Hayfever, asthma and eczema and the atopic march

The atopic march is referred to as the progression of atopic, or allergic conditions starting with atopic dermatitis, leading to asthma and allergic rhinitis in childhood.¹ 

Hypotheses for the prevalence of allergies and atopic conditions in urban environments include: 

• Diet 
• Allergens 
• Infections
• Air pollution
• Genetics
• Excessive hygiene.¹ 

Children with atopic dermatitis within the first 12 months of life were found to be 6 times more likely to have an egg allergy and 11 times more likely to have a peanut allergy.²

What causes the atopic march?

A primary inherited epithelial barrier defect associated with a genetic mutation and proinflammatory factors leading to an increase in mast cell production of T helper 2 cytokines are considered to be predisposing factors in the development of atopic dermatitis and asthma.¹

Atopic manifestations in the skin during infancy have been associated with the presentation of allergic rhinitis and asthma in the later years of life. 

Atopic march progression

Starting with atopic dermatitis, the sequence of the atopic march generally involves the progression to food allergy, rhinitis and asthma, with the potential for each presenting condition to subside and present at different times.¹ 

A strong relationship between atopic dermatitis and food allergies or intolerances has been observed, with early food sensitization or allergies linked to an increase in risk for the development of allergic airway disorders.² The presence of facial atopic dermatitis in infancy has been associated with the development of cows milk allergy in children.³

Fifty per cent of children with atopic dermatitis will develop asthma or allergic rhinitis will develop in 75 per cent.¹ 

Hygiene hypothesis

Considered to be a contributing factor for the prevalence of atopic conditions in certain countries, the hygiene hypothesis suggests that reduced exposure to bacteria throughout infancy shifts the immune system towards a T-helper 2 predominant situation leading to a predisposition to allergies.¹

Epithelial cell, or skin-barrier health

A reduction in the integrity of the dermal epithelial barrier caused by irritants, including allergens, may trigger the commencement of the atopic march. Epithelial weakness may leave the individual vulnerable to microbes and pathogens and promote the development of atopic dermatitis.¹ 

Dermatitis involves cytokine production, inflammation and eczema lesions and can produce a weakening of the tight-gap junctions in the epithelial layer, including in the respiratory epithelial lining. Weakness in the respiratory epithelium leads to an increase in the potential for pollen to penetrate the barrier and allow allergens to cross the tight-gap junctions, leading to increased sensitisation and potentially asthma development.¹

Asthma and atopic dermatitis share common immunological responses including T-helper 2 dominance and raised IgE levels, environmental triggers and eosinophilia in the periphery.¹

Environmental influences

Environmental influences on the health of the skin can influence the development of atopic dermatitis including scratching or skin trauma, low humidity, bacteria, allergens and topical irritants.² An increase in the presence of Staphylococcus aureus on the skin microbiome leading to dysbiosis of the skin of patients has been associated with an increase in the prevalence of atopic dermatitis due to a reduction in barrier function.² The presence of Staphylococcus aureus can also lead to a reduced response to topical steroid treatment.²

Management of atopic conditions

Breastfeeding has been associated with a lower prevalence of allergies which is extended for each month the child is breastfed.⁴

Early oral allergen exposure is thought to help to reduce the culmination of a clinical food allergy and allows for immune tolerance to be formed, even in the presence of an impaired dermal epithelial barrier that may lead to atopic dermatitis.² Oral tolerance to an allergen exposes antigen-presenting cells within the gut mucosa to the allergen and promotes the differentiation of naive T cells and T reg cells that inhibit the T-helper 2 allergic response, mast cell degranulation and IgG4 production.²

Early introduction of egg and peanuts in high-risk infants has been associated with a decreased risk of food allergy in the infant, and evidence now suggests early introduction rather than the previous advise to delay the introduction of common allergens.² In contrast, there is no conclusive evidence to support the early introduction of wheat to breastfeeding babies as a means to reduce allergy.²

Primary prevention of atopic dermatitis includes the application of emollients to protect the dermal epithelial barrier.² Studies suggest that the maternal use of probiotics in high-risk mothers may lower the risk of atopic dermatitis in the child.²

Preventing the progression of the atopic march from atopic dermatitis involves the treatment of atopic dermatitis to lower skin inflammation and epithelial damage through the use of topical moisturisers, allergen avoidance, topical antiinflammatory treatment and the management of skin infections.²

Clinical trials on the manipulation of the skin microbiome to enhance the epithelial barrier integrity are underway. The gut microbiome and the abundant supply of short-chain fatty acids through breastmilk support the health and integrity of the intestinal epithelium and modulate the production of cytokines, kinases and transcription factors while increasing the production of anti-inflammatory mediators have been shown to correlate with a reduced incidence of atopic dermatitis.² Pre and probiotic therapy in the prevention of atopic dermatitis requires more research but shows promising results, however encouragingly, infants fed homemade meals containing high levels of fruits and vegetables have been associated with a lower incidence of food allergy.²

References

1. Spergel, J. M. (2010). From atopic dermatitis to asthma: The atopic march. Annals of Allergy, Asthma and Immunology, 105(2), 99–106. https://doi.org/10.1016/j.anai.2009.10.002 
2. Tham, E. H., Rajakulendran, M., Lee, B. W., & Van Bever, H. P. S. (2020). Epicutaneous sensitization to food allergens in atopic dermatitis: What do we know? Pediatric Allergy and Immunology, 31(1), 7–18. https://doi.org/10.1111/pai.13127 
3. Kawada, S., Futamura, M., Hashimoto, H., Ono, M., Akita, N., Sekimizu, M., Hattori, H., Goto, M., Horibe, K., & Maeda, N. (2020). Association between sites and severity of eczema and the onset of cow’s milk and egg allergy in children. PLoS ONE, 15(10 October), 1–8. https://doi.org/10.1371/journal.pone.0240980 
4. Carucci, L., Nocerino, R., Paparo, L., Di Scala, C., & Berni Canani, R. (2020). Dietary Prevention of Atopic March in Pediatric Subjects With Cow’s Milk Allergy. Frontiers in Pediatrics, 8 (August), 1–9. https://doi.org/10.3389/fped.2020.00440 

‍

Appendix

Appendix One: T helper 1 and 2 function¹ 

Appendix Two: Halting the Atopic March⁴

‍