05 Apr Mechanism of Horrible Itching of Liver Disease Identified in Superficial Skin Cells
MedicalResearch.com Interview with: [caption id="attachment_57070" align="alignleft" width="133"]
Dr. Liedtke[/caption]
Wolfgang Liedtke, M.D., Ph.D.
Professor (tenured) of Neurology, Anesthesiology and NeurobiologyAttending Physician, Duke Neurology Clinics for Headache, Head-Pain and Trigeminal Sensory Disorders
Attending Physician, Duke Clinics for Innovative Pain Therapy at Brier Creek (Dept of Anesthesiology)
Duke University School of Medicine, Center for Translational Neuroscience
Durham NC 27710 Since April 2021 Chair of Neurology Global Development Scientific Council Regeneron Pharmaceuticals Tarrytown NY 10591 MedicalResearch.com: What is the background for this study? Response: There are systemic diseases that are characterized by intense itching, yet without inflammation of the skin and not associated with allergic inflammation. For example and importantly, liver disease with non-functional secretion of bile (cholestatic liver disease, most common primary biliary cholangitis, an autoimmune disease), but also chronic end-stage renal disease (also certain lymphomas and pruritic psoriasis where the itch is whole-body, not only restricted to diseased skin). We thought that these diseases might be great starting points to better understand itch because there is no inflamed skin and no allergies. Thus, there must be some systemic factor that causes itch, and we were intent on discovering such factors, and with them, molecular mechanisms how they cause itch. For cholestatic liver disease, one of the best candidates to fit this profile has been lysophosphatidic acid (LPA), since the pioneering discoveries of Andreas Kremer, one of our co-authors. My research laboratory at Duke has been rooted in my discovery of TRPV4 ion channels 20 years ago, out of the Friedman Lab at The Rockefeller University in NYC. Over the years, with my colleague Yong Chen out of my lab, now leading his own independent research operation, we focused on the role of TRPV4 ion channels in skin. 5 years ago Yong and I published a paper that provided some evidence for TRPV4 in skin perhaps playing a role in itch. Working with phospholipids, we made the serendipitous discovery that lysophosphatidyl choline (LPC) is a more potent itch-inducing lipid molecule than LPA. Of note, LPC is the metabolic precursor of LPA. We then found that LPA does not depend on TRPV4 to elicit itch. The more robust itch evoked by LPC was significantly reduced when we knocked down TRPV4 in skin keratinocytes. Itch was NOT affected when TRPV4 was deleted from sensory nerve cells that innervate the skin. In terms of background, my long-term goal has been to elucidate how innervating peripheral nerve cell and innervated organ, such as skin, talk to one another so that the sensation that is felt is regulated or modulated, e.g how can skin influence itch or pain, how can joint cells influence pain. That became the exciting bedrock of our study, and we took it from there, 5 years of hard work with collaborations spanning the globe, and a final stretch of exhausting work during the pandemic.
Matt Spick[/caption]
Matt Spick, Post-Graduate Researcher
University of Surrey
Faculty of Engineering and Physical Sciences
Guildford, UK
MedicalResearch.com: What is the background for this study? Are you measuring lipids or the virus?
Response: In this study, we aimed to detect what the virus does to us, rather than the virus itself. The gold standard for detecting COVID-19 is the RT-PCR test, but by their nature, PCR tests only provide diagnostic information, and at times during the pandemic the availability of PCR tests has been a bottleneck for the identification of the disease. Our goal was to investigate a novel method for the diagnosis of COVID-19, at the same time as learning more about what the disease does to us through lipidomics.
Anne Cust[/caption]
Anne Cust | PhD, Professor of Cancer Epidemiology
The University of Sydney
Faculty of Medicine and Health
Sydney School of Public Health
MedicalResearch.com: What is the background for this study? Are the screeners specially trained, use full body photographs, dermoscopy etc?
Response: The Melanoma High-risk Clinic Study was developed to optimise the early detection of new melanomas in people at high risk of developing melanoma. A previous single-centre study observed fewer excisions and healthcare costs, thinner melanomas and better quality of life when surveillance of high risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving 6-monthly full body examinations aided by total body photography (TBP) and sequential digital dermoscopy imaging (SDDI). The initial pilot study was performed in a single tertiary referral specialist centre using trained dermatologists who routinely used the diagnostic interventions.
