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Wise et al.

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by duration and chronicity of symptoms. 1,137,138 The timing of symptoms may also help delineate between rhinosinusitis and AR as ARS symptoms typically last days to weeks (but no more than 4 weeks), CRS symptoms persist daily for greater than 12 weeks. In comparison, while AR symptoms are variable in duration, they tend to have seasonal or exposure-related fluctuations. 1,137,138 AR symptoms are present for at least 1 hour on most symptomatic days; however, patients may have symptom-free intervals. 264,265 AR symptoms are also exacerbated by exposure to allergens in a time dependent fashion. 264 The early reaction occurs immediately after exposure and is characterized by sneezing, nasal and ocular itching and rhinorrhea, which typically resolves within 30 minutes. 264 The late reaction takes place up to 6 hours after exposure and is characterized by nasal obstruction and congestion. 264 Superimposed late reactions may blunt the manifestation of acute phase symptoms and make the diagnosis of AR less obvious. When attempting to determine whether a patient has AR, ARS, RARS, or CRS, it is important to elicit a history of specific symptoms from the patient that includes onset and duration of symptoms. A history of allergic symptoms or allergen exposure-related symptoms support a possible diagnosis of AR, as these are not associated with rhinosinusitis and AR may or may not be seasonal in nature, which can also be elicited by history. 264,265 The development of acute, moderate to severe symptoms, and nasal purulence may be consistent with ARS or RARS rather than AR. 1,137,138 A prolonged duration of symptoms (greater than 12 weeks) should raise suspicions for CRS and prompt further investigation. 1,137,138 (See section X.B. Associated conditions - Rhinosinusitis for additional information on this topic.) A background understanding of the pathophysiology and underlying mechanisms of AR is necessary as we examine the clinical presentations, physical manifestations, goals of allergy testing, and response to treatment. This section addresses the cellular inflammation, soluble mediators, local allergic manifestations, and systemic effects associated with AR. While this document is not intended to provide an extensive review of the pathophysiology of AR, the following short section provides a foundation for understanding the clinical expression of AR and its treatment. IV.A.1. Systemic mechanisms and manifestations— The immune response leading to IgE production in AR is often a systemic phenomenon, and patients with AR demonstrate evidence of systemic atopy. 269,270 One manifestation of systemic atopy in AR is the cutaneous reaction elicited during traditional allergy skin testing. 271 Further evidence for the systemic nature of the IgE response in AR includes the temporal relationship of AR to a number of other allergic diseases, including atopic dermatitis (AD), food allergy, and allergic asthma, a phenomenon known as the “atopic march.” 272 This pattern of atopic disease progression is well-known and supported by prospective studies. 273

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IV. Pathophysiology and mechanisms of allergic rhinitis

IV.A. IgE-mediated allergic rhinitis

The immunologic processes underlying IgE-mediated AR are similar to those of other atopic conditions and involve activation of the adaptive immune system. The adaptive immune

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.