- Email: [email protected]
An open study of tinea capitis in 50 children treated with a 2-week course of oral terbinafine
An open study of tinea capitis in 50 children treated with a 2-week course of oral terbinafine Bernice Krafchik, MBChB, FRCPC,a and Janice Pelletier, MDb Toronto, Ontario, and Bangor, Maine Background: Terbinafine is used in the treatment of dermatophyte infections. There have been several studies suggesting a good response to terbinafine in treating tinea capitis, specifically with dermatophytes of the Trichophyton species. Methods: We enrolled 50 consecutive children with a clinical diagnosis of tinea capitis into an open study using terbinafine for 2 weeks. Results: Clinical and mycologic cure occurred in more than 86% of patients with no side effects and good compliance. Conclusion: In this study terbinafine was a safe and effective treatment of tinea capitis in children, particularly when caused by the Trichophyton species. (J Am Acad Dermatol 1999;41:60-3.)
T
erbinafine is a fungicidal allylamine that has been used effectively for the treatment of onychomycosis. Since 1992, there have been a series of articles summarizing its efficacy in treating tinea capitis.1,2 The dose has been based on adult scheduling, the length of treatment has varied from 1 to 8 weeks, and there have been no side effects. These reports prompted us to enroll 50 children with tinea capitis in a trial using a 2-week course of oral terbinafine treatment. After enrolling 29 patients who were followed up for 8 weeks, we considered this to be too short a follow-up period and increased the time to 12 weeks for the second group of 21 patients. Our results indicate that terbinafine is an effective, safe treatment particularly when used for the treatment of Trichophyton tonsurans infection. It has the advantage over other products of shorter treatment duration.
METHODS On their first visit, tinea capitis was diagnosed clinically in all 52 original patients by the presence of scale and/or hair loss, pustules, and kerion formation. Five had scaling
From the Division of Dermatology, The Hospital for Sick Children, University of Toronto,a and Penobscot Pediatrics, Bangor.b Reprints are not available from the authors. Correspondence: Bernice Krafchik, Division of Dermatology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/97685
60
in the scalp without hair loss, 42 had scaling and hair loss, and 5 had kerion formation. The enrollment included 1 white and 51 black children, of whom 35 were boys and 17 girls. The mean age was 7.6 years (range, 24 months to 18 years). They had a history of scalp lesions for an average of 4 months. Negative culture after treatment was considered a cure. Patients were assessed for lymphadenopathy and evidence of tinea corporis and id reactions. The majority had lymphadenopathy and 4 had id reactions before treatment. None of the patients had evidence of tinea corporis. On visit 1, hair/scale was taken either by pulling broken hairs or scraping scale for hyphal identification and fungal growth. Microscopy was done using 20% potassium hydroxide, and specimens were inoculated in inhibitory mold agar with ciprofloxacin and cycloheximide and then Sabouraud’s medium. Treatment with once-daily terbinafine was initiated after the clinical diagnosis but before culture results: 62.5 mg for those under 20 kg, 125 mg for children weighing 20 to 40 kg, and 250 mg for those over 40 kg. Most children fell within the 20 to 40 kg weight range, and tablets of 250 mg were broken in half and given daily with food for 2 weeks. Our first group consisted of 29 patients who returned at 2, 4, and 8 weeks (visits 2, 3, and 4). Two patients dropped out before their first return visit and were not included in the study although their initial culture was positive. In the second group, 21 patients were followed up at 2, 6, and 12 weeks (visits 2, 3, and 4). Clinical assessment, microscopy for hyphae, and fungal culture on hair or scale were performed at each visit. Blood work was obtained for hemoglobin, white blood cell count and differential, liver function tests (AST titer) and creatinine, 2 weeks after cessation of treatment in the first group (at 4 weeks), and
Krafchik and Pelletier 61
J AM A C A D D ERMATOL V OLUME 41, NUMBER 1
A
B Fig 1. Decrease in the number of positive cultures in group 1 (A) followed up for 8 weeks and group 2 (B) for 12 weeks.
immediately after finishing the course of treatment (at 2 weeks) in the second group.