Our objective was to examine longer-term sustainability and expansion of the program to multiple practices including a primary care skin cancer clinic setting. The hypothesis was that the outcomes would be similar if using the same protocol and diagnostic tools. The participating doctors were trained to follow the protocol, which included instruction on how to respond and interpret changing lesions, but not in use of dermoscopy or skin examinations, which were routinely and consistently used in all clinics prior to the study commencing. There were 593 participants assessed as very high risk of melanoma who participated in the Melanoma High-risk Clinic Study from 2012-2018. Nearly all of the participants had had a previous melanoma and had additional melanoma risk factors. 57% were male and the median age at study entry was 58 years.
Dr. Swerlick[/caption]
Robert A. Swerlick, MD
Professor and Alicia Leizman Stonecipher Chair of Dermatology
Emory University School of Medicine
Atlanta, GA 30322
MedicalResearch.com: What is the background for this study?
Response: Financial incentives have the potential to drive provider behavior, even unintentionally. The aim of this study was to evaluate differences in clinic “productivity” measures that occur in outpatient dermatology encounters. Specifically, we used data from 2016-2020 at one academic dermatology practice to evaluate differences in work relative value units (wRVUs, a measure of clinical productivity) and financial reimbursement by patient race, sex, and age. 66,463 encounters were included in this study, among which 70.1% of encounters were for white patients, 59.6% were for females, and the mean age was 55.9 years old. 
Jill Sommerville[/caption]
Jill Sommerville M.Sc
Director of Medical at WaterWipes
MedicalResearch.com: What is the background for this study? How prevalent is diaper dermatitis? Is it more severe in some babies?
Response: The Utah study is an independent clinical study conducted by the University of Utah Hospital NICU, Salt Lake City and recently published in Advances in Neonatal Care journal. It was a year-long study conducted between January 2018 – March 2019. The NICU staff were interested in exploring a new Perineal Skin Care Guideline in their unit, encompassing use of WaterWipes, to decrease the incidence of diaper dermatitis. Their stated aim was to reduce diaper dermatitis by 20% within a 1-year period. The study involved 1,070 premature babies, 11% of which were born at less than 30 weeks of gestational age. The inclusion criteria for the study were all babies who stayed for more than 1 day in the NICU.
Diaper dermatitis is known to cause discomfort and emotional distress in all babies and can be a possible source of infection among NICU babies. Diaper dermatitis remains prevalent, especially in preterm babies. The reported incidence varies from 21% to 25% among newborn intensive care babies. 1
Diaper dermatitis in pre term babies can be multifactorial especially as babies born early have a less well developed stratum corneum, the outer most layer of skin. NICU babies are often exposed to antibiotics and fortified milk to help them catch up growth. Other medical complications in addition can lead to altered gut flora and altered stool composition resulting in more frequency of stool.
The presence of urine and frequent stools necessitates regular cleaning which can result in excessive rubbing of the skin or the use of wipes containing harsh ingredients that can damage the skin.
One example of actinic keratoses on scalp
Dr. Kim[/caption]
Brian Kim, MD
Associate Professor of Dermatology
Co-Director, Center for the Study of Itch & Sensory Disorders
John T. Milliken Department of Internal Medicine
Washington University in St. Louis
MedicalResearch.com: What is the background for this study?
Response: Patients with eczema suffer from chronic itch due to the rashes they have on their body. However, as a physician, I have always noticed that patients with eczema will have sudden flares of their itching all over there body that is often triggered by what appear to be allergens – being around a cat, pollen, mold in a house, etc. Eczema is in the family of allergic diseases such as food allergy, asthma, and hay fever. All of these conditions are noted for patients being reactive to allergens by way of an antibody called IgE that coats a cell called the mast cell. Upon IgE binding an allergen, mast cells produce tons of histamine which can cause symptoms like itching. So we speculated that perhaps because patients with eczema have such misbehaving IgE, that exposure to allergen is what triggers this kind of severe itch flare that we see in patients.
