Speaker: Emma Guttman-Yassky

Adult-onset atopic dermatitis (AOAD) is characterized by the onset of atopic dermatitis symptoms for the first time in adulthood, specifically after age 18. This emerging phenotype is becoming increasingly recognized, particularly as the understanding of atopic dermatitis shifts toward personalized medicine. It is important to note that atopic dermatitis is humans' most common inflammatory skin disease, with a lifetime prevalence of approximately 20%. In developed countries, 5-8% of adults are affected by atopic dermatitis, which imposes a multifaceted burden on individuals, impacting their sleep, mental health, quality of life, and productivity at work or school.

A significant subset of adult patients, between 25% and 50%, experience AOAD, highlighting the necessity for tailored treatments based on the specific needs of this population. Epidemiological studies have shown that the onset of atopic dermatitis is well-distributed across all ages, including older adults. 

Traditionally, most adult cases were thought to originate in childhood; approximately 85% of pediatric-onset atopic dermatitis (POAD) cases occur before the age of 5. While many believed these cases would remit, studies now indicate that 20% to 50% of childhood cases persist into adulthood. AOAD presents with distinct clinical features compared to POAD, including atypical manifestations such as prurigo nodularis, nummular eczema, and follicular eczema. Commonly affected areas include the face, neck, scalp, hands, and feet, with many patients presenting with diffuse eczema. AOAD is also sometimes associated with vesicles and nodules and may exhibit the Hertoghe sign, the loss of the outer third of the eyebrows. Interestingly, AOAD is less frequently associated with pruritus and xerosis than POAD. Understanding these differences in phenotypes and clinical presentations is crucial for developing effective, individualized treatment strategies for patients with AOAD. AOAD is associated with several risk factors, particularly active and passive smoking while exhibiting less correlation with personal and familial atopy. This suggests that, although there is some association with atopic comorbidities, it is not as pronounced as in pediatric populations. 

Differential diagnosis is critical for clinicians evaluating suspected AOAD, as conditions such as cutaneous T-cell lymphoma must be considered, especially when the rash appears later in life. In such cases, a biopsy may be necessary to rule out this serious condition, along with other diagnoses like photosensitive dermatitis, plaque psoriasis, allergic contact dermatitis, and transient acantholytic dermatosis. The exposome, which encompasses various environmental factors such as pollution, diet, and stress, plays a significant role in the trajectory of atopic dermatitis from infancy to adulthood. In adults, factors like pollution, stress, smoking, and alcohol consumption should be assessed during patient evaluations, as they can influence disease progression and management.

Atopic dermatitis is now considered as a spectrum of endophenotypes shaped by numerous factors, including age of onset, ethnicity, skin tone, and IgE levels. While these variables contribute to the immune and barrier abnormalities observed in patients, they also reflect the treatments required. Common to all subtypes is the robust T-helper (Th) cell activation, particularly Th2 and Th22 activation associated with biomarkers such as IL-4, IL-13, and IL-22. However, distinct differences exist between age groups: infants exhibit significant Th3 activation, while adult cases show greater Th1 activation, indicating chronicity of the disease. Research conducted with various age groups, including infants, children, adolescents, and adults, has underscored these distinctions. A study on molecular profiles in skin and blood has been published, highlighting the epidemiological and clinical differences between adult-onset and pediatric-onset atopic dermatitis. 

The study focused on the differences between AOAD and pediatric-onset atopic dermatitis, establishing a clear population definition for adult cases as individuals over the age of 20 diagnosed after this age with moderate to severe disease (SCORing Atopic Dermatitis, SCORAD score > 25; Investigator's Global Assessment, IGA > 3). Exclusion criteria included a personal history of atopic dermatitis or other atopic comorbidities. Pediatric-onset cases were defined as having the condition begin before age 10, with similar severity criteria applied. Healthy controls were matched to both patient groups. All participants underwent skin biopsies and serum sample collection, with subsequent analyses including Ribonucleic Acid (RNA) sequencing, Polymerase Chain Reaction (PCR), immunochemistry, and proteomic studies. The demographics of the study population showed a predominantly white cohort, consistent with the collaboration's nature, and revealed that adults with AOAD had higher rates of hypertension, cardiovascular disease, elevated lipid levels, and diabetes, paralleling existing literature. Histological analysis indicated that pediatric-onset patients exhibited greater epidermal hyperplasia, increased epidermal thickness, elevated keratin 16 levels, and higher inflammatory cell infiltrates in lesional and non-lesional skin. Interestingly, the non-lesional skin of adult patients displayed greater inflammation compared to that of their pediatric counterparts.

Molecular profiling revealed high immune activation in pediatric and adult-onset atopic dermatitis, although pediatric lesions exhibited more pronounced inflammation. The adult-onset group demonstrated a significant Th1 skewing, indicative of chronic disease, while pediatric cases were characterized by Th17 skewing. 

Furthermore, epidermal barrier defects were more pronounced in pediatric-onset patients, possibly attributable to the longer duration of the disease. Correlations between immune gene expressions and disease severity were identified, with variations between adult and pediatric subtypes. Systemic immune activation was markedly higher in adults, correlating with cardiovascular risk factors and markers indicative of atherosclerosis. Notably, Th1 biomarkers exhibited strong correlations in the adult-onset group's skin and blood samples. In adults, cardiovascular and atherosclerosis markers significantly correlated with disease severity, whereas pediatric patients showed stronger correlations with immune markers related to Th2 pathways.

In conclusion, while adult-onset atopic dermatitis shares key characteristics with pediatric-onset forms, including significant Th2 and Th22 immune dysregulation, critical differences were observed, notably greater Th1 skewing and systemic inflammation in adults, pediatric-onset patients presented more substantial barrier defects and inflammation. Adult-onset atopic dermatitis demonstrated a higher expression of inflammatory and cardiovascular risk proteins. This underscores clinicians' need to consider these differences when selecting treatments, particularly regarding potential systemic effects and cardiovascular health.

33, European Academy of Dermatology and Venereology Congress, 25-28 September 2024, Amsterdam.Top of Form