CLINICAL TRIALS
TINEA VERSICOLOR TREATED WITH ELUCONAZOLE SHAMPOO DIMITRIOS RIGOPOULOS, M.D., ANDREAS KATSAMBAS, M.D., CHRISTINA ANTONIOU, M.D., DORIS POLYDOROU, M.D., MARILENA VLACHOU, AND JOHN STRATIGOS, M.D.
Thirty-two patients having tinea versicolor were entered into a comparative study of fluconazole 2% shampoo versus the vehicle shampoo. All patients who met the criteria for inclusion were required to sign an informed consent form before entering the study and were randomized into treatment groups (16 patients each group) for a 5-day trial. Medication was given to each patient in a numbered box, following a sequential order. The characteristics of the patients of these two groups are summarized in Tables 1 and 2. The patients did not have any other treatment for at least 2 weeks prior to the use of the shampoo and for the duration of the study. The diagnosis in each case was based on the clinical picture and was confirmed by direct microscopy. For microscopy, a thin layer of epidermal scales and fungi was obtained by scratching and examined with light microscopy, after processing with KOH solution. Laboratory examination was performed, before entering the study and at days 6 and 15. The patients were told to shampoo their body with fluconazole shampoo 2%* or the placebo shampoo, which came in identical packages. They had to leave the shampoo on for 5 minutes before rinsing. They repeated this procedure for 5 days. A statistical analysis between the two groups, concerning the results, was performed by using t-test for age, sex, and duration of the disease; two-tailed Fisher's exact test for the effectiveness of the shampoo was used.
RESULTS
The patients of both groups were statistically comparable concerning the age and duration of disease (P > 0.1 for mean age, sex, and duration of the disease).
Table 1. Characteristics of Patients treated with Fluconazole 2% Shampoo Men
Number Age Mean age (yr) Duration of TV (mo) Mean duration (mo)
9 15-57 34.6+13.6 0.5-1 7 4.55+4.8
Women 7 16-57 34114.8 0.5-18 4±6.2
Total 16 15-57 34.3±13.7 0.5-18 4.3+5.3
Table 2. Characteristics of Patients treated with Placebo Shampoo Men Total Women Number 6 10 16 17-40 14-40 Age 14-38 30.6±5.2 29.8±7.3 Mean age (yr) 29.817.3 0.5-20 Duration of TV (mo) 0.5-1 9 0.5-20 Mean duration (mo) 4.8±7 5.0+5.5 4.91+5.8
All thirty-two patients returned for the follow-up visits. From the patients of the placebo group, they all had positive microscopic examinations on the 6th day and 2 weeks later. From the group of fluconazole 2 % shampoo, 12 patients (75%) were found negative (direct microscopy-culture) on the sixth day; however, in 4 patients (25%) the fungus was still isolated (Table 3). 81.25% of patients were negative after 2 weeks. Three patients (18.75%) remained positive and are considered treatment failures (Table 4).
DISCUSSION
"• Fluconazole 2% Shampoo was developed by Medochcmie Ltd., Research & Development Department, 1-10 Astronafton & Constantinople Str., Limassol, Cyprus.
Tinea versicolor, a common and chronic, usually superficial fungus infection, is most frequently located on the upper trunk. Lesions, with varying color, from brown to red, are slightly scaly and involve large areas of the body. Hypopigmented patches may also be present.'"'' Tinea versicolor occurs worldwide, but especially in tropical countries. It is caused by a spherical lipophilic yeast known as Pityrosporum orbiculare as it was named by Gordon (1951).'"'
From the Department of Dermatology, Athens University, "A. Sygros" Hospital, Athens, Greece. Address for correspondence: Dimitrios Rigopoulos, M.D., Athens University, Department of Dermatology, "A. Sygros" Hospital, 5 I. Dragoumi Str., 161 2t Athens, Greece. 664
Tinea Versicolor Rigopoulos ct al.
