Rashes are a common side effect of antiseizure medications, occurring in 2 to 16 percent of patients and vary by specific drug.

Although most rashes are not life-threatening, roughly 5 percent indicate life-threatening reactions. The FDA recently issued a warning about serious reactions to two antiseizure medications: levetiracetam and clobazam.

“Dangerous reactions are rare, but patients and caregivers should understand the risk and how to respond if side effects occur,” said Ram Mani, chief of the adult epilepsy division at Rutgers Robert Wood Johnson Medical School and lead author of the study published in Current Treatment Options in Neurology.

“Patients should seek medical treatment if rashes develop rather than waiting for them to disappear,” added co-author Cindy Wassef, an assistant professor of dermatology at Robert Wood Johnson Medical School. “If symptoms are mild, they can contact their neurologist or primary care physician, but serious symptoms like a high fever, skin pain, or blisters warrant a trip to the emergency room or a 911 call.”

Despite these risks, antiseizure medicines are important for many medical conditions. The proper antiseizure medication can stop further seizures in 70 percent of patients. Such medications also help many patients with bipolar disorder, anxiety, migraines and neuropathic pain.

This new review synthesizes published data on individual antiseizure medications and distinguishes the different rashes and their triggers.

Risk factors for severe reactions include the use of aromatic antiseizure medications, rapid dose escalation, genetic predisposition,  and certain drug interactions.

“Patients who react to one medication are more likely to react to others with structural similarities, but with 30 FDA-approved options, we can typically find each patient an effective treatment with minimal to no side effects,” Mani said.

The most common non-disabling reaction is a rash that typically occurs within two weeks of treatment. It typically affects the torso or limbs with a flat rash or hive-like bumps. It usually disappears without treatment a few weeks after patients stop the medication.

Severe conditions, on the other hand, often require urgent treatment. In Stevens-Johnson syndrome or toxic epidermal necrolysis — which produces fever, eye pain and detached skin — inpatient care is often needed.

Mani estimated that several thousand patients suffer severe reactions to antiseizure medications each year, but the numbers could decrease if neurologists consistently put high-risk patients on low-risk medicines.

“I gave a talk on this topic at the American Epilepsy Society Conference last year, and I asked the more than 200 doctors in the room how frequently they perform the recommended HLA screening tests on indicated patients, and only a handful raised their hands,” Mani said. “So there’s definitely room for improvement to increase patient safety.”

“Very few treatments exist for prurigo nodularis and chronic pruritus of unknown origin; patients often suffer for years in horrible discomfort, which can lead to anxiety and depression, severely impacting their quality of life,” said  Shawn Kwatra, MD, the Joseph W. Burnett Endowed Professor and Chair of Dermatology at UMSOM and Chief of Service Dermatology at the University of Maryland Medical Center (UMMC). “The rationale for this study came from my laboratory’s studies findings of altered inflammatory mediators in these conditions that all function through JAK1. Through this trial, we hope to continue to move the needle toward personalized therapies that can provide sustainable relief for coping with these debilitating conditions.”

Affecting at least 130,000 Americans, prurigo nodularis causes dozens of extremely itchy and disfiguring bumps, usually on the chest, arms, and legs. Dr. Kwatra’s previous research indicates that prurigo nodularis occurs more than 3 times as frequently in Black patients than white patients, tends to be more common in women, and is associated with depression, diabetes, chronic kidney disease, and HIV. Chronic pruritus of unknown origin is most prevalent among older adults and causes severe itching lasting longer than six weeks. Current therapies used to help manage symptoms include over-the-counter and prescription itch relief ointments and anti-inflammatory drugs such as antihistamines and corticosteroids. None of these medications, however, provide sustained relief.

The study involved a total of 20 patients, half of whom had prurigo nodularis and half of whom had chronic pruritus of unknown origin. They were all given a 200-milligram pill of abrocitinib once a day for 12 weeks; the patients knew they were being given an experimental treatment, and the study did not include a placebo group. Abrocitinib was found to reduce itching and pain symptoms by 78 percent in the prurigo nodularis patients. Patients with chronic pruritus of unknown origin experienced a 54 percent reduction in itching and pain symptoms. Patients in both groups also reported an improvement in their quality of life and in their sleep habits.

