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Review

Local Allergic Rhinitis: A Different Rhinitis Endotype? Literature Overview

by
Elena Cantone
1,2,*,
Aikaterini Detoraki
3 and
Eugenio De Corso
4
1
Neurosciences, Reproductive and Odontostomatologic Sciences, Unit of Ear, Nose and Throat, Federico II University, 80131 Naples, Italy
2
Head and Neck Department, ENT Section, AOU Federico II University, 80131 Naples, Italy
3
Department of Internal Medicine, Clinical Immunology, Clinical Pathology and Infectious Diseases, Division of Internal Medicine and Clinical Immunology, AOU Federico II University, 80131 Naples, Italy
4
Unit of Otorhinolaryngology Head and Neck Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Appl. Sci. 2022, 12(21), 11141; https://doi.org/10.3390/app122111141
Submission received: 4 September 2022 / Revised: 30 October 2022 / Accepted: 31 October 2022 / Published: 3 November 2022
(This article belongs to the Special Issue Asthma and Respiratory Disease: Prediction, Diagnosis and Treatment)
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Abstract

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Although there are different rhinitis phenotypes and—due to recent research and the spread of knowledge on the physiopathological mechanisms underlying rhinitis—different rhinitis endotypes have been recognized, the differences between them are not always clear. This review focused on the features of local allergic rhinitis (LAR) as a rhinitis endotype independent of allergic rhinitis (AR) and nonallergic rhinitis (NAR).

Abstract

Chronic rhinitis (CR) is commonly divided into allergic rhinitis (AR) and nonallergic rhinitis (NAR). AR is triggered by the immunoglobulin E (IgE)-mediated response to allergens, whereas NAR is characterized by the absence of allergic sensitization. Previous studies have demonstrated the presence of local IgE in the nasal mucosa of patients suffering from typical allergic rhinitis (AR) symptoms but without a history of atopy and a positive response to a nasal allergen challenge (NAC). This condition was recently defined as local allergic rhinitis (LAR), which is supposed to be a different CR characterized by a type 2 (T2) inflammation response with the release of typical T2 mediators. LAR is defined as a phenotype of AR characterized by a localized nasal allergic response that is negative skin prick testing to allergens in the absence of serum-specific IgE. Diagnosis is based on a positive response to NAC. This review is an update of LAR literature, focusing on the definition of LAR as an independent endotype. LAR, AR, and NAR are characterized by the same clinical symptoms, although there are some differences between these three subtypes. However, the literature data are not yet univocal in defining LAR as an independent endotype.

1. Introduction

1.1. Definition of Rhinitis

Rhinitis is a generic term that describes nasal symptoms resulting from inflammation of the nasal mucosa. It is a common chronic disease with two main phenotypes: allergic rhinitis (AR) and nonallergic rhinitis (NAR). AR refers to nasal symptoms that are triggered by the immunoglobulin E (IgE)-mediated response to exposure to allergens, whereas NAR is a heterogeneous group of nasal symptoms without allergic sensitization.

