clinical cure only at 16 weeks,

reported in this study was 61.1% (22/36), 70.5% (24/34), 60.6%
(20/33), 50% (16/32) in the groups treated with terbinafine at 6,
8, 10 and 12 weeks respectively and 80% (24/30) in the griseofulvin group. In the pooled analysis, the control treatment (griseofulvin for 12 weeks) resulted in more cures compared with medium
terbinafine treatment duration (6 to 8 weeks) and long terbinafine
treatment duration (10 to 12 weeks), but this was statistically significant only in the comparison with long-term terbinafine: RR
0.82, 95% CI 0.64 to 1.05; Analysis 2.2 and RR 0.69, 95% CI
0.52 to 0.92; Analysis 2.2, respectively.
This study did not mention any measurement of recurrence of the
The percentage of drop-outs was 22.2% (8/36), 14.7% (5/34),
18.18% (6/33), 34.2% (12/32), and 23.3% (7/30), in the groups
treated with terbinafine for 6, 8, 10, or 12 weeks and griseofulvin,
respectively.
The number of patients with complete cure continued to increase
in all treatment groups, except for the terbinafine 12 week group
during week 2 to 16 of the study.
Comparing different treatment durations of terbinafine (five
studies)

One study (Haroon 1996) compared one, two, and four weeks
of terbinafine therapy. The cure rates at the final follow-up visit
(week 12) were 49% (26/53), 61% (31/51), and 67% (38/57),
respectively. The fungi identified included T. violaceum: 71.5%, T.
tonsurans: 14.9%, T. verrucosum: 4.3%, M. audouinii: 4.3%, M.
canis: 2.5%, T. schoenleinii: 1.9% and T. mentagrophytes: 0.6%.
In an open study (Kullavanijaya 1997) they compared 1, 2, and 4
weeks of terbinafine in 79 children and 3 adults with T. tonsurans
and M. ferrugineum tinea capitis. At week 12, the complete cure
rate was 44% (12/27), 57% (16/28), and 78% (21/27) in the
1, 2, and 4 week therapy groups, respectively. The proportions
and percentages were calculated including the adults participants,
because we were unable to determine which group they belonged
to. One study (Talarico Filho 1998) of 132 participants compared
1, 2, and 4 weeks of terbinafine. Although clinical evaluation at
week 12 showed that some participants achieved cure with 1 and 2
weeks of treatment, the cure rate was significantly higher with a 4

week treatment period. The complete cure rate was 46% (19/42),
53% (23/44), 79% (36/46) for the 1, 2, and 4 week treatment
groups respectively. Another study (Friedlander 2002) compared
different regimens of terbinafine in doses of 3 to 6 mg/kg/day for
1, 2, or 4 weeks. The complete cure rates at 12 weeks were 38%
(21/56), 46% (27/59), and 48% (30/62) respectively. The pooled
analysis of the combinations in these studies showed that a 4 week
treatment duration is clearly better than 1 week (RR 0.67, 95%
CI 0.55 to 0.8; Analysis 3.1) and 2 weeks (RR 0.81, 95% CI 0.68
to 0.96; Analysis 3.1).
Another study of 35 participants (Hamm 1999), which was not
included in the pooled analyses due to unknown number of participants assigned to each group. It compared one and two weeks
of terbinafine. After four weeks without significant improvement
participants were offered a second treatment course lasting four
weeks followed by an eight week observation period. It reported
complete cure rates at the end of the 12 week study period, of
44.4% (4/9) for cases caused by Trichophyton species and 0% (0/
5) for those caused by Microsporum species in the 1 week treatment group. In the 2 week terbinafine treatment group, complete
cure rates were 64% (9/14) for Trichophyton species and 0% (0/7)
for the Microsporum species, however, acceptable cure rates for M.
canis infection were achieved only after an additional four weeks
treatment.
(b) Adverse effects
The following adverse effects were reported in a study comparing
different regimens of terbinafine (Talarico Filho 1998): mild itching and mild constipation in the one week arm; mild headache
and nausea in the two week arm; mild urticaria, swelling of the lips
(labial oedema), mild constipation; and moderate loss of appetite,
mild diarrhoea, mild nausea and moderate/partial loss of taste (recovered within eight weeks) in the four week arm. Another study
comparing different regimens (Hamm 1999) reported: abdominal
pain (mild to moderate) and epistaxis, lack of appetite, headache
and severe facial swelling, coughing and fever (mild to moderate)
in the one week arm; abdominal pain, fatigue, nausea, dyspepsia,
headache and fever in the two week arm. One additional patient
had lack of appetite and gastroenteritis only during the additional
four week treatment period. In a study (Friedlander 2002), around
44% of the participants experienced adverse effects, assessed as
mild to moderate and unlikely to be related to the study medication. The most frequent included upper respiratory tract infections, gastrointestinal upsets and other events common in this patient population. The overall rate of adverse effects did not differ
between treatment groups. Only one open study (Kullavanijaya
1997) did not report adverse effects. One clinical trial (Haroon
1996) comparing three different regimens (at one, two and four
weeks) reported few cases of headache, raised hepatic enzymes,
raised triglycerides, eosinophilia and leucocytosis in the one week
arm; raised hepatic enzymes, eosinophilia in the two week arm

10
and raised hepatic enzymes, raised triglycerides, eosinophilia and

leucocytosis in the four week arm. We did not find any reports or
warnings of frequent severe adverse effects in the separate search.

The proportion of participants (Haroon 1996) with only clinical
cure reported at week 12 was 83% (44/53) in the 1 week arm;
85% (43/51) in the 2 week arm and 86% (49/57) in the 4 week
arm. In 1 study (Talarico Filho 1998) lower rates were seen in
the 1 and 2 week treatment: 54.3% (23/42) and 60.5% (27/44)
respectively. Similar results were seen in the 4 week arm treatment:
84.8% (39/46). The proportion of participants with clinical cure
only in the 3 regimens assessed (Friedlander 2002 ) at week 12
were: 48.2% (27/56) in the 1 week arm; 57.6% (31/59) in the 2
week arm; 58% (36/62) in the 4 week arm. No clinical cure rates
were reported in other trials (Hamm 1999; Kullavanijaya 1997).
None of the studies reported any measurements of recurrence of
the condition after the end of the intervention period.
In one study 81% (107/132) of participants (group unknown)
completed the study (Talarico Filho 1998). The percentage of
drop-outs was in the 1, 2 and 4 week arm reported were 25%(14/
56), 25.4%(15/59) and 19.3% (12/62), respectively (Friedlander
2002) despite the awareness of drop-outs in another study
(Kullavanijaya 1997) but they did not report the drop-outs by
group. No reports of the percentage of drop-outs were reported in
two studies (Hamm 1999; Haroon 1996).
In a study (Friedlander 2002) completed cure rates in all groups
continued to increase over the 12 weeks of observation. The time
taken to cure in another clinical trial (Hamm 1999) was about two
weeks if the causative organism was a Trichophyton. Regarding the
Microsporum, in this study they responded only to an additional
four week treatment course of terbinafine, two to three weeks after
an initial course of one or two weeks. In the other studies (Haroon
1996; Kullavanijaya 1997;Talarico Filho 1998) the time taken to
cure was not reported.
Comparing various doses (1 study)

A recently performed study (Ungpakorn 2004) assessed the efficacy of the standard dose of terbinafine compared to double doses
of terbinafine. These were both given in a pulsed protocol (one
week on, three weeks off ) for the treatment of tinea capitis caused
by Microsporum species. The complete cure rate for the standard
dose group reached 60.8% (14/23), compared to a complete cure
rate of 68.4% (13/19) in the double dose group (RR 1.12, 95%
CI 0.72 to 1.76; Analysis 4.1).
(b) Adverse effects
Not reported in the trial. We did not find any reports or warnings
of frequent severe adverse effects in the separate search.
(a) The proportion of participants with clinical cure only.
Not reported.
Not reported.
Not reported.
(d) The time taken to cure.
At week 20 all participants were cured with the exception of 1 who
at the beginning had moderately severe tinea capitis.
Itraconazole
Efficacy
Itraconazole versus griseofulvin (two studies)

(a) The proportion of participants with complete cure, that is,
clinical and mycological cure.
In 1 study (Lpez-Gmez 1994) involving 34 participants, in
whom M. canis was the most common fungi, the reported complete cure rates were 88% (15/17 and 15/17) for both drugs. This
study compared 6 weeks of treatment with ultra microsized griseofulvin 500 mg/day or itraconazole 100 mg/day with a follow up
of 14 weeks. Although one adult was included in this trial, this individual has been excluded from our calculations of cure rates. According to this trial, in tinea capitis involving Microsporum species,
both itraconazole and griseofulvin reach high complete cure percentages within a treatment period of 6 weeks (RR 1.06, 95% CI
0.81 to 1.39; Analysis 5.1).

11
Another study (Gupta 2001) compared 6 weeks of griseofulvin

and 2 to 3 weeks of itraconazole where the dose was given according the participants weight in a group of 100 participants. This
study showed complete cure rates of 82% (41/50) for the itraconazole group and 92% (46/50) for the griseofulvin group (RR
0.89 CI 0.76 to 1.04). The main causative fungi were stated as T.
tonsurans and T. violaceum, although the exact percentages were
not reported. According to this trial, when Trichophyton species
are the infecting fungi, both griseofulvin and itraconazole reach
high complete cure percentages, although griseofulvin tends to be
more effective. In this case griseofulvin had the disadvantage of
having been used for six weeks treatment while itraconazole was
administered only for two to three weeks.
No significant statistical difference was seen between the different
doses of itraconazole employed in the two studies and griseofulvin
in the pooled analysis (RR 0.94 CI 0.80 to 1.09; Analysis 5.1).
(b) Adverse effects
No adverse effects were reported in the itraconazole group in any
of the two trials. Two participants experienced nausea and intense
stomach ache with severe vomiting at weeks two and four of treatment, requiring discontinuation of therapy (Lpez-Gmez 1994).
The other trial (Gupta 2001) reported three gastric problems and
three cases of nausea. One of the participants who experienced
nausea dropped out of the study. We did not find any reports or
warnings of frequent severe adverse effects in the separate search.

In one study (Lpez-Gmez 1994), total combined symptom
severity score decreased by 9% in the itraconazole group and by
7% in the griseofulvin.
The proportion of participants with clinical cure only at the end of
treatment reported in (Gupta 2001) study were 44% (22/50) and
70% (35/50) in the itraconazole and in the griseofulvin group.
We did not find any reports of measurement of recurrence of the
Percentage of drop-outs (Gupta 2001) were the same in both treatments (8% (4/50)). However, in the other study (Lpez-Gmez
1994) the percentage of drop-outs were 5.5% (1/18) in the itraconazole group and 11.7% (2/ 17) in the griseofulvin group.
None of these studies reported the time taken to cure.
Itraconazole versus terbinafine (two studies)

and mycological cure
One study with 60 participants (Jahangir 1998) compared a 2
week course of itraconazole (50 to 200 mg/day based on weight)
with 2 weeks of terbinafine. T. violaceum was the causative fungus in 82% to 89% of the participants. Twelve weeks after the
start of treatment, 53% (16/30) and 60% (18/30) of participants
were completely cured in the terbinafine and itraconazole groups,
respectively (RR 1.13, 95% CI 0.72 to 1.75; Analysis 6.1). In
another study regarding Trichophyton species (Gupta 2001), itraconazole and terbinafine with a two to three week course of therapy were compared. The complete cure rates at 12 weeks were
94% (47/50) for the terbinafine group and 82% (41/50) for the
itraconazole group (RR 0.87, 95% CI 0.75 to 1.01; Analysis 6.1).
In the pooled analyses there was very little difference in complete
cure rate between itraconazole and terbinafine (as treatment of
Trichophyton species) when used for periods of two to three weeks
(RR 0.93, 95% CI 0.72 to 1.19; Analysis 6.1).
(b) Adverse effects
In one study (Jahangir 1998), two participants reported urticaria
in the itraconazole group. In the terbinafine group, one participant experienced fever, body aches and vertigo, but no participant
showed any significant haematological or biochemical change.
However, none of the participants showed any significant alteration in their haematological or biochemical profile. No adverse
effects were reported in any of the two groups in Gupta 2001. We
did not find any reports or warnings of frequent severe adverse
effects in the separate search.

Only one study (Gupta 2001) reported the proportion of participants with clinical cure only at the end of treatment (week four
for itraconazole and terbinafine) and similar results were seen in
both treatment groups: 40% (20/50) and 44% (22/50) in the
terbinafine and itraconazole groups.
Not reported in these trials.
Only in one study (Gupta 2001) the percentage of drop-outs was
reported, being 4% (2/50) for the terbinafine group and 8% (4/
50) for the itraconazole group.

12
The time taken to cure was not reported in any of the two trials.
Ketoconazole
Efficacy
Ketoconazole is a broad-spectrum antifungal agent proven highly

effective in dermatophyte infections. Due to the widely reported
and occasionally severe hepatic dysfunction which can sometimes
occur with ketoconazole, its use has been largely superceded by
newer azole compounds such as itraconazole and fluconazole. Four
older studies compared ketoconazole versus griseofulvin as a control.
(b) Adverse effects

Despite reports of liver disease, no cases were reported in the included studies. Ketoconazole use was associated with two cases
of abdominal pain and one case of urticaria (Tanz 1985). Only
one patient from the ketoconazole group withdrew from the study
and reported to have nausea. Other than this, there were no serious adverse reactions in any of the two groups (Tanz 1988).
No adverse effects were reported in the ketoconazole group (Gan
1987; Martnez-Roig 1988). One griseofulvin treated participant
showed a two-fold increase in serum alanine aminotransferase
and aspartate aminotransferase after three weeks of treatment but
values returned to normal at the following weekly clinic visits
(Martnez-Roig 1988). We did not find any reports or warnings
of frequent severe adverse effects in the separate search.
Ketoconazole versus griseofulvin (four studies)

A very small study (Martnez-Roig 1988) of 13 participants compared griseofulvin 350 mg/day for 6 weeks with ketoconazole 100
mg/day for 6 weeks in inflammatory tinea capitis (T. mentagrophytes and M. canis). At the end of treatment, 100% (8/8) and
80% (4/5) of children in the ketoconazole and griseofulvin group
respectively had improved clinically, although no mycological or
complete cure data were reported. It needs to be taken into account
that this study talks about 47 participants having tinea capitis or
tinea corporis, but for the purpose of our review we have only
used the results of the 13 tinea capitis participants. In an open
study (Gan 1987) carried out in 80 participants where Trichophyton species predominated, they compared once-daily ketoconazole
5 mg/kg/day with griseofulvin 15 mg/kg/day each given as a single
daily dose. Treatment was stopped when there was either complete
cure or after six months had passed. After 8 weeks of therapy, only
59% (23/40) of ketoconazole-treated participants had complete
cure of their infection compared with 92% (37/40) of the participants given griseofulvin.
Two studies of 22 and 79 participants (Tanz 1985; Tanz 1988)
where T. tonsurans was the most commonly isolated fungus, compared oral ketoconazole at doses of 3.3 to 6.6 mg/kg/day and (Tanz
1988), and 200 mg/day (Tanz 1985), for 12 and 6 weeks with
griseofulvin at doses of 10 to 20 mg/kg/day (Tanz 1988) and 250
to 500 mg/day (Tanz 1985), respectively. This last trial did not
report complete cure rates but stated that there were no statistically significant differences between the mycological cure rates of
the two drugs. In the other study (Tanz 1988), the complete cure
rate, was 48% (16/33) for the ketoconazole group, and 54% (25/
46) for the griseofulvin group.
Only two studies were of sufficient quality to be included in
the pooled analysis (Gan 1987; Tanz 1988). Although cure rates
favoured griseofulvin, these did not reach statistical significance
(RR 0.72, 95% CI 0.50 to 1.02; Analysis 7.1).

