Gayane E. Bagramova’s research while affiliated with Peoples' Friendship University of Russia and other places

Atopic dermatitis is a common chronic skin disease that is always accompanied by itching and has a significant impact on the patient's quality of life. The goal of therapy for atopic dermatitis, like any chronic dermatosis, is to achieve stable remission, which, given the nature of the disease, can be achieved with the help of a drug that has anti-inflammatory potential and a high safety profile. The therapeutic options for the use of pimecrolimus in patients with atopic dermatitis are observed in the Article.

Atopic dermatitis is a hereditary inflammatory skin disease characterized by pruritus, a long recurrent course and certain evolutionary dynamics. Atopic dermatitis of moderate and severe severity is considered a systemic disease that exacerbates the course of associated pathologies, including cardiovascular, neuropsychiatric, and malignant diseases. The current paper presents the essentials about moderate and severe severity atopic dermatitis, statistical epidemiologic and pathogenetic data is thoroughly processed, the issues of the quality of life of such patients are especially accentuated. It is known that a few years ago the therapy of moderate and severe atopic dermatitis was based on systemic corticosteroids and classical immunosuppressants, but they had limited efficacy and were not suitable for long-term treatment due to their safety profile. This article highlights the development of new effective and easy-to-use therapies for atopic dermatitis, which led to the emergence of selective Janus kinase inhibitors. The review presents the way selective inhibitors of Janus kinases works and their effect on the barrier function of the skin. The paper provides the research data on the very first drug from the group of selective inhibitors - upadacitinib, which proved its efficacy on a par with a high degree of safety. The authors presented their own clinical observation of the use of upadacitinib in adolescents with severe atopic dermatitis. The use of upadacitinib in the described clinical cases led to a decrease in the severity of subjective and objective symptoms of inflammatory skin diseases.

Tyrosine kinase inhibitor imatinib is a standard agent for treatment of gastrointestinal stromal tumors (GIST). Treatment courses are quite long and are usually well tolerated. However, skin rash can occur on treatment, with a prevalence of 7 to 88.9%. We describe a clinical case of a patient with GIST, who has been on treatment with imatinib at daily dose of 400 mg for one year. Several weeks from the treatment initiation, she had facial edema, and 4 months thereafter psoriasiform rash appeared which was initially considered to be psoriatic. After 8 months, the patient had lichenoid rash on the inguinal skin and oral, tongue and vulvar mucosae. Clinically, the lichenoid rash was similar with lichen ruber planus. To confirm the diagnosis, we performed biopsy of psoriasiform and lichenoid foci. Histological examination verified the drug-induced rash. Topical treatment of psoriasiform rash with glucocorticosteroids resulted in regression of some plaques, although a proportion of them persisted. Inguinal and vulvar lichenoid rashes completely regressed and numbers of oral and tongue foci decreased after a 6-week daily application of the 0.1% tacrolimus cream. Treatment with imatinib 400 mg daily was not interrupted. The clinical observation illustrates the possibility of skin and mucosal lichenoid and psoriasiform rash simultaneously during treatment with imatinib and demonstrates the first successful experience in the treatment of lichenoid rashes with 0.1% tacrolimus cream.

Мелазма-это хроническое заболевание кожи, связанное с избыточной выработкой и накоплением меланина в участках, подверженных воздействию ультрафиолетового излучения. Лечение мелазмы является длительным и осложняется частыми рецидивами и резистентностью ко многим терапевтическим методам. Патогенез меланодермии очень сложен из-за физиолого-биохимических нарушений метаболизма, происходящих вне пигментных клеток кожи. Он включает в себя фотостарение, увеличение количества тучных клеток, чрезмерный меланогенез, усиление васкуляризации и повреждение базальной мембраны. Кроме того, поражения кожи, связанные с меланодермией, и окружающая их кожа почти на 300 генетических участков отличается от здоровой кожи, что свидетельствует о чрезвычайно высокой сложности и разнообразности механизмов патогенеза. Традиционная терапия мелазмы включает локальное применение препаратов, таких как глюкокортикоиды, гидрохинон, третиноин и различные составы, однако без применения комплексного подхода, включающего химические пилинги, лазерную и световую терапию, микронидлинг и/или использование системной терапии в большинстве случаев невозможно добиться положительного и устойчивого клинического эффекта. Стратегия лечения мелазмы должна начинаться с диагностики, устранения факторов риска, фотопротекции, и только после этого могут применяться индивидуально подобранные методы, включающие в себя не только устранение гиперпигментации, но и регенерацию кожи. В этом обзоре мы рассматриваем современные методы лечения мелазмы, включающие в себя комплексный подход, базирующийся на механизмах патогенеза. Modern methods of diagnosis and treatment of melasma Melasma is a chronic skin disease associated with excessive production and accumulation of melanin in areas exposed to ultraviolet radiation. Treatment of melasma is long and complicated by frequent relapses and resistance to many therapeutic methods. The pathogenesis of melasma is very complicated due to physiological and biochemical metabolic disorders occurring outside the pigment cells of the skin. It includes photoaging, an increased number of mast cells, excessive melanogenesis, increased vascularization and damage to the basement membrane. In addition, skin lesions associated with melasma and the skin surrounding them differ by almost 300 genetic sites from healthy skin, which indicates an extremely high complexity and diversity of pathogenesis mechanisms. Traditional melasma therapy includes the local use of drugs such as glucocorticoids, hydroquinone, tretinoin and various formulations, however, without the use of an integrated approach, including chemical peels, laser and light therapy, microneedling and / or the use of systemic therapy, in most cases it is impossible to achieve a positive and sustained clinical effect. The melasma treatment strategy should begin with diagnosis, elimination of risk factors, photoprotection, and only after that individually selected methods can be applied, including not only the elimination of hyperpigmentation, but also skin regeneration. In this review, we consider modern methods of treating melasma, which include an integrated approach based on the mechanisms of pathogenesis.

