US Pharm. 2021;46(8):34-38.

Most Patients Find Teledermatology Appointments Suitable

Most dermatology patients surveyed find telehealth appointments to be a suitable alternative to in-person office visits, according to a survey study from researchers at the George Washington University (GW) Department of Dermatology. The results are published in the Journal of Drugs in Dermatology.

The COVID-19 pandemic changed many aspects of everyday life, including how patients interact with the healthcare system and seek medical care. Social distancing and stay-at-home orders have led to a move from in-office to virtual visits. While many specialties had to shift to the virtual format because of the pandemic, dermatology had already been experiencing an increase in telehealth visits over the past decade.

“Teledermatology boasts a number of benefits, including increased access to care, cost savings for patients, convenience, and, with the current pandemic, avoids physical contact,” said Samuel Yeroushalmi, a third-year medical student at the GW School of Medicine and Health Sciences and first author of the study. However, virtual appointments do come with some drawbacks, including privacy and security concerns, appropriate image acquisition, and appropriate provider training or experience.

To evaluate patient satisfaction with teledermatology appointments, the team distributed an online survey to dermatology patients at the GW Medical Faculty Associates. The survey assessed the patients’ reasons for scheduling the telehealth visit, as well as any pandemic-related barriers to care and overall satisfaction with the appointment.

Of the respondents to the survey, 47% reported having a previous appointment cancelled due to COVID-19, and 17.7% were new patients who had not previously had an in-office appointment. Patients reported that they most liked their telehealth experience because it was time efficient, did not require transportation, and effectively maintained social distancing. Reasons patients did not like their virtual appointments include lack of physical touch and feeling they received an inadequate assessment.

When asked if they would recommend telehealth services, only a small minority (6.9%) stated they would not.

“Video calling can certainly present challenges with regard to creating an intimate and collaborative physician-patient relationship compared to in-person encounters, not to mention enhancing certain areas that already have deficiencies,” said Adam Friedman, MD, interim chair of the Department of Dermatology and professor of dermatology at the GW School of Medicine and Health Sciences. “Accurate diagnosis of hair, skin, and nails in all skin types has been highlighted as an area in great need of improvement. Telemedicine can easily add an additional layer of complexity, widening the gap and impacting care.”

Overall, the team concluded that most patients who had teledermatology appointments found the visits to be an adequate substitute for in-person appointments. The authors suggest that telehealth can and should continue to provide high-quality care for patients of dermatologists during the COVID-19 pandemic in tandem with proper education to ensure meaningful use.

New Approach to Metastatic Melanoma Discovered

Combining chemotherapy and BRAF oncogene inhibitors is a highly effective strategy for fighting metastatic melanoma, the leading cause of death from skin cancer in the world. This has been demonstrated in a study by researchers in Spain from the Hospital del Mar Medical Research Institute (IMIM), Hospital del Mar, and CIBER Cancer (CIBERONC), in collaboration with the Bellvitge Biomedical Research Institute, which has just been published in the journal Oncogene.

The study, which involved the IMIM’s Stem Cells and Cancer Research Group and doctors from the Dermatology and Pathology Departments at Hospital del Mar, analyzed what effect combining the two types of treatment had on malignant melanoma. In previous studies, the same researchers had already demonstrated the usefulness of blocking BRAF oncogene expression to reduce the ability of colon and rectal cancer cells to repair after chemotherapy treatment.

The researchers tested the two treatments both separately and together in mice and in tumor cells in vitro. The combination of the two approaches proved to be superior in all trials after 1 week of treatment. Furthermore, the benefits were maintained after the end of treatment. “We have demonstrated the therapeutic potential of combining the two treatments to eradicate cancer cells. This strategy not only prevents the appearance of resistance to one of the approaches but also offers a new therapeutic perspective for patients with mutations affecting the BRAF oncogene,” explains Dr. Lluís Espinosa, a researcher at the IMIM-Hospital del Mar and CIBERONC, and an author of the study.