1.2. Different Types of Chronic Rhinitis and LAR Definition

While AR can be definitively diagnosed with skin or serum tests (specifically, IgE) and has a clearly understood physiopathology, NAR lacks available diagnostic tools and clear therapeutic protocols. In addition, patients diagnosed with AR can show a concomitant NAR [1].
Evidence in the literature indicates the existence of a local nasal response in patients suffering from typical AR symptoms, but without a history of atopy, defined as a genetic tendency to develop allergic diseases [2,3,4,5,6].
This condition is supposed to be a new endotype called local allergic rhinitis (LAR) or “entopy” [1,2,3,4,5]. LAR is characterized by the production of specific nasal IgE antibodies.
The inflammatory response in the nasal secretions of LAR is a type 2 (T2) inflammation, with the release of typical mediators such as mast cells, eosinophils, IgE, B cells, and T cells, as well as a positive response to nasal allergen challenge (NAC) with the nasal production of IgE, tryptase, and eosinophil cationic protein (ECP) after exposure to aeroallergens but in the absence of systemic atopy [7].
According to recent research, LAR might affect more than 45% of patients previously given a diagnosis of NAR [8]. In addition to AR, LAR can be classified as seasonal–perennial, intermittent–persistent, and mild–moderate–severe. Moreover, LAR worsens over time, with impairment in quality of life (QoL), persistent and increasing severity of rhinitis, and associations with conjunctivitis and asthma [9].
Interestingly, recent reports in the literature state that LAR could be defined as a different endotype, affecting an underestimated number of chronic rhinitis (CR) patients.
In brief, LAR is characterized by symptoms suggestive of AR (nasal obstruction, rhinorrhea, sneezing, itching) negative skin prick test (SPT) and/or serum IgE tests, the presence of local IgE and local ECP following exposure to aeroallergens, and positive NAC (Figure 1).
In addition, other clinical entities have been described within the LAR spectrum: local allergic asthma (LAA) in non-atopic patients who have positive bronchial provocation tests and dual allergic rhinitis (DAR) in atopic patients (coexistence of LAR and allergic rhinitis) [3,10,11,12]. Furthermore, although the existence of local allergic conjunctivitis (LAC) has not been widely confirmed in the ophthalmologic community, it would represent a different ophthalmologic phenotype [13].
The aim of this review was to update the literature on LAR. In addition, we wanted to focus on the definition of LAR as an endotype independent of AR and NAR.

2. Epidemiological Chronology of LAR

LAR is an underdiagnosed chronic phenotype of rhinitis affecting subjects of different countries, ethnicities, and ages [7]. The prevalence of LAR reported in the literature is about 25.7%. It is prevalent in females and associated with an urban lifestyle and a family history of atopy [14].
Among 3400 patients and healthy controls, Hamizan et al. reported a 24.7% of probability of having positive NAC in patients with rhinitis but negative for both SPT and serum sIgE. Another study by the same authors described a 10.2% chance of detectable nasal IgE among 648 NAR subjects [15,16].
LAR prevails in Mediterranean and Western countries compared with Northern European and Eastern countries, with the house dust mite (HDM)—Dermatophagoides pteronyssinus (Der p)—being the most common allergen [7].
It has been frequently described in adults, whereas the description of the endotype in children is rare [9]. However, the prevalence of LAR in the pediatric population is higher in Western countries (range 36.7–66.6%) compared with East countries. The largest study on the pediatric population ascribed the presence of LAR to several pollens (Phleum spp., Artemisia spp., and birch) confirmed by NAC in 17 (16.6%), 6 (5.9%), and 9 (8.9%) patients, respectively, among 121 NAR children with seasonal rhinitis symptoms [7,9,17].
Patients with SPT-negative test results and who are suspected of having local but not systemic production of allergen-specific IgE were first observed by Huggins et al. in 1975 [18]. However, the evolution of the LAR concept dates back twenty years before the discovery of IgEs, in 1947. Samter et al. found that the nasal secretions of allergic individuals could passively transfer a local reaction to nonallergic individuals [19]. Furthermore, in 1970, Tse and colleagues detected ragweed sIgE in the nasal washing of ragweed AR patients [20]. In 1979, Platts-Mills quantified the relative concentrations of IgG, IgA, and IgE against rye grass pollen (RGP) locally produced in nasal secretions [21]. In 1994, Gabriele Sensi found that IgE production increased faster in the nasal mucosa rather than in the serum of HDM patients after allergen stimulation [22].
In 2000, KleinJan and Cameron found IgE local production in the nasal B cells and plasma cells of AR patients [23,24]. In 2003, Powe et al. introduced the term “entopy” to differentiate local from systemic IgE production and, eventually, in 2009, Rondon formulated the current definition of LAR [25,26]. Recently, Zhang et al. found that the production of polyclonal sIgE due to airborne allergens was induced by Staphylococcus aureus in the nose but not in the serum of patients with nasal polyps [27].

