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Cells Oct 2021In infants, pruritus is frequently considered as absent because they do not scratch themselves. Because pruritus could induce severe adverse effects in this vulnerable... (Review)
Review
In infants, pruritus is frequently considered as absent because they do not scratch themselves. Because pruritus could induce severe adverse effects in this vulnerable population, we aimed to review existing evidence on the ability of young infants to experience itch and on how to assess itch-related discomfort in this population. A literature review was performed (Pubmed, Google Scholar). Neurological itch pathways are well described. Skin development starts early during gestation. At 34 weeks of gestation, skin is almost complete while skin adaptations occur after birth. Newborn skin is neurologically functional, including the ability for young infants to feel pain. Similarities and interactions between pain and pruritus support the hypothesis that infants could feel pruritus. However, the existence of pruritus in infants has never been evidenced. Many itchy conditions can affect them, suggesting non-negligible prevalence of infant pruritus among which atopic dermatitis (AD) is the most studied disease. Studies reported a negative impact of AD on children and their families. There is no existing validated method to assess pruritus in infants, although they may feel pruritus and chronic pruritus can lead to serious adverse effects. To appropriately diagnose pruritus appears of great interest among young infants. Development of a method is required to this aim.
Topics: Biomedical Research; Humans; Infant; Pain; Pruritus; Skin
PubMed: 34685768
DOI: 10.3390/cells10102788 -
Handbook of Experimental Pharmacology 2015Protease-activated receptors (PARs) have been implicated in a variety of physiological functions, as well as somatosensation and particularly itch and pain. Considerable... (Review)
Review
Protease-activated receptors (PARs) have been implicated in a variety of physiological functions, as well as somatosensation and particularly itch and pain. Considerable attention has focused on PARs following the finding they are upregulated in the skin of atopic dermatitis patients. The present review focuses on recent studies showing that PARs are critically involved in itch and sensitization of itch. PARs are expressed by diverse cell types including primary sensory neurons, keratinocytes, and immune cells and are activated by proteases that expose a tethered ligand. Endogenous proteases are also released from diverse cell types including keratinocytes and immune cells. Exogenous proteases released from certain plants and insects contacting the skin can also induce itch. Increased levels of proteases in the skin contribute to inflammation that is often accompanied by chronic itch which is not predominantly mediated by histamine. The neural pathway signaling itch induced by activation of PARs is distinct from that mediating histamine-induced itch. In addition, there is evidence that PARs play an important role in sensitization of itch signaling under conditions of chronic itch. These recent findings suggest that PARs and other molecules involved in the itch-signaling pathway are good targets to develop novel treatments for most types of chronic itch that are poorly treated with antihistamines.
Topics: Animals; Humans; Pruritus; Receptors, Proteinase-Activated
PubMed: 25861783
DOI: 10.1007/978-3-662-44605-8_13 -
Digestive Diseases and Sciences Jun 2023We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary...
BACKGROUND AND AIMS
We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.
RESULTS
Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.
CONCLUSIONS
There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.
Topics: Humans; Young Adult; Adult; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Pruritus; Fibric Acids; Quality of Life
PubMed: 36933112
DOI: 10.1007/s10620-023-07862-z -
Acta Dermato-venereologica Apr 2017Pruritus occurs frequently in the elderly population, but it has not been fully defined and its precise prevalence is unknown. Putative causes of pruritus are numerous... (Review)
Review
Pruritus occurs frequently in the elderly population, but it has not been fully defined and its precise prevalence is unknown. Putative causes of pruritus are numerous and patients' quality of life can be greatly reduced. In the absence of any specific cause, a diagnosis of senile pruritus is proposed, suggesting that itch is secondary to ageing. However, the relationship of pruritus with skin ageing and/or neuronal ageing and/or immune ageing is poorly understood. Many treatments have been reported, but are poorly effective. This paper reviews the literature on senile pruritus, in order to improve understanding of this condition and to enable improved diagnosis and treatment.
Topics: Age of Onset; Aged; Aging; Geriatric Assessment; Humans; Predictive Value of Tests; Prevalence; Pruritus; Quality of Life; Risk Factors; Treatment Outcome
PubMed: 27840888
DOI: 10.2340/00015555-2574 -
Dermatologic Clinics Jul 2016There are several practice gaps in the evaluation and management of itch. These gaps include a dearth of objective measures of itch, infrequent use of validated... (Review)
Review
There are several practice gaps in the evaluation and management of itch. These gaps include a dearth of objective measures of itch, infrequent use of validated patient-reported outcomes for itch, non-evidence-based treatment, and lack of consensus about the ideal workup for generalized itch. The present article reviews these gaps and presents potential solutions.
Topics: Actigraphy; Chronic Disease; Dermatology; Humans; Pruritus; Quality of Life; Severity of Illness Index; Visual Analog Scale
PubMed: 27363881
DOI: 10.1016/j.det.2016.02.008 -
Journal of the American Academy of... Dec 2019Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine...
Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine primarily drives itch (pruritus), cholestatic pruritus is multifactorial and more difficult to treat. Existing therapies are not always effective and have undesirable adverse effect profiles. Here, we conducted a systematic literature review to evaluate conventional treatment strategy, current pathophysiologic understanding, and the role of new therapies in the context of cholestatic pruritus. We discuss novel findings implicating bile acids, lysophosphatidic acid, and bilirubin as potential important mediators of cholestatic itch. New therapies that aim to remove or modulate pruritogens have been supported in observational cohort studies and randomized controlled trials. Although these new therapies show promise, further research is needed to confirm the pathophysiology of cholestatic pruritus so that targeted therapy can be developed.
