Nonallergic Rhinitis With Eosinophilia Syndrome Research Articles

Non-allergic rhinitis with eosinophilia syndrome treated with mepolizumab: A case report

<abstract> <p>Non-allergic rhinitis with eosinophilia syndrome (NARES) is a chronic inflammatory rhinopathy characterized by nasal obstruction, rhinorrhea, sneezing and/or an itchy nose. Although eosinophilic nasal cytology is common in NARES patients, identifying the condition is challenging due to a lack of consensus on the diagnostic processes and the role of nasal cytology in clinical practice. Patients may undergo several allergy tests with negative or inconclusive results and are eventually diagnosed with idiopathic/aspecific rhinitis. Treatment options may include intranasal corticosteroids, intranasal antihistamines or a combination of both types of medication. This case report describes a patient with NARES who was unresponsive to conventional therapies and experienced significant improvement after treatment with Mepolizumab, a drug approved for severe asthma with hypereosinophilia, hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyposis (CRSwNP) and eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab was administered once a month at a dose of 100 mg subcutaneously. The patient experienced a complete remission of symptoms a year after starting the off-label treatment. Blood counts remained stable and no adverse effects were observed. Mepolizumab appears to be a potential therapeutic alternative in patients with NARES who are unresponsive to conventional therapies.</p> </abstract>

Течение хронического риносинусита с синоназальным полипозом у пациентов с эозинофильной астмой на фоне лечения

Background: chronic rhinosinusitis (CRS) with polyps is associated with eosinophilic inflammation where interleukin-5 (IL-5) is acting as a key mediator. Commonly, CRS co-exists with asthma. Aim: to assess the efficacy of reslizumab for the treatment of CRS with sinonasal polyposis in patients with severe eosinophilic asthma. Patients and Methods: the study included 21 patients. For the management of severe asthma all patients received reslizumab as intravenous infusion at a dose of 3 mg/kg body weight, once every 4 weeks. CRS with sinonasal polyposis was found in 19 patients, pathological changes of the paranasal sinuses revealed by computer tomography (CT) — in all patients, and symptoms of chronic non-allergic rhinitis with eosinophilia syndrome (NARES) were present in 2 patients. The efficacy of therapy was evaluated 6 months after the beginning of treatment. Over-time changes in the following indicators were evaluated: nasal symptoms, endoscopic pattern of the nasal cavity and paranasal sinuses, total polyp score (TPS), CT findings in the paranasal sinuses, rhinocytogram, blood eosinophil cationic protein level, and eosinophilia. The effectiveness of asthma control was assessed by the reduction in asthma exacerbation rate and the requirements for systemic corticosteroids, as well as the spirometry results and the asthma control test. Results: along with a noticeable improvement of asthma control, 20 patients had clinical, endoscopic and radiological signs of the decrease in severity of nasal symptoms. A more significant improvement of asthma control was achieved in patients with CRS and polyps. The medical histories of patients with CRS and polyps demonstrated that at the early stages of the disease they had NARES symptoms. This finding suggests that NARES could be a predictor of eosinophilic non-IgE-mediated asthma and nasal polyps. Conclusion: the use of reslizumab for the treatment patients with eosinophilic asthma and comorbid CRS with polyps and NARES enables not only to improve the control of asthma symptoms but also to achieve the notable regression of nasal symptoms. KEYWORDS: chronic rhinosinusitis with polyps, asthma, iterleukin-5, reslizumab, non-allergic rhinitis with eosinophilia syndrome. FOR CITATION: Boyko N.V., Churyukina E.V., Lodochkina O.E., Ukhanova O.P. The clinical course of chronic rhinosinusitis with sinonasal polyposis in patients with eosinophilic asthma amid the treatment. Russian Medical Inquiry. 2023;7(2):103–109 (in Russ.). DOI: 10.32364/2587-6821-2023-7-2-103-109.

Nasal eosinophilia as a preliminary discriminative biomarker of non-allergic rhinitis in every day clinical pediatric practice.

