- Email: [email protected]
Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis
Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis Susan M. Abdel-Rahman, PharmD,a Dwight A. Powell, MD,c and Milap C. Nahata, PharmDb Columbus, Ohio Background: Tinea capitis is prevalent in children. Although widely used as the drug of choice, the response to griseofulvin may be incomplete and an extended duration of therapy is often required. The response to newer antifungals has not been methodically evaluated in children with Trichophyton tonsurans infection. Objective: Our purpose was to determine the efficacy of itraconazole in children with tinea capitis caused by T. tonsurans. Methods: Pediatric patients with culture proven tinea capitis were enrolled from a hospital-based primary care clinic between January and December of 1996. Patients were treated with itraconazole 100 mg/day and a selenium sulfide–containing shampoo for 4 weeks. Children were evaluated mycologically and clinically every 2 weeks for 2 months. Patients were considered successfully treated if they were culture negative and clinically improved at the end of the study period. Children who remained culture positive or who were clinically not improved at 2 months were classified as treatment failures and retreated. Results: Twenty-five patients completed the study, and 10 (40%) were successfully treated. Fifteen children required re-treatment: 14 remained culture positive at week 8, and one was mycologically negative but clinically worse. Conclusion: Itraconazole at a dose of 100 mg/day for 4 weeks may be effective in less than half of children with T. tonsurans tinea capitis. (J Am Acad Dermatol 1998;38:443-6.)
Despite the availability of oral antifungal therapy for the treatment of tinea capitis, this infection remains prevalent in children.1 The current drug of choice in treating tinea capitis is griseofulvin, 10 to 20 mg/kg daily often for 6 to 8 weeks in combination with a selenium sulfide–containing shampoo2; however, treatment failure is not uncommon.3-5 Although response rates in controlled trials have ranged from 80% to 90%,6-9 response rates in a clinical setting may be significantly lower, possibly because of noncompliance,
From College of Pharmacy,a,b Department of Pediatrics,b,c Wexner Institute for Pediatric Research, and the Section of Infectious Diseases,a,b,c Ohio State University and Children's Hospital. Supported in part by the National Institute for Child Health and Human Development Pediatric Pharmacology Research Unit, grant HD 31316. Reprint requests: Milap C. Nahata, PharmD, College of Pharmacy, Ohio State University, 500 W. 12th Ave., Columbus, OH 43210. *Susan M. Abdel-Rahman, PharmD, is now Assistant Professor of Pharmacy and Pediatrics at the University of Missouri–Kansas City. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87652
inadequate drug absorption, reexposure or resistance.10 Newer agents with potentially shorter durations of therapy continue to be evaluated. Itraconazole appeared to demonstrate good efficacy in the treatment of tinea capitis in several case reports and a few clinical trials.3,7,11-13 However, the majority of patients enrolled in controlled clinical trials were infected with pathogens other than Trichophyton tonsurans, the primary pathogen in the United States.7,11,13 Because itraconazole is highly effective in vitro and achieves high and prolonged concentrations in keratinous tissue, it is currently being considered as an alternative to griseofulvin in the United States for the treatment of superficial fungal infections.14,15 The objective of this study was to evaluate the clinical and mycologic efficacy of itraconazole given for 1 month in an open label fashion for the treatment of T. tonsurans tinea capitis in children. METHODS This study was approved by the Human Subjects
443
444 Abdel-Rahman, Powell, and Nahata
Fig. 1. Mean clinical severity score, from baseline through 2 months' follow-up, in children with tinea capitis receiving 1 month of itraconazole therapy. Research Committee at our institution. A written informed consent was obtained from a parent or guardian before enrollment of each child, and assent was obtained from the child when applicable. Patients older than 1 year of age were enrolled during a 12month period from the primary care clinic of a large urban pediatric hospital. Fungal specimens were collected by gently massaging the scalp lesion with a sterile toothbrush (Oral-B) and planting the inoculum on Saboraud's agar with chloramphenicol and cycloheximide (Mycosel, BBL). This technique was selected because, in our experience, it is less threatening to the child and provides a greater inoculum for culture than pulling hairs from the border of the lesion. To prevent bias in interpretation, mycologic identification was performed by personnel unaware of the clinical findings or the status of treatment in patients. Clinical severity was determined as previously described16 by evaluation of alopecia, scaling, crusting, erythema, inflammation, adenopathy, pain, and itching on a scale from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each finding. Thus a score of 0 would represent no discernible disease and a score of 24 would reflect the most severe disease. Patients were prescribed itraconazole (Sporanox, Janssen Pharmaceutica) 100 mg/day and a selenium sulfide–containing shampoo for 1 month. Patients unable to swallow the capsule were instructed to open it and mix the contents with a small amount of soft food such as pudding or applesauce. All patients were instructed to take the daily dose with a meal. Compliance was evaluated by asking the parent, and by pill counts at the 2- and 4-week visit. Noncompliance was defined as greater than or equal to two missed doses per week or four doses per follow-up visit. Patients were observed by the same investigators every 2 weeks during therapy and at 2 and 4 weeks posttherapy. Fungal cultures were performed and a
Journal of the American Academy of Dermatology March 1998
Fig. 2. Mycologic response measured out to 2 months in children receiving 1 month of itraconazole therapy.
