The researchers in the School of Pharmacy have created a customizable wound scaffold that delivers natural, biodegradable antibacterials over time to encourage healing. Researchers Michael Repka, distinguished professor of pharmaceutics and drug delivery; Sateesh Vemula, postdoctoral researcher; and doctoral candidate Nouf Alshammari published their results in the European Journal of Pharmaceutics and Biopharmaceutics.

“People with limited mobility or diabetes often have wounds with reduced oxygen supply,” Vemula said. “This can slow the body’s normal repair process and make wounds more likely to become long-lasting, while also increasing the chance that bacteria can grow and lead to infection.”

Chronic wounds, including diabetic ulcers and pressure sores, can linger for months or even years.

Repka and his team are 3D-printing a breathable, patch-like structure that can be placed over the wound. The patch is made using chitosan – a natural material found in crustaceans, insects and fungi – along with plant-derived antimicrobials that help fight germs. Chitosan helps accelerate the growth of skin cells while reducing inflammation and preventing infection.

This structure acts as a scaffold, encouraging growth while also protecting the wound from outside sources of infection or contamination.

“A lot of bandages are made with organic solvents, which actually hurt the wound-healing process, especially when applied intimately on the wound,” Repka said. “With the materials and technique we’re using, you don’t have organic solvents.

“We’re also not using traditional antibiotics over a long period of time, because that can often cause the bacteria to become resistant. That’s the advantage of using natural products.”

Using a 3D printer to create the scaffold means that the patch can be tailored to fit any wound on any part of the body.

“The materials we used are also biodegradable,” Alshammari said. “With time, the scaffold is going to be absorbed into the skin. And it’s an inactive material, so we don’t have to worry about side effects or toxic residuals.”

Being biodegradable also means that if the material is applied to wounds inside the body, health care professionals don’t have to make a second incision to remove it, Vemula said.

The technology can be applied to other types of wounds where a traditional bandage would not be suitable, the Ole Miss researchers said.

“Depending on what kind of wound it is, a regular bandage might work well and this wouldn’t be necessary,” Repka said. “But there are a lot of applications for this technology. These could be printed in the field for, say, military applications.

“If you have a generator that can run these 3D printers, you can print the scaffold you need based on what kind of wound has occurred.”

Before the scaffold can be used clinically, it will need further testing and review by the Food and Drug Administration.

“The goal is translating this from research to patients,” Repka said.

Image: Michael Repka, distinguished professor of pharmaceutics and drug delivery, works with a 3D-printed medical device in his lab in Shoemaker Hall. Repka’s latest research shows that 3D-printed wound scaffolding could aid in healing chronic wounds. 

View more Credit: Photo by Thomas Graning/Ole Miss Digital Imaging Services

He recently earned his PhD in medical science at Lund University and is a senior consultant at the dermatology clinic in Landskrona, Sweden. In one of the studies included in his dissertation, he investigated the links between common blood pressure medications and cases of basal cell carcinoma, a form of skin cancer. This cancer type is very common, with 70,000 newly discovered cases per year in Sweden. It often appears on skin that has been exposed to intense sun.

“Basal cell carcinoma is a rather mild form of cancer, with a low risk of spreading and low mortality. Treatment usually involves surgically removing the tumour, but it’s often also possible to freeze or scrape it away,” says Johan Kappelin.

Previous studies, both Swedish and international, have shown a likely increased risk of various skin cancers in connection with antihypertensive medications. When focusing specifically on basal cell carcinoma, Johan Kappelin used several large Swedish registries to identify possible statistical associations between the disease and blood pressure medication.

There are many different blood pressure medications, grouped by their active substances. These types were included in Johan Kappelin’s study:

• Thiazides (diuretics)
• ACE inhibitors (angiotensin-converting enzyme inhibitors)
• Angiotensin II receptor blockers (ARBs)
• Calcium channel blockers
• Beta blockers

Among those who used thiazides, ARBs, and calcium channel blockers, the risk of basal cell carcinoma appeared to increase by nine percent. For the thiazide group, however, this only applied to medications containing multiple active substances (so-called combination therapy). For beta blockers, the results showed a seven percent increased risk. For ACE inhibitors, on the other hand, no increased risk was found; according to these study results, the risk even appeared to decrease slightly.

