A Comprehensive Systematic Review of The Relationship between Types of Combination Therapy (Oral and Topical) on the Healing Duration of Tinea Imbricata
Keywords:
Tinea imbricata, Combination therapy, Oral antifungal, Topical antifungal, Healing duration, Recalcitrant dermatophytosis, Systematic reviewAbstract
Introduction: Tinea imbricata is a chronic, recalcitrant dermatophyte infection caused by Trichophyton concentricum, predominantly affecting populations in tropical and subtropical regions. The infection is characterized by concentric, scaly plaques that are often difficult to treat, leading to high relapse rates. Despite various available antifungals, optimal treatment strategies, particularly the role of combination therapy (oral and topical), remain inadequately defined, especially concerning healing duration (A. Leung et al., 2019; Al-Bassam Rana Abdulazeem et al., 2019).
Methods: A comprehensive systematic review was conducted to evaluate the relationship between types of combination therapy (oral and topical) and the healing duration of tinea imbricata. Literature screening was performed across multiple databases using predefined criteria focusing on human studies with clinically/mycologically confirmed tinea imbricata, combination therapy interventions, and quantifiable healing outcomes. Data extraction covered treatment regimens, healing duration, patient characteristics, study design, long-term outcomes, and safety profiles from included studies.
Results: Out of 33 identified sources, only three specifically addressed tinea imbricata, with the majority examining other dermatophytoses. Combination therapies, such as oral terbinafine or itraconazole paired with topical agents (e.g., amorolfine, sertaconazole, keratolytic ointments), demonstrated faster initial response and significantly lower relapse rates compared to monotherapy. For instance, at 2 weeks, itraconazole combined with topical iodine achieved 75.9% improvement versus 24.1% for itraconazole alone (Thamir Abdulmajeed Kubaisi, 2022). Complete cure typically required 4-8 weeks, with extended duration improving outcomes. Safety profiles were generally comparable to monotherapy, with gastrointestinal symptoms being the most common adverse events.
Discussion: The synthesized evidence indicates that combination therapy is particularly advantageous for chronic, recalcitrant, or treatment-resistant infections, likely due to synergistic antifungal mechanisms and enhanced drug penetration. The heterogeneity in study findings can be attributed to variations in infection severity, patient populations, and study designs. The strongest evidence supporting combination therapy comes from comparative studies with adequate follow-up, showing substantial reductions in relapse rates (e.g., 7% vs. 57% for itraconazole + terbinafine vs. itraconazole alone) (Yagub S. Saleh et al., 2025).
Conclusion: Combination antifungal therapy, integrating oral and topical agents, appears to reduce healing duration and relapse rates in difficult-to-treat dermatophytosis, including tinea imbricata. For uncomplicated cases, monotherapy may suffice with adequate duration. Future high-quality, randomized controlled trials focusing specifically on tinea imbricata are essential to establish standardized, evidence-based treatment protocols.
References
A. Leung, Kin Fon Leong, and J. Lam. “Tinea Imbricata: An Overview.” Current Pediatric Reviews, 2019.
A. Wingfield, A.C. Fernandez‐Obregon, F. Wignall, and D. Greer. “Treatment of Tinea Imbricata: A Randomized Clinical Trial Using Griseofulvin, Terbinafine, Itraconazole and Fluconazole.” British Journal of Dermatology, 2004.
Al-Bassam Rana Abdulazeem, Alowami Salem, A. S. Saad, and S. Mohamed. “A SYSTEMATIC REVIEW OF DIAGNOSIS AND TREATMENT OPTIONS FOR TINEA IMBRICATA.” International Journal of Pharma and Bio Sciences, 2019.
Amit Shekar, Geetika Mittal, Rakhamaji D. Chandane, and U. Suranagi. “A PROSPECTIVE RANDOMIZED OPEN-LABELED PARALLEL GROUP STUDY TO COMPARE THE EFFICACY OF ORAL TERBINAFINE VERSUS ORAL TERBINAFINE PLUS ORAL FLUCONAZOLE IN DERMATOPHYTE INFECTIONS.” Asian Journal of Pharmaceutical and Clinical Research, 2023.
Annie Ratnam Nakka, Janardhan Bommakanti, Siva Rami R. Karumuri, and N. Thambisetti. “Evaluation of Newer Imidazoles in Dermatophytosis,” 2019.
Anuragini Gupta, S. Kaur, and P. Gill. “COMBINATION DRUG TREATMENT IN Tinea INFECTIONS OF CUTANEOUS SOFT TISSUES,” 2018.