3. Physiopathology of LAR

Different physiopathological mechanisms implicated in the local production of IgE in LAR have been suggested in the literature. For instance, previous studies have demonstrated a T2 IgE-mediated inflammatory response activating mast cells and eosinophils and releasing mediators such as tryptase and ECP. However, clear phenomena leading to AR have not been found yet in LAR [7].
The evidence suggests that, in the nasal mucosa, B cells express epsilon germline gene transcripts and mRNA for the epsilon heavy chain of IgE. In addition, in situ hybridization studies have demonstrated the presence of a T2 inflammatory pattern with an increased number of IgE+ B cells, mast cells, and eosinophils in patients with negative skin tests. Follicular lymphoid cells (FLCs) found in the tissue and nasal secretions of AR and NAR patients might mediate hypersensitive immune responses involving mast cells. Thus, LAR and AR had a similar leukocyte–lymphocyte phenotype, as demonstrated by cytoflowmetric studies. Furthermore, the presence of nasal sIgE in the absence of exposure to HDM and grass pollen, as well as the fast and progressive increase in IgE following NAC, points to the persistent local production of IgE in the nasal mucosa [7,23,26,28,29,30].

4. Clinical Manifestations of LAR

According to recent studies, LAR is clinically characterized by nasal symptoms (itching, watery rhinorrhea, etc.) whose severity and evolution are similar to AR. LAR patients typically suffer from chronic rhinitis with associated comorbidities. However, it is not associated with cigarette smoking [14].
The allergen most frequently associated with or causing LAR is Dermatophagoides pteronyssinus (Dp) [9,14,31,32]. The prevalence of LAR associated with Dp was recently demonstrated by Tantilipikorn et al. in 24.2% of adults with CR and negative SPT [33]. According to the authors, LAR is moderate–severe and persistent, with a dominant symptom of sneezing, more frequent in LAR than in NAR [33]. Although the description of the LAR endotype both in adults and in children is rare, there is evidence that LAR could progress over time to AR [9,34].
According to the study by Rondon, LAR has a natural tendency to worsen, with a significant impairment of QoL characterized by the persistence and severity of nasal symptoms and an association with asthma and conjunctivitis. The first 5-year period is a critical timepoint in this worsening natural evolution [6].
A recent study on mice by Jung demonstrated that LAR, as well as AR, causes olfactory epithelial damage and suppresses olfactory marker protein (OMP) expression, which can be reversed with intranasal steroids [35].

5. Diagnostic Work Up

The diagnosis of CR is assessed with the clinical history and evaluation using anterior rhinoscopy and nasal endoscopy, which should always be performed to exclude nasal infection, crust formation, and/or anatomic deformities. Notwithstanding, the SPT and the dosage of serum-allergen-specific IgE are determinants for the diagnosis of AR [36,37].
For instance, the position paper of the European Academy of Allergy and Clinical Immunology (EAACI) does not recommend allergen provocation testing, microbiological analysis, nasal cytology or biopsies, or the measurement of the total or allergen-specific IgE as diagnostic tests for NAR. However, NAC and the measurement of IgE in nasal secretions are of the utmost importance to distinguishing between LAR and NAR, whereas the nasal cytology or biopsies may help distinguish between an inflammatory and a neurogenic etiology [37]. Eosinophilic inflammation in the absence of systemic allergy may be attributed to LAR, nonallergic rhinitis with eosinophilia (NARES), or to intolerance to drugs [37].
Hence, NAC is a helpful diagnostic tool; it is the gold standard in assessing clinical reactivity to an allergen and accurately identifying LAR, as well as assessing accurate therapeutic management and choosing patients for clinical trials and translational and clinical research studies [37].
Although NAC is a well-established technique included in the standard diagnostic workup for rhinitis, being useful in discriminating between the different rhinitis endotypes (AR, LAR, NAR, occupational rhinitis, etc.) and designing the composition of allergen immunotherapy (AIT), it remains a time- and resource-consuming technique, whose safety and reproducibility are still limited, especially in children [38]. In addition, NAC is not everywhere available, and it is difficult to apply. However, recently, Eguiluz-Gracia et al. demonstrated that NAC is safe and reproducible and ready to be used in clinical practice in both children and adults with or without asthma [38].
In the absence of systemic atopy, the presence of nasal sIgE and a positive NAC response confirm the diagnosis. According to Colavita, the measurement of IgE in nasal lavage fluid may be considered an easy and rapid method to diagnose LAR in children [39]. IgE is generally determined in nasal lavage fluid during natural exposure or after NAC [40,41]. Single aeroallergen NAC is an important diagnostic tool, and its sensitivity seems to be higher than nasal IgE, tryptase, or ECP level determination [36,40].
The basophil activation test (BAT) is another diagnostic test for LAR, with a sensitivity of 50–66% for HDM and pollens, and with a specificity of >90%. Unlike nasal IgE, the BAT does not require a previous NAC to increase the sensitivity [3,42,43,44,45].
Although recent studies have emphasized the use of next-generation sequencing (NGS) and quantitative real-time PCR (qRT-PCR) in advanced respiratory disease diagnostics, their role in LAR remains elusive. Furthermore, the current biomarker for the clinical use of LAR remains the level of the local IgE [46,47].