One study (Tanz 1988) assessed clinical cure rates at week 12 and
reported that a decrease in severity scores in both groups was statistically significant. However, the difference between mean scores
of groups was not statistically significant at any point. In another
study (Martnez-Roig 1988) the clinical cure rates evaluated at the
end of treatment were 100% (8/8) and 80% (4/5) in the ketoconazole and griseofulvin group respectively.
Only one trial (Martnez-Roig 1988) reported that one of the
childrens clinical status of the griseofulvin group, deteriorated after
the six week treatment.
In a study (Tanz 1985) the percentage of drop-outs was 41.6% (5/
12) and 30% (3/10) in the griseofulvin and ketoconazole, respectively . Higher percentages of drop-outs were reported in another
study (Tanz 1988) being 56.5% (26/46) and 66.6% (22/33) in
the griseofulvin and ketoconazole groups respectively.
In 1 trial (Gan 1987), the time needed to improve was 60 days and
108 days in the ketoconazole and griseofulvin group respectively.
Hair sample cultures took significantly longer to become negative (sterile) in ketoconazole-treated (median eight weeks) than
in griseofulvin-treated (four weeks) participants. Another study
(Martnez-Roig 1988) reported the mean time to clinical cure in
weeks: 4.2 weeks in the griseofulvin group and 5 weeks in the
ketoconazole group. They also reported the mean time needed
to achieve negative cultures in weeks: 3.6 and 4.7 weeks in the
griseofulvin and ketoconazole group respectively. In the other two

13
studies (Tanz 1985; Tanz 1988) the time taken to cure was not
reported.
Fluconazole
Efficacy

None of these trials reported measurements of recurrence.
The same percentage of drop-outs were reported in Gupta 2001
clinical trial (8% (4/50)). However in Dastghaib 2005 study, the
drop-outs by group were not reported.
This was not reported in either of the two studies.
Fluconazole versus griseofulvin (two studies)

Fluconazole versus terbinafine (one study)
Two studies (Gupta 2001; Dastghaib 2005) compared fluconazole
and griseofulvin. The first (Gupta 2001) assessed 100 participants
who were infected with T. tonsurans and/or T. violaceum (the exact
percentages were not reported). They were treated with either fluconazole 6 mg/kg/day for 2 to 3 weeks or with microsized griseofulvin 20 mg/kg/day for 6 weeks. The complete cure rates were
82% (41/50) and 92% (46/50), respectively (RR 0.89, 95% CI
0.76 to 1.04; Analysis 8.1).
The second study (Dastghaib 2005) assessed 40 participants: 16
were infected with T. violaceum, 16 with T. verrucosum, and 8 with
M. canis. The children were treated with 5 mg/kg/day of fluconazole or 15 mg/kg/day griseofulvin for 4 and 6 weeks respectively.
Complete cure was reported for 79% (15/19) of the fluconazole
arm and 76 % (16/21) of the griseofulvin arm (RR 1.04, 95% CI
0.74 to 1.45; Analysis 8.1).
A pooled analysis of the 2 studies failed to show any significant
differences between fluconazole and griseofulvin (RR 0.92, 95%
CI 0.80 to 1.05; Analysis 8.1).
(b) Adverse effects
No adverse effects were reported in these trials regarding fluconazole. In a study (Gupta 2001) they reported three gastric problems
and three cases of nausea. One of the participants who experienced
nausea dropped out of the study. Both studies reported nausea as
an adverse effect in the griseofulvin group. We did not find any
reports or warnings of frequent severe adverse effects in the separate search.

Only one study (Gupta 2001) reported the proportion of participants with clinical cure only at the end of treatment (week 4 for
fluconazole, and week 6 for griseofulvin) 70% (35/50) and 26%
(13/50) in the griseofulvin and fluconazole groups respectively.

The same study (Gupta 2001) analysed the efficacy of fluconazole
for two to three weeks compared with terbinafine, dosed according
to weight for two to three weeks. The complete cure rates were
82% (41/50) for the fluconazole arm and 94% (47/50) for the
terbinafine arm (RR 0.87, 95% CI 0.75 to 1.01; Analysis 9.1).
(b) Adverse effects
No adverse effects were reported in this trial. There was no intolerance to the medication and no laboratory values were abnormal
at any follow-up time. We did not find any reports or warnings of
frequent severe adverse effects in the separate search.

The proportion of participants with clinical cure only at the end
of treatment (week 4 for terbinafine and fluconazole) was nearly
double in the terbinafine group (40% (20/50)) when compared
with the fluconazole group 26% (13/50).
Not mentioned.
The percentage of drop-outs was 4% (2/50) and 8% (4/50) in the
terbinafine and fluconazole groups respectively.
This was not reported in this study.

14
Fluconazole versus itraconazole (one study)

When fluconazole treatment was compared with itraconazole (
Gupta 2001) in participants with Trichophyton tinea capitis, in
doses of 5 mg/kg/day daily for 2 to 3 weeks, the complete cure
rates were 82% (41/50 and 41/50) for both groups (RR 1.00, 95%
CI 0.83 to 1.20; Analysis 10.1).
(b) Adverse effects
No adverse effects were reported in this trial. We did not find
any reports or warnings of frequent severe adverse effects in the
separate search.

The proportion of participants with clinical cure only at the end
of treatment (week four in itraconazole and fluconazole groups)
was nearly double in the itraconazole group: 44% (22/50) when
compared with the fluconazole group: 26% (13/50).
Not reported.
The same percentage of drop-outs as a surrogate for participant
compliance were reported in both treatment groups (8% (4/50)).
The time taken to cure was not reported in this study.
Comparing various doses of fluconazole (one study)

A North American study (Solomon 1997) compared different
doses of fluconazole: 1.5 mg/kg/day, 3 mg/kg/day, and 6 mg/kg/
day, for 20 days in a group of 41 participants with tinea capitis
caused by Trichophyton species. Efficacy was reported only in 27
participants and authors did not report drop-outs by group. However, they reported the total missing participants (34%) in the
study. Thus, we assumed that the same percentage was applied for
the missing participants in each group, being originally 12, 15 and

14 participants randomly assigned in the 1.5 mg/kg/day, 3 mg/
kg/day and 6 mg/kg/day groups respectively. Intention-to-treat efficacy rates in the 1.5 mg/kg/day, 3 mg/kg/day and 6 mg/kg/day
groups were 17% (2/12), 40% (6/15) and 57% (8/14) respectively.
Although higher doses resulted in more cures than lower doses,
none of the comparisons reached statistical significance (3.0 mg
versus 1.5 mg: RR 2.40, 95% CI 0.59 to 9.82; Analysis 11.1. 6.0
mg versus 1.5 mg: RR 3.43, 95% CI 0.89 to 13.15; Analysis 11.1.
6.0 mg versus 3.0 mg: RR 1.43, 95% CI 0.66 to 3.08; Analysis
11.1).
(b) Adverse effects
No adverse effects were reported in this trial. We did not find
any reports or warnings of frequent severe adverse effects in the
separate search.

Clinical improvement was noted on average after 2 weeks (by the
17th day and 116th day) in fluconazole 1.5 mg/kg/day and in
fluconazole 3 mg/kg/day respectively. And before 2 weeks (by the
12th day) in fluconazole 6 mg/kg/day group.
All participants remained clinically and mycologically cured six
weeks and four months after therapy was discontinued.
There was overall a 34% of losses but the authors did not report
the drop-outs by group.
Although Solomon et al commented in their paper that clinical
improvement seemed to occur more quickly when fluconazole was
given in higher doses (e.g. 3 to 6 mg/kg/day), no data on time to
cure was reported (Solomon 1997).
DISCUSSION
Tinea capitis (scalp ringworm) is a very common and troublesome fungal (dermatophyte) infection of the scalp skin and hair of
children living in mainly disadvantaged communities worldwide
(Mhrenschlager 2005).
Summary of main results

15
Benefits and harms
Griseofulvin
Griseofulvin has traditionally been the most widely used systemic

treatment for tinea capitis and is licensed for tinea capitis in most
countries. It is fungistatic (halts growth of the fungus) arresting
cell division and impairing fungal cell wall synthesis. Taking the
drug with fatty food increases absorption and aids bioavailability.
Dosage recommendations vary according to the formulation used,
with higher doses being recommended by some trial authors for
microsized griseofulvin as opposed to ultra microsized griseofulvin,
however, up to 25 mg/kg may be required (Higgins 2000). There is
good evidence to support the use of griseofulvin for treating tinea
capitis caused by T. tonsurans, M. canis, T. mentagrophytes and T.
violaceum. The advantages of griseofulvin are that it is inexpensive,
the suspension dosage form allows for accurate dosing in children,
and that is licensed in most countries with extensive experience.
Unfortunately, one disadvantage is the prolonged treatment required and the potentially significant gastrointestinal side effects
such as nausea. Other adverse effects include headache and rashes.
The studies included in this review registered some infrequent
adverse effects which may or may not be related to griseofulvin
treatment. These were elevated serum liver enzymes, triglycerides
and uric acid, anaemia, eosinophilia, leucocytosis and granulocytopenia. Although none of the observed adverse effects were labelled as severe, periodic monitoring every month of organ system
functions, including hepatic, renal and hematopoietic (blood) systems has been recommended in participants taking griseofulvin
for more than eight weeks (Mhrenschlager 2005).
Griseofulvin has served as a standard for the evaluation of any
newer treatment for tinea capitis. Such new drugs, typically used
for treating fungal infections in adults, have recently been considered for use in children. They include terbinafine, ketoconazole,
itraconazole and fluconazole. Thus it is important to determine
the comparative efficacy and safety profile of all of these drugs.
Furthermore, due to the world-wide distribution of this infection,
the responsiveness of fungal species to different drugs is also very
important. There are many published studies and a large amount
of literature assessing the efficacy and tolerability of these new
antifungals. This systematic review has assessed the systemic antifungals globally, comparing them not only against griseofulvin
but against each other as well. This may help physicians all around
the world to determine their choice when treating tinea capitis in
children.
Terbinafine
Terbinafine is an allylamine (chemical structure) that acts on the

fungal cell membrane and is fungicidal. It has a good safety profile in children and could represent a good alternative to griseofulvin. Terbinafine has the potential advantage over griseofulvin of producing optimum results in a shorter time (four to six
weeks), making participant compliance less of a problem. Effective short-course therapy is especially desirable in children because
prolonged therapy increases the risk of adverse effects and the likelihood of drop-outs. These conclusions agree with those of a recent
meta-analysis (Fleece 2004) comparing terbinafine against griseofulvin. There is good evidence from these results that the efficacy
of terbinafine treatment may vary according to the fungal species
isolated.
Terbinafine is at least as effective as griseofulvin for the treatment of Trichophyton infections of the scalp; however, there is
some evidence of a trend towards higher cure rates with griseofulvin in participants with Microsporum infections. One RCT
(Lipozencic 2002) assessing different long term treatment regimes
of terbinafine (6, 8, 10 and 12 weeks) in Microsporum infections
found difference between cure rates not statistically significant
but with a trend to shorter treatment durations. Limited evidence
from observational studies (Aste 2004; Devliotou 2004) suggests
that longer therapeutic regimens of terbinafine may improve the
cure rates of Microsporum species (Commens 2003). However, a
small sized trial with no drop-outs which took place in Thailand
(Ungpakorn 2004) comparing standard dose terbinafine against
double dose terbinafine (both given in two pulses) in the treatment
of Microsporum species tinea capitis did not show any statistical
difference in the cure rates. On the other hand, there were higher
drop-outs in the long treatment duration groups that can be a
surrogate of a bad compliance.
An important disadvantage of terbinafine in treating young children is that it is available only in tablet form and currently there
is no suspension or liquid formulation. Tablets may need to be
concealed in food. In addition, terbinafine is not licensed for treatment of tinea capitis in children in some countries. In the review of these studies, the most frequent adverse events caused by
terbinafine were gastric problems such as vomiting, nausea, or lack
of appetite, or cutaneous disturbances such as itching and swelling
of the lips. Increases in the level of hepatic enzymes or triglycerides
have no apparent relationship with the drug.
Itraconazole
Itraconazole like other azoles exhibits a fungistatic activity. Limited evidence based on small trials suggests that oral itraconazole
at doses according to the participants weight, is effective and safe
for tinea capitis caused by T. violaceum (two weeks of treatment)
and M. canis (six weeks of treatment). Concerning Trichophyton
species, we found only one study with 100 participants (Gupta
2001) that showed very little difference between itraconazole and
terbinafine, with high complete cure percentages for treatment periods lasting 2 to 3 weeks. In a study of 100 children with tinea
capitis involving Microsporum species (Lpez-Gmez 1994), both
itraconazole and griseofulvin reached complete cure percentages of
82% and 94% respectively within a treatment period of 6 weeks.
Some clinicians (Ginter 2004) have suggested itraconazole for six

