The Evolution of Atopic Disorders: Insights Into the Atopic March

The atopic march encompasses a sequence of allergic conditions, including atopic dermatitis, food allergy, allergic rhinitis, and asthma, that frequently develop in a sequential pattern within the same individual. It was introduced as a conceptual framework aimed at elucidating the developmental trajectory of allergic conditions during childhood. Following the introduction of this concept, it was initially believed that the atopic march represented the sole and definitive trajectory of the development of allergic diseases. This review outlines epidemiologic evidence for the existence of allergic march trajectories (distinct paths of atopy development in individuals); reviews the roles that genetics, environment, and disease endotypes play in determining trajectory outcomes; and discusses the clinical utility of the trajectory model. A systemic immune response to cutaneous inflammation may drive or amplify the development of atopic comorbidities in genetically or immunologically susceptible individuals. However, these observed associations could instead reflect the influence of shared genetic loci and environmental exposures – such as microbiome dysregulation – rather than a true sequential progression of disease. The apparent temporal order of disease onset may simply correspond to the tissue-specific peak incidence of each condition, suggesting a clustering of atopic disorders rather than a unidirectional “march.” Prospective longitudinal cohort studies offer a valuable framework for investigating the post-dermatitis emergence of additional atopic conditions, while also identifying predictive phenotypic, genotypic, and environmental factors. Recent research has identified several risk factors for the development of multiple atopic comorbidities in young children with atopic dermatitis, including disease severity and chronicity, early age of onset, parental history of atopy, filaggrin mutations, polysensitization, and living in nonrural environments. Early intervention trials—targeting epidermal barrier restoration, modulation of microbiome composition, or altered exposure to allergens – may help to clarify the relative contributions of skin barrier dysfunction, genetic predisposition, and environmental exposures to the risk, timing, and progression of Th2-mediated disorders. This evolution calls for a shift from viewing allergic diseases as a linear progression of comorbidities to recognizing them as components of an overlapping multimorbidity model. Such an approach enables proactive patient monitoring based on their predisposition to develop concurrent allergic disorders. Importantly, early onset of atopic disease has been linked to a heightened risk of persistent multimorbidity. Current data also indicate that allergic conditions often co-occur without following a fixed sequence of symptom development. Effective control and timely treatment of allergic diseases may influence the trajectory of the atopic march and potentially prevent its advancement. The application of systems medicine – including integration of clinical data, multi-omics, epidemiology, and mechanistic modeling – will be key to understanding the underlying pathophysiological pathways that drive divergent allergic trajectories. This approach promises to transform diagnosis, treatment, and prognostic accuracy, ultimately enabling the prevention of allergic disease onset.