Johan Kappelin is somewhat surprised that such similar risk increases were seen across several medication types.

“It’s also a bit surprising that medications containing only thiazides as the active substance did not appear to increase the risk of basal cell carcinoma. At the same time, an increased occurrence of basal cell carcinoma was seen in people who received thiazides as combination therapy. Is the risk found in the other agent, or is it the combination itself that creates the risk?” he wonders.

Other questions requiring further research include whether factors such as skin type and/or certain lifestyle factors contribute to the risk of basal cell carcinoma during blood pressure treatment.

“The increase in basal cell carcinoma risk with these medications is quite small in our study, and at present we see no reason to change any recommendations regarding the use of these drugs. However, there may be reason to be extra careful with sun protection when undergoing blood pressure treatment,” recommends Johan Kappelin.

How the Registry Study Was Conducted

To determine possible statistical associations, researchers compare people with basal cell carcinoma to people without such a diagnosed disease.

The approximately 130,000 patient cases come from the national Basal Cell Carcinoma Registry. The control group consists of roughly twice as many individuals, drawn from the Swedish Population Register. Data on prescriptions for antihypertensive medications come from the Prescribed Drug Register. Researchers also collected registry data on other ongoing medications and other diseases among the included individuals.

Many other factors were not examined in the study, such as skin type or lifestyle factors. Therefore, the researchers emphasize, it cannot be definitively determined that it is the blood pressure medications that cause the increased risk of basal cell carcinoma.

The study involved almost 1,900 women, each of whom had their face and back photographed without make-up. Dermatologists assessed the presence and severity of acne on the basis of the images.

Acne was most commonly found on the face, affecting 26 per cent of participants. About 12 per cent had acne on the back, and 6 per cent had both facial and back acne.

Facial symptoms were particularly concentrated in the lower parts of the face, most commonly on the chin and cheeks.

“The results show that acne is not confined to the face, as back acne is surprisingly common. However, it may easily go unnoticed unless the patient is undressed for examination or mentions it themselves. Skin changes on the back may be mistaken for harmless heat spots, even though they are often acne. Both facial and back acne can lead to permanent scarring if left untreated,” says Suvi-Päivikki Sinikumpu, specialist in dermatology and allergology.

Most acne cases in the study were mild, but more than one in ten participants also had a moderate form. Only very few had severe acne.

Many do not recognise their acne

According to the study, participants had poor awareness of their own acne. Only about one-third of the women whose acne was identified by a doctor reported experiencing it themselves. Recognition was even lower in cases of back acne.

This was also reflected in treatment behaviour: both over-the-counter and prescription acne medications were reported to be used only sparingly. Oral antibiotics and isotretinoin were used very rarely even for more severe types of acne, despite being proven effective and safe treatments.

According to the researchers, poor symptom recognition may partly explain why adult acne is often left untreated.

Adult acne is worth treating

Although acne is often thought of as a teenage problem, it is becoming more common among adult women. The researchers note that in adults, acne symptoms typically concentrate around the chin and cheeks. On the other hand, adult acne may not differ greatly in appearance from teenage acne, and in both groups acne can also appear on the back.

“Even mild acne can significantly affect well-being and mood, and adult acne has been shown to have an even greater impact on quality of life than teenage acne. For this reason, its treatment deserves attention. Acne lesions can also be painful,” Sinikumpu notes.

The researchers recommend that healthcare professionals raise the topic of acne more readily with adult patients. “Patients may leave skin symptoms unmentioned, thinking that doctors consider them trivial problems,” Sinikumpu reflects.

The study was published in the international journal Acta Dermato-Venereologica: Telkkälä A, Jokelainen J, Piltonen T, Huilaja L, Sinikumpu SP. The Prevalence and Characteristics of Adult Female Acne: A Cross-sectional Population-based Study
. Acta Derm Venereol. 2025 Oct 29.

