“Atopic dermatitis is complicated and quite controversial. Initially, we thought it was primarily a skin problem with a defective skin barrier. Now we know it’s more complex,” says Weily Soong, MD of Alabama Allergy & Asthma Center in Birmingham. “Eczema is an inflammatory process involving the skin, its exposure to environmental and microbial factors, and the immune system.”
Atopic dermatitis demonstrates the complexity of all allergic diseases. “When most people think of allergy, they think of pollen and dander,” Soong says. “I think of allergy as a type of inflammatory state of the body, not just the particular things like pollen and dander that can trigger this allergic inflammatory state. We know that allergy is just one component of eczema. We now know there are genetic predispositions to skin barrier defects, different types of chronic inflammation and allergic triggers involved with the disease. They all play a role, and how they play the role is controversial.”
Atopic dermatitis is one of the biggest factors in the development of allergic rhinitis, food allergies, and asthma. “We call it the allergic march. The organs affected by allergies march from the skin to the nose, to the lungs and sometimes to the gut,” Soong says. “With infants, we worry about cases of eczema because it is the biggest risk factor in the development of asthma. This can happen quickly in the first six years of life. We also know that eczema is one of the major risk factors for the development of peanut allergies so those children should be allergy tested early.”
Typically, eczema is treated with lotions and topical steroids. Some moderate to severe eczema patients will need more than that, and usually are treated with immuno-suppressants like cyclosporin and methotrexate. However, recent studies have shown that the inflammation in most moderate to severe cases of atopic dermatitis is driven by T-helper 2 (Th2) cells that release IL-4 and IL-13 cytokines.
“We know that Th2 starts the allergic pathway, and a drug called Dupilumab – an anti IL-4 receptor – is being developed to fight that inflammation,” Soong says. “The antibody blocks the signaling production of IL-4 and IL-13. It has shown great results for a good percentage of moderate to severe eczema patients.”
Soong thinks that eventually there will be multiple subsets of atopic dermatitis and that a majority of them, especially the moderate to severe cases, are Th2 driven. “That’s why Dupilumab has worked well so far. Researchers discovered that a majority of moderate to severe eczema patients had very high Th2 markers. The preliminary clinical trials in adults have been very promising, and if everything goes well, Dupilumab might become a game changer in the treatment for atopic dermatitis.”
Dupilumab is still being tested, but Soong looks forward to having another option for patients. “Dupilumab might be the first biologic used specifically for the treatment of atopic dermatitis. Because it targets a specific type of inflammation, we hope it will have fewer side effects compared to other non-specific immuno-suppressants,” he says. “Also, other biologics being developed for other allergic conditions, like asthma, are being looked at for their use in atopic dermatitis treatment.”
Continuing research will focus on the identification of the different phenotypes of atopic dermatitis. “We hope to identify which ones are allergic, which are not allergic, and which cytokines drive atopic dermatitis,” Soong says. “That will be key because those findings will tell us how we should best treat each subset of the disease.”
Soong acknowledges the enormity of this research effort, but he says it is greatly needed. “I think people underestimate the morbidity of this disease. It’s not a disease that will kill you, but there are children and adults who suffer from chronic itching all over their bodies. The itching and the rash cause both physical and psychological burdens for these patients,” he says. “Chronic itching is agony for those affected, and I can’t imagine what these people go through. I’m glad atopic dermatitis is getting a lot of attention now, because people are realizing how bad this disease can be.”