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A double-blind, randomized, placebo-controlled evaluation of short-term treatment with oral itraconazole in patients with tinea versicolor
A double-blind, randomized, placebo-controlled evaluation of short-term treatment with oral itraconazole in patients with tinea versicolor Janet G. Hickman, MD Lynchburg, Virginia
Background: The use of short-term oral azoles is an alternative to topical therapy in patients with linea versicolor. Objective: We compared the efficacy and safety of oral itraconazole with that of placebo in 36 patients with mycologically proven tinea versicolor. Methods: Patients were randomly assigned to 7 days of treatment with either itraconazole, 200 mg once daily, or placebo. A potassium hydroxide examination and assessment of scaling, erythema, pruritus, and global condition were performed at baseline and at 4 weeks after treatment. Results: The itraconazole-treated group demonstrated significant improvement over both baseline (p < 0.01) and placebo (p < 0.02) in scaling, erythema, and pruritus. Sixty-seven percent of itraconazole-treated patients were free of symptoms at week 5, as compared with 12% of placebo-treated patients. Ninety-four percent of itraconazole-treated patients were considered to be healed or markedly improved at the study's end point compared with 6% of placebo-treated patients (p < 0.01). A total of 89% in the itraconazole-treated group had a negative potassium hydroxide examination at the follow-up visit compared with 6% in the placebo-treated group (p < 0.01). There was a single report of a possibly treatment-related adverse event in each treatment group. Conclusion: Short-term treatment with itraconazole is effective and well tolerated in the management of tinea versicolor. (J AM ACAD DEP,MATOL 1996;34:785-7.)
Both topical and systemic therapies have been used for the treatment of tinea versicolor. Although oral azoles have usually been reserved for the treatment of more resistant cases, favorable results have been achieved in treating more routine cases for brief periods. Several studies have demonstrated a positive outcome when oral ketoconazole or itraconazole was administered for 5 to 7 days. l' 2 This study employed a randomized, double-blind, parallel group design to compare the efficacy and safety of a 7-day regimen of oral itraconazole versus placebo in patients with tinea versicolor.
From The Education and Research Foundation. Supported by an unrestricted grant from Janssen Pharmaceutica~ Titusville, N.J. Reprint requests: Janet G. Hickman, MD, 2602 Langhome Rd., Lynchburg, VA 24501. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0
16/1/69839
PATIENTS AND METHODS
Patients 12 years of age or older with a positive potassium hydroxide (KOH) examination at the baseline visit (visit 0) were eligible for study entry. All patients signed a written, informed consent before study entry. Exclusion criteria included patients with systemic fungal infections; oral, vaginal, or chronic mucocutaneous candidiasis; dermatophyte infections; onychomycosis; chronic liver disease; or any serious concurrent disease that might prevent completion of the study. Also excluded were patients who had taken any oral antifungal or oral corticosteroid within the past 30 days; patients who had used any topical anfifungal, selenium sulfide, zinc, or topical corticosteroid within the past 7 days; or patients taking rifampin. Pregnant women, women trying to conceive, and nursing mothers were also excluded. Women of childbearing potential were required to practice reliable contraception. Patients were randomly assigned to receive 7 days of treatment with either itraconazole, 200 mg/day, or placebo. The use of any acid-suppressing drugs was prohibited for at least 2 hours after ingestion of the study drag. 785
786
Journal of the American Academy of Dermatology May 1996
Hi&man
100 -
90807060-
N
504030-
P<0.01
2010-
ITRACONAZOLE
I
PLACEBO
T R E A T M E N T GROUP
Fig. 1. Comparison of overall responses, according to investigator evaluation at week 5. Global evaluation: [-7, Healed; [Y~: markedly improved.