Non-allergic rhinitis (NAR) in children, named local allergic rhinitis (LAR) and non-allergic rhinitis with eosinophilia syndrome (NARES), are recently termed entities in childhood characterized by symptoms suggestive of allergic rhinitis in the absence of systemic atopy. Nasal eosinophils (nEo) are the principal cells involved in the allergy inflammation and nasal allergen provocation test is the gold standard method for the diagnosis, albeit with several limitations. The aim of this study was to validate the presence of nEo in combination with the therapeutic response to nasal steroids, as a preliminary discriminator of NAR in real life data. In a prospective cohort study, 128 children (63.3% male, aged 72 ± 42m) with history of NAR were enrolled and followed up for 52 ± 32m. Nasal cytology was performed and nasal steroids trial was recommended initially in all and repeatedly in relapsing cases. Response to therapy was clinically evaluated using 10-VAS. Significant nEo was found in 59.3% of the cases and was related to reported dyspnea episodes. 23.4% had no response to therapy, whereas 51.5% were constantly good responders. Response to therapy was related to nEo and a cutoff point of 20% was defined as the most reliable biological marker with 94% sensitivity and 77% specificity. In children with symptoms of NAR, the presence of nEo > 20% constantly responding to nasal steroid therapy, is a clear indicator of atopy. In an everyday clinical setting, it emerged as an easy, preliminary, cell biomarker suggestive of further investigation such as NAPT, to discriminate LAR from NARES.

Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis with Eosinophilia Syndrome: a Systematic Review.

Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder. The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP.

Diagnosis of Obstructive Sleep Apnea in Patients with Allergic and Non-Allergic Rhinitis.

Background and objectives: Rhinitis could be considered a risk factor for obstructive sleep apnea (OSA). Studies were conducted to evaluate the relation between OSA and Allergic rhinitis (AR). Non-allergic rhinitis with eosinophilia syndrome (NARES) is a condition with a symptomatology apparently similar to AR. The aim of this study was to evaluate the different presence of OSA in patients suffering from NARES and AR. Materials and Methods: Sixty patients were enrolled and subdivided into NARES, AR and control groups. NARES and AR diagnosis were performed using ARIA (Allergic Rhinitis and its Impact on Asthma) protocol. All patients were screened for OSA with home sleep apnea testing (HSAT) exam analyzing AHI (Apnea Hypopnea Index) values. Results: Results showed that 60% of patients affected by NARES presented OSA. On the contrary, altered AHI was found only in 35% of patients affected by AR and in 10% of patients belonging to the control group. Conclusions: In conclusion, data showed that there was an increased risk of OSA in NARES patients respect to AR patients and healthy patients.

Charcot-Leyden Crystal Protein in Nasal Secretions of Patients with Nonallergic Rhinitis with Eosinophilia Syndrome

Introduction: Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation. Objective: The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES). Methods: Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA. Results: CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (r_s = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate. Conclusions: CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment.

Diagnosis and management of nonallergic rhinitis with eosinophilia syndrome using cystatin SN together with symptoms

BackgroundThe diagnosis and treatment of nonallergic rhinitis with eosinophilia syndrome (NARES) remain controversial. The aim of this study was to evaluate whether Cystatin SN together with symptoms can be used to diagnose NARES and to measure the efficiency of medical treatment. MethodsSeventy-five patients with chronic rhinitis (CR) and 18 control subjects were enrolled. Their clinical characteristics were reviewed and laboratory parameters were evaluated. The concentration of Cystatin SN in nasal secretions was determined using the enzyme-linked immunosorbent assay. The histological assessment of Cystatin SN in the nasal mucosa was conducted by hematoxylin and eosin staining. The logistic regression and receiver operating characteristic curves were used to assess the predictive value of parameters for NARES. ResultsNasal obstruction, sneezing, loss of smell, and total visual analogue scale (VAS) score were significantly different among the patients with CR. In particular, olfaction score was higher in patients with NARES than in those without NARES (AR, LAR, or IR). Similarly, the Cystatin SN level was significantly different between the control subjects and patients with CR. After treatment for 2 weeks, the Cystatin SN level and VAS score were significantly decreased in the NARES group. The accuracy of Cystatin SN together with local sIgE and loss of smell to diagnose NARES was up to 0.987 (sensitivity, 100%; specificity, 93.1%). ConclusionsCystatin SN with local sIgE and loss of smell may serve as one of the reliable and alternative biomarkers for the diagnosis of NARES and be used to evaluate disease severity and NARES treatment efficacy.

