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Tinea capitis: Itraconazole in Trichophyton tonsurans infection
THERAPY
Tinea capitis: Itraconazole in Trichophyton tonsurans infection Boni E. Elewski, MD Cleveland, Ohio Background: Although griseofulvin is considered the standardtreatmentof tineacapitis, alternatives are being investigated in hopes of identifying more rapid and better cure rates. Objective: Our purpose was to determine the efficacy of itraconazole as therapy for tinea capitis. Methods: Anopenlabel studywas performed onthreepatients who didnotrespond toorcould not tolerate griseofulvin therapy. Results: A 30-day course of 100mg of itraconazo1e daily resulted in clinical and mycologic cure in all threepatients; no sideeffects were reported. Conclusion: Although theseresults need to be confirmed by larger, controlled trials, it appears thatitraconazole offers a viable alternative to griseofulvin forthe treatment ofchildren withtinea capitis. (1 AM ACAD DERMATOL 1994;31:65-7.)
Tinea capitis most frequently affects prepubescent children. I In the United States, it most commonly occurs in urban areas and is often associated with crowded living conditions. I The clinical presentation of tinea capitis is diverse, ranging from a scaly subclinical infectionto a kerion. Although Microsporum canis and Microsporum audouinii were the predominant causative organisms in the past, most tinea capitis in the United States today is causedby Trichophyton tonsuransl The emergence of T tonsurans as a principal cause of tinea capitis has also made diagnosis more difficult because the organism does not fluoresce on Wood's lamp examination.' In addition, direct examination of potassium hydroxide (KOH)-treated material can be difficult to interpret. 4 Furthermore, the "black dots" often associatedwith infectionmay be inconspicuousor absent.However,fungal culture yields high isolation rates of identifiable dermatophytes and is therefore the most reliable means of confirming the diagnosis of tinea capitis." 5 Since its efficacy was first demonstrated in 1958, the standard therapy for tinea capitis has been oral From CaseWestern Reserve University, University Hospitals ofCleveland. Reprint requests: Boni E. Elewski, MD, Assistant Professor, Case WesternReserve University, University Hospitals ofCleveland, 2074 Abington Rd., Cleveland, OH 44106. Copyright@ 1994by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/53126
griseofulvin. 6 However, alternatives have been sought because not all patients respond to this agent; in those who do, infection often clears slowly, occasionally requiring several months for complete resolution/' Until recently, the only other alternative therapy was ketoconazole. We describe three children with mycologically confirmed tinea capitis caused by T. tonsurans that resolved after a 30-day course of oral itraconazole. CASE REPORTS
Case 1 An ll-year-oldblackboywho wasa kidney transplant recipient had tineacapitis. He had previously received a 2-week course of oral griseofulvin (10 mg/kg), but this medication was stopped because signs of organrejection developed. The scalp infection wasthen treated withketoconazole cream. Griseofulvin wasresumed a few weeks later, but again was discontinued because shortness of breath and weakness developed. When first seen by me, his entire scalp was red and scaly, with abscesses, hair loss, and prominent anterior andposterior cervical lymphadenopathy. Thefungalculture grew T. tonsurans. The patient was given a l-month course of oral itraconazole, 100 mg daily, with daily ketoconazole shampoo andtopical ketoconazole cream. Because of his cyclosporine therapy, weekly serum levels weremeasured along with weekly liver profile tests. All of these were normal. Two weeks after starting therapy, the patient's scalp wasclinically clear; in some patches, therewas ev-
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Journal of the American Academy of Dermatology July 1994
Elewski
Fig. 1. Case 2. An l l-year-old black boy. Patient had been taking ultramicrosized griseofulvin, 250 to 375 mg twice daily, for 6 weeks. Culture was still positive for T. tonsurans.
Fig. 2. Case 2. Eight weeks after patient finished 30-day course of itraconazole, 100 mg twice daily. Note regrowth of hair.
idence of hair regrowth. Two months after treatment, the patient's scalp was still clear and new hair had regrown.