With the unenviable record of the highest melanoma rates in the world – two in three people are diagnosed with skin cancer by the age of 70 – a new approach is needed to reverse this trend, say University of South Australia (UniSA) researchers in the nursing journal Collegian.

Launched in February 2023, the model utilises primary care nurses trained in dermoscopy and artificial intelligence (AI) software to detect suspicious skin lesions. This has been rolled out across 13 South Australian regional and rural mobile clinics with great impact.

More than 1200 people have been screened and hundreds of suspicious lesions identified, including 96 suspected melanoma cases.

The initiative has demonstrated that primary care nurses can detect suspected skin cancer early and consumers overwhelmingly accept this model of care, according to lead author Dr Kim Gibson, from UniSA’s Rosemary Bryant AO Research Centre (RBRC).

“The current reliance on opportunistic, GP-led skin checks leaves significant healthcare gaps for Australians, particularly those living in rural and regional areas who face major barriers in accessing skin cancer screening,” Dr Gibson says.

Each year, more than 2200 Australians lose their lives to skin cancer, with 1400 of these deaths caused by melanoma. The national economic burden is expected to reach $8.7 billion by 2030 if urgent reforms are not introduced.

“In country areas there are serious GP shortages, long waiting times, out-of-pocket costs, and limited access to dermatologists.

“Nurses represent the largest health workforce in regional areas and are ideally placed to bridge this gap. By empowering and equipping them to lead skin cancer detection, we can save lives.”

Since February 2023, the Rosemary Bryant AO Research Centre has trained 51 nurses in dermoscopy (the use of a specialised tool) and AI to identify suspicious lesions and refer for follow-up care. The aim is to educate 600 primary care nurses nationally.

Co-author and RBRC Director, Professor Marion Eckert, says that with additional training, nurse practitioners will also be able to perform biopsies and excisions, further reducing pressure on overstretched medical services.

“This approach is all about reducing inequities. Rural Australians are not only more likely to develop melanoma due to predominately being outdoor workers but are also more likely to die from it. This model tackles that inequity by bringing services to communities and using nurses’ expertise to detect skin cancer earlier,” Prof Eckert says.

The timing of the proposal is significant, given that Australia is currently developing a National Targeted Skin Cancer Screening Program that will focus on high-risk groups, such as those in rural and regional areas.

The UniSA team advocates for nurses to play a central role in this national strategy.

“By embedding nurses into the frontline of melanoma detection, the national program can be more efficient, accessible and cost-effective,” Prof Eckert says.

“Nurse-led models are already improving other areas of healthcare such as breast cancer screening, and skin cancer is a natural next step.”

The research was supported by The Hospital Research Foundation, Preventative Health SA, Skin Check Champions, and Country SA Primary Health Network, with training support from Skin Smart Australia.

‘A nurse-led model of care in response to Australia’s skin cancer crisis: A discussion paper’ is published in Collegian, the official journal of the Australian College of Nursing. DOI: 10.1016/j.colegn.2025.07.002

The findings were presented on Sept. 17, 2025 at the European Academy of Dermatology and Venereology (EADV) Congress 2025.

Lead author Ralf Ludwig, MD, Professor and Director at the Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany, said, “Our findings suggest that GLP-1 receptor agonists may offer benefits beyond their effects on weight and glucose control, particularly for cardiovascular and psychiatric outcomes in people with psoriasis.”

For this retrospective study, the investigators extracted data from the global TriNetX database. They compared 3,048 adult subjects with psoriasis who were treated for diabetes or obesity with GLP-1RA during a follow-up period of 2 years to 3,049 similar subjects treated with other systemic anti-diabetic or obesity drugs for the same period of time.

In matched cohorts of patients with psoriasis treated with GLP-1RA (60.37% females, mean age 56.94 years) versus other antidiabetic and obesity drugs (61.91% females, mean age 56.42 years), GLP-1RA treatment was associated with significantly decreased all-cause mortality (78% decrease, p<0.0001) and reduced risk for major adverse cardiac events (44% decrease, p<0.0001).

