scholarly journals Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

2021 ◽  
Vol 8 ◽  
Author(s):  
Aylin Ruppenstein ◽  
Maren M. Limberg ◽  
Karin Loser ◽  
Andreas E. Kremer ◽  
Bernhard Homey ◽  
...  
Keyword(s):  
Immune Cells ◽  
Skin Diseases ◽  
Treatment Options ◽  
Nerve Fibers ◽  
Special Focus ◽  
Spinal Neurons ◽  
Inflammatory Skin Diseases ◽  
Underlying Causes ◽  
Specific Receptors ◽  
Chronic Pruritus

Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.

scholarly journals Itch in Atopic Dermatitis – What Is New?

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat
Keyword(s):  
Atopic Dermatitis ◽  
Intracellular Signaling ◽  
Sleep Disturbances ◽  
Skin Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Short And Long Term ◽  
Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

scholarly journals Improvement of granulomatous skin conditions with tofacitinib in three patients: A case report

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110394
Author(s):  
Meghan L McPhie ◽  
William C Swales ◽  
Melinda J Gooderham
Keyword(s):  
Skin Diseases ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Inflammatory Skin Diseases ◽  
Efficacious Treatment ◽  
Inflammatory Skin ◽  
Granulomatous Disorder ◽  
Skin Conditions

Granulomatous skin conditions are poorly understood inflammatory skin diseases consisting predominantly of macrophages. Granuloma annulare (GA) is the most common granulomatous skin disease and the generalized variant is particularly difficult to treat due to the prolonged course and lack of efficacious treatment options. Necrobiosis lipoidica (NL) is another granulomatous disorder of uncertain etiology. There is a growing body of evidence for the use of Janus kinase (JAK) inhibitors in the management of inflammatory skin diseases. In our report, we describe three patients with recalcitrant granulomatous disease including NL and generalized GA who responded favourably to treatment with the JAK inhibitor tofacitinib. JAK inhibitors may be a beneficial therapeutic option for patients with granulomatous skin diseases that are unresponsive to conventional therapies. Further research is required to determine the long-term efficacy and safety of JAK inhibitors in treating granulomatous skin conditions.

scholarly journals Systemic treatment of psoriasis: from methotrexate to biologics

2020 ◽  
Vol 96 (3) ◽  
pp. 7-26
Author(s):  
Olga Yu. Olisova ◽  
Ekaterina M. Anpilogova
Keyword(s):  
Skin Diseases ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Certolizumab Pegol ◽  
Severe Psoriasis ◽  
Unknown Etiology ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Complete Clinical Remission

Psoriasis is one of the most frequent chronic inflammatory skin diseases and it has been of interest to many scientists for ages. The review presents data on all systemic treatment options, that are to date officially registered in Russian Federation for moderate-to-severe psoriasis. Aspects of the mechanism of action, efficacy and tolerability of both basic drugs (methotrexate, cyclosporine, acitretin) and biologics (infliximab, adalimumab, etanercept, certolizumab pegol, ustekinumab, guselkumab, secukinumab, ixekizumab, netakimab) and small molecules (tofacitinib, apremilast) are considered in detail. Special emphasis is placed on the important nuances of biological therapy: immunogenicity, drugs' survival and switch due to lack of efficacy. Invention of biologics signified a new era of moderate-to-severe psoriasis treatment. It became possible to achieve complete clinical remission more safely, which significantly improved the quality of life of patients. However, due to the unknown etiology of psoriasis, there is still no universal remedy that would allow to cure every patient, this fact makes scientists from all over the world keep conducting numerous clinical trials to find even more effective and safe therapeutic options.

scholarly journals Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain

2018 ◽  
Author(s):  
Devin M. Barry ◽  
Xue-Ting Liu ◽  
Qianyi Yang ◽  
Xian-Yu Liu ◽  
Xiansi Zeng ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Nerve Fibers ◽  
List Type ◽  
Spinal Neurons ◽  
Genetic Ablation ◽  
Conditional Deletion ◽  
Pain Transmission ◽  
Chronic Pruritus ◽  
Stimulation Of

AbstractGastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.HighlightsValidated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skinOpto-activation of Grp sensory neurons evokes itch behaviorConditional deletion of Grp in sensory neurons reduces non-histaminergic itch behaviorIntersectional ablation of Grp spinal neurons does not affect itch or pain behaviors

scholarly journals The interaction between the immune system and the peripheral sensory nerves in pruritus

2021 ◽  
Author(s):  
Hiroyuki Irie ◽  
Kenji Kabashima
Keyword(s):  
Mental Health ◽  
Atopic Dermatitis ◽  
Immune Cells ◽  
Peripheral Nerves ◽  
Skin Diseases ◽  
Daily Life ◽  
Sensory Nerves ◽  
Inflammatory Skin Diseases ◽  
Heavy Burden ◽  
Peripheral Sensory