Table 3. Results from Patients Treated with Flueonazole 2% Shampoo (6th day) Laboratory examination Negative Positive Total
Men
Women
Total
7
5
12
(75%) (25%)
3
1
4
10
7
16
In conclusion, fluconazole 2% shampoo seems to be an effective, safe, cosmetically attractive and quick treatment of tinea versicolor.
REFERENCES
1.
Table 4. Results from Patients Treated with Fluconazole 2% Shampoo (15th day) Laboratory examination Negative Positive Total
Men
Women
8 2
5
10
6
1
2.
Total 13
3.
16
4.
(81.25% 3 (18.75%
Fluconazole is a new antifungal triazole and is currently approved for the therapy of oropharyngeal, esophageal, systemic candidiasis, and acute therapy and suppression of relapsed cryptoccocal meningitis. Its mode of action is mainly based on inhibition of ergosterol biosynthesis, which is essential for the normal growth pattern of yeasts and other fungi.'"- " hi vitro studies revealed that fluconazole was most active against yeast such as Candida spp. and Cryptoccocus neoformans and less active against dermatophytic fungi. \n vivo studies treating acute systemic candidiasis model in the mouse with fluconazole, and ketoconazole as a comparative agent, revealed that fluconazole was more active than the comparative agent." Cure rates for tinea versicolor treatment range from 71.5% to 1 0 0 % . ' - ' ' In our study, fluconazole 2 % , shampoo was shown to be effective in the treatment of tinea versicolor. The cure rate was 81.25%. None of the patients complained of any side effects. They all thought that the shampoo was cosmetically acceptable. The statistical analysis of the results was very significant in favor of fluconazole 2% shampoo (two-tailed Fisher exact test less than 0.0001 both on the 6th and on the 15th day).
5. 6.
7.
8.
9.
10. 11.
12.
13.
Faergemann J. Pityriasis versicolor, tinea nigra and piedra. In: Jacobs PH, ed. Antifungal drug therapy: a complete guide for the practitioner. New York: Marcel Dekker, 1990:23. Roberts S. Pityrosporum orbiculare incidence and distribution on clinically normal skin. Br I Dermatol 1969; 81:264-269. Parisis N, Stratigos J, Marcelou-Kinti U, Capetanakis f. Pityriasis, versicolor in Griecbenland und ihre Pradispositionsfaktoren. Hautarzt 1977; 28:259. Borelli D, Jacobs P, Nail L. Tinea versicolor epidemiologic, clinical and therapeutic aspects. J Am Acad Dermatol 1991; 25:300-305. Faergeman J, Fredriksson 1. Tinea versicolor. Acta Derm Venereol (Stockh) 1980; 60:92-93. Faergemann J, Fredriksson T. Tinea versicolor witb regard to seborrbeic dermatitis. Arch Dermatol 1979115:966-968. Faergemann J, Fredriksson T. Tinea versicolor. Some new aspects on etiology, patbogenesis and treatment. IntJ Dermatol 1982; 21:8-10. Faergemann J, Fredriksson T. Age incidence of Vityrosporum orbiculare on buman skin. Acta Derm Venereol (Stockb) 1980; 60:531-532. Perez H. A comparison between one and two weeks treatment witb bifonnzole in pityriasis versicolor. ) Am Acad Dermatol 1986; 14:561-562. Fromtling R. Fluconazole: A new antifungal triazole. Drugs Today 1990; 26:547-556. Henderson J. Fluconazole: a significant advance in tbe management of human fungal disease. In: Fromtling RA, ed. Recent trends in tbe discovery, development and evaluation of antifungal agents. Prous Science Publishers, S.A. 1987:77. Faergemann J, Fredriksson T. An open trial of tbe effect of a zinc piryrbione sbampoo in tinea versicolor. Cutis 1982; 25:668-669. Selim M, Krubec K. Pityriasis versicolor. Epidemiological and tberapeutical study. Mycoses 1988; 32:100-103.