RESULTS On their initial visit, microscopy for hyphae was positive in 32 of the 52 patients (Fig 1). Fungal culture was positive in 47 of 52 patients. T tonsurans was isolated from 41, T soudanense from 4, T violaceum from 1, and Microsporum audouinii from 1. One patient had a mixed infection, initially growing T tonsurans and on reculture M audouinii. Five patients were initially culture-negative; of these, 3 were positive for T tonsurans from scrapings taken on their second visit. Two patients remained culturenegative throughout the study although 1 of these had a kerion, a condition in which cultures are often negative, and the other was treated because of obvious clinical infection. At visit 2, 48 patients returned. Two patients withdrew from the study before their second visit. Two others missed their second visit but came subsequently, leaving 50 patients who completed the study. Reduction in the tenderness and size of all kerions was noted by the parents and patients with-
in 2 to 3 days of taking the medication. On examination less scale was seen in all patients, but no noticeable hair regrowth. Lymphadenopathy was markedly decreased. Seven patients had an id reaction on the face, upper chest, and back, consisting of small, flesh-colored papules. The results of samples taken on visit 2 showed hyphae in 10, with positive fungal growth in 32 and negative in 16 of the 48 patients. Forty-five patients returned at visit 3. There was a further decrease in scale, and flattening of lesions in those with kerions. Hair regrowth was seen in most patients. Microscopy for hyphae was positive in 5 patients and negative in 26. There was insufficient scale in 14 patients. Culture was positive in 10 patients and negative in 35. On the final visit at 8 weeks for group 1 and 12 weeks for group 2, 39 patients returned. Eleven patients did not come for their final visit, but 10 of these had been culture-negative at their third visit and all had shown some hair regrowth. Of the 39 patients, 2 had hyphae on microscopy, 26 were negative, and the remainder had insufficient scale. Fungal culture was positive in 7 and negative in 32.
62 Krafchik and Pelletier
Of the 50 patients who took the medication, 43 became culture-negative at the end of the study, giving a success rate of 86%. Of the remaining 7 patients, 3 who improved clinically became culturenegative on subsequent follow-up despite no further treatment, making the percentage success rate even higher for 2 weeks of treatment. Four were re-treated for another 2 weeks because of ongoing clinical evidence of infection (cultures from 2 of these grew M audouinii). Blood work was normal in 44 patients. Four patients refused blood work and 2 patients in 1 family had low white blood cell counts of 3.2 (109/L) after a viral illness at the time of treatment. These had both returned to normal within 1 month.
DISCUSSION Since the first release of terbinafine in the United Kingdom and Denmark in 1991, it has been used by more than 5 million people, mainly for the treatment of onychomycosis, with excellent cure rates and few adverse associated events.3 Terbinafine is a fungicidal allylamine that inhibits fungal cell squalene epoxidase, leading to the accumulation of fungal squalene.3 The drug is well absorbed both with food and on an empty stomach. It is keratophilic and lipophilic.4 The metabolism of terbinafine is similar in adults and children, but children have a shorter elimination half-life.1 Metabolism is slower in patients with liver disease, and in patients with impaired renal function it is excreted more slowly.4 In the doses that were used in our treatment regimen, the concentration remaining in hair 50 days after cessation of treatment is sufficient for continued fungicidal activity.4 This would account for many of the fungal cultures becoming negative despite no further treatment. Despite positive microscopy, fungal elements may be nonviable; the only certain criterion of continued infection is a positive fungal culture. Between 1992 and 1997 there were several reports of various regimens using terbinafine for the treatment of tinea capitis in children and adults.2 Since this review, other studies on the use of terbinafine for treating tinea capitis in children have been reported.5-8 The results of oral terbinafine monotherapy for the Trichophyton species have been excellent.5.6 Our study has shown similar results with a 2-week course of treatment. Improvement occurred in all clinical parameters and mycologic cure was obtained in 86% of cases. This is a conservative estimate because 3 other patients became culture-negative on further follow-up and no treatment. This probably reflects the overwhelming predominance of Trichophyton species seen in North America. In our study of 50 patients it was nec-
