**6. Local allergic rhinitis and comorbidity**

AR is an essential part of the "atopic march" [17] and thereby associated with comorbidities, such as asthma, atopic dermatitis, food allergies eosinophilic esophagitis, allergic conjunctivitis, chronic rhinosinusitis with nasal polyposis (CRSwNP), and more [18]. The association of these comorbidities with local allergic rhinitis (LAR) was less explored [19], although bronchial symptoms have been reported in patients with LAR [20] and any chronic rhinitis is a risk factor for poorly controlled asthma with recurrent hospital visits [19]. Recently, self-reported bronchial symptoms, suggestive of asthma, were reported in over 30% of patients with LAR, suggesting a new asthma phenotype, "local allergic asthma" [21, 22]. As in classical allergic rhinitis, conjunctival symptoms were also associated with LAR. It was shown that patients with LAR experience ocular symptoms during nasal exacerbations due to allergen exposure or during in vitro nasal provocation tests [20]. In one study, this was the most prevalent comorbidity associated with LAR [23]. In a recent study by Rondon et al. [19], a 10-year follow-up of 176 LAR patients entailed other comorbidities, such as food allergy and drug hypersensitivity, which were documented only in few patients.

## **7. Treatment of LAR**

In daily practice NAPT, BAT, or other specific tests are rarely performed. Hence, performing a therapeutic trial with antihistamines may be beneficial for diagnosis of LAR. Early and substantial response to antihistamine further supports an allergic histamine-driven mechanism. In the same line of thought, treatment with nasal corticosteroid spray may be clinically beneficial, but will not enable to differentiate causes of chronic rhinitis. Most LAR patients are currently treated similarly to AR patients, and according to the allergic rhinitis and its impact on asthma (ARIA) guidelines. This is done by using personal and environmental education, allergen avoidance measures and non-specific pharmacologic modalities, such as, intranasal corticosteroids, and oral and intranasal antihistamines [7–10]. Having said that, such non-specific therapy for LAR will ameliorate symptoms but alike AR will not change the natural progression of disease.

Immunotherapy is a common therapeutic modality for moderate to severe unresponsive AR. Allergen immunotherapy is based on gradual exposure to a culprit allergen via subcutaneous or sublingual exposure. This will eventually result in "induced tolerance" to the targeted allergen and amelioration of the allergic response. Allergen immunotherapy is highly effective and safe and confers longterm clinical benefit in adequately selected patients. Furthermore, it is the only etiological treatment for AR and asthma which conveys disease-modifying effect that can actually change the natural course of the disease [8, 9]. Thus, although LAR is by definition a local rather than systemic disease, few studies provide evidence for clinical benefit of allergen immunotherapy among LAR patients. These studies demonstrated a significant symptom improvement, an increase in the number of medication free days, and a beneficial effect on ocular symptoms, asthma control, and quality of life compared to placebo, as well as tolerance induction defined by an increase in allergen-specific IgG4 [6–8, 10].

### **8. Conclusions**

In the last decade, growing evidence indicates that nasal reactivity to aeroallergens can occur in the absence of evidence of systemic atopy. The published literature raised the suspicion that many patients diagnosed previously as suffering from non-allergic rhinitis actually suffer from LAR. This may be of importance as treatment options differ between non-allergic and AR/LAR diseases. Diagnosis of LAR remains a challenge, as none of the diagnostic methods suggested are optimal nor commonly available in most centers. Therefore, high index of suspicion, utilizing specific methods if accessible as well as therapeutic challenge, may enable correct and early diagnosis. This may enable specific allergen-directed interventions (e.g., allergen immunotherapy), as well as early detection and treatment of comorbidities (like asthma and conjunctivitis). In this regard, implementation of NAPT, BAT, and other methods of diagnosis, especially in referral centers, as well as long-term studies to better define the mechanisms, course, and response to therapy of LAR, is needed.

**23**

**Author details**

Shirly Frizinsky1

Ramit Maoz-Segal1†

†Equally contributed

provided the original work is properly cited.

*Local Allergic Rhinitis: An Old Story but a New Entity DOI: http://dx.doi.org/10.5772/intechopen.86212*

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Irena Veksler-Offengenden1

,

, Diti Machnes-Maayan1,2†

2 Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel

\*Address all correspondence to: nancy.agmon-levin@sheba.health.gov.il

Diseases, Sheba Medical Center, Tel Hashomer, Israel

, Soad Hajyahia1,2 and Nancy Agmon-Levin1,2\*

1 Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune

*Local Allergic Rhinitis: An Old Story but a New Entity DOI: http://dx.doi.org/10.5772/intechopen.86212*

*Rhinosinusitis*

**7. Treatment of LAR**

change the natural progression of disease.

increase in allergen-specific IgG4 [6–8, 10].

**8. Conclusions**

of LAR, is needed.

In daily practice NAPT, BAT, or other specific tests are rarely performed. Hence, performing a therapeutic trial with antihistamines may be beneficial for diagnosis of LAR. Early and substantial response to antihistamine further supports an allergic histamine-driven mechanism. In the same line of thought, treatment with nasal corticosteroid spray may be clinically beneficial, but will not enable to differentiate causes of chronic rhinitis. Most LAR patients are currently treated similarly to AR patients, and according to the allergic rhinitis and its impact on asthma (ARIA) guidelines. This is done by using personal and environmental education, allergen avoidance measures and non-specific pharmacologic modalities, such as, intranasal corticosteroids, and oral and intranasal antihistamines [7–10]. Having said that, such non-specific therapy for LAR will ameliorate symptoms but alike AR will not

Immunotherapy is a common therapeutic modality for moderate to severe unresponsive AR. Allergen immunotherapy is based on gradual exposure to a culprit allergen via subcutaneous or sublingual exposure. This will eventually result in "induced tolerance" to the targeted allergen and amelioration of the allergic response. Allergen immunotherapy is highly effective and safe and confers longterm clinical benefit in adequately selected patients. Furthermore, it is the only etiological treatment for AR and asthma which conveys disease-modifying effect that can actually change the natural course of the disease [8, 9]. Thus, although LAR is by definition a local rather than systemic disease, few studies provide evidence for clinical benefit of allergen immunotherapy among LAR patients. These studies demonstrated a significant symptom improvement, an increase in the number of medication free days, and a beneficial effect on ocular symptoms, asthma control, and quality of life compared to placebo, as well as tolerance induction defined by an

In the last decade, growing evidence indicates that nasal reactivity to aeroallergens can occur in the absence of evidence of systemic atopy. The published literature raised the suspicion that many patients diagnosed previously as suffering from non-allergic rhinitis actually suffer from LAR. This may be of importance as treatment options differ between non-allergic and AR/LAR diseases. Diagnosis of LAR remains a challenge, as none of the diagnostic methods suggested are optimal nor commonly available in most centers. Therefore, high index of suspicion, utilizing specific methods if accessible as well as therapeutic challenge, may enable correct and early diagnosis. This may enable specific allergen-directed interventions (e.g., allergen immunotherapy), as well as early detection and treatment of comorbidities (like asthma and conjunctivitis). In this regard, implementation of NAPT, BAT, and other methods of diagnosis, especially in referral centers, as well as long-term studies to better define the mechanisms, course, and response to therapy

**22**
