Onikomikoz ve Tedavi Yaklaşımları

Year 2022, Volume: 7 Issue: 3, 587 - 612, 01.12.2022

Merve Gül , İhsan Çiftçi

https://doi.org/10.25279/sak.1053918

Abstract

Onikomikoz, tırnak hastalıklarının yaklaşık %50'sini oluşturan başlıca tırnak enfeksiyonlarından biridir. Hastaların tedavi uyumsuzluğu, yüksek maliyet, uzun tedavi süreleri ve hastalığın tekrarlama olasılığının yüksek olması gibi pek çok faktör onikomikoz tedavisinde zorluk yaratır. Doğru ve uygun maliyetli onikomikoz tedavisi için tanıyı doğru koymak da önemlidir. Farklı tanı yöntemleri kullanılsa da, en sık tercih edilen yöntem fungal kültürdür. Onikomikozun tedavisinde oral ve topikal tedavi yöntemleri ayrı ayrı veya kombine olarak uygulanabilir. Oral tedavide allilaminler ve azoller kullanılmakta olup, etkinlik yüksektir. Ancak hepatotoksik etki ve ilaç-ilaç etkileşimleri oral tedavi için büyük problemler yaratabilir. Topikal tedavide ise en sık siklopiroks, amorolfin, efinaconazole ve tavaborole kullanılır. Topikal tedavi yöntemi olarak farklı antifungaller çözeltiler veya bitkisel ekstratlar da kullanılmaktadır. Topikal ilaçların uygulanması daha kolaydır ve çok daha az yan etki gösterir, ancak tırnakların keratin açısından zengin yapısı yetersiz penetrasyona neden olur. Bu derlemede, onikomikoz, tanı yöntemleri ve tedavideki yeni yaklaşımların neler olduğu gözden geçirilmiştir.

Keywords

Onikomikoz, Tırnak, Tedavi, Tinea unguium

Onıcomycosıs and Treatment Approaches

Abstract

Onychomycosis is one of the main nail infections, accounting for approximately 50% of nail diseases. Many factors create difficulties in the treatment of onychomycosis, such as treatment non-compliance, high cost, long treatment period, and the high probability of recurrence of the disease. It is also important to make an accurate diagnosis for the treatment of onychomycosis accurately and cost-effectively. Although different diagnostic methods are used, the most preferred method is fungal culture. In the treatment of onychomycosis, oral and topical treatment methods can be applied separately or in combination. Allylamines and azoles are used in the oral treatment and the efficiency is high. However, hepatotoxic effects and drug-drug interactions can create major problems for oral therapy. In topical treatment, ciclopirox, amorolfine, efinaconazole, and tavborole are most commonly used. Different antifungals solutions or herbal extracts are also used as topical treatment method. Topical medications are easier to apply and have far fewer side effects, but the keratin-rich structure of the nails causes poor penetration. In this review, the diagnostic methods and new approaches in the treatment of onychomycosis are reviewed.

Keywords

Onychomycosis, Diagnosis, Nail, Tinea unguium

References

• Aggarwal, R., Targhotra, M., Kumar, B., Sahoo, P. K. ve Chauhan, M. K. (2020). Treatment and management strategies of onychomycosis. Journal de Mycologie Médicale, 30(2), 100–949. doi:https://doi.org/10.1016/j.mycmed.2020.100949
• Aggarwal, R., Targhotra, M., Sahoo, P. K. ve Chauhan, M. K. (2020). Onychomycosis: Novel strategies for treatment. Journal of Drug Delivery Science and Technology, 57, 4–7. doi:https://doi.org/10.1016/j.jddst.2020.101774
• Akpinar Kara, Y. (2021). The change of causative pathogens in toenail onychomycosis. Journal of Cosmetic Dermatology, 20(7), 2311–2316. doi:https://doi.org/10.1111/jocd.13819
• Aksu, O. (2009). Onikomikozda Klinik ve Mikolojik Araştırmalar. https://docplayer.biz.tr/4372883-O-dkomdkozda-kld-dk-ve-mdkolojdk-arastirma.html adresinden erişildi.