16
weeks as a regimen for M. canis tinea capitis, although a proportion

of children may require longer treatment duration. Itraconazole is
currently not licensed in some countries for use in tinea capitis and
for use in children (Higgins 2000). Pulsed (intermittent drug administration in combination with drug-free periods) shorter treatment regimens are possible but more studies are needed to confirm
the paediatric requirements of itraconazole.
The most common adverse effects of itraconazole were headache,
skin rash (cutaneous eruption) and gastrointestinal complaints. In
the studies reviewed, the gastrointestinal complaints were the most
frequent adverse effects. Most rarely a reversible increase of serum
aminotransferases was seen.
Fluconazole
Fluconazole is a broad-spectrum antifungal of the triazole chemical class. A variety of limited trials using this drug have shown
promising results in the treatment of tinea capitis in children. Fluconazole efficacy was assessed in two trials (Gupta 2001; Dastghaib
2005) both with majority of tinea capitis infections by Trichophyton species. The efficacy of four weeks of fluconazole seems comparable to six weeks of griseofulvin (Dastghaib 2005). However,
there is not enough evidence to establish a clear dosage regimen
with fluconazole for tinea capitis in children. A small North American study (Solomon 1997) where T. tonsurans was the predominant fungi showed that when fluconazole is given in daily doses
of 6 mg/kg, clinical improvement may occur quicker. It should
be noted, however, that this study had losses of more than 50%
therefore only limited evidence suggests that fluconazole continuously at 6 to 8 mg/kg/day for 3 weeks and intermittently at 6 to
8 mg/kg/week for 4 to 8 weeks is effective and safe for treating T.
tonsurans tinea capitis in children. We are aware of a large RCT
of participants infected mainly with T. tonsurans which compared
fluconazole 6 mg/kg/day for 3 and 6 weeks versus griseofulvin 11
mg/kg/day for 6 weeks: that trial is currently awaiting assessment
(Foster 2005).
The safety profile for fluconazole in children is very good and the
availability in both tablet and liquid formulation, making dosing
in young children more convenient, although it is not licensed
for this indication in children in some countries. The reasons for
treatment failures may include lack of compliance with the long
courses of treatment, as well as a suboptimal absorption of the drug,
causing a relative insensitivity of the organism and reinfection.
Fluconazole is generally well tolerated in children. Adverse effects
occur in about 16% of participants who receive the drug for longer
than 7 days (gastrointestinal tract disturbances, headache, cutaneous eruption, liver function test abnormalities). Most of these
adverse effects are mild and reversible, only two studies included
in this review (Gupta 2001; Dastghaib 2005) registered adverse
events related to the use of the drug. Suggested monitoring may
include complete blood count, liver and renal function tests before
and during therapy (at monthly intervals).
Ketoconazole
Ketoconazole is an antifungal of the same chemical family as itraconazole and fluconazole and was one of the first alternatives to
griseofulvin studied for the treatment of tinea capitis in children.
Some physicians strongly believe that ketoconazole should not be
used in children because of potential adverse effects, especially
hepatotoxicity (Elewski 2000). In fact there is also a concern regarding the safety profile of all reviewed antifungals in children
due to the possibility of rare but potentially serious side-effects,
such as liver toxicity and drug interaction (Blumer 1999).
We are aware of an unpublished single-blind RCT (Pather 2006)
that has explored an inexpensive, safe and easily implemented intervention in a poor community outside Cape Town (South Africa)
using a weekly high-dose intermittent regimen of griseofulvin versus a daily low-dose regimen. We will include data from that study
in our next update as soon as it becomes available.
Other factors when prescribing these antifungals should be taken
into account. When talking about equally effective therapies, tolerability, safety, compliance and cost have to be considered. Griseofulvin, terbinafine, itraconazole and fluconazole have a good safety profiles and in clinical practice none of these agents require
laboratory monitoring at the recommended lengths of treatment
for tinea capitis. The percentage of drop-outs as a surrogate for
participant compliance did not show any important difference
among treatments. In children, research regarding any kind of intervention should attempt to find shorter treatment durations as
well as making oral treatments easy to take to ensure better compliance. In contrast with the newer treatment, griseofulvin is generally available in an oral suspension in most countries. The newer
antifungals cost can be an issue, which is an important consideration given that tinea capitis is endemic in some of the poorest communities in the world. This review offers the context and guidance
on the important issue of cost effectiveness with respect to the new
antifungals, an area of prescribing which can represent significant
expenditure and impact on the budget in some countries. It also
will help to develop and improve guidelines for the management
of tinea capitis as the prepared for the British Association of Dermatologists (Higgins 2000).
The use of additional anti-inflammatory drugs (such as oral or topical corticosteroids) or other preventive and adjuvant (additional)
measures does not fall within the scope of this review, however, we
found some studies (Ginsburg 1987; Honig 1994; Hussain 1999).
It is important to assess adjunctive topical therapies, as antifungal
shampoos to reduce the risk of transmission and the evaluation
and treatment of infected contacts as factors affecting the cure of
tinea capitis (Higgins 2000). Tinea capitis requires systemic treatment because antifungal creams are unable to penetrate the hair
shaft sufficiently to clear the infection. It is believed that the use of
topical antifungal treatment alone may contribute to the creation
of participants whose symptoms and clinical signs are minimal but
who are capable of transmitting infection (Fuller 2003). Systemic
therapy is required to clear scalp ringworm and diagnosis should

17
be confirmed by mycological analysis before starting treatment.

In conclusion, this review has shown that terbinafine and griseofulvin had similar efficacy when used at comparable doses according to weight, for infections involving Trichophyton species. The
treatment duration, however, appears to be shorter for terbinafine
(four weeks) than for griseofulvin (eight weeks). The comparative
fair efficacy of itraconazole and fluconazole with griseofulvin, as
well as terbinafine, is based on limited evidence. All these drugs
have good safety profiles in children. However, these newer systemic drugs have not been approved by health authorities in many
countries for use in tinea capitis of childhood. Although the newer
antifungals agents may have more consistent absorption rates and
longer periods of retention in infected tissues, the use of griseofulvin continues to result in high cure rates of tinea capitis in
children, with limited toxicity.
This systematic review may help physicians worldwide to weight
the advantages and disadvantages of the treatment options when
treating children with tinea capitis. This review draws on detailed
information derived from clinical trials assessing the efficacy of
treatment for tinea capitis, but caution should be exercised in interpreting the data. It may be necessary or even desirable to depart
from clinical experience in the interests of individual participants
and special circumstances in individual local communities.
AUTHORS CONCLUSIONS
may constitute an alternative drug which is well tolerated and

has few side effects. Long-term (more than six weeks) terbinafine
therapy cannot be recommended on the basis of this review. In
the case of M. canis infections it may require treatment for six to
eight weeks, but griseofulvin remains the treatment of choice for
Microsporum tinea capitis, and is certainly more cost effective.
Some evidence based on few studies shows that oral itraconazole at
doses according to children weight for two to six weeks is effective
and safe for tinea capitis caused by T. violaceum (two weeks of
treatment) and M. canis (six weeks of treatment). There is also
some evidence that four weeks of fluconazole are comparable to
six weeks of griseofulvin, especially with tinea capitis caused by
Trichophyton species.
Implications for research

It would be interesting to see more comparisons between the newer
and relatively expensive antifungals for tinea capitis in children.
There are currently a limited number of trials involving different
doses, and further information is needed on treatment doses and
frequency for all antifungals including griseofulvin. There is a need
for further research on the clinical effectiveness of a broader range
of different doses and duration of treatment. Furthermore, trials to
establish which antifungal is more effective would be helpful, as the
majority of the literature is currently concerned with griseofulvin.
Importantly, further research is also required regarding the impact
on mode of administration and compliance in children.
Implications for practice

There is reasonable evidence to support the use of griseofulvin to
treat tinea capitis in children, caused by T. tonsurans, M. canis, T.
mentagrophytes and T. violaceum. Overall griseofulvin is considered
to be safe in children. On the basis of the studies described, the
recommended dosage regimen for children is continuous therapy
with tablets or suspension, adjusted according to childrens weight
for six to eight weeks including microsized and ultra microsized
preparations.
Moderate RCT evidence indicates that terbinafine at standard
doses according to patient weight for two to four weeks, is effective and safe for the treatment of Trichophyton tinea capitis.
Terbinafine when compared with griseofulvin produces good results in a shorter time of treatment (four to six weeks), making
participant compliance less of a problem. One potential disadvantage, however, is that it is only available in tablet form. While
tablets may be preferred by some children (age five years and older
perhaps), they may not allow for dosage individualization. This
review supports the idea that although griseofulvin will continue
to remain the antifungal drug of choice in tinea capitis, terbinafine
ACKNOWLEDGEMENTS
We wish to acknowledge Sally Hollis, Jo Leonardi-Bee (Statistical Editor of the Cochrane Skin Group) and Philippa Middleton
(Methods Editor of the Cochrane Skin Group) for their advice
on the assessment of methodological quality and results, Hywel
Williams for his helpful comments as lead editor and Mariona
Pinart for her help in the edition of this review.
The editorial base would like to thank the following people who
were external peer referees for the review: Antonio Chuh and
Matthias Moehrenschlager (content experts) and Shirley Manknell
(consumer) as well as Josep Maria Torres for his participation in
the development of the Review protocol.
This review has been funded by the Cochrane Child Health Field.
Alberta Research Centre for Child Health Evidence, University
of Alberta, Canada, and The Spanish Society of Dermato-Epidemiology and Evidence-based dermatology (SEDE-DBE), and
the Clnica Plat. Fundaci Privada of Barcelona.

18
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of Dermatology 1998;139:6724.
Kullavanijaya 1997 {published data only}
Kullavanijaya P, Reangchainam S, Ungpakorn R.

Randomized single-blind study of efficacy and tolerability
of terbinafine in the treatment of tinea capitis [comment in
Journal of the American Academy of Dermatol 1998; 39
(1):136]. Journal of the American Academy of Dermatology
1997;37(2 Pt 1):2723.
Lipozencic 2002 {published data only}
Lipozencic J, Skerlev M, Orofino-Costa R, Zaitz VC,

Horvath A, Chouela E, et al.A randomized, double-blind,
parallel-group, duration-finding study of oral terbinafine
and open-label, high-dose griseofulvin in children with
tinea capitis due to Microsporum species. British Journal of
Dermatology 2002;146(5):81623.
Lpez-Gmez 1994 {published data only}
Lpez-Gmez S, Del Palacio A, Van Cutsem J, Cutara

MS, Iglesias L, Rdriguez Noriega A. Itraconazole versus
griseofulvin in the treatment of tinea capitis: A doubleblind randomized study in children [comment in the
International Journal of Dermatology 1994;33(10):701.
International Journal of Dermatology 1994;33(10):7437.
Martnez-Roig 1988 {published data only}
Martnez-Roig A, Torres-Rodrguez JM, Bartlettcoma A.

Double blind study of ketoconazole and griseofulvin in
dermatophytoses. The Pediatric Infectious Disease Journal
1988;7(1):3740.

19
Memisoglu 1999 {published data only}
Memisoglu HR, Erboz S, Akkaya S, Akan T, Aksungur

VL, nal I, et al.Comparative study of the efficacy and
tolerability of 4 weeks of terbinafine therapy with 8 weeks of
griseofulvin therapy in children with tinea capitis. Journal
of Dermatological Treatment 1999;10:18993.
Foster 2005 {published data only}

Foster KW, Friedlander SF, Panzer H, Ghannoum MA,
Elewski BE. A randomized controlled trial assessing the
efficacy of fluconazole in the treatment of pediatric tinea
capitis. Journal of the American Academy of Dermatology
2005;53(5):798809.
Rademaker 1998 {published data only}
Rademaker M, Havill S. Griseofulvin and terbinafine in

the treatment of tinea capitis in children. New Zealand
Medical Journal 1998;111(1060):557.
Pather 2006 {unpublished data only}

Pather S. A prospective, randomized, single-blinded trial to
determine the efficacy of single and weekly dose regimens
of oral griseofulvin versus 6 weeks of daily dosing in the
treatment of tinea capitis in children. British Journal of
Dermatology. 2006; Vol. 155 (Suppl. 1):106-19.
Solomon 1997 {published data only}
Solomon BA, Collins R, Sharma R, Silverberg N, Jain AR,

Sedgh J, et al.Fluconazole for the treatment of tinea capitis
in children. Journal of the American Academy of Dermatology
1997;37(2 Pt 1):2745.
Talarico Filho 1998 {published data only}
Talarico Filho T, Cuc LC, Foss NT, MArques SA,

Santamaria JR. Efficacy, safety and tolerability of terbinafine
for tinea capitis in children: Brazilian multicentric study
with daily oral tablets for 1, 2 and 4 weeks. Journal of the
European Academy of Dermatology & Venereology 1998;11
(2):1416.
Tanz 1985 {published data only}
Tanz RR, Stagl S, Burton Esterly N. Comparison of

ketoconazole and griseofulvin for treatment of tinea capitis
in childhood: A preliminary study. Pediatric Emergency
Care 1985;1(1):168.
Tanz 1988 {published data only}
Tanz RR, Hebert AA, Burton Esterly N. Treating tinea

capitis: Should ketoconazole replace griseofulvin?. Journal
of Pedriatics 1988;112(6):98791.
Ungpakorn 2004 {published data only}
Ungpakorn R, Ayutyanont T, Reangchainam S, Supanya

S. Treatment of Microsporum spp. tinea capitis with pulsed
oral terbinafine. Clinical and Experimental Dermatology
2004;29:3003.
References to studies excluded from this review

Ginsburg 1987 {published data only}
Ginsburg C, Ghan NV, Petruska M. Randomized controlled
trial of intralesional corticosteroid and griseofulvin vs.
griseofulvin alone for treatment of kerion. The Pediatric
Infectious Disease Journal 1987;6(12):10847.
Honig 1994 {published data only}
Honig PJ, Caputo GL, Leyden JJ, McGinley K, Selbst SM,
McGravey AR. Treatment of kerions. Pediatric Dermatology
1994;11:6971.
Hussain 1999 {published data only}
Hussain I, Muzaffar F, Rashid T, Ahmad TJ, Jahangir M,
Haroon TS. A randomized, comparative trial of treatment
of kerion celsi with griseofulvin plus oral prednisolone vs.
Griseofulvin alone. Medical Mycology 1999;37:979.
References to studies awaiting assessment
Additional references
Aly 1999
Aly R. Ecology, epidemiology and diagnosis of tinea capitis.
The Pediatric Infectious Diseases Journal 1999;18:1805.
Aste 2004
Aste N, Pau M. Tinea capitis caused by Microsporum canis
treated with terbinafine. Mycoses 2004;47(9-10):42830.
Bennet 2000
Bennet ML, Fleischer AB, Loveless JW, Feldman. Oral
griseofulvin remains the treatment of choice for tinea capitis
in children. Pediatric Dermatology 2000;17:3049.
Blumer 1999
Blumer JL. Pharmacologic basis for the treatment of tinea
capitis. The Pediatric Infectious Disease Journal 1999;18:
1919.
Commens 2003
Commens C. Which drug is most effective in treating
childhood tinea capitis caused by Microsporum species?.
The Medical Journal of Australia 2003;178(11):5778.
Devliotou 2004
Devliotou-Panagiotidou D, Koussidou-Eremondi TH.
Efficacy and tolerability of 8 weeks treatment with
terbinafine in children with tinea capitis caused by
Microsporum canis: a comparison of three doses. Journal of
the European Academy of Dermatology & Venereology 2004;
18(2):1559.
Elewski 2000
Elewski BE. Tinea capitis: a current perspective. Journal of
the American Academy of Dermatology 2000;42:124.
Fleece 2004
Fleece D, Guaghan JP, Stephen C, Aronoff C. Griseofulvin
versus terbinafine in the treatment of tinea capitis: a metaanalysis of randomized, clinical trials. Pediatrics 2004;114
(5):13125.
Friedlander 2000
Friedlander SF. The optimal therapy for tinea capitis.
Pediatric Dermatology 2000;17:3256.
Fuller 2003
Fuller LC, Child FJ, Midgley G, Higgins EM. Diagnosis
and management of scalp ringworm. BMJ 2003;326:
53941.

