Mikhail A. Kochetkov

Background. Autoimmune thyroid diseases are the most common comorbid pathology of vitiligo. Presence of elevated levels of antibodies to the thyroid tissue in the blood of patients is one of the signs of autoimmune thyreopathies. In foreign studies, a higher detection rate of antithyroid antibodies has been established in patients with vitiligo compared to healthy people. In Russia, the frequency of antithyroid antibodies carriage in patients of this category has not been studied before. Objective. To evaluate the frequency of antibodies to thyroid peroxidase (AT-TPO) and thyroglobulin (AT-TG) carriage in patients with vitiligo as well as to identify factors associated with the carriage of antithyroid antibodies. Material and methods. During the study, 35 patients with vitiligo and 29 healthy volunteers were examined. The research protocol included determination of serum concentrations of thyroid-stimulating hormone, free thyroxine, AT-TPO and AT-TG, thyroid ultrasound. IBM SPSS Statistics software package (version 26.0) was used for statistical data analysis. Results. A higher frequency of AT-TPO, AT-TG carriage and simultaneous AT-TPO and AT-TG carriage has been established in patients with vitiligo compared to healthy volunteers (p<0.05). Mean levels of AT-TPO and AT-TG in patients were 13.6 and 9.7 times higher, respectively, than those of healthy volunteers. It has been found when performing a multidimensional logistic regression analysis that age of patient, vitiligo duration, area of depigmentation, late onset of the disease and vitiligo duration of 10 years or more are the independent factors associated with AT-TPO carriage. Age of patient, age of vitiligo manifestation, late onset of the disease and vitiligo duration of 10 years or more are independent factors associated with AT-TG carriage. Conclusion. The obtained results indicate the advisability of inclusion of the AT-TPO and AT-TG levels investigation in screening of vitiligo patients for early detection of autoimmune thyroid pathology along with the determination of thyroid hormone content.

Alopecia areata (AA) is a chronic inflammatory disease that causes partial or complete hair loss and is based on autoimmune processes. Current studies are actively investigating the use of JAK inhibitors for AA treatment, but data on the safety and efficacy of these drugs in patients with congenital immunodeficiency are practically non-existent. A unique clinical case of familial form of severe AA in two sisters with congenital immune disorders, that caused certain difficulties in treatment, is presented. The older sister, 24 years old, has been diagnosed with primary immunodeficiency — selective IgA deficiency combined with IgG2 deficiency, and the younger sister, 18 years old, is under observation with suspicion of immunodeficiency with a predominant defect of antibodies. Both patients receive targeted therapy with tofacitinib, in presence of which a partial hair regeneration, more pronounced in the younger sister, has been noted. This clinical case emphasizes the need for multidisciplinary interaction of dermatologists, immunologists and geneticists in treating patients with AA and congenital immune disorders. Special attention should be paid to clinical and laboratory monitoring to minimize the risk of infections associated with therapy using JAK inhibitors. Our observation contributes to the understanding of genetic and immune mechanisms of AA and confirms the possibility of JAK inhibitors application in patients with autoimmune diseases affected by immunodeficiency. These data may serve as an addition to the development of new recommendations and treatment algorithms in such cases, and still the final efficacy and safety of such therapy require further study.