• Angelo, T., Borgheti-Cardoso, L. N., Gelfuso, G. M., Taveira, S. F. ve Gratieri, T. (2016). Chemical and physical strategies in onychomycosis topical treatment: A review. Medical Mycology, 55(5), 461–675. doi:https://doi.org/10.1093/mmy/myw084
• Arrese, J. E. ve Piérard, G. E. (2003). Treatment Failures and Relapses in Onychomycosis: A Stubborn Clinical Problem. Dermatology, 207(3), 255–260. doi:https://doi.org/10.1159/000073086
• Baran, R., Hay, R., Haneke, E., Tosti, A. ve Piraccini, B. M. (2006). Part 5: Mycological examination. Onychomycosis: The Current Approach to Diagnosis and Therapy-Google Kitaplar içinde (ss. 28–32). London: Martin Dunitz Ltd. https://books.google.com.tr/books?hl=tr&lr=&id=WdX_X08cyRoC&oi=fnd&pg=PA28&dq=Onychomycosis:+The+current+approach+to+diagnosis+and+therapy&ots=KA0IZPg2j9&sig=FCGiYMmaW2zpRy1pSTRv4AtmCx4&redir_esc=y#v=onepage&q&f=false adresinden erişildi.
• Baran, R. ve Kaoukhov, A. (2005). Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapy. Journal of the European Academy of Dermatology and Venereology, 19(1), 21–29. doi:https://doi.org/10.1111/j.1468-3083.2004.00988.x
• Baran, R., Sigurgeirsson, B., de Berker, D., Kaufmann, R., Lecha, M., Faergemann, J., … Sidou, F. (2007). A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix invol. The British journal of dermatology, 157(1), 149–57. doi:10.1111/j.1365-2133.2007.07974.x
• Belenky, P., Camacho, D. ve Collins, J. J. (2013). Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway. Cell Reports, 3(2), 350–358. doi:https://doi.org/10.1016/j.celrep.2012.12.021
• Bohn, M. ve Kraemer, K. T. (2000). Dermatopharmacology of ciclopirox nail lacquer topical solution 8% in the treatment of onychomycosis. Journal of the American Academy of Dermatology, 43(4), 57–69. doi:10.1067/mjd.2000.109072
• Bührer, C., Bahr, S., Siebert, J., Wettstein, R., Geffers, C. ve Obladen, M. (2002). Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23–26 weeks gestation. Journal of Hospital Infection, 51(4), 305–307. doi:https://doi.org/10.1053/jhin.2002.1249
• Ceren, E., Ekmekçi, T. R., Sakız, D., Köşlü, A. ve Bayraktar, B. (2008). Onikomikoz tanısında kullanılan yöntemlerin karşılaştırılması. Türkderm-Deri Hastalıkları ve Frengi Arşivi. 5 Eylül 2021 tarihinde https://app.trdizin.gov.tr/makale/T0RVd05UTXo=/onikomikoz-tanisinda-kullanilan-yontemlerin-karsilastirilmasi adresinden erişildi.
• CLAYTON, Y. M. (1989). In vitro activity of terbinafine. Clinical and Experimental Dermatology, 14(2), 101–103. doi:10.1111/j.1365-2230.1989.tb00901.x
• Del Rosso, J. Q. (2014). The role of topical antifungal therapy for onychomycosis and the emergence of newer agents. The Journal of clinical and aesthetic dermatology, 7(7), 10–8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106353/ adresinden erişildi.
