VITILIGO : MODERN CONCEPTS OF PATHOGENESIS, GENETICS, BIOMARKERS AND INNOVATIVE TREATMENT METHODS

Full Text

Vitiligo is a chronic autoimmune skin disease characterized by the destruction of melanocytes and the formation of depigmented lesions. Modern research in recent years has significantly expanded the understanding of the pathogenetic mechanisms of the disease and opened up new therapeutic possibilities. A.Kh. Batchaeva, A.M. Sampiev, O.N. Denisenko in their 2023 study substantiated the convergent theory of the pathogenesis of vitiligo, based on a combination of several pathogenetic mechanisms, including genetic predisposition, impaired immune regulation and a melanocyte defect (Fig. 1). The authors conducted a comprehensive analysis of modern concepts of the pathogenesis of the disease and highlighted the leading role of the autoimmune theory [ 1].

Modern concepts of the pathogenesis of vitiligo

Autoimmune reactions in vitiligo are characterized by the infiltration of CD8+ T lymphocytes, which mediate the destruction of melanocytes via the perforin-granazyme pathway. The imbalance of immune regulation is manifested by increased activity of Th-17 cells and decreased functional activity of regulatory T cells (Treg), which contributes to the progression of the disease. An important role in the pathogenesis is played by interferon-γ, which induces the expression of the chemokine CXCL10, enhancing the migration of cytotoxic lymphocytes to the lesions. Genetic factors, such as polymorphism of the PTPN22 gene, contribute to the violation of immune tolerance and increase the predisposition to autoimmune reactions. Oxidative stress aggravates the pathological process by reducing the activity of antioxidant enzymes (SOD2, GSTP1) and the accumulation of reactive oxygen species, which leads to mitochondrial dysfunction and apoptosis of melanocytes (Fig. 2). Impaired melanogenesis is associated with decreased expression of key genes such as TYR and TYRP1, as well as dysregulation of transcription factors MITF and SOX10, which control melanocyte differentiation [ 2].

Modern genetic studies have significantly expanded our understanding of the molecular basis of vitiligo. A large population-based study by HJ Kim, HS Ahn, SZ Kazmi and co-authors conducted based on data from the Korea National Health Insurance Service , established important patterns of familial aggregation of the disease. The researchers developed specific algorithms to identify vitiligo cases, and the validation of diagnoses was performed by two qualified dermatologists with the analysis of medical data and photographs. The results showed that the incidence rate for monozygotic twins was 11.74, for sibs - 6.37, while the transmission of vitiligo through the maternal line exceeded that through the paternal line with a coefficient of 4.26 versus 3.36 [ 3].

In 2024, V.V. Petunina confirmed the leading role of the autoimmune theory in the pathogenesis of the disease in her fundamental analysis of immunological markers of vitiligo. The key biomarkers of the process activity are interleukin-17, imbalance of lymphocyte subpopulations with a violation of the ratio between Th1/Th17 and Tregs/Th2, as well as cytokine imbalance. The author identified molecular targets for modern therapy: JAK1 and JAK2 kinases, chemokines CXCL9 and CXCL10, granzyme B as a marker of cytotoxic activity, and INF-γ as a key proinflammatory cytokine [ 4].

The role of autoimmune mechanisms

1. Katz and JE Harris studied in detail the role of cytotoxic CD8+ T lymphocytes in the pathogenesis of vitiligo. The authors found that cytotoxic CD8+ T cells selectively destroy melanocytes, while experimental data obtained from the analysis of T cells isolated directly from skin lesions confirmed the autoimmune theory. The researchers found circulating CD8+ T cells in patients with vitiligo expressing the receptor of the skin-associated leukocyte antigen [ 5].

ML Frisoli, K. Essien, JE Harris in their work published a year earlier studied not only the role of cytotoxic T lymphocytes, but also general aspects of the autoimmune theory. The authors established the central role of CD8+ T cells, showing that autoreactive cytotoxic CD8+ T cells directly interact with melanocytes and contribute to the progression of the disease. The researchers found that interferon-gamma acts as a key mediator triggering a cascade of inflammatory reactions through a chemokine positive feedback loop, in which interferon-gamma-induced chemokines are secreted by surrounding keratinocytes for further recruitment of T cells into the skin.