The study also indicates that chemotherapy administered at low doses, thereby avoiding its toxicity, combined with the standard treatment with BRAF inhibitors, can have an enormous effect on the progression of metastatic melanoma. Furthermore, because the combined treatment eliminates tumor cells rather than stopping their growth, it would also avoid lengthy treatments and the possible development of resistance. The researchers also believe that this approach could be applied to other types of cancer, including some rare subtypes of melanoma that are currently untreatable as they lack mutations in the BRAF oncogene. The authors of the study believe that this possibility is easily assessed, as the treatments already exist and are being used routinely for several types of tumors.

In this case, “the mechanism is simple: by combining low-dose chemotherapy, which has very low toxicity, with BRAF inhibitors, we damage the cell’s DNA with the chemotherapy while at the same time we prevent the cell from repairing itself thanks to the BRAF inhibitors. This not only enhances the effect of each of the treatments, but it might make the effect irreversible,” said Dr. Fernando Gallardo, head of the Dermatology Department and an author of the study. One of the main problems encountered with BRAF inhibitor treatment, the gold standard approach to this disease, is that the cancer cells regrow and become resistant to this therapy, as the inhibitor only stops them and does not eliminate them. The possibility of using this in combination with chemotherapy could eliminate the problem of certain resistance and relapse.

Balanced Diet May Reduce Skin, Joint Inflammation

The secret to healthier skin and joints may reside in gut microorganisms. A study led by University of California (UC) Davis Health researchers has found that a diet rich in sugar and fat leads to an imbalance in the gut’s microbial culture and may contribute to inflammatory skin diseases such as psoriasis.

The study, published in the Journal of Investigative Dermatology, suggests that switching to a more balanced diet restores the gut’s health and suppresses skin inflammation.

“Earlier studies have shown that Western diet, characterized by its high sugar and fat content, can lead to significant skin inflammation and psoriasis flares,” said Sam T. Hwang, professor and chair of dermatology at UC Davis Health and senior author on the study. “Despite having powerful anti-inflammatory drugs for the skin condition, our study indicates that simple changes in diet may also have significant effects on psoriasis.”

Psoriasis is a stubborn skin condition linked to the body’s immune system. When immune cells mistakenly attack healthy skin cells, they cause skin inflammation and the formation of scales and itchy red patches.

Up to 30% of patients with psoriasis also have psoriatic arthritis, with symptoms such as morning stiffness and fatigue, swollen fingers and toes, pain in joints, and changes to their nails.

Food is one of the major modifiable factors regulating the gut microbiota, the community of microorganisms living in the intestines. Eating a Western diet can cause rapid change to the gut’s microbial community and its functions. This disruption in microbial balance—known as dysbiosis—contributes to gut inflammation.

Since bacteria in the gut may play key roles in shaping inflammation, the researchers wanted to test whether intestinal dysbiosis affects skin and joint inflammation. They used a mouse model to study the effect of diet on psoriasis and psoriatic arthritis. They injected mice with interleukin-23 (IL-23) minicircle DNA to induce a response mimicking psoriasis-like skin and joint diseases.

IL-23 is a protein generated by the immune cells responsible for many inflammatory autoimmune reactions, including psoriasis and inflammatory bowel disease. Dr. Hwang and his colleagues found that a short-term Western diet appears sufficient to cause microbial imbalance and to enhance susceptibility to IL-23–mediated, psoriasis-like skin inflammation.

“There is a clear link between skin inflammation and changes in the gut microbiome due to food intake,” Dr. Hwang said. “The bacterial balance in the gut disrupted shortly after starting a Western diet and worsened psoriatic skin and joint inflammation.”

One critical finding of their work was identifying the intestinal microbiota as a pathogenic link between diet and the displays of psoriatic inflammation. The study also found that antibiotics block the effects of the Western diet, reducing skin and joint inflammation.

The researchers wanted to test if switching to a balanced diet can restore the gut microbiota, despite the presence of IL-23 inflammatory proteins. They fed mice a Western diet for 6 weeks before giving them an IL-23–inducing agent to trigger psoriasis and psoriatic arthritis features. Then, they randomly divided the mice into two groups: a group that continued the Western diet for another 4 weeks and a group that switched to a balanced diet for the same duration.

Their study showed that eating a diet high in sugar and fat for 10 weeks predisposed mice to skin and joint inflammation. Mice that were switched to a balanced diet had less scaling of the skin and reduced ear thickness than mice on a Western diet. The improvement in skin inflammation for mice taken off the Western diet indicates a short-term impact of the Western diet on skin inflammation.