• Derby, R., Rohal, P., Jackson, C., Beutler, A. ve Olsen, C. (2011). Novel Treatment of Onychomycosis using Over-the-Counter Mentholated Ointment: A Clinical Case Series. The Journal of the American Board of Family Medicine, 24(1), 69–74. doi:10.3122/jabfm.2011.01.100124
• Dettenkofer, M., Jonas, D., Wiechmann, C., Rossner, R., Frank, U., Zentner, J. ve Daschner, F. D. (2002). Effect of Skin Disinfection with Octenidine Dihydrochloride on Insertion Site Colonization of Intravascular Catheters. Infection, 30(5), 282–285. doi:10.1007/s15010-002-2182-2
• Dominicus, R., Weidner, C., Tate, H. ve Kroon, H.-A. (2012). Open-label study of the efficacy and safety of topical treatment with TDT 067 (terbinafine in Transfersome®) in patients with onychomycosis. British Journal of Dermatology, 166(6), 1360–1362. doi:10.1111/j.1365-2133.2011.10766.x
• Ebihara, M., Makimura, K., Sato, K., Abe, S. ve Tsuboi, R. (2009). Molecular detection of dermatophytes and nondermatophytes in onychomycosis by nested polymerase chain reaction based on 28S ribosomal RNA gene sequences. British Journal of Dermatology, 161(5), 1038–1044. doi:10.1111/j.1365-2133.2009.09249.x
• Elewski, B.E., Ghannoum, M. A., Mayser, P., Gupta, A. K., Korting, H.-C., Shouey, R. J., … Sigurgeirsson, B. (2013). Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs. Journal of the European Academy of Dermatology and Venereology, 27(3), 287–294. doi:10.1111/j.1468-3083.2011.04373.x
• Elewski, Boni E., Aly, R., Baldwin, S. L., González Soto, R. F., Rich, P., Weisfeld, M., … Pollak, R. (2015). Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies. Journal of the American Academy of Dermatology, 73(1), 62–69. doi:10.1016/j.jaad.2015.04.010
• Elewski, Boni E., Rich, P., Pollak, R., Pariser, D. M., Watanabe, S., Senda, H., … Olin, J. T. (2013). Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies. Journal of the American Academy of Dermatology, 68(4), 600–608. doi:10.1016/j.jaad.2012.10.013
• Erkan, F., Doğruk Kaçar, S., Özuğuz, P., Aşık, G., Tokyol, Ç. ve Karaca, Ş. (2014). Onikomikoz Tanısında Kullanılan 5 Farklı Yöntemin Etkinlik ve Maliyet Karşılaştırması. TURKDERM, 48(1), 21–25. doi:10.4274/turkderm.36034
• Faergemann, J. ve Baran, R. (2003). Epidemiology, clinical presentation and diagnosis of onychomycosis. British Journal of Dermatology, 149(suppl. 65), 1–4. doi:10.1046/j.1365-2133.149.s65.4.x
• Flores, F. C., Beck, R. C. R. ve da Silva, C. de B. (2016). Essential Oils for Treatment for Onychomycosis: A Mini-Review. Mycopathologia, 181(1–2), 9–15. doi:10.1007/s11046-015-9957-3
• Friedlander, S. F., Chan, Y. C., Chan, Y. H. ve Eichenfield, L. F. (2013). Onychomycosis Does Not Always Require Systemic Treatment for Cure: A Trial Using Topical Therapy. Pediatric Dermatology, 30(3), 316–322. doi:10.1111/pde.12064
• Gradišar, H., Friedrich, J., Križaj, I. ve Jerala, R. (2005). Similarities and Specificities of Fungal Keratinolytic Proteases: Comparison of Keratinases of Paecilomyces marquandii and Doratomyces microsporus to Some Known Proteases. Applied and Environmental Microbiology, 71(7), 3420–3426. doi:10.1128/AEM.71.7.3420-3426.2005
• Grover, C. ve Khurana, A. (2012). Onychomycosis: Newer insights in pathogenesis and diagnosis. Indian Journal of Dermatology, Venereology, and Leprology, 78(3), 263–269. doi:10.4103/0378-6323.95440
• Gupta, A.K., Stec, N., Summerbell, R. C., Shear, N. H., Piguet, V., Tosti, A. ve Piraccini, B. M. (2020). Onychomycosis: a review. Journal of the European Academy of Dermatology and Venereology, 34(9), 1972–1990. doi:10.1111/jdv.16394
• Gupta, Aditya K., Daigle, D. ve Foley, K. A. (2014). Topical Therapy for Toenail Onychomycosis: An Evidence-Based Review. American Journal of Clinical Dermatology, 15(6), 489–502. doi:10.1007/s40257-014-0096-2
