Atopic dermatitis through midlife

A long-term study of 2 British cohorts with atopic dermatitis (AD) reveals 4 distinct disease patterns occurring between birth and midlife. These patterns include a newly identified subtype that increases in probability with age and is associated with poor general and mental health.¹ The study appeared online September 1 in JAMA Dermatology.

“We’ve seen high rates of [AD] among adults. Yet we don’t fully understand the disease course from childhood,” says lead author Katrina Abuabara, MD, MA, MSCE. She is Associate Professor of Dermatology, University of California San Francisco, and Associate Adjunct Professor of Epidemiology, University of California, Berkeley, School of Public Health.

AD studies commonly focus on children, she says, perhaps following them into teen years. “But understanding that transition and whether the adults we see with [AD] also had it when they were children is very important for understanding what causes, triggers, and perpetuates the disease. There may be different subtypes that we need to treat differently.”

Investigators analyzed data from the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS70), each including more than 17,000 patients. Each cohort had subsequent waves of follow-up occurring at approximately 5- to 10-year intervals. Excluding follow-up years and patients without AD data, the study population included 15,939 and 14,966 subjects, respectively.

The proportions of patients who reported eczema at one or more time points in the NCDS and BCS70 cohorts were 16.7% and 24.4%, respectively. Using latent class analysis and other methods, investigators divided respondents with AD into 4 classes grouped by probability of AD with age—88% to 91% of patients had rare or no eczema symptoms. The corresponding proportions of patients with decreasing, increasing, and persistently high probability of reporting eczema with age were 4%, approximately 5%, and 2% to 3%, respectively.

“The key take-home message is that many people have later-onset disease. Traditionally, we thought of [AD] as a disease exclusively of early childhood onset. But when you extend the window of observation into midlife, there’s a very large group of people who are more likely to have symptoms as they get older.”

The study’s findings are relevant clinically, she says, because when adults present with new-onset eczema, dermatologists often worry that they have missed something. “While it’s appropriate to rule out other causes of the condition, it’s helpful for clinicians and patients to know that it’s not unusual develop disease later on.”

As expected, early-life factors that differentiated groups with eczema from the rare/no eczema group included gender, region of residence, social class, in utero tobacco smoke exposure, and breast-feeding. Compared with the rare/no AD subgroup, female gender was associated with higher odds of the high and increasing AD subtypes, and lower odds of the decreasing subtype.

Additionally, patients from higher social classes and those who were breast-fed were more likely to fall into the high and decreasing AD subgroups. Somewhat counterintuitively, Abuabara adds, breast-feeding was associated with a higher risk of all eczema subtypes, while in utero smoking exposure was linked with lower odds of the high-probability subtype.

Medical literature shows mixed results regarding breast-feeding, smoking, and AD.^2,3 “There there are very clear health risks of smoking during pregnancy, and very clear benefits of breast-feeding. The results we found should not be interpreted as implying otherwise,” she says.

Also somewhat surprising, Abuabara adds, is that in comparisons between all subgroups, only female gender was associated with increased risk of the high-probability versus the decreasing subtype (odds ratio (OR) 1.99; 95% confidence interval (CI) 1.66 to 2.38). “It would be nice to offer parents more information about which subtype their child is most likely to have and what the future will likely hold. Unfortunately, the factors that we often measure in early life don’t seem to reliably predict the different disease courses.”

Having AD conferred increasing odds of other atopic diseases such as asthma and rhinitis in midlife. Patients in the high AD subtype were by far most likely to develop these illnesses over time. However, investigators found that the newly identified subtype was less likely to be associated with asthma and rhinitis. “Because those are part of the diagnostic criteria,” Abuabara says, “it’s important for clinicians to know that it’s possible to have adult-onset eczema and not necessarily have atopic comorbidity.”

Regarding other comorbidities, patients with increasing AD likelihood over time reported poor general health and mental health in midlife. Compared to the rare/no eczema subgroup, ORs for the increasing group were 1.29 (95% CI 1.09 to 1.53) and 1.45 (95% CI 1.23 to 1.72), respectively.

