Allergic rhinitis and conjunctivitis: update on pathophysiology

Abstract

Our understanding of the development and mechanism(s) of allergic diseases has changed dramatically over the last 20 years. With the advent of genetic studies it has now become clear that the linear model, as defined by the allergic march, is no longer tenable. Instead, we must consider all allergies as complex multi-compartment models in which genes which control IgE production and also genes which govern other aspects of allergic disease, such as epithelium integrity, both play an important role. To explore such possibilities, this chapter asks four questions:
1. Is there any evidence of an abnormality in the conjunctival or nasal mucosa which would allow increased allergen penetration? Epithelial changes which are likely to facilitate allergen penetration are present in both allergic conjunctivitis and rhinitis, but they appear different. For example, epithelial PAR-2 expression is elevated in allergic rhinitis whereas in seasonal allergic conjunctivitis, many structural proteins, including E-cadherin, CD44, desmosomes, keratins K5/6, K7, K8, K13, K14, K18 and PAR-2 are all reduced. 2. What is known about the immunology of sensitization in allergic conjunctivitis and allergic rhinitis? Clearly, great strides are being made with respect to the biology of dendritic cells and T regulatory cells and to the possibility of local IgE production, but there is little evidence to suggest differences between the mechanisms of sensitization in the eye and nose. 3. What is the pattern of mediator release in the immediate allergic response and the development of allergic inflammation in allergic conjunctivitis and allergic rhinitis? The pattern of the early phase allergic response in the eye and nose seem similar. While an eosinophil dominated late phase response and allergic inflammation are present in allergic rhinitis, they are only present in the more severe forms of allergic conjunctivitis such as AKC and VKC. 4. Is there any evidence for clinically relevant persistent inflammation or organ remodelling in allergic conjunctivitis and allergic rhinitis? A sustained inflammation and tissue remodelling are well established in the lower airways in asthma where they contribute significantly to the symptoms. However, in upper airways, although there do appear to be functional changes in sensory neurone structure and function in the nose during prolonged allergen exposure, tissue damage seems to be more limited and overt remodelling does not appear to occur in allergic conjunctivitis and is questionable in allergic rhinitis.

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