Short duration treatment with terbinafine for tinea capitiscaused by Trichophyton or Microsporum species

H.HAMM, A.SCHWINN, M.BRAUTIGAM,* G.WEIDINGER* AND THE STUDY GROUP†Department of Dermatology, University of Wurzburg, Wurzburg, Germany*Clinical Research, Novartis Pharma GmbH, Roonstraße 25, 90429 Nuremberg, Germany

Accepted for publication 27 August 1998

Summary Thirty-five patients with mycologically proven scalp infections were enrolled in a randomized,double-blind clinical trial with oral terbinafine (dose adjusted according to patient weight) for either1 or 2 weeks. Patients were observed for 12 weeks; after 4 weeks, non-responders were offered anadditional 4 weeks of treatment followed by a second observation period. The causative organismswere Microsporum canis (n ¼ 12), Trichophyton tonsurans (n ¼ 12) and other Trichophyton spp.(n ¼ 11). The Trichophyton infections were treated effectively in five of nine (56%) patients treatedfor 1 week and 12 of 14 (86%) patients treated for 2 weeks. Three of the non-responders were treatedfor an additional 4 weeks, and one responded. In the Microsporum group only one of seven patientstreated for 1 week and none of five treated for 2 weeks responded. However, treatment was effective infour of six (66%) patients treated for an additional 4 weeks. Mild to moderate adverse events believedto be drug related occurred in four patients in each of the two groups. Terbinafine is well tolerated,and requires 2 weeks of treatment in most patients with Trichophyton scalp infections and 4 weeks ormore in Microsporum scalp infections, to achieve a successful clinical and mycological response.

Keywords: Microsporum canis, terbinafine, tinea capitis, Trichophyton species

In the past, tinea capitis has required prolonged oraltreatment (6–12 weeks) with griseofulvin.1 Infectionswith Microsporum spp. required longer treatment thanthose with Trichophyton.2 Terbinafine is a highly effec-tive antifungal drug for topical and oral use in cuta-neous dermatophyte infections,3 and is well toleratedand effective in children.4 Although the presently recom-mended course of treatment of tinea capitis is 4 weeks fororal terbinafine, shorter treatment times may be possible.5

To investigate this possibility, and to provide data on theresponsiveness of different species of dermatophytes, amulticentre, randomized clinical trial of terbinafine wasperformed in patients with tinea capitis. We comparedtreatment times of 1 or 2 weeks, and non-responderswere offered an additional 4 weeks of treatment.

Materials and methods

Thirty-five patients with clinically diagnosed tinea

capitis were enrolled for treatment in eight centres inGermany. Sixteen patients received 1 week of treatmentwith terbinafine and 19 patients received 2 weeks of treat-ment. Because of insufficient response after 4 weeks, ninepatients were treated for a further 4 weeks. Patients weregiven oral terbinafine at a daily dose according to theirweight: 10–20 kg, 62·5 mg; 20–40 kg, 125 mg; over40 kg, 250 mg (the full adult dose).

At a baseline visit, the extent and severity of theinfection was recorded for each patient, with mycologi-cal confirmation by microscopy of scrapings and cultureon Sabouraud’s agar. Clinical signs and symptoms wereevaluated by scoring the degree of erythema, scaling,hair loss, pustules and deep tissue inflammation on aseven-point scale. The scores were totalled to yield anoverall severity score for each patient at baseline andduring the study period. Clinical and mycologicalassessments were repeated at weeks 1, 2, 4 and 12after the start of treatment. Effective treatment wasdefined as negative microscopy and culture for derma-tophytes and a decrease in the clinical signs and symp-toms to a total score # 2, excluding hair loss, which isknown to require several months to return to normal, ifat all, after the infection has been successfully treated.

British Journal of Dermatology 1999; 140: 480–482.

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Correspondence: Matthias Brautigam.†The study group comprises S.Wever, B.Hornschuh (Wurzburg),K.Grunder, P.Mayser (Gießen), G.Falker (Frankenberg), J.Knop,B.Morsches, R.Schopf (Mainz), E.Schopf, A.Pfister-Wartha (Freiburg),F.A.Bahmer, J.Ponnighaus (Homburg), R.Happle, C.Enschede(Marburg), S.Borelli and H.Hoffmann (Munchen).

Complete cure was recorded when all signs andsymptoms except alopecia had disappeared. An evalua-tion of efficacy and tolerability was made at the end ofthe 12-week study period. Adverse events were recordedat each visit and haematological and biological testingwas done at baseline and at the end of treatment. After4 weeks without significant improvement, patients wereoffered a second treatment course lasting 4 weeks fol-lowed by an 8-week observation period.

Data were summarized as mean 6 SD. Statisticalcomparisons of effective treatment and complete curewere done using the two-tailed Fisher’s exact test. Thestudy was approved by an independent ethics committeeand was performed according to the guidelines of theDeclaration of Helsinki. All patients or their parents/guardians gave their informed consent before they wererecruited.

Results

The study population comprised 35 patients (16 males,19 females, mean 6 SD age 9·3 6 7·8 years, mean 6 SDweight 28·5 6 15·9 kg). Causative organisms were M.canis (seven patients treated for 1 week þ five treated for2 weeks), T. tonsurans (six þ six), T. violaceum (one þ

five), T. mentagrophytes (two þ one), T. soudanense(none þ one) and T. verrucosum (none þ one). Changesin mycological results (culture) for infections with Tri-chophyton spp. during the study period are shown inFigure 1. Most infections with Trichophyton spp. weretreated successfully by 1 or 2 weeks of treatment withterbinafine: only three of 23 patients failed to be myco-logically cured. Two had a T. tonsurans and one a T.soudanense infection. In comparison, only one of 12patients with an M. canis infection was cured mycolo-gically by short course treatment. Six of the 12 patientsentered the re-treatment period of 4 weeks, and four ofthem were mycologically cured.