Introduction. Systematization of dermatoscopic signs of monomorphic rashes in mastocytosis has important practical significance.Aim. To carry out an analysis of dermatoscopic patterns of monomorphic eruption in monomorphic maculopapular cutaneous mastocytosis (mMPCM) and indolent systemic mastocytosis (ISM) and compare the results obtained with pathomorphological signs of mastocytosis.Materials and methods. The study included 6 children aged 4 to 14 years, 27 adolescents and adult aged 15 to 40 years with a monomorphic type of maculopapular cutaneous mastocytosis (MPCM) and 3 patients (minimum age 18 years, maximum – 54 years) with indolent systemic mastocytosis (ISM), who were under observation at Moscow scientific and practical Center of dermatovenereology and cosmetology from 2022 to 2024. Dermatoscopic examination was performed using polarization and immersion dermatoscopy with 20-fold magnification.Results. The presence of mild vascular signs (punctate vessels) and the absence of a pigment pseudonetwork were the features of monoMPCM in children. In adolescents and adults, pigment network was detected in 77.8%, more often in men. The vascular erythematous component in adults was more intense than in children and was detected in 74.1% of patients. Yellow-brown structureless areas, brown reticular lines (pigment pseudonetwork) are due to hyperpigmentation of the basal cell layer, while the vascular pattern was the result of dilation of vessels in the papillary dermis. With ISM, a pronounced vascular pattern (intense erythematous background and reticular vascular pattern) and the obligatory presence of pseudonetwork were observed. The pathomorphological picture of ISM differed from MPCM by the presence of perivascular lymphomonocytic infiltrates and an insignificant number of eosinophilic granulocytes.Conclusion. In this study, age-related dermatoscopic features of monomorphic rashes in mastocytosis were systematized for the first time and compared with the pathomorphological signs of MPCM and ISM.

Relevance.Amonomorphic type of maculo-­papular cutaneous mastocytosis was allocated relatively recently. Inchildren and adolescents with amonomorphic type of MPCM (adult type pattern), clinical manifestations persist into adulthood and can transform into asystemic process, which determines the need for regular monitoring of this category of patients.Theaimwas to analyse the results of clinical, laboratory and instrumental examinations of an adolescent with amonomorphic type of MPCM.Materials and Methods. The study of an adolescent patient included data of laboratory examination, pathomorphological examination, ultrasound examination of the abdominal organs and cKIT gene of an adolescent with amonomorphic type of MPCM, observed at “Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology”.Resultsand Discussion.The process was represented by multiple rashes on the skin of the trunk and limbs. Darier’s sign is positive. The patient’s serum tryptase level exceeded the age norm. The late onset (atthe age of 12)of the disease, elevated tryptase levels, neurological symptoms, and the risk of anaphylaxis caused alertness regarding the development of the systemic form, therefore an ultrasound examination of the abdominal organs was performed and the presence of amutation in the cKIT gene in peripheral blood was determined.Conclusion.Clinical report of an adolescent patient in Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology was presented. Thus, the combination of clinical and laboratory data allows minimizing the number of invasive procedures in children with CM. Assessment of the tryptase level, mutation detection in the cKIT gene and ultrasound examination of abdominal organs can be useful for timely diagnosis of systemic mastocytosis, which allows to carry out the necessary correction of the disease status and drug therapy.

The growing number of children with rare diseases such as cutaneous mastocytoma and juvenile xanthogranuloma turning to dermatologists, as well as their clinical similarity, dictate the need for specialists to pay careful attention to these diseases. cutaneous mastocytoma is a clinical form of cutaneous mastocytosis. According to the WHO classification (2022), isolated (one focus) and multiple cutaneous mastocytoma (no more than three foci) are distinguished. juvenile xanthogranuloma belongs to the group of non-Langerhans cell histiocytosis, a broad group of related diseases characterized by the proliferation of histiocytes other than Langerhans cells. We describe a case of an unusual clinical course of solitary juvenile xanthogranuloma in a 3-year-old boy referred to Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology with suspected cutaneous mastocytoma. The size, unusual shape, localization of the lesion and elevated levels of serum tryptase exceeding the age norm (20 μg/l), and AST values, as well as ultrasound signs of hepatomegaly were revealed. Features of the dermoscopic and pathomorphological picture demonstrated patterns characteristic of infiltration and increased activity of mast cells. Cutaneous mastocytoma and juvenile xanthogranuloma are rare and benign skin diseases that usually begin in childhood. Diagnosis of rare diseases often requires complex differential diagnosis. Features of the modern course of cutaneous mastocytoma and juvenile xanthogranuloma are an atypical clinical picture and a high risk of developing extracutaneous symptoms. The presented clinical cases demonstrate the need for interdisciplinary monitoring of patients with these diseases and change the stereotypes of treating them as independent and regressive processes without a trace.