ML Frisoli and JE Harris in 2020 proposed an innovative concept of the mechanism of disease relapse, attributing responsibility for this on autoreactive resident memory T cells. The authors noted that disease relapses that occur after treatment discontinuation necessitate the development of new treatment strategies focused on the elimination of resident memory T cells to achieve a long-term effect [ 6].

The role of regulatory T cells in the implementation of the autoimmune mechanism

The study by PS Giri and co-authors presented fundamentally new data on the functional state of regulatory T cells in generalized vitiligo. The authors conducted a comprehensive analysis of 55 patients with generalized vitiligo and 45 healthy volunteers using modern cell biology methods. The aim of the work was to assess the suppressive function of Tregs and analyze the production of key cytokines. The results demonstrated a significant decrease in the suppressive activity of regulatory T cells in patients with vitiligo. When analyzing the interaction with CD8+ T cells, the suppressive function was 30.80 ± 3.19% versus 46.35 ± 4.08% in the control group. The differences between active and stable vitiligo were especially pronounced, where the figures were 29.62 ± 3.86% and 35.52 ± 4.01%, respectively. The authors were the first to establish a correlation between the functional activity of Tregs and the severity of the disease, assessed by the VASI scale. A critically important discovery was the role of the transcription factor NFATC1, first described in vitiligo (Fig. 3). P. S. Giri and colleagues found a positive correlation between NFATC1 and FOXP3, indicating the existence of a regulatory axis NFATC1-FOXP3 in maintaining the function of regulatory T cells. Disruption of this axis leads to defects in Tregs and contributes to the development of the autoimmune process [ 7].

Genetic aspects of vitiligo

The studies by C. Bergqvist and K. Ezzedine provided groundbreaking data on the genetic architecture of vitiligo. The authors reported the identification of 23 new risk loci through genome-wide association studies, which significantly expanded our understanding of the genetic basis of the disease. Deep genotyping allowed us to prove the complex mechanisms of heritability of autoimmune vitiligo. Particular attention was paid to the polygenic inheritance of common risk alleles. Familial clustering of vitiligo occurs mainly from polygenic inheritance, which explains the complex structure of the disease and its variability in the population [ 8].

1. A. Katina reported elevated CXCL10 chemokine concentrations in the serum of vitiligo patients. After CXCL10 binds to the CXCR3 receptor, autoreactive T cells migrate to the epidermis and destroy melanocytes. The cytokine profile is characterized by elevated IL-2, IL-6, IL-17 and decreased IL-4 [ 9].
2. Jacquemin et al. presented data on the role of NKG2D+ CD8+ memory T cells in vitiligo skin. A study of 48 patients revealed increased NKG2D expression on CD8+ T cells in the skin, stable after TCR activation. NKG2D is considered as a reliable molecular target for future therapeutic approaches. Of particular importance is IL-15 as an important soluble factor for the promotion of NKG2D in effector memory CD8+ T cells. IL-15 is released by epidermal cells and can be transpresented via the IL-15α receptor to promote memory T cells [ 10].

Current disease biomarkers were studied in detail by PS Giri, M. Dwivedi, BC Laddha, R. Begum et al. in their study of molecular mechanisms of regulatory T cell dysfunction in vitiligo. The aim of the study was to evaluate the expression of nuclear factors of activated T cells, FOXP3 and their associated genes in regulatory T cells of patients with generalized vitiligo, as well as to analyze the correlation of FOXP3 promoter polymorphisms with the disease phenotype. The sample included 48 patients with generalized vitiligo and 45 healthy volunteers, divided into subgroups with active and stable vitiligo. The authors used modern research methods, including isolation of Tregs using MACSxpress® Whole Blood Treg Isolation Kit with 90% purity, flow cytometry, molecular genetic analysis with real-time PCR and genotyping of FOXP3 promoter polymorphisms. New genetic data have identified FOXP3 promoter polymorphisms rs3761547 and rs3761548 associated with vitiligo susceptibility and affecting FOXP3 expression. Novel molecular biomarkers include transcription factors NFATs with significant reduction of NFATC1, NFATC3, NFATC4 and NFAT5, as well as key regulatory genes FOXP3, IL10, TGFB and CTLA4 with critical reduction in their expression [ 11].

A seminal study by GHL Roberts, SA Santorico, and RA Spritz (2020) was the first to demonstrate the absence of “missing heritability” in vitiligo. The authors analyzed 8,034 first-degree relatives of 2,122 unrelated probands and performed a genotype-based analysis of 2,812 vitiligo cases and 37,079 controls using deep imputation to Haplotype Reference Consortium data. The study found virtually identical familial heritability (0.75–0.83) and SNP heritability (0.78), indicating the feasibility of fully capturing the genetic architecture of vitiligo through modern genomic technologies [ 12].