Additionally, the investigators reported lower risks for alcohol and substance abuse among subjects with psoriasis treated with GLP-1RA

Adverse drug events were not more frequent in the GLP-1RA cohort.

The authors concluded, “GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or type 2 diabetes.”

Ludwig added, “Psoriasis management has traditionally focused on controlling skin symptoms, but these findings emphasise the need to consider the wider health risks faced by patients. GLP-1RAs may offer a valuable dual benefit, improving both metabolic control and long-term health outcomes, representing an important step forward in holistic care for people living with psoriasis.”

In a study published in the Journal of Dermatologic Science and Cosmetic Technology, a team of researchers from Centre Testing International Group Co., Ltd. And Better Invention (Thailand) Company Limited retrospectively analyzed how skin color, season, and age affect UV protection capability.

“Skin’s UV defense varies significantly with pigmentation, season, and environmental humidity,” explains lead researcher Yu Sun. “Lighter skin showed lower unprotected MED values—indicating higher UV sensitivity—while winter conditions correlated with greater UV tolerance, likely due to stratum corneum hydration changes in cold, dry climates.”

The key finding of the study include:

• Skin color (measured by ITA°) negatively correlated with unprotected MED but not MPPD.
• Age had minimal impact, but seasonal differences were pronounced: higher MED in winter, elevated MPPD in autumn/winter.
• These variations may stem from temperature- and humidity-driven skin barrier adaptations.

“Our study redefines sunscreen testing,” adds co-author Yingge Chen. “Tailoring tests to target demographics’ skin tones and seasonal usage scenarios—like winter sports products tested in winter—ensures real-world efficacy aligns with lab results.”

The team advocates for lab-specific MED/MPPD prediction models to enhance testing precision, accelerating the shift toward precision sunscreens, optimizing UV protection for diverse populations.

The study employed a double-blind, split-face design, comparing the left and right sides of the face and using advanced instruments along with subject self-assessments. The set of instruments used, together with the findings, is reported in the team’s published article in the Journal of Dermatologic Science and Cosmetic Technology.

“Our results indicated that the pterostilbene emulsion remarkably improved skin elasticity, firmness, and reduced wrinkles, such as forehead, undereye, and Crow’s feet wrinkles, shares co-author Zhiyuan Chen, Founder of Guangzhou Luanying Cosmetics Co., Ltd. “It also increased the thickness of the epidermis layer, enhanced collagen and elastic fibers, and minimized skin pores.”

Compared to the control emulsion, the pterostilbene emulsion brought about statistically significant improvements, and all subjects expressed higher satisfaction with the pterostilbene emulsion. These results collectively demonstrated the superior anti-aging efficacy of the pterostilbene emulsion through multiple mechanisms.

According to corresponding author Xueping Chen, the findings advance our understanding of pterostilbene’s role in skincare by providing evidence of its potent anti-ageing effects and supporting its use as an active ingredient in cosmetics. “It also offers a new perspective on natural compounds’ applications in the skincare industry,” says Chen. “The significant improvements in various skin parameters and the subjects’ positive feedback highlight the effectiveness of pterostilbene, which may change the way we approach anti-ageing skincare formulations.”

The authors propose a longer study period to fully understand the impact of pterostilbene.

Publishing in the journal Cancer Research online June 10, the study featured data generated from experiments with human tissues and cells from patients with advanced melanoma that were implanted into mice. Results uncovered therapeutic targets that could limit melanoma growth in patients whose cancer failed to respond to initial treatment with immune checkpoint inhibitors.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the study focused on a subgroup of melanoma patients with mutations in the neurofibromin 1 (NF1) gene. NF1 mutations — random changes in the molecular “letters” that make up this gene’s DNA code — are just one type among several mutations, including those in the BRAF, NRAS, and PARP genes, that are linked to many cases of cancer, particularly melanoma. As many as 27% of melanoma patients are estimated to have NF1 mutations.

While immunotherapy, which stimulates the immune system to attack cancer cells as it would an invading virus, has proved to be a successful treatment, it does not work well for more than half of NF1-mutant melanoma patients.