Case 2 An It-year-old black boy had tinea capitis and hair loss of 1 year's duration. He had received several courses of griseofulvin (10 rug/kg), which were unsuccessful. He had also received cefaclor to control secondary bacterial infection of the scalp. The posterior scalp and crown had tender patches of oozing, crusting, abscess formation, and alopecia with
prominent posterior cervical lymphadenopathy. T. tonsurans was cultured. Bacterial cultures were negative. He was treated with ultramicrosized griseofulvin (250 mg twice daily), ketoconazole shampoo daily, and econazole nitrate cream twice daily. Five days later his condition was worsening, and the griseofulvin dosage was increased to 325 mg twice daily. Two weeks later, only minimal improvement was noted. There was still abscess formation, prominent adenopathy, and no evidence of hair growth. Cefaclor, 250 mg twice daily, was added to treat presumed secondary
Journal of the American Academy of Dermatology Volume 31, Number 1
bacterial infection. Two weeks later, he still had prominent adenopathy, and boggy areas were present. The cefaclor was stopped, and the griseofulvin dosage was increased to 375 mg twice daily. Two weeks later, oral erythromycin was begun. He still had persistent abscesses, and a fungal culture was positive for T. tonsurans. Griseofulvin therapy was stopped, and the patient was given itraconazole (lao mgdaily) (Fig. I). Thirteen days later, he had no boggy areas or abscess formation, and there was evidence of new hair growth. The itraconazole dosage was continued, and he was given daily ketoconazole shampoo and topical econazole nitrate cream for 30 days. Two months after cessation of itraconazole therapy, his scalp was clear and new hair was regrowing (Fig. 2); a KOH preparation, and fungal and bacterial cultures were negative.
Case 3 A 7-year-old girl had been given microsized griseofulvin (125 mg twice daily) (10 mg/kg/day) for 2 months for treatment of persistent tinea capitis, but her condition was worsening. Physical examination revealed a 3 to 4 cm scaly, erythematous patch in the lateral scalp, with boggy areas. She had prominent posterior cervical lymphadenopathy. T. tonsurans was grown on culture. Griseofulvin treatment was discontinued and itraconazole (100 mg daily) and ketoconazole shampoo used daily were begun. Eight days later the improvement was considerable. Although the patient did not return to clinic, follow-up telephone conversations with the parents indicated the patient had completed a 3D-day course of oral itraconazole and her scalp was clinically clear; new hair growth began 5 weeks after finishing therapy. DISCUSSION
Until the availability of itraconazole, oral ketoconazole was the only alternative to griseofulvin for treatment of tinea capitis. Infections caused by M. canis and M. audouinii generally respond well to griseofulvin. T. tonsurans has proved more recalcitrant to griseofulvin, with increasing dosages necessary to clear infections. Some authors advocate dosages up to 15 mg/kg/day of microsized griseofulvin." Systemic ketoconazole has demonstrated variable success and is not as effective as griseofulvin for M. canis infections. In two double-blind, randomized comparison studies of III evaluable children, treatment results
Elewski 67 were significantly better with oral griseofulvin than with oral ketoconazole." 5 Therefore oral ketoconazole is generally limited to situations in which griseofulvin resistance is encountered despite adequate blood levels and in cases of griseofulvin intolerance or allergy. Thus, despite its availability for a decade, orally administered ketoconazole has not supplanted griseofulvin as the drug of first choice in the treatment of tinea capitis," Although to date no controlled studies of itraconazole in tinea capitis have been published, initial results are promising. In a report of seven uncontrolled studies, in which itraconazole dosages ranged from 25 to 100 mg daily, 47 of 50 children younger than IO years of age (94%) with either M. canis or T. tonsurans responded to an average 30-day course of 100 mg daily.f A mycologic cure rate of 93% was reported. OUf experience, as these case studies illustrate, supports these findings. Although all three patients failed to respond to griseofulvin, they responded to a 30-day course of itraconazole (100 mg daily). No significant side effects were reported, nor, to our knowledge, has relapse occurred. Although our results need to be confirmed by larger controlled trials, based on our limited experience, and previously published reports, itraconazole may be used as an alternative to either griseofulvin or ketoconazole in the treatment of children with tinea capitis.
REFERENCES 1. Habif F. Clinical dermatology. 2nd ed. St Louis: CV Mosby, 1990:318-22. 2. RipponJ W, ed.The pathogenic fungi and pathogenic actinomytes. 3rd ed.Philadelphia: WB Saunders, 1988:186-96. 3. Prevost E. The rise and fall of fluorescent tinea capitis. Pediatr DermatoI1983;1:127-33. 4. Gan VN, Petruska M, Ginsburg CM. Epidemiology and treatment of tinea capitis: ketoconazole vs. griseofulvin. Pediatr Infect Dis J 1987;6:46-9. 5. Tanz RR, Hebert AA, Esterly NB. Treating tinea capitis: Should ketoconazole replace griseofulvin? J Pediatr 1988; 112:987-91. 6. Williams DI, Marten RH. Oral treatment of ringworm with griseofulvin. Lancet 1958;2:1212-3. 7. SilvermanRA. Pediatric mycoses.In: ElewskiB, ed. Cutaneousfungal infections. N ewYork: Igaku-Shoin,1992:21228. 8. Legendre R, Esola-Macre J. Itraconazole in the treatment of tinea capitis. J AM ACAD DERMATOL 1990;23(suppl): 559-60.
