Published online November 1, 2004
PEDIATRICS Vol. 114 No. 5 November 2004, pp. 1312-1315 (doi:10.1542/peds.2004-0428)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fleece, D.
Right arrow Articles by Aronoff, S. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fleece, D.
Right arrow Articles by Aronoff, S. C.
Related Collections
Right arrow Infectious Disease & Immunity
Right arrowRelated AAP Red Book topics:
Tinea Capitis (Ringworm of the...

REVIEW ARTICLE

Griseofulvin Versus Terbinafine in the Treatment of Tinea Capitis: A Meta-analysis of Randomized, Clinical Trials

David Fleece, MD*, John P. Gaughan, PhD{ddagger} and Stephen C. Aronoff, MD*

* Departments of Pediatrics
{ddagger} Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective. Tinea capitis, a common pediatric infection in the United States, is caused mainly by Trichophyton species and affects many urban children. Although the current treatment of choice is oral griseofulvin, terbinafine has been shown to be variably effective in several comparative, randomized trials. The purpose of this study was to perform a meta-analysis of randomized, clinical trials comparing the efficacies of oral terbinafine and oral griseofulvin for the treatment of childhood tinea capitis.

Methods.The Medline database was searched for randomized, clinical studies comparing griseofulvin and terbinafine for the treatment of tinea capitis. Acceptance criteria included oral administration of griseofulvin for at least 6 weeks and the identification of a pathogenic dermatophyte from the scalp at the time of enrollment in the study. Scalp culture status at least 8 weeks after enrollment was used as the outcome. The common odds ratio (OR) with 95% confidence intervals (CIs), the Cochran-Mantel-Haenszel test for significance, and the Breslow-Day test for homogeneity were calculated.

Results.Six articles that satisfied all inclusion criteria were identified. These studies were combined by using outcomes at 12 to 16 weeks after enrollment. The common OR was 0.86 (95% CI: 0.57–1.27). When the 5 studies that identified Trichophyton species as the predominant pathogen were combined, using outcomes 12 weeks after enrollment, the results nearly favored terbinafine (OR: 0.65 [95% CI: 0.42–1.01]). For outcomes at 8 weeks after enrollment, no difference was found between the agents (OR: 0.84 [95% CI: 0.54–1.32]).

Consclusions.A 2- to 4-week course of terbinafine is at least as effective as a 6- to 8-week course of griseofulvin for the treatment of Trichophyton infections of the scalp. Griseofulvin is likely to be superior to terbinafine for the rare cases caused by Microsporum species.

Key Words: tinea capitis • Trichophyton • Microsporum • terbinafine • griseofulvin • meta-analysis

Abbreviations: OR, odds ratio • CI, confidence interval

Tinea capitis is an increasingly common pediatric infection, with the highest incidence in this country occurring primarily in black children in inner-city populations.1,2 The most common etiology in the United States is Trichophyton tonsurans, with recent data showing a rise in both the prevalence and percentage of cases of tinea capitis caused by this organism.3,4 Current treatment requires a 6- to 8-week course of oral griseofulvin given once daily. Recent studies have investigated the use of newer oral antifungal agents including terbinafine, fluconazole, and itraconazole in the treatment of tinea capitis. Potential advantages over griseofulvin include improved efficacy as well as a shorter treatment course with associated cost savings and improved compliance.5 Of the newer antifungal agents, terbinafine is the most widely studied in trials against griseofulvin. To determine if any therapeutic difference exists between terbinafine and griseofulvin, we undertook this meta-analysis of randomized, comparative trials of the treatment of tinea capitis.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Identification
The Medline and EBM (Evidence-Based Medicine) Reviews/Cochrane Central Register of Controlled Trials databases were searched using both the Ovid and PubMed search engines, covering the period from 1966 to the present. "English only" was used as a filter. Search terms included "tinea capitis," "terbinafine," and "griseofulvin," with a focus on the subtopics "treatment" and "therapy." A review of the bibliographies of selected references was also performed.

Study Selection and Data Abstraction
Inclusion criteria were selected to identify studies that compared terbinafine and griseofulvin in a randomized fashion, identified an infecting agent, and used posttherapy culture results as an outcome measure. A minimum duration of 6 weeks of griseofulvin therapy was required, which represents current standard treatment duration.