None of the patients experienced serious adverse events. The most common side effect, in 10 percent of patients, was small acne-like bumps.

Abrocitinib is a JAK1 inhibitor drug that works to suppress inflammation, specifically pro-inflammatory chemicals called cytokines that are involved in an overactive immune system. The drugs appear to slow down immune activity by suppressing intracellular signaling of these cytokines.

“This is not only an encouraging study but also sets the stage for a Phase 3 clinical trial,” said Mark T. Gladwin, MD,  who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. “It holds promise for introducing a novel treatment to patients in underserved communities disproportionately affected by prurigo nodularis, a condition historically overlooked by dermatology.”

Since beginning his position at UMSOM, Dr. Kwatra has created the Maryland Itch Center at UMMC and is currently continuing his research there.

Study co-authors included faculty from Duke University, Johns Hopkins University, and The George Washington University.

Pfizer, Inc., manufacturer of abrocitinib, provided funding (as well as the drug) for the study. When employed at Johns Hopkins University, Dr. Kwatra served as a paid consultant for Pfizer and, he is also funded by the National Institutes of Health.

Skin cancer now accounts for half of all cancers in England and Wales, though many, including 86% of melanomas, can be prevented with safer sun exposure.

Despite continuing advice to avoid intentional sunbathing, the public, including children, often has positive views of tanned skin for health or appearance.

Skin and cancer specialists agree there is no such thing as a ‘safe tan’, highlighting the importance of understanding and addressing the reasons behind this misconception.

To date, no work has been done in Wales to study the thoughts of children, their parents and educators on tanning and how healthier attitudes can be encouraged and adopted from a young age.

SunChat: SUN Safety Conversations about Healthy Attitudes to Tanning is using existing networks and school partners to explore this subject through:

1. Workshops with schoolchildren aged 5 to 8 in Healthy School Clubs to understand their perceptions of tanning and their existing sun-safety habits. Activities include colouring, role-play, drawing, collage techniques, videos and posters.
2. An online multiple-choice survey with parents and carers of primary school children to better understand their perceptions, attitudes, and behaviours towards tanning, both for themselves and their children.
3. An informal online focus group with primary school educators to not only understand their current perceptions of tanning but also explore challenges in engaging with the school community in the Curriculum for Wales.

Funded by the Morgan Advanced Studies Institute (MASI), SunChat is a collaboration between Swansea University’s Department of Education and Childhood Studies, the Swansea Trials Unit, and Cardiff and Vale University Health Board.

Dr Julie Peconi of Swansea University Medical School, one of the lead researchers for SunChat, said: “We know that overexposure to the sun as a child greatly increases the risk of skin cancer in later life, making early and accessible sun safety education and promotion of sun-safe behaviours key.

“Through SunChat, we hope to raise awareness of the importance of challenging and changing the common assumption that having a tan is desirable. The Curriculum for Wales, with its designated area for Health and Well-being and autonomy for schools in designing curriculum, is the ideal opportunity to support schools in empowering and educating children to become healthy and informed adults, alleviating unnecessary pressure on future NHS dermatology services and care.”

Project co-lead Dr Gisselle Tur Porres of Swansea University School of Social Sciences added: “We take the known problem of skin cancer and address it in a novel way by engaging directly with children through creative activities to facilitate and prioritise their participation.”

More details of the SunChat project have recently been published in the journal PLOS ONE – “Exploring perceptions of and attitudes towards tanning with school children, parents/carers and educators in Wales: A mixed methods study protocol for the SunChat study”.

A high sodium diet may increase the risk of eczema, according to researchers at UC San Francisco (UCSF), who found that eating just one extra gram of sodium per day – the amount in a Big Mac – increases the likelihood of flares by 22%.

Eczema, also known as atopic dermatitis, is a chronic disease that causes dry, itchy skin. It’s one of the most common skin conditions, affecting more than 31 million people in the U.S., and one in 10 people will develop it at some point.

It has become increasingly common in recent years, especially in industrialized countries, implicating environmental and lifestyle factors like diet.

Sodium, which most people consume in the form of salt, increases the risk of hypertension and heart disease. And scientists recently discovered that sodium is stored in the skin, where it may play a role in the inflammation in eczema.

