DIAGNOSIS AND THERAPY OF ONYCHOMYCOSIS CAUSED BY TRICHOPHYTON SCHOENLEINII AND YEAST-LIKE FUNGI OF THE CANDIDA GENUS

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Introduction. Onychomycosis is a common clinical type of dermatophytosis, where the most common pathogen (in more than 90% of cases) is Trichophyton rubrum. Other pathogens include dermatophytes (Trichophyton mentagrophytes var. interdigitale, Epidermophyton floccosum), yeast-like (Candida), mold and soil fungi (Scopulariopsis, Mucor, Phizopus, Absidia, Geotrichum, Aspergillus, etc.). The clinical picture of onychomycosis is dominated by changes in the color, shape and structure of the nail plates, in connection with which hypertrophic (manifested mainly by subungual hyperkeratosis), normotrophic (appearance of yellow or white stripes), atrophic (thinning, rejection of the nail plates) forms are distinguished, and by localization - distal, proximal, lateral, superficial and total forms [1]. Mycosis of the nail plates most often affects the toenails, with a long course can move to smooth skin (for example, interdigital spaces). Onychomycosis of the hands is less common, sometimes it is the result of autoinoculation [2]. Diagnosis of onychomycosis based on complaints, anamnesis and clinical picture is often difficult, the diagnosis must be confirmed by microscopic (often repeated) examination, as well as the results of cultural sowing with determination of sensitivity to antimycotics [3]. Fungi penetrate the skin due to microtrauma, flat feet, excessive sweating or dry skin, other dermatoses and chronic diseases, especially diabetes mellitus, immunodeficiencies, circulatory disorders, long-term use of immunosuppressants, hormones, antibiotics, etc. When moving from the nail plates to smooth skin, mycosis can become widespread, which is also typical for comorbid patients [4]. The problem of diagnosis and treatment of onychomycosis in the elderly. The effectiveness of treatment of onychomycosis in older people currently depends on many factors, including: the adequacy of laboratory diagnostics (single microscopy and culture studies are often uninformative and allow identifying the pathogen in about 36% of cases), the need for long-term treatment (an average of 3 months or more) and a combination of systemic and external therapy, antifungal resistance, the presence of other diseases, including dermatoses [5]. In general, there is a high prevalence of onychomycosis among the elderly, reaching 40%, some authors note that onychomycosis is the most common concomitant pathology in the elderly in hospitals of multidisciplinary medical institutions [5]. At the same time, in approximately 40% of cases, even with pronounced clinical manifestations of mycosis, the results of laboratory tests are false negative, and changes in the shape and structure of the nails are associated with age and concomitant diseases [6]. And although it is noted that repeated microscopic examination increases the likelihood of successful detection of fungi to 80-90%, in clinical practice, the patient rarely undergoes a repeat study of the material for fungi with the first negative result [6]. All these factors together lead to a high prevalence of onychomycosis in the elderly, significantly reducing the quality of life and complicating the course of concomitant diseases, including skin diseases [7].
Objective. To study the clinical features of the course, diagnosis and therapy of onychomycosis caused by combined flora. Materials and methods. The patient, 85 years old, was examined. She had been under observation for 14 days in a 24-hour hospital at the State Budgetary Healthcare Institution "Republican Skin and Venereal Diseases Dispensary" in Ufa. Standard methods recommended by the Federal Clinical Guidelines were used to diagnose the disease: microscopic examination for fungi, culture culture, general clinical blood and urine tests, general biochemical screening [1]. The patient's complaints and anamnesis were collected, physical examination was performed, microscopy of the material and culture culture of pathological material from the nail plates, systemic and external antifungal treatment were administered. Results. Patient Z.M., 85 years old, lives in a rural area of ​​the Blagovarsky District of the Republic of Bashkortostan, independently contacted a dermatovenereologist at the outpatient department of the State Budgetary Healthcare Institution "Republican Skin and Venereal Diseases Dispensary" in Ufa to decide on hospitalization on October 14, 2024. Complaints upon seeking medical help: severe generalized itching of the skin, the presence of "blisters" on the hands and feet, insomnia, an increase in body temperature to 37-37.5 C, changes in "all nails". Emotionally labile, also complained of the lack of effect from previously administered therapy.