This suggests that changes in diet could partially reverse the proinflammatory effects and alteration of gut microbiota caused by the Western diet. “It was quite surprising that a simple diet modification of less sugar and fat may have significant effects on psoriasis,” said Zhenrui Shi, visiting assistant researcher in the UC Davis Department of Dermatology and lead author on the study. “These findings reveal that patients with psoriatic skin and joint disease should consider changing to a healthier dietary pattern.”

“This work reflects a successful collaboration among researchers, especially with Professor Satya Dandekar and her team at the Department of Medical Microbiology and Immunology and Professor Yu-Jui Yvonne Wan at the Department of Medical Pathology and Laboratory Medicine,” Dr. Hwang said.

Device Detects Skin Disorders Based on Tissue Stiffness

By putting a piece of soft, strain-sensing sheet on the skin we may soon be able to detect skin disorders noninvasively and in real-time. A research team co-led by a scientist from City University of Hong Kong (CityU) has designed a simple electromechanical device that can be used for deep-tissue pathology diagnosis, such as psoriasis, in an automated and noninvasive fashion. The findings will lay a foundation for future applications in the clinical evaluation of skin cancers and or dermatology diseases.

The research is co-led by Dr. Yu Xinge, assistant professor from CityU’s Department of Biomedical Engineering, and scientists from Northwestern University in the United States. Their findings have been published in the science journal Nature Biomedical Engineering, titled “Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue.”

Electromechanical systems that enable precise, rapid measurements of the stiffness of soft tissues of the human body can provide useful clinical information for monitoring, diagnosing, and treating various pathologies, particularly those of the skin. However, existing diagnostic evaluations, e.g., magnetic resonance elastography, usually involve huge instruments at hospitals and trained practitioners. And the latest tissue stiffness–measuring technology based on sensing can only measure to superficial depths of upper skin, up to micrometer scale.

To address the issue, the research team designed a simple, miniature electromechanical device for high-precision, real-time evaluations of deep-tissue stiffness. The team used a miniature electromagnetic system that integrates a vibratory actuator and a soft strain-sensing sheet to monitor in real time the Young’s modulus, i.e, the tensile stiffness, of skin and other soft biological tissues at depths of approximately 1 to 8 mm, depending on the sensor designs.

The team evaluated the device’s performance with a range of synthetic and biologic materials, such as hydrogels and pigskin, and on various parts of human skin. “The lesions exhibited higher stiffness than those of the nearby skin, primarily due to differences in skin elasticity and hydration. These simple measurements have potential clinical significance in rapidly identifying and targeting skin lesions, with capabilities that complement those of recently reported methods for sensing mechanical properties at tissue surface (typically micrometer-scale),” explained Dr. Yu. He pointed out that cancer tissue is typically stiffer or softer than normal tissue, and this difference can be used as diagnostic biomarkers for a range of skin conditions, such as skin cancer or tumors under the skin.

Studying Skin-Related Side Effects of Cancer Immune Therapies

Immune checkpoint inhibitors, which boost the immune system’s response against tumor cells, have transformed treatment for many advanced cancers, but short-term clinical trials and small observational studies have linked the medications with various side effects, most commonly involving the skin.

A more comprehensive, population-level analysis now provides a thorough look at the extent of these side effects and provides insights on which patients may be more likely to experience them. The research was led by investigators at Massachusetts General Hospital (MGH) and is published in the Journal of the American Academy of Dermatology.

“Immunotherapies, which include immune checkpoint inhibitors, are an increasingly common treatment modality for advanced cancers, with more than 200,000 patients being started on these therapies annually,” said co-senior author Yevgeniy R. Semenov, MD, an investigator in the Department of Dermatology at MGH. “As the use of immune checkpoint inhibitors increases, so will the incidence of adverse events, underscoring the importance of research into their incidence, type, and severity.”

Dr. Semenov and his colleagues used a Big Data approach to study the U.S. prevalence of skin-related side effects, as well as when they arise and how they are treated, in a large population of patients who received immune checkpoint inhibitors.