The role of the fern test in the treatment of rhinitis

The fern test is a method for assessing the characteristics of the nasal section in the treatment of patients with mucous dysfunction of the airway. The aim of this study was to investigate the role of the fern test in patients with rhinitis and to assess the classification of each type of rhinitis (types I-IV) in clinical practice. A cross-sectional study, which included consecutive patients from a third level Rhinology Unit, worked with 182 patients with rhinitis and 30 healthy subjects as control. The patients were subdivided according to their type of rhinitis: allergic rhinitis (59), infectious rhinitis (32), polyps (31), NARES (Non-allergic rhinitis with eosinophilia syndrome) (30) and NARNE (non-allergic rhinitis with neutrophils) (30). The control subjects had only type I or II rhinitis, whereas patients with rhinitis usually showed type III or IV. Allergic rhinitis and nasal polyps had the most serious deterioration according to the fern test (type IV). The fern test is effective for assessing mucus alterations in patients with rhinitis and it could be included as a new parameter in the study of rhinitis as a potential biomarker of the function of damaged epithelial cells.

Endotypes of chronic rhinitis: A cluster analysis study.

Chronic rhinitis (CR) is currently regarded as a syndrome, which presents as several endotypes. The aim of this study was to identify the CR endotype clusters and investigate the inflammatory patterns associated with the different endotypes. A total of 259 CR patients and 20 control subjects were enrolled in this prospective study. Twelve clinical variables were analyzed using cluster analysis and five inflammatory variables were measured to investigate the inflammatory patterns associated with the different clusters. Six endotype clusters of CR were defined in the Chinese CR patients. Patients in cluster 1 (38.6%) were diagnosed as allergic rhinitis (AR) without asthma, and in cluster 2 (13.5%) as AR with asthma, with all demonstrating positive results for local eosinophils and high levels of local and serum IgE. Similarly, patients in cluster 3 (18.6%) were diagnosed as nonallergic rhinitis with eosinophilia syndrome (NARES) without asthma and in cluster 5 (5.0%) as NARES with asthma, with all demonstrating positive results for local eosinophils, and negative results for both local and serum IgE. Patients in cluster 4 (4.6%) were diagnosed as local allergic rhinitis and showed positive results for local eosinophils and local IgE, but negative results for serum IgE, whereas patients in cluster 6 (19.7%) were diagnosed as idiopathic rhinitis because of high symptoms scores, but negative findings for local eosinophils, local IgE, and serum IgE. Chinese CR patients may be clustered into six endotypes with different inflammatory patterns, which may help in delivering individualized treatment.

Granulocyte-Macrophage Colony-Stimulating Factor Production and Tissue Eosinophilia in Chronic Rhinitis.

Introduction Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a strong proinflammatory cytokine that takes part in allergic nasal inflammation as an eosinophil colony-stimulating factor. However, the role of GM-CSF in non-allergic rhinitis has not been fully explored. Objectives The aim of this investigation was to assess the concentration of GM-CSF in nasal secretions of patients with non-allergic rhinitis with eosinophilia syndrome (NARES) in comparison to patients with perennial allergic rhinitis (PAR) and healthy subjects, as well as to assess the relationship with the degree of eosinophilic inflammation and clinical characteristics of the patients. Methods Fourteen patients with diagnosis of NARES, 14 PAR patients, and 14 healthy subjects were included in this cross-sectional study. All patients underwent symptom score assessment, nasal endoscopy, allergy testing, and cytological evaluation. The concentration of GM-CSF in nasal secretions of all participants was measured by enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher levels of GM-CSF in patients with NARES than in the control group (p = 0.035). The percent of eosinophils in nasal mucosa was higher in NARES patients in comparison to patients with PAR (p < 0.001) and control patients (p < 0.0001). We found positive correlations between GM-CSF levels and eosinophil counts only in NARES patients. Conclusion The concentrations of GM-CSF in nasal secretions correlate well with eosinophil counts in the nasal mucosa of NARES patients. These facts indicate a possible role of GM-CSF as a favorable marker for assessment of nasal disease severity and the degree of chronic eosinophilic inflammation in the nasal mucosa.

Nonselective chemokine levels in nasal secretions of patients with perennial nonallergic and allergic rhinitis.