20
Ginter 2004
Ginter-Hanselmayer G, Smolle J, Gupta A. Itraconazole in
the treatment of tinea capitis caused by Microsporum canis:
experience in a large cohort. Pediatric Dermatology 2004;21
(4):499502.
Gonzlez 2003
Gonzlez U. Tinea capitis. In: Williams H, Bigby M,
Diepgen T, Herxeimer A, Naldi L, Rzany B editor(s).
Evidence-based Dermatology. London: BMJ Books, 2003:
46989.
Gupta 1999
Gupta AK, Hofstader SLR, Adam P. Tinea capitis: An
overview with emphasis on management. Pediatric
Dermatology 1999;16:17189.
Higgins 2000
Higgins EM, Fuller LC, Smith CH. Guidelines for the
management of tinea capitis. British Journal of Dermatology
2000;143:538.
Juni 2001
Juni P, Altman DG, Egger M. Systematic reviews in health
care: Assessing the quality of controlled trials. British
Medical Journal 2001;323:426.
Mhrenschlager 2005
Mhrenschlager M, Seidl HP, Ring J, Abeck D. Pediatric
tinea capitis. Recognition and management. American
Journal of Clinical Dermatology 2005;6:20313.
Indicates the major publication for the study

21
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Cceres-Ros 2000
Methods
Follow up: 12 weeks.

Randomisation: unclear.
Blinded assessment: participants, clinicians and outcome assessors blinded
Loss to follow up: one drop-out, group not stated.
Sample size calculation declared: no.
Inclusion criteria: yes.
Exclusion criteria: yes.
Reporting of type of fungi involved: yes.
Baseline comparability:
severity of infection: griseofulvin group: black dot 32% (8/25); white-greyish hair 68% (17/25); terbinafine
group: black dot 8% (2/25); white-greyish hair 92% (23/25).
age: griseofulvin group: 6.72; terbinafine group: 6.84.
sex: griseofulvin group: males: 10; females: 15; terbinafine group: males: 13; females: 12.
duration of complaint: from one week to four years.
Funding: not mentioned.
Participants
Lima (Per)
n = 50
Aged between 1 and 14.
23 males/27 females.
Inclusion criteria: to have a clinical and mycologic diagnosis of non-inflammatory tinea capitis; to weigh
more than 10 kg; to have a normal baseline laboratory evaluation (complete blood cell count, erythrocyte
sedimentation rate, liver function tests and urinalysis)
Exclusion criteria: to have received antimycotic therapy during the month before consultation; to have
bacterial superinfection, systemic illness or unknown intolerance or allergy to terbinafine or griseofulvin
Fungi isolated:
T. tonsurans: 74%.
M. canis: 26%.
No mention of compliance assessment.
Interventions
Griseofulvin (microsized) tablet, 10 to 20 kg: 125 mg/day; 20 to 40 kg: 250 mg/day; > 40 kg: 500 mg/
day, for 8 weeks.
n = 25
Terbinafine tablet, 10 to 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day; > 40 kg: 250 mg/day, once a day
for 4 weeks plus 4 weeks of placebo.
n = 25
No co-treatment.
Outcomes
The proportion of participants with complete cure at 12 weeks.

The frequency and type of adverse effects.
The proportion of participants with clinical cure only at 12 weeks
Notes

22
Cceres-Ros 2000
(Continued)
Risk of bias
Bias
Authors judgement
Support for judgement
Allocation concealment?
Unclear risk
B - Unclear
Dastghaib 2005
Methods
Follow up: eight weeks

Blinded assessment: single-blind, investigators blinded, participants not blinded
Loss to follow up: five participants discontinued therapy or were lost to follow up
Sample size calculation declared: not mentioned.
Baseline comparability: mean age: griseofulvin (8.66); fluconazole (7.71).
Sex: ; griseofulvin ( males: 17; females: 4), fluconazole(males: 15; females: 4)
Mean weigh (Kg): griseofulvin (23.61); fluconazole(21.60)
Severity of disease: Similar in both groups at first examination
Participants
Iran
n = 40
Aged between from 1 to 16; 80% were boys and 20% girls.
Inclusion criteria: Clinical and mycologic diagnosis of non-inflammatory tinea capitis
Exclusion criteria: a history of allergy to imidazoles; use of oral antifungals within eight weeks or use of
topical antifungals within four weeks before screening; a history of congenital or acquired immunodeficiency or disorders affecting kidney or liver function; concurrent therapy with other drugs; and systemic
illness
Fungi isolated:
T. verrucosum: fluconazole: 26.3%; griseofulvin: 52.4%; Total: 40%
T. violaceum: fluconazole: 52.6%; griseofulvin: 28.6%; Total: 40%
M. canis: fluconazole: 21.1%; griseofulvin: 19%; Total: 20%
Interventions
Griseofulvin 15 mg/kg/day for 6 weeks

n = 21
Fluconazole 5 mg/kg/day for 4 weeks
n = 19
Outcomes
The proportion of participants with complete cure after eight weeks.

Mycologic cure at the end of treatment.
Notes
Risk of bias

23
Dastghaib 2005
(Continued)
Bias
Authors judgement
Unclear risk
B - Unclear
Friedlander 2002
Methods

Loss to follow up:
terbinafine for 1 week, post-randomisation exclusions 14.
terbinafine for 2 weeks, post-randomisation exclusions 15.
Reporting of type fungi involved: yes.
severity of infection: not stated.
age: terbinafine for 1 week: 7.1 y; terbinafine for 2 weeks: 8.5 y; terbinafine for 4 weeks: 6.6 y.
sex: terbinafine for 1 week (males 28, females 28); terbinafine for 2 weeks: (males 32, females 27);
terbinafine for 4 weeks: (males 31, females 31)
Participants
North America
n = 177
Age was 4 years or older (98% participants < 18 years old; mean age, 7.4 years old), only 3 adults.
78% were black.
57.2% males.
Inclusion criteria: male and female participants aged four years or older, with clinically diagnosed tinea
capitis caused by Trichophyton species
Exclusion criteria: Any systemic treatment for tinea capitis in the month before enrolment. Kerions that
required immediate treatment, concurrent seborrhoeic dermatitis, or other scalp conditions such as scabies,
head lice, psoriasis, or atopic dermatitis. Immunocompromised participants or a history of malignancy
within five years. Chronic or active liver disease. Serious gastrointestinal disease. Hypersensibility to
terbinafine or placebo. Treatment with any other investigative agent within the previous eight weeks.
Pregnancy or lactation
Fungi isolated:
T. tonsurans: 98.74%.
T. soudanense: 0.63%.
T. verrucosum: 0.63%.
Compliance assessed by asking participants to return unused medication at each visit
Interventions
Oral terbinafine 3 to 6 mg/kg/day for 1 week.

n = 56
Oral terbinafine 3 to 6 mg/kg/day for 2 weeks.
n = 59
Oral terbinafine 3 to 6 mg/kg/day for 4 weeks.

24
Friedlander 2002
(Continued)
n = 62
Followed by placebo to complete four weeks when needed.
Co-treatment: non medicated shampoo twice weekly.
Outcomes

The proportion of participants with clinical cure only at 12 weeks.
Percentage of drop-outs as a surrogate for participant compliance.
The time taken to cure.
Mycological cure at 12 weeks.
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Fuller 2001
Methods

Randomisation: adequate (computer generated, participants randomised in blocks of four)
Blinded assessment: open.
Loss to follow up:
group terbinafine:
post-randomisation exclusions 37, later losses 25.
45 completed the study.
group griseofulvin:
post-randomisation exclusions 26, later losses 27.
50 completed the study.
We are unaware of all the reasons for the drop-outs in any of the groups, 68% discontinued because they
were unable to attend clinic visits
Sample size calculation declared: yes.
severity of infection: not reported
age: group terbinafine: 5.6; group griseofulvin: 6.
sex: group terbinafine: males:69%, females: 31%; group griseofulvin: males:64%, females: 36%.
duration of complaint: unknown.
Conflict of interest: funded by Novartis Pharmaceuticals UK Ltd (Terbinafine)
Participants
UK
n = 210
Aged between 2 and 16 years old.
Inclusion criteria: Children aged 2 to 16 years old with clinical diagnosis of tinea capitis
Exclusion criteria: immunocompromised children and those receiving any topical antifungal agents within

25
Fuller 2001
(Continued)
seven days or systematic antifungal agents within 6 weeks prior to the start of the treatment
Fungi isolated:
Microsporum audouini: 13% (13/103) in the terbinafine and 11.4% (12/107) in the griseofulvin; M.
canis: 1.3% (1/103) in the terbinafine and 1.4% (2/107) in the griseofulvin; M.rivalieri: 0% in the
terbinafine and 1.4% (2/107) in the griseofulvin.
Trichophyton tonsurans: 64.9% (67/103) in the terbinafine and 72.9% (78/107) in the griseofulvin; T.
soudanense: 10.4% (11/103) in the terbinafine and 4.3% (5/107) in the griseofulvin; T. violaceum: 2.
6% (3/103) in the terbinafine and 0% in the griseofulvin; Trichophyton species unknown: 2.6% (3/103)
in the terbinafine and 0% in the griseofulvin.
Compliance assessed by direct questioning.
Interventions
Griseofulvin suspension, 10 mg/kg/day, for 8 weeks.

n = 107
Terbinafine tablet, <20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day ; > 40 kg: 250 mg/day, for 4 weeks.
n = 103
Co-treatment: selenium sulphide shampoo, twice weekly for the first two weeks of treatment
Outcomes

Percentage of drop-outs as a surrogate for participant compliance: terbinafine group.
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

26
Gan 1987
Methods

Randomisation: adequate (table of random numbers).
Loss to follow up:
griseofulvin group, post-randomisation exclusions: 11.
ketoconazole group, post-randomisation exclusions: six.
Exclusion criteria : yes.
severity of infection: not reported.
age (in months): griseofulvin group (63); ketoconazole group (62).
sex: griseofulvin group (males: 13, females: 15); ketoconazole group (males: 16, females: 20).
duration of complaint (in weeks): griseofulvin group (5.6); ketoconazole group (5.8)
Participants
USA (Dallas)
n = 80
Age between 2.1 and 11 years (mean age 5.2 years).
The remaining children after the dropouts were 63; 55% of those were female
Inclusion criteria: children with tinea capitis were eligible for the study
Exclusion criteria: presence of kerion; if their parents were unable to make a commitment for followup visits, or if there was a history of hepatocellular dysfunction or finally if they had received a systemic
antifungal agent in the preceding six weeks
Fungi isolated:
94% of the participants had positive fungal cultures:
T. tonsurans: 70%.
M. canis: 11.6%.
T. mentagrophytes: 1.6%.
T. violaceum: 1.6%.
Uncertain classification: 15%.
Compliance assessed by history and by quantifying the amount of residual medication brought in by the
parents
Interventions
Griseofulvin tablet or suspension, 15 mg/kg/day, single daily dose; 2 to 6 weeks depending on the patients
clinical response to therapy.
n = 40
Ketoconazole tablet or crushed tablets suspended in sucrose syrup, 5 mg/kg/day, single daily dose 2 to 6
weeks depending on the patients clinical response to the therapy.
n = 40
No co-treatment.
Outcomes

The time taken to cure (scalp clearing).
Notes
Risk of bias
27
Gan 1987
(Continued)
Bias
Authors judgement
Unclear risk
B - Unclear
Gupta 2001
Methods

Blinded assessment: participants not blinded, clinicians and outcome assessors blinded
Loss to follow up:
griseofulvin group, post-randomisation exclusions four.
terbinafine group, post-randomisation exclusions two.
itraconazole group, post-randomisation exclusions four.
fluconazole group, post-randomisation exclusions four.
Inclusion criteria: yes (only culture positive).
severity of infection: mild: griseofulvin group: 18; terbinafine group: 20; itraconazole group: 9; fluconazole
group: 9; moderate: griseofulvin group: 28; terbinafine group: 27; itraconazole group: 36; fluconazole
group: 28; severe: griseofulvin group: 4; terbinafine group: 2; itraconazole group: 4; fluconazole group:
11; kerion: griseofulvin group: 0; terbinafine group: 1: itraconazole group: 1; fluconazole group: 2.
age: griseofulvin group: 5.9; terbinafine group: 5.6; group C: 5.2; fluconazole group: 5.9.
sex: griseofulvin group: males: 38, females: 12; terbinafine group: males: 37, females: 13; itraconazole
group: males: 27, females: 23; fluconazole group: males: 32, females: 18.
duration of complaint: not mentioned.
Participants
Canada & South Africa

n = 200
Inclusion criteria: children aged 6 months or older, with clinical signs and symptoms of tinea capitis with
mycology that was positive for Trichophyton species
Exclusion criteria: those who had been or were on topical or oral antifungal agents for two or four weeks,
respectively, prior to the starting therapy
Fungi isolated:
griseofulvin group
T. tonsurans: 39/50 and T. violaceum: 11/50
terbinafine group
itraconazole group
fluconazole group

28
Gupta 2001
(Continued)
Interventions
Griseofulvin microsized 20 mg/kg/day for 6 weeks.

n = 50
Terbinafine < 20 kg: 62.5 mg; 20 to 40 kg: 125 mg; > 40 kg: 250 mg for 2 to 3 weeks.
n = 50
Itraconazole 5 mg/kg/day for 2 to 3 weeks.
n = 50
Fluconazole 6 mg/kg/day for 2 to 3 weeks.
n = 50
Outcomes

The proportion of participants with clinical cure only at the end of treatment.
Mycologic cure at 12 weeks.
Effective therapy (mycologic cure with clinical cure or few residual symptoms) at 12 weeks
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Hamm 1999
Methods

Loss to follow up: any drop-out
mentioned.
Exclusion criteria: no.
severity of infection: studied but not shown.
age: we are unaware of the mean age for each group.
sex: we are unaware of the number of females and males in each group.
duration of complaint: not stated.
Funding: Novartis (terbinafine).
Participants
Germany
n=35
16 males and 19 females.
The mean age was 9.3 years for males and 7.8 for females.
Inclusion criteria: mycologically proven scalp infection.
Fungi isolated:

29
Hamm 1999
(Continued)
M. canis: terbinafine for 1 week: 43.7%; terbinafine for 2 weeks: 26.3%.

T. tonsurans: terbinafine for 1 week: 37.5%; terbinafine for 2 weeks: 31.5%.
T. violaceum: terbinafine for 1 week: 6.25%; terbinafine for 2 weeks: 26.3%.
T. mentagrophytes: terbinafine for 1 week: 12.5%; terbinafine for 2 weeks: 5.3%.
T. verrucosum: terbinafine for 2 weeks: 5.3%.
Interventions
Terbinafine 10 to 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day; > 40 kg: 250 mg/day once daily for 1
week.
n = 16
Terbinafine same dose for two weeks.
n = 19
No co-treatment.
Outcomes

Notes
Participants were observed for 12 weeks. After four weeks, non-responders were offered an additional four
weeks of treatment followed by a second observation period
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Haroon 1995
Methods

Blinded assessment: no mention of blinding.
Loss to follow up: any drop-out mentioned.
severity of infection: not known.
age: terbinafine: 8.6; griseofulvin: 9.1.
sex: terbinafine: Male: 24, Female: 32; griseofulvin: Male: 25, Female: 24.
duration of complaint: not known.
Funding: Sandoz.
Participants
Pakistan
n = 105
49 males.
56 females.
Aged between 2 and 65, and 94 were younger than 12 years.

