scholarly journals Challenges in Treating Genodermatoses: New Therapies at the Horizon

2022 ◽  
Vol 12 ◽  
Author(s):  
Marie-Anne Morren ◽  
Eric Legius ◽  
Fabienne Giuliano ◽  
Smail Hadj-Rabia ◽  
Daniel Hohl ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Genetic Defect ◽  
Unmet Need ◽  
Early Death ◽  
Therapeutic Trial ◽  
Allogeneic Bone ◽  
Normal Functioning ◽  
Preimplantation Genetic Testing ◽  
Inflammatory Reactions ◽  
Cell Therapies

Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a “read through” strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus.

scholarly journals ROLE OF MACROPHAGES IN IMMUNOPATHOGENESIS OF PSORIASIS AND OBESITY

2018 ◽  
Vol 18 (4) ◽  
pp. 122-127 ◽  
Author(s):  
Ya. Yemchenko
Keyword(s):  
Weight Loss ◽  
Systemic Inflammation ◽  
Genetic Factor ◽  
Skin Diseases ◽  
Inflammatory Reactions ◽  
Multifactorial Diseases ◽  
Psoriatic Disease ◽  
Close Relationship ◽  
Unified View

Psoriasis is one of the most common chronic recurrent multifactorial diseases of the skin with a predominance of genetic factor. The disease is characterized by hyperproliferation of epidermal cells, impairment in the keratinisation process against inflammatory reactions in the dermis, and by lesions on the nails, joints and scalp. According to the results of clinical and epidemiological research, about 3-4% of the population of our planet has psoriasis, regardless of gender, age and ethnic group, while the share of this pathology in the overall structure of skin diseases reaches from 1% - to 40% [4, 5], according to various data. However, despite the widespread of psoriasis and the large number of works on this problem, there is still no unified view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it is necessary to take into account the insufficiently studied comorbidities typically associated with this pathology. Recently, there has been a tendency towards the growth of psoriatic disease and obesity in the pathogenesis of which a significant role is assigned to systemic inflammation and macrophages. According to the results of this research, it has been found out that obesity and psoriasis has a common link of the pathogenesis, systemic inflammation, which manifests itself in the increased number of macrophages producing a large number of proinflammatory cytokines. Thus, obesity and inflammation causes a vicious circle of cause-and-effect relationships. Obesity provokes inflammation, and inflammation, in turn, increases obesity and prevents weight loss. The close relationship between psoriasis and obesity is extremely important in selecting patient-centred therapy. Therefore, the goal of further research is to carry out detailed study of the psoriatic comorbidities that will contribute into revealing new targets for the treatment of this dermatosis.

Experience in using Topicream soothing cream CICA for rehabilitation of skin and mucous membranes after destructive dermatocosmetological procedures in combination therapy of dermatoses

2021 ◽  
pp. 33-38
Author(s):  
L.V. Hrechanska ◽  
O.V. Podluzhna ◽  
S.Р. Ostapenko ◽  
А.Е. Alatorskyh
Keyword(s):  
Clinical Practice ◽  
High Efficiency ◽  
Skin Diseases ◽  
Secondary Infection ◽  
Skin Neoplasms ◽  
Skin Surface ◽  
Punch Biopsy ◽  
Duration Of Treatment ◽  
Inflammatory Reactions ◽  
Mucous Membranes

The widespread introduction of the destructive methods of treatment into the clinical practice of dermatovenerologists is caused by the significant spread of benign skin and mucous neoplasms. At the same time, any effect on the skin — chemical, physical or mechanical — causes damage. Thus, patients using these procedures need proper care for damaged skin and mucous membranes to prevent secondary infection and scaring. Disruption of the epidermal barrier after removal of benign skin neoplasms, carrying out biopsy and chemical peels always requires application of topical agents promoting full recovery of the epidermis. In addition, many skin diseases are accompanied by inflammatory reactions, which are complicated by secondary infection. The use of drugs with anti­inflammatory and reparative properties reduces the duration of treatment and promotes skin recovery.Objective — to evaluate the clinical efficacy and tolerability of using Topicream soothing cream CICA after derma­tocosmetological procedures on the skin and mucous membranes and to investigate the efficacy of its use at various skin and mucous membranes diseases including children.Materials and methods. The study included 57 patients aged 1 to 75 years with various skin diseases, benign skin and mucosal neoplasms, after punch biopsy and cosmetology procedures. Topical application of the Topicream soothing cream CICA on the damaged skin and mucosal areas was recommended to all participants of the study twice a day. Results and discussion. The use of the regenerating cream after dermatological treatment of benign skin neoplasms with apparatus methods, chemical peelings and punch biopsy, as well as the auxiliary treatment of skin diseases such as cheilitis, herpes, perianal fissure, allergic contact dermatitis (including in children) localized in folds and on the face, contributes to a significant reduction in signs of inflammation and subjective sensations, as well as rapid healing of the affected skin surface. At the same time, there is a good tolerance and the absence of side effects of Topicream soothing cream CICA, which allows it to be widely used in clinical dermatovenerology, gynecology and pediatrics.Conclusions. High efficiency and safety of Topicream soothing cream CICA allow its widespread use in clinical practice of dermatovenerologists, gynecologists and pediatricians.

