Filaggrin Mutations, Skin Barrier Dysfunction, and Sensitization in Allergic Rhinitis

Allergic rhinitis (AR) is a common disorder with an estimated prevalence of 20,000 per 100,000 Europeans. Classical clinical signs include sneezing, coughing, and itchy and runny nose and eyes, which may be accompanied by more severe symptoms such as head

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18

Tatiana A. Vogel and Marie-Louise A. Schuttelaar

Contents

18.1

18.1

Introduction ..............................................

183

18.2

Definition and Clinical Features .............

184

18.3

Diagnosis ...................................................

184

18.4

Genetics .....................................................

184

18.5

Filaggrin and the Atopic Syndrome .......

184

18.6

Research on FLG Mutations and Allergic Rhinitis in Perspective ....... 18.6.1 Association Between FLG Variants and Allergic Rhinitis .................... 18.6.2 The Lack of Expression of Filaggrin in Mucosal Tissue ......................................

185 185 188

18.7 Discussion.................................................. 18.7.1 The Outside-In Hypothesis ........................ 18.7.2 Atopic Dermatitis and the Atopic Syndrome Versus Ichthyosis Vulgaris........ 18.7.3 From Cutaneous Sensitization to Systemic Allergy.................................... 18.7.4 Atopy Patch Testing Strengthens Percutaneous Priming Hypothesis ............. 18.7.5 Filaggrin Null Mutations and Peanut Allergy ..................................... 18.7.6 Oral Tolerance ............................................ 18.7.7 The Perfect Prevention for the Onset of Allergic Rhinitis.....................................

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191

References ...............................................................

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T.A. Vogel, MD • M.-L.A. Schuttelaar, MD, PhD (*) Department of Dermatology, University Medical Centre Groningen, Hanzeplein 1, Groningen 9700 RB, The Netherlands e-mail: [email protected]

Introduction

Allergic rhinitis (AR) or hay fever is a common chronic inflammatory disease of the nasal mucosa with an estimated prevalence in adults from Western Europe that ranges from 3 to 19 % [1]. Research has shown a relatively low rate of physician-based diagnosis of about 13 % [2], and it was presumed that around 45 % of all AR patients remain undiagnosed. This same phenomenon was found in multiple different studies over time. Therefore, the expected prevalence of AR in adults from Western Europe is around 30 %. Children are slightly more often affected than adults [2, 3]. This very common disease was first described in 1819 by the physician John Bostock in his case report “Periodical affection of the eyes and the chest” [4]. In this first report about AR, the classical symptoms were described of itchy, runny nose and eyes accompanied by a slumping feeling occurring in spring- and summertime. At that time, therapeutic advice included obtaining fresh air and the avoidance of a moist and closed atmosphere. Unfortunately, the reported patient experienced no improvement of his complaints. However, during an unusually warm summer season, he stayed indoors almost all summer and experienced a relief of his complaints. A few decades later, Charles Harrison Blackley discovered that the mechanism behind AR was caused by pollen, and therefore, he named it “hay fever” [5].

J.P. Thyssen, H. Maibach (eds.), Filaggri