Limiting dietary sodium could be an easy way for eczema patients to manage their disease.

“Most Americans eat too much salt and can safely reduce their intake to recommended levels,” said Katrina Abuabara, MD, associate professor of dermatology at UCSF and corresponding author of the study, which appears June 5, 2024, in JAMA Dermatology.

“Eczema flares can be difficult for patients to cope with,” said Abuabara, who is also associate adjunct professor of epidemiology at the UC Berkeley School of Public Health, “especially when they are unable to anticipate them and don’t have recommendations on what they can do to avoid them.”

For their cross-sectional study, the researchers analyzed data from more than 215,000 people between 30 and 70 years old from the UK Biobank, which includes urine samples and electronic medical records.

They could tell how much sodium each person was eating from urine samples; and they could see whether people had a diagnosis of atopic dermatitis, as well as the severity, from prescription codes.

They found that each additional gram of sodium excreted in urine over 24 hours was associated with 11% higher odds of an eczema diagnosis; 16% higher odds of having an active case; and 11% higher odds of increased severity.

Then, they looked at 13,000 U.S. adults in the National Health and Nutrition Examination Survey and found that eating just one additional gram a day of sodium – about half a teaspoon of table salt – was associated with 22% higher odds that someone would have an active case of eczema.

Authors: Other UCSF authors include, Brenda M. Chiang, MS; Morgan Ye, MPH; Aheli Chattopadhyay, BS; Yagmur Halezeroglu, MS; and Erin L. Van Blarigan, ScD.

Funding: The Medical Student in Aging Research Program; the National Institute on Aging (T35AG026736); and the National Eczema Association.

Disclosures: Please see the paper.

“There is no such thing as a healthy tan, as it’s really just a visual manifestation of damage to the skin,” said Rajesh Nair, MD, an oncology surgeon at the Orlando Health Cancer Institute. “But we’re fighting against a perceived positive image and health benefits of something that actually has a totally opposite reality, which is that suntanned skin represents an increased risk of a deadly disease.”

The survey, conducted by Ipsos, also found that young adults are likely to believe myths and misinformation on sun protection that may lead them away from proven methods of skin cancer prevention. About one in seven (14%) adults under 35 think daily sunscreen use is more harmful to the skin than direct sun exposure and nearly a quarter (23%) believe drinking water and staying hydrated prevents a sunburn.

“There is no scientific data suggesting that drinking water provides any protection from the sun,” Nair said. “As for sunscreens, the protective benefits far outweigh any known risks, but if you’re concerned about chemicals or ingredients in a sunscreen, mineral sunscreens like zinc oxide that offer a physical barrier to the sun are proven to be safe, as well as clothing with SPF protection.”

Nair says, with so many sources of information—and misinformation—these days, it’s difficult to decipher good advice from the bad.

“We have really hectic and busy lives, and we’re trying to find information to guide us on healthy choices and decision-making to the best of our ability. But the overwhelming number of people and organizations claiming to have the right answers makes it really hard to know what to believe,” Nair said. “Our fear is that people buy into a lot of really dangerous ideas that put them at added risk.”

It’s something Brianna Starr, 29, sees a lot of, with trends on social media spreading quickly and easily.

“I think a lot of people get their information from TikTok, Instagram, Twitter, that might not be actually legit,” Starr said. “And you’re very influenced by your friends and peers, so you see a video or hear something from your friend, you’re like, ‘Oh, yes. I need to try that,’ and you believe it.”

Starr admits that skin cancer was not top of mind in her teens and twenties and was more concerned with getting a golden tan as she laid out in the sun sans sunscreen. But after her sister was diagnosed with melanoma at the age of 19, she got serious about protecting herself.

“There is a history of melanoma in my family, and so I started seeing a dermatologist every six months and actually flagged two separate moles, one on my neck and one on my shoulder, that were dysplastic and could have developed into melanoma.”

Starr is now diligent about applying and reapplying sunscreen whenever she’s outdoors. Experts recommend using sunscreens with an SPF of 30 or higher and reapplying it every two hours, especially if you are sweating or are in the water.

Regular skin cancer screenings with a dermatologist or your primary care physician are also critical to catch any developing skin cancer early.