scholarly journals THE ROLE OF PPAR IN THE PATHOGENESIS OF PSORIASIS AND OBESITY

2019 ◽  
Vol 19 (2) ◽  
pp. 224-229
Author(s):  
Ya. Yemchenko
Keyword(s):  
Skin Diseases ◽  
Social Activity ◽  
Future Research ◽  
Social Significance ◽  
Inflammatory Reactions ◽  
Multifactorial Diseases ◽  
The Social ◽  
Excessive Body Weight ◽  
Depth Study

Psoriasis is one of the most common chronic recurrent multifactorial diseases of the skin with a predominance of genetic predisposition. The disease is characterized by hyperproliferation of epidermal cells, impairment of the keratinisation against the background of inflammatory reactions in the dermal layer, the nails, joints and scalp involvement. According to the results of clinical and epidemiological research, about 3-4% of the population of our planet has psoriasis, regardless of sex, age and ethnic group, while the share of this pathology in the overall structure of skin diseases reaches from 1% - to 40%, according to some reports. However, despite the wide prevalence of psoriasis and a huge number of works on this issue, there is still no shared view on the pathogenesis of this dermatosis. The data presented by many clinical studies show that there has been a recent increase in cases of comorbidity of psoriasis and obesity, leading to severe, atypical, disabling and resistant to the treatment forms of dermatosis. All this considerably impairs the quality of life of patients with psoriasis, reduces their working capacity and social activity that lays emphasis on not only the medical but also the social significance of the problem. Immunological disorders and genetic defects have been proven as the causes of psoriasis and abdominal obesity. The distinctive feature of the pathogenesis in the patients having comorbidity of psoriasis and obesity, in contrast to the patients without excessive body weight, is a statistically significant increase in hyperleptinomia and in systemic cytokine proinflammatory potential. Therefore, the vision for the future research is in-depth study of the pathogenesis of comorbid disease in patients with psoriasis that will contribute to reveal new targets for the treatment of this dermatosis.

scholarly journals Reduced Fecal Calprotectin and Inflammation in a Murine Model of Atopic Dermatitis Following Probiotic Treatment

2020 ◽  
Vol 21 (11) ◽  
pp. 3968
Author(s):  
Myoung-Ju Kim ◽  
Ji-Young Kim ◽  
Minje Kang ◽  
Moo-Ho Won ◽  
Seok-Ho Hong ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Intestinal Inflammation ◽  
Probiotic Strain ◽  
Skin Lesions ◽  
Fecal Calprotectin ◽  
Therapeutic Effects ◽  
Inflammatory Reactions ◽  
Probiotic Treatment ◽  
Intense Pruritus

Atopic dermatitis (AD) is one of the most common skin diseases with inflammation, chronic relapses, and intense pruritus. Its pathogenesis includes genetic susceptibility, an abnormal epidermal lipid barrier, and an increased production of IgE due to immune dysregulation. Recently, AD has been reported to be associated with intestinal inflammation and dysbiosis in human and murine models. Various probiotics are being used to control intestinal dysbiosis and inflammatory reactions. However, it is difficult to predict or determine the therapeutic effects of the probiotics, since it is rare for clinicians to use the probiotics alone to treat AD. It is also difficult to check whether the intestinal inflammation in patients with AD has improved since probiotic treatment. The aim of the present study was to determine whether mice with induced atopic dermatitis had any changes in fecal calprotectin, an indicator of intestinal inflammation, after probiotic administration. Our results showed that the fecal calprotectin levels in mice with induced dermatitis decreased significantly after the administration of probiotics. In addition, epidermal skin lesions were attenuated and inflammatory-related cytokines were downregulated after the administration of probiotics in mice with induced dermatitis. These results suggest that changes in fecal calprotectin levels could be used to assess the effectiveness of a probiotic strain as an adjuvant treatment for AD.

scholarly journals THE ROLE OF LOCAL INFLAMMATION IN THE IMMUNOPATHOGENESIS OF PSORIASIS

2019 ◽  
Vol 19 (1) ◽  
pp. 109-114
Author(s):  
Ya. Yemchenko
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Skin Diseases ◽  
Systemic Disease ◽  
Inflammatory Reactions ◽  
Endogenous Factors ◽  
Multifactorial Diseases ◽  
Depth Study ◽  
Regulatory Lymphocytes

