Combination therapy of cutaneous candidiasis in patients with concomitant systemic pathology

Candida fungus is an integral part of the normal human microbiome, but disruption of skin integrity and malperformance of immune function can transform it into a pathogenic form. Some Candida strains are capable of modulating the immune response through suppressing the production of proinflammatory cytokines and inducing T-helper differentiation toward a Th2 response, which contributes to the chronification of inflammation. In this article, we take a detailed look at exogenous and endogenous risk factors. Particular focus has been placed on comorbidities: the present-date knowledge on the role of Candida spp. in exacerbating the course of atopic dermatitis and psoriasis is provided. The authors presented clinical case reports of candidiasis treatment in patients with aggravated histories. Case report 1: a 19-year-old man with complaints of pain, redness, and swelling in the periungual fold area combined with changes in the color and texture of the nail plate. Diagnosis: Periungual fold candidiasis. Onychomycosis. Treatment with 2% sertaconazole cream was prescribed. After 4 weeks, clinical regression of the inflammation process and partial restoration of the nail plate structure was observed. Case report 2: a 37-year-old man with complaints of severe itching, burning, and redness in the groin folds. Diagnosis: Candidal intertrigo of the groin folds associated with antibiotic therapy due to obesity. The prescribed stepwise therapy included: 0.05% clotrimazole + 0.1% gentamicin + 1% betamethasone for 7 days, then 2% sertaconazole cream for 2 weeks. After a three-week therapy, the rash regressed and post-inflammatory hyperpigmentation developed in a patient. Case report 3: a 58-year-old woman with complains of intense itching, burning, pain, and oozing in the abdominal fold within 3 weeks. The patient's medical history told a story of chronic illness. Diagnosis: Candidal intertrigo. The prescribed stepwise therapy included: 0.05% clotrimazole + 0.1% gentamicin + 1% betamethasone for 7 days, then 2% sertaconazole cream for 2 weeks. After a three-week course of treatment, the inflammation regressed. In all cases, skin scrapings showed negative follow-up microscopic examination results.

1. Singh AK, Mazumder R, Dogra A. Development of Novel Approaches for the Treatment of Cutaneous Candidiasis. Curr Pharm Des. 2026;32(17):1293–1307. https://doi.org/10.2174/0113816128379927250807064636.

2. Müller VL, Kreuter A, Uhrlaß S, Nenoff P. Relevant aspects of Candida species in dermatology: An overview. Dermatologie. 2025;76(9):544–550. https://doi.org/10.1007/s00105-025-05538-5.

3. Alqarihi A, Singh S, Edwards JE, Ibrahim AS, Uppuluri P. NDV-3A vaccination prevents C. albicans colonization of jugular vein catheters in mice. Sci. Rep. 2019;9:6194. https://doi.org/10.1038/s41598-019-42517-y.

4. Hostelidi SN, Serebryanaya NB. Immunotherapy for Candida spp. infections: myth or reality? Russian Journal of Infection and Immunity. 2025;15(1):27–36. (In Russ.) https://doi.org/10.15789/2220-7619-IOC-17696.

5. Chen T, Gao Ch. Innate immune signal transduction pathways to fungal infection: Components and regulation. Cell Insight. 2024;3(3):100154. https://doi.org/10.1016/j.cellin.2024.100154.

6. Jensen O, Trujillo E, Hanson L, Ost KS. Controlling Candida: immune regulation of commensal fungi in the gut. Infect Immun. 2024;92(9):e0051623. https://doi.org/10.1128/iai.00516-23.

7. Rakhmatulina MR, Lipova EV, Nyanenko VA. Pathogenetic aspects and modern possibilities of therapy of vulvovaginal candidiasis. Vestnik Dermatologii i Venerologii. 2024;100(6):30–40. https://doi.org/10.25208/vdv16820.

8. Zhao Y, Zhou Z, Cai G, Zhang D, Yu X, Li D et al. Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response. PLoS Pathog. 2025;21(3):e1012865. https://doi.org/10.1371/journal.ppat.1012865.

9. Ravid A, Michael F, Daniel C, Esther S. Dermatomycoses in the Israeli defense forces-Epidemiological and clinical aspects. Mycoses. 2020;63(1):65–70. https://doi.org/10.1111/myc.13015.

10. Sepahvand A, Behzadifar M, Raiesi O, Yarahmadi M. Prevalence of Tinea pedis in military personnel: a systematic review and meta-analysis. BMC Public Health. 2025;25(1):3116. https://doi.org/10.1186/s12889-025-24308-5.

