Atopic march mechanisms

The atopic march is a well-known concept that describes the natural progression of allergic diseases, particularly during childhood. It refers to the sequential development of different allergic conditions in a predictable pattern within the same individual¹.

Epidemiology and Clinical Progression of Atopic March

• Atopic dermatitis affects approximately 17–24% of children and 10% of adults worldwide.
• Among children with mild atopic dermatitis, the prevalence of asthma is approximately 20%.
• In children with severe atopic dermatitis, the prevalence of asthma increases to over 60%.
• Among children with asthma, approximately 74–81% also develop allergic rhinitis.
• Allergic rhinitis typically appears early, with a mean onset age of 2.9 ± 1.7 years.

This sequential pattern highlights the interconnected nature of allergic diseases and underscores the importance of early recognition and management to potentially reduce progression along the atopic march².

Pathophysiology of Atopic March

• Epithelial Barrier Dysfunction: Genetic factors, such as filaggrin mutations, impair skin barrier integrity, allowing allergen penetration and sensitization.
• Immune Dysregulation: A predominant T helper 2 (Th2) response leads to increased interleukin-4, interleukin-5, and interleukin-13, promoting immunoglobulin E production and eosinophilic inflammation. Reduced regulatory T-cell activity further contributes to allergic progression.
• Neurogenic Inflammation: Chronic itching triggers the release of neuropeptides that worsen inflammation and barrier disruption.
• Molecular Pathways: Epithelial cytokines such as thymic stromal lymphopoietin, interleukin-25, and interleukin-33 activate innate and adaptive immune responses. IgE-mediated sensitization primes mast cells, while microbiome dysbiosis in the skin, gut, and airways further facilitates disease progression.

The atopic march arises from a combination of epithelial barrier dysfunction, immune dysregulation, and environmental influences. Atopic dermatitis is often the earliest manifestation. Early recognition and intervention are critical, as they may help prevent disease progression and reduce the long-term burden of allergic conditions³.

References

1. Mrkić Kobal I, Plavec D, Vlašić Lončarić Ž, Jerković I, Turkalj M. Atopic March or Atopic Multimorbidity—Overview of Current Research. Medicina (Kaunas). 2023;60(1):21. doi:10.3390/medicina60010021
2. Tsuge M, Ikeda M, Matsumoto N, Yorifuji T, Tsukahara H. Current Insights into Atopic March. Children (Basel). 2021;8(11):1067. doi:10.3390/children8111067
3. Maiello N, Comberiati P, Giannetti A, Ricci G, Carello R, Galli E. New Directions in Understanding Atopic March Starting from Atopic Dermatitis. Children. 2022;9(4):450.https://doi.org/10.3390/children9040450