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Clinical Medicine (London, England) Aug 2015Pruritus (itch) is a common complication of cholestatic liver diseases (CLD). It can be a distressing and debilitating symptom, causing significant impairment in quality... (Review)
Review
Pruritus (itch) is a common complication of cholestatic liver diseases (CLD). It can be a distressing and debilitating symptom, causing significant impairment in quality of life. Treatment of pruritus in liver diseases can be challenging and requires specific management with early initiation and a step-wise approach using specific drugs. Clinical trials are ongoing with novel agents that demonstrate potential efficacy. Patients with cholestatic pruritus are likely to present to a variety of clinicians who would benefit from medical awareness of available treatment options. In this review, we outline the pharmaceutical agents currently used to treat cholestatic pruritus and provide the evidence base for targeted symptom control of itch in liver diseases. We also highlight recent developments in the pathophysiology of cholestatic pruritus and the emerging novel therapies.
Topics: Anticholesteremic Agents; Cytochrome P-450 CYP2B6 Inducers; Humans; Liver Diseases; Pruritus; Quality of Life; Selective Serotonin Reuptake Inhibitors
PubMed: 26407384
DOI: 10.7861/clinmedicine.15-4-351 -
Drugs Jun 2017Chronic pruritus remains a central societal issue because of its high occurrence and the substantial decrease in quality of life it may cause to affected individuals.... (Review)
Review
Chronic pruritus remains a central societal issue because of its high occurrence and the substantial decrease in quality of life it may cause to affected individuals. Not only dermatological conditions, but also systemic, neurological, or psychiatric diseases may lead to chronic pruritus. Additionally, various underlying conditions may coexist or the cause may be unknown. Due to its heterogeneity, the therapeutic approach is complex and remains a challenge for the clinician. Basic measures such as emollients to avoid xerosis and treatment of the underlying disease should be initiated regardless of the duration of the symptom. Depending on the indication, other topical (e.g., calcineurin inhibitors, topical corticosteroids, capsaicin) and systemic agents (immunosuppressive drugs, gabapentinoids, antidepressants, mu-opioid receptor antagonists) may provide further relief. Additionally, accompanying disorders such as sleep impairment, depression, or anxiety should also be treated. New insights into pathways involved in the development and maintenance of chronic pruritus have led in the past years to the development of a considerable number of novel antipruritic drugs. Several randomized controlled trials have been recently completed or are currently underway testing biological compounds with promising approaches. These include antagonists for nerve growth factor, neuropeptides, histamine 4 receptors, certain interleukin receptors, and opioid receptors.
Topics: Antipruritics; Chronic Disease; Double-Blind Method; Humans; Pruritus; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28466423
DOI: 10.1007/s40265-017-0746-9 -
Giornale Italiano Di Dermatologia E... Oct 2016Skin diseases (atopic eczema, psoriasis, idiopathic urticaria), systemic diseases (chronic hepatic or renal failure, morbus Hodgkin, diabetes mellitus) and psychiatric... (Review)
Review
Skin diseases (atopic eczema, psoriasis, idiopathic urticaria), systemic diseases (chronic hepatic or renal failure, morbus Hodgkin, diabetes mellitus) and psychiatric disorders (obsessive compulsive disorders, depression, delusions of parasitosis) can occur with itching. The aim of this review is to clarify the link between pruritus and psychiatric morbidity and emphasize the importance of a psychiatric consultation for patients with a chronic itching, without a skin disease. In the last years, there is a growing awareness regarding psychogenic itch, although these types of itch are significantly less studied in comparison to other types of pruritus. Psychogenic pruritus is usually a diagnosis of exclusion. There are not controlled studies about treatment of psychogenic itch, but the same drugs prescribed for neuropathic pain, depression, and anxiety are used. There is a strong association between pruritus and psyche; so, it is important that the dermatologist evaluates psychosomatic dimension. According to the analysis of scientific literature and our clinical experience, pruritus seems to be a rather common phenomenon in patients suffering from depression. Future works should explain the basis of psychopathology of chronic itching thanks to studies of selected groups of patients with a particular type of chronic itching, highlighting the clinical features to establish appropriate and individual targeted care, based on the several types of pruritus. Some questions still unanswered could be clarified in this way. It is really important to decrease the symptoms "itching", because the quality of life of the patient will be improved, but the goal is to identify the underlying mechanisms of itch and establish a targeted therapy, depending on the biological changes and the underlying disease.