“Unfortunately we’re seeing skin cancer more and more in patients of a young age. And because it’s something that’s often not on their radar, it tends to be diagnosed in more advanced stages,” Nair said. “We don’t want to discourage people from being outside and being active because there are so many health benefits to that, but it’s also important to know that sun protection can be lifesaving, and the only effective way of protecting yourself is limiting the effects of UV radiation on the skin.”

IMAGE: RAJESH NAIR, MD, PERFORMS A ROUTINE SKIN CANCER SCREENING ON A PATIENT AT THE ORLANDO HEALTH CANCER INSTITUTE. NAIR SAYS HE’S SEEN AN INCREASE IN SKIN CANCER CASES AMONG YOUNG ADULTS AND THAT SUN PROTECTION IS CRITICAL TO PREVENTION.

view more CREDIT: ORLANDO HEALTH CANCER INSTITUTE

The authors of the new JAMA Network Open paper say their findings show how vital early detection of cancer can be, while also highlighting the importance of considering unintended side effects in any future pandemic planning.

Co-lead author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) said: “When lockdowns were introduced as a much-needed measure to stop the spread of Covid-19, there were extensive unintended consequences. Many screenings were cancelled and medical treatments were delayed.

“As many people missed appointments to detect or treat skin cancer, their cancer progressed to a later stage, which resulted in more expensive care and a greater risk that the treatment would not be successful.

“It’s alarming that for just one disease, there were many years of life lost, a lower quality of life for many thousands of people, and billions of pounds of economic impact – this may be just the tip of the iceberg of the consequences of delayed diagnosis and treatment due to lockdowns. While the lockdowns did save many lives by mitigating the toll of Covid-19 itself, it is important that we learn from the experience to ensure that if another pandemic arises, we can effectively balance different healthcare priorities.”

The team of researchers, from the UK, Switzerland, Germany, US, Italy, Australia and Hungary, were investigating the health economic consequences of delays in diagnosing melanoma, a common type of skin cancer and one of the 10 most common cancers in Europe. The analysis was based on information from 50,072 patients of two cancer treatment centres in Switzerland and Italy, supported by further data from the UK and Belgium.

The researchers estimated how many people’s cancer would have progressed from one stage to the next due to delays in beginning or continuing treatment, as both screening services and treatments were disrupted in 2020 and 2021 due to lockdown restrictions, staff shortages, and fear of infection. They estimated that for roughly 17% of people with melanoma, their cancer would have progressed to a higher stage in 2020-2021, due to delays in diagnosis or treatment of two to three months or longer.

The research team then estimated the additional medical costs, as treating later-stage cancer is more expensive and comes with a lower chance of success. These cost estimates included both the direct costs to healthcare providers (such as the NHS), as well as the broader impacts such as the loss of productivity (indirect costs) due to disability and years of life lost.

The researchers estimated that delays to melanoma diagnoses contributed to 111,464 years of life lost across 31 countries in Europe, with a total economic cost of £6.1bn (€7.1bn or $7.7bn USD). Most of the costs (94.5%) were indirect costs such as loss of productivity.

Co-lead author Dr Elisabeth Roider (University Hospital of Basel) said: “Our findings show that preventative healthcare always needs to be a top priority, both in normal times and in times of crisis; any plans for potential future pandemics need to consider unintended side effects on a wide range of health conditions and plan holistically.

“Delays to diagnosis and treatment can be devastating to people affected by cancer, so getting prompt evaluation and treatment is vital for people concerned about their health, while screening programmes need to be treated as a priority by healthcare system leaders.”

The research was supported by the Research Foundation of the University of Basel, the ProPatient Foundation, University Basel, the Goldschmidt Jacobson Foundation, and the Swiss National Science Foundation.

Investigators selected 129,682 osteoporosis cases and 34,999 major osteoporotic fracture (MOF) cases and matched them with 518,728 and 139,996 controls (without osteoporosis or MOF) by sex and age.