• Gupta, Aditya K., Drummond-Main, C., Cooper, E. A., Brintnell, W., Piraccini, B. M. ve Tosti, A. (2012). Systematic review of nondermatophyte mold onychomycosis: Diagnosis, clinical types, epidemiology, and treatment. Journal of the American Academy of Dermatology, 66(3), 494–502. doi:10.1016/j.jaad.2011.02.038
• Gupta, Aditya K., Fleckman, P. ve Baran, R. (2000). Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. Journal of the American Academy of Dermatology, 43(4), 70–80. doi:10.1067/mjd.2000.109071 Gupta, Aditya K., Paquet, M. ve Simpson, F. C. (2013). Therapies for the treatment of onychomycosis. Clinics in dermatology, 31(5), 544–554. doi:https://doi.org/10.1016/j.clindermatol.2013.06.011
• Gupta, Aditya K. ve Skinner, A. R. (2004). Onychomycosis in children: a brief overview with treatment strategies. Pediatric dermatology, 21(1), 74–79. doi:https://doi.org/10.1111/j.0736-8046.2004.21117.x
• Gupta, Aditya K., Surprenant, M. S., Kempers, S. E., Pariser, D. M., Rensfeldt, K. ve Tavakkol, A. (2021). Efficacy and safety of topical terbinafine 10% solution (MOB-015) in the treatment of mild to moderate distal subungual onychomycosis: A randomized, multicenter, double-blind, vehicle-controlled phase 3 study. Journal of the American Academy of Dermatology, 85(1), 95–104. doi:https://doi.org/10.1016/j.jaad.2020.06.055
• Gupta, Aditya K, Ryder, J. E. ve Baran, R. (2003). The use of topical therapies to treat onychomycosis. Dermatologic Clinics, 21(3), 481–489. doi:https://doi.org/10.1016/S0733-8635(03)00025-1
• Haldane, D. J. M. ve Robart, E. (1990). A comparison of calcofluor white, potassium hydroxide, and culture for the laboratory diagnosis of superficial fungal infection. Diagnostic Microbiology and Infectious Disease, 13(4), 337–339. doi:https://doi.org/10.1016/0732-8893(90)90027-S
• Hongcharu, W., Dwyer, P., Gonzalez, S. ve Anderson, R. R. (2000). Confirmation of onychomycosis by in vivo confocal microscopy. Journal of the American Academy of Dermatology, 42(2), 214–216. doi:10.1016/S0190-9622(00)90128-2
• Hsiao, Y.-P., Lin, H.-S., Wu, T.-W., Shih, H.-C., Wei, S.-J., Wang, Y.-L., … Yang, J.-H. (2007). A comparative study of KOH test, PAS staining and fungal culture in diagnosis of onychomycosis in Taiwan. Journal of Dermatological Science, 45(2), 138–140. doi:https://doi.org/10.1016/j.jdermsci.2006.09.006
• Hübner, N.-O., Siebert, J. ve Kramer, A. (2010). Octenidine Dihydrochloride, a Modern Antiseptic for Skin, Mucous Membranes and Wounds. Skin Pharmacology and Physiology, 23(5), 244–258. doi:10.1159/000314699
• Hui, X., Shainhouse, Z., Tanojo, H., Anigbogu, A., Markus, G. E., Maibach, H. I. ve Wester, R. C. (2002). Enhanced Human Nail Drug Delivery: Nail Inner Drug Content Assayed by New Unique Method. Journal of Pharmaceutical Sciences, 91(1), 189–195. doi:https://doi.org/10.1002/jps.10003
• Jayatilake, J. A. M. S., Tilakaratne, W. M. ve Panagoda, G. J. (2009). Candidal onychomycosis: A Mini-Review. Mycopathologia, 168(4), 165–173. doi:https://doi.org/10.1007/s11046-009-9212-x
• Jones, T. ve Tavakkol, A. (2013). Safety and Tolerability of Luliconazole Solution 10-Percent in Patients with Moderate to Severe Distal Subungual Onychomycosis. Antimicrobial Agents and Chemotherapy, 57(6), 2684–2689. doi:https://doi.org/10.1128/AAC.02370-12
• Kalokasidis, K., Onder, M., Trakatelli, M.-G., Richert, B. ve Fritz, K. (2013). The Effect of Q-Switched Nd:YAG 1064 nm/532 nm Laser in the Treatment of Onychomycosis In Vivo. Dermatology Research and Practice, 2013, 1–10. doi:10.1155/2013/379725
• Karadağ Köse, Ö. ve Güleç, A. T. (2016). Onikomikoz Tanı ve Tedavisi. Türkiye Klinikleri Dermatoloji - Özel Konular, 9(3), 13–19. https://www.turkiyeklinikleri.com/article/tr-onikomikoz-tani-ve-tedavisi-75519.html adresinden erişildi.