30
Haroon 1995
(Continued)
Inclusion criteria: clinical evidence of dermatophytosis of the scalp; participant of any age that weighed
more than 10 kg
Exclusion criteria: concomitant treatment with systemic or X-ray therapy; topical antifungal therapy
within two weeks or oral antifungal within four weeks of entering the study
Fungi isolated included:
T. violaceum: 87.6% (92/105).
T. tonsurans: 38% (4/105).
T. rubrum: 0.95% (1/105).
T. verrucosum: 6.6% (7/105).
M. audouinii: 0.95% (1/105).
Interventions
Terbinafine 62.5 to 250 mg for 4 weeks, plus 4 weeks of placebo.

n = 56
Griseofulvin 125 to 500 mg for 8 weeks.
n = 49
Outcomes

Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Haroon 1996
Methods

baseline comparability:
severity of infection: not mentioned.
age: we are unaware of the mean age in each group.
sex: we are unaware of the number of females and males in each group, only the total stated.
Funding: Sandoz (terbinafine).
Participants
Pakistan
n = 161
90 males.

31
Haroon 1996
(Continued)
71 females.
Aged between 3 and 13 years old.
156 were children below 12.
Inclusion criteria: clinical and mycological evidence of dermatophytosis of the scalp; participants of any
age that weighed more than 10 kg
Exclusion criteria: concomitant treatment with systemic or X-ray therapy; topical antifungal therapy
within two weeks or oral antifungal within four weeks of entering the study
Fungi isolated:
T. violaceum: 71.5%.
T. tonsurans: 14.9%.
T. verrucosum: 4.3%.
M. audouinii: 4.3%.
M. canis: 2.5%.
T. schoenleinii: 1.9%.
T. mentagrophytes: 0.6%.
Interventions
Terbinafine, 10 to 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day ; > 40 kg: 250 mg/day, once daily for 1
week plus 3 weeks of placebo.
n = 53
Terbinafine same dose for two weeks plus two weeks of placebo.
n = 51
Terbinafine same dose for four weeks.
n = 57
No co-treatment.
Outcomes

The proportion of participants with clinical cure only at 12 weeks
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

32
Jahangir 1998
Methods

severity of infection: not declared.
age: itraconazole group: 7.9 +- 4.58; terbinafine group: 7.8 +- 4.58.
sex: male to female ratio itraconazole group: 1:1; terbinafine group: 1.1.3
Participants
Pakistan
n = 55
Inclusion criteria: subjects of either sex or any age, weighing 10 kg or more and suffering from mycologically
confirmed tinea capitis
Exclusion criteria: history of allergy to imidazoles or allylamines, use of oral antifungals within eight weeks
or topical antifungals within four weeks before screening, concurrent therapy with rifampicin, phenytoin,
digoxin, oral anticoagulants, cyclosporin, astemizole and terfenadine, psoriasis of the scalp, history of any
systemic illness or abnormal liver and renal function tests
Fungi isolated:
T. violaceum: itraconazole group: 82.1%; terbinafine group: 88.9%.
T. tonsurans: itraconazole group: 7.1%; terbinafine group: 3.7%.
T. mentagrophytes: itraconazole group: 7.1%; terbinafine group:3.7%.
T. verrucosum: itraconazole group: 3.7%; terbinafine group: 3.7%
Interventions
Itraconazole, < 20 kg: 50 mg; 20 to 40 kg: 100 mg; > 40 kg: 200 mg - supposed daily - for 2 weeks .
n = 28
Terbinafine, < 20 kg: 62.5 mg; 20 to 40 kg: 125 mg; > 40 kg: 200 to 250 mg - supposed daily - for 2
weeks.
n = 27
No co-treatment.
Outcomes

Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

33
Kullavanijaya 1997
Methods

Blinded assessment: described as single blind and open trial study but no mention of which one (patient
or observers)
Loss to follow up: seven were lost to follow up and were excluded. No further information
Inclusion criteria: very poor.
Exclusion criteria: not mentioned.
Baseline comparability: yes, though no statistical differences were noted either reported, among the three
groups with regard to age, weigh and sex ratio
Participants
Bangkok (Thailand)
n = 82
All participants were children seven years or older, except for three adults, all living in an orphanage
Fungi isolated:
T. tonsurans and M. ferrugineum: we are unaware of the percentages of each fungus
Interventions
Terbinafine 62.5 to 250 mg according to body weigh - supposed once daily - for 1 week.
n = 27 (completed the study).
Terbinafine same dose for two weeks.
n = 28 (completed study).
Terbinafine same dose for four weeks.
n = 27 (completed study).
Outcomes
The proportion of participants with complete cure at 12 weeks
Notes
The proportions and percentages were done including the adults, because we are unaware of to which
group they belonged to
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

34
Lipozencic 2002
Methods

Blinded assessment: participants, clinicians and outcome assessors blinded, except for the arm taking
griseofulvin, where both participants and investigators were informed from day 1
Loss to follow up:
terbinafine for six weeks, post-randomisation exclusions: seven.
terbinafine for eight weeks, post-randomisation exclusions: four.
terbinafine for ten weeks, post-randomisation exclusion six.
terbinafine for 12 weeks, post-randomisation exclusion 12.
griseofulvin group, post-randomisation exclusions: seven.
age: terbinafine for 6 weeks: 9.5; terbinafine for 8 weeks: 7; terbinafine for 10 weeks: 6.8; terbinafine for
12 weeks: 8.8; griseofulvin group: 6.3.
sex: % of males: terbinafine for 6 weeks: 66%; terbinafine for 8 weeks: 73%; terbinafine for 10 weeks:
70%; terbinafine for 12 weeks: 53%; griseofulvin group: 50%
Funding: Novartis Pharma AG.
Participants
Europe and South America (22 centres)

n = 165
The majority of participants were Caucasian (77%); 63% were males and the mean age was 7.7, only 3
adults were enrolled in the study; 67% weighed between 20 and 40 kg
Inclusion criteria: Male or female aged four or older, with tinea capitis confirmed by positive culture of
Microsporum species, who were otherwise healthy out-patients and able to swallow the study drug tablets
Exclusion criteria: participants with conditions that could interfere with gastrointestinal absorption of
terbinafine, with confirmed liver or renal impairment, with kerion or any severe concurrent disease of
the scalp. As well as those using any antifungal therapy, radiotherapy, systemic therapy with cytostatic or
immunosuppressive drugs within one month prior to the start of the study, and known intolerance or
allergy to drugs used in the study
In addition, participants receiving griseofulvin treatment in this study were subject to exclusion according
to the label instruction of that drug
Fungi isolated:
M. canis: 98.5%.
Only two participants were infected with M. audouinii.
Interventions
Terbinafine tablets < 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day; > 40 kg: 250 mg/day for 6 weeks,
followed by placebo to complete the 12 week double-blind treatment phase.
n = 36
Terbinafine same dose for 8 weeks, followed by placebo to complete the 12 week double-blind treatment
phase.
n = 34
phase.
n = 33

35
Lipozencic 2002
(Continued)
phase.
n = 32
Griseofulvin oral suspension 20 mg/kg/day for 12 weeks (open label).
n = 30
Participants were provided with baby-shampoo to clean the scalp
Outcomes

Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Lpez-Gmez 1994
Methods

Loss to follow up:
itraconazole group, post-randomised exclusions: one.
griseofulvin group, post-randomisation: two.
Exclusion criteria: not mentioned.
age: itraconazole group: 2 to 11; griseofulvin group: 2 to 10.
sex: itraconazole group: males: 12, females: 6; griseofulvin group: males: 11, females: 6.
duration of complaint: not reported.
Funding: Janssen (Itraconazole).
Participants
Madrid (Spain)
n=35
All participants were children younger than 12 years old, except for one adult who was 60 years old.
23 males and 12 females.
Inclusion criteria: the presence of dermatophytes.
Fungi isolated:
T. tonsurans: itraconazole group: 5.5%.

36
Lpez-Gmez 1994
(Continued)
M. canis: itraconazole group: 88.8%; griseofulvin group: 94.1%.

T. mentagrophytes: itraconazole group: 5.5%.
T .violaceum: griseofulvin group: 5.9%.
Interventions
Itraconazole 100 mg/day for 6 weeks.

n = 17 + 1 adult = 18
Griseofulvin (ultra microsized) 500 mg/day for 6 weeks.
n = 17
No co-treatment.
Outcomes

Percentage of drop-outs as a surrogate for participant compliance
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Martnez-Roig 1988
Methods
Follow up: sixweeks.

Randomisation: adequate (computer generated random number table)
Loss to follow up: see notes.
Baseline comparability: not reported.
Funding: Laboratories Dr. Esteve (ketoconazole).
Participants
Barcelona (Spain)
n = 13
Children between 2 and 16 years old.
Sex distribution not reported.
Inclusion criteria: children suffering from dermatophytic lesions
Exclusion criteria: not to have received previous antifungal therapy
Fungi isolated:
T. mentagrophytes, M. canis and Epidermophyton floccosum.
Compliance assessed.

37
Martnez-Roig 1988
(Continued)
Interventions
Ketoconazole tablet, 100 mg/day at 12-hourly intervals for 6 weeks.

n=8
Griseofulvin tablet, 350 mg/day, at 12-hourly intervals for 6 weeks.
n=5
Co-treatment: manual depilation in cases of inflammatory tinea capitis
Outcomes

The proportion of participants with clinical cure only at the end of treatment.
Measurement of recurrence of the condition after the end of the intervention period.
Notes
Tinea corporis and tinea capitis study, information poorly stated

It needs to be taken into account that the study talks about 47 participants, which is the total, tinea capitis
and tinea corporis participants, but for the purpose of our review we have only used the results of the 13
tinea capitis participants
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Memisoglu 1999
Methods

Loss to follow up:
griseofulvin group, post-randomisation exclusions seven.
terbinafine group, post-randomisation exclusions four.
severity of infection: not stated.
age: griseofulvin group: 6.6; terbinafine group: 7.
sex: griseofulvin group: males 26, females 9 ; terbinafine group: males 21, females 11.
Participants
Turkey
n = 78
Children aged 2 to 13 years old.
Inclusion criteria: participants with clinically suspected tinea capitis, provisionally confirmed by detection
of fungal hyphae in KOH
Exclusion criteria: the evidence of concomitant candida or bacterial infection
Fungi isolated:

38
Memisoglu 1999
(Continued)
T. violaceum: griseofulvin group: 11.4% (4/35); terbinafine group: 15.6% (5/32).

T. rubrum: griseofulvin group: 22.8% (8/35); terbinafine group: 15.6%(5/32).
M. canis: griseofulvin group: 48.5% (17/35); terbinafine group: 46.8%(15/32).
T. tonsurans: griseofulvin group: 5.7% (2/35); terbinafine group: 6.25% (2/32).
T. mentagrophytes: griseofulvin group: 5.7% (2/35); terbinafine group: 3.1% (1/32).
T. verrucosum: griseofulvin group: 5.7% (2/35); terbinafine group: 3.1% (1/32).
M. audouinii: terbinafine group: 3.1% (1/32).
Unidentified: terbinafine group: 6.25% (2/32).
Interventions
Griseofulvin microsized 20 mg/kg/day for 6 weeks.

n = 50
Terbinafine < 20 kg: 62.5 mg; 20 to 40 kg: 125 mg; > 40 kg: 250 mg for 2 to 3 weeks.
n = 50
Itraconazole 5 mg/kg/day for 2 to3 weeks.
n = 50
Fluconazole 6 mg/kg/day for 2 to 3 weeks.
n = 50
Outcomes

The proportion of participants with clinical cure only was scored at 12 weeks.
Notes
At the beginning there were 39 participants in each group, after the drop-outs there were 32 and 35 left,
and so the percentages do not match:
T. violaceum: 13.4%
T. rubrum: 19.4%
M. canis: 47.7%
T. tonsurans: 5.9%
T. mentagrophytes:4.5%
T. verrucosum: 4.5%
M. audouinii : 1.5%
Unidentified: 3%
These fungi percentages are the total over 67 ,not over 78 participants
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

39
Rademaker 1998
Methods

Loss to follow up: not mentioned.
Exclusion criteria: no.
severity of infection: only total stated.
age: only total stated.
sex: only total stated.
Participants
New Zealand
n = 24
16 male and 8 female.
Age ranged between 2 and 15 years old.
Inclusion criteria: paediatric participants, under 16 years old with culture positive tinea capitis
Fungi isolated:
M. canis 71%; T. verrucosum 29%.
Interventions
Griseofulvin 10 mg/kg/day for 8 weeks.

n = 14
Terbinafine < 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day; > 40 kg: 250 mg/day for 4 weeks.
n = 10
Co-treatment: ketoconazole shampoo twice a week and econazole cream nightly was recommended as
well
Outcomes

The proportion of participants with clinical cure only.
Measurement of recurrence of the condition after the end of the intervention period
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

40
Solomon 1997
Methods

Blinded assessment: participants not blinded; clinicians and outcome assessors blinded
Loss to follow up: 14 were lost to follow up, but no further information is given
age: not reported.
sex: not reported.
duration of complaint: not reported.
Participants
New York (USA)

n = 27
15 females and 13 males between ages of 2 and 15 years old.
Inclusion criteria: mycologic confirmation of infection before initiation of therapy; children from 2 to
15 years of age; normal complete blood cell count with differential, liver function test, and SMA-7; and
parental consent
Exclusion criteria: participants who had received antimycotic therapy within 2 weeks of initial visit; a
history of kidney or liver disease; participants with history of hypersensitivity reaction to any of the ingredients of fluconazole; participants receiving interactive medications within preceding 30 days; participants
with coexisting immunosuppressive disease; and participants with inflammatory tinea capitis
Fungi isolated:
T. tonsurans 100%.
Interventions
Fluconazole tablets or suspension 1.5 mg/kg/day for 20 days.

Fluconazole tablets or suspension 3 mg/kg/day for 20 days.
Fluconazole tablets or suspension 6 mg/kg/day for 20 days.
No co-treatment.
Outcomes
The proportion of participants with complete cure at 6 to 16 weeks.