Topics: Depression; Humans; Mental Disorders; Pruritus; Quality of Life; Skin
PubMed: 25854671
DOI: No ID Found -
Wounds : a Compendium of Clinical... Jan 2018Chronic itch continues to be a problem that plagues millions of humans and animals. Pruritus has a negative impact on patient quality of life and many patients... (Review)
Review
Chronic itch continues to be a problem that plagues millions of humans and animals. Pruritus has a negative impact on patient quality of life and many patients experience sleep deprivation, anxiety, and depression, similar to patients with chronic pain. This review provides an overview of clinical pruritus research with special emphasis on itch that wound care providers may see. In addition, the need for using multifactorial questionnaires for better research in pruritus is summarized. Similarities and differences in itch characteristics, triggers, and relievers in various patient populations are discussed. A brief overview of itch receptors and pathways is provided to help the reader better understand the complexity of the resultant itch sensation. Also, some nonpharmacological and pharmacological antipruritic therapies and their mechanisms of action are included.
Topics: Animals; Antipruritics; Chronic Disease; Cicatrix; Humans; Nociceptors; Peripheral Nervous System; Pruritus; Quality of Life; Wound Healing; Wounds and Injuries
PubMed: 29406293
DOI: No ID Found -
Acta Dermato-venereologica Jan 2020Chronic pruritus is a frequent global condition. The pathophysiology, underlying aetiology, clinical manifestation, associated burden and response to therapy of chronic... (Review)
Review
Chronic pruritus is a frequent global condition. The pathophysiology, underlying aetiology, clinical manifestation, associated burden and response to therapy of chronic pruritus varies from patient to patient, making clinical research and management of this condition challenging. There are still several unmet needs, such as the need to standardize translational research protocols, diagnostic and therapeutic procedures and to enhance the knowledge of the humanistic and economic burden associated with chronic pruritus. Basic and clinical research is of the utmost importance to target these matters. Clinical research has the potential to identify new relevant mechanisms in affected patients, which may lead to identification of novel therapy targets. This article discusses in depth current shortcomings in the daily care of patients with chronic pruritus and the challenges clinical researchers and physicians treating chronic pruritus face in addressing these matters.
Topics: Animals; Antipruritics; Biomedical Research; Chronic Disease; Humans; Pruritus; Research Design; Risk Factors; Treatment Outcome
PubMed: 31940048
DOI: 10.2340/00015555-3348 -
Acta Dermato-venereologica Jan 2020Chronic itch occurs in many skin diseases, but also in a variety of systemic, neurological, and psychogenic/psychosomatic disorders, or is caused by drug intake. When... (Review)
Review
Chronic itch occurs in many skin diseases, but also in a variety of systemic, neurological, and psychogenic/psychosomatic disorders, or is caused by drug intake. When several diseases or causes co-exist, chronic itch is categorized as "mixed origin". These patients present with unaltered skin or with chronic scratch lesions including chronic prurigo. Precise diagnostics are necessary to evaluate the underlying aetiology, to enable identification of the best treatment available, and to improve patients' quality of life. This is of particular relevance in elderly people in whom chronic itch is often of systemic or mixed origin. Xerosis cutis is a frequent cofactor contributing to chronic itch of non-dermatological origin. Treatment is frequently multimodal, considering age, comorbidities, current drug intake, quality and intensity of itch. With regard to the demographic situation of the population, characterized by increasing life expectancy and polypharmacy, itch of non-dermatological origin will represent an increasing medical challenge in the future.
Topics: Chronic Disease; Humans; Prognosis; Pruritus; Risk Factors
PubMed: 31940045
DOI: 10.2340/00015555-3345 -
BioMed Research International 2019Scalp pruritus is a frequent problem encountered in dermatological practice. This disorder is caused by various underlying diseases and is a diagnostic and therapeutic... (Review)
Review
Scalp pruritus is a frequent problem encountered in dermatological practice. This disorder is caused by various underlying diseases and is a diagnostic and therapeutic challenge. Scalp pruritus may be localized to the scalp or extended to other body areas. It is sometimes not only associated with skin diseases or specific skin changes, but also associated with lesions secondary to rubbing or scratching. Moreover, scalp pruritus may be difficult to diagnose and manage and may have a great impact on the quality of life of patients. It can be classified as dermatologic, neuropathic, systemic, and psychogenic scalp pruritus based on the potential underlying disease. A thorough evaluation of patients presenting with scalp pruritus is important. Taking history and performing physical examination and further investigations are essential for diagnosis. Therapeutic strategy comprises removal of the aggravating factors and appropriate treatment of the underlying condition. All treatments should be performed considering an individual approach. This review article focuses on the understanding of the pathophysiology and the diagnostic and therapeutic management of scalp pruritus.