11. Sokolova TV, Glad’ko VV, Malyarchuk AP, Gura OV, Ihshneli NG. Superficial candidiasis in the clinical practice of dermatovenereologists and related specialists. Bulletin of the Medical Institute of Continuing Education. 2024;41(2):8–22. (In Russ.) https://doi.org/10.36107/2782-1714_2024-4-1-8-22.

12. Teoh F, Pavelka N. How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions. Pathogens. 2016;5(1):6. https://doi.org/10.3390/pathogens5010006.

13. Caldarola G, De Luca E, Amato S, Belcastro A, Bernardini N, Bianchi L et al. Predictive factors for eczematous eruptions and candidiasis during anti-interleukin-17 treatment in patients with psoriasis: a multicentre real-life experience in Lazio region, Italy. Clin Exp Dermatol. 2025;50(11):2185–2191. https://doi.org/10.1093/ced/llaf271.

14. Drummond RA, Desai JV, Ricotta EE, Swamydas M, Deming C, Conlan S et al. Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria. Cell Host Microbe. 2022;30(7):1020–1033.e6. https://doi.org/10.1016/j.chom.2022.04.013.

15. Savage HP, Bays DJ, Tiffany CR, Gonzalez MAF, Bejarano EJ, Carvalho TP et al. Epithelial hypoxia maintains colonization resistance against Candida albicans. Cell Host Microbe. 2024;32(7):1103–1113.e6. https://doi.org/10.1016/j.chom.2024.05.008.

16. Elizondo-Elizondo M, González-Silva A, de Oca-Sánchez GM, Tirado-Sánchez A, Frias-De-León MG, Diaz-Molina V et al. Superficial fungal infections in patients with diabetes. Is hyperglycemia the only associated factor?. Future Microbiol. 2026;21(1):59–72. https://doi.org/10.1080/17460913.2025.2607353.

17. Wu BY, Wu BJ, Lee SM, Sun HJ, Chang YT, Lin MW. Prevalence and associated factors of comorbid skin diseases in patients with schizophrenia: a clinical survey and national health database study. Gen Hosp Psychiatry. 2014;36(4):415–421. https://doi.org/10.1016/j.genhosppsych.2014.02.008.

18. Douvali T, Paparizos V, Vasalou V, Gregoriou S, Chasapi V, Rigopoulos D et al. A 30-Year Epidemiological Study of Opportunistic Fungal Infections in People Living with HIV in Greece: Associations with Demographic Characteristics and Immune Status. J Clin Med. 2025;14(17):5936. https://doi.org/10.3390/jcm14175936.

19. Mapesi H, Ramírez A, Tanner M, Hatz C, Letang E; KIULARCO Study Group. Immune reconstitution inflammatory syndrome associated with dermatophytoses in two HIV-1 positive patients in rural Tanzania: a case report. BMC Infect Dis. 2016;16:495. https://doi.org/10.1186/s12879-016-1824-4.

20. Szczepańska M, Blicharz L, Nowaczyk J, Makowska K, Goldust M, WaśkielBurnat A et al. The Role of the Cutaneous Mycobiome in Atopic Dermatitis. J Fungi. 2022;8(11):1153. https://doi.org/10.3390/jof8111153.

21. Storz L, Schmid B, Bosshard PP, Schmid-Grendelmeier P, Brüggen MC, Lang C. Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis. Front Med. 2024;11:1353784. https://doi.org/10.3389/fmed.2024.1353784.

22. Esionova EV, Mavlyanova ShZ, Izvekova OV, Alimukhamedova YuA, Sabirkulov ShU. Properties of Candida Albicans: Mycogenic Sensitization as a Trigger of Atopic Dermatitis and Psoriasis Vulgaris. 23 September 2025, Preprint (Version 1). https://doi.org/10.21203/rs.3.rs-7641034/v1.

23. Halvaee S, Daie Ghazvini R, Hashemi SJ, Zibafar E, Yekaninejad S, Geramishoar M et al. Investigation of Intertriginous Mycotic and Pseudomycotic (Erythrasma) Infections and Their Causative Agents with Emphasize on Clinical Presentations. Iran J Public Health. 2018;47(9):1406–1412. Available at: https://pubmed.ncbi.nlm.nih.gov/30320016.

24. Разнатовский КИ, Котрехова ЛП. Микозы кожи и ногтей. М.: ГЭОТАР-Медиа; 2020. 232 с.

25. Дубенский ВВ, Дубенский ВВ, Кубанова АА, Рахматуллина МР. Дерматовенерология. В: Чучалин АГ, Хохлов АЛ (ред.). Федеральное руководство по использованию лекарственных средств. Вып. XVIII. М.: Видокс; 2017. С. 379–400.

26. Климко НН. Микозы: диагностика и лечение. М.; 2007. С. 124–178.

