Breakthrough Treatments for Severe Eczema
Recent eczema advances have helped tremendously, but it turns out, they’re just scratching the surface. Here, a look at what’s next.
Severe eczema isn’t just a skin issue; it’s a quality of life issue. It’s an itch that can wake you from the deepest sleep—and keep you up for hours. It’s painful (and embarrassing) red, crusty skin that can make you call in sick to work. It’s topical treatments that don’t deliver lasting relief, making you feel completely hopeless.
Moderate-to-severe eczema, which affects 3.2 million of the 31.6 million adults and children in the US who have the chronic inflammatory condition, can be both physically and emotionally draining. So, having new options to get—and keep—skin clear and calm is a very big deal for patients and doctors alike. “It’s a really exciting time with several revolutionary therapies emerging,” says Emily Milam, M.D., instructor of dermatology at the Ronald O. Perelman Department at NYU Grossman School of Medicine in New York City. Follow along as we take a closer look at some of these breakthroughs and find out what they mean for your skin—and sanity.
Recap: What’s Severe Eczema?
Eczema is really a bucket term for all sorts of itchy, rashy, inflammatory skin conditions. There are seven different forms of eczema ranging from contact dermatitis (rashes from something your skin touches) to statis dermatitis, a painful condition that occurs when fluid leaks from your veins under your skin. The most common form (and the one used interchangeably with eczema) is atopic dermatitis (AD), marked by sore, painful patches of itchy skin that flares when triggered. It’s thought to be a combo of an immune response and an impaired skin barrier (the outermost layer, which seals in moisture and plays a protective role against irritants and allergens).
So, what makes eczema severe? When diagnosing, dermatologists consider how much surface areas it covers (usually more than 10% of the body), its resistance to topical treatments, how long flares last, and, in the new age way of thinking, patient experience, says Adam Friedman, M.D., professor and chair of dermatology at George Washington University School of Medicine and Health Sciences in Washington, D.C. “We have so much data on the burden of disease and how impactful it is on quality of life,” he says.
In a recent study published in the Annals of Allergy, Asthma & Immunology, AD limited lifestyle, led to less social interactions, and impacted activities. The same study showed that eczema presented a worse quality of life than other chronic conditions including diabetes and high blood pressure. In severe cases, the itch and pain from eczema is excruciating, unrelenting, and stressful. “Patients are worried about the next flare while they’re still in the middle of their current one,” he says. For these people and their doctors, new drug treatments offer new hope.
The last breakthrough in care for severe eczema came in 2017 when a drug called dupilumab hit the scene. “Dupilumab is a type of ‘biologic,’ or a drug that acts as an antibody to block certain immune system cells, or cytokines, that cause skin inflammation,” says Dr. Miliam. It’s an injectable treatment dosed every two weeks, which, more specifically, blocks signals interleukin (IL) 4 and 13, cytokines that turn on itch and rashes. It’s approved for adults and children as young as age six. Since its FDA approval, the race has been on for additional biologics that can offer long-term relief for severe eczema patients. There are currently 25 different biologics in development.
Biologics, like dupilumab, are very specific. “They target one single molecule,” says Emma Guttman, M.D., director of the Center for Excellence in Eczema in Mount Sinai Hospital in New York City. “For this reason, they’re very safe compared to eczema drugs we don’t use anymore, such as oral prednisone, which targeted everything, and so you had a lot of side effects,” she says. They also pose less serious side effects than immunosuppressants, which have been used for severe eczema.
Some new biologics coming down the pipeline focus on a similar pathway as dupilumab and work to block interleukin-13 and its receptors. Tralokinumab and lebrikizumab are both in phase III of their trials. In published studies on tralokinumab, eczema patients saw improvement by week 16, and continued improvement at one year. Lebrikizumab was also effective at 16 weeks, but less itch was reported at just two days.
Nemolizumab, another biologic in the works, targets a different receptor, IL-31, which is found on nerve cells as well as immune cells that are involved in the sensation of itch, says Dr. Milam. Those immune cells also play a role in preventing a healthy skin barrier. In phase II trials, researchers saw an improvement in their eczema in just four weeks.