Modern data by E.V. Dvoryankova and I.M. Korsunskaya (2020) confirm the polygenic nature of the disease. A genome-wide association study identified 54 gene loci associated with vitiligo. The genetic factor is present in approximately 80% of cases of the disease, with heritability observed in 40% of patients. Most of the identified gene loci are regulatory, which explains the complex mechanism of inheritance of autoimmune hypomelanosis [ 13].

A.V. Snitko and R.N. Voloshin presented a modern classification of vitiligo according to the international consensus, dividing the disease into non-segmental and segmental vitiligo. Segmental vitiligo usually develops at a younger age and is characterized by different treatment efficacies: non-segmental vitiligo shows a good response to narrow-band UVB therapy, while segmental vitiligo demonstrates a poor response [ 14].

 

Molecular mechanisms of vitiligo development

A pioneering study on the molecular mechanisms was conducted by N. Boukhedouni, C. Martins, AS Darrigade and co-authors led by K. Boniface in 2020. The aim of the study was to investigate the relationship between the type 1 inflammatory response and the disappearance of melanocytes in vitiligo. The authors used a comprehensive methodology including the analysis of skin samples from patients with vitiligo, transcriptomic analysis using Nanostring technology, immunohistochemistry and experimental procedures on animals approved by the Ethics Committee of the University of Bordeaux. The sample included patients with vitiligo and a healthy control group with written informed consent from all participants. A key finding was the detection in vitiligo skin of a significant proportion of suprabasal melanocytes associated with impaired expression of E-cadherin, the main protein involved in melanocyte adhesion. The researchers found that apoptotic melanocytes were observed predominantly after cell detachment from the basal layer of the epidermis, and interferon-gamma regulates MMP-9 production and E-cadherin degradation to promote melanocyte loss [ 15].

 

Psychosocial aspects of vitiligo

1. Hamidizadeh et al. conducted a comparative case-control study involving 99 patients with vitiligo and 100 healthy volunteers. The aim of the study was to assess hopelessness, anxiety, depression, and general health in patients with vitiligo. The study showed statistically significant differences in general health between patients and the control group, with women with vitiligo demonstrating higher levels of anxiety and hopelessness compared to men [ 16].

Jung Min Bae et al. conducted a multicenter willingness-to-pay study involving 617 patients from 7 hospitals. The study found that patients with vitiligo had the highest willingness-to-pay values among all skin disease patients studied (median $2,000 versus $1,000 for psoriasis for complete cure), and their quality of life index scores were lower than for other dermatoses. The authors explained this by the fact that vitiligo is characterized as a disease whose main problem is the psychosocial burden, including stigma, isolation, and low self-esteem. The standard DLQI cannot fully assess the psychological burden of stigma, since it is based on questions about physical symptoms, which makes the willingness-to-pay method more suitable for assessing the psychosocial burden in vitiligo [ 17].

Sach T. H. , Thomas​ K. S. and co-authors used a set of validated instruments to assess the psychological status of patients. The Beck Depression Inventory includes 21 questions to assess feelings of sadness, guilt, and social isolation. The Beck Hopelessness Scale contains 20 statements measuring negative attitudes toward the future. The General Health Questionnaire (GHQ-28) showed that 49.5% of patients have poor mental health versus 33.0% in the control group. These data highlight the need for a comprehensive approach to the treatment of vitiligo, taking into account psychosocial factors [ 18].

 

Innovative methods of diagnostics and activity assessment

SE Uitentuis et al. (2020) validated UV photography in combination with digital surface measurement for the first time to determine the area of vitiligo lesions. In a cohort study of 31 lesions in 17 patients, the authors demonstrated the superiority of UV photography over a conventional digital camera: 100% of the images were rated as good or very good versus only 26% with conventional photography. The intraclass correlation coefficients between the different measurement methods reached 0.983-0.988, confirming the high validity of the method [ 19].

1. van Geel et al. developed and validated the Vitiligo Signs of Activity Score (VSAS), a standardized tool for assessing clinical signs of vitiligo activity. The tool is based on three key clinical signs: confetti-like depigmentation as a sign of rapidly progressing vitiligo, the Koebner phenomenon, and hypochromic areas. The reliability results exceeded the thresholds for acceptable inter- and intra-rater reliability, demonstrating significant correlations between the VSAS scores and PGA expert assessments for all raters [ 20].