J AM A C A D D ERMATOL JULY 1999
essary to re-treat only 4 patients who remained culture-positive. Two of these were infected with M audouinii and required re-treatment for a further 2 weeks. Treatment of the Microsporum species with oral terbinafine has not been as successful as with the Trichophyton species.7 The adverse events associated with oral terbinafine are few. In our series, the results of blood work were normal except in 2 children who had low white blood cell counts with neutropenia. This was thought to be due to a preceding viral infection, and counts returned to normal in 1 month. Side effects that are commonly cited,3 such as taste impairment and gastrointestinal complaints, were not seen in our series, probably because of the short duration of treatment. Seven patients experienced id reactions when terbinafine was first started, but the lesions cleared rapidly with continued treatment and would presumably have occurred with any effective treatment. Treatment regimens with terbinafine have varied from 1 to 8 weeks with continuous or pulsed therapy. Our results indicate that a 2 week course of continuous therapy is sufficient for treating T tonsurans infection. In our institution, the cost of 2 weeks of terbinafine is equivalent to the cost of 6 weeks of treatment with griseofulvin, but compliance is an important issue in patients who must take medication for 6 to 8 weeks. It is an added benefit to have a treatment schedule that is as short as possible. Although successful, it is not warranted to use terbinafine in a pulsed dosage because this merely prolongs treatment in an often noncompliant population.9 It is difficult to compare the clinical parameters of cure between terbinafine, griseofulvin, and the azoles. Scale, hair loss, erythema, and kerion vary considerably among patients. In addition, hair regrowth in an area of alopecia often takes upwards of 10 weeks, whether or not mycological cure takes place at an early stage. There have been several studies using the azoles, initially comparing ketoconazole and griseofulvin with equivocal results.10,11 Ketoconazole treatment may be complicated by liver function abnormalities and is therefore not widely used in this indication.12 Recently, itraconazole, a second-generation azole, has been used in the treatment of tinea capitis, both continuously13,14 and as pulsed therapy.15,16 Despite the azoles being fungistatic, the cure rate, particularly with the Trichophyton species, was equal to terbinafine in one study13 and less successful in another despite 1 month’s treatment.14 It was also less successful in treating Microsporum infections.13 Fluconazole17,18 had a success rate greater than 85%, but the cost of the medication for 20 days is much higher than terbinafine for a 2-week course. The
J AM A C A D D ERMATOL V OLUME 41, NUMBER 1
action of the azoles is through the P-450 cytochrome enzyme pathway, making drug interactions a real possibility. In conclusion, our experience with 2 weeks of terbinafine therapy in children with tinea capitis is encouraging. The cure rate was excellent, compliance was good, and adverse events minimal. Given the fact that Trichophyton species are the predominant fungi causing tinea capitis in Canada and the United States, we propose a 2-week course of terbinafine treatment while awaiting the result of the fungal culture, and we suggest that an additional 2 weeks be considered if a member of the Microsporum genus is isolated. The terbinafine tablets were provided by Novartis Pharma Canada, Inc. REFERENCES 1. Jones TC. Overview of the use of terbinafine (Lamisil) in children. Br J Dermatol 1995;132:683-9. 2. Krafchik BR. The clinical efficacy of terbinafine in the treatment of tinea capitis. Rev Contemp Pharmacother 1997;8:313-24. 3. Gupta AK, Shear NH. Terbinafine: an update. J Am Acad Dermatol 1997;37:979-88. 4. Faergemann J. Pharmacokinetics of terbinafine. Rev Contemp Pharmacother 1997;8:289-97. 5. Kullavanijaya P, Reangchainam S, Ungpakorn R. Randomized single-blind study of efficacy and tolerability of terbinafine in the treatment of tinea capitis. J Am Acad Dermatol 1997;37: 272-3.