Clinicians must recognize that these patients’ inflammation may be more than skin deep, Abuabara adds. “As we have more research on comorbidities and screening recommendations, these may be the patients that we need to screen more carefully or treat more aggressively.”

The finding of poor general and mental health for the increasing AD subgroup moreover indicates that AD duration and activity may augur outcomes and should be included in studies of AD comorbidities, she says. “If you just examine everyone who’s an adult with eczema and their risk of cardiovascular disease, for example, you may be obscuring some important differences.” Possibly, Abuabara explains, patients with later-onset AD may have a subtype that is at higher risk for cardiovascular comorbidities compared to people whose AD has improved or continued into adulthood.

“Another take-home point is that for a subgroup of patients, the probability of eczema remains high into adulthood. Many older textbooks talk about how most kids with eczema get better by adolescence. There is an increasing recognition that this is an episodic disease that can continue beyond adolescence for a subset of patients.”

The study’s main limitation reflects its statistical strength, Abuabara says, in that researchers lacked detailed information on disease severity and other clinical parameters over time. However, investigators followed 2 cohorts including more than 30,000 individuals for nearly 50 years. “So it’s a trade-off.” Investigators were willing to sacrifice some detail, she says, because a large cohort with long-term follow-up was essential to their objectives.

In previous research, Abuabara and colleagues identified differences between patients who reported childhood-onset versus adult-onset AD.⁴ “We initially had looked at the simple binary classification of whether people first reported symptoms before or after adulthood,” she says. “That’s important clinically because we often think of childhood versus adult-onset disease.” The current paper uses data from a large population at multiple time points to add the nuance of how the probability of eczema development looks over time.

“In general, we are moving towards trying to understand subtypes of atopic dermatitis in many different ways. There’s a lot of work on endotypes or looking at how gene expression profiles differ between subgroups of patients.”^5,6 The present study represents a piece of this work, she says.

“We know that eczema is a heterogeneous disease. And as we get better at understanding all the different subtypes, hopefully we’ll get better at more precisely treating those subtypes. As we have more immunomodulatory drugs on the market—and many on the way—I envision a day when we’ll have methods to better identify which patients would most benefit from which treatments. Some of that will have to do with disease course.”

References:

1. Abuabara K, Ye M, Margolis DJ, et al. Patterns of atopic eczema disease activity from birth through midlife in 2 British birth cohorts [published online ahead of print, 2021 Sep 1]. JAMA Dermatol. 2021;10.1001/jamadermatol.2021.2489. doi:10.1001/jamadermatol.2021.2489

2.Friedman NJ, Zeiger RS. The role of breast-feeding in the development of allergies and asthma. J Allergy Clin Immunol. 2005;115(6):1238-1248. doi:10.1016/j.jaci.2005.01.069

3.Kantor R, Kim A, Thyssen JP, Silverberg JI. Association of atopic dermatitis with smoking: a systematic review and meta-analysis. J Am Acad Dermatol. 2016;75(6):1119-1125.e1. doi:10.1016/j.jaad.2016.07.017

4. Abuabara K, Ye M, McCulloch CE, et al. Clinical onset of atopic eczema: results from 2 nationally representative British birth cohorts followed through midlife. J Allergy Clin Immunol. 2019;144(3):710-719. doi:10.1016/j.jaci.2019.05.040

5. Butler DC, Simpson E, Guttman-Yassky E, et al. The atopic dermatitis spectrum disorder. Recognizing the clinical heterogeneity in patients with atopic related skin conditions in order to improve therapeutic decision-making and outcomes: an expert panel consensus statement [published online ahead of print, 2021 Aug 16]. J Dermatolog Treat. 2021;1-3. doi:10.1080/09546634.2021.1966356

6.Nattkemper LA, Tey HL, Valdes-Rodriguez R, et al. The genetics of chronic itch: gene expression in the skin of patients with atopic dermatitis and psoriasis with severe itch. J Invest Dermatol. 2018;138(6):1311-1317. doi:10.1016/j.jid.2017.12.029

DISCLOSURES:

Abuabara reports grants from Pfizer and personal fees from Target RWE during the time of but unrelated to the study.