In patients with Trichophyton infections the signs andsymptoms score decreased during the observationperiod from 12·9 to 3·8 with 1 week of treatment andfrom 11·3 to 0·6 with 2 weeks of treatment. Patientswith Microsporum infection did not greatly benefit from1 or 2 weeks of treatment, with a decrease in symptomscore at week 4 from 12·1 to 8·0 in the 1-week groupand from 15·2 to 11·4 in the 2-week group. However,with an additional 4 weeks of treatment the symptomscore decreased from 12·3 to 2·0 in six patients. Table 1shows the overall efficacy at the end of the 12-weekstudy period for each duration of treatment. These dataconfirm that 2 weeks of treatment is suitable to curemost Trichophyton scalp infections, whereas in M. canisacceptable cure rates can be achieved only after anadditional 4-week course of treatment.

There were adverse events recorded in four patients ineach of the two treatment groups (1 and 2 weeksterbinafine). The following are believed to be drugrelated: in the 1-week treatment group, abdominalpain (one patient), abdominal pain and epistaxis (one),lack of appetite, headache and facial oedema (one), andcoughing and fever (one). All events were mild tomoderate, except for the headache, which was recordedas severe. Adverse events in the 2-week treatment groupwere abdominal pain (one patient), abdominal pain andfatigue (one), nausea, dyspepsia and headache (one),and fever (one). One additional patient reported lack ofappetite and gastroenteritis only during the additional4-week treatment period. Haematological and biochem-ical parameters remained normal.

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q 1999 British Association of Dermatologists, British Journal of Dermatology, 140, 480–482

Figure 1. Percentage of positive culture results at evaluation times inTrichophyton infections.

Table 1. Overall efficacy of terbinafine treatment in 35 patients withtinea capitis

No. (%) No. (%)Treatment group effective treatmenta complete cureb

Trichophyton species1 week terbinafine 5/9 (56%) 4/9 (44%)2 weeks terbinafine 12/14 (86%)c 9/14 (64%)d

4 weeks terbinafinee 1/3 (33%) 1/3 (33%)Microsporum species

1 week terbinafine 1/7 (14%) 0/5 (0%)2 weeks terbinafine 0/5 (0%) 0/7 (0%)4 weeks terbinafinee 4/6 (66%) 2/6 (33%)

a Defined as negative mycological tests and a signs and symptoms score# 2, excluding hair loss; b defined as negative mycology and no clinicalsymptoms except alopecia; c 1 week terbinafine vs. 2 weeks terbinafine:P ¼ 0·181; d 1 week terbinafine vs. 2 weeks terbinafine: P ¼ 0·293;e non-responder group to 1–2 weeks of treatment who were treated foran additional 4 weeks.

Discussion

This study confirms that terbinafine is effective and safein the treatment of tinea capitis, as demonstrated inearlier studies4,6,7 mainly investigating Trichophytonscalp infections. Based on these data and the results ofthe present study, a treatment period of 2 weeks isrecommended if the causative organism is a Trichophy-ton sp. However, >50% of the patients were successfullytreated by only 1 week of terbinafine, and future studiesshould try to identify factors such as disease extent,patient age and dermatophyte species that will enableselection of patients likely to be cured by a 1-weektreatment. It has been suggested that Microsporumspp. are more difficult to treat with previously usedantifungal drugs2 as well as with terbinafine.4,8 Thedifference in clinical response cannot be explained by alower susceptibility of Microsporum spp. to antimycoticssuch as terbinafine, but may be related to the ectothrixinfection pattern of Microsporum spp. as opposed to theendothrix pattern associated with the genus Tricho-phyton, with a consequently decreased accessibility ofantimycotics to the fungal spores.

In our study, most patients with Microsporum infec-tions responded only to an additional 4-week treatmentcourse of terbinafine, 2–3 weeks after an initial courseof 1 or 2 weeks. It is unclear whether the response isdetermined by the cumulative dose of terbinafine, by thenumber of treatment days or by the total duration oftreatment including off-treatment periods. We suggestthe following procedure for the treatment of tineacapitis with terbinafine: if a Trichophyton sp. is identifiedin the pretreatment culture, terbinafine should be dis-continued after 2 weeks of treatment. If the pathogen isa Microsporum sp. or cannot be identified, therapyshould be stopped after 4 weeks if there is considerableclinical improvement, and after 8 weeks if there isonly minor improvement at week 4. In case of relapse orclinical deterioration, another 4-week course of

terbinafine is recommended. It usually takes 4–8 weeksfor cultures to become negative after discontinuation oftreatment, and topical antifungal therapy for 4 weeksshould be considered to prevent disease transmission.Because these recommendations are based on limiteddata, further studies on duration of treatment withterbinafine in Microsporum scalp infections are needed.

Acknowledgments

We thank G.Petry, Seligenstadt, V.Lehnert, Gießen, andU.Geißler and M.Bauer, Nuremberg, who were respon-sible for monitoring and logistics, and T.C.Jones for helpin manuscript preparation. The study was supportedby a grant from Sandoz AG Nuremberg, Germany (nowNovartis Pharma GmbH). M.Brautigam and G.Weidin-ger are employees of Novartis Pharma GmbH.

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