Abstracts of all recovered articles were reviewed to select only those studies that compared terbinafine and griseofulvin for the treatment of tinea capitis. The methods section of each study that survived the initial culling was evaluated independently by 2 reviewers (S.C.A. and Marla Mikelait, MD) to ensure compliance with inclusion criteria. The reviewers were blinded with respect to title, authors, study size, and results.

Data Analysis
The data for each trial were expressed in 2 x 2 tables and compared cures and failures for each treatment. "Cure" was defined as having a negative scalp fungal culture and either no symptoms ("complete cure") or minimal symptoms ("mycologic cure"). Odds ratios (ORs) were calculated such that values < 1 favored terbinafine, and values >1 favored griseofulvin. The Cochran-Mantel-Haenszel test for conditional independence was used to test the null hypothesis that the conditional odds for each 2 x 2 table = 1; the Breslow-Day statistic was used to test for homogeneity among the ORs for each 2 x 2 table. Common ORs with 95% confidence intervals (CIs) were also calculated by using the Mantel-Haenszel method.6 All statistics and calculations used SAS 9.1 (SAS Institute Inc, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The initial search yielded 43 articles; 8 of these articles included both griseofulvin and terbinafine in the abstract and were subjected to additional review.7–14 One study12 was rejected because it did not meet the outcome criterion, and 1 study14 was rejected because it contained preliminary data that were included in another article. Table 1 is a summary of the studies included in the analysis.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Summary of Studies Included in the Meta-analysis

 
Table 2 presents a comparison of the cure rates of griseofulvin and terbinafine for each of the studies included. Of the 6 studies, 2 revealed statistically significant differences in cure rates. Lipozencic et al7 found a higher cure rate for griseofulvin than for terbinafine (88.0% vs 64.2%). Conversely, Cáceres-Ríos et al10 found that the cure rates favored terbinafine over griseofulvin at 12 weeks (76.0 vs 44.0, respectively) but not at 8 weeks (72.0 vs 76.0, respectively).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Summary of Cure Rates for Individual Studies

 
The results of the meta-analysis are shown in Table 3 and Fig 1. The ORs are calculated such that values <1 favor terbinafine, and values >1 favor griseofulvin. Three separate meta-analyses were performed. Analysis I included all 6 studies using culture status at least 12 weeks after enrollment in the study as the outcome. The common OR was 0.86 (95% CI: 0.57–1.27; P = .444). The Breslow-Day test for homogeneity was significant (P = .015), indicating that the studies were heterogeneous. Unlike the other reports, the study by Lipozencic et al7 strongly favored griseofulvin, and Microsporum species were the predominant pathogens. Analysis II included only the 5 studies in which Trichophyton species were the predominant pathogens and outcome was assessed at least 12 weeks postenrollment. The test for homogeneity was not significant. The common OR favored terbinafine and almost achieved significance (OR: 0.65; 95% CI: 0.042–1.01; P = .054). Analysis III included the 4 studies that provided outcome data at 8 weeks postenrollment. This analysis was undertaken given the finding by Cáceres-Ríos et al10 of diminishing efficacy for griseofulvin in the month after treatment. The test for homogeneity was not significant. The overall common OR failed to show any difference between the drugs (OR: 0.84; 95% CI: 0.54–1.32; P = .462).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Summary of Meta-analyses

 

Figure 1
View larger version (15K):
[in this window]
[in a new window]
  		Fig 1 Meta-analysis of 6 studies comparing the efficacies of terbinafine and griseofulvin for the treatment of childhood tinea capitis. {blacksquare} indicates OR; —, 95% CI.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Currently, the recommended therapy for tinea capitis is a 6- to 8-week course of oral griseofulvin. Griseofulvin has a long-standing history of safety and efficacy when used to treat fungal scalp infections in children.15 For these reasons, it has remained the current standard first-line therapy for tinea capitis in the United States. Issues that would favor alternative, equally effective therapies include compliance, cost, and tolerability. Griseofulvin must be taken daily for 6 weeks and has potentially significant gastrointestinal side effects. Newer antifungal agents including terbinafine offer the potential advantages of improved compliance, shorter courses of therapy, and cost savings.