 

Modern therapeutic approaches

There is currently no completely satisfactory treatment for vitiligo, so further development of new drugs and publication of data on the long-term efficacy and safety of existing treatments is needed.

 

Biological therapy: possibilities and limitations

A.R. Tavitova, A.A. Krinitsyna, and K.M. Lomonosov (2020) conducted a systematic review of the use of biological drugs in vitiligo. The results of therapy were inconclusive. TNFα inhibitors showed conflicting results: adalimumab at a dose of 80 mg subcutaneously at week 0, then 40 mg every 2 weeks was well tolerated, but did not demonstrate efficacy. Infliximab at 5 mg/kg intravenously did not lead to repigmentation in any of the 6 patients. More encouraging results were obtained with efalizumab: in a 52-year-old patient with universal vitiligo, partial repigmentation of the depigmented skin of the face and hands was observed after 6 weeks of therapy with subcutaneous injections of 1 mg/kg weekly. The authors identified an important clinical fact: in patients treated with etanercept, infliximab and adalimumab, the risk of developing vitiligo increased approximately 2-fold compared to traditional therapy. The risk was especially high in women and patients under 40 years of age [ 21].

 

JAK inhibitors as a breakthrough in vitiligo therapy

1. Konieczna, A. Winnicki and J. Krysiński presented data on new perspectives of JAK/STAT inhibitors in vitiligo. Tofacitinib as a 2% cream showed efficacy in a pilot study in combination with narrowband UVB therapy for the treatment of facial vitiligo. Puxolitinib showed positive results in a 32-week open-label extension study of topical application with optional narrowband ultraviolet B therapy [ 22].

The most recent clinical studies of JAK inhibitors are presented by the work of V. Azzolino, L. Zapata, M. Garg, M. Gjoni, RL Riding, JP Strassner, JM Richmond, JE Harris in 2021. The aim of the study was to evaluate the efficacy of JAK inhibitors tofacitinib and ruxolitinib in the treatment of vitiligo in a mouse model, to study the effect on resident memory T cell populations in the skin and to determine the mechanisms of action. The authors used a mouse model of vitiligo with disease induction by adoptive transfer of melanocyte-specific CD8+ T cells and performed an analysis using flow cytometry, clinical assessment and immunophenotyping (Fig. 4). In the prophylactic model, tofacitinib showed a statistically significant decrease in vitiligo score, while ruxolitinib demonstrated a slight decrease. In a reversal model, both drugs showed significant restoration of pigmentation while preserving the resident memory T cell population [ 23].

A clinical case presented by M. Komnitski and colleagues demonstrated the revolutionary potential of tofacitinib in the treatment of vitiligo. A 40-year-old woman with rheumatoid arthritis and vitiligo received tofacitinib 5 mg twice daily for two years. The results showed partial repigmentation without exposure to ultraviolet radiation. The mechanism of action of tofacitinib is based on the inhibition of JAK 1/3 kinases, which blocks IFN-γ signaling. Since IFN-γ signal transduction occurs through JAK 1/2, tofacitinib effectively reduces CXCL10 expression and interrupts vitiligo activity. After 8 months of treatment, the first signs of improvement appeared with the formation of repigmentation islands in the hands and face. After two years of therapy, complete repigmentation of the forehead and perioral macules, partial repigmentation of the back of the neck and upper chest were observed [ 24] .

1. Rosmarin et al. presented data on topical ruxolitinib as the first topical JAK1/2 inhibitor for the treatment of vitiligo. Concentrations of 0.15%, 0.5% and 1.5% ruxolitinib cream were studied. The mechanism of action is based on the suppression of immune autoreactivity in the skin through topical inhibition of JAK, which allows for the restoration of the number and function of melanocytes [ 25].

 

Immune checkpoints

An innovative concept of using immune checkpoints was proposed by M. Willemsen , C. J. M. Melief , M. W. Bekkenk , R. M. Luiten in 2020. The authors developed a revolutionary concept of therapeutic enhancement of the PD- 1 /PD- L1 axis for the treatment of vitiligo, which is the opposite of oncoimmunotherapy. If in oncology PD-1/PD- L1 is blocked to activate immunity, in vitiligo it is proposed to enhance them to induce anergy of active autoreactive T cells and restore tolerance. The authors highlighted the role of dendritic cells and macrophages as key cellular targets, while potential therapeutic strategies include PD-L1 agonists in the form of soluble forms for systemic action and topical drugs for local use [ 26].

