Local Allergic Rhinitis

Local allergic rhinitis

Sadudee Boonmee, MD

Topic outline

• Etiologic classification of rhinitis• Epidemiology of LAR• Pathophysiology of LAR• Clinical manifestration • Diagnostic approach• Treatment

Classification of rhinitis

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

• Local allergic rhinitis is a newly described type of rhinitis involving nasal production of specific immunoglobulin (sIg) E antibodies in the absence of atopy (SPT –ve, serum sIgE -ve)

J Investig Allergol Clin Immunol 2010; Vol. 20(5): 364-371

• NAR : idiopathic rhinitis and NARES most frequent diagnosed

• Idiopathic rhinitis - Dx by exclusion - pathophysiology : unknown ( neurologic, inflammatory , change in mucosal permeability?)

Local allergic rhinitis: Concept, pathophysiology, andmanagement. J Allergy Clin Immunol2012 ( article in press)

• True prevalence data are not available• European centers suggest that among patients

with negative SPT responses and undetectable sIgE antibodies in serum

LAR 47% to 62.5% of patients with perennial and seasonal


• Few information published identified prevalent of allergens as LAR culprits

• HDM, grass, and olive pollen


Local IgE production in tissue

• 1947s : Samter M, Becker E. evaluation of locally produced IgE outside the regional lymph, was recognized that the nasal secretions of ragweed allergic individuals could be used to passively transfer a local reaction to previously nonallergic individuals

• 1970s : Tse KS, Wicher K. reported ragweed specific IgE in the nasal washings of ragweed allergic patients

Ragweed reagins in nasal secretion. Proc Soc Exp Biol Med. 1947:140 –141.

IgE antibodies in nasal secretions of ragweed-allergic subjects. J Allergy. 1970;46:352–357

• Patients history suggestive of allergic rhinitis to HDM - 14 pt : SPT negative to Der p- 6 pt : SPT positive to Der p - 5 : healthy controls

• Nasal provocation test - The allergen extracts were diluted in 50% glycerolsaline to 40, 200, and 1000 protein nitrogen units per ml. administered as an aerosol, beginning with the lowest dose- positive reaction : sneezed or reported itching and nasal obstruction

• RAST assays were performed on both nasal secretion and serum

Results • Two groups of pt

1. study group : history of HDM allergy but SPT -ve2. positive control group : both a positive history and SPTBoth group responded to HDM on nasal provocation

Serum RAST assays were performed on all patients- SPT +ve gr. raised serum-RAST levels- No significant difference between the serum-RAST level of the study group(SPT -ve) and the non-atopic controls

Nasal secretion for RAST that indicated the presence of sIgE- RAST titer raised in all patient when compare with non atopic control- presence of sIgE Ab in all pt. who proven HDM allergy ( SPT +ve /-ve or raised serum RAST or not)

Discussion

• We identified a group of pt. with allergic to HDM confirm by nasal provocation test who do not response to SPT or negative serum RAST

• We demonstrated that pts. have sIgE Ab in their nasal secretion indicating local production of Ab in nasal mucosa

• 23 pt. with idiopathic rhinitis compared to 8 perennial AR and 8 normal control

• Nasal saline challenges were performed to exclude nasal hypersensitivity

• Bilateral nasal challenge using metered spray aerosal delivering 100 µL of reconstituted freeze dried allergen solution (Dp+Df, cat, dog and grass pollen) performed weekly for each allergen

• Nasal patency assess by anterior rhinometry ( before and after nasal allergen challenge 15 min ) and positive if > 50% increase in unilateral nasal resistance

Inclusion criteria

• 62 % of IR had positive challenge at least unilaterally (nasal resistance increase > 50%)

• Medial change of 278% in nasal resistance• 85% had +ve challenge to HDM

• Conclusion : Significant proportion of IR have positive nasal challenge

• These finding add to the evidence of “ local allergy” may exist in absence of systemic atopic marker

• Two groups have performed much of the work regarding local IgE production in NAR: - Rondon et al. in Spain- Powe et al. in the Netherlands

• Division of Otorhinolaryngology at Queen’s Medical Centre (QMC), Nottingham, UK

• Objective : hypothesized that it is possible to have an allergic Th2 disease pathway localized in the nasal mucosa of ‘non-allergic’ rhinitis subjects despite an absence of atopic responses

• non-atopic persistent rhinitis (n=10) and atopic persistent rhinitis (n = 11) compared to normal control (n=12)

• age 17-61 yr• Nasal mucosal biopsy

D. G. Powe, et.al, Clin Exp Allergy 2003; 33:1374–1379

SPT : HDM, cladosporium, grass ,tree pollen mix, silver birch, cat,dog danders, and bird allergens.