The proportion of participants with clinical cure only.
Measurement of recurrence of the condition after the end of the intervention period
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear

41
Talarico Filho 1998

Methods

Blinded assessment: only participants blinded.
Loss to follow up:
terbinafine for one week, post-randomisation exclusions six.
terbinafine for two weeks, post-randomisation exclusion six.
severity of infection: studied but not shown.
age: terbinafine for 1 week: 6.5; terbinafine for 2 weeks: 6.5; terbinafine for 4 weeks: 6.1.
sex: terbinafine for 1 week: Males 26, females 16; terbinafine for 2 weeks: Males 17, females 27; terbinafine
for 4 weeks: males 26, females 20.
duration of complaint: studied but not shown.
Participants
Brazil
n = 132
Aged 1 to 14 years old.
63 females and 69 males
Inclusion criteria: children of both sexes with tinea capitis, aged 1 to 12, weighing 20 kg or more
Exclusion criteria: use of any systemic antifungal therapy within 1 month or topical antifungal therapy
within two weeks prior to the start of the study or both; conditions that could interfere with gastrointestinal absorption of terbinafine; confirmed liver/renal impairment, hematological disorders; radiotherapy,
systemic therapy with cytostatic or immunosuppressive drugs, or therapy with antibacterial, antiviral or
antihelmintic drugs, either currently or during the two weeks preceding the beginning of the study
Fungi isolated:
T. tonsurans: terbinafine for 1 week: 88.6% (3/35); terbinafine for 2 weeks: 18.5% (7/38); terbinafine for
4 weeks: 26.5% (9/34).
T. mentagrophytes: terbinafine for 1 week: 2.8% (1/35); terbinafine for 4 weeks: 5.9% (2/34).
M. canis: terbinafine for 1 week: 77.1% (27/35); terbinafine for 2 weeks: 73.3% (28/38); terbinafine for
4 weeks: 55.9% (19/34).
T. rubrum: terbinafine for 1 week: 8.6% (3/35); terbinafine for 2 weeks: 7.9% (3/38); terbinafine for 4
weeks:5.9% (2/34).
T. schoenleini: terbinafine for 1 week: 2.8% (1/35); terbinafine for 4 weeks: 2.9% (1/34).
M. gypseum: terbinafine for 4 weeks: 2.9% (1/34).
Interventions
Terbinafine 10 to 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day; > 40 kg: 250 mg/day once daily for 1
week plus 3 weeks of placebo.
n = 42
Terbinafine same dose for two weeks plus two weeks of placebo .
n = 44
Terbinafine same dose for four weeks same dose.
n = 46
No co-treatment.

42
Talarico Filho 1998
(Continued)
Outcomes

Percentage of drop-outs as a surrogate for participant compliance
Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Tanz 1985
Methods
Follow up: six weeks.

Loss to follow up:
griseofulvin group, post-randomisation exclusions three.
ketoconazole group, post-randomisation five.
severity of infection: (minimum score = 0, maximum score = 21): griseofulvin group: 9.3; ketoconazole
group: 8.3.
age: griseofulvin group: 6.4; ketoconazole group: 5.7.
sex: (Male : Female): griseofulvin group: 0 : 7; ketoconazole group: 2 : 5.
duration of complaint: (weeks): griseofulvin group: 16.5; ketoconazole group: 24
Funding: Janssen (ketoconazole).
Participants
Chicago (USA)
n = 22
Inclusion criteria: children 2 to 16 years old were eligible if they had clinically diagnosed or mycologically
proven tinea capitis
Exclusion criteria: those that had received systemic antimycotic therapy within one month of enrolment, if
griseofulvin therapy was contraindicated; if they had a serious concurrent disease or a history of hepatitis;
if they were taking warfarin-like anticoagulants or barbiturates, or if they were pregnant
Fungi isolated:
T. tonsurans: 50% (11/22).
Scopulariopsis spp. : 4.5% (1/22).
Penicillium spp. :4.5% (1/22).
Unidentified fungus: 4.5% (1/22).
Compliance assessed.

43
Tanz 1985
(Continued)
Interventions
Griseofulvin tablet, 500 mg/day, plus ketoconazole placebo tablet (participants < 40 kg: half tablet) for
6 weeks.
n = 12
Ketoconazole tablet, 200 mg/day, plusgriseofulvin placebo tablet (participants weighing < 40 kg: half
tablet) for 6 weeks.
n = 10
Co-treatment: antiseborrhoeic shampoo.
Outcomes

Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Tanz 1988
Methods

Loss to follow up:
griseofulvin group, post-randomisation exclusions 3, later losses 17.
ketoconazole group, post-randomisation exclusions two, later losses nine
Baseline comparability: taken into account but not reported.
(There were no statistically significant differences between the groups in terms of age, sex, weigh or
duration of infection)
Funding: Janssen (ketoconazole).
Participants
Chicago (USA)
n = 79
65% female
92% black
Inclusion criteria: children aged 2 to 16 years old, with tinea capitis or mycologic evidence of dermatophyte
infection of the scalp.
Exclusion criteria: participants receiving systemic antimycotic therapy within 30 days of the initial visit; if
they had a history of porphyria, liver disease, or immunodeficiency; if they were pregnant or if they were
receiving warfarin-like anticoagulants or barbiturates
Fungi isolated:
T. tonsurans: 64% of the enrolled participants and 74% of the evaluable participants.

44
Tanz 1988
(Continued)
M. canis: 12% of the enrolled participants and 13% of evaluable participants

Compliance not assessed.
Interventions
Griseofulvin (microsized) 250 mg tablet ( 10 to 20 mg/kg/day) plus ketoconazole placebo tablet, single
daily dose, for 12 weeks.
n = 46
Ketoconazole 200 mg tablet (3.3 to 6.6 mg/kg/day) plus griseofulvin placebo tablet in a single daily
dose for 12 weeks.
n = 33
Co-treatment: antiseborrhoeic shampoos.
Outcomes

The proportion of participants with clinical cure at 12 weeks.
Notes
Not much information given apart from the total cured results.
The enrolled : 79 were randomised, 46 were evaluable
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Ungpakorn 2004
Methods

Baseline comparability: sex: 35 male, 7 female; age range: 2 to 12 years; mean age: 8 years
Funding: Institute of Dermatology Research Funds and Novartis (Thailand)
Participants
Thailand
n = 42
Inclusion criteria: not to have received any topical or systemic antifungal therapy in the preceding two or
four weeks, respectively
Fungi isolated: Microsporum spp.:
M. ferrugineum 50% (21/42).
M. canis 47.6% (20/42).
M. gypseum 2.3% (81/42).

45
Ungpakorn 2004
(Continued)
Interventions
Oral Terbinafine 10 to 20 kg: 62.5 mg/day; 20 to 40 kg: 125 mg/day;

over 40 kg: 250 mg/day, in a pulsed regimen
n = 23
Oral Terbinafine at double dose, in a similar pulsed regimen
n = 19
Outcomes

Notes
Risk of bias
Bias
Authors judgement
Unclear risk
B - Unclear
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Ginsburg 1987
Excluded because this study evaluates the therapy for inflammatory lesions caused by tinea capitis.The main aim of
this study is to analyse the treatment of kerions in tinea capitis, combining the tinea capitis treatment of griseofulvin
plus intralesional corticoteroid to try to reduce the inflammation
Honig 1994
Excluded because this study evaluates the therapy for inflammatory lesions caused by tinea capitis. It combines
griseofulvin for the tinea capitis with steroids to modulate the immune-mediated inflammation, hasten resolution
of kerions and minimize scar formation
Hussain 1999
Excluded because this study evaluates the therapy for inflammatory lesions caused by tinea capitis. It combines
griseofulvin treatment and griseofulvin treatment plus prednisolone, a glucocorticoid

46
DATA AND ANALYSES
Comparison 1.
follow-up
Terbinafine (4 weeks) versus griseofulvin (8 weeks); short treatment duration; 12 to 24 weeks
Outcome or subgroup title

1 complete cure
1.1 Trichophyton infections
1.2 Microsporum infections
1.3 Mixed
Trichophyton/Microsporum
infections
No. of
studies
No. of
participants
5
3
1
2
539
382
29
128
Statistical method
Risk Ratio (M-H, Random, 95% CI)
Effect size
1.11 [0.96, 1.29]
1.09 [0.95, 1.26]
0.64 [0.19, 2.20]
1.24 [0.64, 2.42]
Comparison 2. Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum infections; 16 weeks
follow-up

1 complete cure
1.1 medium terbinafine
treatment duration (6 to 8
weeks)
1.2 long terbinafine treatment
duration (10 to 12 weeks)
2 clinical cure
2.1 medium terbinafine
treatment duration (6 to 8
weeks)
2.2 long terbinafine treatment
duration (10 to 12 weeks)
No. of
studies
No. of
participants
Statistical method
Effect size
1
1

Totals not selected

0.0 [0.0, 0.0]
0.0 [0.0, 0.0]
1
1

Totals not selected

0.0 [0.0, 0.0]
0.0 [0.0, 0.0]

47
Comparison 3. Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections; 12 to 20 weeks
follow-up

1 complete cure
1.1 1 week versus 2 weeks
1.3 2 weeks versus 4 weeks
2 clinical cure
No. of
studies
5
4
4
4
1
1
1
1
1
1
4
3
3
3
1
1
1
1
1
1
No. of
participants
360
370
374
70
69
68
67
66
65
305
316
319
70
69
68
67
66
65
Statistical method
Effect size
Subtotals only
0.82 [0.66, 1.01]
0.67 [0.55, 0.81]
0.81 [0.68, 0.96]
0.94 [0.60, 1.49]
1.27 [0.74, 2.17]
1.6 [0.87, 2.94]
1.34 [0.79, 2.28]
1.69 [0.93, 3.10]
1.26 [0.65, 2.45]
Subtotals only
0.96 [0.83, 1.11]
0.82 [0.63, 1.07]
0.88 [0.72, 1.07]
0.87 [0.62, 1.22]
1.01 [0.69, 1.47]
1.22 [0.79, 1.89]
1.16 [0.82, 1.65]
1.41 [0.94, 2.12]
1.21 [0.78, 1.89]
Comparison 4. Terbinafine (standard dose compared to double dose) in Microsporum infections; 20 weeks followup

1 complete cure
No. of
studies
No. of
participants
Statistical method
Effect size
Totals not selected
Comparison 5. Itraconazole (6 and 2 weeks, respectively) versus griseofulvin (6 weeks) in Trichophyton and
Microsporum infections

1 complete cure
No. of
studies
No. of
participants
135
Statistical method

Effect size
0.94 [0.80, 1.09]
48
Comparison 6. Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections

1 complete cure
2 clinical cure
No. of
studies
No. of
participants
2
1
160
Statistical method
Risk Ratio (M-H, Fixed, 95% CI)
Effect size
0.93 [0.72, 1.19]
Totals not selected
Comparison 7. Ketoconazole (6 weeks) versus griseofulvin (8 to 12 weeks) in Trichophyton infections; 12 weeks

follow-up

1 complete cure
No. of
studies
No. of
participants
159
Statistical method
Effect size
0.72 [0.50, 1.02]
Comparison 8. Fluconazole (2 and 4 weeks respectively) versus griseofulvin (6 weeks) in Trichophyton infections;
8 -12 weeks

1 complete cure
No. of
studies
No. of
participants
140
Statistical method
Effect size
0.92 [0.80, 1.05]
Comparison 9. Fluconazole (2 to 3 weeks) versus terbinafine (2 to3 weeks) in Trichophyton infections; 12 weeks
follow-up

1 complete cure
No. of
studies
1
No. of
participants
Statistical method

Effect size
Subtotals only
49
Comparison 10. Fluconazole (2 to 3 weeks) versus itraconazole (2 to 3 weeks) in Trichophyton infections; 12

weeks follow-up

1 complete cure
No. of
studies
No. of
participants
Statistical method
Effect size
Totals not selected
Comparison 11. Fluconazole (different doses compared: 1.5, 3 and 6 mg/kg/day) in Trichophyton infections; 4
months follow-up
No. of
studies
1 complete cure
1.1 1.5 mg versus 3 mg
1.2 1.5 mg versus 6 mg
1.3 3 mg versus 6 mg
1
1
1
1
No. of
participants
Statistical method

Effect size
Totals not selected
0.0 [0.0, 0.0]
0.0 [0.0, 0.0]
0.0 [0.0, 0.0]
50
Analysis 1.1. Comparison 1 Terbinafine (4 weeks) versus griseofulvin (8 weeks); short treatment duration;
12 to 24 weeks follow-up, Outcome 1 complete cure.
Review:
Comparison: 1 Terbinafine (4 weeks) versus griseofulvin (8 weeks); short treatment duration; 12 to 24 weeks follow-up
Outcome: 1 complete cure
Study or subgroup
terbinafine
griseofulvin
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Haroon 1995
52/56
39/49
32.9 %
1.17 [ 0.99, 1.37 ]
Fuller 2001
32/88
26/89
9.8 %
1.24 [ 0.81, 1.90 ]
Gupta 2001
47/50
46/50
41.6 %
1.02 [ 0.92, 1.14 ]
194
188
84.3 %
1.09 [ 0.95, 1.26 ]
1 Trichophyton infections
Subtotal (95% CI)
Total events: 131 (terbinafine), 111 (griseofulvin)

Heterogeneity: Tau2 = 0.01; Chi2 = 3.52, df = 2 (P = 0.17); I2 =43%
Test for overall effect: Z = 1.28 (P = 0.20)
2 Microsporum infections
Fuller 2001
3/14
5/15
1.4 %
0.64 [ 0.19, 2.20 ]
14
15
1.4 %
0.64 [ 0.19, 2.20 ]
Subtotal (95% CI)

Heterogeneity: not applicable
3 Mixed Trichophyton/Microsporum infections
Memisoglu 1999
15/39
17/39
6.7 %
0.88 [ 0.52, 1.50 ]
C ceres-R os 2000
19/25
11/25
7.6 %
1.73 [ 1.05, 2.83 ]
Subtotal (95% CI)
64
64
14.3 %
1.24 [ 0.64, 2.42 ]
100.0 %
1.11 [ 0.96, 1.29 ]

Total (95% CI)
272
267

0.1 0.2
0.5
Favours griseofulvin
10
Favours terbinafine

51
Analysis 2.1. Comparison 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum
infections; 16 weeks follow-up, Outcome 1 complete cure.
Review:
Comparison: 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum infections; 16 weeks follow-up
Study or subgroup
terbinafine
griseofulvin
n/N
n/N
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
1 medium terbinafine treatment duration (6 to 8 weeks)

Lipozencic 2002
36/70
21/30
0.73 [ 0.53, 1.02 ]
21/30
0.51 [ 0.34, 0.76 ]
2 long terbinafine treatment duration (10 to 12 weeks)

Lipozencic 2002
23/65
0.1 0.2
0.5
10
Favours terbinafine
Analysis 2.2. Comparison 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum
infections; 16 weeks follow-up, Outcome 2 clinical cure.
Review:
Comparison: 2 Terbinafine (6 to12 weeks) versus griseofulvin (12 weeks) in Microsporum infections; 16 weeks follow-up
Outcome: 2 clinical cure
Study or subgroup
terbinafine
griseofulvin
n/N
n/N
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
1 medium terbinafine treatment duration (6 to 8 weeks)

Lipozencic 2002
46/70
24/30
0.82 [ 0.64, 1.05 ]
24/30
0.69 [ 0.52, 0.92 ]
2 long terbinafine treatment duration (10 to 12 weeks)

Lipozencic 2002
36/65
0.1 0.2
0.5

10
Favours terbinafine
52
Analysis 3.1. Comparison 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections;
12 to 20 weeks follow-up, Outcome 1 complete cure.
Review:
Comparison: 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections; 12 to 20 weeks follow-up
Study or subgroup
shorter
longer
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Haroon 1996
26/53
31/51
31.8 %
0.81 [ 0.57, 1.15 ]
Kullavanijaya 1997
12/27
16/28
18.9 %
0.78 [ 0.46, 1.32 ]
Talarico Filho 1998
19/42
23/44
24.7 %
0.87 [ 0.56, 1.34 ]
Friedlander 2002
21/56
27/59
24.6 %
0.82 [ 0.53, 1.27 ]
178
182
100.0 %
0.82 [ 0.66, 1.01 ]
1 1 week versus 2 weeks
Subtotal (95% CI)