A KOH examination was performed at the baseline visit and 4 weeks after study completion (week 5). A culture was performed at the baseline visit to rule out dermatophytosis. The following scale was used to assess the degree of scaring, erythema, and pruritus at the baseline visit and at week 5:3 -- severe, 2 = moderate, 1 = mild, and 0 = none present. Global clinical evaluations at week 5 were rated as "healed" (no visual evidence of disease), "markedly improved" (mild, residual scaling, but no visual evidence of active disease), "considerable residual lesions" (active disease, with some improvement), "unchanged," or "deteriorated." Patients who had a negative KOH examination and a global clinical evaluation of healed or markedly improved were considered to be clinical responders. A positive KOH examination at week 5 or a global evaluation of considerable residual lesions, unchanged, or deteriorated indicated clinical nonresponders. Routine blood studies and urinalysis were performed at the baseline visit and at week 5. Women of childbearing potential also had a serum or urine pregnancy test at the baseline visit. A serum pregnancy test was repeated if there were any changes in menstrual cycle. RESULTS
A total of 36 patients were enrolled in the study; 18 were randomly assigned to treatment with itraconazole and 18 to treatment with placebo. One pa-
tient in the placebo group discontinued treatment after 5 days and was lost to follow-up. The demographics of each group were similar. Patients treated with itraconazole demonstrated significant (p < 0.001) improvement over baseline in scaling, erythema, and pruritus. No significant changes from basefine were seen in the placebotreated group. The differences between the two groups for each of these three signs of tinea versicolor were statistically significant (p < 0.02). Twelve of the 18 patients (67%) in the itraconazole-treated group became free of symptoms, as compared with 2 of the 17 patients (12%) in the placebo-treated group. Itraconazole also produced a significantly (p < 0.01) better overall response than placebo (Fig. 1). Twelve of the 18 itraconazole-treated patients (66.7%) were rated as healed and five (27.8%) were markedly improved. Only 1 of the 17 patients (6%) treated with placebo was rated as healed and none were rated as markedly improved. Conversely, eight patients (47%) receiving placebo were rated as unchanged or deteriorated, whereas only one patient (5%) receiving itraconazole was rated as unchanged, and none were considered to have deteriorated. A significantly (p <0.01) greater percentage of patients in the itraconazole-treated group than in the placebo-treated group had negative K O H examinations at week 5 (89% vs 6%, respectively). Significantly more patients treated with itraconazole were clinical responders (p < 0.01) when compared with those treated with placebo (89% vs 6%, respectively). There were two reports of adverse experiences that were possibly treatment-related. One patient in the itraconazole group reported mild dyspepsia and flatulence, and one patient in the placebo group reported moderate nausea and flatulence. DISCUSSION
In recent years, oral antifungal therapy has gained growing acceptance for the treatment of tinea versicolor. 2-5 In this trial, a single oral dosage of itraconazole, 200 mg for 7 days, produced statistically significant improvement over placebo in the treatment of tinea versicolor. Ninety-four percent of the patients receiving active treatment were rated as healed or markedly improved at week 5, whereas only 6% of
Journal of the American Academy of Dermatology Volume 34, Number 5, Part 1
placebo-treated patients received a favorable rating. These findings were closely paralleled b y the mycologic cure rates and by the percentage o f clinical responders. There were no significant differences between itraconazole and placebo in the incidence o f adverse experiences (a single patient in each treatment group).
Hickman 787 2. Delescluse J. Itraconazole in tinea versicolor: a review. J AM ACADDE~V~ATOL1990;23:551-4. 3. Faergemann J, Jarv L. Tinea versicolor: treatment and prophylaxis with ketoconazole. Curls 1982;30:542-5. 4. Jones HE. Ketoconazole today: a review of clinical experience. Manchester, UK: Adis Press, 1987. 5. Faergemann J. Treatment of pityriasis versicolor with itraconazole: a double-blind placebo-controlled study. Mycoses 1988;31:377-9.
REFERENCES 1. Hay RJ, Midgley G. Short course ketoconazole therapy in pityriasis versicolor. Clin Exp Dermatol 1984;9:571-3.
CALL FOR PATIENTS WITH INHERITED DISEASES OF THE SKIN We in San Francisco as well as skin biologists in other cities are interested in finding the chromosomal location and eventually identifying the genes whose abnormalities underlie several inherited diseases of the skin. Initially, the group believes diseases for which this strategy offers the most likely insights include several disorders of keratinization (ichthyoses, Darier's disease, and Halley-Halley disease), several forms of epidermolysis bullosa, several forms of Ehlers-Danlos syndrome, psoriasis, atopic dermatitis, and keloids. Indeed, ongoing studies of several such diseases have already been fruitful. We are eager to identify kindreds with these conditions--larger kindreds for the more common disorders (e.g., psoriasis, atopic dermatitis), and smaller as well as larger kindreds for the less common disorders (e.g. Darier' s disease). If you know of such a kindred, please contact Ervin Epstein, Jr., MD, Room 269, Bldg. 100, 1001 Potrero St., San Francisco, CA 94110; telephone: 1-800-285-1267; fax: (415)282-5998. Investigators interested in collaborating more actively in such a linkage analysis at either the clinical or the laboratory level also are most welcome to contact Dr. Epstein.