• Karimzadegan-Nia, M., Mir-Amin-Mohammadi, A., Bouzari, N. ve Firooz, A. (2007). Comparison of direct smear, culture and histology for the diagnosis of onychomycosis. Australasian Journal of Dermatology, 48(1), 18–21. doi:https://doi.org/10.1111/j.1440-0960.2007.00320.x
• Kaur, M., Gupta, A., Mahajan, R. ve Gill, M. (2020). 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, 10(4), 260. doi:https://doi.org/10.4103/ijabmr.IJABMR_207_20
• Kaur, R., Kashyap, B. ve Bhalla, P. (2008). Onychomycosis - epidemiology, diagnosis and management. Indian Journal of Medical Microbiology, 26(2), 108. doi:https://doi.org/10.4103/0255-0857.40522
• Kermanshahi, T. R. ve Rhatigan, R. (2010). Comparison between PAS and GMS stains for the diagnosis of onychomycosis. Journal of cutaneous pathology, 37(10), 1041–1044. doi:https://doi.org/10.1111/J.1600-0560.2009.01468.X
• Khengar, R. H., Jones, S. A., Turner, R. B., Forbes, B. ve Brown, M. B. (2007). Nail Swelling as a Pre-formulation Screen for the Selection and Optimisation of Ungual Penetration Enhancers. Pharmaceutical Research, 24(12), 2207–2212. doi:https://doi.org/10.1007/s11095-007-9368-3
• Kim, G. B., Yoon, Y. J., Shin, T. J., Youn, H. S., Gho, Y. S. ve Lee, S. J. (2008). X-ray imaging of various biological samples using a phase-contrast hard X-ray microscope. Microscopy Research and Technique, 71(9), 639–643. doi:https://doi.org/10.1002/jemt.20601
• Kimura, U., Takeuchi, K., Kinoshita, A., Takamori, K., Hiruma, M. ve Suga, Y. (2012). Treating onychomycoses of the toenail: clinical efficacy of the sub-millisecond 1,064 nm Nd: YAG laser using a 5 mm spot diameter. Journal of drugs in dermatology : JDD, 11(4), 496–504. http://www.ncbi.nlm.nih.gov/pubmed/22453588 adresinden erişildi.