clinical severity score calculated at the time of all visits. Patients were considered successfully treated if cultures became negative and clinical symptoms were alleviated. Clinical improvement was defined as no or mild residual signs and symptoms (with the exception of alopecia, which was expected to clear more slowly). Patients who remained culture positive or were culture negative but clinically unchanged or worse at week 8 were considered treatment failures and subsequently re-treated at the physician's discretion. Statistical significance was determined for baseline and follow-up clinical response by means of a twotailed paired t test. A 95% confidence interval was calculated for overall response rate. A Cox proportional hazard test was used to determine whether response was a function of age. A chi-square test was used to determine whether response was a function of gender. Statistical significance was defined by a p value of less than 0.05. RESULTS
A total of 25 children completed the study. The age of patients completing the study ranged from 1.5 to 11 years (mean, 5.3 ± 2.7 years). The majority were male (80%) and African-American (100%). The mean clinical severity score at the time of enrollment was 7.3 ± 4.0, with a median of 7. The mean score improved to 6.2 at week 2, 4.9 at week 4, 4.2 at week 6, and 4.0 at week 8 (Fig. 1). The mean clinical severity score at each visit was significantly lower than the initial mean score (p < 0.05). Mean scores also improved significantly between weeks 2 and 4; however, there was no significant difference in mean scores between weeks 4 through 8.
Journal of the American Academy of Dermatology Volume 38, Number 3
At the end of the study period, 11 patients (44%) were mycologically negative. Cumulative percentage of mycologic cure was 3% at week 2, 10% at week 4, 31% at week 6, and 44% at week 8 (Fig. 2). Fourteen patients remained culture positive. One patient who was mycologically negative at the end of the study, however, had significant worsening of clinical lesions and was classified as a treatment failure. Overall, 15 patients (60%) did not respond to therapy (95% confidence interval: 21% to 57%) and were subsequently re-treated. There was no relation between response and age or gender. Two patients presented initially with severe inflammation and kerion, and both were additionally treated with prednisone 1 mg/kg for 7 to 10 days. These patients were culture negative and clinically improved by week 4 (not including alopecia). Three additional patients were receiving concomitant antibiotic therapy for sinusitis, one each receiving amoxicillin, trimethoprim-sulfamethoxazole, and loracarbef. Adverse events associated with itraconazole were reported in seven patients. One patient reported headache and two had vomiting; these subsequently abated without the need for discontinuation of therapy. Diarrhea was reported in one child who was simultaneously receiving loracarbef twice daily; itraconazole was continued. Itraconazole was discontinued in three children because of adverse effects. Caregivers stopped itraconazole in two patients because of epistaxis in one and vomiting in another. The investigators discontinued itraconazole in the third child who had seizures; however, a subsequent evaluation of serum drug concentration revealed no measurable itraconazole in the blood. An additional 29 patients were enrolled but were unable to be evaluated. Fifteen patients were lost to follow-up. An attempt was made to contact all of these patients by phone and mail. These patients were dropped from the study after a minimum of four unsuccessful attempts to contact the caregiver. In addition, five patients were culture negative at enrollment; three demonstrated inadequate compliance; three discontinued drug because of adverse events; patient insurance would not cover the cost of itraconazole in two cases; and one child refused to take food mixed with itraconazole.