Krafchik and Pelletier 63
6. Gupta AK, Adam P.Terbinafine pulse therapy is effective in tinea capitis. Pediatr Dermatol 1998;15:56-8. 7. 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;14:46-8. 8. Rademaker M, Havill S. Griseofulvin and terbinafine in the treatment of tinea capitis in children. N Z Med J 1998;111:55-7. 9. Gupta AK, Adam P. Terbinafine pulse therapy is effective in treating tinea capitis. Pediatr Dermatol 1998;15:56-8. 10. Gan VN, Petruska M, Ginsburg CM. Epidemiology and treatment of tinea capitis: ketoconazole versus griseofulvin. Pediatr Infect Dis J 1987;6:46-9. 11. Tanz RR, Herbert A, Burton-Esterly N. Treating tinea capitis. Should ketoconazole replace griseofulvin? J Pediatr 1988;112: 987-91. 12. Abdel-Rahman SM, Nahata MC. Treatment of tinea capitis. Ann Pharmacother 1997;31:338-48. 13. Abdel-Rahman SM, Powell DA, Nahata MC. Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis. J Am Acad Dermatol 1998;38:443-6. 14. Degreef H. Itraconazole in the treatment of tinea capitis. Cutis 1996;58:90-3. 15. Gupta AK, Alexis ME, Raboobee N, Hofstader SL, Lynde CW, Adam P, et al. Itraconazole pulse therapy is effective in the treatment of tinea capitis in children: an open multicentre study. Br J Dermatol 1997;137:251-4. 16. Gupta AK, Adam P. Itraconazole pulse therapy for tinea capitis: a novel treatment. Pediatr Dermatol 1998;15:225-8. 17. Solomon BA, Collins R, Sharma R, Silverberg N, Jain AR, Sedgh J, et al. Fluconazole for the treatment of tinea capitis in children. J Am Acad Dermatol 1997;37:274-5. 18. Mercurio MG, Silverman RA, Elewski BE. Tinea capitis: fluconazole in Trichophyton tonsurans infection. Pediatr Dermatol 1998;15:229-33.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the Journal of the American Academy of Dermatology are available to subscribers (only) for the 1999 issues from the Publisher at a cost of $123.00 for domestic, $151.94 for Canadian, and $142.00 for international for volume 40 (January-June) and volume 41 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Inc., Periodical Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318. USA: phone (800) 453-4351; (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.
T
erbinafine is a fungicidal allylamine that has been used effectively for the treatment of onychomycosis. Since 1992, there have been a series of articles summarizing its efficacy in treating tinea capitis.1,2 The dose has been based on adult scheduling, the length of treatment has varied from 1 to 8 weeks, and there have been no side effects. These reports prompted us to enroll 50 children with tinea capitis in a trial using a 2-week course of oral terbinafine treatment. After enrolling 29 patients who were followed up for 8 weeks, we considered this to be too short a follow-up period and increased the time to 12 weeks for the second group of 21 patients. Our results indicate that terbinafine is an effective, safe treatment particularly when used for the treatment of Trichophyton tonsurans infection. It has the advantage over other products of shorter treatment duration.