• Koburger, T., Hubner, N.-O., Braun, M., Siebert, J. ve Kramer, A. (2010). Standardized comparison of antiseptic efficacy of triclosan, PVP-iodine, octenidine dihydrochloride, polyhexanide and chlorhexidine digluconate. Journal of Antimicrobial Chemotherapy, 65(8), 1712–1719. doi:10.1093/jac/dkq212
• Krammer, S., Krammer, C., Vladimirova, G., Salzer, S., Ruini, C., Sattler, E., … Hartmann, D. (2020). Ex vivo Confocal Laser Scanning Microscopy: A Potential New Diagnostic Imaging Tool in Onychomycosis Comparable With Gold Standard Techniques. Frontiers in Medicine, 7. doi:https://doi.org/10.3389/fmed.2020.586648
• Lawry, M. A., Haneke, E., Strobeck, K., Martin, S., Zimmer, B. ve Romano, P. S. (2000). Methods for Diagnosing Onychomycosis. Archives of Dermatology, 136(9), 1112–1116. doi:10.1001/archderm.136.9.1112
• Lecha, M., Effendy, I., Feuilhade de Chauvin, M., Di Chiacchio, N. ve Baran, R. (2005). Treatment options - development of consensus guidelines. Journal of the European Academy of Dermatology and Venereology, 19(s1), 25–33. doi:10.1111/j.1468-3083.2005.01284.x
• Ledon, J. A., Savas, J., Franca, K., Chacon, A. ve Nouri, K. (2014). Laser and light therapy for onychomycosis: a systematic review. Lasers in Medical Science, 29(2), 823–829. doi:https://doi.org/10.1007/s10103-012-1232-y
• Lee, O., Ha, S., Lee, G., Kim, J., Huang, J., Jin, K. ve Oh, C. (2010). Phase-contrast hard X-ray microscopy using synchrotron radiation for the diagnosis of onychomycosis. Microscopy Research and Technique, 73(12), 1110–1114. doi:https://doi.org/10.1002/jemt.20857
• Li, X., Tian, W., Wang, H., Chen, H., Shen, Y., Lv, G. ve Liu, W. (2011). Direct detection and differentiation of causative fungi of onychomycosis by multiplex polymerase chain reaction-based assay. European Journal of Dermatology, 21(1), 37–42. doi:https://doi.org/10.1684/ejd.2010.1152
• Li, Y., Yu, S., Xu, J., Zhang, R. ve Zhao, J. (2014). Comparison of the efficacy of long-pulsed Nd:YAG laser intervention for treatment of onychomycosis of toenails or fingernails. Journal of drugs in dermatology : JDD, 13(10), 1258–1263. https://jddonline.com/articles/dermatology/S1545961614P1258X adresinden erişildi.
• Lim, C. S.-H. (2011). New Contrast Stain for the Rapid Diagnosis of Onychomycosis. Archives of Dermatology, 147(8), 981–982. doi:10.1001/archdermatol.2011.208
• Lipner, S. R., Friedman, G. ve Scher, R. K. (2017). Pilot study to evaluate a plasma device for the treatment of onychomycosis. Clinical and Experimental Dermatology, 42(3), 295–298. doi:https://doi.org/10.1111/ced.12973
• Lipner, Shari R ve Scher, R. K. (2015). Efinaconazole 10% topical solution for the topical treatment of onychomycosis of the toenail. Expert review of clinical pharmacology, 8(6), 719–731. doi:https://doi.org/10.1586/17512433.2015.1083418
• Litz, C. E. ve Cavagnolo, R. Z. (2010). Polymerase chain reaction in the diagnosis of onychomycosis: a large, single-institute study. British Journal of Dermatology, 163(3), 511–514. doi:https://doi.org/10.1111/j.1365-2133.2010.09852.x
• Liu, H. N., Lee, D. D. ve Wong, C. K. (1993). KONCPA: A New Method for Diagnosing Tinea unguium. Dermatology, 187(3), 166–168. doi:https://doi.org/10.1159/000247235
• Mahoney, J. M., Bennet, J. ve Olsen, B. (2003). The diagnosis of onychomycosis. Dermatologic clinics, 21(3), 463–467. doi:https://doi.org/10.1016/s0733-8635(03)00035-4
• Mohorčič, M., Torkar, A., Friedrich, J., Kristl, J. ve Murdan, S. (2007). An investigation into keratinolytic enzymes to enhance ungual drug delivery. International Journal of Pharmaceutics, 332(1–2), 196–201. doi:10.1016/j.ijpharm.2006.09.042