6. NAC Technique

NAC is of the utmost importance in the diagnosis of LAR according to the Task Force (TF) on the “Standardization on Nasal Allergen Challenges” of the Ear, Nose and Throat (ENT) section of the European Academy of Allergy and Clinical Immunology (EAACI) [48].
Systemic or local therapies can alter the response to NAC, so, according to the EAACI, any drug with an elevated risk of intolerance, allergic reaction, or drug interference should be discontinued for a given washout period depending on the different medications [48].
The EAACI proposed the use of a standardized test solution, with two puffs (0.1 mL per nostril) of bilateral spray with an allergen and a subjective–symptomatic visual analog scale (VAS) or other questionnaires and objective evaluations of clinical outcomes. However, the EAACI also suggested that the ideal subjective scale should contain the key symptoms of sneezing, nasal pruritus, rhinorrhea, nasal obstruction, and ocular symptoms. The use of VAS for congestion, sneezing, itching, and rhinorrhea with a vertical line on a scale between 0 and 100 mm is a clear and easy-to-use method for measuring the severity of symptoms [48].
In general, objective evaluation includes rhinomanometry or a Pick Nasal Inspiratory Flow meter (PNIF), although other objective measurements can be used, such as Acoustic rhinometry (AcRh) and 4-phase-rhinomanometry (4PR) [48].
Allergen applications with spray bottles with 50 lL/puff nozzles are recommended by the EAACI. Different manufacturers of allergen provocation solutions are available on the market [48].
The current NAC technique is divided into three measurement steps, (1) baseline measurement, (2) control challenge, and (3) allergen challenge, with subjective and objective assessments of nasal ventilation in each step [48].
At baseline, nasal ventilation is assessed before the application of any substance, comparing the results of the control and the allergen challenge with the baseline value [48].
Since allergen solutions may contain preservatives, it is then necessary to perform a control challenge with the same diluent, which is used to prepare the allergen solutions to verify reactions with the nasal mucosa, or hyperreactivity, which may occur in all types of rhinitis. The EAACI suggests bilaterally challenging control and allergen substances [48].
Next, the allergen is applied when the control causes <50% of the positivity criteria. When the control agent is ≥50% of a positive reaction, the EAACI recommends a new test after a few days [48]. To obtain the best comparability of the control with the allergen reaction, the timing of the assessment should also be unified; 10 or 15 min are advisable [48]. Ten minutes after applying the control solution, clinical symptoms and changes in the objective measurements of the nasal patency by the rhinomanometry (or another objective measurement) should be assessed [48]. Then, the symptoms and rhinomanometric parameters are recorded 10 min after applying the allergen. Symptom scores must be filled out once, whereas rhinomanometric parameters (or another objective measurement) must be measured with three measurements in a row to eliminate technical problems. However, a single measurement is sufficient if the test outcome is positive; conversely, when the test is negative, the measurement should be repeated after another 10 min [48].
The NAC is positive in cases of a strong increase in the objective measurement, a strong increase in the subjective symptoms, or a moderate increase in the two criteria (the objective and subjective measurements) [48]. Afterward, NAC patients should be kept under observation for at least half an hour until the reaction ceases; then, they should have access to topical nasal decongestants and topical or systemic antihistamines. Systemic reactions should be treated. A delayed reaction of up to 12 h can occur, and patients should be advised of this [48].