Background: The use of short-term oral azoles is an alternative to topical therapy in patients with linea versicolor. Objective: We compared the efficacy and safety of oral itraconazole with that of placebo in 36 patients with mycologically proven tinea versicolor. Methods: Patients were randomly assigned to 7 days of treatment with either itraconazole, 200 mg once daily, or placebo. A potassium hydroxide examination and assessment of scaling, erythema, pruritus, and global condition were performed at baseline and at 4 weeks after treatment. Results: The itraconazole-treated group demonstrated significant improvement over both baseline (p < 0.01) and placebo (p < 0.02) in scaling, erythema, and pruritus. Sixty-seven percent of itraconazole-treated patients were free of symptoms at week 5, as compared with 12% of placebo-treated patients. Ninety-four percent of itraconazole-treated patients were considered to be healed or markedly improved at the study's end point compared with 6% of placebo-treated patients (p < 0.01). A total of 89% in the itraconazole-treated group had a negative potassium hydroxide examination at the follow-up visit compared with 6% in the placebo-treated group (p < 0.01). There was a single report of a possibly treatment-related adverse event in each treatment group. Conclusion: Short-term treatment with itraconazole is effective and well tolerated in the management of tinea versicolor. (J AM ACAD DEP,MATOL 1996;34:785-7.)
Both topical and systemic therapies have been used for the treatment of tinea versicolor. Although oral azoles have usually been reserved for the treatment of more resistant cases, favorable results have been achieved in treating more routine cases for brief periods. Several studies have demonstrated a positive outcome when oral ketoconazole or itraconazole was administered for 5 to 7 days. l' 2 This study employed a randomized, double-blind, parallel group design to compare the efficacy and safety of a 7-day regimen of oral itraconazole versus placebo in patients with tinea versicolor.
From The Education and Research Foundation. Supported by an unrestricted grant from Janssen Pharmaceutica~ Titusville, N.J. Reprint requests: Janet G. Hickman, MD, 2602 Langhome Rd., Lynchburg, VA 24501. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0
16/1/69839
PATIENTS AND METHODS
Patients 12 years of age or older with a positive potassium hydroxide (KOH) examination at the baseline visit (visit 0) were eligible for study entry. All patients signed a written, informed consent before study entry. Exclusion criteria included patients with systemic fungal infections; oral, vaginal, or chronic mucocutaneous candidiasis; dermatophyte infections; onychomycosis; chronic liver disease; or any serious concurrent disease that might prevent completion of the study. Also excluded were patients who had taken any oral antifungal or oral corticosteroid within the past 30 days; patients who had used any topical anfifungal, selenium sulfide, zinc, or topical corticosteroid within the past 7 days; or patients taking rifampin. Pregnant women, women trying to conceive, and nursing mothers were also excluded. Women of childbearing potential were required to practice reliable contraception. Patients were randomly assigned to receive 7 days of treatment with either itraconazole, 200 mg/day, or placebo. The use of any acid-suppressing drugs was prohibited for at least 2 hours after ingestion of the study drag. 785
786
Journal of the American Academy of Dermatology May 1996
Hi&man
100 -
90807060-
N
504030-
P<0.01
2010-
ITRACONAZOLE
I
PLACEBO
T R E A T M E N T GROUP
Fig. 1. Comparison of overall responses, according to investigator evaluation at week 5. Global evaluation: [-7, Healed; [Y~: markedly improved.