• Naumann, S., Meyer, J.-P., Kiesow, A., Mrestani, Y., Wohlrab, J. ve Neubert, R. H. H. (2014). Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems. Journal of Controlled Release, 180(1), 60–70. doi:10.1016/j.jconrel.2014.02.013
• Pföhler, C., Hollemeyer, K., Heinzle, E., Altmeyer, W., Graeber, S., Müller, C. S. L., … Tilgen, W. (2009). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a new tool in diagnostic investigation of nail disorders? Experimental Dermatology, 18(10), 880–882. doi:10.1111/j.1600-0625.2008.00838.x
• Pichardo-Geisinger, R., Mora, D. C., Newman, J. C., Arcury, T. A., Feldman, S. R. ve Quandt, S. A. (2014). Comorbidity of Tinea Pedis and Onychomycosis and Evaluation of Risk Factors in Latino Immigrant Poultry Processing and Other Manual Laborers. Southern Medical Journal, 107(6), 374–379. doi:10.14423/01.SMJ.0000450705.67259.26
• Piraccini, B. ve Alessandrini, A. (2015). Onychomycosis: A Review. Journal of Fungi, 1(1), 30–43. doi:10.3390/jof1010030
• Piraccini, B. M. ve Gianni, C. (2013). Update on the management of onychomycosis. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, 148(6), 633–8. doi:https://pubmed.ncbi.nlm.nih.gov/24442043/
• Polak, A. (1992). Preclinical Data and Mode of Action of Amorolfine. Dermatology, 184(1), 3–7. doi:https://doi.org/10.1159/000247588
• Rigopoulos, D., Rallis, E., Gregoriou, S., Larios, G., Belyayeva, Y., Gkouvi, K. ve Katsambas, A. (2009). Treatment of Pseudomonas Nail Infections with 0.1% Octenidine Dihydrochloride Solution. Dermatology, 218(1), 67–68. doi:10.1159/000171816
• Roberts, D.T., Taylor, W. D. ve Boyle, J. (2003). Guidelines for treatment of onychomycosis. British Journal of Dermatology, 148(3), 402–410. doi:10.1046/j.1365-2133.2003.05242.x
• Roberts, David T. (1994). Oral therapeutic agents in fungal nail disease. Journal of the American Academy of Dermatology, 31(3 Pt 2), 78–81. doi:https://doi.org/10.1016/s0190-9622(08)81274-1
• Rock, F. L., Mao, W., Yaremchuk, A., Tukalo, M., Crépin, T., Zhou, H., … Alley, M. R. K. (2007). An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site. Science, 316(5832), 1759–1761. doi:10.1126/science.1142189
• Romero-Cerecero, O., Román-Ramos, R., Zamilpa, A., Jiménez-Ferrer, J. E., Rojas-Bribiesca, G. ve Tortoriello, J. (2009). Clinical trial to compare the effectiveness of two concentrations of the Ageratina pichinchensis extract in the topical treatment of onychomycosis. Journal of Ethnopharmacology, 126(1), 74–78. doi:10.1016/j.jep.2009.08.007
• Romero-Cerecero, O., Zamilpa, A., Jiménez-Ferrer, J. E., Rojas-Bribiesca, G., Román-Ramos, R. ve Tortoriello, J. (2008). Double-blind clinical trial for evaluating the effectiveness and tolerability of Ageratina pichinchensis extract on patients with mild to moderate onychomycosis. A comparative study with ciclopirox. Planta medica, 74(12), 1430–5. doi:https://doi.org/10.1055/s-2008-1081338
• Scher, R. K., Tavakkol, A., Sigurgeirsson, B., Hay, R. J., Joseph, W. S., Tosti, A., … Elewski, B. E. (2007). Onychomycosis: Diagnosis and definition of cure. Journal of the American Academy of Dermatology, 56(6), 939–944. doi:10.1016/j.jaad.2006.12.019
• Seebacher, C., Brasch, J., Abeck, D., Cornely, O., Effendy, I., Ginter-Hanselmayer, G., … Tietz, H.-J. (2007). Onychomycosis. Mycoses, 50(4), 321–327. doi:10.1111/j.1439-0507.2006.01351.x