Dr. Gernand[/caption]
Jeremy M. Gernand
![MedicalResearch.com Interview with: Selin Tokez, PhD Student Department of Dermatology Erasmus MC, Rotterdam MedicalResearch.com: What is the background for this study? Response: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer worldwide with still increasing incidence rates. Given these high incidence rates together with the associated health costs and possibility of fatal progression, it is extremely important to have accurate and complete data on the epidemiology of this disease. Nevertheless, national cancer registries in many countries do not routinely record cSCC cases and therefore currently known numbers are mainly based on incomplete data sources. Additionally, if cSCC cases are registered, this usually only concerns the first cSCC per patient while we know that, contrary to many other malignant neoplasms, patients may develop numerous cSCCs over time. MedicalResearch.com: What are the main findings? Response: In the present study, we analyzed Dutch nationwide data comprising about 145,000 patients with a first invasive cSCC diagnosis between the years 1989 and 2017. We found that the incidence rates of a first cSCC per patient almost tripled in male patients and increased about fivefold in female patients in this 30-year time period. Also, we had data on all cSCCs per patient for the year 2017 and could therefore compare this with the data on only the first cSCC per patient: incidence rates increased by 58% for men and 35% for women when multiple cSCCs were considered. In absolute numbers, this resulted in an increase of 45% in cSCC diagnoses in 2017. Lastly, we extended our analyses by predicting future cSCC incidence rates up to 2027. Given that no substantially effective measures are undertaken in the near future, current cSCC incidence rates will increase with 23% in males and 29% in females in the next decade. MedicalResearch.com: What should readers take away from your report? Response: We could summarize our main message in two points: while people generally know that cSCC is a very common disease with increasing incidence rates, it is not taken into account that these numbers are often based on incomplete data registries and that the real numbers are even higher. In this paper, we provided these numbers for a period of 30 years based on highly accurate data from the Netherlands Cancer Registry. On top of that, as a second main finding, we showed that the real burden caused by cSCC is approximately 50% higher (taken males and females together) when all cSCC diagnoses in 1 year are registered instead of only the first tumor per patient. Together with our prediction analyses that showed an on average 26% further increase for the coming decade, this will have enormous implications for the dermato-oncological health care planning and cost management. Our results urgently call for revision of skin cancer health policies to be able to cope with this rising burden of cSCC management. Ultimately, primary prevention will remain the key strategy to halt the increasing trend in cSCC incidence and the occurrence of multiple cSCCs per patient, which we hope to further stimulate with our paper as well. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: As we had data on multiple cSCCs for only one year, we would suggest to perform trend analyses for multiple cSCCs per patient as well when a longer follow-up duration has been reached. Furthermore, it would be very relevant to identify high-risk cSCCs or patients at risk for multiple cSCCs in order to be able to establish efficient follow-up regimens and take these high risk groups into account when revising skin cancer health policies. MedicalResearch.com: Is there anything else you would like to add? Response: The authors of this study have no conflicts of interest that are relevant to this article. Citation: Tokez S, Hollestein L, Louwman M, Nijsten T, Wakkee M. Incidence of Multiple vs First Cutaneous Squamous Cell Carcinoma on a Nationwide Scale and Estimation of Future Incidences of Cutaneous Squamous Cell Carcinoma. JAMA Dermatol. Published online October 28, 2020. doi:10.1001/jamadermatol.2020.3677 [subscribe] Last Modified: [last-modified] The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.](https://medicalresearch.com/wp-content/uploads/2020/10/squamous-cell-cancer-dermnetnz-image.jpg)
Dr. Maslin[/caption]
Dr. Douglas Maslin, MPhil, MB BCHir
Dermatologist and Pharmacologist
Addenbrooke's Hospital
Cambridge, UK
MedicalResearch.com: What is the background for this study?
Response: I’d like to answer this question in three parts:
Dr. Lara-Corrales[/caption]
Irene Lara-Corrales, MD
Associate Professor of Pediatrics at the University of Toronto
Staff physician in Pediatric Dermatology at the
Hospital for Sick Children in Toronto, Canada
She is a member of the 
Dr. Huang[/caption]
Jennifer Huang, MD
Dr. Huang is a pediatric dermatologist at Boston Children’s Hospital and Dana-Farber Cancer Institute.
She is an Associate Professor of Dermatology at Harvard Medical School.
Dr. Huang is a member of the 
Alyssa M. Thompson[/caption]
Alyssa M. Thompson is currently a 2nd year medical student at the UA-COM Tucson. She graduated from the University of Arizona, Summa Cum Laude in 2018 as the athletic department's Valedictorian with a degree in Physiology and an Entrepreneurship certificate. Her passion for research and dermatology stems from her innovative and integrative mindset with specific interest in inflammatory skin disease.
MedicalResearch.com: What is the background for this study?
Response: Eczema is very common in children. Prescription medications are important for managing eczema flares, but a lot of the work in treating eczema is preventative, done by consistently moisturizing the skin at home with drug store products. Allergic contact dermatitis occurs more commonly in people with eczema. A previous study was done in characterizing the allergenic potential of drug-store moisturizers and found that 88% of moisturizers contain at least one common allergen. Many moisturizers are marketed specifically to eczema, but the allergen content of these products are unknown.