|Year : 2022 | Volume
| Issue : 1 | Page : 100-103
Ketoconazole 2% cream versus a combination of ketoconazole 2% cream and adapalene 0.1% gel in the treatment of pityriasis versicolor
Khaled M Tawfik1, Waleed A Mahmmoud1, Amira G.E. Ali2
1 Department of Dermatology, Venerology and Andrology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
2 Student Health Care Unit, Al-Azhar University, Assiut, Egypt, Egypt
|Date of Submission||24-Aug-2021|
|Date of Decision||15-Sep-2021|
|Date of Acceptance||16-Oct-2021|
|Date of Web Publication||4-Mar-2022|
Source of Support: None, Conflict of Interest: None
Background and aim Pityriasis versicolor is a common chronic superficial fungal infection that manifests during or after puberty in hot humid temperatures. Topical treatments, which are the first line of treatment, are divided into nonspecific and specific antifungal agents; however, the therapeutic approaches for pityriasis versicolor depend mainly on synthetic antifungal drugs, in particular ketoconazole. However, due to the frequent recurrence of this disease, and the widespread application of azole drugs, resistant strains have emerged leading to increasingly failed treatment rates. Retinoic acid creams are also effective against pityriasis versicolor. Especially adapalene gel that has less irritation compared with other topical retinoid products and also has rapid onset of action. Therefore, we aimed to evaluate the efficacy and safety of a combination treatment of ketoconazole cream 2% and adapalene gel 0.01% in the treatment of pityriasis versicolor.
Patients and methods In all, 100 patients were divided equally into two groups: group 1 patients were treated with topical application ketoconazole 2% cream and adapalene 0.1% gel once daily for a total duration of 2 weeks. Group 2 patients were treated with a topical application ketoconazole 2% cream for a total duration of 2 weeks.
Results There was significant improvement rates in the combined group than ketoconazole-only group with P value=0.023. Adepalene+ketoconacole group had more irritation as a side effect than the ketoconazole group with significant P value=0.001.
Conclusion The combination of adapalene 0.1% gel and ketoconazole 2% cream is safe, rapid, and effective in the treatment of pityriasis versicolor.
Keywords: adapalene, efficacy, ketoconazole, pityriasis versicolor, side effects
|How to cite this article:|
Tawfik KM, Mahmmoud WA, Ali AG. Ketoconazole 2% cream versus a combination of ketoconazole 2% cream and adapalene 0.1% gel in the treatment of pityriasis versicolor. Al-Azhar Assiut Med J 2022;20:100-3
|How to cite this URL:|
Tawfik KM, Mahmmoud WA, Ali AG. Ketoconazole 2% cream versus a combination of ketoconazole 2% cream and adapalene 0.1% gel in the treatment of pityriasis versicolor. Al-Azhar Assiut Med J [serial online] 2022 [cited 2022 Jun 29];20:100-3. Available from: http://www.azmj.eg.net/text.asp?2022/20/1/100/339082
| Introduction|| |
Pityriasis versicolor is a superficial fungal infection  that manifests mainly in the tropical population . Diagnosis is based on clinical signs and symptoms and is confirmed by microscopy , dermoscopy , and Wood’s lamp .
Topical medications are the first-line therapy for pityriasis versicolor in particular ketoconazole . The misuse of azoles leads to the appearance of resistant strains with high recurrence of pityriasis versicolor leading to failed treatment .
To improve the efficacy of drugs and prevent the development of resistant strains, we combine ketoconazole with nonspecific antifungal drugs, such as retinoids specially adapalene that has rapid onset of action and least irritation . In this study we aimed to evaluate the efficacy and safety of a combination treatment of ketoconazole cream 2% and adapalene gel 0.01% in the treatment of pityriasis versicolor.
| Patients and methods|| |
The study was carried out on 100 patients showing various clinical forms of pityriasis versicolor, who had not received any antifungal treatment during the last 2 weeks. The patients selected were those attending the Dermatology and Andrology Outpatient Clinic, of Al-Azhar University Hospital in Assiut, between December 2019 and December 2020. The Committee of Local Institutional Ethics of Faculty of Medicine, Al-Azhar University, approved the study and informed written consent was obtained from all participants. The study is conducted in accordance with Helsinki standards as revised in 2013.
Patients with pityriasis versicolor were included after diagnosis, while pregnant and nursing patients, patients diagnosed with other autoimmune diseases or receiving immunosuppressive drugs, and patients who had received any therapy for pityriasis versicolor during the last 2 weeks before enrollment into the study were excluded from the study.
The patients were divided into two groups:
- Group 1: included 50 patients with pityriasis versicolor, and examined clinically and photographed (after taking an informed consent from the patients) before and after being treated with topical application ketoconazole 2% cream and adapalene 0.1% gel once daily for a total duration of 2 weeks.
- Group 2: included 50 patients with pityriasis versicolor, examined clinically, and photographed (after taking informed consent from the patients) before and after being treated with a topical application ketoconazole 2% cream for a total duration of 2 weeks.
We used dermoscopy to confirm the diagnosis; there was a decreased reticulate pigmentary network in comparison to the normal surrounding skin with fine scales in hypopigmented variants, while in hyperpigmented variants there was increased reticulate pigmentary network.
In addition, Wood’s light was used to confirm diagnosis that was seen in yellow-green fluorescent color.
Sample size was calculated using Stata/IC, version 16.1 for windows (StataCrop., LLC, College Station, Taxes, USA). Using the estimated sample sizes for a two-sample proportion test using Pearson’s χ2 test, we found that a sample size of 100 patients give at least 80% power showing a difference of 0.233 between the null hypothesis that the proportion in both group is 0.7 and our hypothesis that the proportion in the group treated with a combination of ketoconazole and adapalene is 0.933 associated with a significance level of 0.05.