Medical history: considers herself ill for the last five years, when she first began to notice itching, "blisters" and cracks on the skin of her feet and hands, which subsequently spread to other areas of the skin, as well as changes in the nail plates - according to her, some of them crumbled, exfoliated, and some changed color (became white or yellowish, some - black). She had never been observed for onychomycosis before, and no microscopic or bacteriological examination was performed. She associates the nail damage with a skin disease for which she was observed by a dermatovenerologist (she notes that she was diagnosed with "dermatitis" and "eczema" in different years), she considers the previously prescribed treatment to be ineffective, she tried to move to regions with a warm climate (without improvement). She was actively self-medicating (hot baths with celandine, succession, chamomile, zinc paste on the affected areas of the skin, she lubricated her nails with table vinegar - without effect).
Life history: lives alone in a private house in the countryside, in the warm season she takes care of the garden area. She grew and developed in accordance with her gender and age. Of the diseases she has suffered, she notes type 2 diabetes mellitus, and 5 years ago, according to her words, she suffered from an illness with damage to the scalp in the form of rashes and subsequent hair loss, for which she was not observed anywhere and did not seek help, since subjectively it almost did not bother her. Allergological anamnesis: according to her words, negative. Family history: her father suffered from eczema. She takes medications: metformin, periodically antihypertensives (she does not remember the names).
The current deterioration has been observed in the last 3 months, when "blisters" began to appear on the skin of the feet and hands, which she treated with celandine, made herbal baths and rubbed with herbal solutions (succession, chamomile). She associates the deterioration with the onset of autumn. She contacted a dermatovenerologist at the local clinic in early September 2024, where she was diagnosed with "Unspecified dermatitis" (L30.9) and prescribed a topical glucocorticosteroid (0.1% methylprednisolone aceponate ointment once a day), which the patient refused. No additional examination methods were performed. The second and third visits to the dermatovenerologist at the place of residence also took place in September, the diagnosis did not change (L30.9), in addition, in order to reduce itching, a cream based on synthetic tannin was prescribed 2 times a day on the lesions (the patient did not use this drug). Against the background of unsuccessful self-treatment, the patient noted a deterioration in her condition - severe itching spreading from the feet and hands to the limbs and body, pain when pressing on the skin of the feet when walking, "redness" of the skin, thinning and delamination of the nails. She began to independently take chloropyramine 25 mg 2-3 times a day, did hot baths for the feet and hands (without effect).
General condition upon admission of moderate severity: body temperature 37.2º C, weakness, emotional lability, lack of appetite. Primary examination of the skin was difficult, since the patient independently completely treated the skin (including the face and scalp) with zinc paste. Status localis after skin cleansing: against the background of diffuse erythema in the area of ​​the feet and hands, single small vesicles of 4-5 mm with serous contents are determined, severe itching in the area of ​​the rash, turgor is significantly reduced upon palpation, Nikolsky's symptom is negative. The nail plates of the feet and hands are thinned, partially crumbling, have a changed color (Figures 1-2). The mucous membranes of the oral cavity are of normal color, there is no rash, the tongue is slightly coated white, dry. The skin of other parts of the body (upper and lower limbs, trunk, scalp and face) is hyperemic, dry, elements of the rash are single serous vesicles on the back of the hands and feet, other areas of the skin are free of rashes. On the scalp, the hair is sparse, gray, shoulder-length. Lymph nodes (anterior and posterior auricular, occipital, anterior and posterior cervical, supraclavicular and subclavian, submandibular, inguinal) are not palpable.
The patient was referred to the 24-hour inpatient department with a preliminary diagnosis of "Mycosis of the feet". Blood was taken for a general clinical blood and urine test, general biochemical screening, and a complex of serological reactions (CSR) (10/14/2024) (Table 1).
Microscopic and cultural methods for examining material from lesions. Material was taken from the lesions (nail plates) for microscopic examination (twice with an interval of 2 days, on October 14 and 16, 2024), and a scraping was also taken from the lesion (skin near the lesions, nail plates) for bacteriological examination (Table 2).

The first microscopy revealed yeast-like fungi, the second microscopy revealed mycelium, as well as yeast-like fungi in large quantities.
Based on the collected anamnesis, examination data and laboratory tests, the main clinical diagnosis was established: mycosis of the feet and hands caused by combined flora. Complication: allergies. Concomitant: type 2 diabetes mellitus, subcompensation. When studying the sensitivity to antifungal agents 2 weeks after sowing, high sensitivity of the detected fungus (Trichophiton schoenleinii) to systemic antifungal agents - griseofulvin and itraconazole (Table 3) was found. Bacteriological examination was carried out on a nutrient medium (standard Sabouraud agar medium with the addition of antifungal agents).
Treatment was complex and included a systemic and topical antifungal agent, treatment of the nail plates and skin. Despite the fact that the sowing was carried out once, and it was possible to achieve the growth of only Trichophyton schoenleinii, taking into account the yeast-like cells detected twice in large quantities during microscopic examination, as well as taking into account the indicators of liver transferases of the patient Z.M., itraconazole was chosen as a systemic antimycotic, showing activity against both Trichophyton and Candida fungi, according to the regimen of 400 mg per day (200 mg 2 times a day) 1 week per month for at least 3 months. Additionally, to reduce itching, a 2nd generation antihistamine was prescribed - loratadine 10 mg per day in the evening, on areas of the skin clear of rashes - emollients. Local treatment of the affected skin was carried out after softening the nail plates with a cream based on 40% urea, after cutting the nails, the treatment was carried out with 2% sertaconazole cream 2 times a day. Two weeks after the start of specific therapy, clinical improvement of the skin and nail plates was observed. The appearance of new vesicles on the back of the hands and feet ceased, the existing elements dried up without opening, erythema disappeared. Repeated administration (corresponded to the 3rd course of itraconazole) nail plates were unevenly thinned, did not crumble, normal color, there were no inflammatory phenomena, the general condition of the patient was satisfactory (Figures 3-4).
Then the patient was under dispensary observation at the place of residence until healthy nails grew back with the corresponding microscopic examination until three negative results (once every 7 days) [1].