A KOH examination was performed at the baseline visit and 4 weeks after study completion (week 5). A culture was performed at the baseline visit to rule out dermatophytosis. The following scale was used to assess the degree of scaring, erythema, and pruritus at the baseline visit and at week 5:3 -- severe, 2 = moderate, 1 = mild, and 0 = none present. Global clinical evaluations at week 5 were rated as "healed" (no visual evidence of disease), "markedly improved" (mild, residual scaling, but no visual evidence of active disease), "considerable residual lesions" (active disease, with some improvement), "unchanged," or "deteriorated." Patients who had a negative KOH examination and a global clinical evaluation of healed or markedly improved were considered to be clinical responders. A positive KOH examination at week 5 or a global evaluation of considerable residual lesions, unchanged, or deteriorated indicated clinical nonresponders. Routine blood studies and urinalysis were performed at the baseline visit and at week 5. Women of childbearing potential also had a serum or urine pregnancy test at the baseline visit. A serum pregnancy test was repeated if there were any changes in menstrual cycle. RESULTS
A total of 36 patients were enrolled in the study; 18 were randomly assigned to treatment with itraconazole and 18 to treatment with placebo. One pa-
tient in the placebo group discontinued treatment after 5 days and was lost to follow-up. The demographics of each group were similar. Patients treated with itraconazole demonstrated significant (p < 0.001) improvement over baseline in scaling, erythema, and pruritus. No significant changes from basefine were seen in the placebotreated group. The differences between the two groups for each of these three signs of tinea versicolor were statistically significant (p < 0.02). Twelve of the 18 patients (67%) in the itraconazole-treated group became free of symptoms, as compared with 2 of the 17 patients (12%) in the placebo-treated group. Itraconazole also produced a significantly (p < 0.01) better overall response than placebo (Fig. 1). Twelve of the 18 itraconazole-treated patients (66.7%) were rated as healed and five (27.8%) were markedly improved. Only 1 of the 17 patients (6%) treated with placebo was rated as healed and none were rated as markedly improved. Conversely, eight patients (47%) receiving placebo were rated as unchanged or deteriorated, whereas only one patient (5%) receiving itraconazole was rated as unchanged, and none were considered to have deteriorated. A significantly (p <0.01) greater percentage of patients in the itraconazole-treated group than in the placebo-treated group had negative K O H examinations at week 5 (89% vs 6%, respectively). Significantly more patients treated with itraconazole were clinical responders (p < 0.01) when compared with those treated with placebo (89% vs 6%, respectively). There were two reports of adverse experiences that were possibly treatment-related. One patient in the itraconazole group reported mild dyspepsia and flatulence, and one patient in the placebo group reported moderate nausea and flatulence. DISCUSSION
In recent years, oral antifungal therapy has gained growing acceptance for the treatment of tinea versicolor. 2-5 In this trial, a single oral dosage of itraconazole, 200 mg for 7 days, produced statistically significant improvement over placebo in the treatment of tinea versicolor. Ninety-four percent of the patients receiving active treatment were rated as healed or markedly improved at week 5, whereas only 6% of
Journal of the American Academy of Dermatology Volume 34, Number 5, Part 1
placebo-treated patients received a favorable rating. These findings were closely paralleled b y the mycologic cure rates and by the percentage o f clinical responders. There were no significant differences between itraconazole and placebo in the incidence o f adverse experiences (a single patient in each treatment group).
Hickman 787 2. Delescluse J. Itraconazole in tinea versicolor: a review. J AM ACADDE~V~ATOL1990;23:551-4. 3. Faergemann J, Jarv L. Tinea versicolor: treatment and prophylaxis with ketoconazole. Curls 1982;30:542-5. 4. Jones HE. Ketoconazole today: a review of clinical experience. Manchester, UK: Adis Press, 1987. 5. Faergemann J. Treatment of pityriasis versicolor with itraconazole: a double-blind placebo-controlled study. Mycoses 1988;31:377-9.
REFERENCES 1. Hay RJ, Midgley G. Short course ketoconazole therapy in pityriasis versicolor. Clin Exp Dermatol 1984;9:571-3.
CALL FOR PATIENTS WITH INHERITED DISEASES OF THE SKIN We in San Francisco as well as skin biologists in other cities are interested in finding the chromosomal location and eventually identifying the genes whose abnormalities underlie several inherited diseases of the skin. Initially, the group believes diseases for which this strategy offers the most likely insights include several disorders of keratinization (ichthyoses, Darier's disease, and Halley-Halley disease), several forms of epidermolysis bullosa, several forms of Ehlers-Danlos syndrome, psoriasis, atopic dermatitis, and keloids. Indeed, ongoing studies of several such diseases have already been fruitful. We are eager to identify kindreds with these conditions--larger kindreds for the more common disorders (e.g., psoriasis, atopic dermatitis), and smaller as well as larger kindreds for the less common disorders (e.g. Darier' s disease). If you know of such a kindred, please contact Ervin Epstein, Jr., MD, Room 269, Bldg. 100, 1001 Potrero St., San Francisco, CA 94110; telephone: 1-800-285-1267; fax: (415)282-5998. Investigators interested in collaborating more actively in such a linkage analysis at either the clinical or the laboratory level also are most welcome to contact Dr. Epstein.