Eczema: Studies for New Treatment

We face a very exciting and very optimistic time in the treatment of eczema, or atopic dermatitis (AD). Initially we thought eczema — an inflammatory skin disease that affects four to seven percent of adults, and 15 to 25 percent of children worldwide (with the highest numbers in Asia) — was caused by defects in the epidermal skin barrier, or the outer layer of the skin. Now we know that eczema is an immune-driven disease that in turn causes secondary defects in the epidermal barrier. That’s a real paradigm shift.

A substantial proportion of the U.S. population, 31.6 million, has eczema; at least 17.8 million have moderate to severe cases. The prevalence of childhood eczema in the U.S. is 10.7 percent overall and as high as 18.1 percent in some states. For many years, eczema was considered mainly a disease of childhood; 85 percent of the time, it begins in early childhood. A recent study found that the prevalence of eczema in adults is 10.2 percent, which suggests that most children with eczema continue to be affected even in adulthood.

In eight out of 10 cases, eczema has a genetic background and a family history of eczema, seasonal allergies or asthma. I grew up in Romania and Israel and had eczema as a child. It was never so severe that I needed systemic treatments; it was mainly treated topically. Now I still get it in winter, as does my daughter, who’s 11; we treat hers with topical steroids. When she was younger, she really had it all over. (My son, who’s 15, has asthma.)

My daughter and I both get eczema more in winter. Eczema generally exacerbates in winter, when it’s dry, or in the summer, when there is increased sweating. An intractable itch, which affects sleep and daily activities, is associated with eczema. Increased accidents, due to lack of sleep, are often reported in both patients and parents.

There are still very large unmet needs for the treatment of patients with eczema.

Current treatments for eczema are still limited:

  • Oral prednisone has multiple side effects, and the moment you stop taking it, the eczema returns.
  • Cyclosporine suppresses the immune system, but its possible side effects include kidney damage after one to two years of treatment.
  • Phototherapy, or light therapy, is effective for most patients, but requires that patients come to the doctor’s office three times a week.

Latest Eczema Treatment Research

My research, which started at Rockefeller University and now continues at Mount Sinai, has provided the most comprehensive molecular maps available today of the mechanisms of eczema, mapping out the immune circuits characterizing this disease and the accompanying barrier defects. My laboratory is composed of postdocs, medical students, research associates, and clinical fellows working on the clinical front. I also have wide collaborations with other institutions, particularly with the Investigative Dermatology Laboratory at the Rockefeller University, and with national and international institutions and investigators.

Until a few years ago, eczema was believed to be driven by a type of white blood cell called Th2 lymphocyte. Lymphocytes produce inflammatory molecules, and normally these molecules are produced in low amounts required for maintaining a steady state. In eczema patients, the lymphocytes are activated and overproduce inflammatory molecules, ultimately leading to skin inflammation. In 2009, I was the principal investigator of a studythat found that a novel, previously unreported lymphocyte, T helper 22 or Th22, plays a key role in eczema. Th22 cells produce interleukin 22 (IL-22), an inflammatory product that has major effects on the epidermal barrier, such as thickening and abnormal differentiation, ultimately weakening the skin barrier. Thus, the effects of this cytokine might link the barrier and immune defects in eczema.

We are currently testing in clinical trials at Mount Sinai Dermatology several treatments that target not the whole immune system but specific molecules in the immune system. Some of our studies are part of larger clinical trials being done on a national or international level, but for some we are a single center or part of a few centers (together with Rockefeller University, for example) performing these trials. One of these ongoing trials, recently funded by the National Institutes of Health, is the first to explore the biological effects of blocking the IL-22 molecule on eczema disease activity and associated skin pathology. We have enrolled in these studies approximately 60 patients in the course of the last year, with new studies opening up this year that will offer many opportunities for patients to participate in these trials.

Using cyclosporine A, which suppresses the entire immune system, we were able to reverse the barrier pathology of the disease (skin thickness, and increased permeability of the skin barrier leading to penetration by irritants and allergens, and increased inflammation and itching). We are now testing treatments that specifically target the immune pathways involved in the immune activation in eczema, namely Th2, Th22 and others. Some of them, such as dupilumab, a biologic (meaning it is made from living cells), are showing great promise in terms of both safety and efficacy in early trials. These treatments are given either subcutaneously, intravenously or orally. There are also a few topical treatments for patients with milder forms of the disease.

Another study my laboratory is involved with, in collaboration with Dr. Amy Paller, a pediatric dermatologist and the chair of dermatology at Northwestern University Feinberg School of Medicine, aims to find out whether eczema in children and adults are comparable. This study is crucial in finding out whether we are dealing with a single disease in children and adults, and in developing drugs to target the pediatric population.

The new therapies will likely start becoming available in two to five years, pending the outcomes of clinical trials and then government approvals. In 10 years, I believe, we should have a wealth of new, safer and effective systemic and topical medications. Although emollients and barrier-targeting creams will still be important, we do need to target the immune system to be able to treat the disease effectively.