Introduction. Flushing is a subjective feeling of warmth that is accompanied by redness of the skin on any part of the body, but mainly on the face, neck and upper trunk. Episodic flushing with other symptoms associated with mast cell mediators can be observed in 30–50% of children with cutaneous mastocytosis (CM).Aim. To analyze the frequency of flushing in children with various clinical forms of cutaneous mastocytosis. To study serum tryptase levels in children with flushing.Materials and methods. The study included data from 275 children aged from 6 months to 17 years inclusive, who were undergoing outpatient treatment and observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology from March 2022 until January 2024. The concentration of tryptase in the blood was determined by immunofluo-rescence on a three-dimensional porous solid phase (ImmunoCAP technology, Pharmacia Diagnostics AB, Sweden). Polarization and immersion dermatoscopy with 20x magnification were performed.Results. Flushings were observed in 17.5% of patients out of 275 observed children with CM. The level of tryptase more than 15 µg/l was determined in 20.8% of children with flushing, above 11.0 µg/l – in 37.5%. Tryptase levels were higher than 8.0 µg/L in 22 (45.8%) patients. In 25.0% of patients with flushing, tryptase levels did not exceed 5 µg/L. The severity of the vascular pattern in lesions and apparently healthy skin was characteristic of patients with frequent or prolonged flushing and tryptase levels above 8.0 µg/L.Conclusion. This study was the first in the Russian Federation to demonstrate the prevalence of flushing in children with various clinical forms of cutaneous mastocytosis. The results showed that the assessment of serum tryptase levels should be performed in all children with flushing, regardless of the clinical form of mastocytosis, including those with isolated and multiple skin mastocytomas. Clinical laboratory and dermatoscopic monitoring are important for the development of individual therapeutic tactics and prevention of mediator reactions and anaphylaxis.

One of the most common comorbid conditions associated with vitiligo is autoimmune thyroiditis (AIT). However, the prevalence of AIT among patients with vitiligo varies significantly across different studies. Objective. The study aimed to investigate the frequency of AIT in patients with vitiligo attending outpatient clinics and to explore possible associations between AIT and clinical and anamnestic indicators. Material and methods. The study involved 85 patients (mean age 28 years): 53 adults and 32 children. A dermatologist and an endocrinologist examined all patients. The assessment included blood tests to determine the levels of thyroid-stimulating hormone (TSH), free T4, antibodies to thyroid peroxidase (TPO), and thyroglobulin (TG). Additionally, thyroid ultrasound examinations were performed. MS Excel and SPSS 13.0 for Windows were utilized for database management and statistical analysis. Results. AIT was identified in 22 out of 85 patients (25.9%), including 18 adults and 4 children: 21 patients had non-segmental vitiligo, and one had segmental vitiligo. The prevalence of AIT in vitiligo patients significantly exceeded the occurrence of thyroiditis in the general population of the Russian Federation (Ye.A. Troshina et al., 2021): odds ratio (OR) 81.24 (95% CI 47.59—130.64) (p<0.001). In 9 patients (40.9%), vitiligo appeared 1—17 years before the onset of AIT. In both the overall group, including adults and children, and the adult-only group, AIT was associated with A later age of vitiligo onset (p<0.001 and p=0.005, respectively) and a more frequent family history of AIT (p=0.008 and p=0.014, respectively). Conclusion. The prevalence of autoimmune thyroiditis (AIT) in vitiligo patients attending outpatient clinics significantly exceeds the occurrence of thyroiditis in the general population of the Russian Federation. In nearly half of the patients, the onset of vitiligo preceded the development of thyroiditis. AIT was statistically significantly associated with an older age of vitiligo onset and a more frequent family history of AIT. These findings highlight the need to develop recommendations for thyroid function screening in vitiligo patients and guidelines for monitoring them to ensure early detection of endocrine disorders.