METHODS On their first visit, tinea capitis was diagnosed clinically in all 52 original patients by the presence of scale and/or hair loss, pustules, and kerion formation. Five had scaling
From the Division of Dermatology, The Hospital for Sick Children, University of Toronto,a and Penobscot Pediatrics, Bangor.b Reprints are not available from the authors. Correspondence: Bernice Krafchik, Division of Dermatology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/97685
60
in the scalp without hair loss, 42 had scaling and hair loss, and 5 had kerion formation. The enrollment included 1 white and 51 black children, of whom 35 were boys and 17 girls. The mean age was 7.6 years (range, 24 months to 18 years). They had a history of scalp lesions for an average of 4 months. Negative culture after treatment was considered a cure. Patients were assessed for lymphadenopathy and evidence of tinea corporis and id reactions. The majority had lymphadenopathy and 4 had id reactions before treatment. None of the patients had evidence of tinea corporis. On visit 1, hair/scale was taken either by pulling broken hairs or scraping scale for hyphal identification and fungal growth. Microscopy was done using 20% potassium hydroxide, and specimens were inoculated in inhibitory mold agar with ciprofloxacin and cycloheximide and then Sabouraud’s medium. Treatment with once-daily terbinafine was initiated after the clinical diagnosis but before culture results: 62.5 mg for those under 20 kg, 125 mg for children weighing 20 to 40 kg, and 250 mg for those over 40 kg. Most children fell within the 20 to 40 kg weight range, and tablets of 250 mg were broken in half and given daily with food for 2 weeks. Our first group consisted of 29 patients who returned at 2, 4, and 8 weeks (visits 2, 3, and 4). Two patients dropped out before their first return visit and were not included in the study although their initial culture was positive. In the second group, 21 patients were followed up at 2, 6, and 12 weeks (visits 2, 3, and 4). Clinical assessment, microscopy for hyphae, and fungal culture on hair or scale were performed at each visit. Blood work was obtained for hemoglobin, white blood cell count and differential, liver function tests (AST titer) and creatinine, 2 weeks after cessation of treatment in the first group (at 4 weeks), and
Krafchik and Pelletier 61
J AM A C A D D ERMATOL V OLUME 41, NUMBER 1
A
B Fig 1. Decrease in the number of positive cultures in group 1 (A) followed up for 8 weeks and group 2 (B) for 12 weeks.
immediately after finishing the course of treatment (at 2 weeks) in the second group.
RESULTS On their initial visit, microscopy for hyphae was positive in 32 of the 52 patients (Fig 1). Fungal culture was positive in 47 of 52 patients. T tonsurans was isolated from 41, T soudanense from 4, T violaceum from 1, and Microsporum audouinii from 1. One patient had a mixed infection, initially growing T tonsurans and on reculture M audouinii. Five patients were initially culture-negative; of these, 3 were positive for T tonsurans from scrapings taken on their second visit. Two patients remained culturenegative throughout the study although 1 of these had a kerion, a condition in which cultures are often negative, and the other was treated because of obvious clinical infection. At visit 2, 48 patients returned. Two patients withdrew from the study before their second visit. Two others missed their second visit but came subsequently, leaving 50 patients who completed the study. Reduction in the tenderness and size of all kerions was noted by the parents and patients with-
in 2 to 3 days of taking the medication. On examination less scale was seen in all patients, but no noticeable hair regrowth. Lymphadenopathy was markedly decreased. Seven patients had an id reaction on the face, upper chest, and back, consisting of small, flesh-colored papules. The results of samples taken on visit 2 showed hyphae in 10, with positive fungal growth in 32 and negative in 16 of the 48 patients. Forty-five patients returned at visit 3. There was a further decrease in scale, and flattening of lesions in those with kerions. Hair regrowth was seen in most patients. Microscopy for hyphae was positive in 5 patients and negative in 26. There was insufficient scale in 14 patients. Culture was positive in 10 patients and negative in 35. On the final visit at 8 weeks for group 1 and 12 weeks for group 2, 39 patients returned. Eleven patients did not come for their final visit, but 10 of these had been culture-negative at their third visit and all had shown some hair regrowth. Of the 39 patients, 2 had hyphae on microscopy, 26 were negative, and the remainder had insufficient scale. Fungal culture was positive in 7 and negative in 32.
62 Krafchik and Pelletier
Of the 50 patients who took the medication, 43 became culture-negative at the end of the study, giving a success rate of 86%. Of the remaining 7 patients, 3 who improved clinically became culturenegative on subsequent follow-up despite no further treatment, making the percentage success rate even higher for 2 weeks of treatment. Four were re-treated for another 2 weeks because of ongoing clinical evidence of infection (cultures from 2 of these grew M audouinii). Blood work was normal in 44 patients. Four patients refused blood work and 2 patients in 1 family had low white blood cell counts of 3.2 (109/L) after a viral illness at the time of treatment. These had both returned to normal within 1 month.