7. Clinical Management

First-line therapy for LAR should be nasal corticosteroids with/without antihistamines [3,10].
Previous randomized studies have demonstrated that AIT is able to control nasal and ocular symptoms, decrease the need for rescue medication, and improve QoL in LAR individuals [3,10,49]. AIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma [50,51,52].
Although AIT is effective in LAR patients, it might not always achieve the expected treatment effect.
Previous studies have suggested that a combination of biologics and AIT may promote a better effect and a long-lasting state of tolerance to specific allergens [53].
A very recent study by Bozec demonstrated that biologics may increase the effectiveness of AIT in patients with severe LAR [53].
In that study, the authors evaluated the effectiveness of omalizumab in perennial LAR with or without AIT. Similar studies on the effectiveness of omalizumab added to AIT were previously conducted for AR [53].
The first study evaluated the positive effects of a combination of AIT and omalizumab therapy on AR in polysensitized children and adolescents. Another study assessed the efficacy of 24 weeks of therapy with omalizumab alone in perennial AR [52].
According to the authors, this therapeutic protocol significantly reduced serum IgE and the clinical response to NAC [53].
AIT might reduce IgE secretion in the nasal mucosa. Combining AIT therapy with omalizumab in LAR may be an innovation in managing patients in whom only a partial effect has been achieved after AIT [53].
In conclusion, omalizumab may be a valuable treatment that increases the effectiveness of immunotherapy in patients with severe LAR, although these observations require further research [53].

8. Rhinitis Endotypes

8.1. LR vs. AR

Although there are different rhinitis endotypes, the differences between them are not always clear [54].
AR and LAR share many clinical features, such as a positive NAC response, markers of TH2 nasal inflammation (including IgE in nasal secretions), and a significant rate of asthma development [11].
However, some LAR patients seem to not develop the typical IgE-dependent response. According to previous studies, if this response occurs, it will develop differently without switching IgG + B to IgE [12]. In addition, local mechanisms underlying LAR immunological responses to an allergen might be more numerous than those underlying AR and involve IgE reactions. Thus, IgE-dependent responses might not be the only ones [54].
In a recent study, it was demonstrated that the nasal mucosa’s exposure to allergens leads to the accumulation of IgE+ plasmablasts in LAR patients, which display markers of sequential class switch recombination to IgE (IgM → IgG → IgE). LAR patients seem to express specific IgE on the membrane of peripheral basophils and a higher level of serum sIgG than healthy individuals [55].
Although many similarities exist, LAR seems to not be the first stage of AR according to the recent literature; however, it should be considered a differential diagnosis in subjects of any age with symptoms suggestive of AR but without evidence of systemic atopy [11,54]. However, the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification system does not consider LAR a distinct disease [32].
According to some studies, LAR is a consistent entity that does not evolve to AR with systemic atopy over time, although patients have a significant impairment in QoL and an increase in the severity of nasal symptoms over time. Lower airways can also be involved [54]. Other studies on mice have shown that “entopic” patients might be at risk of systemic IgE-dependent reactions. It is likely that studies in humans have demonstrated positive reactions in skin prick tests and serum IgE over several years of follow-up in LAR groups [9,26,56,57].

8.2. LAR vs. NAR

Differentiating between LAR and NAR is necessary for the accurate therapeutic management of patients. However, the differential diagnosis between LAR and NAR has become a challenge for the clinician. NAR is a heterogeneous group of nasal conditions with chronic nasal symptoms, and the diagnosis is made by excluding an endonasal infection and signs of AR and LAR [5]. LAR cannot be considered an “idiopathic rhinitis” within the NAR group, as it is based on an IgE-mediated reaction triggered by well-known allergens [14].
Most likely, LAR patients represent a subgroup of those formerly defined as NARES [37]. Previous studies classified LAR as a spontaneous process involving inflammatory markers without NAC. According to recent studies, the presence of allergen-specific IgE in the nasal lavage fluid of both NAR and healthy subjects suggests that nasal IgE production could represent the expression of an innate response rather than a specific local reactivity [58]. In addition, recently, Eckrich et al., evaluating the prevalence of potential LAR in patients suffering from NAR in a non-selected group of subjects, found IgE in subjects with HDM allergy, but not in NAR. [59] Hence, the authors concluded that, in the non-selected population, the exclusive local production of IgE was absent, challenging the concept of LAR [54] (Table 1).