An increased production of several chemoattractants, responsible for guiding the eosinophilic inflammatory process, has been reported in chronic rhinitis. The aim of this study was to evaluate nasal secretion levels of monocyte chemoattractant protein-1 (MCP-1), MCP-3, and regulated on activation normal T cell expressed and secreted (RANTES) and to correlate those levels with nasal symptoms and degree of eosinophilia in patients with nonallergic rhinitis with eosinophilia syndrome (NARES) and perennial allergic rhinitis (PAR). Fourteen patients with PAR and 14 NARES patients were recruited for this cross-sectional study. Fourteen healthy subjects were included as controls. The concentrations of MCP-1, MCP-3, and RANTES in nasal secretions were measured using enzyme-linked immunosorbent assay (ELISA). Eosinophil counts were performed by percentage of differential granulocyte counts during cytological examination of scraped nasal mucosa obtained from the inferior turbinate. Therefore, we scored rhinitis patients according to nasal symptom score. We found significantly higher concentrations of MCP-1 (p < 0.0001), MCP-3 (p = 0.018), and RANTES (p < 0.0001) in nasal fluid of NARES patients compared to patients with PAR. In PAR patients, we found positive correlation between RANTES levels and nasal symptom score and eosinophil counts. In patients with NARES, the concentrations of MCP-1 and RANTES were associated with nasal symptom score and percentage of eosinophils. NARES is characterized by higher degree of eosinophilic inflammation than PAR. RANTES correlates well with the level of eosinophilic inflammation in both diseases. The measurement of chemokine levels in nasal secretions could be useful in evaluating the degree of chronic nasal inflammation.

Peculiarities of non-allergic rhinitis with eosinophilia syndrome

Nonallergic rhinitis with eosinophilia syndrome (NARES) is a syndrome containing the symptoms similar to allergic rhinitis, with absence of atopy and the presence of eosinophila more than 20% in smears from nasal mucosa. Pathophysiology of NARES has not been studied completely, but permanent eosinophilic inflammation is the keystone of NARES pathogenesis. This disease is marked by local eosinophilic infiltration without atopy, confirmed by negative skin tests, normal levels of total and specific IgE in serum, negative nasal provocation tests with allergens. Nowadays this nosology is considered to be poorly understood.

Non-allergic rhinitis with eosinophilia syndrome is not associated with local production of specific IgE in nasal mucosa.

Non-allergic rhinitis with eosinophilia syndrome (NARES) is an eosinophilic inflammation of the nasal mucosa without evidence of an allergy or other nasal pathologies. Patients complain about perennial symptoms like nasal obstruction, rhinorrhea, itchiness and sneezing of the nose sometimes accompanied by hyposmia. The aim of the study was to better characterize NARES patients using immunoassay-biochip technology to examine serum and nasal secretion. Sera and nasal secretion of patients with NARES (perennial nasal symptoms, no evidence of acute or chronic rhinosinusitis with or without polyps, negative SX1-Screening test and/or negative skin prick test, eosinophilic cationic protein in nasal secretion >200ng/ml) were tested by immunoassay-biochip technology (ImmunoCAP(®) ISAC, Phadia). 112 different allergen components from 51 allergen sources were tested on the chip. Furthermore, serum and nasal secretion were tested for specific IgE to Staphylococcus aureus enterotoxin TSST-1 by fluorescence-enzyme-immunoassay (UniCAP(®), Phadia). Unrecognized systemic sensitization could be ruled out by negative ISAC results in sera of all patients. Testing of nasal secretion for allergen-specific IgE by ISAC chip technology was negative as well in all cases. In one patient, a systemic sensitization to Staphylococcus aureus superantigen TSST-1 was detectable but no allergen-specific IgE to TSST-1 was measurable in nasal secretion of any patient. The results demonstrate that NARES is not associated with local allergy (entopy) nor with a local inflammation driven by Staphylococcus aureus enterotoxin TSST-1. Further studies are necessary to better understand the underlying mechanisms of NARES.

Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation.