27. Seebacher C, Abeck D, Brasch J, Effendy I, Ginter-Hanselmayer G, Haake N et al. Candidiasis of the skin. J Dtsch Dermatol Ges. 2006;4(7):591–596. https://doi.org/10.1111/j.1610-0387.2006.05888.x.

28. Metin A, Dilek N, Demirseven DD. Fungal infections of the folds (intertriginous areas). Clin Dermatol. 2015;33(4):437–447. https://doi.org/10.1016/j.clindermatol.2015.04.005.

29. Sokolova TV, Maliarchuk AP, Maliarchuk TA. Results of a multicenter trial to investigate the incidence of superficial mycoses in the regions of the Russian Federation and to evaluate the efficiency of their treatment with sertaconazole. Klinicheskaya Dermatologiya i Venerologiya. 2013;11(5):28–39. (In Russ.) Available at: https://www.mediasphera.ru/issues/klinicheskayadermatologiya-i-venerologiya/2013/5/031997-2849201355.

30. Романенко ИМ, Кулага ВВ, Афонин СЛ. Лечение кожных и венерических болезней: руководство в 2-х т. М.: МИА; 2015. С. 222–235.

31. Stepanova ZhV. Candidiasis of smooth skin. Lechaschi Vrach. 2006;(5):12–15. (In Russ.) Available at: https://www.lvrach.ru/2006/05/4533880.

32. Boyko-Maksimova GI, Paliy LI, Trofimuk VA. Clinical aspects of oral mucosal candidiasis. Sovremennaya stomatologiya. 2017;(4):37–40. (In Russ.) https://doi.org/10.24412/fdhj7jcbr8a.

33. Dorko E, Virágová S, Pilipcinec E, Tkáciková L. Candida--agent of the diaper dermatitis? Folia Microbiol. 2003;48(3):385–388. https://doi.org/10.1007/BF02931371.

34. Croxtall JD, Plosker GL. Sertaconazole: a review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69(3):339–359. https://doi.org/10.2165/00003495-200969030-00009.

35. Carrillo-Muñoz AJ, Torres-Rodriguez JM. In-vitro antifungal activity of sertaconazole, econazole, and bifonazole against Candida spp. J Antimicrob Chemother. 1995;36(4):713–716. https://doi.org/10.1093/jac/36.4.713.

36. Liebel F, Lyte P, Garay M, Babad J, Southall MD. Anti-inflammatory and antiitch activity of sertaconazole nitrate. Arch Dermatol Res. 2006;298(4):191–199. https://doi.org/10.1007/s00403-006-0679-8.

37. Sur R, Babad JM, Garay M, Liebel FT, Southall MD. Anti-inflammatory activity of sertaconazole nitrate is mediated via activation of a p38-COX-2-PGE2 pathway. J Invest Dermatol. 2008;128(2):336–344. https://doi.org/10.1038/sj.jid.5700972.

38. Carrilo-Muñoz AJ, Tur C, Torres J. In-vitro antifungal activity of sertaconazole, bifonazole, ketoconazole, and miconazole against yeasts of the Candida genus. J Antimicrob Chemother. 1996;37(4):815–819. https://doi.org/10.1093/jac/37.4.815.

39. Pfaller MA, Sutton DA. Review of in vitro activity of sertaconazole nitrate in the treatment of superficial fungal infections. Diagn Microbiol Infect Dis. 2006;56(2):147–152. https://doi.org/10.1016/j.diagmicrobio.2006.04.006.

40. Borelli C, Klövekorn G, Ernst TM, Bödeker RH, Korting HC, Neumeister C. Comparative study of 2% sertaconazole solution and cream formulations in patients with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis. Am J Clin Dermatol. 2007;8(6):371–378. https://doi.org/10.2165/00128071-200708060-00007.

41. Bonifaz A, Tirado-Sánchez A, Graniel MJ, Mena C, Valencia A, Ponce-Olivera RM. The efficacy and safety of sertaconazole cream (2%) in diaper dermatitis candidiasis. Mycopathologia. 2013;175(3-4):249–254. https://doi.org/10.1007/s11046-013-9642-3.

42. Jerajani H, Janaki C, Kumar S, Phiske M. Comparative assessment of the efficacy and safety of sertaconazole (2%) cream versus terbinafine cream (1%) versus luliconazole (1%) cream in patients with dermatophytoses: a pilot study. Indian J Dermatol. 2013;58(1):34–38. https://doi.org/10.4103/0019-5154.105284.

43. Khondker L. Role of Sertaconazole in the Treatment of Dermatophytosis. Medicine Today. 2024;36(1):62–66. https://doi.org/10.3329/medtoday.v36i1.72905.