Local allergic rhinitis: Concept, pathophysiology, and management

doi:10.1016/j.jaci.2012.02.032

Journal of Allergy and Clinical Immunology

Volume 129, Issue 6, June 2012, Pages 1460-1467

https://doi.org/10.1016/j.jaci.2012.02.032 Get rights and content

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T_H2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.

Section snippets

Etiologic classification of rhinitis

From an etiologic point of view, noninfectious rhinitis has been traditionally classified as allergic and nonallergic, and the diagnosis has been based on the clinical history, skin prick test (SPT) responses, and serum sIgE levels to inhalant allergens.¹⁴ However, evidence has recently suggested that this approach is incomplete because patients previously given a diagnosis of NAR or idiopathic rhinitis (IR) might actually be classified as having LAR.6, 7, 8, 9, 11, 12, 13

AR is the most common

Epidemiologic, clinical, and pathophysiologic aspects of LAR

The identification of a subgroup of patients who could be characterized as having LAR has generated a number of important questions:

1.
What are the prevalence and overall effect of LAR, and what is the influence of environmental factors on the epidemiology of this condition?
2.
Are the allergens associated with LAR the same as those involved in conventional AR?
3.
How definitive is the evidence that IgE is produced locally in the nasal mucosa?
4.
Is IgE production limited to the nose and why?
5.
Is LAR a

Nasal symptoms and comorbidities

Patients with LAR often present with symptoms typical of AR (ie, rhinorrhea, obstruction, sneezing, and itching), which are often associated with ocular symptoms, and good response to oral antihistamines and nasal corticosteroids.8, 9, 12 Patients with LAR and systemic AR report anterior rhinorrhea, sneezing, and itching as the most frequent symptoms.8, 9 Patients with LAR can be grouped according to the classical (seasonal, perennial, and occupational) and Allergic Rhinitis and its Impact on

Diagnostic approach

Several nonallergic conditions can mimic AR symptoms, but because management differs in each case, it is very important to differentiate between AR and NAR. Knowledge of the existence of a localized allergic response in the nasal mucosa demonstrates the need for a thorough allergologic workup. Rondón et al¹⁵ have proposed a new diagnostic approach with a nasal allergologic evaluation in all patients with a clinical history suggestive of AR but with negative SPT responses and a lack of sIgE

Therapeutic options

The correct differentiation between LAR and NAR is a key point for the management of this new entity. The management of AR includes the following: allergen avoidance, pharmacologic treatment, immunotherapy, and education.¹⁴ Patients with LAR have reported a good response to topical nasal corticosteroids and oral antihistamines.8, 9 This might be one phenotypic characteristic of patients with LAR in contrast with those with nonatopic rhinitis. Double-blind, placebo-controlled clinical trials

Future research

Increasing evidence of a localized allergic response in nonatopic patients raises important questions about LAR, many of them outlined in this article: studies of prevalence and incidence in adults and children, influence of the allergenic load in the production of disease, lower airway and conjunctival involvement, effectiveness of pharmacologic treatment, and specific immunotherapy.

Concerning natural history, it is relevant to know whether these patients remain stable over long periods of

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Risk of Chronic Rhinosinusitis With Nasal Polyps in Endotypes of Dermatophagoides pteronyssinus-Induced Rhinitis
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Observation of the natural history of two emerging endotypes of allergic rhinitis, local-sensitization rhinitis (LAR) and dual-allergic rhinitis (DAR), compared with systemic-sensitization rhinitis (AR), could improve knowledge of the role of allergy in chronic rhinosinusitis with nasal polyps (CRSwNP).
To test the hypothesis that endotypes of Dermatophagoides pteronyssinus (DP)-induced rhinitis were risk factors for CRSwNP and adult-onset asthma and to investigate whether delayed hypersensitivity to DP, assessed by atopy patch test, could be a contributing factor.
We conducted a prospective observational study over 15 years on a cohort of 999 patients: 468 with AR, 333 with LAR, and 198 with DAR. The latter endotype was characterized by the coexistence of seasonal disease caused by systemic sensitization to pollen in patients with DP-induced LAR. The study design included a physical visit; ear, nose, and throat examination with anterior rhinoscopy; skin prick test; serum-specific IgE; DP-atopy patch test; nasal allergen provocation test with DP; paranasal sinuses computed tomography scan; nasal endoscopy; and spirometry.
During 15 years of follow-up, 194 patients developed CRSwNP with a higher rate of LAR (28.2%) and DAR (22.2%) than AR (12%). For LAR and DAR, 7.5% and 10.6% of patients developed adult-onset asthma temporally linked to CRSwNP in 68% and 71.4% of cases, respectively. A total of 858 patients with rhinitis had delayed hypersensitivity to DP. Moreover, DP-ATP was an independent predictive factor for CRSwNP and had elevated positive and negative predictive values for localized allergic disease of the nasal mucosa.
Endotypes of DP-induced allergic rhinitis represent risk factors for CRSwNP. Patients with local-sensitization rhinitis and DAR are more at risk than those with AR. In these emerging endotypes, progression toward CRSwNP is often associated with the development of adult-onset asthma. Chronic rhinosinusitis with nasal polyps shows several possible indicators for type 2 endotype. Delayed hypersensitivity to DP is an independent predictive factor for CRSwNP.
CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model
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The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.
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: Disclosure of potential conflict of interest: W. J. Fokkens has received research support from GlaxoSmithKline and Medtronic and has served as an advisor to GlaxoSmithKline, MSD, and Stallergenes. The rest of the authors declare that they have no relevant conflicts of interest.

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Reviews and feature articleLocal allergic rhinitis: Concept, pathophysiology, and management

Section snippets

Etiologic classification of rhinitis

Epidemiologic, clinical, and pathophysiologic aspects of LAR

Nasal symptoms and comorbidities

Diagnostic approach

Therapeutic options

Future research

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Local production of IgG, IgA and IgE antibodies in grass pollen hay fever

J Immunol

Expression of epsilon germ-line gene transcripts and mRNA for the epsilon heavy chain of IgE in nasal B cells and the effects of topical corticosteroid

Eur J Immunol

Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis

J Immunol

Evidence for an inflammatory pathophysiology in idiopathic rhinitis

Clin Exp Allergy

Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?

Clin Exp Allergy

‘Entopy’: localized mucosal allergic disease in the absence of systemic responses for atopy

Clin Exp Allergy

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response

Allergy

Reviews and feature article
Local allergic rhinitis: Concept, pathophysiology, and management