DISCUSSION Since the first release of terbinafine in the United Kingdom and Denmark in 1991, it has been used by more than 5 million people, mainly for the treatment of onychomycosis, with excellent cure rates and few adverse associated events.3 Terbinafine is a fungicidal allylamine that inhibits fungal cell squalene epoxidase, leading to the accumulation of fungal squalene.3 The drug is well absorbed both with food and on an empty stomach. It is keratophilic and lipophilic.4 The metabolism of terbinafine is similar in adults and children, but children have a shorter elimination half-life.1 Metabolism is slower in patients with liver disease, and in patients with impaired renal function it is excreted more slowly.4 In the doses that were used in our treatment regimen, the concentration remaining in hair 50 days after cessation of treatment is sufficient for continued fungicidal activity.4 This would account for many of the fungal cultures becoming negative despite no further treatment. Despite positive microscopy, fungal elements may be nonviable; the only certain criterion of continued infection is a positive fungal culture. Between 1992 and 1997 there were several reports of various regimens using terbinafine for the treatment of tinea capitis in children and adults.2 Since this review, other studies on the use of terbinafine for treating tinea capitis in children have been reported.5-8 The results of oral terbinafine monotherapy for the Trichophyton species have been excellent.5.6 Our study has shown similar results with a 2-week course of treatment. Improvement occurred in all clinical parameters and mycologic cure was obtained in 86% of cases. This is a conservative estimate because 3 other patients became culture-negative on further follow-up and no treatment. This probably reflects the overwhelming predominance of Trichophyton species seen in North America. In our study of 50 patients it was nec-
J AM A C A D D ERMATOL JULY 1999
essary to re-treat only 4 patients who remained culture-positive. Two of these were infected with M audouinii and required re-treatment for a further 2 weeks. Treatment of the Microsporum species with oral terbinafine has not been as successful as with the Trichophyton species.7 The adverse events associated with oral terbinafine are few. In our series, the results of blood work were normal except in 2 children who had low white blood cell counts with neutropenia. This was thought to be due to a preceding viral infection, and counts returned to normal in 1 month. Side effects that are commonly cited,3 such as taste impairment and gastrointestinal complaints, were not seen in our series, probably because of the short duration of treatment. Seven patients experienced id reactions when terbinafine was first started, but the lesions cleared rapidly with continued treatment and would presumably have occurred with any effective treatment. Treatment regimens with terbinafine have varied from 1 to 8 weeks with continuous or pulsed therapy. Our results indicate that a 2 week course of continuous therapy is sufficient for treating T tonsurans infection. In our institution, the cost of 2 weeks of terbinafine is equivalent to the cost of 6 weeks of treatment with griseofulvin, but compliance is an important issue in patients who must take medication for 6 to 8 weeks. It is an added benefit to have a treatment schedule that is as short as possible. Although successful, it is not warranted to use terbinafine in a pulsed dosage because this merely prolongs treatment in an often noncompliant population.9 It is difficult to compare the clinical parameters of cure between terbinafine, griseofulvin, and the azoles. Scale, hair loss, erythema, and kerion vary considerably among patients. In addition, hair regrowth in an area of alopecia often takes upwards of 10 weeks, whether or not mycological cure takes place at an early stage. There have been several studies using the azoles, initially comparing ketoconazole and griseofulvin with equivocal results.10,11 Ketoconazole treatment may be complicated by liver function abnormalities and is therefore not widely used in this indication.12 Recently, itraconazole, a second-generation azole, has been used in the treatment of tinea capitis, both continuously13,14 and as pulsed therapy.15,16 Despite the azoles being fungistatic, the cure rate, particularly with the Trichophyton species, was equal to terbinafine in one study13 and less successful in another despite 1 month’s treatment.14 It was also less successful in treating Microsporum infections.13 Fluconazole17,18 had a success rate greater than 85%, but the cost of the medication for 20 days is much higher than terbinafine for a 2-week course. The
