Racial Disparities in Prurigo Nodularis (Extremely Itchy Lumps)

MedicalResearch.com Interview with:

Prurigo Nodularis credit: Johns Hopkins Medicine

Prurigo Nodularis
credit: Johns Hopkins Medicine

Dr. Shawn Kwatra MD
Assistant Professor of Dermatology
Johns Hopkins University School of Medicine 

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by prurigo nodularis? 

Response: Prurigo nodularis is a skin condition where patients develop extremely itchy nodules throughout the body. Little is known about why this happens or which groups of people are predisposed to develop this condition.

MedicalResearch.com: What are the main findings?

Response We found that prurigo nodularis disproportionately affects African-Americans as compared to the general population. Diabetes, Hepatitis C, chronic kidney disease, and HIV are also more common in patients with prurigo nodularis than the general population or patients with other inflammatory skin diseases studied, such as atopic dermatitis and psoriasis.

We also found that people with prurigo nodularis are more likely to be depressed than patients with other inflammatory skin diseases, such as atopic dermatitis or psoriasis. 

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Bezafibrate: Potential Treatment for PBC and Itching From Biliary Disease

MedicalResearch.com Interview with:

Dr Christophe Corpechot Centre de Référence Maladie Rares: Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes (MIVB-H) Filière Maladies Rares: Maladies Rares du Foie de l’Adulte et de l’Enfant Hôpital Saint-Antoine (APHP) et Sorbonne Universités Paris

Dr. Corpechot

Dr Christophe Corpechot
Centre de Référence Maladie Rares: Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes (MIVB-H)
Filière Maladies Rares: Maladies Rares du Foie de l’Adulte et de l’Enfant
Hôpital Saint-Antoine (APHP) et Sorbonne Universités
Paris

MedicalResearch.com: What is the background for this study?

Response: Primary biliary cholangitis (PBC, previously known as “primary biliary cirrhosis”) is a rare, chronic, slowly progressive liver disease of unknown cause, mainly affecting women of middle age. It is characterized by serum marks of autoimmunity (specific auto-antibodies), chronic inflammation and destruction of small intra-hepatic bile ducts, and consequent bile secretion impairment (chronic cholestasis) leading to the progressive development of cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the only first-line approved treatment for PBC. It improves the biochemical measures of cholestasis and prolongs survival without liver transplantation. However, 30% to 40% of UDCA-treated patients continue to have clinically significant abnormalities of their biochemical liver tests and those patients remain at high risk of developing end-stage liver disease complications.

Recently (2016), obeticholic acid (OCA) in association with UDCA has been conditionally approved in patients with an inadequate response to UDCA. This approval (FDA, EMA) was based one the results of a 1-year randomized, double-blind, placebo-controlled trial of OCA in patients with an incomplete response or intolerance to UDCA (POISE trial). In this trial, OCA was shown to improve the biochemical features of cholestasis (alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range and a reduction of at least 15% from baseline) but was associated with a significant increase of pruritus, a characteristic, potentially debilitating symptom of PBC. BEZURSO is the first ever placebo-controlled phase 3 trial of a fibrate (a class of drugs known to be agonists of the peroxisome proliferator-activated receptors alpha) in PBC. In this 2-year randomized double-blind trial, 100 patients with an incomplete response to UDCA were assigned to bezafibrate 400 mg/day (n=50) or placebo (n=50), all in association with continued UDCA therapy.

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Topical Cannabinoids May Fight Itch and Inflammatory Skin Diseases

MedicalResearch.com Interview with:
Jessica S. Mounessa, BS

University of Colorado School of Medicine
Aurora, Colorado and
Robert Dellavalle, MD, PhD, MSPH
Professor of Dermatology and Public Health
University of Colorado School of Medicine
Colorado School of Public Health
Chief, Dermatology Service
US Department of Veterans Affairs
Eastern Colorado Health Care System
Denver, CO 80220 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One in 10 adult cannabis users in the U.S. use it for medicinal purposes. Medicinal cannabis is well studied for its uses in chronic pain, anorexia, and nausea. Numerous recent studies have highlighted other medicinal uses for cannabinoids and related compounds.

We conducted a comprehensive review of the literature on the potential role of cannabinoids in conditions affecting the skin.

Our study reveals the potential benefit of topically prepared cannabinoid compounds, especially for pruritus and eczema.  For example, creams containing Palmitoylethanolamide (PEA), which enhances cannabinoid-receptor binding, have been successful in relieving itch both in the literature, and anecdotally in our clinics.