Tinea capitis: Itraconazole in Trichophyton tonsurans infection Boni E. Elewski, MD Cleveland, Ohio Background: Although griseofulvin is considered the standardtreatmentof tineacapitis, alternatives are being investigated in hopes of identifying more rapid and better cure rates. Objective: Our purpose was to determine the efficacy of itraconazole as therapy for tinea capitis. Methods: Anopenlabel studywas performed onthreepatients who didnotrespond toorcould not tolerate griseofulvin therapy. Results: A 30-day course of 100mg of itraconazo1e daily resulted in clinical and mycologic cure in all threepatients; no sideeffects were reported. Conclusion: Although theseresults need to be confirmed by larger, controlled trials, it appears thatitraconazole offers a viable alternative to griseofulvin forthe treatment ofchildren withtinea capitis. (1 AM ACAD DERMATOL 1994;31:65-7.)
Tinea capitis most frequently affects prepubescent children. I In the United States, it most commonly occurs in urban areas and is often associated with crowded living conditions. I The clinical presentation of tinea capitis is diverse, ranging from a scaly subclinical infectionto a kerion. Although Microsporum canis and Microsporum audouinii were the predominant causative organisms in the past, most tinea capitis in the United States today is causedby Trichophyton tonsuransl The emergence of T tonsurans as a principal cause of tinea capitis has also made diagnosis more difficult because the organism does not fluoresce on Wood's lamp examination.' In addition, direct examination of potassium hydroxide (KOH)-treated material can be difficult to interpret. 4 Furthermore, the "black dots" often associatedwith infectionmay be inconspicuousor absent.However,fungal culture yields high isolation rates of identifiable dermatophytes and is therefore the most reliable means of confirming the diagnosis of tinea capitis." 5 Since its efficacy was first demonstrated in 1958, the standard therapy for tinea capitis has been oral From CaseWestern Reserve University, University Hospitals ofCleveland. Reprint requests: Boni E. Elewski, MD, Assistant Professor, Case WesternReserve University, University Hospitals ofCleveland, 2074 Abington Rd., Cleveland, OH 44106. Copyright@ 1994by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/53126
griseofulvin. 6 However, alternatives have been sought because not all patients respond to this agent; in those who do, infection often clears slowly, occasionally requiring several months for complete resolution/' Until recently, the only other alternative therapy was ketoconazole. We describe three children with mycologically confirmed tinea capitis caused by T. tonsurans that resolved after a 30-day course of oral itraconazole. CASE REPORTS
Case 1 An ll-year-oldblackboywho wasa kidney transplant recipient had tineacapitis. He had previously received a 2-week course of oral griseofulvin (10 mg/kg), but this medication was stopped because signs of organrejection developed. The scalp infection wasthen treated withketoconazole cream. Griseofulvin wasresumed a few weeks later, but again was discontinued because shortness of breath and weakness developed. When first seen by me, his entire scalp was red and scaly, with abscesses, hair loss, and prominent anterior andposterior cervical lymphadenopathy. Thefungalculture grew T. tonsurans. The patient was given a l-month course of oral itraconazole, 100 mg daily, with daily ketoconazole shampoo andtopical ketoconazole cream. Because of his cyclosporine therapy, weekly serum levels weremeasured along with weekly liver profile tests. All of these were normal. Two weeks after starting therapy, the patient's scalp wasclinically clear; in some patches, therewas ev-
65
66
Journal of the American Academy of Dermatology July 1994
Elewski
Fig. 1. Case 2. An l l-year-old black boy. Patient had been taking ultramicrosized griseofulvin, 250 to 375 mg twice daily, for 6 weeks. Culture was still positive for T. tonsurans.
Fig. 2. Case 2. Eight weeks after patient finished 30-day course of itraconazole, 100 mg twice daily. Note regrowth of hair.
idence of hair regrowth. Two months after treatment, the patient's scalp was still clear and new hair had regrown.