JAK Inhibitors for Eczema
Another ground-breaking class of eczema meds are oral drugs called JAK Inhibitors, which are currently being reviewed by the FDA for the treatment of moderate-to-severe eczema. “Janus kinase (JAK) proteins are a family of receptors, or immune system ‘switches,’ that signal a cascade of inflammation, says Dr. Milam. “JAK inhibitors help prevent the domino effect of inflammatory cells that otherwise elicit eczema-related inflammation.”
How do they differ from biologics? JAK work along different parts than biologics do from start to finish. Those inflammatory molecules, cytokines, that we mentioned, interact with what’s known as the JAK-STAT pathway, which is found inside our cells. By targeting JAK enzymes (there are four in all), you can reduce the amount of cytokines, which means you reduce inflammation and itch.
Things to note: Unlike biologics, oral JAK inhibitors do require blood monitoring, and there are some safety concerns especially with the risk of infection and blood clots, says Dr. Freidman. There are JAK inhibitors already being used in dermatology for psoriatic arthritis. Three coming soon for AD: abrocitinib, baricitinib, and upadacitinib.
A topical JAK inhibitor, ruxolitinib, is also close to approval for AD, and the data is impressive. In trials, 50% to 60% of patients on the topical had an improvement in symptoms compared to 14% on a non-medicated cream. And unlike the oral drugs, the topical JAK inhibitor doesn’t require blood monitoring. The safety hasn’t been established yet for children, but according to the National Eczema Foundation, one or more may be approved for kids.
The Cannabinoid Calm
Another area gaining buzz in the treatment of eczema is topical cannabinoids such as THC and CBD. Two small studies published in the Journal of Drugs and Dermatology and Dermatology Online Journal showed promising results with a cannabinoid-containing gel.
“From a biological standpoint, cannabinoids could work on eczema,” says Dr. Freidman. “Simply put, eczema is a horrible relationship between immune dysfunction and skin barrier dysfunction,” he says. “And if you pick the right ones, cannabinoids can address both of those things.” Cannabinoids are not anti-inflammatory, he says. “They’re pro-inflammation resolution,” he says. “Which means they help resolve inflammation and regulate how the skin makes itself.”
The key—and the challenge—is getting them into the skin. The CBD and THC molecules have to be small enough to penetrate skin deeply enough to produce an effect. Dr. Friedman is currently working on a nanoparticle formulation of CBD for skin lupus, so, if successful, this may be an emerging category in eczema and other severe skin conditions.
Which Treatment Is Right for Your Severe Eczema?
It may take a little trial and error to know for sure. “Eczema is a multifaceted disease and thus its treatment is not a one-size-fits all approach,” says Dr. Milam. “Some of these agents may work for certain patients, and not others, have limiting side effects, or even lose their efficacy over time if the body develops an immunity to the drug, she says. Still, it’s an exciting time for this challenging skin condition, and these breakthroughs are sure to change the rough and bumpy landscape of eczema.
Eczema Stats: Allergy & Asthma Network. (n.d.). “Eczema (Atopic Dermatitis0 Statistics.” https://allergyasthmanetwork.org/what-is-eczema/eczema-statistics/
Quality of Life and Eczema: Annals of Allergy, Asthma & Immunology. (2018). “Patient Burden and Quality of Life in Atopic Dermatitis in US Adults.” https://www.annallergy.org/article/S1081-1206(18)30567-2/fulltext
Biologic Background: National Eczema Association. (2021). “ Biologics are Changing the Landscape of Eczema Treatment.” https://nationaleczema.org/biologics-eczema-treatment/
JAK Inhibitor Background: National Eczema Association. (2021). “JAK Inhibitors are Coming and They Are the Biggest Development in Years.” https://nationaleczema.org/jak-inhibitors-research/
Topical JAK Inhibitor: Frontiers in Immunology. (2019). “Emerging Topical and Systemic JAK Inhibitors in Dermatology.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901833/