8.3. LAR and Asthma

The association of LAR and concurrent asthma symptoms have been reported in 20–47% of patients [60]. According to another study, the 50% of patients with LAR had a positive methacholine test [60]. In addition, 83.3 % of AR patients and 57.9% of NAR patients are diagnosed with asthma. Furthermore, the bronchial allergen challenge (BAC) is reported as positive in 28.8 % of patients with LAR and 83.3% of patients with AR but negative in NAR patients and healthy controls [60].
Methacholine testing increased airway hypersensitivity after exposure to an allergen, and eosinophils and monocytes in the sputum were significantly elevated [60]. In addition, a significant increase in eosinophils, monocytes, and ECP were observed in the sputum of BAC+ patients with and without atopy but not in BAC- patients [60].

8.4. LAR and Conjunctivitis

Some LAR patients experience ocular symptoms such as redness, itching, tearing, and burning after exposure to allergens, as well as NAC. Pollen-reactive subjects seem to be more prone to ocular symptoms than dust mite-reactive subjects [61].
The most recent literature has described the ocular counterpart of LAR in non-atopic patients, characterized by conjunctivitis and the presence of IgE in tears [61].
However, knowledge of the nature of ocular symptoms is still lacking.
In addition, it is not clear whether there is real conjunctival sensitization or whether the ocular symptoms occur because of nasal–ocular reflexes due to allergen exposure [61].

9. Discussion

CR is generally divided into AR and NAR. AR represents an important public health issue for both its increasing incidence and its impact on QoL and school and job performance. AR is identified by SPT and/or serum-allergen-specific IgE. The current classification of CR into AR and NAR appears to be obsolete; indeed, it does not consider the rhinitis that produces local IgE in the nasal mucosa known as LAR [61].
A localized immune response in the nose is the disease concept of LAR and the assumption of its definition. The term LAR describes a T2 nasal mucosal inflammatory condition characterized by the local production of specific IgE antibodies and positive NAC in the absence of systemic atopy [61].
However, the mechanisms underlying LAR are still debated, and some clinical features of LAR are similar to AR, but LAR patients are generally younger than AR ones, with more severe symptomatology and family histories of atopy [60,61].
Lacking systemic atopy, the differential diagnosis of LAR is assessed by the induction of allergic symptoms such as sneezing, nasal itching, rhinorrhea, nasal obstruction by antigen administration in the nasal mucosa, and the presence of IgE antibodies in the nasal mucosa [48].
Since its first description in the literature, much has been discussed about the “true” nature of LAR—i.e., whether LAR is an independent endotype of chronic rhinitis, or whether it is the expression of AR or NAR. More recently, it has been also discussed whether LAR is the evolution or the consequence of another chronic rhinitis endotype, such as AR, NAR, or NARES, thus not representing, per se, an independent endotype [18,19].
From a clinical point of view, LAR, AR, and NAR are CR characterized by the same clinical symptoms, such as rhinorrhea, sneezing, itching, and nasal obstruction [61]. However, there are some differences between these three subtypes [61]. While rhinosinusitis, sleep disorders, learning difficulties, otitis media with effusion, and reduction in QoL are common in all CR subtypes, allergic comorbidities such as asthma and conjunctivitis are more frequently associated with AR and LAR [61]. A strong association has also been described between asthma, AR, and chronic rhinosinusitis [61].
Furthermore, it has been reported that the association with asthma increases in the pediatric population in the presence of AR [61].
Recent studies have also reported an increase in bronchial symptoms and lower airway symptoms after 10 years of disease evolution in patients with LAR [60].
However, according to the previous literature, LAR seems to not be the first stage of AR, so it should be considered a different entity [11,54]. Thus, LAR could be an independent entity that does not evolve into AR and involves lower airways [55]. Conversely, ARIA does not consider LAR a distinct disease [32].
While SPT and/or serum IgE are diagnostic tools useful in the assessment of AR, NAC, nasal IgE, and/or BAT are useful for revealing LAR patients (Table 1).
Surprisingly, human studies have shown a positive reaction to allergy tests over several years of follow-up in patients with LAR [9,26,56,57].
Although the differentiation between LAR and NAR is necessary to treat patients, the differential diagnosis between these two entities is quite difficult for clinicians, and the diagnosis of NAR is often made by excluding other chronic rhinitis types [6]. In addition, LAR could also represent a subgroup of chronic rhinitis formerly defined as NARES [37].
The presence of nasal-allergen-specific IgE in NAR, as well as in healthy subjects, suggests that nasal IgE production could represent the expression of an innate response rather than a specific local reactivity [58].