Psoriasis is one of the most prevalent chronic recurrent multifactorial diseases of the skin with a predominance of a genetic factor characterized by hyperproliferation of epidermal cells, the keratinisation impairment against the background of inflammatory reactions in the dermis, as well as lesions of the nails, joints and scalp, provoked by exogenous and endogenous factors. This disease can also be characterized by erythema, scaly elements, papules and plaques. According to the results of clinical and epidemiological research, about 3 – 4% of the population worldwide is diagnosed to have psoriasis, regardless of gender, age and ethnic group. The share of this pathology in the overall structure of skin diseases reaches from 1% - to 40%, according to various authors. They consider psoriasis as a systemic disease involving not only the skin, but also joints and viscera, and call it as a “psoriasis disease”. The causes of psoriasis are immunological disorders and genetic defects. Recently inflammation in the skin of psoriasis patients is considered as an autoimmune process, in which a key role is played by T-cells sensitized to keratinocytes. One of the most probable self-antigens that trigger an immune inflammation in psoriasis may be cytosolic DNA. We describe the functions of the subpopulations of immune cells and the effects of secreted cytokines in the pathogenesis of psoriasis: the dendritic cells — Langerhans cells, plasmacytoid dendritic cells, CD11c+ dendritic cells; T-cells — T helper type 1 and 17, cytotoxic T lymphocytes, T-regulatory lymphocytes. The development of T-cell memory and intradermal proliferation of T-cells in the skin of patients plays an important role in the development of relapses of psoriasis. Therefore, the goal of further research is to carry out more in-depth study of the immunopathogenesis of psoriatic disease that will reveal new targets for the treatment of this dermatosis.

scholarly journals Cellular and humoral components of the immune system of the skin

2016 ◽  
Vol 19 (1) ◽  
pp. 12-17
Author(s):  
Natalie V. Makhneva
Keyword(s):  
Immune System ◽  
Structural Damage ◽  
Skin Diseases ◽  
General Concept ◽  
The Body ◽  
Immunocompetent Cells ◽  
Inflammatory Reactions ◽  
Neoplastic Processes ◽  
New Therapeutic Approaches ◽  
Protein Components

Along with mucous membranes the skin as the main barrier to the outside world creates a system of protection against any influences of the world. It is not only the place of realization of immunological processes, but it also actively participates in them due to the existence of its own elements of the immune system which are able to actively participate in the development of inflammatory reactions and neoplastic processes. Skin cells interact with cells of the immune system by setting a direct contact or by secreting a number of soluble factors, called cytokines, and other protein components such as proteins of the complement system. The general concept of skin-associated lymphoid tissue and skin’s immune system with immunocompetent cells in the epidermis and dermis, for cooperation of which in various stages of the immune response requires identity concerning anti-genes of HLA system, is presented in the review. Thus, specific immunological reaction with antibody formation promote the release of antigen from the body of both exogenous and endogenous origin. However, at violation of any element of immunological protection there is a delay of antigen elimination process, that results in own tissue structural damage. Interaction with foreign antigens (physical, chemical, infectious, etc.), denaturation of its own proteins or disclosure of tissue structures (antigens), that did not contact with immunocompetent cells, promote the formation of autoantigens and the production of autoantibodies against them. Thus, skin is a highly organized structure with a network of immunocompetent cells and soluble mediators. Introduction of molecular and biological methods as a knowledge tool is continually expanding the information about the skin as an organ of the immune system. The gained knowledge will definitely promote the development of new therapeutic approaches to skin diseases.

scholarly journals Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy

2018 ◽  
Vol 9 (9) ◽  
pp. 159-170 ◽  
Author(s):  
Lieneke F.M. Ariëns ◽  
Daphne S. Bakker ◽  
Jorien van der Schaft ◽  
Floor M. Garritsen ◽  
Judith L. Thijs ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Guidelines ◽  
Human Monoclonal Antibody ◽  
Treatment Algorithm ◽  
Unmet Need ◽  
Current Treatment ◽  
Phase Iii ◽  
Treatment Standards ◽  
Inflammatory Skin Diseases

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The prevalence of AD is increasing and is currently estimated at 10–20% in adults worldwide. In the majority of patients, AD can be adequately controlled with topical treatment or ultraviolet light therapy, but there is a high unmet need for effective and safe therapeutics in patients with more severe or difficult to treat AD. During the past decade, new advances in the understanding of the underlying immune pathogenesis of AD have led to the development of new, more targeted therapies. Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4 receptor α, thereby blocking the IL-4 and IL-13 pathway, is one of the first biologics that has been developed for AD. Dupilumab has shown promising results in phase III trials and has recently been approved by the US Food and Drug Administration and the European Commission for the treatment of moderate to severe AD. With the approval of dupilumab, we are entering a new era of biological therapeutics in AD management. The place of dupilumab should be established in the current treatment standards. Based on current treatment guidelines and experts’ opinions in the management of AD, we have built a proposal for a treatment algorithm for systemic treatment of AD in European countries.

scholarly journals Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3058-3065 ◽  
Author(s):  
SJ Rosenfeld ◽  
J Kimball ◽  
D Vining ◽  
NS Young
Keyword(s):  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Severe Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Current Treatment ◽  
Subsequent Treatment ◽  
Severe Aplastic Anemia ◽  
Therapeutic Trial ◽  
Allogeneic Bone ◽  
Actuarial Survival

Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia.

Sign in / Sign up

Export Citation Format

Share Document