 

Clinical trials of new drugs

The study by A. Khemis et al. presented the results of a 52-week prospective, randomized, placebo-controlled study of apremilast in combination with narrowband UVB therapy. 80 patients were randomized into two groups to evaluate the effectiveness of combination therapy. The results showed no additional effect of apremilast to NB-UVB therapy. In the apremilast + UVB group, the average VASI score decreased from 23.63 to 19.49, while in the placebo + UVB group, a more pronounced improvement was observed from 21.57 to 15.25. Intergroup differences were insignificant, which emphasizes the need to search for alternative therapeutic approaches [ 27].

1. Kanokrungsee and colleagues conducted a randomized, single-blind, controlled trial comparing the efficacy of 0.01% bimatoprost with 0.1% tacrolimus in non-segmental facial vitiligo. Sixteen patients received both drugs on different areas of the face for 12 weeks. Bimatoprost is a synthetic analogue of prostaglandin F2α, originally used to treat glaucoma. The mechanism of action is based on the stimulation of melanocyte dendriticity through activation of prostaglandin receptors. Keratinocytes are the main source of prostaglandin production in human skin [ 28].

Modern approaches to the treatment of vitiligo include combination methods to achieve maximum effect. D. Rosmarin et al. emphasized the importance of light in the treatment of vitiligo with JAK inhibitors. The synergistic effect of the combination of topical JAK inhibitors with narrowband UVB radiation opens up new opportunities for therapy optimization. TH Sach et al. presented the first complete economic evaluation of the treatment of localized vitiligo. The study showed that home NB-UVB therapy using portable devices can be a cost-effective alternative to traditional treatments [ 25].

 

Modern methods of assessing the effectiveness of vitiligo treatment

1. Kanokrungsee et al. presented modern methods for assessing the effectiveness of vitiligo treatment. The 6-point Vitiligo Activity Scale (VIDA) is used to assess disease activity. Digital photography and VISIA analysis allow for an objective assessment of repigmentation dynamics. The quartile repigmentation assessment scale includes five degrees from no changes to 76-100% repigmentation. Additional methods include measuring intraocular pressure in eyelid lesions and assessing patient satisfaction using a visual analog scale [ 28].

 

Prospects for the development of vitiligo therapy

Modern research opens new horizons in the treatment of vitiligo. A. Konieczna et al. identified promising areas: antioxidant therapy with systemic use of vitamins A, C, E, alpha-lipoic acid, golden fern extract and ginkgo biloba; local therapy with gel with catalase and superoxide dismutase in combination with UVB phototherapy; innovative combinations of narrow-band UVB with topical drugs, including tofacitinib, latanoprost, pimecrolimus and tacrolimus [ 22].

Promising therapeutic directions are represented by studies of CAR-Treg therapy. YR Mohseni, SL Tung, C. Dudreuilh et al. conducted a study in 2020 to develop future directions of regulatory T cell therapy using CAR technologies and to analyze the prospects for the introduction of CAR technology into Treg therapy. The authors used methodological approaches including antigen-specific therapy using antigen-presenting cells to generate Tregs with specific reactivity, CAR-Treg technology with chimeric antigen receptors to improve specificity and efficacy, and various in vivo imaging approaches to understand the biodistribution of the injected Tregs. Innovative results showed that kidney transplant patients were treated with donor-specific Tregs, additional clinical trials in transplant patients are investigating the use of donor-reactive Tregs, demonstrating the development from the use of antigen-presenting cells to the generation of Tregs with specificity [ 29].

LZ Li, Z. Zhang, VG Bhoj in 2021 highlighted the factors determining the efficacy of CAR-T therapy. VG Bhoj, being a co-author of patents on CAR engineering technologies, made significant contributions to the development of proprietary technologies and the transition from basic research to clinical application. The authors emphasize the fundamental importance of the correct choice of target antigens, optimization of the structure of chimeric receptors for maximum efficacy, and the need for switching systems to prevent unwanted effects [ 30].