Total events: 78 (shorter), 97 (longer)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.10, df = 3 (P = 0.99); I2 =0.0%

Haroon 1996
26/53
38/57
30.2 %
0.74 [ 0.53, 1.02 ]
Kullavanijaya 1997
12/27
21/27
20.1 %
0.57 [ 0.36, 0.91 ]
Talarico Filho 1998
19/42
36/46
27.1 %
0.58 [ 0.40, 0.83 ]
Friedlander 2002
21/56
30/62
22.7 %
0.78 [ 0.51, 1.19 ]
178
192
100.0 %
0.67 [ 0.55, 0.81 ]
Subtotal (95% CI)


3 2 weeks versus 4 weeks
Haroon 1996
31/51
38/57
29.3 %
0.91 [ 0.68, 1.21 ]
Kullavanijaya 1997
16/28
21/27
22.1 %
0.73 [ 0.50, 1.07 ]
Talarico Filho 1998
23/44
36/46
26.4 %
0.67 [ 0.48, 0.92 ]
Friedlander 2002
27/59
30/62
22.2 %
0.95 [ 0.65, 1.38 ]
182
192
100.0 %
0.81 [ 0.68, 0.96 ]
Subtotal (95% CI)


0.1 0.2
0.5
Favours longer
10
Favours shorter
(Continued . . . )

53
(. . .
Study or subgroup
shorter
Lipozencic 2002
Subtotal (95% CI)
longer
Risk Ratio
MH,Random,95%
CI
Weight
Continued)
Risk Ratio
MH,Random,95%
CI
n/N
n/N
18/36
18/34
100.0 %
0.94 [ 0.60, 1.49 ]
36
34
100.0 %
0.94 [ 0.60, 1.49 ]
18/36
13/33
100.0 %
1.27 [ 0.74, 2.17 ]
36
33
100.0 %
1.27 [ 0.74, 2.17 ]
18/36
10/32
100.0 %
1.60 [ 0.87, 2.94 ]
36
32
100.0 %
1.60 [ 0.87, 2.94 ]
18/34
13/33
100.0 %
1.34 [ 0.79, 2.28 ]
34
33
100.0 %
1.34 [ 0.79, 2.28 ]
18/34
10/32
100.0 %
1.69 [ 0.93, 3.10 ]
34
32
100.0 %
1.69 [ 0.93, 3.10 ]
13/33
10/32
100.0 %
1.26 [ 0.65, 2.45 ]
33
32
100.0 %
1.26 [ 0.65, 2.45 ]

Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)

0.1 0.2
0.5
Favours longer
10
Favours shorter

54
Analysis 3.2. Comparison 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections;
12 to 20 weeks follow-up, Outcome 2 clinical cure.
Review:
Comparison: 3 Terbinafine for 1, 2, and 4 weeks in Trichophyton and Microsporum infections; 12 to 20 weeks follow-up
Study or subgroup
shorter
longer
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Haroon 1996
44/53
43/51
58.3 %
0.98 [ 0.83, 1.17 ]
Talarico Filho 1998
23/42
27/44
21.0 %
0.89 [ 0.62, 1.28 ]
Friedlander 2002
27/56
31/59
20.7 %
0.92 [ 0.64, 1.32 ]
151
154
100.0 %
0.96 [ 0.83, 1.11 ]
Subtotal (95% CI)


Haroon 1996
44/53
49/57
54.8 %
0.97 [ 0.82, 1.13 ]
Talarico Filho 1998
23/42
39/46
25.0 %
0.65 [ 0.48, 0.87 ]
Friedlander 2002
27/56
36/62
20.2 %
0.83 [ 0.59, 1.17 ]
151
165
100.0 %
0.82 [ 0.63, 1.07 ]
Subtotal (95% CI)


Haroon 1996
43/51
49/57
51.4 %
0.98 [ 0.84, 1.15 ]
Talarico Filho 1998
27/44
39/46
27.9 %
0.72 [ 0.56, 0.94 ]
Friedlander 2002
31/59
36/62
20.8 %
0.90 [ 0.66, 1.25 ]
154
165
100.0 %
0.88 [ 0.72, 1.07 ]
Subtotal (95% CI)

Lipozencic 2002
Subtotal (95% CI)
22/36
24/34
100.0 %
0.87 [ 0.62, 1.22 ]
36
34
100.0 %
0.87 [ 0.62, 1.22 ]

0.1 0.2
0.5
Favours longer
10
Favours shorter
(Continued . . . )

55
(. . .
Study or subgroup
Risk Ratio
MH,Random,95%
CI
Weight
Continued)
Risk Ratio
MH,Random,95%
CI
shorter
longer
n/N
n/N
22/36
20/33
100.0 %
1.01 [ 0.69, 1.47 ]
36
33
100.0 %
1.01 [ 0.69, 1.47 ]
22/36
16/32
100.0 %
1.22 [ 0.79, 1.89 ]
36
32
100.0 %
1.22 [ 0.79, 1.89 ]
24/34
20/33
100.0 %
1.16 [ 0.82, 1.65 ]
34
33
100.0 %
1.16 [ 0.82, 1.65 ]
24/34
16/32
100.0 %
1.41 [ 0.94, 2.12 ]
34
32
100.0 %
1.41 [ 0.94, 2.12 ]
20/33
16/32
100.0 %
1.21 [ 0.78, 1.89 ]
33
32
100.0 %
1.21 [ 0.78, 1.89 ]

Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)


Lipozencic 2002
Subtotal (95% CI)

0.1 0.2
0.5
Favours longer
10
Favours shorter

56
Analysis 4.1. Comparison 4 Terbinafine (standard dose compared to double dose) in Microsporum
Review:
Comparison: 4 Terbinafine (standard dose compared to double dose) in Microsporum infections; 20 weeks follow-up
Study or subgroup
double dose
standard dose
n/N
n/N
Ungpakorn 2004
13/19
14/23
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
1.12 [ 0.72, 1.76 ]
0.1 0.2
0.5
Favours standard
10
Favours double
Analysis 5.1. Comparison 5 Itraconazole (6 and 2 weeks, respectively) versus griseofulvin (6 weeks) in
Trichophyton and Microsporum infections, Outcome 1 complete cure.
Review:
Comparison: 5 Itraconazole (6 and 2 weeks, respectively) versus griseofulvin (6 weeks) in Trichophyton and Microsporum infections
Study or subgroup
itraconazole
griseofulvin
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Gupta 2001
41/50
46/50
71.6 %
0.89 [ 0.76, 1.04 ]
L pez-G mez 1994
15/17
15/18
28.4 %
1.06 [ 0.81, 1.39 ]
67
68
100.0 %
0.94 [ 0.80, 1.09 ]
Total (95% CI)
Total events: 56 (itraconazole), 61 (griseofulvin)

0.1 0.2
0.5
10
Favours itraconazole

57
Analysis 6.1. Comparison 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections,
Outcome 1 complete cure.
Review:
Comparison: 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections

Study or subgroup
itraconazole
terbinafina
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Jahangir 1998
18/30
16/30
24.0 %
1.13 [ 0.72, 1.75 ]
Gupta 2001
41/50
47/50
76.0 %
0.87 [ 0.75, 1.01 ]
80
80
100.0 %
0.93 [ 0.72, 1.19 ]
Total (95% CI)
Total events: 59 (itraconazole), 63 (terbinafina)

0.1 0.2
0.5
Favours terbinafine
10
Analysis 6.2. Comparison 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections,
Outcome 2 clinical cure.
Review:
Comparison: 6 Itraconazole versus terbinafine (both 2 weeks) in Trichophyton infections

Study or subgroup
Gupta 2001
itraconazole
terbinafine
n/N
n/N
22/50
20/50
Risk Ratio
Risk Ratio
M-H,Fixed,95% CI
M-H,Fixed,95% CI
1.10 [ 0.69, 1.75 ]
0.1 0.2
0.5
Favours terbinafine

10
58
Analysis 7.1. Comparison 7 Ketoconazole (6 weeks) versus griseofulvin (8 to 12 weeks) in Trichophyton

Review:
Comparison: 7 Ketoconazole (6 weeks) versus griseofulvin (8 to 12 weeks) in Trichophyton infections; 12 weeks follow-up
Study or subgroup
ketoconazole
griseofulvin
n/N
n/N
Gan 1987
23/40
37/40
60.8 %
0.62 [ 0.47, 0.82 ]
Tanz 1988
16/33
25/46
39.2 %
0.89 [ 0.57, 1.39 ]
73
86
100.0 %
0.72 [ 0.50, 1.02 ]
Total (95% CI)
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
Total events: 39 (ketoconazole), 62 (griseofulvin)

0.1 0.2
0.5
10
Favours ketoconazole
Analysis 8.1. Comparison 8 Fluconazole (2 and 4 weeks respectively) versus griseofulvin (6 weeks) in
Trichophyton infections; 8 -12 weeks, Outcome 1 complete cure.
Review:
Comparison: 8 Fluconazole (2 and 4 weeks respectively) versus griseofulvin (6 weeks) in Trichophyton infections; 8 -12 weeks
Study or subgroup
fluconazole
griseofulvin
n/N
n/N
Dastghaib 2005
15/19
16/21
17.5 %
1.04 [ 0.74, 1.45 ]
Gupta 2001
41/50
46/50
82.5 %
0.89 [ 0.76, 1.04 ]
69
71
100.0 %
0.92 [ 0.80, 1.05 ]
Total (95% CI)
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
Total events: 56 (fluconazole), 62 (griseofulvin)

0.1 0.2
0.5
10
Favours fluconazole

59
Analysis 9.1. Comparison 9 Fluconazole (2 to 3 weeks) versus terbinafine (2 to3 weeks) in Trichophyton
Review:
Comparison: 9 Fluconazole (2 to 3 weeks) versus terbinafine (2 to3 weeks) in Trichophyton infections; 12 weeks follow-up
Study or subgroup
fluconazole
Gupta 2001
terbinafine
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
n/N
n/N
41/50
47/50
0.87 [ 0.75, 1.01 ]
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 41 (fluconazole), 47 (terbinafine)
Test for overall effect: Z = 0.0 (P < 0.00001)
0.1 0.2
0.5
Favours terbinafine
10
Favours fluconazole
Analysis 10.1. Comparison 10 Fluconazole (2 to 3 weeks) versus itraconazole (2 to 3 weeks) in Trichophyton

Review:
Comparison: 10 Fluconazole (2 to 3 weeks) versus itraconazole (2 to 3 weeks) in Trichophyton infections; 12 weeks follow-up
Study or subgroup
Gupta 2001
fluconazole
itraconazole
n/N
n/N
41/50
41/50
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
1.00 [ 0.83, 1.20 ]
0.1 0.2
0.5

10
Favours fluconazole
60
Analysis 11.1. Comparison 11 Fluconazole (different doses compared: 1.5, 3 and 6 mg/kg/day) in
Trichophyton infections; 4 months follow-up, Outcome 1 complete cure.
Review:
Comparison: 11 Fluconazole (different doses compared: 1.5, 3 and 6 mg/kg/day) in Trichophyton infections; 4 months follow-up
Study or subgroup
high dose
low dose
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
n/N
n/N
6/15
2/12
2.40 [ 0.59, 9.82 ]
8/14
2/12
3.43 [ 0.89, 13.15 ]
8/14
6/15
1.43 [ 0.66, 3.08 ]
1 1.5 mg versus 3 mg
Solomon 1997
2 1.5 mg versus 6 mg
Solomon 1997
3 3 mg versus 6 mg
Solomon 1997
0.1 0.2
0.5
Favours low dose
10
Favours high dose
ADDITIONAL TABLES
Table 1. Quality criteria
Studies
Randomisation
Concealment
Blinded
assessment
Loss
to Sample
follow up size
CceresRios 2000
Unclear
Unclear
ParticiOne drop- No
pants, clin- out, group
icians and not stated
outcome
assessors
blinded

Inclusion/ Type
exclusion fungi
Yes
Yes
of Baseline
Adequate
Funding
Not mentioned
61
(Continued)
Dastghaib
2005
Unclear
Unclear
Participants not
blinded,
investigators
blinded.
Friedlander 2002
Unclear
Unclear baseline comparability: conflict of interest: not

mentioned
Participants, clinicians and

outcome
assessors
blinded
with
respect to
terbinafine
treatment
duration
of each patient
Fuller
2001
Adequate
(computer
generated)
Unclear

outcome
assessors not
blinded
Five partic- No
ipants discontinued
therapy or
were lost to
follow up,
group not
stated
Yes
Yes
Adequate
Not mentioned
No
Yes
Yes
Adequate
Not mentioned
Griseoful- Yes
vin group,
postrandomisation
exclusions
37/107
(35%)
,
later
losses 0,
Yes
Yes
Adequate
Novartis
Terbinafine
for 1 week
group,
postrandomisation
exclusions
14/56
(25%);
terbinafine
for 2 weeks
group,
postrandomisation
exclusions:
15/59
(25%);
terbinafine
for 4 weeks
group,
postrandomisation
exclusions:
12/62
(19%)

62
(Continued)
intention
to treat 0
(only 45
completed
the study);
terbinafine
group,
postrandomisation
exclusions
26/103
(25%)
,
later
losses 0,
intention
to treat 0
(only 50
completed
the study)
.
We are unaware of all
the reasons
for
the
drop-outs
in any of
the groups,
68%
discontinued because they
were unable to attend clinic
visits
Gan 1987
AdUnclear
equate (table of random numbers)
Not
blinded
Griseoful- No
vin group,
post-randomisation exclusions: 11/
40 (28%)
; ketoconazole group,
post-randomisation exclu-

Yes
Yes
Adequate
Not mentioned
63
(Continued)
sions: 6/40
(15%)
Gupta
2001
Unclear
Unclear
Participants not
blinded,
clinicians and
outcome
assessors
blinded
Griseoful- No
vin group,
postrandomisation
exclusions:
4/50 (8%);
terbinafine
group,
postrandomisation
exclusions:
2/50 (4%)
; itraconazole group,
postrandomisation
exclusions:
4/50 (8%)
; fluconazole group,
postrandomisation
exclusions:
4/50 (8%)
Yes
Yes
Adequate
Hamm
1999
Unclear
Unclear
ParticiAny drop- No
pants, clin- out menicians and tioned
outcome
assessors
blinded
Yes
Yes
Not stated Novartis

Age: We
are
unaware of
the
mean age
for each
group
Sex: We are
unaware of
the number of females and
males in
each
group.