3/10 pt detect sAb for HDM & GP

7/11 pt detect sAb for HDM & GP


• Conclusion :- This evidence supports the concept local mucosal inflammatory responses can occur independent of remote atopic responses- This is the first report of mucosal allergen capture in non-atopic rhinitis subjects -‘entopy’ (Greek ‘entopos’ – meaning local resident) describe a localized mucosal response independent of systemic atopic responses


• Objective: To evaluate in the nose the inflammatory response, specific IgE to Dermatophagoides pteronyssinus (DP), and the response to a nasal allergen provocation test with DP (NAPTDP), in patients with persistent nonallergic rhinitis (PNAR) compared with patients with persistent allergic rhinitis (PAR) and healthy controls

• 110 subjects : PNAR = 50 pt , PAR = 30 pt, and 30 healthy control (age 18-70 yr)

J Allergy Clin Immunol 2007;119:899-905


• SPT : - HDM (DP, DF, lepidoglyphus destructor, and blomia tropicalis)- pollens (poa, phleum, lolium, cassuarina, eucalyptus, cupresus, platanus, olea, helianthus, chenopodium, plantago, artemisia, parietaria judaica, salsola kali, rumex and ricinus), - - molds (alternaria, aspergillus, cladosporium and penicillium), - latex- animal epithelia (dog, cat, and hamster)

• Intradermal skin test : all PNAR pt. with Der p 1 • Nasal larvage and sample : standard anterior rhinoscopy • Flow cytometry (nasal fluid) : CD16, CD8, CD4, CD33, CD3, and

CD45• Albumin, ECP, total IgE, and specific IgE ( Serum,nasal fluid

sIgE to DP )• NAPT : freshly reconstituted freeze-dried allergen solutions of

Der p 1J Allergy Clin Immunol 2007;119:899-905

• Result

PNAR 6 pt had nasal sIgE –DPPAR : 25/30 pt had sIgE-DP in serum a/o nasal lavage : 8 /30 pt only had sIgE –DP in nasal larvage


PNAR and PAR groups presented similar levels of CD45+ cells, neutrophils, eosinophils, basophils, and CD3+ CD8+ T cell populations

PNAR patients with positive nasal sIgE-DP and/orNAPT-DP showed a similar leukocyte phenotype to the PAR group, with increased levels of Eo (P <0.001), CD3 +T cells (P < .005), and CD3+CD4+T cells (P < .05) compared with control

Result


• Result : NAPT

54%

• Of the 27/50 pt with a positive NAPT-DP in the PNAR group, 6 had selective nasal sIgE-DP (22%)• PNAR pt with +ve response to NAPT-DP, found a significant + ve correlation between nasal sIgE-DP and % of Eo in nasal larvage fluid , P=0.001


For pt. with PNAR the response after NAPT-DPImmediate = 63%Dual = 37% No isolated late response

• Summary • Nasal lavage analysis of the cell by flow cytometry

and the supernatant of PNAR showed similarities with PAR and clear differences with healthy controls

• specific IgE Ab to other perennial allergens needs further study

• do not know whether these patients will progress to the classic disease ( serum sIgE +ve )or whether they will remain unchanged


• Aim : to study nasal inflammation, presence of nasal sIgE and NAPT response to grass and Olea europea pollen common seasonal allergens in Spain, in patients with IR with seasonal symptoms only during the spring

• Subjected : 147 pt. (age 18-70 yr) divided to 4 group - 32 with seasonal IR- 35 with persistent AR to pollen (PAR-P) (symptom occur only during spring)- 30 with persistent AR to HDM (PAR-HDM) (symptom occur most of the year- 50 healthy control (HC)