Atopic dermatitis is an inflammatory skin disease that is most frequently occurred in children, but also common in adults. The disease is characterized as chronic, but only 20% of children have severe atopic dermatitis, while the other 80% achieve a longterm remission by the age of 8 and earlier. The article summarizes the main details about atopic dermatitis including statistical epidemiological and pathogenetic data, and places special emphasis on the issues of patients’ quality of life and steroidophobia. It is known that combination treatment regimens are often used in the treatment of atopic dermatitis. The article highlights approaches to the tactics of choosing topical therapy according to the European guidelines for the treatment of atopic dermatitis 2018. Despite the fact that topical calcineurin inhibitors were made available for the treatment about 15 years ago, this group of drugs take the lead in the treatment of atopic dermatitis due to a pronounced anti-inflammatory mechanism of action with a steroid-sparing effect. The review presents the main mechanisms of action of topical calcineurin inhibitors and their effect on the skin’s barrier function. Literature data on the proven efficacy and high safety profile of Tacrolimus, the very first drug from the topical calcineurin inhibitor group, are presented. In the article, the authors described examples of the successful use of Tacrolimus, which can suppress the T-lymphocyte activation and reduce the production of pro-inflammatory cytokines in patients with moderate to severe atopic dermatitis, as well as with other chronic allergic dermatoses. The use of Tacrolimus in the presented clinical cases led to a reduction of severity of subjective and objective symptoms of the inflammatory skin diseases.

Photodermatoses represent a heterogeneous group of disorders characterized by the development of pathological skin reaction to solar radiation. The development or intensification of inflammatory skin reaction after exposure to ultraviolet or electromagnetic spectrum that is visible to the human eye is a distinctive feature of all photosensitive photodermatoses. Although photodermatoses are less common in children than in adults, they are often associated with genetic or congenital metabolic disorders, and may also point to diffuse connective tissue diseases. Paediatric photodermatoses are often the result of genetic or congenital metabolic disorders, and may also indicate diffuse connective tissue diseases. The epidemiological studies have showed that the global prevalence of photodermatoses diagnosed with photopatch tests is above or equal to 5.7%. The authors presented a modern classification of photosensitive dermatoses according to the etiological factor. The article provides up-to-date information about photosensitive dermatoses, including statistical epidemiological data, pathogenesis features, and also emphasis is placed on the issues of the quality of life of children and their parents. The authors described the clinical presentations of the most common paediatric photosensitive dermatoses and the basic principles of their therapy. Among topical glucocorticosteroids, methylprednisolone aceponate has proven itself in the treatment of paediatric photodermatoses as it has not only a pronounced anti-inflammatory effect, but also is easy-to-use. The timely diagnosis of paediatric photosensitivity will help to minimize the development of complications associated with delayed treatment and insufficient prevention (photoprotection).

Langerhans cell histiocytosis (LCH) belongs to histiocytic proliferative diseases, which are rare in clinical practice; however they pose significant challenges both for their diagnosis and choice of therapeutic strategies. Histiocytic proliferative diseases are the scope of oncology; nevertheless, at the diagnostic stage the patients are referred to pediatricians or dermatologists. That is why the interdisciplinary interaction of various specialties and common approaches to their classification, diagnosis and treatment are important for the management of patients with histiocytic proliferative disorders. Accumulation of the studies on the LCH pathophysiology has promoted the development of new diagnostic algorithms and treatment methods. After the fact of MAPK signal pathway activation had been established, the potential target for therapy was identified. Neoplastic nature of LCH has been hypothesized. If confirmed, we can expect actual diagnostic algorithms being elaborated, in particular, the potential to predict the disease depending on the tumor clone mutation type. The unique characteristics of LCH including proliferate clonality (presumable of neoplastic nature), the disease course with spontaneous regression and frequent relapses and tropism to certain tissues (target organs) make up the grounds for further in-depth studies of the disease.