HOFFMAN'S DROPS
From the collection of "La Pharmacie Fran^aise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 665
TINEA VERSICOLOR TREATED WITH ELUCONAZOLE SHAMPOO DIMITRIOS RIGOPOULOS, M.D., ANDREAS KATSAMBAS, M.D., CHRISTINA ANTONIOU, M.D., DORIS POLYDOROU, M.D., MARILENA VLACHOU, AND JOHN STRATIGOS, M.D.
Thirty-two patients having tinea versicolor were entered into a comparative study of fluconazole 2% shampoo versus the vehicle shampoo. All patients who met the criteria for inclusion were required to sign an informed consent form before entering the study and were randomized into treatment groups (16 patients each group) for a 5-day trial. Medication was given to each patient in a numbered box, following a sequential order. The characteristics of the patients of these two groups are summarized in Tables 1 and 2. The patients did not have any other treatment for at least 2 weeks prior to the use of the shampoo and for the duration of the study. The diagnosis in each case was based on the clinical picture and was confirmed by direct microscopy. For microscopy, a thin layer of epidermal scales and fungi was obtained by scratching and examined with light microscopy, after processing with KOH solution. Laboratory examination was performed, before entering the study and at days 6 and 15. The patients were told to shampoo their body with fluconazole shampoo 2%* or the placebo shampoo, which came in identical packages. They had to leave the shampoo on for 5 minutes before rinsing. They repeated this procedure for 5 days. A statistical analysis between the two groups, concerning the results, was performed by using t-test for age, sex, and duration of the disease; two-tailed Fisher's exact test for the effectiveness of the shampoo was used.
RESULTS
The patients of both groups were statistically comparable concerning the age and duration of disease (P > 0.1 for mean age, sex, and duration of the disease).
Table 1. Characteristics of Patients treated with Fluconazole 2% Shampoo Men
Number Age Mean age (yr) Duration of TV (mo) Mean duration (mo)
9 15-57 34.6+13.6 0.5-1 7 4.55+4.8
Women 7 16-57 34114.8 0.5-18 4±6.2
Total 16 15-57 34.3±13.7 0.5-18 4.3+5.3
Table 2. Characteristics of Patients treated with Placebo Shampoo Men Total Women Number 6 10 16 17-40 14-40 Age 14-38 30.6±5.2 29.8±7.3 Mean age (yr) 29.817.3 0.5-20 Duration of TV (mo) 0.5-1 9 0.5-20 Mean duration (mo) 4.8±7 5.0+5.5 4.91+5.8
All thirty-two patients returned for the follow-up visits. From the patients of the placebo group, they all had positive microscopic examinations on the 6th day and 2 weeks later. From the group of fluconazole 2 % shampoo, 12 patients (75%) were found negative (direct microscopy-culture) on the sixth day; however, in 4 patients (25%) the fungus was still isolated (Table 3). 81.25% of patients were negative after 2 weeks. Three patients (18.75%) remained positive and are considered treatment failures (Table 4).
DISCUSSION
"• Fluconazole 2% Shampoo was developed by Medochcmie Ltd., Research & Development Department, 1-10 Astronafton & Constantinople Str., Limassol, Cyprus.
Tinea versicolor, a common and chronic, usually superficial fungus infection, is most frequently located on the upper trunk. Lesions, with varying color, from brown to red, are slightly scaly and involve large areas of the body. Hypopigmented patches may also be present.'"'' Tinea versicolor occurs worldwide, but especially in tropical countries. It is caused by a spherical lipophilic yeast known as Pityrosporum orbiculare as it was named by Gordon (1951).'"'
From the Department of Dermatology, Athens University, "A. Sygros" Hospital, Athens, Greece. Address for correspondence: Dimitrios Rigopoulos, M.D., Athens University, Department of Dermatology, "A. Sygros" Hospital, 5 I. Dragoumi Str., 161 2t Athens, Greece. 664
Tinea Versicolor Rigopoulos ct al.