“There is a pressing need for new drug therapies for melanoma patients with neurofibromin 1 mutations that do not respond to the latest immunotherapy, and for which there are no subsequent effective treatment options,” said study lead investigator Milad Ibrahim, PhD. Ibrahim is a postdoctoral fellow in the Dr. Iman Osman Laboratory in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine.

To investigate why these patients were treatment resistant, investigators examined tumor cells from 30 melanoma patients who did not respond to immunotherapy. NF1 mutations were found in 40% of these melanoma samples. The samples came from NYU Langone’s extensive repository from more than 6,000 melanoma patients.

Molecular testing showed that the signaling pathway built around a protein called epidermal growth factor receptor (EGFR) was more active in NF1 mutant melanoma cells than in cells with other melanoma-gene mutations. Increased EGFR activity has long been linked to abnormal cell growth in tumors and shorter survival with various cancers. The researchers also found that NF1 mutant melanoma cells depended on increased EGFR activity for survival, regardless of the presence of other mutations.

Because EGFR-inhibiting drugs are already used to treat some head and neck cancers, as well as colorectal and lung cancers, researchers then tested two drugs in the class, cetuximab and afatinib, in both NF1 mutant cell cultures and cancer cell lines without NF1 mutations. After transplanting both tumor cell types into mice and treating them with these drugs, results showed that both EGFR inhibitors were effective against cells and transplanted tumors with NF1 mutations, and they had no effect on melanomas without NF1 mutations.

“Our study results reveal a unique vulnerability in melanoma patients with neurofibromin 1 mutations, that an overexpression of the epidermal growth factor receptor pathway is essential for their survival and growth,” said study senior investigator Iman Osman, MD. Osman is the Rudolf L. Baer Professor in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine and a member of the Perlmutter Cancer Center. Osman is also director of the interdisciplinary melanoma program and associate dean of clinical research strategy at NYU Langone.

“While further tests are needed, our results support a novel approach of deploying EGFR inhibitors either alone or in combination with other immunotherapies for treatment of melanoma patients whose tumors harbor NF1 mutation,” said study co-senior investigator Markus Schober, PhD. Schober is an associate professor in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine and a member of the Perlmutter Cancer Center.

However, Schober says this requires further testing in a clinical trial, which the research team plans to develop. He adds that if trial findings prove successful, the team’s research could provide a lifeline for many of these melanoma patients.

Metastatic melanoma, as the disease is formally called, kills nearly 10,000 Americans annually.

Funding for the study was provided by National Institutes of Health grants P50CA225450, U54CA263001, and P30CA016087. Additional funding support was provided by Melanoma Research Foundation grant 1287389.

Besides Ibrahim, Osman and Schober, NYU Langone researchers involved in this study are co-investigators Irineu Illa-Bochaca, George Jour, Eleazar Vega-Saenz de Miera, Joseph Fracasso, Kelly Ruggles, and Jeffrey Weber.

In 2023, Gao’s team cleared the first hurdle toward achieving that goal by showing that a smart bandage they developed could provide real-time data about chronic wounds in animal models, while also accelerating the healing process through the timely application of medication or electrical fields to stimulate tissue growth.

Now Gao and his colleagues from Caltech and the Keck School of Medicine of USC have cleared another hurdle by demonstrating that an improved version of their bandage, which they call iCares, was able to continually sample fluid, which the body sends to wound sites as part of the inflammatory response, in 20 human patients with chronic wounds. These wounds were not able to heal either because of diabetes or poor blood circulation; the researchers also studied additional patients before and after surgery.

The smart bandage, outfitted with three different microfluidic components—miniature modules that channel and otherwise control the flow of liquids—clears excess moisture from wounds while providing real-time data about biomarkers present.

“Our innovative microfluidics remove moisture from the wound, which helps with healing. They also make sure that samples analyzed by the bandage are fresh, not a mixture of old and new fluid. To get accurate measurements, we need to sample only the newest fluid at a wound site,” says Gao, who is also a Heritage Medical Research Institute Investigator. “In this way, iCares can watch in real time for important biomarkers of inflammation and infection.”