Compared with griseofulvin, terbinafine has been shown to be less effective against Microsporum species in 2 separate trials.7,16 Dragos and Lunder16 treated 22 children infected with Microsporum canis with a 6-week course of terbinafine. At 14 weeks, only 7 of the 22 patients had achieved mycologic cure. Lipozencic et al7 compared the efficacy of griseofulvin and terbinafine in a population of 134 children with tinea capitis caused by Microsporum species; the cure rate for griseofulvin was significantly higher than that for terbinafine (88% vs 64%; P = .03). These observations suggest that griseofulvin may be the preferred agent for Microsporum infections. Memisoglu et al,11 however, treated a population of 67 children in which the etiologies were split between Microsporum and Trichophyton species and found no significant difference between terbinafine and griseofulvin.

Recent studies suggest that the incidence and prevalence of tinea capitis caused by Microsporum infections in American children has declined significantly.1–4 Weitzman et al4 surveyed dermatophyte culture results from 23 states and >40 laboratories between 1993 and 1995. Compared with prior studies performed 10 to 15 years earlier, T tonsurans increased in prevalence from 28% to 41%; M canis accounted for only 3% of the total isolates. Williams et al1 cultured 224 black school students in Philadelphia aged 5 to 13 years. Of 125 positive cultures, T tonsurans was recovered from 96%. Ghannoum et al2 cultured the scalps of 937 elementary school children in Cleveland. Fungal cultures from 13% of the children were positive, and all but 1 yielded T tonsurans. Similar results were reported from the San Francisco Bay area.3 These studies suggest that Trichophyton species are the predominant cause of tinea capitis among American children.

Our initial meta-analysis combining all 6 studies and including 603 patients failed to show a significant difference between the efficacies of the 2 medications. Notably, 1 of the studies was markedly different in that all pathogens were from the Microsporum genus. When this study was removed from the meta-analysis, the 5 remaining studies were homogeneous. When outcomes 12 weeks after enrollment were compared, 469 patients were included; the common OR favored short courses of terbinafine, and statistical significance was almost reached (OR: 0.65; 95% CI: 0.42–1.01; P = .054). When outcomes 8 weeks after enrollment were compared, 4 studies with a total of 369 patients were included; no significant difference was found between the drugs. These observations suggest that if a difference between the agents does exist, it may become more apparent with increasing time after treatment.

Together, these observations suggest that 2 to 4 weeks of terbinafine therapy is at least as effective as 6 to 8 weeks of griseofulvin therapy for the treatment of tinea capitis caused by Trichophyton species in children. Additional factors that may influence the choice between equally effective therapies include tolerability, safety, compliance, and cost. None of the 6 studies included here found any significant differences in tolerability or adverse effects between terbinafine and griseofulvin, with all authors concluding that both drugs were safe and well tolerated. There is some uncertainty as to the need for hematologic and biochemical monitoring when using the newer antifungal agents in children. In this series, 3 of the 6 studies required blood work during treatment, including complete blood counts and serum transaminases. No clinically serious laboratory abnormalities were identified.

The potential cost savings from using terbinafine depend on the length of the treatment course. In our hospital's outpatient pharmacy, a 6-week course of griseofulvin liquid for a 25-kg child would cost approximately $280, compared with $145 for a 4-week course of terbinafine and only $70 to $80 for a 2-week course. Factors that currently deter routine first-line use of terbinafine in children with tinea capitis include the lack of both a liquid preparation and Food and Drug Administration approval for this indication.


   ACKNOWLEDGMENTS
 
We thank Marla Mikelait, MD, for help in independently reviewing the articles before their inclusion in the meta-analysis.


   FOOTNOTES
 
Accepted May 10, 2004.

Address correspondence to David Fleece, MD, Department of Pediatrics, Temple University Children's Medical Center, 5th Floor, 3509 N Broad St, Philadelphia, PA 19140. E-mail: fleeced{at}tuhs.temple.edu