Case 2 An It-year-old black boy had tinea capitis and hair loss of 1 year's duration. He had received several courses of griseofulvin (10 rug/kg), which were unsuccessful. He had also received cefaclor to control secondary bacterial infection of the scalp. The posterior scalp and crown had tender patches of oozing, crusting, abscess formation, and alopecia with
prominent posterior cervical lymphadenopathy. T. tonsurans was cultured. Bacterial cultures were negative. He was treated with ultramicrosized griseofulvin (250 mg twice daily), ketoconazole shampoo daily, and econazole nitrate cream twice daily. Five days later his condition was worsening, and the griseofulvin dosage was increased to 325 mg twice daily. Two weeks later, only minimal improvement was noted. There was still abscess formation, prominent adenopathy, and no evidence of hair growth. Cefaclor, 250 mg twice daily, was added to treat presumed secondary
Journal of the American Academy of Dermatology Volume 31, Number 1
bacterial infection. Two weeks later, he still had prominent adenopathy, and boggy areas were present. The cefaclor was stopped, and the griseofulvin dosage was increased to 375 mg twice daily. Two weeks later, oral erythromycin was begun. He still had persistent abscesses, and a fungal culture was positive for T. tonsurans. Griseofulvin therapy was stopped, and the patient was given itraconazole (lao mgdaily) (Fig. I). Thirteen days later, he had no boggy areas or abscess formation, and there was evidence of new hair growth. The itraconazole dosage was continued, and he was given daily ketoconazole shampoo and topical econazole nitrate cream for 30 days. Two months after cessation of itraconazole therapy, his scalp was clear and new hair was regrowing (Fig. 2); a KOH preparation, and fungal and bacterial cultures were negative.
Case 3 A 7-year-old girl had been given microsized griseofulvin (125 mg twice daily) (10 mg/kg/day) for 2 months for treatment of persistent tinea capitis, but her condition was worsening. Physical examination revealed a 3 to 4 cm scaly, erythematous patch in the lateral scalp, with boggy areas. She had prominent posterior cervical lymphadenopathy. T. tonsurans was grown on culture. Griseofulvin treatment was discontinued and itraconazole (100 mg daily) and ketoconazole shampoo used daily were begun. Eight days later the improvement was considerable. Although the patient did not return to clinic, follow-up telephone conversations with the parents indicated the patient had completed a 3D-day course of oral itraconazole and her scalp was clinically clear; new hair growth began 5 weeks after finishing therapy. DISCUSSION
Until the availability of itraconazole, oral ketoconazole was the only alternative to griseofulvin for treatment of tinea capitis. Infections caused by M. canis and M. audouinii generally respond well to griseofulvin. T. tonsurans has proved more recalcitrant to griseofulvin, with increasing dosages necessary to clear infections. Some authors advocate dosages up to 15 mg/kg/day of microsized griseofulvin." Systemic ketoconazole has demonstrated variable success and is not as effective as griseofulvin for M. canis infections. In two double-blind, randomized comparison studies of III evaluable children, treatment results
Elewski 67 were significantly better with oral griseofulvin than with oral ketoconazole." 5 Therefore oral ketoconazole is generally limited to situations in which griseofulvin resistance is encountered despite adequate blood levels and in cases of griseofulvin intolerance or allergy. Thus, despite its availability for a decade, orally administered ketoconazole has not supplanted griseofulvin as the drug of first choice in the treatment of tinea capitis," Although to date no controlled studies of itraconazole in tinea capitis have been published, initial results are promising. In a report of seven uncontrolled studies, in which itraconazole dosages ranged from 25 to 100 mg daily, 47 of 50 children younger than IO years of age (94%) with either M. canis or T. tonsurans responded to an average 30-day course of 100 mg daily.f A mycologic cure rate of 93% was reported. OUf experience, as these case studies illustrate, supports these findings. Although all three patients failed to respond to griseofulvin, they responded to a 30-day course of itraconazole (100 mg daily). No significant side effects were reported, nor, to our knowledge, has relapse occurred. Although our results need to be confirmed by larger controlled trials, based on our limited experience, and previously published reports, itraconazole may be used as an alternative to either griseofulvin or ketoconazole in the treatment of children with tinea capitis.
REFERENCES 1. Habif F. Clinical dermatology. 2nd ed. St Louis: CV Mosby, 1990:318-22. 2. RipponJ W, ed.The pathogenic fungi and pathogenic actinomytes. 3rd ed.Philadelphia: WB Saunders, 1988:186-96. 3. Prevost E. The rise and fall of fluorescent tinea capitis. Pediatr DermatoI1983;1:127-33. 4. Gan VN, Petruska M, Ginsburg CM. Epidemiology and treatment of tinea capitis: ketoconazole vs. griseofulvin. Pediatr Infect Dis J 1987;6:46-9. 5. Tanz RR, Hebert AA, Esterly NB. Treating tinea capitis: Should ketoconazole replace griseofulvin? J Pediatr 1988; 112:987-91. 6. Williams DI, Marten RH. Oral treatment of ringworm with griseofulvin. Lancet 1958;2:1212-3. 7. SilvermanRA. Pediatric mycoses.In: ElewskiB, ed. Cutaneousfungal infections. N ewYork: Igaku-Shoin,1992:21228. 8. Legendre R, Esola-Macre J. Itraconazole in the treatment of tinea capitis. J AM ACAD DERMATOL 1990;23(suppl): 559-60.