Though not strictly considered an endocannabinoid, as it does not directly bind to CB1 and CB2 receptors, PEA works by enhancing endocannabinoid binding to these receptors.** Furthermore, the majority of the cannabinoid compounds we studied did not contain psychoactive effects.

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Leaky Gate Model Connects Intense Itch With Pain

MedicalResearch.com Interview with:

Xinzhong Dong PhD The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology Howard Hughes Medical Institute Johns Hopkins University School of Medicine Baltimore, MD 21205

Dr. Xinzhong Dong

Xinzhong Dong PhD
The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology
Howard Hughes Medical Institute
Johns Hopkins University School of Medicine
Baltimore, MD 21205

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is a puzzle that troubles the field for many years that how pain and itch, two closely related sensations (once thought as one sensation), are differentiated by the nervous systems. Coding of pain and itch are heatedly debated for decades. The current specificity theory suggests that these two kinds of signals are carried by separate pathways, with some interactions, for example pain can inhibit itch and that explains why we all scratch to inhibit pain. It is true in the periphery (our previous study indicate a small population of neurons in the periphery only codes for itch sensation), but now our study suggests that there could be more crosstalk between these two sensations in the central than we expected.

People might not notice in real life, but in human psychophysical studies, well-isolated experimental environments, when human subjects are given itchy substances, they typically report intense itch sensations accompanied by minor noxious sensations, such as pricking, stinging and burning. Our new leaky gate model suggest in certain circumstances intense itch signals can trigger minor pain sensations, which can explain such phenomenon.

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Two Channels That Transmit Itch Sensation To Brain Identified

MedicalResearch.com Interview with:

Dr. Devin M. Barry, PhD, postdoc fellow Center for the Study of Itch,. 2Department of Anesthesiology Washington University School of Medicine St. Louis, MO 63110

Dr. Devin Barry

Dr. Devin M. Barry, PhD, postdoc fellow
Center for the Study of Itch,.
Department of Anesthesiology
Washington University School of Medicine
St. Louis, MO 63110

MedicalResearch.com: What is the background for this study?

Response: Our group is interested in understanding the molecular and cellular mechanisms that underly itch sensation. Our study focused on peripheral sensory neurons of the DRG that mediate responses to itch-inducing stimuli, in particular the inflammatory mediator histamine and the antimalarial drug chloroquine. It has been shown that histamine and chloroquine activate distinct G protein–coupled receptors (GPCRs) in sensory neurons innervating the skin. Two members of the transient receptor potential (TRP) family of ion channels, TRPV1 and TRPA1, have been found to be important mediators of histamine- and chloroquine-induced itch signaling, respectively.

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Serum IL-31 Linked to Itching in Hemodialysis Patients

MedicalResearch.com Interview wth:
Mei-Ju Ko, MD, PhD
Department of Dermatology, Taipei City Hospital
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Medical Research: What are the main findings of the study?

Dr. Ko: In this study, not only did we find that serum levels of interleukin (IL)-31 were significantly higher in hemodialysis patients with pruritus symptoms, but we also demonstrated a positive exposure-response relationship between IL-31 levels and visual analog scale (VAS) scores of pruritus intensity. We also noted an inverse correlation between the severity of pruritus and the dialysis dose assessed by Kt/V.
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New Antibody Can Block Pain and Itch Simultaneously

MedicalResearch.com Interview with:
Seok-Yong Lee, Ph.D. Assistant Professor of BiochemistrySeok-Yong Lee, Ph.D.
Assistant Professor of Biochemistry and

Ru-Rong Ji, Ph.D. Distinguished Professor  of Duke University Professor of Anesthesiology  and Neurobiology Chief of Pain ResearchRu-Rong Ji, Ph.D.
Distinguished Professor  of Duke University
Professor of Anesthesiology  and Neurobiology
Chief of Pain Research
Duke University Medical Center
Durham, NC 27710

MedicalResearch: What are the main findings of the study?



Answer: We have developed an antibody that can block the pain and itching sensations in mice simultaneously with high efficacy. We would like to point out that our discovery has the potential to be applied to human once the antibody is humanized. Given the high selectivity, general safety profile, and long half-lives of monoclonal antibodies, this method we developed to raise antibodies against therapeutic targets (e.g., ion channels) can have broad applications to other diseases.
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