Ayesha Sharmeen, S. Amin, M. Adil, and Iti Varshney. “Study of Effect of Oral Itraconazole with 2% Sertaconazole Cream Versus Oral Terbinafine with 2% Sertaconazole Cream in Dermatophytosis.” International Journal of Research in Dermatology, 2023.
Farhana Yeasmin, Shahin Ara, L. Khondker, Md. Nazrul Islam, Ibrahim Md. Sharaf, Nelofar Yasmin, and Gulam Kazem Ali Ahmad. “Comparison on Efficacy Between Itraconazole and Terbinafine in the Treatment of Cutaneous Dermatophytosis.” International Journal of Advanced Multidisciplinary Research and Studies, 2024.
G. AshwiniS, and Waheeda Banu. “A CLINICAL OBSERVATIONAL STUDY TO EVALUATE THE COMBINED EFFECT OF DADRUGHNA LEPA AND PITTAKUSTAHARA KASHAYA IN MANAGEMENT OF DADRU (TINEA).” International Journal of Ayurveda and Pharma Research, 2020.
G. Deshmukh, Vishalakshi Vishwanath, Pradnya Londhe, Dakshata Tare, and D. Dhoot. “Effectiveness and Safety of Combination of Itraconazole and Amorolfine in Management of Patients with Recalcitrant Multi-Site Dermatophytosis Who Failed Previous Combination Antifungal Therapy.” IP Indian Journal of Clinical and Experimental Dermatology, 2020.
Lazara Alacán Pérez, J. Travieso, Evelyn Anie González Pla, Yeni González Liriano, O. R. G. Lovio, Elizabeth Sanler Wong, Maylen Rodríguez Ordaz, et al. “Comparative Study of the Efficacy and Safety of the Ozonated Sunflower Oil, Ketoconazole and Terbinafine in Patients with Dermatophytosis.” Journal of Mycology and Infection, 2024.
Lokhande Pooja A, and Sathe Aparna N. “MISUSE OF TOPICAL STEROID AN ALARMING PROBLEM IN DERMATOPHYTOSIS.” December, 2020.
M. Kaur, Anuragini Gupta, R. Mahajan, and Manharan Gill. “Efficacy, Safety, and Cost Evaluation of the Topical Luliconazole Therapy Versus Topical Clotrimazole Therapy in Patients with Localized Dermatophytosis in a Tertiary Care Hospital: An Observational Study.” International Journal of Applied and Basic Medical Research, 2020.
M. Shahidullah, K. Islam, S. Islam, A. Asma, R. Sultana, M. Rahman, A. K. Nandi, and P. Das. “Systemic Therapy of Dermtophytosis with Voriconaole: A Clinical Observational Study of 250 Bangladeshi Patients.” Mymensingh Medical Journal, 2021.
M. Singh, and S. Bali. “Comparative Study Between Terbinafine and Griseofulvin Indermatophytosis in Children Between 5 Years to 15 Years.” IP Indian Journal of Clinical and Experimental Dermatology, 2020.
Maira Ali, Najia Ahmed, Seemab Khan, and Afshan Kiran. “EFFICACY OF ORAL VORICONAZOLE VERSUS ORAL ITRACONAZOLE, IN THE TREATMENT OF DERMATOPHYTE INFECTIONS.” Journal of Ayub Medical College, 2024.
Mohammad Mofizul Islam Khan, Md. Shirajul Islam Khan, and Ahm Kazi Mostofa Kamal. “Efficacy and Safety of Oral Terbinafine Versus Itraconazole in the Treatment of Dermatophytosis: A Randomized Clinical Trial.” Journal of Armed Forces Medical College Bangladesh, 2025.
Mohsena Akter, Md. Abdulla-Hel Kafi, Syed Shair Ahmed, and Ishrat Bhuiyan. “Comparative Study of Efficacy of Terbinafine 500mg Vs Terbinafine 250mg and Itraconazole 200mg in the Treatment of Dermatophytosis.” Z H Sikder Women's Medical College Journal, 2022.
N. Ullah, Abdur Rahim Khan, Kalsoom Aslam, and Syed Obaid. “Efficacy of Itraconazole Vs Itraconazole Plus Isotretinoin in Treatment of Chronic Tinea.” Pakistan Journal of Medical & Health Sciences, 2021.
Pranjal Salunke, S. Someshwar, and Mayur R Bhobe. “Efficacy of Daily Oral Terbinafine Versus Pulse Fluconazole Therapy in the Treatment of Tinea Corporis, Tinea Cruris, and Tinea Faciei: A Comparative Study,” 2020.