Topics: Animals; Humans; Pruritus; Quality of Life; Scalp; Skin
PubMed: 30766878
DOI: 10.1155/2019/1268430 -
Cell Reports Apr 2023Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon...
Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV1/MrgprA3 prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin.
Topics: Chloroquine; Histamine; Pruritus; Skin
PubMed: 36961815
DOI: 10.1016/j.celrep.2023.112283 -
JAMA Dermatology Sep 2023Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting...
IMPORTANCE
Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor α, is a promising novel therapy for the treatment of moderate to severe PN. The biological mechanisms by which nemolizumab promotes improvement of itch and skin lesions in PN are unknown.
OBJECTIVE
To characterize changes in plasma protein biomarkers associated with clinical response to nemolizumab in patients with PN.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cohort study included patients recruited from Austria, France, Germany, Poland, and the US from a phase 2 clinical trial. Adults diagnosed with moderate to severe PN with severe pruritus for at least 6 months were included in the original trial. Patients in the nemolizumab group were included in the present study if they achieved at least a 4-point decrease in the Peak Pruritus Numerical Rating Scale (PP-NRS) from baseline to week 12 during nemolizumab treatment. Placebo controls did not experience a 4-point decrease in PP-NRS. Mass spectrometry with tandem mass tags to enrich skin-specific protein detection was used to characterize changes in plasma protein expression in nemolizumab and placebo groups. Data were collected from November 2, 2017, to September 26, 2018, and analyzed from December 6, 2019, to April 8, 2022.
INTERVENTION
As part of the clinical trial, patients were treated with 3 doses of nemolizumab or placebo at 0, 4, and 8 weeks.
MAIN OUTCOMES AND MEASURES
Changes in plasma and epidermal protein expression in nemolizumab-treated patients compared with the placebo group at 0, 4, and 12 weeks.
RESULTS
Among the 38 patients included in the analysis (22 women and 16 men; mean [SD] age, 55.8 [15.8] years), enrichment analysis of canonical pathways, biological functions, and upstream regulators showed downregulation of terms involving inflammation (IL-6, acute-phase response, signal transducer and activator of transcription 3, and interferon γ), neural processes (synaptogenesis signaling and neuritogenesis), tissue remodeling and fibrosis (transforming growth factor β1 and endothelin-1), and epidermal differentiation (epithelial mesenchymal transition) in the plasma of nemolizumab group.
CONCLUSIONS AND RELEVANCE
In this cohort study, differences between nemolizumab and placebo groups included modulation of inflammatory signaling, neural development, and epithelial differentiation, suggesting a promising potential approach for clinical management of PN.
Topics: Adult; Male; Humans; Female; Middle Aged; Prurigo; Cohort Studies; Pruritus; Biomarkers
PubMed: 37556125
DOI: 10.1001/jamadermatol.2023.2609 -
Expert Opinion on Emerging Drugs Sep 2015Chronic pruritus occurs in 13% of the general population without age limitation. There is a high unmet need here as effective treatment options are still missing. (Review)
Review
INTRODUCTION
Chronic pruritus occurs in 13% of the general population without age limitation. There is a high unmet need here as effective treatment options are still missing.
AREAS COVERED
Clinical and experimental research during the past decade identified new mechanisms in chronic pruritus allowing the definition of a broad range of specific treatment targets for the first time. This refers specifically to inflammatory pruritic dermatoses, uremic and cholestatic pruritus. Targets identified are, for example, receptors for substance P, IL-31 and nerve growth factor. Search was made for current studies addressing these diseases and targets in the available clinical registration databases.
EXPERT OPINION
The current pharmacological development is very promising especially for patients suffering from chronic pruritus in inflammatory dermatoses, chronic kidney diseases and hepatobiliary diseases. However, there are still several pruritic diseases in which neither mediators nor specific target populations (e.g., children) nor stages of diseases, have been identified; however, it can be assumed that within the next 10 years, major changes in the possibilities of antipruritic treatment will take place.
Topics: Animals; Antipruritics; Chronic Disease; Drug Design; Humans; Molecular Targeted Therapy; Pruritus
PubMed: 26027744
DOI: 10.1517/14728214.2015.1051964