The team found clear dose–response relationships between long-term use of topical corticosteroids and osteoporosis and MOF. For example, compared with no doses, low, medium, and high cumulative of doses topical corticosteroids were associated with 1.22-, 1.26-, and 1.34-times higher odds of developing osteoporosis over five years. These respective doses were linked with 1.12-, 1.19-, and 1.29-times higher odds of experiencing MOF. Women had higher risks of osteoporosis and MOF than men. Also, younger people (<50 years) had a higher risk of osteoporosis compared with other age groups.

“This study emphasizes that using topical corticosteroids to treat inflammatory skin conditions should be done very carefully and clinicians should be aware of these potential side effects,” said corresponding author Chia-Yu Chu, MD PhD, of National Taiwan University Hospital and National Taiwan University College of Medicine.

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/jdv.19697

Until now, the importance of bacteriophages (“bacteria eaters”, also called phages) in the human body has been known primarily from analyses of the intestine. In the search for innovative therapeutic measures for atopic dermatitis (AD), the MedUni Vienna research team has now investigated the interaction of phages and bacteria in the skin for the first time. After all, it has long been known that the progression of AD is accompanied by massive changes in the skin microbiome. The microbiome is the sum of all microorganisms on the skin and has been primarily investigated for its bacterial constituents. It has been unknown whether viruses also contribute to the nature of the bacterial microbiome in healthy and diseased skin. Phages are viruses of different types and functions whose sole aim is to infect bacteria, thereby either destroying them – or stimulating them to multiply.

New phages identified
“In our study, we discovered previously unknown phages in the microbiome of the skin samples of AD patients, which help certain bacteria to grow faster in different ways,” note first authors Karin Pfisterer and Matthias Wielscher from the Department of Dermatology at MedUni Vienna. The resulting shift in the balance between phages and bacteria was not detected in the comparative samples from healthy individuals and may be one explanation for the overpopulation of the skin microbiome with bacteria called Staphylococcus aureus found in AD. These findings contribute significantly to a better understanding of the skin bioflora in AD patients and pave the way for the development of new targeted therapeutic interventions: By identifying and culturing phages specialized for Staphylococcus aureus, a promising new option is available.

Specialists for targeted therapy
Bacteriophages are found not only in the body, but in every habitat populated by bacteria. There are 10³¹ different phage species, which makes a number with 31 zeros. One of their characteristics is that they prove to be extremely specific when it comes to choosing their target of infection: Most phages specialize in a particular genus, and in many cases in only a single species of bacteria. While that makes it a challenge for scientists to identify the type of phage needed for a particular purpose, it also enables them to use them in a targeted manner. Bacterial viruses do not make any difference between antibiotic-resistant and other bacteria, thus they are being researched as possible weapon in the fight against multi-resistant pathogens. Further studies are now planned to confirm phage therapy for topical use in atopic dermatitis.

Prolonged exposure to UVR is associated with damage to DNA in skin cells, inflammation, and premature skin aging, yet intentional sun-seeking behaviors remain common.

Due to a lack of studies focusing on how individual behavior influences UVR-associated microbiota shifts, and how this may relate to skin health, researchers in the UK have now examined the effects of sun-seeking behaviors on the skin microbiota composition of holidaymakers.

“Here we show in a cohort of holidaymakers that their sun exposure behavior significantly affects the diversity and composition of their skin microbiota,” said Dr Abigail Langton, principal investigator at The University of Manchester and corresponding author of the study published in Frontiers in Aging.

“We have demonstrated that the development of a tan is associated with lower Proteobacteria abundance immediately post-holiday. However, the microbiota of all holidaymakers was recovered a few weeks after they stopped spending extended time periods in the sun.”

Sun-seeking harms skin bacteria

Prior to vacations to sunny destinations, which lasted at least seven days, the researchers analyzed participants’ skin. The skin microbiota is largely made up of three bacterial communities on the surface: Actinobacteria, Proteobacteria, and Firmicutes. On day one, 28, and 84 post-holiday, participants’ skin microbiota was assessed again.

Additionally, each holidaymaker was assigned a group based on individual tanning response. Eight out of 21 participants, who picked up a tan while on holiday, were deemed ‘seekers.’ The ‘tanned’ group was made up of seven individuals who already had a tan at departure and kept it throughout their holiday. These two groups were classified as ‘sun-seekers.’ The remaining six participants were deemed ‘avoiders;’ their skin tone was the same pre- and post-holiday.