Enteropathic acrodermatitis is a rare form of genodermatoses, a group of hereditary disorders with prevailing skin lesions. The disease manifestation in children is associated with withdrawal of breastfeeding and switch to the cow milk-based products, which makes it difficult to differentiate enteropathic acrodermatitis from allergic dermatoses. We describe a familial case of enteropathic acrodermatitis in a 4-month old girl with advanced skin lesions and diarrhea. The familial history positive for enteropathic dermatitis made it possible to immediately suspect this diagnosis in the patient and to administer a zinc sulfate-containing agent before the genetic test results have become available. The response to therapy was obtained within a few days. Genetic testing of the patient identified a new mutation in exon 10 of the SLC39A4 gene. Proper collection of the past history and physician's vigilance to zinc-deficient conditions in acral dermatitis combined with alopecia and diarrhea in infants would allow for a timely and proper diagnosis and choice of a subsequent management strategy.

Background: Palmar-plantar psoriasis is characterized by a torpid course and resistance to conventional systemic treatments. Phototherapy is usually considered as an adjuvant treatment of a patient with psoriasis. The potential use of phototherapy as a basic treatment strategy in limited psoriasis, including its plantar-palmar localization, could be of interest. Aim: To study the efficacy, safety and tolerability of the narrowband phototherapy (UVB 311 nm) in the treatment of different forms of psoriasis with predominant palmar-plantar involvement. Materials and methods: We retrospectively analyzed the results of treatment of 77 in-patients admitted to the Department of Dermatology for treatment of various types of psoriasis with prevailing palmar and plantar lesions. The main group consisted of 42 patients who were administered combination therapy including topical corticosteroids, hepatic protectors, antihistaminic agents and, in addition, the narrowband phototherapy with a phototherapy device Dermalight 500-1 (Dr. Hnle Medizintechnik GmbH, Germany). The initial radiation doses were set without the determination of the minimal erythema dose, depending on the patient's skin type, in accordance with the guidelines from the manufacturer. At each consecutive session, the dose was increased by 0.060.3 J/cm. The sessions were conducted 5 times a week with a total of 1421 sessions. The mean cumulative dose was 22.8 J/cm. The control group included 35 age-, gender- and psoriasis severity-matched patients who received the same treatments, except the narrowband phototherapy. The treatment efficacy was assessed by changes in the Palmoplantar Pustulosis Area and Severity Index (PPPASI). Clinical results of treatment were evaluated at day 10 after the treatment course had been completed. Results: No serious adverse events were registered during the treatment. In the patients with psoriasis vulgaris and predominant palmoplantar lesions, receiving the narrowband phototherapy, the PPPASI reduction was higher than in the patients who received only conventional treatment (U-test, p = 0.015). A PPPASI decrease of 50% was observed in 83.3% (25/30) and 60% (15/25) of the patients, respectively. Clinical efficacy criteria were achieved in 66.6% (8/12) of the patients with palmoplantar pustular psoriasis receiving the combination treatment with phototherapy and in 40% (4/10) of the conventionally treated patients in the control group; however, the difference in the distribution of remission achievement was non-significant (U-test, p = 0.123). Conclusion: The study has demonstrated the efficacy of UVB 311 nm narrowband phototherapy in the treatment of patients with psoriasis with predominant palmoplantar lesions. The results obtained make it possible to recommend the inclusion of the narrowband phototherapy UVB 311 nm at mean cumulative dose of 22.8 J/cm into the standardized set of treatments of patients with psoriasis vulgaris with predominant palmoplantar lesions, not only as an adjuvant technique, but also as the main therapeutic strategy. The role of the narrowband phototherapy UVB 311 nm in the treatment of palmoplantar pustular psoriasis, as well as the dosing regimens of the radiation and determination of the necessary follow-up duration should be the subject of further studies.

Lichen sclerosus is one of the clinical variants of limited scleroderma, a feature of which is the defeat of the anogenital zone. The issues of the etiology and pathogenesis of lichen sclerosus remain not fully understood, despite numerous studies in which the polygenic nature of inheritance and multifactoriality in the implementation of dermatosis are noted. With the progression of the scleroatrophic process and the absence of timely pathogenetic therapy, there is a high probability of the development of comorbid pathology with a whole range of symptoms, such as urinary (dysuria, recurrent urinary tract infections - cystitis, urethritis, cystourethritis), gastrointestinal (pain during defecation, chronic constipation), vaginal severe dryness and increased sensitivity of the vaginal mucosa, burning, itching). Treatment of patients with lichen sclerosus with lesions of the anogenital zone causes great difficulties. In cases of isolated localization of scleroatrophic lesions of anogenital localization, difficulties may arise in the differential diagnosis with diseases of similar localization, such as vitiligo, atrophic lichen planus, basal cell carcinoma, contact dermatitis, nonspecific balanoposthitis, Keir's erythroplasia. Treatment of limited scleroderma, the clinical variant of which is lichen sclerosus, should be multi-course and complex, with the obligatory use of penicillin antibiotics, hyaluronidase-based drugs, drugs that improve microcirculation, vitamins, immunoregulators and physiotherapeutic methods. Thus, early diagnosis and timely pathogenetic therapy contribute to the prevention of the risks of developing genitourinary syndrome, progression of tissue sclerosis, and psychoemotional disorders. This article presents a clinical case of diagnosis and treatment of a patient with lichen sclerosus.