The study involved analyzing information from a national health insurance claims database pertaining to 8,637 patients who were treated with immune checkpoint inhibitors as well as an equal number of patients with cancer who did not receive these medications. The overall incidence of skin-related side effects was 25.1%, with a median time of onset of 113 days. “We found that only 10 of more than 40 skin conditions previously reported to be linked to immune checkpoint inhibitors are actually seen at a higher incidence among patients on these medications compared with other patients who were matched by demographics, cancer type, and comorbidities,” said Dr. Semenov.

These conditions manifested with symptoms of itching, inflammation, rash, skin color loss, swelling, or blisters. Patients with melanoma or kidney cancer and those receiving multiple types of immune checkpoint inhibitors were at an especially high risk of developing these skin problems.

The investigators’ real-world data also found that skin-related symptoms tended to arise later than those noted in clinical trials. In addition, they found that clinicians often prescribed systemic corticosteroids to treat them even though these drugs should generally be avoided due to concerns that they may blunt the anti-tumor effects of immunotherapy.

“These findings are of particular clinical relevance to both dermatologists and oncologists caring for patients receiving immune checkpoint inhibitors,” said Dr. Semenov. For example, clinicians should be on the lookout for the 10 conditions identified in this analysis as patients continue taking these medications. “The real-world delays in the time to presentation of many of these conditions should also revise clinicians’ understanding of when to expect patients to present with these toxicities and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” added Dr. Semenov.

The findings also suggest an opportunity for improving care for patients, he said: “Dermatologists can work with oncologists to facilitate evaluations of these vulnerable patients so that they can take steps to prevent progression to more severe toxicities.”

Enzymes Protect Skin by Ignoring Microbes and Viruses

The human body is constantly exposed to various environmental actors, from viruses to bacteria to fungi, but most of these microbial organisms provoke little or no response from our skin, which is charged with monitoring and protecting from external dangers.

Until now, researchers weren’t quite sure how that happened—and why our skin wasn’t constantly alarmed and inflamed.

In a study published in May in Science Immunology, scientists at the University of California (UC)  San Diego School of Medicine identify and describe two enzymes responsible for protecting our skin and body’s overall health from countless potential microbial intruders. These enzymes, called histone deacetylases (HDACs), inhibit the body’s inflammatory response in the skin.

“We have figured out why we tolerate certain microbes living on our skin, while the same bacteria would make us very sick if exposed elsewhere in the body,” said Richard Gallo, MD, PhD, Ima Gigli distinguished professor of dermatology and chair of the Department of Dermatology at UC San Diego School of Medicine. “In our research, we identified enzymes that act on the chromosome of specific skin cells that provide immune tolerance by the skin.

“Without these enzymes telling our cells to ignore certain bacteria, we’d have a constant rash on our skin.”

Dr. Gallo and colleagues say the potential mechanism for how the environment can interact and alter cell function is through epigenetic control of gene expression. Within the skin cells, proteins called toll-like receptors (TLRs) allow the cells to sense their surroundings and potential dangers.

In most organs, TLRs act as a warning system that triggers an inflammatory response to threats. But in skin cells, the two identified HDAC enzymes, HDAC8 and HDAC9, inhibit the inflammatory response.

“This is one of the first demonstrations of how the microbiome can interact with epigenetic factors in the skin and modulate the skin’s behavior through the inflammatory response,” said George Sen, PhD, associate professor of dermatology and cellular and molecular medicine at UC San Diego School of Medicine. “Whatever environment we’re facing can change a person’s specific response to it. Since this epigenetic change is reversible, unlike alterations to our DNA, we can potentially control our skin inflammatory response through targeting of these enzymes.”

The research was initially conducted in mouse models in which HDAC8 and HDAC9 had been genetically knocked out. As a result, the mices’ skin could not tolerate microbial or viral exposures, resulting in a heightened immune reaction. The team then reproduced the findings with human cells in a culture dish.

Dr. Gallo said the work could change how doctors treat certain types of skin inflammation or other dermatologic conditions.

“This is a completely new way to think about skin immune regulation,” Dr. Gallo stated. “Through alterations in HDAC activity, we’ve provided a possible way to explore and quiet down unnecessary inflammation by working with skin cells themselves. In the future, drugs designed to turn these enzymes on or off could help treat skin disease as an alternative to antibiotics.”

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