WASHINGTON, DC — The onset of atopic dermatitis (AD) in older adulthood — even in adults aged ≥ 90 years — is a phenomenon documented in the literature in recent years, with reports showing age-related immune differences and differences in risk factors, Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.
"I walked out of residency under the impression that if it didn't start in the first year or two of life, it's not AD," said Silverberg, professor of dermatology and director of clinical research at George Washington University. "The numbers tell us a very different story."
The prevalence of AD in the United States fluctuates between 6%-8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease.
The investigators, including Silverberg, identified 25 observational studies —studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).
The research demonstrates that "the age of onset is distributed well throughout the lifespan," Silverberg said, with the data "indicating there are many elderly-onset cases of true AD as well." (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80).
A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a "fascinating" bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18 to 49 years, after which, "into the 50s, 60s and beyond, you started to see a steady climb again."
Also intriguing, he continued, are findings from a study of outpatient healthcare utilization for AD in which he and his co-investigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).
"The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that's when the disease is more common and more severe but also partially because that's when parents and caregivers are first learning [about] the disease and trying to understand how to gain control," Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns.
"It's fascinating — there's a much greater utilization in the elderly population. Why? The short answer is, we don't know," he said.
Risk Factors, Immune Differences
People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom, Silverberg pointed out.
Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)
Data is limited, but "mechanistically," AD in much older adults appears to have a unique serum cytokine pattern, Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.
Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And "interestingly," compared with healthy controls, older patients with AD had "higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels…and a variety of cytokines related to the Th17, TH1 axes, etc.," he said.
"So, we're seeing a fascinating new profile that may be a little different than younger-onset cases," he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a "decent biomarker" for AD.
[In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients compared with healthy controls.
Research also suggests that air pollution may play a role in the onset of AD in older age, Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.
The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And "to a lesser extent," Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).
The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). "This means that yes, genetics can contribute even to later-onset disease…but environment may play an even more important role," Silverberg said.
In the Clinic
In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, between 2014 and 2019 through pre-visit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Silverberg, a co-investigator of the study.
Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [OR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (adjusted OR, 1.88; 95% CI, 1.05-3.39).
"The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition," Silverberg said. "But it's amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it's our natural inclination to prescribe antihistamines for their sedative properties."
Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that "there's some evidence that high-dose antihistamines may exacerbate dementia."
Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, "I'm a big fan of 'soak and smears'…but you have to ask, can you get out of a bathtub safely?" Silverberg said. "And you have to ask, can you reach the areas you need to [in order] to apply topicals?"
With oral Janus kinase inhibitors and other systemic medications, as with other drugs, "our older population is the most vulnerable from a safety perspective," he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and "a really clean safety profile," said Silverberg, the lead author. "We really need more of these types of post hocs to have some relative contextualization" for older adults.
Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.