Abstract Pruritus is a skin-specific sensation that is observed in various skin diseases, especially in inflammatory skin diseases such as atopic dermatitis, and is deeply involved in their pathogenesis. Pruritus also adversely affects patients’ sleep and mental health, placing a heavy burden on daily life. As such, pruritus control is important to the maintenance of health. The mechanism of pruritus has recently been clarified and the discovery of various pruritus mediators, the identification of specific nerves that transmit pruritus and the accumulation of knowledge on pruritus perception have led to a better understanding of all aspects of pruritus generation, transmission and recognition. In the case of pruritus caused by dermatitis, immune cells infiltrating the skin secrete inflammatory cytokines, which also act on peripheral nerves as pruritus mediators and induce an inflammatory response. Interestingly, there has been accumulating evidence that peripheral nerves are also involved in the inflammation via neuropeptides. In this article, we summarize the findings on pruritus mediators secreted by immune cells and the roles of peripheral nerves in pruritus in terms of their interactions with immunity.

scholarly journals Novel treatment options in immune-mediated inflammatory skin diseases

2019 ◽  
Vol 95 (2) ◽  
pp. 60-64
Author(s):  
Róbert Kui ◽  
◽  
Ekaterine Paschali ◽  
Réka Kovács ◽  
Magdolna Gaál ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Treatment Options ◽  
Inflammatory Skin Diseases ◽  
Novel Treatment ◽  
Immune Mediated ◽  
Inflammatory Skin

scholarly journals Efficacy of Kampo Medicine in Treating Atopic Dermatitis: An Overview

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Tadamichi Shimizu
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Options ◽  
Current Treatment ◽  
Term Treatment ◽  
Kampo Medicine ◽  
Inflammatory Skin Diseases ◽  
Long Term Treatment ◽  
Inflammatory Skin

Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Current treatment options for AD include topical agents, such as topical corticosteroids and oral antiallergic drugs. Providing effective long-term treatment is sometimes difficult due to the chronic, relapsing nature of AD; therefore, there is a need to identify better therapeutic options with minimal side effects that are well tolerated over the variable course of the disease. Traditional herbal medicine, also known as Kampo medicine in Japan, has a long history and plays a role in the prevention and treatment of various diseases, including AD. Some Kampo medicines are useful for treating inflammatory skin diseases, and there has been increased interest in using Kampo medicine to develop new therapeutic agents for AD. Standard Kampo formulas for AD are effective in removing the symptoms of “Netsu Sho,” “Ketsu-Kyo,” “Ki-Kyo,” and “O-Ketsu.” This paper discusses the efficacy of Kampo medicines in treating AD. Knowledge of the mechanisms of action of Kampo medicines will result in greater choices of pharmacotherapeutic agents for AD.

scholarly journals Crosstalk between keratinocytes and immune cells in inflammatory skin diseases

2021 ◽  
pp. 418-431
Author(s):  
Xinhui Ni ◽  
Yuping Lai
Keyword(s):  
Immune Cells ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Cell Type ◽  
Physical Barrier ◽  
Inflammatory Skin Diseases ◽  
Major Cell Type ◽  
Inflammatory Skin ◽  
Different Cell Types

Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antimicrobial peptides/proteins (AMPs). Keratinocytes, as the major cell type of the epidermis, not only form a passive physical barrier, but also actively participate in the pathogenesis of many, if not all, inflammatory skin diseases. Keratinocytes highly interact with immune cells to shape, amplify or regulate inflammatory responses, thus triggering and/or sustaining these inflammatory skin diseases. In this review, crosstalk between keratinocytes and immune cells is summarized, and its contributions to two major inflammatory skin disorders including psoriasis and atopic dermatitis are highlighted.

scholarly journals Pathophysiology of Atopic Dermatitis and Psoriasis: Implications for Management in Children

Children ◽  
2019 ◽  
Vol 6 (10) ◽  
pp. 108 ◽  
Author(s):  
Chovatiya ◽  
Silverberg
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Options ◽  
Skin Barrier ◽  
T Helper ◽  
T Helper 1 ◽  
Inflammatory Skin Diseases ◽  
Current State ◽  
Related Quality ◽  
Health Related

Atopic dermatitis (AD) and psoriasis are chronic inflammatory skin diseases associated with a significant cutaneous and systemic burden of disease as well as a poor health-related quality of life. Here, we review the complex pathophysiology of both AD and psoriasis and discuss the implications for treatment with current state-of-the-art and emerging topical and systemic therapies. Both AD and psoriasis are caused by a complex combination of immune dysregulation, skin-barrier disruption, genetic factors, and environmental influences. Previous treatments for both diseases were limited to anti-inflammatory agents that broadly suppress inflammation. Emerging insights into relevant pathways, including recognition of the role of T-helper type 2 driven inflammation in AD and T-helper 1 and 17 driven inflammation in psoriasis, have led to a therapeutic revolution. There are a number of novel treatment options available for AD and psoriasis with many more currently under investigation.

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