PRavindra Babu, AJ S Pravin, G. Deshmukh, D. Dhoot, A. Samant, and Bhavesh P Kotak. “Efficacy and Safety of Terbinafine 500 Mg Once Daily in Patients with Dermatophytosis.” Indian Journal of Dermatology, 2017.
S. Baveja, D. Vashisht, R. Kothari, Ruby Venugopal, and Rajneesh Kumar Joshi. “Comparative Evaluation of the Efficacy of Itraconazole with Terbinafine Cream Versus Itraconazole with Sertaconazole Cream in Dermatophytosis: A Within Person Pilot Study.” Medical Journal Armed Forces India, 2021.
S. Brigida, and A. Elizabeth. “A Comparative Study of Efficacy of Oral Terbinafine and Oralitraconazole in Tinea Corporis / Tinea Cruris Infection,” 2021.
S. Fonseka, B. Subhani, and P. Kumarasiri. “Effectiveness of Modified Whitfield’s Ointment with Oral Griseofulvin in the Treatment of Dermatophytosis Poorly Responsive to Standard Antifungal Therapy: A Randomized, Double Blind, Within Patient Placebo Control.” International Journal of Clinical Trials, 2019.
S. Fonseka, D. D. J. Bandara, Dasun Chathumina Wickramaarachchi, Narankotuwe Gedara Kumudu Hasanka Heshani Narankotuwa, and Pallegoda Vithana Ranjith Kumarasiri. “Treatment of Difficult-to-Treat-Dermatophytosis: Results of a Randomized, Double-Blind, Placebo-Controlled Study.” Journal of Infection in Developing Countries, 2021.
S. Singh, Najuma Subba, and R. Tilak. “Efficacy of Terbinafine and Itraconazole in Different Doses and in Combination in the Treatment of Tinea Infection: A Randomized Controlled Parallel Group Open Labeled Trial with Clinico-Mycological Correlation.” Indian Journal of Dermatology, 2020.
Saima Naseem, M. Nawab, S. H. Fatima, Ahmed Minhajuddin, and Asif Ahmad Khan. “Assessing the Efficacy and Safety of Unani Pharmacopoeial Formulations in Dermatophytosis (Quba) – a Randomized Controlled Trial.” Drug Metabolism and Personalized Therapy, 2022.
Saket Thaker, D. Mehta, H. Shah, J. Dave, and K. Kikani. “A Comparative Study to Evaluate Efficacy, Safety and Cost-Effectiveness Between Whitfield's Ointment + Oral Fluconazole Versus Topical 1% Butenafine in Tinea Infections of Skin.” Indian Journal of Pharmacology, 2013.
Suraj B. Pawar, and A. Deshmukh. “To Compare the Efficacy of Oral Terbinafine Alone Against the Combination of Oral Terbinafine and Intense Pulsed Light (IPL) in Difficult to Treat Tinea Patients.” MGM Journal of Medical Sciences, 2021.
Thamir Abdulmajeed Kubaisi. “Recurrent Dermatophytosis: A Comparative Therapeutic Study Using Oral Itraconazole Alone and in Combination with Topical Tincture of Iodine.” Research Journal of Pharmacy and Technology, 2022.
Yagub S. Saleh, Bassim I Mohammad, and Thamir Kubaisi. “Efficacy and Safety of Oral Itraconazole and Griseofulvin Versus Itraconazole Alone in Patients with Tinea Corporis and Cruris Infection: A Comparative Clinical Study.” Mustansiriya Medical Journal, 2024.
Yagub S. Saleh, Thamir A. Kubaisi, and Bassim I. Mohammad. “Oral Itraconazole and Terbinafine Vs. Itraconazole as a Novel Regimen for the Newly Emergent Chronic Tinea: A Comparative Clinical Study.” Iraqi Journal of Pharmaceutical Sciences, 2025.
Zinab Rabia Abo Almaati Hassaan, Hassan Abou Khodair Mohamed, R. Eldahshan, and M. Elsaie. “Comparison Between the Efficacy of Terbinafine and Itraconazole Orally Vs. The Combination of the Two Drugs in Treating Recalcitrant Dermatophytosis.” Scientific Reports, 2023.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Agustina Vonny Moa (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors publishing here keep copyright but grant the journal first publication rights, under a Creative Commons Attribution-NonCommercial 4.0 License. They can distribute their work non-exclusively elsewhere with an acknowledgment of its first publication in this journal. Posting the work online before and during submission for earlier and greater citation is encouraged, reflecting Open Access benefits.