“This study was performed in real-life holidaymakers and provides important insights into how sun exposure resulting in a tanning response – even over a relatively short sunny period – can lead to an acute reduction in Proteobacteria abundance, which decreased skin microbiota diversity,” Dr Thomas Willmott, the study’s first author and researcher at the University of Manchester, explained.

Despite the rapid reduction of Proteobacteria and the accompanying shift in skin microbiota diversity, the bacterial community structure had recovered 28 days after individuals had returned from vacation. “This indicates that UV exposure on holiday has an acute effect on the skin microbiota, but recovery is relatively rapid once the person returns to a less sunny climate,” Willmott continued.

Microbiota disturbance can cause health problems

“Proteobacteria dominate the skin microbiota. Accordingly, it is not surprising that there would be rapid recovery of the microbiota to re-establish optimal functioning conditions for the skin,” Langton pointed out. The authors state that what might be more concerning is the rapid alteration of microbiota diversity, which has been linked to disease states. A decrease in skin bacterial richness, for example, has been previously associated with dermatitis. Fluctuation in Proteobacteria diversity specifically has been associated with skin problems like eczema and psoriasis.

Future studies should examine why Proteobacteria seem to be particularly sensitive to UVR and how this change in diversity impacts skin health in the longer term, the researchers noted. “Ideally, such studies will aim to increase the number of participants to allow further insights,” Langton said.

The analysis, which included almost 500 psoriasis cases from the National Health and Nutrition Examination Survey (NHANES), showed a linear relationship between increasing psoriasis severity and decreasing vitamin D levels measured through blood tests.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said Rachel K. Lim, an MD candidate at the Warren Alpert Medical School of Brown University. “Our results suggest that a vitamin D-rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

Lim will present the findings at NUTRITION 2023, the annual flagship meeting of the American Society for Nutrition held July 22-25 in Boston.

The research team was led by Eunyoung Cho, ScD, an associate professor in the Department of Dermatology at the Warren Alpert Medical School of Brown University who studies the role of nutrition and environmental factors in skin cancer and inflammatory skin diseases such as psoriasis. Vitamin D is thought to influence the development of skin diseases by affecting the body’s immune response and through direct effects on the cells involved in skin repair.

“With growing public interest in vitamin supplementation, we wanted to further examine the connection between vitamin D levels and psoriasis severity,” said Cho. “Few studies have looked for this association in groups of people, especially in large U.S. populations, or examined this relationship through a clinical nutrition lens.”

For the new study, the researchers identified 491 psoriasis cases from more than 40,000 NHANES participants, with 162 cases from 2003-2006 and 329 from 2011-2014. They also extracted data on vitamin D levels, self-reported psoriasis-affected body surface area and other factors including age, gender, race, body mass index, and smoking status.

After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity. The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.

“Only one previous study, published in 2013, has used NHANES data to analyze the relationship between vitamin D and psoriasis,” said Lim. “We were able to add more recent data, which more than tripled the number of psoriasis cases analyzed, making our results more up-to-date and statistically powerful than previously available data.”

Although dietary vitamin D toxicity is rare, the researchers advise people with psoriasis to consult their physicians and dermatologists before taking supplements.

Lim will present this research at 10:17 a.m. on Tuesday, July 25, during the Micronutrients, Supplements and Chronic Disease Mechanisms Poster Theater Flash Session in the Sheraton Boston, Fairfax (abstract; presentation details).

Please note that abstracts presented at NUTRITION 2023 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

Led by researchers at NYU Grossman School of Medicine, the study mapped hidden features of inflammation and how they compared in cases of increasing severity of psoriatic disease. The team’s findings may help explain how small areas of skin inflammation can have wide-ranging effects in other parts of the body. Up to one-fifth of those with the skin disease, the researchers note, go on to develop inflammation in the joints, or psoriatic arthritis. The study results, they say, may also offer clues as to why psoriasis can trigger this and other conditions, such as type 2 diabetes, heart disease, and inflammatory bowel disease.

Publishing in the journal Science Immunology online June 2, the new analyses revealed that the location of clusters of cells called fibroblasts, key regulators of inflammation, along with macrophages, a type of white blood cell, varied and were more common in upper layers of the skin in more severe cases of psoriasis.

