Comparison of safety and efficacy of Oral Terbinafine with Amphotericin B gel and Sertaconazole cream for the treatment of Tinea Corporis and its effect on quality of life of patients

Background: Tinea Corporis is a superfi cial fungal infection affecting 20-25% of the world’s population. Management involves using topical and oral antifungal drugs. Terbinafi ne has been used commonly for the treatment of tinea corporis to prevent the emergence of resistance combination of drugs is used. Hence, this study was designed to compare the safety and effi cacy of Sertaconazole and Amphotericin B when either is used with oral Terbinafi ne. Methodology: This open-label, randomized, prospective and parallel group study was conducted on patients suffering from tinea corporis visiting the Department of Dermatology. All patients underwent a thorough clinical examination to establish the diagnosis of tinea corporis and were divided into two groups. Patients in Group A received treatment with Sertaconazole and Terbinafi ne. Group B received treatment with Amphotericin B and Terbinafi ne. At the end of treatment phase patients were assessed clinically for the disease symptoms erythema, pruritus, and scaling; adverse effects experienced and Dermatological life quality index (DLQI). Results: Fifty two (52) patients were enrolled in the study, both groups were comparable at baseline. After 2 weeks of treatment, complete clinical cure was found in 6 patients in Group A and 5 patients in Group B. The treatment also showed improvement in clinical disease activity as there was clinical improvement seen in 22 patients in group A as compared to 25 patients in Group B. Greater number of patients in Group B reported with symptomatic improvement. There was no serious adverse event reported in both groups and DLQI score was comparable. Conclusion: The use of topical antifungals along with systemic antifungals has been found to be useful in early achievement of clinical cure and improvement in clinical symptoms of tinea corporis. Review Article Comparison of safety and effi cacy of Oral Terbinafi ne with Amphotericin B gel and Sertaconazole cream for the treatment of Tinea Corporis and its effect on quality of life of patients Sumedha Sirohi1, Sumit Bhutani1, Cherry Cheema1, Gurleen Kaur2, S P Singh3, Prithpal S Matreja4* 1MBBS Student, Fourth Year, Gian Sagar Medical College and Hospital, Village Ram Nagar, District Patiala, Punjab, India-140601 2Assistant Professor, Department of Pharmacology, Gian Sagar Medical College and Hospital, Village Ram Nagar, District Patiala, Punjab, India-140601 3Professor & HOD, Department of Dermatology, Gian Sagar Medical College and Hospital, Village Ram Nagar, District Patiala, Punjab, India-140601 4Professor and Head, Department of Pharmacology, Teerthankar Mahaveer Medical College & Research Center, TMU, Moradabad, 244001, Uttar Pradesh, India Dates: Received: 07 July, 2017; Accepted: 07 September, 2017; Published: 09 September, 2017 *Corresponding author: Prithpal Singh Matreja, Department of Pharmacology, Professor and Head, TeerthankarMahavir Medical College Research Center, TMU Moradabad, UP, India, Tel: +91-9855001847; E-mail:


Introduction
Tinea Corporis is a superfi cial fungal infection (dermatophytosis) anywhere on the body except the scalp, beard, feet, or hands. Fungal infections of the skin and nails have been found to affect 20-25% of the world's population, making them one of the most frequent forms of infection [1].
It may occur on any part of the body, and may have a variety of appearances, most easily identifi able by enlarging raised red rings with a central area of clearing [2]. The disease can be acquired by person to person transfer usually via direct skin contact with affected individual. The fungus also spreads by touching inanimate objects like personal care products, bed linen, combs, athletic gear or hair brushes contaminated by affected person [2]. Generally a mild and non-threatening condition, tinea can affect people at any age. Individuals at high risk include those living in crowded or humid conditions, sweat excessively, wear tight constrictive clothing with poor circulation, and have weakened immune system. The quality of life has been shown to be impaired with tinea corporis [3].
The pharmacological management of tinea corporis involves using topical and oral antifungal drugs like allylamines, azoles, polyene antibiotics. The topical agents are more commonly used; the oral drugs being used for extensive lesions [4,5]. are commonly prescribed drugs. A meta-analysis by Rotta et al, found terbinafi ne (allylamine) to be superior to azoles group of antifungal drugs [6]. Sertaconazole, an imidazole antifungal drug, inhibits the synthesis of ergosterol and posses potent anti-infl ammatory action also [4,7]. A prospective, single blind, randomized control trial done to compare topical sertaconazole with topical terbinafi ne showed that at the end of 3 weeks both terbinafi ne and sertaconazole groups had complete cure. Sertaconazole was as effective as terbinafi ne and both drugs showed good tolerability with no adverse effects [7]. Another study done to compare effi cacy of Sertaconazole and Clotrimazole in Tinea corporis patients showed signifi cant reduction in erythema, itching, and margins of lesion (p<0.001) among Sertaconazole group within a span of three weeks in the treatment [8].
A study done to assess the safety, tolerability and effi cacy in mucocutaneous fungal infection of amphotericin B gel showed that appreciable number of patients was cured at the end of treatment with no serious adverse effect reported [9]. Lipid based Amphotericin B gel formulation is more compatible with skin, showed encouraging clinical results and has lesser adverse drugs reactions like; blistering, itching, redness, peeling, dryness or irritation of the skin [4,9].
Terbinafi ne has been used commonly for the treatment of tinea corporis but in recent years, the resistance has been increasing. To prevent the emergence of resistance and wide coverage, combination of drugs from different groups of antifungals should be used [4,5,10].
Not many studies are there to compare the combination therapy of oral with topical agents in the treatment of tinea corporis. Most of the data till date available about the treatment of the disease is mainly from studies done in other parts of world. Hence, this study was designed to compare the safety and effi cacy of Sertaconazole cream and Amphotericin B gel when either is used along with oral Terbinafi ne. Also, this study assessed the improvement in quality of life of patients of tinea corporis after treatment with these drugs.

Material and Methods
This open-label, randomized, prospective and parallel group study was conducted in the outpatient department of dermatology in a tertiary care hospital after approval from Institutional Ethics Committee (IEC) for duration of 2 months from April to May 2016. A total of 52 patients suffering from tinea corporis visiting the Department of dermatology were enrolled in the study after they gave a written informed consent. The clinical diagnosis of tinea corporis was made based upon the presenting signs and symptoms of the patient.
Patients clinically diagnosed with tinea corporis infection, of either sexes and less than 60 years of age were included in the study. All patients enrolled in the study had positive skin scraping under direct microscopy.
Patients suffering from diabetes mellitus, sub acute cutaneous lupus erthematosus [11], clinical cases of eczema, lichen planus, drug induced eruptions, urticaria, tinea ungium and any chronic medical illness were excluded from the study. Patients with known history of hypersensitivity to any component of drug, substance abuse, pregnant and lactating mothers were also excluded from the study.

Statistical analysis
The data was tabulated as mean ± standard deviation (SD). Results were analyzed using various non-parametric tests (ChiSquare Test) and parametric tests (two-tailed student t-test). A p<0.05 was considered statistically signifi cant.

Results
Fifty two (52) patients were enrolled after they gave their written informed consent. The baseline parameter were comparable in both the groups at baseline, no signifi cant difference was found in gender, age, and duration of disease and family history of the disease between the two groups, indicating similar demographic profi le of the patients in the two groups (Table 1).

Treatment effectiveness
After 2 weeks of treatment, complete clinical cure was found in 6 patients in Group A and 5 patients in Group B. The treatment also showed improvement in clinical disease activity as there was clinical improvement seen in 22 patients in group A as compared to 25 patients in Group B (Figure 1). The difference between the effi cacy in the two groups was statistically insignifi cant with p-value of 0.16.
Greater number of patients in Group B reported with symptomatic improvement though it was not statistically signifi cant. Erythema in two groups, it was seen that redness was resolved in 7 and 11 patients of Group A and Group B respectively. Similarly, improvement in itching showed 10 and 12 patients with 100% resolved symptom in the group A and Group B respectively (Figure 2). Similarly more number of patients had improvement in scaling in Group B (Figure 2).

