Atopic March

The atopic march (or “allergic march”) is the classic model in which Atopic Dermatitis appears first in infancy, then Food Allergy, then Asthma, and finally Allergic Rhinitis (hay fever) in later childhood. It was proposed as a framework for how allergic disease develops across childhood. It rests on two observations. Children with eczema are more likely to develop the other conditions, and the conditions tend to peak at different ages (Medicina 2024). The usual explanation is barrier-first. A leaky skin barrier (Skin Barrier Dysfunction) lets allergens in through inflamed skin, and this primes a body-wide Th2 Immune Response that later shows up in the gut, lungs and nose. The Dual-Allergen Exposure Hypothesis describes the eczema → food allergy step of this model.

Atopic Dermatitis [precedes] Food Allergy Food Allergy [precedes] Asthma Asthma [precedes] Allergic Rhinitis Skin Barrier Dysfunction [causes] Atopic March Th2 Immune Response [part-of] Atopic March

How many children actually follow it? Belgrave et al. (PLoS Med 2014) studied 9,801 children from two UK birth cohorts (MAAS and ALSPAC), checked at ages 1, 3, 5, 8 and 11. A machine-learning latent-class model found eight profiles. These were no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later rhinitis (4.7%), persistent wheeze with later rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%) and rhinitis only (9.6%). That works out to 3.1% of all children, or fewer than 7% of children with any symptoms, following a march-like path. The authors concluded that eczema, wheeze and rhinitis follow mixed, varied paths, and that “atopic march” does not describe most children. Reviewers now often use “atopic multimorbidity” instead: conditions that co-occur and share risk factors, but do not follow a fixed sequence (Medicina 2024). For a parent, this means a toddler with eczema has a higher risk of asthma or hay fever, but most children with eczema will not move through the full sequence. The largest single group in Belgrave’s data had eczema only.

Atopic March [relates] Allergic Rhinitis

Conflict: [Classic atopic-march model, cohorts reviewed in Medicina 2024] says early AD progresses in sequence to asthma and rhinitis. [Belgrave et al., PLoS Med, 2014] says only 3.1% of all children (<7% of those with symptoms) follow that trajectory, and that profiles are heterogeneous. Unresolved — add to open_questions.

Risk factors for progression. The cohorts reviewed in Medicina 2024 link progression to several factors: younger age at onset, greater AD severity, persistent AD, a family history of atopy, Filaggrin (FLG) loss-of-function mutations, urban living, and sensitisation to several allergens. Severity was the strongest single predictor in the MAS cohort. Asthma affects about 20% of children with mild AD but more than 60% of those with severe AD. BAMSE also tied AD severity to asthma onset. A genome-wide study (Marenholz) found seven gene regions linked to the march, with FLG at the top of the list. FLG mutations matter because they weaken the skin barrier, so they fit the barrier-first explanation.

Filaggrin [worsens] Atopic March Atopic Dermatitis [relates] Asthma

Can treating eczema early prevent it? Not proven so far. The skin barrier is the suggested starting point, so the main idea has been to protect it from birth. The results are mixed (Medicina 2024):

• Emollients from birth. Small early studies were encouraging. PEBBLES, a pilot of a ceramide-rich emollient used to 6 months, reduced food sensitisation at 6–12 months. The large trials were negative. In BEEP, daily emollient did not lower eczema rates at age 2. In PreventADALL, emollients did not reduce AD by 12 months; the 3.1% higher rate in the emollient group was not statistically significant (95% CI −0.3 to 6.5; Skjerven, Lancet 2020), and emollients did not prevent food allergy at 36 months either.
• Early allergen introduction. Giving peanut early to high-risk infants cut peanut allergy (LEAP Trial); in the general-population EAT Trial the benefit for peanut and egg was seen only per-protocol, not in the intention-to-treat analysis. This breaks the food-allergy step, not the whole march.
• Asthma and rhinitis. House-dust-mite avoidance and preventive sublingual immunotherapy have not shown enough benefit for routine use. No trial has yet shown that treating toddler eczema well, with Emollient Therapy or Topical Corticosteroids, prevents later asthma or hay fever.

Even so, good eczema control is worthwhile for itch, sleep and quality of life. Whether it also changes the allergic course is still an open question.

Emollient Therapy [relates] Atopic March BEEP Trial [contradicts] Emollient Therapy LEAP Trial [prevents] Food Allergy

Connections

• Atopic Dermatitis — precedes; contested model, source: Medicina 2024
• Skin Barrier Dysfunction — barrier defect may allow epicutaneous sensitisation to aeroallergens, source: Elias & Wakefield 2011
• Th2 Immune Response — shared type 2 pathway, source: Papapostolou 2022
• Dual-Allergen Exposure Hypothesis — explains eczema→food allergy step, source: Papapostolou 2022
• Food Allergy — second step of the classic sequence, source: Medicina 2024
• Asthma — ~20% with mild AD vs >60% with severe AD, source: Medicina 2024
• Allergic Rhinitis — final step of the classic sequence, source: Belgrave 2014
• Filaggrin — FLG mutations are a leading genetic risk factor for progression, source: Medicina 2024
• BEEP Trial — daily emollient from birth did not prevent eczema, source: Medicina 2024
• LEAP Trial — early peanut cuts peanut allergy (food step only), source: Medicina 2024
• EAT Trial — early allergen introduction trial, source: Medicina 2024
• SCORAD — severity, a key predictor of progression, is graded with SCORAD/EASI, source: Medicina 2024
• Dupilumab — sponsor meta-analysis: fewer new/worsening allergies (IRR 0.66), adult-dominated, source: Geba JACI 2023
• Eczema Prognosis — persistence and comorbidity outlook; AD→asthma as shared phenotype not progression, source: Illi 2004; Paternoster 2018
• PreventADALL Trial — emollients did not reduce AD (non-significant +3.1%), source: Medicina 2024; Skjerven Lancet 2020