J AM A C A D D ERMATOL V OLUME 41, NUMBER 1
action of the azoles is through the P-450 cytochrome enzyme pathway, making drug interactions a real possibility. In conclusion, our experience with 2 weeks of terbinafine therapy in children with tinea capitis is encouraging. The cure rate was excellent, compliance was good, and adverse events minimal. Given the fact that Trichophyton species are the predominant fungi causing tinea capitis in Canada and the United States, we propose a 2-week course of terbinafine treatment while awaiting the result of the fungal culture, and we suggest that an additional 2 weeks be considered if a member of the Microsporum genus is isolated. The terbinafine tablets were provided by Novartis Pharma Canada, Inc. REFERENCES 1. Jones TC. Overview of the use of terbinafine (Lamisil) in children. Br J Dermatol 1995;132:683-9. 2. Krafchik BR. The clinical efficacy of terbinafine in the treatment of tinea capitis. Rev Contemp Pharmacother 1997;8:313-24. 3. Gupta AK, Shear NH. Terbinafine: an update. J Am Acad Dermatol 1997;37:979-88. 4. Faergemann J. Pharmacokinetics of terbinafine. Rev Contemp Pharmacother 1997;8:289-97. 5. Kullavanijaya P, Reangchainam S, Ungpakorn R. Randomized single-blind study of efficacy and tolerability of terbinafine in the treatment of tinea capitis. J Am Acad Dermatol 1997;37: 272-3.
Krafchik and Pelletier 63
6. Gupta AK, Adam P.Terbinafine pulse therapy is effective in tinea capitis. Pediatr Dermatol 1998;15:56-8. 7. 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;14:46-8. 8. Rademaker M, Havill S. Griseofulvin and terbinafine in the treatment of tinea capitis in children. N Z Med J 1998;111:55-7. 9. Gupta AK, Adam P. Terbinafine pulse therapy is effective in treating tinea capitis. Pediatr Dermatol 1998;15:56-8. 10. Gan VN, Petruska M, Ginsburg CM. Epidemiology and treatment of tinea capitis: ketoconazole versus griseofulvin. Pediatr Infect Dis J 1987;6:46-9. 11. Tanz RR, Herbert A, Burton-Esterly N. Treating tinea capitis. Should ketoconazole replace griseofulvin? J Pediatr 1988;112: 987-91. 12. Abdel-Rahman SM, Nahata MC. Treatment of tinea capitis. Ann Pharmacother 1997;31:338-48. 13. Abdel-Rahman SM, Powell DA, Nahata MC. Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis. J Am Acad Dermatol 1998;38:443-6. 14. Degreef H. Itraconazole in the treatment of tinea capitis. Cutis 1996;58:90-3. 15. Gupta AK, Alexis ME, Raboobee N, Hofstader SL, Lynde CW, Adam P, et al. Itraconazole pulse therapy is effective in the treatment of tinea capitis in children: an open multicentre study. Br J Dermatol 1997;137:251-4. 16. Gupta AK, Adam P. Itraconazole pulse therapy for tinea capitis: a novel treatment. Pediatr Dermatol 1998;15:225-8. 17. Solomon BA, Collins R, Sharma R, Silverberg N, Jain AR, Sedgh J, et al. Fluconazole for the treatment of tinea capitis in children. J Am Acad Dermatol 1997;37:274-5. 18. Mercurio MG, Silverman RA, Elewski BE. Tinea capitis: fluconazole in Trichophyton tonsurans infection. Pediatr Dermatol 1998;15:229-33.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the Journal of the American Academy of Dermatology are available to subscribers (only) for the 1999 issues from the Publisher at a cost of $123.00 for domestic, $151.94 for Canadian, and $142.00 for international for volume 40 (January-June) and volume 41 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Inc., Periodical Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318. USA: phone (800) 453-4351; (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.