Table 3. Results from Patients Treated with Flueonazole 2% Shampoo (6th day) Laboratory examination Negative Positive Total
Men
Women
Total
7
5
12
(75%) (25%)
3
1
4
10
7
16
In conclusion, fluconazole 2% shampoo seems to be an effective, safe, cosmetically attractive and quick treatment of tinea versicolor.
REFERENCES
1.
Table 4. Results from Patients Treated with Fluconazole 2% Shampoo (15th day) Laboratory examination Negative Positive Total
Men
Women
8 2
5
10
6
1
2.
Total 13
3.
16
4.
(81.25% 3 (18.75%
Fluconazole is a new antifungal triazole and is currently approved for the therapy of oropharyngeal, esophageal, systemic candidiasis, and acute therapy and suppression of relapsed cryptoccocal meningitis. Its mode of action is mainly based on inhibition of ergosterol biosynthesis, which is essential for the normal growth pattern of yeasts and other fungi.'"- " hi vitro studies revealed that fluconazole was most active against yeast such as Candida spp. and Cryptoccocus neoformans and less active against dermatophytic fungi. \n vivo studies treating acute systemic candidiasis model in the mouse with fluconazole, and ketoconazole as a comparative agent, revealed that fluconazole was more active than the comparative agent." Cure rates for tinea versicolor treatment range from 71.5% to 1 0 0 % . ' - ' ' In our study, fluconazole 2 % , shampoo was shown to be effective in the treatment of tinea versicolor. The cure rate was 81.25%. None of the patients complained of any side effects. They all thought that the shampoo was cosmetically acceptable. The statistical analysis of the results was very significant in favor of fluconazole 2% shampoo (two-tailed Fisher exact test less than 0.0001 both on the 6th and on the 15th day).
5. 6.
7.
8.
9.
10. 11.
12.
13.
Faergemann J. Pityriasis versicolor, tinea nigra and piedra. In: Jacobs PH, ed. Antifungal drug therapy: a complete guide for the practitioner. New York: Marcel Dekker, 1990:23. Roberts S. Pityrosporum orbiculare incidence and distribution on clinically normal skin. Br I Dermatol 1969; 81:264-269. Parisis N, Stratigos J, Marcelou-Kinti U, Capetanakis f. Pityriasis, versicolor in Griecbenland und ihre Pradispositionsfaktoren. Hautarzt 1977; 28:259. Borelli D, Jacobs P, Nail L. Tinea versicolor epidemiologic, clinical and therapeutic aspects. J Am Acad Dermatol 1991; 25:300-305. Faergeman J, Fredriksson 1. Tinea versicolor. Acta Derm Venereol (Stockh) 1980; 60:92-93. Faergemann J, Fredriksson T. Tinea versicolor witb regard to seborrbeic dermatitis. Arch Dermatol 1979115:966-968. Faergemann J, Fredriksson T. Tinea versicolor. Some new aspects on etiology, patbogenesis and treatment. IntJ Dermatol 1982; 21:8-10. Faergemann J, Fredriksson T. Age incidence of Vityrosporum orbiculare on buman skin. Acta Derm Venereol (Stockb) 1980; 60:531-532. Perez H. A comparison between one and two weeks treatment witb bifonnzole in pityriasis versicolor. ) Am Acad Dermatol 1986; 14:561-562. Fromtling R. Fluconazole: A new antifungal triazole. Drugs Today 1990; 26:547-556. Henderson J. Fluconazole: a significant advance in tbe management of human fungal disease. In: Fromtling RA, ed. Recent trends in tbe discovery, development and evaluation of antifungal agents. Prous Science Publishers, S.A. 1987:77. Faergemann J, Fredriksson T. An open trial of tbe effect of a zinc piryrbione sbampoo in tinea versicolor. Cutis 1982; 25:668-669. Selim M, Krubec K. Pityriasis versicolor. Epidemiological and tberapeutical study. Mycoses 1988; 32:100-103.
HOFFMAN'S DROPS
From the collection of "La Pharmacie Fran^aise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 665