Topics: Cholestasis; Humans; Pruritus
PubMed: 31009666
DOI: 10.1016/j.jaad.2019.04.035 -
International Journal of Molecular... Sep 2022Chronic itch is one of the most prominent clinical characteristics of diverse systematic diseases. It is a devastating sensation in pathological diseases. Despite its... (Review)
Review
Chronic itch is one of the most prominent clinical characteristics of diverse systematic diseases. It is a devastating sensation in pathological diseases. Despite its importance, there are no FDA-labelled drugs specifically geared toward chronic itch. The associated complex pathogenesis and diverse causes escalate chronic itch to being one of the top challenges in healthcare. Humanized antibodies against IL-13, IL-4, and IL-31 proved effective in treatment of itch-associated atopic dermatitis but remain to be validated in chronic itch. There are still no satisfactory anti-itch therapeutics available toward itch-related neuropeptides including GRP, BNP, SST, CGRP, and SP. The newly identified potential itch targets including OSM, NMB, glutamate, periostin, and Serpin E1 have opened new avenues for therapeutic development. Proof-of-principle studies have been successfully performed on antagonists against these proteins and their receptors in itch treatment in animal models. Their translational interventions in humans need to be evaluated. It is of great importance to summarize and compare the newly emerging knowledge on chronic itch and its pathways to promote the development of novel anti-itch therapeutics. The goal of this review is to analyze the different physiologies and pathophysiologies of itch mediators, whilst assessing their suitability as new targets and discussing future therapeutic development.
Topics: Animals; Dermatitis, Atopic; Humans; Neuropeptides; Pruritus
PubMed: 36077340
DOI: 10.3390/ijms23179935 -
Indian Journal of Dermatology,... 2014Pruritus is the most common symptom secondary to skin diseases. Advances in the fields of neurobiology, immunology and physiology have made it possible for us to... (Review)
Review
Pruritus is the most common symptom secondary to skin diseases. Advances in the fields of neurobiology, immunology and physiology have made it possible for us to understand and unravel the deeper pathophysiological basis of pruritus. This review aims to update our current understanding of the mechanisms and mediators of pruritus. Special attention is paid to endogenous itch mediators particularly newly identified ones like endovanilloids, opioids, neurotrophins, cannabinoids, proteases and cytokines. Various theories explaining the peripheral encoding of itch are reviewed. Multiple neural pathways including the central itch pathways as well as supraspinal processing of itch and brain areas involved in pruritus are highlighted. Apart from peripheral itch mediators, spinal neural receptors are also involved in control of itch and should form part of the development of a novel antipruritic strategy. Further studies are required to fill the lacunae in our current understanding of the pathophysiology of pruritus.
Topics: Humans; Nerve Fibers, Unmyelinated; Pruritus; Skin; Skin Diseases
PubMed: 24685845
DOI: 10.4103/0378-6323.129377 -
Actas Dermo-sifiliograficas Jun 2023Pruritus is the most common symptom of dermatologic and systemic diseases. The diagnosis of pruritus is clinical, although additional tests may be necessary to identify... (Review)
Review
Pruritus is the most common symptom of dermatologic and systemic diseases. The diagnosis of pruritus is clinical, although additional tests may be necessary to identify or confirm the cause. Translational medicine has led to the discovery of new mediators of itch, or pruritogens, as well as new receptors. Knowing how to properly recognize the main pathway that mediates itch in each patient is the key to successful treatment. Although the histaminergic pathway predominates in conditions like urticaria or drug-induced pruritus, it is the nonhistaminergic pathway that predominates in nearly all other skin diseases covered in this review. Part 1 of this 2-part review discusses the classification of pruritus, additional testing, the pathophysiology of itch and the pruritogens implicated (including cytokines and other molecules), and central sensitization to itch.
Topics: Humans; Dermatology; Pruritus; Skin Diseases; Cytokines
PubMed: 36965771
DOI: 10.1016/j.ad.2023.03.003 -
Dermatologic Therapy 2010Chronic itch could be a presenting sign of malignancy. Pruritus of lymphoma is the common prototype of paraneoplastic itch and can precede other clinical signs by weeks... (Review)
Review
Chronic itch could be a presenting sign of malignancy. Pruritus of lymphoma is the common prototype of paraneoplastic itch and can precede other clinical signs by weeks and months. Paraneoplastic pruritus has also been associated with solid tumors and is an important clinical symptom in paraneoplastic skin diseases such as erythroderma, Grovers disease, malignant acanthosis nigricans, generalized granuloma annulare, Bazex syndrome, and dermatomyositis. In any case with high index of suspicion a thorough work-up is required. This review highlights the association between itch and malignancy and presents new findings related to pathophysiological mechanisms and the treatment of itch associated with malignancy. Combinative therapies reducing itch sensitization and transmission using selective serotonin and neuroepinephrine reuptake inhibitors, Kappa opioids, and neuroleptics are of prime importance in reducing this bothersome symptom.
Topics: Antipruritics; Chronic Disease; Humans; Paraneoplastic Syndromes; Pruritus; Treatment Outcome
PubMed: 21054705
DOI: 10.1111/j.1529-8019.2010.01366.x