Abdel-Rahman, Powell, and Nahata 445 DISCUSSION
Although griseofulvin is currently the drug of choice in treating tinea capitis, effective therapy often requires 6 to 8 weeks and response rates may be variable. Randomized controlled trials with griseofulvin suggest response rates of more than 80%.6-9 However, a study previously conducted by us suggested that this may not be the case in clinical practice.10 We evaluated medical records of 122 children seen at an outpatient clinic and treated with griseofulvin for mycologically confirmed infection. Of those, 39.3% returned to the clinic requiring additional treatment. The search for alternative agents with potentially shorter treatment durations and increased efficacy continues. Reports in the literature suggested that itraconazole may provide an appropriate alternative to griseofulvin in the treatment of tinea capitis,3,7,11 although this was not demonstrated in this study. Only 40% of patients treated with 4 weeks of itraconazole (100 mg/day) responded to therapy; the remaining children required additional therapy. The reasons for poor response to itraconazole are unclear. Itraconazole is given once daily in a similar manner to griseofulvin; however, the dose of itraconazole used in this study may have been inadequate for the treatment of tinea capitis. Similarly, the duration of therapy may not have been adequate. Greer12 reported a 90% cure rate in 10 children receiving itraconazole (100 mg/day) for 8 weeks, suggesting that extending therapy beyond 1 month may be necessary. Reexposure to the pathogen from family members, friends, or fomites may also contribute to the low response rate despite extensive efforts to educate caregivers about avoiding reexposure. Four patients who completed the study (two responders and two nonresponders) have returned (between 2 and 6 months after study completion) with reinfection. Long-term epidemiologic studies are needed to identify whether children such as these are reacquiring infection or whether current therapy is ineffective at eradicating carriage of the fungus. The limitations of this study include the lack of a control group and the high dropout rate. Attrition was high in spite of aggressive efforts to contact the caregivers, and this could have biased the results toward nonresponse. Despite a relative-
Journal of the American Academy of Dermatology March 1998
446 Abdel-Rahman, Powell, and Nahata ly small number of patients studied, a statistical difference was observed in clinical response. However, this needs to be considered in concert with fungal eradication in the assessment of overall cure. Future studies should include a control group with griseofulvin or another antifungal agent. Itraconazole appeared to be relatively safe in our population. However, with an acquisition cost approximately two to three times that of griseofulvin and the lack of evidence for greater efficacy, we currently cannot recommend routine use of itraconazole in the treatment of tinea capitis. Larger comparative studies in children with T. tonsurans tinea capitis are needed to clarify the usefulness of itraconazole in therapy compared with griseofulvin.
7.
8. 9. 10. 11. 12. 13.
REFERENCES 1. Rosenthal JR. Pediatric fungal infections from head to toe: what's new. Curr Opin Pediatr 1994;6:435-41. 2. Prose NS. Treatment of tinea capitis. Rep Pediatr Infect Dis 1995;5:8. 3. Elewski B. Tinea capitis: itraconazole in Trichophyton tonsurans infection. J Am Acad Dermatol 1994;31:65-7. 4. Jacobs PH. Treatment of fungal skin infections: state of the art. J Am Acad Dermatol 1990;23:549-51. 5. Presser SE, Blank H. Cimetidine: adjunct in treatment of tinea capitis. Lancet 1981;1:108-9. 6. Alvi KH, Iqbal N, Khan KA, Haroon TS, Hussain I, Aman S, et al. A randomized double-blind trial of the efficacy and tolerability of terbinafine once daily com-
14.
15.
16.
pared to griseofulvin once daily in the treatment of tinea capitis. In: Shuster S, Jafary MH, editors. Royal Society of Medicine Services International Congress Series No. 205; 1992. p. 35-40. Lopez-Gomez S, Del Palacio A, Van Custem J, Cuetara MS, Iglesias L, Rodriguez-Noriega A. Itraconazole versus griseofulvin in the treatment of tinea capitis: a double-blind randomized study in children. Int J Dermatol 1994;33:743-7. Tanz RR, Hebert AA, Esterly NB. Treating tinea capitis: Should ketoconazole replace griseofulvin? J Pediatr 1988;112:987-91. Martinez-Roig A, Torres-Rodriguez JM, Bartlett-Coma A. Double blind study of ketoconazole and griseofulvin in dermatophytoses. Pediatr Infect Dis J 1988;7:37-40. Abdel-Rahman SM, Nahata MC, Powell DA. Response to initial griseofulvin therapy in pediatric patients with tinea capitis. Ann Pharmacother 1997;31:406-10. Legendre R, Esola-Macre J. Itraconazole in the treatment of tinea capitis. J Am Acad Dermatol 1990;23:559-60. Greer DL. Treatment of tinea capitis with itraconazole. J Am Acad Dermatol 1996;35:637-8. Degreef H. Itraconazole in the treatment of tinea capitis. Cutis 1996;58:90-3. Goh CL, Tay YK, Ali KB, Koh MT, Seow CS. In vitro evaluation of griseofulvin, ketoconazole and itraconazole against various dermatophytes in Singapore. Int J Dermatol 1994;33:733-7. Cauwenbergh G, Degreef H, Heykants J, Woestenborghs R, Van Rooy P, Haeverans K. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Acad Dermatol 1988;18:263-8. Tanz RR, Stagl S, Esterly NB. Comparison of ketoconazole and griseofulvin for treatment of tinea capitis in childhood: a preliminary study. Pediatr Emerg Care 1985;1:16-8.