Indeed, in a new paper in the journal Science Translational Medicine, Gao and his colleagues show that the smart bandage can detect molecules such as nitric oxide, an indicator of inflammation; and hydrogen peroxide, a biomarker of infection; potentially one to three days before patients experience symptoms.

In a further advance, the team has developed a machine-learning algorithm that can successfully classify the patients’ wounds and predict healing time with a level of accuracy comparable to that of an expert clinician.

The bandage is composed of a flexible, biocompatible polymer strip that can be 3D printed at low cost. It integrates nanoengineered biomarker sensor array, which is disposable for hygiene and single-use applications. The system also includes a reusable printed circuit board that handles signal processing and wireless data transmission to a user interface, such as a smartphone. The triad of microfluidic modules within iCares includes a membrane that sucks wound fluid from the surface of the wound, a bioinspired component that shuttles the fluid across the device onto a sensor array where it is analyzed, and a micropillar module that carries the sampled fluid away to the outside of the bandage.

The co-lead authors of the paper, “A microfluidic wearable device for wound exudate management and analysis in human chronic wounds,” are Caltech graduate students Canran Wang and Kexin Fan. David G. Armstrong, Distinguished Professor of Surgery and Neurological Surgery at the Keck School of Medicine of USC, is a co-author of the study. Additional authors from Caltech include Jose A. Lasalde-Ramirez, Wenzheng Heng, Jihong Min (PhD ’24), Samuel A. Solomon, Jiahong Li, Hong Han, Gwangmook Kim, Soyoung Shin, and Alex Seder; former graduate students Minqiang Wang and Ehsan Shirzaei Sani, who is now at the University of Central Florida, are authors who contributed while at Caltech. Authors from the Keck School of Medicine of USC are Chia-Ding Shih (also of Casa Colina Hospital and Centers for Healthcare in Pomona, California) and David Armstrong. The work was supported by grants from the National Institutes of Health, the National Science Foundation, the American Cancer Society, the Army Research Office, US Army Medical Research Acquisition Activity, and by the Heritage Medical Research Institute. Caltech’s Kavli Nanoscience Institute provided critical support and infrastructure for this work.

Image: A smart bandage that promotes healing and monitors wound conditions is applied to the skin of a human volunteer.

View more Credit: Caltech

Dermatitis is characterized by inflammation, itching, or burning sensations on the skin, and can result from various conditions including TSW and eczema. Eczema, also known as atopic dermatitis, is a common cause of dermatitis and affects 10 to 30% of children and 2 to 10% of adults each year in the United States. Topical steroids—specifically glucocorticoids or topical corticosteroids—have long been used as a first-line treatment for dermatitis caused by eczema because the drugs are safe, effective, easy to apply, and considered well-tolerated.

Some people experience dermatitis after using topical steroids for prolonged periods of time and then stopping—a condition called TSW. Diagnosing and treating this condition is difficult because TSW is not well understood. Symptoms include skin redness, burning sensations, skin heat (thermal dysregulation), itching and peeling, which can even occur on parts of the body where topical steroids were not applied. As TSW and eczema have similar symptoms, it has been difficult to distinguish the two disorders.

To better understand TSW, a team led by scientists in NIAID’s Laboratory of Clinical Immunology and Microbiology evaluated a previous survey that included 1,889 adults with symptoms similar to eczema. By dividing the participants into those with self-reported TSW and those without, the researchers identified characteristics unique to TSW. The researchers then conducted a pilot study including 16 people with symptoms consistent with TSW, 10 people with eczema but no symptoms of TSW, and 11 people without skin disease. They found that people with TSW symptoms had elevated levels of NAD⁺ in their blood serum and skin, while NAD⁺ levels were within a typical range in people without TSW symptoms.

The researchers subsequently used cultured skin cells and a mouse model to mimic TSW conditions. They found that NAD⁺ was produced in response to topical steroids and caused inflammation. The models suggested that administration of a drug that blocked the formation of NAD⁺—called a mitochondrial complex I blockade—would improve TSW symptoms. In a pilot study to further assess this treatment strategy, the researchers evaluated subjective responses among study participants who used the mitochondrial complex I-blocking drugs metformin, berberine, or both. After three to five months of use, most participants reported improvement in TSW symptoms.