C. Rondon et al. Allergy 2008: 63: 1352–1358

• Natural exposure to pollen (April-June)- SPT house dust mite, pollens, molds, latex and animal epithelia - ID performed in the IR pt. with grass pollen mixture and O. europea

• Nasal lavage and flow cytometry : CD33+, CD16+ ,CD3+CD4+ (T cell),CD3+CD8+ (cytotoxic T cell)

• Inflammatory mediators, total and sIgE in serum and nasal lavage : ECP , total IgE , sIgE (same for SPT)

• NAPT outside the pollen season (Oct - Nov): freshly reconstituted grass : O. europea extract


• ResultsEpidemiological and clinical data

P = 0.009C. Rondon et al. Allergy 2008: 63: 1352–1358

• SPT- PAR-P positive to grass pollen in 17/35 (49%) and to O. europea in 10/35 (28%), with 8/35 subjects positive to both (23%)- negative in all the IR patients


Determinations made during natural exposure to pollen (April–June)

• Results

• Results


Frequency and severity of symptom during the pollen season

• ResultsLaboratory data during the pollen season in seasonal IR subjects regardless of response to NAPT


Flow cytometry

Nasal larvage

Serum

• Results

• IR group 20 pt. had +ve NAPT to grass (62.5%) and five to O. europea (15.62%)

• All cases with nasal sIgE had + ve NAPT

Determinations made outside the pollen season (October–November)


62.5%

15.62%

• Results

• In all cases, the response was immediate or dual; no isolated late responses

• Most of pt. had bilateral response to acoustic rhinometry

Grass Olea europa


• ResultsLaboratory data outside the pollen season in seasonal IR subjects with positive or negative response to NAPT

Serum

Nasal larvage

Flow cytometry

IR-PosNAPT showed - similar inflammatory response to the PAR-PPatients - significant +ve between nasal sIgE to grass pollen and nasal ECP ( Rho = 0.836, P < 0.05)- significant +ve between ECP and % of Eo in nasal mucosa (Rho = 0.813, P < 0.05)

IR-NegNAPT showed - similar levels to the PAR-P groupin CD45+ T cells, neutrophils, eosinophils and basophilsmastCell- significantly lower levels of serum and nasal ECP (P < 0.05), nasal total lymphocytes (P = 0.01) and CD3+ T cells (P = 0.002)


similar toPAR-P group

• 35% of IR-PosNAPT pt.(7/20) had nasal sIgE Ab to grass and two to both grass and olive• all cases with nasal local sIgE had a positive NAPT to grass or olive• support an IgE mechanism (has not been reported previously)


• IR-PosNAPT : inflammatory pattern in the nasal fluid during the seasonal exposure

- increased nasal Eo- increase total lymphocytes and ECP

• IR-PosNAPT had significantly higher in basophil-mast cells and CD3+ T cells

Similar to PAR-P

IR-NegNAPT group also showed a nasal inflammatory pattern compared with HCs, but only with increased levels of eosinophils and nasal ECP

Summary • patients with IR who develop well-defined

symptoms during the pollen season show an inflammatory pattern equivalent to that existing in PAR-P patients produced by pollen, with an important percentage having a positive NAPT response and nasal sIgE antibodies


Local allergic rhinitis: Concept, pathophysiology, and management. J Allergy Clin Immunol 2012 ( article in press)

• OPD ENT of the Leyenburge Hospital in medical centre Rotterdam university , Netherland

• 65 symptomatic IR pt. and 20 healthy control (age 16-64 yr)• Nasal biopsy for cells density of CD1, CD3, CD4, CD8, CD14,

CD25, CD68, chymase, tryptase, IgE and BMK13 (Eo) by incubated nasal biopsy tissue with monoclonal Ab

• Daily record for defined nasal symptom in pt. with IR

Selection criteria• Inclusion criteria

- Age between 16 and 64 years.- Negative skin prick test: house dust mite, tree pollen mix, grass pollen mix, mugwort, alternaria, aspergillus, cladosporium,penicillum, dog, cat, parakeet, rabbit, hamster, horse, guinea pig. (ALK-Diephuis, Holland)- Negative Phadiatop (Pharmacia, Uppsala, Sweden)- Symptoms for more than 1 year.- Periods of nasal discharge, sneezing and congestion for an average of at least 1 h per day on at least 5 days during a period of 14 days.