Not mentioned
64
(Continued)
Duration
of
complaint: Not
stated
Haroon
1995
Unclear
Unclear
No
No drop- No
mention of out menblinding
tioned
Yes
Yes
Adequate
Sandoz
Haroon
1996
Unclear
Unclear
ParticiNo drop- No
outcome
assessors
blinded
Yes
Yes
Not stated
Sandoz
Jahangir
1998
Unclear
Unclear
ParticiNo drop- No
outcome
assessors
blinded
Yes
Yes
Adequate
Not mentioned
Kullavanijaya 1997
Unclear
Unclear
Described
as single
blind and
open trial
study but
no
mention of
which one
(participants or
observers)
The inclu- Yes

sion criteria
are poorly
stated and
the exclusion criteria are not
mentioned
Adequate
Sandoz
Lipozencic
2002
Unclear
Unclear

outcome
assessors
blinded.
Yes
Adequate
Novartis Pharma
AG
Seven par- No
ticipants were
lost to follow up and
were
excluded,
but no further information is
given
Yes
Terbinafine
for
6
weeks,
36 (19%);
terbinafine
for
8
weeks,
post-randomisa-

Yes
65
(Continued)
tion exclusions: 4/
34 (12%);
terbinafine
for
10
weeks,
postrandomisation exclusion: 6/
33 (18%);
terbinafine
for
12
weeks,
postrandomisation
exclusion:
12/32
(38%);
Griseofulvin group,
postrandomisation
exclusions:
7/30
(23%)
LpezGmez
1994
Unclear
Unclear

outcome
assessors
blinded.
ItraconaNo
zole group,
post-randomised
exclusions:
1/18 (6%)
; griseofulvin group,
post-randomisation: 2/17
(12%)
Only in- Yes

clusion criteria mentioned.
Adequate
Janssen
MartnezRoig 1988
Adequate
Unclear
(computer generated random number table)

outcome
assessors
blinded
Very diffi- No
cult to follow
the
drop-outs
as it mixes
tinea corporis and
No
Not stated
Laboratories Dr. Esteve

Yes
66
(Continued)
tinea capitis, we do
not know
to which of
the
two groups
they
belong
Unclear
Unclear

outcome
assessors
blinded
Griseoful- No
vin group,
post-randomisation exclusions: 7/39
(18%), intention to
treat: 32;
terbinafine
group,
(10%), intention to
treat: 35
Yes
Rademaker
1998
Unclear
Unclear
Not
blinded
No drop- No
out mentioned
Solomon
1997
Unclear
Unclear
Participants not
blinded,
clinicians and
outcome
assessors
blinded
Talarico
Unclear
Filho 1998
Unclear
Memisoglu
1999
Adequate
Not mentioned
Only in- Yes

clusion criteria mentioned
Not stated
Not mentioned
Fourteen
No
were lost to
follow up,
but no further information
was given
Yes
Yes
Not stated
Not mentioned
Only parNo
ticipants
Terbinafine
blinded
for 1 week,
Yes
Yes
Adequate
Sandoz

Yes
67
(Continued)
42 (14%);
terbinafine
for
2
weeks,
postrandomisation exclusion: 6/
44 (14%);
terbinafine
for
4
weeks,
postrandomisation
exclusions:
12/46
(26%)
Tanz 1985
Unclear
Unclear

outcome
assessors
blinded
Griseoful- No
vin group,
(25%)
; ketoconazole group,
post-randomisation: 5/10
(50%)
Yes
Yes
Adequate
Janssen
Tanz 1988
Unclear
Unclear

outcome
assessors
blinded
Griseoful- No
vin group,
(7%), later
losses: 17;
ketoconazole group,
(6%), later
losses: 9
Yes
Yes
Adequate
Janssen

68
Ungpakorn
2004
Unclear
(Continued)
Unclear
ParticiAny drop- Yes

outcome
assessors
blinded
Yes
Yes
Adequate
Institute of
Dermatology Research
Funds and
Novartis
(Thailand)
APPENDICES
Appendix 1. Search strategy for Cochrane Skin Group Specialized Register
(scalp* or hair* or capitis) and (tinea or fung* or hyph* or spore* or dermatophyt* or dermatomycos* or myceli* or mycos* or mycete*
or microspor* or epidermophyt* or trichophy* or ringworm or kerion*)
Appendix 2. Cochrane Central Register of Controlled Trials

#1scalp or hair or capitis in All Fields in all products
#2MeSH descriptor Scalp Dermatoses explode all trees in MeSH products
#3tinea or fung* or hyph* or spore* or dermatophyt* in All Fields in all products
#4dermatomycos* or myceli* or mycos* or mycete* or microspor* in All Fields in all products
#5epidermophyt* or trichophy* or ringworm or kerion* in All Fields in all products
#6(#1 OR #2)
#7(#3 OR #4 OR #5)
#8(#6 AND #7)
#9griseofulvin or ketoconazole or terbinafine in All Fields in all products
#10itraconazole or fluconazole in All Fields in all products
#11antifungal* in All Fields in all products
#12systemic or oral in All Fields in all products
#13(#9 OR #10 OR #11 OR #12)
#14(#8 AND #13)
Appendix 3. Medline (OVID) search strategy

1. RANDOMIZED CONTROLLED TRIAL.pt.
2. CONTROLLED CLINICAL TRIAL.pt.
3. RANDOMIZED CONTROLLED TRIALS.sh.
4. RANDOM ALLOCATION.sh.
5. DOUBLE BLIND METHOD.sh.
6. SINGLE-BLIND METHOD.sh.
7. or/1-6
8. animal/ not human/
9. 7 not 8
10. CLINICAL TRIAL.pt.
69
11. exp CLINICAL TRIALS/

12. (clin$ adj25 trial$).ti,ab.
13. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.
14. PLACEBOS.sh.
15. placebo$.ti,ab.
16. random$.ti,ab.
17. RESEARCH DESIGN.sh.
18. or/10-17
19. 18 not 8
20. 19 not 9
21. COMPARATIVE STUDY.sh.
22. exp EVALUATION STUDIES/
23. FOLLOW UP STUDIES.sh.
24. PROSPECTIVE STUDIES.sh.
25. (control$ or prospectiv$ or volunteer$).ti,ab.
26. or/21-25
27. 26 not 8
28. 27 not (9 or 20)
29. 9 or 20 or 28
30. scalp dermatoses.mp. or exp Scalp Dermatoses/
31. (hair or capitis).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
32. 30 or 31
33. exp TINEA/ or tinea.mp.
34. exp SPORES, FUNGAL/ or fungal.mp.
35. spore$.mp.
36. dermatophytes.mp. or exp Arthrodermataceae/
37. dermatomycoses.mp. or exp DERMATOMYCOSES/
38. mycelium.mp. or exp MYCELIUM/
39. exp Fungi/ or mycete.mp.
40. microsporum.mp. or exp MICROSPORUM/
41. epidermophyton.mp. or exp EPIDERMOPHYTON/
42. trichophyton.mp. or exp TRICHOPHYTON/
43. ringworm.mp.
44. kerion.mp.
45. 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46. griseofulvin.mp. or exp GRISEOFULVIN/
47. ketoconazole.mp. or exp KETOCONAZOLE/
48. exp Antifungal Agents/ or exp Itraconazole/ or terbinafine.mp.
49. fluconazole.mp. or exp FLUCONAZOLE/
50. systemic.mp.
51. 46 or 47 or 48 or 49 or 50
52. 29 and 32 and 45 and 51
53. limit 52 to yr=2003 - 2005

70
Appendix 4. EMBASE (OVID) search strategy

1. random$.mp.
2. factorial$.mp.
3. crossover$.mp.
4. placebo$.mp. or PLACEBO/
5. (doubl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer,
drug manufacturer name]
6. (singl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer,
drug manufacturer name]
7. assign$.mp.
8. volunteer$.mp. or VOLUNTEER/
9. Crossover Procedure/
10. Double Blind Procedure/
11. Randomized Controlled Trial/
12. Single Blind Procedure/
13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12
14. tinea capitis.mp. or exp Tinea Capitis/
15. capitis.mp.
16. exp HEAD/ or head.mp.
17. exp SCALP HAIR/ or scalp.mp. or exp SCALP/
18. 14 or 15 or 16 or 17
19. TINEA/
20. fung$.mp.
21. hyphae.mp. or exp Fungus Hyphae/
22. spore$.mp.
23. dermatophyte$.mp. or exp DERMATOPHYTE/
24. dermatomycose$.mp. or exp Dermatomycosis/
25. mycelium.mp. or exp MYCELIUM/
26. mycoses.mp. or exp Mycosis/
27. mycete$.mp.
28. exp MICROSPORUM/ or microsporum.mp.
29. exp EPIDERMOPHYTON/ or epidermophyton.mp.
30. trichophyton.mp. or exp TRICHOPHYTON/
31. ringworm.mp.
32. kerion.mp.
33. 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32
34. griseofulvin.mp. or exp GRISEOFULVIN/
35. ketoconazole.mp. or exp KETOCONAZOLE/
36. terbinafine.mp. or exp TERBINAFINE/
37. itraconazole.mp. or exp ITRACONAZOLE/
38. fluconazole.mp. or exp FLUCONAZOLE/
39. antifungal.mp. or exp Antifungal Agent/
40. exp SYSTEMIC THERAPY/
41. 34 or 35 or 36 or 37 or 38 or 39 or 40
42. 13 and 18 and 33 and 41
43. limit 42 to yr=2003 - 2005
44. from 43 keep 1-16

71
Appendix 5. LILACS Search Strategy in English and Spanish/Portuguese

(in English)
1. exp Scalp Dermatoses/ or Scalp or Hair or Capitis
2. Tinea
3. Fungus or Fungal or Fungi or Hyphae
4. Spore$
5. Dermatophyte$ or Dermatomycoses
6. Mycelium or Mycos$ or Mycetes
7. Microspor$ or Epidermophyto$ or Trichophyto$
8. 2-7 or
9. 1 and 8
10. Ringworm
11. Kerion$
12. 9 or 10 or 11
(in Spanish and Portuguese)
1. Cuero or Couro or Pelo or Cabelludo or Cabeludo
2. Capitis or Cabeza
3. 1 or 2
4. Hongo$ or Fungico$
5. Espora$
6. Dermatofito$ or Dermatomicosis
7. Micosis
8. Tinea or Tia or Tina or Tinha
9. 4-8 or
10. 3 and 9
11. Querion or Kerion
12. 10 or 11
Appendix 6. MEDLINE (OVID) Search Strategy for Serious Adverse Events6

1. exp DEATH/ or death.mp.
2. exp ANAPHYLAXIS/ or anaphylaxis.mp.
3. severe morbidity.mp.
4. exp Hospitalization/ or hospitalisation.mp.
5. 1 or 2 or 3 or 4
6. Humans/
7. 5 and 6
8. ketoconazole.mp. or KETOCONAZOLE/
9. griseofulvin.mp. or GRISEOFULVIN/
10. Itraconazole. mp or ITRACONAZOLE/
11. terbinafine.mp or TERBINAFINE/
12. fluconazole.mp or FLUCONAZOLE/
13. 8 or 9 or 10 or 11 or 12
14. (systemic or oral).mp
15. 13 and 14
16. 7 and 15

72
WHATS NEW
Last assessed as up-to-date: 22 August 2007.
Date
Event
Description
20 June 2012
Amended
Contact details updated.
HISTORY
Protocol first published: Issue 1, 2004
Review first published: Issue 4, 2007
Date
Event
Description
21 July 2008
Amended
Converted to new review format.
22 August 2007
New citation required and conclusions have changed
Substantive amendment
30 May 2007
New search has been performed
Minor update
CONTRIBUTIONS OF AUTHORS
Urb Gonzlez wrote the draft-protocol for this review. George Bergus, Terry Seaton, Josep Maria Torres and Jim Jacobson (consumer
co-author) revised and contributed to the final version of it.
George Bergus and Urb Gonzlez devised and ran the strategy for identification of studies. Terry Seaton and Urb Gonzlez extracted
data from trials. Urb Gonzlez and Cecilia Martnez-Monzn carried out the analysis of trials.
DECLARATIONS OF INTEREST
None known
SOURCES OF SUPPORT

73
Internal sources
Spanish Society of Dermato-Epidemiology and Evidence-based Dermatology (SEDE-DBE) and Clnica Plat, Barcelona, Spain.
External sources
Cochrane Child Health Field. Alberta Research Centre for Child Health Evidence, University of Alberta, Canada.
INDEX TERMS
Medical Subject Headings (MeSH)
Antifungal Agents [ therapeutic use]; Fluconazole [therapeutic use]; Griseofulvin [therapeutic use]; Itraconazole [therapeutic use];
Naphthalenes [therapeutic use]; Randomized Controlled Trials as Topic; Tinea Capitis [ drug therapy]
MeSH check words

Child; Humans

74

Systemic Antifungal Therapy For Tinea Capitis in Children (Review)

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Systemic antifungal therapy for tinea capitis in children

Systemic antifungal therapy for tinea capitis in children (Review)

Systemic antifungal therapy for tinea capitis in children (Review)

Systemic antifungal therapy for tinea capitis in children

PLAIN LANGUAGE SUMMARY

Description of the condition

There are over eight species of dermatophytes characteristically

Description of the intervention

Systemic antifungal therapy for tinea capitis in children (Review)

Why it is important to do this review

To assess the effects of systemic antifungal drugs for tinea capitis

Criteria for considering studies for this review

Systemic antifungal therapy for tinea capitis in children (Review)

Types of outcome measures

(a) The proportion of participants with complete cure i.e. clinical

(a) The proportion of participants with clinical cure only.

Search methods for identification of studies

We obtained unpublished, on-going trials and grey literature via

We stated in the protocol that we would search the conference

We asked pharmaceutical companies for surveillance data on adverse events.

We imposed no language restrictions.

Data collection and analysis

Searching other resources

References from published studies

Data extraction and management

We searched the bibliographies of all papers identified by these

At least two authors (TS and UG) extracted data independently

Systemic antifungal therapy for tinea capitis in children (Review)

We recorded the information in a table of quality criteria (Table

Assessment of methodological quality of included studies

In order to assess the quality of each included study we evaluated

To estimate differences between treatments, we pooled trials that

Subgroup analysis and investigation of heterogeneity

Results of the search

Systemic antifungal therapy for tinea capitis in children (Review)

with griseofulvin, one with terbinafine, one with itraconazole and

Risk of bias in included studies

All included studies stated or implied that treatment allocation

In total, we studied five different antifungal agents: griseofulvin,

None of the included studies had adequate reporting of allocation

Systemic antifungal therapy for tinea capitis in children (Review)

Incomplete outcome data

Follow up and exclusions

Other potential sources of bias

Systemic antifungal therapy for tinea capitis in children (Review)

Griseofulvin has been used as the standard antifungal against

Griseofulvin was associated with a small number of adverse effects

Unless otherwise stated, the standard dosing for terbinafine in the

Short-term use of terbinafine versus griseofulvin (six studies)

(1) Primary outcomes

mg/kg/day of griseofulvin for 8 weeks in 105 participants, of whom

Systemic antifungal therapy for tinea capitis in children (Review)

No participants reported intolerance to either griseofulvin or

(2) Secondary outcomes

24.2% (26/107) (Fuller 2001) and 4% (2/50) vs 8% (4/50) (Gupta

Medium to long-term use of terbinafine versus griseofulvin

(1) Primary outcomes

(2) Secondary outcomes

Systemic antifungal therapy for tinea capitis in children (Review)

The proportion of participants with clinical cure only at 16 weeks,

(1) Primary outcomes

weeks of treatment, the cure rate was significantly higher with a 4

Systemic antifungal therapy for tinea capitis in children (Review)