Further, the research team found that in skin samples from patients with moderate-to-severe psoriatic disease, gene activity increased in more than three dozen molecular pathways tied to metabolism and control of lipid levels, factors known to go awry in diabetes and cardiovascular diseases. This increased gene activity even occurred in clear skin far away from any lesions.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” said study co-senior investigator Jose Scher, MD.

“Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,” said Scher, the Steere Abramson Associate Professor of Medicine in the Department of Medicine at NYU Langone Health, where he also serves as director of its Psoriatic Arthritis Center, and the Judith and Stewart Colton Center for Autoimmunity.

“Our study serves as a valuable resource for the scientific community, offering the most comprehensive archive of cellular and molecular features involved in both diseased and healthy skin,” added study co-senior investigator Shruti Naik, PhD. Naik is an assistant professor in the departments of Pathology, Medicine, and the Ronald O. Perelman Department of Dermatology at NYU Langone.

More than 8 million Americans, and 125 million people worldwide, are estimated to have psoriatic disease. The condition affects men and women equally.

Scher notes that the new study was designed to go beyond current diagnostic tools that focus heavily on visible signs of skin lesions instead of looking at their invisible systemic and molecular effects. While many available therapies, including steroids and immunosuppressive drugs, reduce inflammation and symptoms, they do not address the underlying causes of the disease.

The new study relied on spatial transcriptomics, a technique that carefully charts the molecular and cellular interactions occurring in a specific tissue. Researchers analyzed intact skin samples from 11 men and women with mild to severe cases of psoriatic disease, plus three healthy adults without psoriasis. Spatial transcriptomics, they say, is more powerful than other commonly used techniques that track single cells because it creates a broad image-based map of.where cells are located in tissues and what other cells with which they are communicating.

Naik says the team next plans to use their latest analysis to identify the biological mechanisms involved in skin inflammation in one area and how it affects skin or other organs in another part of the body. Further research is also planned in larger groups of patients and in lesioned and nonlesioned skin from the same patients to determine how disease clears on its own in some and why patients respond differently to the same anti-inflammatory medications.

For the benefit of researchers worldwide, study co-lead investigator and bioinformatician Ikjot Sidhu has archived its spatial transcriptomics analysis online at https://zenodo.org/record/7813973 and https://zenodo/org/record/7562864 .

In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

The researchers can now show data from the first clinical study on humans, in which the main objective was to establish safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. In addition, the time to first recorded healing was reduced by an average of 6 days, and by 10 days at the highest dose. The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase.

“Our study shows that bacteria modified to produce and deliver human protein for local effects can be used as drugs to accelerate the healing of wounds. This is the first time this has been shown in controlled human studies, and it can be expected that the effect is greater in patients with diseases that negatively affect wound healing,” explains Mia Phillipson, Professor at the Department of Medical Cell Biology at Uppsala University.

The favourable safety profile and the beneficial effects on wound healing observed here support further clinical development of ILP100-Topical for the treatment of complex and hard-to-heal wounds in patients, which is already under way.

Many immune-active proteins are inherently unstable and degrade quickly, so supplying them from lactic acid bacteria to the exact site of action is one way to develop them as drugs.

“The potential is really endless when you consider how important a role proteins play in various processes in the body, and how many diseases we currently do not have good enough treatments for. We have already produced another drug candidate to cure and reduce inflammation in the gut of cancer patients – ILP100-Oral – and in the future we will start a research project with another chemokine for the treatment of lung diseases,” concludes Phillipson.

Methods: SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, phase 1 study (EudraCT 2019-000680-24) consisting of a single ascending dose (SAD) part for each participant and a multiple ascending dose (MAD) part for each participant. Both parts of the study each consisted of three dose cohorts. A total of 240 wounds were induced on the upper arms of 36 healthy volunteers, including 4 wounds (2/arm) in 12 participants in the SAD arm, and 8 wounds (4/arm) in 24 participants in the MAD arm. The wounds were randomised for treatment using a placebo, saline or ILP100-Topical. The study was conducted at the Phase 1 unit at Uppsala University Hospital in Uppsala, Sweden, and sponsored by Ilya Pharma.