Despite the availability of oral antifungal therapy for the treatment of tinea capitis, this infection remains prevalent in children.1 The current drug of choice in treating tinea capitis is griseofulvin, 10 to 20 mg/kg daily often for 6 to 8 weeks in combination with a selenium sulfide–containing shampoo2; however, treatment failure is not uncommon.3-5 Although response rates in controlled trials have ranged from 80% to 90%,6-9 response rates in a clinical setting may be significantly lower, possibly because of noncompliance,
From College of Pharmacy,a,b Department of Pediatrics,b,c Wexner Institute for Pediatric Research, and the Section of Infectious Diseases,a,b,c Ohio State University and Children's Hospital. Supported in part by the National Institute for Child Health and Human Development Pediatric Pharmacology Research Unit, grant HD 31316. Reprint requests: Milap C. Nahata, PharmD, College of Pharmacy, Ohio State University, 500 W. 12th Ave., Columbus, OH 43210. *Susan M. Abdel-Rahman, PharmD, is now Assistant Professor of Pharmacy and Pediatrics at the University of Missouri–Kansas City. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87652
inadequate drug absorption, reexposure or resistance.10 Newer agents with potentially shorter durations of therapy continue to be evaluated. Itraconazole appeared to demonstrate good efficacy in the treatment of tinea capitis in several case reports and a few clinical trials.3,7,11-13 However, the majority of patients enrolled in controlled clinical trials were infected with pathogens other than Trichophyton tonsurans, the primary pathogen in the United States.7,11,13 Because itraconazole is highly effective in vitro and achieves high and prolonged concentrations in keratinous tissue, it is currently being considered as an alternative to griseofulvin in the United States for the treatment of superficial fungal infections.14,15 The objective of this study was to evaluate the clinical and mycologic efficacy of itraconazole given for 1 month in an open label fashion for the treatment of T. tonsurans tinea capitis in children. METHODS This study was approved by the Human Subjects
443
444 Abdel-Rahman, Powell, and Nahata
Fig. 1. Mean clinical severity score, from baseline through 2 months' follow-up, in children with tinea capitis receiving 1 month of itraconazole therapy. Research Committee at our institution. A written informed consent was obtained from a parent or guardian before enrollment of each child, and assent was obtained from the child when applicable. Patients older than 1 year of age were enrolled during a 12month period from the primary care clinic of a large urban pediatric hospital. Fungal specimens were collected by gently massaging the scalp lesion with a sterile toothbrush (Oral-B) and planting the inoculum on Saboraud's agar with chloramphenicol and cycloheximide (Mycosel, BBL). This technique was selected because, in our experience, it is less threatening to the child and provides a greater inoculum for culture than pulling hairs from the border of the lesion. To prevent bias in interpretation, mycologic identification was performed by personnel unaware of the clinical findings or the status of treatment in patients. Clinical severity was determined as previously described16 by evaluation of alopecia, scaling, crusting, erythema, inflammation, adenopathy, pain, and itching on a scale from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each finding. Thus a score of 0 would represent no discernible disease and a score of 24 would reflect the most severe disease. Patients were prescribed itraconazole (Sporanox, Janssen Pharmaceutica) 100 mg/day and a selenium sulfide–containing shampoo for 1 month. Patients unable to swallow the capsule were instructed to open it and mix the contents with a small amount of soft food such as pudding or applesauce. All patients were instructed to take the daily dose with a meal. Compliance was evaluated by asking the parent, and by pill counts at the 2- and 4-week visit. Noncompliance was defined as greater than or equal to two missed doses per week or four doses per follow-up visit. Patients were observed by the same investigators every 2 weeks during therapy and at 2 and 4 weeks posttherapy. Fungal cultures were performed and a
Journal of the American Academy of Dermatology March 1998
Fig. 2. Mycologic response measured out to 2 months in children receiving 1 month of itraconazole therapy.