• Exclusion criteria- The use of systemic or inhaled corticosteroids within the previous month.- Use of inhaled sodium cromoglycate or nedocromil sodium within the previous month.- Use of astemizole within the previous month.- Inability of the patient to stop taking medication affecting nasal function.- A serious and/or unstable disease.- Nasal surgery within the previous 6 weeks.- Nasal polyps or a history of nasal polyps.- Significant anatomical abnormalities affecting nasal function.- Nasal or paranasal sinus infection (abnormal sinus X-ray).- Pregnancy or lactation.- Abnormal findings at physical examination.- Abnormal laboratory results for: blood: Na, K, Ca, total protein, albumin, urea, creatinine, bilirubin, alkaline phosphatase, aspartate aminotransferase,alanine aminotransferase, gammaglutamyl transpeptidase, haemoglobin, red blood cell count, plasma cell volume, mean corpuscular volume, platelets, total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, basophils.

• urine: blood, protein, glucose.

• Result

• Conclusion : Inflammatory cells do not seem to play an important role in this meticulously characteristic of IR pt.

• To determine the prevalence of localized allergy in patients with negative skin prick test results via nasal challenges with an array of allergens

• Single- blinded prospective study of 20 perennial NAR (age 24-62 y)

and 3 AR (positive control)• Nasal provocation test : placing 100 μL of solution onto inferior

turbinate via pipette , sequential challenge every 15 min

Before each challenge, total symptom scores, nasal smears, and peak nasal inspiratory flow rates were obtained

Ann Allergy Asthma Immunol. 2008;100:533–537.

• Provocation test +ve if TSS ≥ 5, the remaining challenges were postponed for another day (3 to 5 months later)

• If the TSS was negative, subsequent challenges with cockroach mix, timothy grass, cat hair and D pteronyssinus

• Peak nasal inspiratiry flow (PNIF): nasal inspiratory flow meter with a cushioned face mask, significant decline in PNIF greater than 20% from the baseline

• Nasal Eosinophil Counts : obtained by having the patient blow into wax paper


• Result - Total symptom score 4 IR pt. +ve glycerin nasal challenges did not

undergo further nasal allergen challenges 11 pt. had -ve symptom scores after sequential nasal

challenges with Alternaria, cockroach, timothy grass, cat hair, and HDM

5 pt. (25%) with NAR + ve nasal challenges ≥ 1 allergen challenges, return to rechallenge in 3 mo

3 Positive control +ve nasal challenge with HDM (2 pt, TSS 9 and 10 ) and cat (1 pt , TSS 11 )


• % change in PNIF for pt. with +ve challenge did not significantly differ from % change for the other patients challenged after each respective allergen

• no significant correlation between symptom scores and change in PNIF values after allergen challenges

• Nasal Eo very low numbers- no correlation between TSS and Eo counts in patients with –ve and + ve challenge


• In conclusion : this study does not support the concept of localized allergy in the nose : The positive nasal challenges in patients with perennial nonallergic rhinitis were not reproducible on repeated allergen challenge : The positive challenges did not correlate with PNIF values or nasal eosinophil numbers : Thus, further investigation with larger numbers of patients is warranted.