10. Conclusions

Although different rhinitis endotypes exist, the differences between them are not always clear. LAR is a T2 inflammatory disease caused by a localized allergic reaction in the nasal mucosa [60]. However, the literature data are not yet univocal in defining LAR as an independent endotype despite most of the recently published works moving in that direction.
In light of the recent literature and in the era of precision medicine, it is of fundamental importance to start new studies to define and understand the “true” nature of LAR and to confirm the possible hypothesis of LAR as an independent endotype. Further studies are also needed to find simpler and more reliable diagnostic strategies, not only in the adult population but also in children, although the incidence and evolution of LAR in the pediatric population are still unknown. For instance, some adults suffering from LAR reported the onset of LAR during childhood, suggesting that LAR might be a stable endotype since childhood [8]. Conversely, another study reported that LAR is the first, initial, and transient stage in the evolution of the disease to AR, particularly in the first two decades of life and in polysensitized children [8].
Regarding therapy, no controlled studies have evaluated the effect of standard therapies such as oral antihistamines, intranasal or inhaled corticosteroids, or bronchodilators in LAR subjects. Since both AR and LAR share many clinical and physiopathological features, including eosinophilia, it is reasonable, as suggested by clinical experience, to expect that patients would benefit from treatment with nasal steroids and antihistamines.

Author Contributions

Conceptualization, E.C. and A.D.; methodology, E.C.; validation, E.C., A.D. and E.D.C.; formal analysis, E.C. and E.D.C.; data curation, E.C., A.D. and E.D.C.; writing—original draft preparation, E.C., A.D. and E.D.C.; writing—review and editing, E.C., A.D. and E.D.C.; visualization, E.D.C.; supervision, E.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Applsci 12 11141 g001 550
Figure 1. Nasal Symptoms in chronic rhinitis: (AR) allergic rhinitis; (NAR) nonallergic rhinitis; (LAR) local allergic rhinitis.
Figure 1. Nasal Symptoms in chronic rhinitis: (AR) allergic rhinitis; (NAR) nonallergic rhinitis; (LAR) local allergic rhinitis.
Applsci 12 11141 g001
Table
Table 1. Differential diagnosis of chronic rhinitis. Markers for the diagnosis of rhinitis endotypes.
Table 1. Differential diagnosis of chronic rhinitis. Markers for the diagnosis of rhinitis endotypes.
Chronic RhinitisSPT 1Serum IgENasal IgENAC 2BAT 3Reference
AR++(−)+(−)++[36,37]
NAR−−−−−[36,37]
LAR−−+(−)++(−)[36,37]
1 SPT: skin prick test, 2 NAC: nasal allergen challenge, 3 BAT: basophil activation test.
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Cantone, E.; Detoraki, A.; De Corso, E. Local Allergic Rhinitis: A Different Rhinitis Endotype? Literature Overview. Appl. Sci. 2022, 12, 11141. https://doi.org/10.3390/app122111141

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Cantone E, Detoraki A, De Corso E. Local Allergic Rhinitis: A Different Rhinitis Endotype? Literature Overview. Applied Sciences. 2022; 12(21):11141. https://doi.org/10.3390/app122111141

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Cantone, Elena, Aikaterini Detoraki, and Eugenio De Corso. 2022. "Local Allergic Rhinitis: A Different Rhinitis Endotype? Literature Overview" Applied Sciences 12, no. 21: 11141. https://doi.org/10.3390/app122111141

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