Discussion. Trichophiton schoenleinii is an atroponotic fungus that causes favus (scab) in humans. The source of infection is a sick person, in rare cases - rodents [8]. Mycosis is characterized by a long, sometimes multi-year course with an outcome in cicatricial atrophy, and often affects the scalp, which was presumably the cause of the disease suffered by this patient 5 years ago [9]. In rare cases, Trichophiton schoenleinii can primarily affect the nails, however, in this case, autoinoculation from the scalp to the nail plates is assumed, which occurred given long-term self-medication, the lack of adequate diagnostics and the presence of concomitant diseases (diabetes mellitus). Additional difficulties in diagnosing this mycosis were the anamnestic indication of "unspecified dermatitis" and "eczema", however, upon examination of the skin upon admission, no corresponding signs of an eczematous reaction were found, and isolated vesicular rashes without acute inflammatory phenomena can presumably be associated with sensitization of the body to fungal antigens, which was stopped by long-term use of antihistamines [10]. Of great importance in diagnosing mycosis was the need for repeated microscopic examination, which made it possible to detect yeast-like fungi in both samples, and fungal mycelium only during the second study, and, conversely, the detection of Trichophyton schoenleinii growth in a culture study without the growth of Candida fungi, which corresponds to literary data on the low efficiency of single samples for laboratory research [5, 6]. Finally, taking into account the clinical, anamnestic and laboratory data, as well as the patient's age, liver transferase indices, itraconazole was chosen as a systemic antifungal agent according to the pulse therapy regimen (although both itraconazole and griseofulvin are metabolized via cytochrome P450 (especially CYP3A4), only isolated cases of pronounced hepatotoxic action of itraconazole have been proven, while liver diseases and liver failure are direct contraindications to the use of griseofulvin (for itraconazole - only hypersensitivity)) [11]. Conclusion. This clinical case demonstrates the features of the latent and prolonged course of onychomycosis in elderly people caused by combined fungal flora, which, together with self-medication and the presence of concomitant diseases, led to late diagnosis. It is noted that repeated microscopic confirmation of the fungal nature of the disease is necessary in case of damage not only to the skin but also to the nail plates, especially against the background of a long course and the presence in the anamnesis of a previous disease of presumably fungal etiology.
Funding source. The authors declare that there was no external funding for the study.
Consent for publication. Written consent was obtained from the patient for publication of relevant medical information and all of accompanying images within the manuscript.
Competing interests. The authors declare that they have no competing interests.
Author contribution. All authors confirm that their authorship meets the international ICMJE criteria (all authors have made a significant contribution to the development of the concept, research and preparation of the article, read and approved the final version before publication). Z.R. Hismatullina — literature review, collection and analysis of literary sources, editing the article, patient supervision; I.V. Giniyatova — literature review, collection and analysis of literary sources, preparation and writing of the article; K.M. Koreshkova — supervision, patient treatment, collection and analysis of literary sources, preparation and writing of the article.

About the authors

Kseniya Mikhailovna Koreshkova

Federal State Budgetary Educational Institution of Higher Education «Bashkir State Medical University» of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: saitik16@yandex.ru
ORCID iD: 0000-0001-6039-8311
SPIN-code: 4010-2873

PhD, Associate Professor of the Department of Dermatovenereology

Russian Federation, 450000, Ufa, Lenin St., 3

Zarema Rimovna Hismatullina

Federal State Budgetary Educational Institution of Higher Education «Bashkir State Medical University» of the Ministry of Health of the Russian Federation

Email: hzr07@mail.ru
ORCID iD: 0000-0001-8674-2803
SPIN-code: 6602-4060

MD, Professor, Head of the Department of Dermatovenereology

Russian Federation, 450000, Ufa, Lenin St., 3

Irina Valerievna Giniyatova

Federal State Budgetary Educational Institution of Higher Education «Bashkir State Medical University» of the Ministry of Health of the Russian Federation

Email: detki78@mail.ru
ORCID iD: 0000-0002-0659-0721
SPIN-code: 2771-1661

Assistant of the Department of Dermatovenereology

450000, Ufa, Lenin St., 3

References

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