clinical severity score calculated at the time of all visits. Patients were considered successfully treated if cultures became negative and clinical symptoms were alleviated. Clinical improvement was defined as no or mild residual signs and symptoms (with the exception of alopecia, which was expected to clear more slowly). Patients who remained culture positive or were culture negative but clinically unchanged or worse at week 8 were considered treatment failures and subsequently re-treated at the physician's discretion. Statistical significance was determined for baseline and follow-up clinical response by means of a twotailed paired t test. A 95% confidence interval was calculated for overall response rate. A Cox proportional hazard test was used to determine whether response was a function of age. A chi-square test was used to determine whether response was a function of gender. Statistical significance was defined by a p value of less than 0.05. RESULTS
A total of 25 children completed the study. The age of patients completing the study ranged from 1.5 to 11 years (mean, 5.3 ± 2.7 years). The majority were male (80%) and African-American (100%). The mean clinical severity score at the time of enrollment was 7.3 ± 4.0, with a median of 7. The mean score improved to 6.2 at week 2, 4.9 at week 4, 4.2 at week 6, and 4.0 at week 8 (Fig. 1). The mean clinical severity score at each visit was significantly lower than the initial mean score (p < 0.05). Mean scores also improved significantly between weeks 2 and 4; however, there was no significant difference in mean scores between weeks 4 through 8.
Journal of the American Academy of Dermatology Volume 38, Number 3
At the end of the study period, 11 patients (44%) were mycologically negative. Cumulative percentage of mycologic cure was 3% at week 2, 10% at week 4, 31% at week 6, and 44% at week 8 (Fig. 2). Fourteen patients remained culture positive. One patient who was mycologically negative at the end of the study, however, had significant worsening of clinical lesions and was classified as a treatment failure. Overall, 15 patients (60%) did not respond to therapy (95% confidence interval: 21% to 57%) and were subsequently re-treated. There was no relation between response and age or gender. Two patients presented initially with severe inflammation and kerion, and both were additionally treated with prednisone 1 mg/kg for 7 to 10 days. These patients were culture negative and clinically improved by week 4 (not including alopecia). Three additional patients were receiving concomitant antibiotic therapy for sinusitis, one each receiving amoxicillin, trimethoprim-sulfamethoxazole, and loracarbef. Adverse events associated with itraconazole were reported in seven patients. One patient reported headache and two had vomiting; these subsequently abated without the need for discontinuation of therapy. Diarrhea was reported in one child who was simultaneously receiving loracarbef twice daily; itraconazole was continued. Itraconazole was discontinued in three children because of adverse effects. Caregivers stopped itraconazole in two patients because of epistaxis in one and vomiting in another. The investigators discontinued itraconazole in the third child who had seizures; however, a subsequent evaluation of serum drug concentration revealed no measurable itraconazole in the blood. An additional 29 patients were enrolled but were unable to be evaluated. Fifteen patients were lost to follow-up. An attempt was made to contact all of these patients by phone and mail. These patients were dropped from the study after a minimum of four unsuccessful attempts to contact the caregiver. In addition, five patients were culture negative at enrollment; three demonstrated inadequate compliance; three discontinued drug because of adverse events; patient insurance would not cover the cost of itraconazole in two cases; and one child refused to take food mixed with itraconazole.
