What are new treatment concepts in systemic itch?

Kremer, Andreas E.

doi:10.1111/exd.14024

Cited by 21 publications

(17 citation statements)

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“…Drugs influencing the opioid system are applied for the treatment of pruritus in systemic diseases such as chronic kidney disease-associated pruritus (CKDaP) and hepatic pruritus (1). The oral µ-opioid antagonist naltrexone induced a mild antipruritic effect in two smaller randomized placebo-controlled trials (32,33) in cholestatic patients.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis, comparing the itch-reducing effect of several drugs, clearly indicated inferiority of naloxone and naltrexone compared to rifampicin (17). Nalfurafine, a κ-opioid agonist, is licensed in Japan, but not in Europe or USA, for treatment of CKDaP and hepatic pruritus (1). In a randomized, placebo-controlled trial including a rather inhomogeneous group of 318 patients with different liver diseases, treatment with nalfurafine resulted in a statistically significant but clinically questionable reduction of pruritus (16).…”

Section: Discussionmentioning

confidence: 99%

“…Chronic pruritus, defined as itch lasting for 6 weeks or more, represents a serious and challenging symptom in several systemic diseases, including chronic kidney disease (CKD), hematological disorders, and hepatobiliary diseases (1,2). Up to one fifth of patients with generalized pruritus suffers from a systemic disease (3).…”

Section: Introductionmentioning

confidence: 99%

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Endogenous Opioid Levels Do Not Correlate With Itch Intensity and Therapeutic Interventions in Hepatic Pruritus

et al. 2021

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Background: Chronic pruritus affects up to 70% of patients with immune-mediated hepatobiliary disorders. Antagonists of the μ-opioid receptor (MOR) and agonists of the κ-opioid receptor (KOR) are used to treat hepatic itch, albeit with limited success. An imbalance between ligands of MOR and KOR receptors has recently been suggested as a potential mechanism of hepatic pruritus. In this study, we therefore investigated systemic levels of important endogenous opioids such as β-endorphin, dynorphin A, Leu- and Met-enkephalin in plasma of a large cohort of well-characterized patients with immune-mediated cholestatic disorders, including patients with liver cirrhosis, and during effective anti-pruritic therapy.Methods: Plasma samples and clinical data were prospectively collected from well-characterized patients with primary/secondary sclerosing cholangitis (PSC/SSC), primary biliary cholangitis (PBC) and overlap syndromes suffering from pruritus (n = 29) and age-, gender- and disease-matched controls without pruritus (n = 27) as well as healthy controls (n = 20). General laboratory testing for hepatobiliary and renal function was performed. Levels of β-endorphin, dynorphin A, Leu- and Met-enkephalin were quantified in plasma by ELISA. Intensity of pruritus over the last week was evaluated using a visual analog scale (VAS, 0–10).Results: PBC and PSC patients with or without pruritus did neither differ in disease entity, disease stage, nor in the presence of cirrhosis. While both dynorphin A and β-endorphin concentrations were lower in pruritic patients compared to those without pruritus and healthy controls, the MOR/KOR ligand ratio was unaltered. No significant differences were observed for Leu- and Met-enkephalin concentrations. Opioid levels correlated with neither itch intensity nor stage of disease. Cirrhotic patients displayed higher concentrations of MOR agonist Leu-enkephalin and KOR agonist dynorphin A. Endogenous opioid levels remained largely unchanged after successful treatment with the potent anti-pruritic drugs rifampicin and bezafibrate.Conclusions: Endogenous opioid levels and the MOR/KOR ligand ratio neither correlate with itch intensity nor differentiate pruritic from non-pruritic patients with immune-mediated liver diseases. Thus, endogenous opioids may modulate signaling pathways involved in hepatic pruritus, but are unlikely to represent the major pruritogens in liver disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Endogenous Opioid Levels Do Not Correlate With Itch Intensity and Therapeutic Interventions in Hepatic Pruritus

et al. 2021

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“…Newly developed KOR agonists, such as nalfurafine, or the combined MOR antagonist/KOR agonist nalbuphine have recently shown mild but significant efficacy in reducing pruritus in ESRD patients. These appear to be associated with a lower risk for central nervous adverse events (77). Currently, nalfurafine is only licensed for uremic and cholestatic pruritus in Japan.…”

Section: Opioid Receptor Antagonists/agonistsmentioning

confidence: 99%

Itch in Atopic Dermatitis – What Is New?

Legat

2021

Front. Med.

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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.

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“…It is well known that psychological factors contribute to chronic pruritus and related scratching behaviour; these and other novel factors have been discussed by Evers and her team (Leiden, The Netherlands) . Several articles have focused on therapeutic options for chronic pruritus such as UV therapy and its effect on pruritus (F. Legat, Graz, Austria), psychoactive drug use in pruritus (Reszke and Szepietowski, Wroclaw, Poland), new treatment concepts in systemic itch (Kremer, Erlangen, Germany), and the last article describes what is in the pipeline of therapeutic treatments for itch (Metz, Berlin, Germany).…”

mentioning

confidence: 99%