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Williams JV, Honig PJ, McGinley KJ, Leyden JJ. Semiquantitative study of tinea capitis and the asymptomatic carrier state in inner-city school children. Pediatrics. 1995;96 :265 –267[Abstract/Free Full Text]
  2. Ghannoum M, Isham N, Hajjeh R, et al. Tinea capitis in Cleveland: survey of elementary school students. J Am Acad Dermatol. 2003;48 :189 –193[CrossRef][ISI][Medline]
  3. Wilmington M, Aly R, Frieden IJ. Trichophyton tonsurans tinea capitis in the San Francisco Bay area: increased infection demonstrated in a 20-year survey of fungal infections from 1974 to 1994. J Med Vet Mycol. 1996;34 :285 –287[ISI][Medline]
  4. Weitzman I, Chin NX, Kunjukunju N, Della-Latta P. A survey of dermatophytes isolated from human patients in the United States from 1993 to 1995. J Am Acad Dermatol. 1998;39 :255 –261[CrossRef][ISI][Medline]
  5. Friedlander SF. The evolving role of itraconazole, fluconazole and terbinafine in the treatment of tinea capitis. Pediatr Infect Dis J. 1999;18 :205 –210[CrossRef][ISI][Medline]
  6. Agresti A. An Introduction to Categorical Data Analysis. New York, NY: John Wiley & Sons; 1996:53 –66
  7. Lipozencic J, Skerlev M, Orofino-Costa R, 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. Br J Dermatol. 2002;146 :816 –823[CrossRef][ISI][Medline]
  8. Fuller LC, Smith CH, Cerio R, et al. A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis. Br J Dermatol. 2001;144 :321 –327[CrossRef][ISI][Medline]
  9. Gupta AK, Adam P, Dlova N, et al. Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: griseofulvin versus the new oral antifungal agents, terbinafine, itraconazole, and fluconazole. Pediatr Dermatol. 2001;18 :433 –438[CrossRef][ISI][Medline]
  10. Cáceres-Ríos H, Rueda M, Ballona R, Bustamante B. Comparison of terbinafine and griseofulvin in the treatment of tinea capitis. J Am Acad Dermatol. 2000;42 :80 –84[CrossRef][ISI][Medline]
  11. Memisoglu HR, Erboz S, Akkaya S, 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. J Dermatol Treat. 1999;10 :189 –193
  12. Rademaker M, Havill S. Griseofulvin and terbinafine in the treatment of tinea capitis in children. N Z Med J. 1998;111 :55 –57[ISI][Medline]
  13. Haroon TS, Hussein I, Aman S, et al. A randomized double-blind, comparative study of terbinafine vs griseofulvin in tinea capitis. J Dermatol Treat. 1995;3 :167 –169
  14. Haroon TS, Hussein I, Aman S, et al. A randomized double-blind, comparative study of terbinafine vs griseofulvin in tinea capitis. J Dermatol Treat. 1992;3 :25 –27
  15. Bennett ML, Fleischer AB, Loveless JW, Feldman SR. Oral griseofulvin remains the treatment of choice for tinea capitis in children. Pediatr Dermatol. 2000;17 :304 –309[CrossRef][ISI][Medline]
  16. Dragos V, Lunder M. Lack of efficacy of 6-week treatment with oral terbinafine for tinea capitis due to Microsporum canis in children. Pediatr Dermatol. 1997;14 :46 –48[ISI][Medline]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics



This article has been cited by other articles:


Home page
 DTBHome page
Managing scalp ringworm in children.
DTB, December 1, 2007; 45(12): 89 - 92.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
D. M. Saunte, F. Simmel, N. Frimodt-Moller, L. B. Stolle, E. L. Svejgaard, M. Haedersdal, C. Kloft, and M. C. Arendrup
In Vivo Efficacy and Pharmacokinetics of Voriconazole in an Animal Model of Dermatophytosis
Antimicrob. Agents Chemother., September 1, 2007; 51(9): 3317 - 3321.
[Abstract] [Full Text] [PDF]

Home page
 JWatch PediatricsHome page
Treatment for Tinea Capitis: Griseofulvin or Terbinafine?
Journal Watch Pediatrics and Adolescent Medicine, November 29, 2004; 2004(1129): 3 - 3.
[Full Text]

Home page
 JWatch GeneralHome page
Treatment for Tinea Capitis: Griseofulvin or Terbinafine?
Journal Watch (General), November 16, 2004; 2004(1116): 1 - 1.
[Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fleece, D.
Right arrow Articles by Aronoff, S. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fleece, D.
Right arrow Articles by Aronoff, S. C.
Related Collections
Right arrow Infectious Disease & Immunity
Right arrowRelated AAP Red Book topics:
Tinea Capitis (Ringworm of the...