• Shemer, A., Trau, H., Davidovici, B., Grunwald, M. ve Amichai, B. (2007). Collection of fungi samples from nails: comparative study of curettage and drilling techniques. Journal of the European Academy of Dermatology and Venereology, 22(2), 182–185. doi:10.1111/j.1468-3083.2007.02361.x
• Silva-Neves, V., Hugo, V., Alves, P., Amado, J. C., Pais-Vieira, C., Sousa, F., … Pais-Vieira, M. (2021). Quality of life and therapeutic regimen management in onychomycosis patients and in vitro study of antiseptic solutions. Scientific Reports, 11(1), 12789. doi:10.1038/s41598-021-92111-4
• Singal, A. ve Khanna, D. (2011). Onychomycosis: Diagnosis and management. Indian Journal of Dermatology, Venereology, and Leprology, 77(6), 659–670. doi:10.4103/0378-6323.86475
• Tandel, A. A., Agrawal, S. ve Wankhede, S. S. (2012). Transungual permeatıon of the vorıconazole naıl lacquer agaınst trıchophyton rubrum. Journal of Drug Delivery and Therapeutics, 2(1), 25–26. doi:https://doi.org/10.22270/jddt.v2i1.61
• Tietz, A., Frei, R., Dangel, M., Bolliger, D., Passweg, J. R., Gratwohl, A. ve Widmer, A. F. (2005). Octenidine Hydrochloride for the Care of Central Venous Catheter Insertion Sites in Severely Immunocompromised Patients. Infection Control & Hospital Epidemiology, 26(8), 703–707. doi:10.1086/502606
• Tietz, H.-J., Hay, R., Querner, S., Delcker, A., Kurka, P. ve Merk, H. F. (2013). Efficacy of 4 weeks topical bifonazole treatment for onychomycosis after nail ablation with 40% urea: a double-blind, randomized, placebo-controlled multicenter study. Mycoses, 56(4), 414–421. doi:https://doi.org/10.1111/myc.12037
• Tsunemi, Y., Takehara, K., Miura, Y., Nakagami, G., Sanada, H. ve Kawashima, M. (2014). Screening for tinea unguium by Dermatophyte Test Strip. British Journal of Dermatology, 170(2), 328–331. doi:10.1111/bjd.12660
• Van Hoogdalem, E. ., Van den Hoven, W. ., Terpstra, I. ., Van Zijtveld, J., Verschoor, J. S. . ve Visser, J. . (1997). Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. European Journal of Pharmaceutical Sciences, 5(3), 119–127. doi:10.1016/S0928-0987(97)00270-4
• Vlahovic, T. C. ve Gupta, A. K. (2021). Efinaconazole topical solution (10%) for the treatment of onychomycosis in adult and pediatric patients. Expert Review of Anti-infective Therapy, 1–13. doi:10.1080/14787210.2021.1939011
• Weinberg, J. M., Koestenblatt, E. K., Tutrone, W. D., Tishler, H. R. ve Najarian, L. (2003). Comparison of diagnostic methods in the evaluation of onychomycosis. Journal of the American Academy of Dermatology, 49(2), 193–197. doi:https://doi.org/10.1067/S0190-9622(03)01480-4
• Welsh, O., Vera-Cabrera, L. ve Welsh, E. (2010). Onychomycosis. Clinics in Dermatology, 28(2), 151–159. doi:10.1016/j.clindermatol.2009.12.006
• Westerberg, D. P. ve Voyack, M. J. (2013). Onychomycosis: Current trends in diagnosis and treatment. American family physician, 88(11), 762–70. https://www.aafp.org/afp/2013/1201/p762.html?printable=afp adresinden erişildi.
• Wulkan, A. J. ve Tosti, A. (2013). Pediatric nail conditions. Clinics in Dermatology, 31(5), 564–572. doi:10.1016/j.clindermatol.2013.06.017 Zhang, R., Wang, D., Zhuo, F., Duan, X., Zhang, X. ve Zhao, J. (2012). Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis. Chinese medical journal, 125(18), 3288–3291. doi:https://doi.org/10.3760/cma.j.issn.0366-6999.2012.18.017
• Zuzarte, M., Lopes, G., Pinto, E. ve Salgueiro, L. (2021). Are Natural Products an Alternative Therapy for Dermatophytosis? J.-P. B. Chaturvedi, P. Nenoff, A. K. Gupta ve C. Vişnu (Ed.), Dermatophytes and Dermatophytoses içinde (1. bs., ss. 473–519). Cham: Springer International Publishing. doi:10.1007/978-3-030-67421-2_22