The scientists provisionally established criteria that can be used by health care providers to identify TSW in people. People who have stopped topical steroid treatment and meet the criteria may be diagnosed by practitioners as having TSW. The researchers suggest that patients identified as having TSW could be treated using the proposed mitochondrial complex I-blocking drugs.

The results of this study may help practitioners identify TSW in patients and work towards developing safe and effective treatments. According to the researchers, more research is needed to determine whether all patients with TSW have an excess of NAD⁺, or if there are other features that define TSW. Additionally, the diagnostic criteria will help health care providers and researchers to better understand the prevalence of TSW and evaluate the effects of using topical steroids.

ARTICLE: 
N Shobnam, G Ratley, S Saksena et al. Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD⁺. Journal of Investigative Dermatology 10.1016/j.jid.2024.11.026 (2025).

WHO:
Ian Myles, M.D. M.P.H., Principal Investigator, Epithelial Therapeutics Unit in NIAID’s Laboratory of Clinical Immunology and Microbiology is available to discuss this research.

CONTACT:
To schedule interviews, please contact NIAID News & Science Writing Branch, 301-402-1663, niaidnews@niaid.nih.gov.

Topical steroid withdrawal (TSW) is a phenomenon commonly described as extremely red and painful skin arising when cortisone cream treatment is tapered or stopped.

While TSW is not an established diagnosis, the name indicates that the skin has become dependent on cortisone. Little research has been conducted to identify a dependency mechanism, so scientific support is lacking. At the same time, the term has become commonplace on social media, raising concerns among patients about cortisone cream safety.

Now, a national research group in Sweden, headed by Sahlgrenska Academy at the University of Gothenburg, has conducted the first study in which a larger group has been asked to provide a detailed account of what they consider to be TSW.

Questionnaire via social media

The study targeted adults with atopic eczema, a group that often uses cortisone cream, who also identified as suffering from TSW. The study was conducted by means of an anonymous questionnaire presented in Swedish in social media forums, with the option to share a link to invite other potential participants. The questionnaire was answered by almost one hundred people aged 18–39, the majority of whom were women.

“We wanted to gain more knowledge about how those who identify as suffering from TSW define the phenomenon and which symptoms they describe,” says Mikael Alsterholm, a researcher at the University of Gothenburg and a senior consultant in dermatology and venereology at Sahlgrenska University Hospital.

The results, published in the journal Acta Dermato-Venereologica, show variations in how the participants defined TSW. Most common was to define it as a dependence on cortisone, with symptoms arising when tapering or stopping its use, although many others also defined TSW as a reaction to cortisone already during its use.

It was also common to define TSW on the basis of the symptoms seen in the skin, such as redness and pain. While the symptoms described varied, they were largely similar to the symptoms seen in an exacerbation of atopic eczema.

In addition to the skin becoming red, dry, and blistered – mainly on the face, neck, torso, and arms – the participants also described sleep problems due to itching as well as signs of anxiety and depression.

Healthcare and research involvement

A majority of the participants described concurrent symptoms of both atopic eczema and TSW. Cortisone cream was most often cited as the triggering factor, while some cited cortisone tablets and a few cortisone-free treatments.

“It’s important that healthcare professionals and researchers are involved in the discussion on TSW and contribute science-based knowledge where possible. Cortisone cream is an effective and safe treatment for most people, and at present there’s no support for avoiding its use for fear of the types of symptoms described in the context of TSW,” says Mikael Alsterholm.

“At the same time, there’s a patient group with different experiences, expressed as TSW, and their symptoms and the potential causes need to be investigated by means of both research and practical healthcare. To do this, we first need to define TSW. While we understand that this is complicated, we hope that this study can help establish such a definition,” he ends.

Image: Mikael Alsterholm, Sahlgrenska Academy at the University of Gothenburg.