The aim of the present study was to measure eotaxin-3 (CCL26) and eotaxin-2 (CCL24) in nasal lavage fluid of patients with different forms of chronic sinonasal eosinophilic inflammation to evaluate their role in the pathophysiology of nasal hypereosinophilia. The study was an analytic cross-section study, level of evidence 3b. Patients (n = 80) with nasal hypereosinophilia were randomly recruited and grouped in the following categories: persistent allergic rhinitis (AR) (n = 25), nonallergic rhinitis with eosinophilia syndrome (NARES) (n = 30), and chronic rhinosinusitis with polyps (CRSwNP) (n = 25). Non-rhinitic volunteers (n = 20) were recruited as controls. CCL24 and CCL26 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) Quantikine Human Immunoassays (R&D Systems, Minneapolis, MN) in nasal lavage fluids. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped from the inferior turbinate. Mean CCL26 levels were significantly higher (p < 0.05) in AR and in NARES (132.0 pg/mL and 187.63 pg/mL, respectively) than in the control group (13.5 pg/mL); in patients with CRSwNP, CCL26 values were increased compared to controls even though the difference was not statistically significant (58.9 pg/mL vs 16.5 pg/mL). Mean CCL24 levels measured in AR, NARES, and CRSwNP were significantly increased (p < 0.05) compared to controls (96.7 pg/mL, 135.4 pg/mL, and 107.0 pg/mL, respectively, vs 32.2 pg/mL). Moreover, we observed a significant correlation between CCL24 and CCL26 levels, evaluating them intraindividually by Spearman's rank correlation test. Finally, a significant correlation was found between CCL24 and CCL26 levels and the percentage of eosinophilic infiltration of nasal mucosa. Our data suggest that CCL26 and CCL24 are likely involved in the pathogenesis of chronic nasal hypereosinophilia, with a complex cooperation and different involvement of the various members of eotaxin family. Further studies are necessary to better understand the actual physiopathologic mechanism, possible clinical relevance, and therapeutic implications.

Study on the correlation between subjective symptoms and function of nasal ventilation in nonallergic rhinitis with eosinophilia syndrome

Objective To analyze the correlation between subjective symptoms and function of nasal ventila-tion in nonallergic rhinitis with eosinophilia syndrome （ NARES） ,in order to provide the basis for the clinical diagno-sis.Methods 44 patients with NARES were selected as the NARES group ,and 50 healthy people were selected as the control group at the same time .The total nasal resistance （ TNR ） , MCA of the two groups were compared , and Pearson or Spearman correlation was used to analyze the subjective symptoms and objective test indexes in patients with NARES.Results Before contraction,the TNR values of NARES group in 75Pa and 150Pa were higher than those of the control group （Mann-Whiteny Z=7.365,8.125,all P〈0.05）.After contraction,the differences of TNR values in 75Pa and 150Pa,MCA,the correlation analysis in 8 subjective symptoms and 7 objective index of NARES had no statistically significant differences between the two groups （ all P 〉0.05）.Conclusion The correlation between subjective symptoms and function of nasal ventilation in NARES patients is not obvious .Clinical diagnosis should be comprehensive ,in case of missed diagnosis and misdiagnosis . Key words: Rhinitis; Eosinophilia

Chapter 14: Nonallergic rhinitis.

Rhinitis is characterized by one or more of the following nasal symptoms: congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is classified as allergic or nonallergic, the latter being a diverse syndrome that is characterized by symptoms of rhinitis that are not the result of IgE-mediated events. Excluding infectious rhinitis and underlying systemic diseases, clinical entities that can be classified among the disorders that make up the nonallergic rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa), hormone induced, senile rhinitis (of the elderly), rhinitis associated with chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant formerly known as vasomotor rhinitis but more accurately denoted as nonallergic rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be one-third that of allergic rhinitis, affecting ∼7% of the U.S. population or ∼22 million people. NAR is the most common of the nonallergic rhinitis subtypes, comprising at least two-thirds of all nonallergic rhinitis sufferers. Although certain precipitants such as perfume, strong odors, changes in temperature or humidity, and exposure to tobacco smoke are frequently identified as symptom triggers, NAR may occur in the absence of defined triggers. The diagnosis of nonallergic rhinitis is purely clinical and relies on a detailed history and physical exam. Skin testing or in vitro testing to seasonal and perennial aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because of the heterogeneous nature of this group of disorders, treatment should be individualized to the patient's underlying pathophysiology and/or symptoms and is often empiric.