Safety profi le
There was no serious adverse event reported in both groups. None of the patients required reduction in dose or any therapy for treatment of adverse events. No patient was lost to the follow up.

DLQI score
The mean ± SD DLQI score in Group A and Group B was 7.38 ± 2.91 and 7 ± 2.48 respectively at the end of two weeks of treatment. There was statistically insignifi cant difference between the DLQI scores in both groups.

Discussion
Despite the increasing prevalence of cutaneous dermatophytosis across the world, and especially in tropical countries like India, the data on guidelines on the management of tinea corporis are not adequate [4]. Few Cochrane reviews on topical therapy in tinea corporis have helped to bridge this knowledge gap but still some guidelines/ trials on the dose and duration of the combination of systemic and oral antifungal in tinea corporis are conspicuous by their absence [4,10].
Our study did not fi nd any signifi cant difference in the age, gender, age, and duration of disease and family history of the disease. A similar study with no signifi cant differences in the age, sex, duration of disease, family members with fungal infections found 34 years as mean age [15].
After 2 weeks of treatment, complete clinical cure was found in 23% patients in Group A and 19% patients in Group B. A study by Voravutinon also had similar result (19.4%) at the end of 2 weeks of treatment with terbinafi ne [15]. Similarly, Cochrane review on the topical antifungal treatments for tinea corporis suggested that treatment with terbinafi ne is effective with few adverse effects [16]. Improvement in clinical symptoms of tinea corporis was found in 85% of the patients on Terbinafi ne and Sertaconazole and 96% of the patients on Terbinafi ne and Amphotericin B in our study. A study by Cole et al also found similar improvement rates of 87% with 500 mg of oral Terbinafi ne for 6 weeks [17].
There was effective therapy in 77.4% at 2 weeks treatment and 87.1% at 6 weeks treatment with 250 mg oral terbinafi ne once   daily. An effective therapy in 89.2% patients of tinea corporis was seen after 2 weeks of therapy with amphotericin B gel in a studyby Sheikh et al. [9].
According to a study, 4 patients had mild adverse effects (nausea, diarrhea, and headache) but they subsided and all were able to complete their full course of treatment with Terbinafi ne [15]. Our study did not report any adverse effect.
The reason for the difference could be due to the less dose and duration of the therapy. Moreover, in one of the groups, we used natural lipids as Amphotericin B gel, which reduced the chances of adverse reactions, making it compatible to the skin, and minimizing allergic reactions.Sheikh et al also did not report any adverse event in 83 patients of their study using lipid based amphotericin B gel [9].
We used 250 mg oral terbinafi ne with either Sertaconzole cream or Amphotericin B gel for 2 weeks treatment. It has been proved in various trials that the use of topical antifungals along with systemic antifungals has been found to be more useful in early achievement of clinical and mycological cure as well as decreasing the duration of oral antifungals leading to better patient compliance [4].
Comparing the skin related quality of life (DLQI) score; it was found that the mean in Group A and Group B was 7.38 and 7 respectively. A study by Hongbo reported the overall mean DLQI score of 4.86, which is comparable [14].
Various drawbacks of this study are as follows: the study could have a follow-up after 2 weeks to assess the complete cure of the patients of tinea corporis and to assess the adverse effects after 2 weeks after treatment with combination therapy.
Also, the duration of treatment could also be increased to assess the effi cacy of the treatment regime after 2 weeks of treatment.

Conclusion
The

Source of Funding
This projects is a part of ICMR-STS (Indian Council of Medical Research -Short term Studentship Program) 2016.
The project has been supported by ICMR-STS 2016 program.