Abdel-Rahman, Powell, and Nahata 445 DISCUSSION
Although griseofulvin is currently the drug of choice in treating tinea capitis, effective therapy often requires 6 to 8 weeks and response rates may be variable. Randomized controlled trials with griseofulvin suggest response rates of more than 80%.6-9 However, a study previously conducted by us suggested that this may not be the case in clinical practice.10 We evaluated medical records of 122 children seen at an outpatient clinic and treated with griseofulvin for mycologically confirmed infection. Of those, 39.3% returned to the clinic requiring additional treatment. The search for alternative agents with potentially shorter treatment durations and increased efficacy continues. Reports in the literature suggested that itraconazole may provide an appropriate alternative to griseofulvin in the treatment of tinea capitis,3,7,11 although this was not demonstrated in this study. Only 40% of patients treated with 4 weeks of itraconazole (100 mg/day) responded to therapy; the remaining children required additional therapy. The reasons for poor response to itraconazole are unclear. Itraconazole is given once daily in a similar manner to griseofulvin; however, the dose of itraconazole used in this study may have been inadequate for the treatment of tinea capitis. Similarly, the duration of therapy may not have been adequate. Greer12 reported a 90% cure rate in 10 children receiving itraconazole (100 mg/day) for 8 weeks, suggesting that extending therapy beyond 1 month may be necessary. Reexposure to the pathogen from family members, friends, or fomites may also contribute to the low response rate despite extensive efforts to educate caregivers about avoiding reexposure. Four patients who completed the study (two responders and two nonresponders) have returned (between 2 and 6 months after study completion) with reinfection. Long-term epidemiologic studies are needed to identify whether children such as these are reacquiring infection or whether current therapy is ineffective at eradicating carriage of the fungus. The limitations of this study include the lack of a control group and the high dropout rate. Attrition was high in spite of aggressive efforts to contact the caregivers, and this could have biased the results toward nonresponse. Despite a relative-
Journal of the American Academy of Dermatology March 1998
446 Abdel-Rahman, Powell, and Nahata ly small number of patients studied, a statistical difference was observed in clinical response. However, this needs to be considered in concert with fungal eradication in the assessment of overall cure. Future studies should include a control group with griseofulvin or another antifungal agent. Itraconazole appeared to be relatively safe in our population. However, with an acquisition cost approximately two to three times that of griseofulvin and the lack of evidence for greater efficacy, we currently cannot recommend routine use of itraconazole in the treatment of tinea capitis. Larger comparative studies in children with T. tonsurans tinea capitis are needed to clarify the usefulness of itraconazole in therapy compared with griseofulvin.
7.
8. 9. 10. 11. 12. 13.
REFERENCES 1. Rosenthal JR. Pediatric fungal infections from head to toe: what's new. Curr Opin Pediatr 1994;6:435-41. 2. Prose NS. Treatment of tinea capitis. Rep Pediatr Infect Dis 1995;5:8. 3. Elewski B. Tinea capitis: itraconazole in Trichophyton tonsurans infection. J Am Acad Dermatol 1994;31:65-7. 4. Jacobs PH. Treatment of fungal skin infections: state of the art. J Am Acad Dermatol 1990;23:549-51. 5. Presser SE, Blank H. Cimetidine: adjunct in treatment of tinea capitis. Lancet 1981;1:108-9. 6. Alvi KH, Iqbal N, Khan KA, Haroon TS, Hussain I, Aman S, et al. A randomized double-blind trial of the efficacy and tolerability of terbinafine once daily com-
14.
15.
16.
pared to griseofulvin once daily in the treatment of tinea capitis. In: Shuster S, Jafary MH, editors. Royal Society of Medicine Services International Congress Series No. 205; 1992. p. 35-40. Lopez-Gomez S, Del Palacio A, Van Custem J, Cuetara MS, Iglesias L, Rodriguez-Noriega A. Itraconazole versus griseofulvin in the treatment of tinea capitis: a double-blind randomized study in children. Int J Dermatol 1994;33:743-7. Tanz RR, Hebert AA, Esterly NB. Treating tinea capitis: Should ketoconazole replace griseofulvin? J Pediatr 1988;112:987-91. Martinez-Roig A, Torres-Rodriguez JM, Bartlett-Coma A. Double blind study of ketoconazole and griseofulvin in dermatophytoses. Pediatr Infect Dis J 1988;7:37-40. Abdel-Rahman SM, Nahata MC, Powell DA. Response to initial griseofulvin therapy in pediatric patients with tinea capitis. Ann Pharmacother 1997;31:406-10. Legendre R, Esola-Macre J. Itraconazole in the treatment of tinea capitis. J Am Acad Dermatol 1990;23:559-60. Greer DL. Treatment of tinea capitis with itraconazole. J Am Acad Dermatol 1996;35:637-8. Degreef H. Itraconazole in the treatment of tinea capitis. Cutis 1996;58:90-3. Goh CL, Tay YK, Ali KB, Koh MT, Seow CS. In vitro evaluation of griseofulvin, ketoconazole and itraconazole against various dermatophytes in Singapore. Int J Dermatol 1994;33:733-7. Cauwenbergh G, Degreef H, Heykants J, Woestenborghs R, Van Rooy P, Haeverans K. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Acad Dermatol 1988;18:263-8. Tanz RR, Stagl S, Esterly NB. Comparison of ketoconazole and griseofulvin for treatment of tinea capitis in childhood: a preliminary study. Pediatr Emerg Care 1985;1:16-8.