• There are other limitations to this study - Circadian variation of nasal congestion (confounding variable)- Imaging to exclude sinusitis was not routinely performed, and this could have affected the results.- A priming effect could have conceivably affected the resultsof patient 18 because his initial positive challenge to timothyGrass occurred during the grass pollinating season, and hissubsequent negative challenge was performed outside theseason.- There was no known exposure change to dust mite or cat allergen in the other relevant patients

Local Allergic Response in PatientsWith Allergic Rhinitis


• Class switching to IgE originally considered a process restricted to the germinal centers of lymphoid tissue, such as regional LN and spleen

• Ig E found in local respiratory tissue (nasal and bronchial mucosa) was believed to migrate from regional lymphoid tissue or serum

Joseph P. Forester, Christopher W. Calabria, Ann Allergy Asthma Immunol. 2010;105:249 –256

• B cells require 2 signal to undergo class switching recombination(CSR) 1. IL-4, IL-13 produced from Th2 (mast cell and Eo) activates IgE production by B-cells2. Th2 cells express CD40L activates CD40 on Bcells and allows CSR to continue

• CSR to an ε heavy chain occur in 3 step – germline gene transcription – DNA recombination with heavy chain locus producing ε circle transcriptions(ε

CTs) – Synthesis of heavy chain mRNA

Local isotype switching to IgE in airwaymucosa ,Pierre Olivier Fiset, Lisa Cameron, J Allergy Clin Immunol 2005;116:233-6.

• 13 pt. with asymptomatic SAR (+ve SPT to ragweed) were undergo inferior turbinate biopsy

• 9 nonallergic subject • These sections were placed on filtered inserts, in well with 2 mL of defined

medium with or without 250 μL of ragweed allergen (5, 50, 500, or 1000 protein nitrogen units [PNU]/mL) and incubated in 5% CO2/95% air for a period of 24 hours


• Simultaneous immunocytochemistry and in situ hybridization- Alkaline phosphatase antialkaline phosphatase immunocytochemistry was carried out with antibody against CD20 (B cell), CD3 (T cells) , or tryptase (mast cells) - sections were then hybridized with 35S-labeled probes for Cε, Iε, IL-4, or IL-13 mRNA - Double-positive cells were visualized as those associated with both a red stain for CD20, CD3, or tryptase immunoreactivity and an accumulation of silver grains corresponding to hybridized antisense riboprobes


• Results Nasal mucosal tissue was cultured for 24 hours in the presence orabsence of specific allergen ( isolated from systemic circulation )

• B lymphocyte identified on the basis of CD 20 immunoreactivity within allergic nasal mucosa cultured for 24 hr in ragweed allergen

B lymphocyte with in nasal mucosa


• CD20+ cells are a component of both allergic and nonallergic nasal tissue, allergic significantly higher number of cells (10.5 [5.8-6.3] vs 5 [2-5] cells; P < 0.05

• B cells seem to migrate and infiltrate epithelial layer and to cluster into groups of 3 or 4 cells within the submucosa of allergic tissue cultured with allergen.


Allergen-induced expression of Iε and Cε RNA

P < 0.05

P < 0.05

• Significantly higher numbers of Iε and Cε RNA+ cell in allergen-stimulated compared with unstimulated allergic tissue but not within tissue obtained from nonallergic patients


• Because ε germline gene transcripts (Iε+/Cε+) also encode the Cε gene sequence, the observed increase in Cε RNA+ cells may be due either to previously switched B cells or to those presently undergoing ε germline transcription

• Gene encoding Iε is deleted from genome during isotype switching ε germline transcripts are not produced by cells expressing mature ε mRNA and IgE protein

• ΔCε (Cε RNA+ cells minus Iε RNA+ cells) within allergic tissue cultured with allergen was significantly higher than the baseline number of Cε RNA+ cells in unstimulated tissue suggests the production of mature ε mRNA• Cε RNA+ cells (mature ε mRNA) observed in unstimulated tissue was most likelyattributed to B cells that had previously switched to IgE before biopsy

• significant increase in number of cells expressing Iε RNA in allergen-stimulated compared with unstimulated tissue demonstrates that ε germline transcription was induced locally, since the ex vivo exposure excludes the possibility that it occurred elsewhere

P < 0.05


• IL-4 and IL-13 mRNA+ cell found in allergic and non-allergic tissue

• Simultaneous immunocytochemistry and in situ hybridization demonstrated that the majority of these cells were T cells and mast cells

Allergen-induced expression of IL-4 and IL-13 mRNA


• Here, we provide first-time evidence for the allergen-Induced production of IL-4 and IL-13 from T cells (68% and 44%, respectively) residing within the nasal mucosa itself

