Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.
Epidemiology of AD and ACD
Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.1 In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.2 Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.1 This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.3
In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.4 In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).6
In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.
Immune Mechanism
The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly TH2 helper T-cell response with high levels of IL-4, IL-5, and IL-137; TH22, TH17, and TH1 also have been implicated.8 Notably, TH17 is found in high levels during the acute eczema phase, while TH1 and TH22are associated with the chronic phase.7
The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.9 Allergic contact dermatitis initially was thought to be driven by TH1 cytokines and IL-17 but now is understood to be more complex.10 Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a TH1/TH17 response, whereas fragrance and rubber accelerators skew to TH2; TH9 and TH22 also may be involved depending on the causative allergen.11,12
Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.13 However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared TH1 pathway.14 Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.15 This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.