Statistical analysis was done using Stata/IC, version 16.1. The test of normality was computed by the Kolmogorov–Smirnov test. We used Student’s t test to compare the mean between the normally distributed variables. Mann–Whitney U test was also used. On the other hand, the χ2 test was used to compare the percentages of category variables. P value less than 0.05 was considered significant.
| Results|| |
In all, 50 patients were included in a group treated with a combination of adapalene and ketoconazole and 50 patients were treated with ketoconazole alone. The demographic data of our studied population are shown in [Table 1]. The duration of the disease ranged between 1 and 8weeks as shown in [Table 1].
There were a statistically significant differences between adapalene+ketoconazole and ketoconazole-alone group, with significant P value=0.023 as shown in [Table 2].
|Table 2 Comparison between the studied groups regarding overall clinical improvement|
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The adapalene group had more side effects such as irritation than the ketoconazole group with significant P value=0.001 as shown in [Table 3].
|Table 3 Comparison between the studied groups regarding side effects and patients’ satisfaction|
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The degree of improvement according to the patient opinion (grade 1 was unsatisfied, grade 2 was moderately satisfied, and grade 3 was well satisfied). There was a significant difference in satisfaction between the adapalene+ketoconazole group and ketoconazole-alone group, P=0.045 as shown in [Table 3].
| Discussion|| |
In this study, we found that the combination of ketoconazole 2% cream and adapalene 0.1% gel had a more significant effect against pityriasis versicolor than ketoconazole 2% cream alone.
In this study, the frequency of improvement according to the quartile grading scale was significantly higher with the combination therapy (96 vs. 74%; P=0.023) as compared with the ketoconazole alone. Our results are in conformity with the previously published report by Shi et al. , who reported that addition of adapalene 0.1% gel to 2% ketoconazole cream significantly increased the frequency of patients (92 vs. 72%; P=0.0009). Our result also come in accordance with the study by Bakr et al. , as they reported that 28 (93.3%) patients in the combination group achieved significantly improvement; however, 25 (83.3%) patients in the monotherapy group were significantly improved.
Another study by Ashraf  reported 87.5% improvement rate in the combination group; however, only 47.5% of patients were improved in the group treated with ketoconazole alone.
In our study, 88% of patients in the combination group was satisfied about their improvement; however 76% of patients in the monotherapy group were satisfied regarding their improvement. Our result come in accordance with the study by Bakr et al.  as they reported that 96.7% of patients were satisfied about the improvement in the combination therapy group and 80% in the ketoconazole monotherapy group.
In this study, mild irritation as a side effect was reported in 34% in adapalene+ketoconazole group and only in 6% in the ketoconazole monotherapy group.
However, in the study by Bakr et al.  they reported that 3% of patients in the combination therapy group developed irritation as a side effect; however, none of the patients in the ketoconazole group reported having an irritation.
The present study confirms the advantage of combination therapy over monotherapy with no or mild side effects. Clinical superiority of the combination treatment was observed, and statistical superiority was noted. The improvement was faster and greater in the combination group versus the monotherapy group. Thus, we believe that the rapid effect of the combination treatment will prevent drug resistance.
The limitations of this trial were that the sample size was not very large. The lack of long-term follow-up to assess safety and relapse was also a limitation, necessitating future studies that address these issues.
Further studies must be conducted with a large number of patients with versicolor, and long follow-up periods are needed to clarify the therapeutic effect and to assess the safety and relapse of therapeutic agents.
Further comparative studies with other treatment modalities can be assessed in the treatment of pityriasis versicolor.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tligui H, El Ftouh S, Oudaina W. Epidemioclinical and mycological patterns of pityriasis versicolor in the urban area. J Med Surg Res 2020; 6:702–704.
Honnavar P, Dogra S, Handa S, Chakrabarti A, Rudramurthy SM. Molecular identification and quantification of malassezia species isolated from pityriasis versicolor. Indian Dermatol Online J 2020; 11:167–170. [Full text]
Karray M, McKinney WP. Tinea (pityriasis) versicolor. Treasure Island, FL: StatPearls Publishing; 2019.
Al Aboud DM, Gossman W. ‘Woods Light’, StatPearls. 2020.
Kaur I, Jakhar D, Singal A. Dermoscopy in the evaluation of pityriasis versicolor: a cross sectional study. Indian Dermatol Online J 2019; 10:682–685.
Gupta AK, Foley KA. Antifungal treatment for pityriasis versicolor. J Fungi (Basel, Switzerland) 2015; 1:13–29.
Snelders E, Van Der Lee HA, Kuijpers J, Rijs AJM, Varga J, Samson RA et al.
Emergence of azole resistance in Aspergillus fumigatus
and spread of a single resistance mechanism. PLoS Med 2008; 5:e219.
Shi T-W., Ren X-K., Yu H-X., Tang Y-B. Roles of adapalene in the treatment of pityriasis versicolor. Dermatology 2012; 224:184–188.
Shi T-W., Zhang J-A., Tang Y-B., Yu H-X., Li Z-G., Yu J-B. A randomized controlled trial of combination treatment with ketoconazole 2% cream and adapalene 0.1% gel in pityriasis versicolor. J Dermatol Treat 2015; 26:143–146.
Bakr E, Abdo H, Abd‐Elaziz H, Abd‐Elrazek H, Amer M. Adapalene gel 0.1% vs ketoconazole cream 2% and their combination in treatment of pityriasis versicolor: a randomized clinical study. Dermatol Ther 2020; 33:e13319.
Ashraf S. Comparison of topical ketoconzole alone versus topical ketoconazole plus topical adapalene in the treatment of patients with pityriasis versicolor. J CMH Lahore Med Coll 2018; 2:5–8.
[Table 1], [Table 2], [Table 3]