 

Conclusion

Modern studies have confirmed the convergent theory of vitiligo pathogenesis based on the interaction of genetic predisposition, autoimmune mechanisms and melanocyte dysfunction. The key role in pathogenesis is played by cytotoxic CD8+ T lymphocytes, mediating selective destruction of melanocytes via the perforin-granzyme pathway, while the critical role of the interferon-γ-induced chemokine loop CXCL10-CXCR3 in attracting autoreactive cells to lesions has been established.

Recent genetic studies have demonstrated revolutionary discoveries in understanding the molecular architecture of the disease. Genome-wide association studies have identified 54 gene loci associated with vitiligo, with the genetic heritability of the disease being almost completely determined, with familial and SNP heritability rates of 0.75–0.83 and 0.78, respectively. A maternal predominance in the inheritance of vitiligo has been established, with a coefficient of 4.26 versus 3.36 for paternal transmission, indicating epigenetic mechanisms of inheritance.

Novel disease biomarkers include the transcription factor NFATC1, first described in vitiligo and correlating with the functional activity of regulatory T cells, FOXP3 promoter polymorphisms rs3761547 and rs3761548 associated with susceptibility to the disease, as well as NKG2D+ CD8+ memory T cells as promising molecular targets for therapeutic interventions. The cytokine profile is characterized by an increase in IL-17, an imbalance of lymphocyte subsets with a violation of the Th1/Th17 and Tregs/Th2 ratios, which opens up new opportunities for a personalized approach to therapy.

Clinical trials of drugs demonstrate the promise of JAK inhibitors as a breakthrough direction in the treatment of vitiligo. Topical ruxolitinib as the first approved topical JAK1/2 inhibitor shows efficacy through suppression of immune autoreactivity in the skin, while tofacitinib demonstrates systemic efficacy through blockade of IFN-γ signaling. Innovative therapeutic approaches include the concept of therapeutic enhancement of the PD-1/PD-L1 axis as opposed to oncoimmunotherapy, as well as the prospects of CAR-Treg therapy using chimeric antigen receptors to increase the specificity of regulatory T cells.

This paper is a comprehensive analysis of the latest advances in understanding vitiligo as a multifactorial autoimmune disease based on research from 2020-2025. For the first time, modern data on the polygenic architecture of vitiligo are systematized with an emphasis on newly identified genetic loci and their functional significance in the pathogenesis of the disease. A critical analysis of new biomarkers is presented, including cytokine profiles, microRNAs, and metabolomic signatures that can serve as indicators of the activity of the depigmentation process and prognostic factors for the effectiveness of therapy. Particular attention is paid to a review of the results of modern clinical trials of innovative therapeutic approaches, including targeted immunotherapy, gene therapy, and personalized treatments. The work contributes to the understanding of the molecular mechanisms of the interaction of genetic predisposition and environmental factors in the development of vitiligo, opening up new prospects for the development of pathogenetically based diagnostic and treatment methods.

The results of this review have direct clinical implications for dermatologists and researchers studying autoimmune diseases.

Systematized information on new genetic markers can be used to develop genetic testing panels to identify patients with a high risk of developing vitiligo and predict the course of the disease. The presented data on modern biomarkers create the basis for the introduction of a personalized approach to monitoring disease activity and assessing the effectiveness of therapy. Analysis of the results of clinical trials of new drugs provides practicing physicians with up-to-date information on modern therapeutic options and their evidence base. The data obtained can be used to optimize existing vitiligo treatment protocols and develop new clinical guidelines. In addition, the identified promising areas of research help determine priorities for future scientific projects in the field of skin dyschromia .

About the authors

jihene amami

Federal state budgetary educational institution of higher education "Ryazan state medical University named after academician I. P. Pavlov" of the Ministry of health of the Russian Federation

Author for correspondence.
Email: jihene.amami1997@gmail.com
ORCID iD: 0009-0004-9326-3703

 

Resident physician in the specialty Dermatovenereology .

Russian Federation, 390026, Russia, Ryazan, Vysokovoltnaya street,house 9.

Elena Egorovna Zhiltsova

Federal state budgetary educational institution of higher education "Ryazan state medical University named after academician I. P. Pavlov" of the Ministry of health of the Russian Federation

Email: elen_egorovna@mail.ru
ORCID iD: 0000-0001-9406-6841
SPIN-code: 5688-0672

Doctor of medicine, Associate Professor, Head of the Department of Dermatovenerology and laboratory diagnostic

Russian Federation, 390026, Russia, Ryazan, Vysokovoltnaya street,house 9.

References

Supplementary files