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Neurodermatitis therapies: New drugs promise relief from the skin disease

Jonathan Edward by Jonathan Edward
October 11, 2021
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Neurodermatitis therapies: New drugs promise relief from the skin disease
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Extremely dry and reddened skin that flakes and, above all, itches unbearably: for people with neurodermatitis, these symptoms are often all too familiar. The chronic disease is one of the most common skin diseases and so far cannot be cured. For moderate and severe cases in particular, two new forms of therapy now promise relief.

Neurodermatitis limits self-protection of the skin

In Germany, about 3.5 million people have neurodermatitis, including about 1.3 million children. In most of them, the disease, which is presumably genetically determined, already manifests itself in infancy and toddlerhood, but improves in the majority of patients in the course of their lives. A number of trigger factors can promote the onset of the chronic inflammatory skin disease.

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The climate, for example, plays a role: considerably more people are affected in sunless, cooler regions than in warmer climates, and the symptoms can also be more pronounced in winter than in summer. In both cases, lower humidity promotes the drying out of the skin – however, those affected should avoid this at all costs. In the case of neurodermatitis, the skin’s self-protection is limited and the immune system is out of balance. As a result, the skin loses moisture due to the impaired barrier function, becomes dry, itches and reacts sensitively. If it is then scratched open, bacteria, viruses and fungi can penetrate more easily.

Consider trigger factors in everyday life

Finally, sensitization can occur. As a reaction, the immune system produces more defensive substances – even against actually harmless allergens such as pollen, cosmetic products or animal hair. The defensive substances in turn fuel the inflammatory process by stimulating other immune cells to release pro-inflammatory substances. “The result is a vicious circle of itching and scratching, which is therefore based on the one hand on a disturbance of the skin barrier and on the other hand on an immune disorder,” summarizes Peter Elsner, Director of the Clinic for Skin Diseases at the University Hospital Jena.

According to Elsner, also spokesman for the German Dermatological Society (DDG), the predisposition to neurodermatitis is widespread in Germany: “About one third of people in this country have such an atopic disposition,” he explains. However, this initially only means that one must learn to deal with this predisposition by taking trigger factors into account. Apart from the climatic aspects already mentioned, this includes airborne allergens such as pollen, grass and animal hair, but also frequent hot baths or showers.

Mild atopic dermatitis can be treated well

If “atopic dermatitis” or “atopic eczema”, as the disease is actually correctly called, does break out, it manifests itself in very different degrees of severity and courses. While in some people it is mainly the typical areas in the crooks of the elbows and backs of the knees as well as the hands that are affected, other people experience atopic dermatitis all over the body. Symptoms can range from skin redness to fine skin cracks and skin thickening to inflamed, weeping and bleeding areas.

“Mild atopic dermatitis with itching and dryness can usually be treated well in a basic therapy with a simple care cream containing urea or glycerin, or even UV light,” lists physician Elsner. In contrast, more severe cases require systemic, i.e. internally acting, therapy. “Until two to three years ago, there were only two options for this,” explains Elsner: “One was the use of internal cortisone, and the other was treatment with the immunosuppressant ciclosporin, which actually comes from transplant medicine.” Both drugs would achieve good results against the disease, but were associated with sometimes severe side effects. “We had always hoped for agents that act directly on the inflammatory processes,” the dermatologist said.

New neurodermatitis drug in clinical development

Two new therapies in the form of specific antibodies and so-called small molecules now offer precisely this. The antibody-based therapies, also known as “biologics,” include dupilumab, which has been approved since September 2017 for treatment in adults and since November 2020 also for children aged six and older with moderate to severe atopic dermatitis. The active ingredient blocks two central proteins of the immune response and thus neutralizes their pro-inflammatory effects.

Tralokinumab, which was approved as a drug in the EU in June this year, is also based on this principle, as are other biologics currently in clinical development. “The advantage of dupilumab is that we now have an option for those with severe disease that works very well in 60 to 70 percent of patients,” explained Michael Hertl, DDG president and director of the Department of Dermatology and Allergology at Marburg University Hospital, in a statement on World Neurodermatitis Day (Sept. 14).

Neurodermatitis can cause learning disorders in children

In addition, the biologics approved so far are very well tolerated, adds Peter Elsner: “About one fifth of patients report burning eyes or eye inflammation as annoying but harmless side effects, which many accept because the agonizing itch is finally gone.” In fact, the consequences of severe atopic dermatitis are serious for some sufferers. “The symptoms can massively reduce the quality of life of those affected if severe. At night, itching and pain disturb sleep, and the visible skin changes are perceived by some in the social environment as ‘repulsive,’ which can lead to stigmatization,” says Ralph von Kiedrowski, president of the Professional Association of German Dermatologists (BVDD) and a dermatologist in private practice in Selters.

Studies from Denmark and the U.S. also suggest that atopic dermatitis in children is associated with learning disabilities and poorer academic achievement. “This shows that neurodermatitis is a disease that extends far beyond the skin,” Peter Elsner emphasizes. This makes new treatment options such as biologics all the more welcome, although they have to be injected. This is not an option for all patients: “Here we have another new therapy option in the form of Janus kinase inhibitors.” These JAK inhibitors are small molecules that inhibit signal transduction in the cell with the effect that the inflammation can subside. “The JAK inhibitors show a very specific effect with few side effects,” Elsner describes. What’s more, the active ingredients, which are approved for adults, can be taken in tablet form.

Understanding of inflammatory mechanisms is improving all the time

Both forms of therapy – biologics and the small molecules – are primarily suitable for severe cases of atopic dermatitis, he said, but in some cases they achieve rapid success. “Some patients report drastically reduced itching after just a few days and can sleep through the night for the first time in a long time,” says DDG spokesman Elsner. For him, the new therapies are not least the result of a now increasingly better understanding of the inflammatory mechanisms underlying the skin disease: “This better understanding allows us to intervene in a more targeted way.”

In addition, studies are no longer carried out over just a few weeks, but in the form of long-term studies, some of which run for three to five years – a procedure that is absolutely necessary in the case of a disease that often progresses in episodes. And finally, the disease is now viewed and treated in a more holistic way, which also benefits patients with mild or moderate symptoms: “In therapy, it is now a matter of course to pay more attention to psychosocial factors, which include the patient’s quality of life and his or her overall well-being,” Elsner describes.

Disease requires individual therapy

This aspect is also part of the neurodermatitis training courses recommended in the DDG guideline, in which those affected learn how to deal with the disease, which has so far been incurable. “This is particularly important for the long-term management of the disease,” says Elsner. In addition, a balanced lifestyle, an appropriate diet and strategies for coping with stress would have a helpful effect.

The dermatologist, however, does not think much of alternative medicine or homeopathic promises of healing without scientific proof of efficacy, or of “neurodermatitis diets” which, for example, call for a blanket renunciation of eggs or milk. “Of course, there are patients who react to certain foods with a flare-up – but these should then have an allergy test done for clarification,” he emphasizes. In general, the disease has a very broad spectrum and requires an individual therapy: “No neurodermatitis is like the other. That’s why it’s all the more important that we have different therapy options.”

 

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