Alopecia Areata and its Connections With Atopic Dermatitis

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In this insightful interview, Dr Emma Guttman-Yassky sheds light on the intricate nature of alopecia areata (AA), exploring its diverse phenotypes and connections with atopic dermatitis (AD). Addressing challenges and considerations in managing patients with these conditions, Dr Guttman-Yassky offers practical guidance and emphasizes the importance of comprehensive patient assessment.

The Dermatologist: Can you discuss the complexities of AA and its various phenotypes?

Dr Guttman-Yassky: Alopecia is much more complex than we used to think because we were thinking about it as one size fits all. And now we understand there are multiple clinical phenotypes that also may have some differences in their immune abnormalities. For example, we now know that patients who have an allergic background, either AD, or asthma, or a familial allergic background, in addition to alopecia have more of a tendency to have a type-2 immunity. And we know that with disease chronicity, for example, more chronic diseases are associated with more type-1 abnormalities. So, we are still learning about AA, its different phenotypes, and how these affect response to treatment and across different treatments.

The Dermatologist: Can you discuss the commonalities between AA and AD? How do you consider these connections in your diagnostic and treatment approach?

Dr Guttman-Yassky: I always like to say that I got into AA a little bit through the back door. I come from the world of AD, and I started to notice that many of my patients with AD also had AA. That was at a time when AA was considered to be a purely type-1 immune disease. And AD and allergic diseases are type-2 immune diseases. So, something did not make sense to me. And then I started to notice that some patients who were on the dupilumab trial for eczema at our site happened to also have AA. And we started to notice that in at least some of them, they grew hair. So, then I said, let me do a little bit deeper dive into AA.

I pulled all the literature and, like I tell my residents, sometimes you find your answers in older literature. But I did not need to go back that much. I found quite a few publications basically pointing to the idea that the comorbidity associated the most with AA is allergy in general and AD or eczema in particular. Then I saw an important publication showing that IL13 is the gene mostly associated with AA, both in patients with and without AD. And then I also looked at some other publications showing that type-2 biomarkers such as IgE are increased in AA.

So, then I said, okay, dogmas sometimes need to be challenged. And I said, let me do my own study on AA. One thing that is important to mention is the studies done up to that point were mostly in mice. And the few studies in humans were with very few patients. There was not a big study that was comprehensive in patients with alopecia. We set a study that had almost 30 patients with AA in which we took scalp biopsies and we compared to patients with AD and psoriasis. We found that the profile in the scalp of patients with AA was quite similar to patients with AD in terms of the type-2 immunity.

Type-1 immunity is upregulated in all of 3 of these diseases, AA, AD, and psoriasis. And later we associated the type-1 immunity with chronicity of AA, whereas the type-2 immunity we associated with the severity of AA. We have also done a study in patients with AA on dupilumab and we showed that it helps those patients who have atopy or those with high Ig. This led to many other studies, including a study in children with AA and in adults who have atopy. So, this is a good example of how you take an idea from the clinic, bring it to the laboratory, and drag it back to the clinic because at the end of the day, we want this to benefit patients.

The Dermatologist: In your experience, what are some of the challenges and considerations when managing patients with AA and its comorbidities such as AD? How do you navigate these complexities in your clinical practice?

Dr Guttman-Yassky: This is an excellent question. The challenge is that you need to really understand patients with AA because it takes a big emotional toll. I think it is important to address their expectations. We need to tell them that there are many new treatments that will help, but it is not going to happen tomorrow. It is important they understand that before we say no to an agent and go to a different one, we need to exhaust at least 6 to 12 months because some agents for AA like dupilumab, and even the Janus kinase (JAK) inhibitors, take time. So, the challenge is to explain to them that unlike AD, where you may see results in 4 to 8 weeks, AA treatment is kind of like a marathon.

The Dermatologist: What advice or guidance can you provide to fellow practitioners who encounter patients with AA or AD? Are there any specific considerations or best practices to keep in mind?

Dr Guttman-Yassky: Think about whether the patient has only AA or has comorbidities like allergic comorbidities, and then think if these comorbidities are significant enough to put a patient on a treatment. And then try to think about classes of conditions together. You need to ask patients whether they have asthma because this will impact the consideration. For example, for a patient who has AD, asthma, and AA, you can think about dupilumab either in a study or through insurance. For a patient who does not have these comorbidities, you will think about a JAK inhibitor. It is important to understand the patient as a whole, not only the AA portion.

The Dermatologist: What are the key takeaways or important points you would like fellow practitioners to remember about the complexity of AA and its relationships with AD?

Dr Guttman-Yassky: The thing about AA is that it is a complex disease, and you need to really question patients carefully. For example, if they had eczema in childhood, if they have anybody in the family with atopy, if they have another atopic condition like asthma, hay fever, and so on. It is important to have these discussions and not just say, “You have alopecia.”