• Both these cytokines induce ε germlinegene transcription in vitro

• Although only a modest proportion of the total T cell (11% and 11%, respectively) and mast cell (12% and 11%, respectively) populations were responsible for the production of these cytokines, it appears to have been sufficient for inducing ε germline transcription in neighboring B cells

• In addition to these cytokines, CD40 activation is required for DNA recombination and IgE synthesis

• Because activated T cells and mast cells both express CD40L, it is possible that these B cells were class switching to IgE

• No significant increase in the number of cells expressing IL-4 or IL-13 mRNA was observed in either stimulated orunstimulated nonallergic tissue


• Summary- The results shown here provide clear evidence that ε germline gene transcription, as well as mast cell and T cell production of IL-4 and IL-13, occur within allergic nasal mucosa- Further work is required to determinewhether the cells actually undergo recombination- These findings suggest the nasal mucosa as a site of IgE synthesis and local regulation of the allergic response to allergen


METHODS: Nasal mucosal scrapings and washes were collected withIRB approval from controls and patients with allergic (positive SPT) andnon-allergic rhinitis (negative SPT). RNA was purified from sample tissueand converted to cDNA which was amplified via two cycles of nested PCRfor the epsilon germline transcripts.RESULTS: Local mucosal IgE isotype switching suggestive of an ongoing allergic inflammatory process was confirmed in 3/6 allergic rhinitic subjects.Interestingly, active production of epsilon germline transcripts wasobserved in 10/10 subjects with non-allergic rhinitis.CONCLUSIONS: Epsilon germline transcription takes place in the nasalmucosa in a subset of patients with active allergic disease which reflectslocal IgE production. Similarly, patients with NAR demonstrated epsilongermline transcripts indicating that this disease may, in fact, reflect an allergic process

JACI vol 127, Issue 2, Supplement, February 2011, Page AB52

Clinical manifestration of LAR• Nasal symptoms and comorbidities

- present with symptoms typical of AR(ie, rhinorrhea, obstruction, sneezing, and itching)- frequently associated with conjunctivitis (25% to 57%) and asthma (33% to 47%)- can be grouped : seasonal, perennial, and occupational: intermittent and persistent (mostly persistent rhinitis with moderate-to-severe symptoms)


Diagnostic approach

• LAR can be confirmed based on - detection of nasal sIgE- positive NAPT response- absence of systemic atopy

or both

• Nasal sIgE high specificity but low sensitivity (22%-40%)

• NAPT very useful diagnostic test with higher sensitivity

Diagnostic approach


Treatment

• correct differentiation between LAR and NAR is a key point for the management

• Pt. with LAR have reported a good response to topical INS oral antihistamines (contrast with NAR)


Local allergic rhinitis: allergen tolerance and immunologic changes after preseasonalimmunotherapy with grass pollen.• Pilot observational study in patients with LAR sensitized to

grass pollen• 50% of pt were treated with pre seasonal grass specific SCIT

for 6 months in the spring (SCIT group), VS 50% of pt received rescue medication alone (control group)

• SCIT with grass pollen increased tolerance to the aeroallergen and reduced symptoms and rescue medication in patients with LAR compared with control group

• Need phase II DBPC to evaluated wheater LAR might be consider a new indication for IT

Carmen Rondo´ n J Allergy Clin Immunol 2011;127: 1069-71

• Once allergy has been ruled out, most of these patients are not usually followed up in allergy clinics, despite the persistence of rhinitis symptoms

• This study re-evaluate over time the severity, accompanying disorders, and possible allergen sensitizations in subjects with NAR

• Randomly selected 180 pt. diagnoses of NAR in allergy clinic between 2000 and 2004 (age 19 to 69 years)

Carmen Rondo´ n , et.al, J Allergy Clin Immunol 2009;123:1098-102

• Clinical questionnaire and medical interviewFirst evaluation initial data from medical recordsecond evaluation Questionaire