Diffuse cutaneous mastocytosis (DCM) is the rarest and most severe clinical form of mastocytosis in children. The frequency of DCM among forms of skin mastocytosis varies from 1 to 13%. Major spontaneous vesicles formation is the leading clinical sign of disease in neonatal and infant periods. Rubbing or scratching of skin lesions during DCM causes immediate release of mast cell mediators and leads to flushing reactions, urticaria, up to the development of anaphylactic shock and death. The clinical case of DCM in a 3 months old boy with multiple vesicular rashes, yellow-brown infiltrated plaques and areas of atrophy on the scalp, face, body, upper and lower limbs is presented. In the morphological study of skin bioptate, pigmentation of the basal epidermis layer’s keratinocytes without signs of pigment deposition, massive infiltration of the upper dermis layer by lymphomonocyte subpopulations and separation with the formation of subepidermal vesicle were determined. The positive reaction was shown in immunohistochemical staining with antibodies to CD117. Reaction with antibodies to Melan A, S100 and Langerin was negative. Immunohistochemical examination in the observed patient allowed to eliminate hematological diseases and cancer. The blood serum tryptase level was 14.2 μg/l (normal value is less than 11 μg/l). During the dermatoscopic rash examination a vesicle of yellow-brown color and with rounded outlines was visualized in the focus center. Intense yellow coloring with linear vascular structures was on its periphery. Clinical diagnostics of DCM requires comprehensive differential diagnosis and interdisciplinary interaction. For this reason, the focus is on the results of pathomorphological and immunohistochemical examinations of bioptate. Parents should be informed about the serious complications that may develop from the massive release of mast cell mediators. Follow-up of patients with DCM requires dermatologist’s follow-up, monitoring of the state of internal organs’ functions, hematological indicators and tryptase level.

The importance of melanoma early diagnostics is a key factor in improving patient survival. Prevention and early detection of melanoma have led to progress in skin cancer diagnostics, including the technologies development in the sphere of artificial intelligence (AI). Assessment of possibilities and limitations of AI in dermatology has a prime importance for its future development and practical application. AI, realized as a chat-bot format, can help in melanoma early diagnostics and has a special value at the interface between primary and secondary health care. The new technology is an excellent opportunity for doctors to learn melanoma diagnostics in a playful way, realizing the capabilities of this new diagnostic tool and promoting its safe and ethical integration into the health system. As a part of this solution development, it’s planned to expand the educational data set to check the dermatologists’ skills of melanoma identification by dermatoscopic images. In addition, it’s planned to add unclassified images to classify them in future by system users, who received the best results in statistics of proper answers. The introduction of new images by doctors will allow to continue the learning of AI algorithm to improve disease’s machine detection based on uploaded image.

The approach to diagnosis and treatment in dermatovenerology has changed significantly with the introduction of new technologies and inventions. Computer algorithms have been used to assist dermatovenerologists in diagnosing diseases, including malignant melanoma of the skin. Instrumental methods for diagnosing skin melanoma, based on the processing of dermatoscopic images, can be improved by using artificial intelligence. Machine learning is a subset of artificial intelligence in which computer programs automatically learn from experience without explicit operation instructions. The most promising direction is deep learning of artificial neural networks. In this paper, several models of artificial neural networks were studied to assess the prospects for their use for the early diagnosis of skin melanoma. The efficacy of the various models was analyzed using the HAM10000 dataset image classification. Models of convolutional neural networks, pre-trained neural networks with transfer learning, and the “soft attention” mechanism were evaluated: Xception, ResNet50, RAN50, SEnet50, ARL-CNN50, Inception Resnet V2 — IRv2 12x12+SA, IRv2 5x5+SA. The results showed that the most promising model was Inception Resnet V2 with the addition of a «soft attention» mechanism.