View more Credit: Photo by Karin Olsson

Tapinarof is an aryl hydrocarbon receptor (AhR) agonist. It reduces inflammation and normalises skin barrier function by ligand-dependent activation of AhR, resulting in downregulation of inflammatory Th2 cytokines implicated in AD, modulation of keratinocyte differentiation and increased expression of skin-barrier components, including proteins (filaggrin, loricrin, hornerin, and involucrin) and ceramides.¹

The approval was supported by the pivotal ADORING 1 and ADORING 2 studies. These were double-blind, randomised, vehicle-controlled phase 3 trials (NCT05014568, NCT05032859), that assessed the efficacy and safety of tapinarof cream 1%, once daily, in adults and children of two years of age and older with AD.

The results of the eight-week trials showed that significantly higher proportions of patients achieved the efficacy endpoint (a score of 0 or 1 (clear or almost clear) on the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), along with at least a 2-grade improvement from baseline to week 8).

• ADORING 1: 45.4% with tapinarof vs 13.9% with vehicle (P < .0001)
• ADORING 2: 46.4% with tapinarof vs 18% with vehicle (P < .0001)

Significant improvements were also reported in the secondary endpoints – Eczema Area and Severity Index (EASI) score and the Peak Pruritus Numerical Rating Scale (PP-NRS).  Notably, patients and caregivers reported itch improvement as early as 24 hours after first application of Vtama cream.

Safety

Common treatment-emergent adverse events (TEAEs) (≥5% in any arm) were folliculitis, headache, and nasopharyngitis. Most TEAEs were mild or moderate and were associated with low discontinuation rates. There were few serious TEAEs and none were considered treatment related. Trial discontinuation due to AEs was more frequent in the vehicle arms than with tapinarof.

It is of interest that studies show minimal-to-no systemic absorption tapinarof from the cream under maximal usage conditions, including in children down to two years of age with extensive AD, and in adults with plaque psoriasis and extensive disease.¹

ADORING 3 – Long-term evaluation

ADORING 3, a 48-week open-label, LTE study, enrolled eligible patients from ADORING 1, ADORING 2, and other suitable patients who did not meet pivotal studies’ inclusion criteria.

In ADORING 3, patients (N=728) were followed for up to 48 weeks, with safety and efficacy endpoints that included the achievement of complete disease clearance (vIGA-AD=0), and the achievement of clear or almost clear skin (vIGA-AD=0 or 1). Patients entering with any disease activity (vIGA-AD≥1) were treated with Vtama cream, 1% until complete disease clearance was achieved (vIGA-AD=0) or study completion. For the 378 patients who entered with or achieved complete disease clearance (vIGA-AD=0) in ADORING 3 and discontinued treatment with Vtama cream, the mean duration of the first period of remission was approximately 80 consecutive days. Patients whose AD returned to mild or above (vIGA-AD≥2) were re-treated with VTAMA cream until complete disease clearance was achieved again or study completion. The safety profile with long term use was generally consistent with the safety profile observed at Week 8.

Itch-relief

“Vtama cream approval in AD is important because it can be prescribed for children as young as 2 years old. Vtama cream has the potential to bring much needed relief to a significant number of children suffering from this disease,” said Adelaide A. Hebert, MD, Professor and Chief of Paediatric Dermatology at McGovern Medical School at UT Health Houston and Children’s Memorial Hermann Hospital and lead investigator for the ADORING program. “Moreover, because the prevalence of itch makes this condition extremely burdensome to patients and their families, the itch data from the ADORING program demonstrates reduction of one of the condition’s most prevalent symptoms with use of Vtama cream.”

Take home message

In these 8-week trials, tapinarof cream 1%, once daily was superior to vehicle in the treatment of AD in adults and children. Tapinarof potentially fills a gap in the treatment armamentarium for a highly effective, nonsteroidal topical treatment that can be used down to two years of age without restrictions on the severity of disease, duration of use, total body surface area treated, or sites of application.¹

Reference

1. Silverberg J, Eichenfield LF, Hebert AA et al. Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials. J Am Acad Dermatol. 2024; 94: 457-465