• SPTs and specific IgE measurement

SPT : Dermatophagoides pteronyssinus, Dermatophagoides farinae, Lepidoglyphus destructor, Blomia tropicalis, Poa, Phleum, Lolium, Casuarina, Eucalyptus, Cupressus arizonica, Platanus, Olea europea, Helianthus, Chenopodium, Plantago, Artemisia, Parietaria judaica, Salsola kali, Rumex, Ricinus, Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, Penicillium notatum, and animal epithelia of dog, cat, and hamster

specific IgE to D pteronyssinus, O. europea, grass, Cupressus arizonica, P judaica, Alternaria alternata, Aspergillus fumigatus, cat, and dog were determined in patients with a negative SPT response

• Lung function tests : FEV1, FEV1/FVC


• Results12%

9%

24%23%

15%

11%

10%

• Results


• Result Newly sensitization : evaluate by SPT & sIgE

18%

11.5%

3.85%


Summary

• this study confirms that de novo sensitization to aeroallergens, new comorbidities, and worsening in the persistence, severity, and effect on quality of life are frequent in the natural evolution of adults with NAR

• Patients with NAR need to be evaluated over time to identify new comorbidities, including the appearance of AR.


• Pt. with NAR might have local sIgE antibody in absence of systemic sIgE

• Nasal provocation test is the gold standard to show evidence for local IgE mediated allergy in nonallergic pt., standardized are required

• Futher research - Prevalence , incidence in adult and children- Natural Hx : LAR AR - Treatment : IT ??

Rhinitis

Allergic rhinitis

Allergic rhinitis with systemic

atopy

Seasonal Perennial

Local allergic rhinitis without systemic atopy

IntermittentPersistent

Non allergic rhinitis

InfectiousOccupationalDrug-induced

HormonalIrritantFood

EmotionalAtrophic

GERIdiopathic (NARES include)


Thank you

Pathophysiological Characteristics ofLocal Allergic Rhinitis

• Specific IgE and Inflammatory mediators in nasal secretion

• TH 2 Nasal Inflammatory pattern• Positive response to nasal allergen

provocation test

• The possible reasons for not detecting sIgE in patients with LAR with a positive NAPT response might be - low sensitivity of the assays used (dilutional effect of nasal lavage)- another immunologic mechanism, such as the possibility of nonspecific protease activity stimulation of HDM on airway innate immune cell- others

Class switching to IgE

• IgE have 2 heavy chain and 2 light chain • Fc portion binds to the high affinity receptor (FcεRI) on mast

cell and Basophil• Fab portion binds to specific antigen • Cross-linked of adjacent, membrane bound, allergen specific

IgE molecules on mast cells lead to immediated hypesensitivity reaction cell degranulation and release of mediators (eg. Histamine, tryptase and leukotriene) and cytokine (eg. IL-4, IL-13)


cellSubjects had to fulfill the following requirements:1. General inclusion criteria for the PNAR and PAR groups: subjectsaged 18-70 years, with no evidence of other immunologicdisease, chronic rhinosinusitis and/or nasal polyposisby CT scanning, vasomotor rhinitis (clear rhinorrhea and responseto ipratropium bromide), or respiratory infection duringthe previous 4 weeks (purulent sputum or rhinorrhea,fever, or abnormal laboratory test for white blood cells); notreatment with systemic or nasal corticosteroids during the previousmonth or systemic antihistamines or nasal vasoconstrictorsduring the previous 2 weeks. No patient was pregnant orbreast feeding.2. Specific inclusion criteria for the PNAR group: a history of persistentrhinitis for at least 2 years, negative skin prick test andserum specific IgE to perennial aeroallergens, negative intradermalskin test to DP, and fulfilling the exclusion criteria foridiopathic rhinitis outlined in the ARIA1 and Rijswijk reviews.93. Specific inclusion criteria for the PAR group: history of persistentrhinitis for at least 2 years, positive skin prick test(>5-mm wheal) and/or positive serum specific IgE to DP.All PAR subjects had to have a positive response to NAPTDPand no evidence of treatment with immunotherapy duringthe previous 10 years.4. Inclusion criteria for the CG: age 18-70 years, healthy, noallergic or nasal diseases, no pregnancy or lactation, negativeskin prick test, negative serum specific IgE to aeroallergens,and negative NAPT-DP.

Health & Medicine

Local Allergic Rhinitis