Diagnosis of Allergic Rhinitis

Rhinitis is divided into allergic and non-allergic rhinitis. Non-allergic rhinitis includes inflammatory rhinitis, such as non-allergic rhinitis with eosinophilia syndrome (NARES) and infective rhinitis, and non-inflammatory rhinitis, such as vasomotor rhinitis and idiopathic rhinitis. Allergic rhinitis is diagnosed based on the presence of allergen-specific IgE and the documentation of relationship between the allergen and symptoms in patients with typical rhinitis symptoms, such as rhinorrhea, nasal obstruction, itchiness and/or sneezing. Local allergic rhinitis can be considered for differential diagnosis. Allergic rhinitis should be differentiated from non-allergic rhinitis by using skin prick test, serum specific IgE test, nasal cytology and/or allergen nasal provocation test. Allergic rhinitis should be differentiated from structural nasal diseases, such as septal deviation and nasal polyps. Rhinitis is frequently accompanied by paranasal sinusitis, which should be recognized in clinical practice. Management strategies differ between allergic and nonallergic rhinitis. In addition to pharmacotherapy, allergen avoidance and allergen-specific immunotherapy can be tried in patients with allergic rhinitis. Thus, the exact diagnosis is very important for the effective treatment in allergic rhinitis. The diagnostic tests for allergic rhinitis are reviewed. (Korean J Med 2013,85:452-456)

Mediators and Cytokines in Persistent Allergic Rhinitis and Nonallergic Rhinitis with Eosinophilia Syndrome

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1β, IL-17, IFN-γ, TNF-α and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1β was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL- 5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES.

Nasal lavage CCL24 levels correlate with eosinophils trafficking and symptoms in chronic sino-nasal eosinophilic inflammation

The aim of our study was to measure CCL24 (eotaxin-2) levels in nasal lavage fluid of patients with different forms of sinonasal chronic eosinophilic inflammation to verify the relationship with nasal hypereosinophilia and symptoms. Patients with nasal hypereosinophilia were randomly recruited and grouped in persistent allergic rhinitis, non-allergic rhinitis with eosinophilia syndrome (NARES) and chronic rhinosinusitis with polyps. Non rhinitic volunteers were recruited as controls. CCL24 concentration was measured by `Quantikine Human CCL24 Immunoassay`. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped by inferior turbinate. CCL24 levels measured in patient groups were significantly higher compared to control group with the highest levels in NARES patients. Eotaxin- 2 levels were significantly correlated to severity of symptoms and to the percentage of eosinophils in nasal tissue. We revealed high levels of CCL24 in all patient groups showing a significant correlation with the degree of eosinophilia and clinical symptoms. A prolonged accumulation of CCL24 inside the nasal mucosa may sustain the process of unspecific self-perpetuating eosinophil recruitment pathognomonic of these patients.

Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis

Allergic rhinitis is characterized by mast cell degranulation induced by antigen cross-linking of IgE. It has been proposed that some patients with rhinitis show nasal allergy in the absence of systemic markers of atopy, termed entopy. Recent murine studies suggest the existence of an IgE-independent hypersensitivity response involving antigen-induced mast cell activation, mediated by immunoglobulin free light chains (FLCs). To determine whether FLC is associated with mast cell-mediated nasal hypersensitivity and its relationship with eosinophilic activity in allergic and nonatopic rhinitis. Patients with allergy and nonallergic rhinitis with eosinophilia syndrome (NARES) had levels of soluble FLC measured in nasal secretions and serum. In addition, levels of the nasal inflammatory mediators mast cell tryptase and eosinophil cationic protein were quantified. Cellular expression of kappa and lambda FLC was characterized in the nasal mucosa of allergic and nonatopic idiopathic rhinitis and control subjects by using immunohistochemistry. Immunopositive cells were phenotyped by using laser microdissection and PCR. Free light chain was significantly increased in nasal secretions of subjects with allergy and NARES, and in serum of patients with NARES. Nonatopic patients with allergy showed significantly increased nasal mast cell tryptase and eosinophil cationic protein. FLC-positive cells were significantly increased in allergic and nonatopic mucosa, and were shown to be mast cells and plasma cells. Nasal FLC is significantly increased in allergic and nonatopic rhinitis nasal mucosa, suggesting a role in nasal hypersensitivity. Further studies are needed to identify which allergens trigger FLC-mediated responses in nonatopic rhinitis.