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, and
management. J Allergy Clin Immunol
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
article in press

• Few information published identified
prevalent of allergens as LAR culprits
• HDM, grass, and olive pollen

article in press

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

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

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 -ve
2. positive control group : both a positive history and
SPT
Both 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

• 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

3/10 pt detect sAb for
HDM & GP

7/11 pt detect sAb
for HDM & GP

SPT : HDM, cladosporium, grass ,tree pollen mix, silver birch,
cat,dog danders, and bird allergens.
D. G. Powe, et.al, Clin Exp Allergy 2003; 33:1374–1379

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

• 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 -

• 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 1


• Result

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


Result

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/or
NAPT-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 : NAPT
For pt. with PNAR
the response after
NAPT-DP
54%
Immediate = 63%
Dual = 37%
No isolated late
response

• 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

• 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


• Results
Epidemiological and clinical data

P = 0.009

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


• Results Frequency and
severity of
symptom
during the
pollen season

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

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

Serum

Nasal larvage

Flow cytometry

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

• Results
Determinations made outside the pollen
season (October–November)
• IR group 20 pt. had +ve NAPT to grass (62.5%) and five to
O. europea (15.62%)
62.5%

15.62%

• All cases with nasal sIgE had + ve NAPT


• 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

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

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

IR-PosNAPT showedIR-NegNAPT showed
Serum - similar inflammatory
- similar levels to the
response to the PAR-PPAR-P group
Nasal larvage
Patients in CD45+ T cells,
- significant +ve neutrophils, eosinophils
Flow cytometry between nasal sIgE to basophilsmast
and
grass pollen and nasal
Cell
ECP ( Rho = 0.836, P - significantly lower
<
0.05) levels of serum and nasal
- significant +ve ECP (P < 0.05), nasal total
between ECP and % of lymphocytes (P = 0.01)
Eo in nasal mucosa (Rho CD3+ T cells (P =
and
= 0.813, P < 0.05) 0.002)


• 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 Similar to to
similar
PAR-P
PAR-P group
- increase total lymphocytes and ECP
• IR-PosNAPT had significantly higher in basophil-mast cells and
CD3+ T cells

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 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 Exclusion criteria
- The use of systemic or inhaled corticosteroids
- Age between 16 and 64 within the previous month.
years. - Use of inhaled sodium cromoglycate or nedocromil
- Negative skin prick test: sodium within the previous month.
house dust mite, tree pollen - Use of astemizole within the previous month.
mix, grass pollen - Inability of the patient to stop taking medication
affecting nasal function.
mix, mugwort, alternaria, aspe
- A serious and/or unstable disease.
rgillus, cladosporium,
- Nasal surgery within the previous 6 weeks.
penicillum, dog, cat, parakeet, - Nasal polyps or a history of nasal polyps.
rabbit, hamster, horse, guinea - Significant anatomical abnormalities affecting nasal
pig. (ALK-Diephuis, Holland) function.
- Negative Phadiatop - Nasal or paranasal sinus infection (abnormal sinus
(Pharmacia, Uppsala, Sweden) X-ray).
- Pregnancy or lactation.
- Symptoms for more than 1 - Abnormal findings at physical examination.
year. - Abnormal laboratory results for: blood: Na, K, Ca,
- Periods of nasal total protein, albumin, urea, creatinine, bilirubin,
discharge, sneezing and alkaline phosphatase, aspartate aminotransferase,
congestion for an average of at alanine aminotransferase, gammaglutamyl
least 1 h per day on at least 5 transpeptidase, haemoglobin, red blood cell count,
plasma cell volume, mean corpuscular volume,
days during a period of 14 platelets, total white blood cell count, neutrophils,
days. lymphocytes, monocytes, eosinophils, basophils.
• urine: blood, protein, glucose.

• 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
results
of patient 18 because his initial positive challenge to
timothy
Grass occurred during the grass pollinating season, and his
subsequent negative challenge was performed outside the
season.
- There was no known exposure change to dust mite or cat
allergen in the other relevant patients

Local Allergic Response in Patients
With Allergic Rhinitis

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

• 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-cells
2. 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 airway
mucosa ,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

J Allergy Clin Immunol 2000;106:46-52

• 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)
35
- sections were then hybridized with S-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 or
absence of specific allergen ( isolated from systemic circulation )
B lymphocyte with in nasal mucosa

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


• 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
P < 0.05 • Cε RNA+ cells (mature ε mRNA) observed in
unstimulated tissue was most likely
attributed 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


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

• 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

• 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 germline
gene 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 or
unstimulated 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 determine
whether 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 with
IRB approval from controls and patients with allergic (positive SPT) and
non-allergic rhinitis (negative SPT). RNA was purified from sample tissue
and converted to cDNA which was amplified via two cycles of nested PCR
for 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 was
observed in 10/10 subjects with non-allergic rhinitis.
CONCLUSIONS: Epsilon germline transcription takes place in the nasal
mucosa in a subset of patients with active allergic disease which reflects
local IgE production. Similarly, patients with NAR demonstrated epsilon
germline 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)

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

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

• 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 preseasonal
immunotherapy 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:
-

• 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 interview
First evaluation initial data from medical record
second 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

2009;123:1098-102

• Results
12%
9%

23%
24%
15%

10%

11%

• Results

2009;123:1098-102

• Result
Newly sensitization :
evaluate by SPT & sIgE

18%

11.5%

3.85%

2009;123:1098-102

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.

2009;123:1098-102

• 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

Non allergic
Allergic rhinitis
rhinitis

Allergic rhinitis Local allergic Infectious
with systemic rhinitis without Occupational
atopy systemic atopy
Drug-induced
Hormonal
Irritant
Seasonal Intermittent Food
Perennial Persistent Emotional
Atrophic
GER
J Investig Allergol Clin Immunol 2010; Vol. 20(5): 364-371 Idiopathic (NARES include)

Pathophysiological Characteristics of
Local 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)

Subjects had to fulfill the following requirements:
1. General inclusion criteria for the PNAR and PAR groups: subjects
cell
aged 18-70 years, with no evidence of other immunologic
disease, chronic rhinosinusitis and/or nasal polyposis
by CT scanning, vasomotor rhinitis (clear rhinorrhea and response
to ipratropium bromide), or respiratory infection during
the previous 4 weeks (purulent sputum or rhinorrhea,
fever, or abnormal laboratory test for white blood cells); no
treatment with systemic or nasal corticosteroids during the previous
month or systemic antihistamines or nasal vasoconstrictors
during the previous 2 weeks. No patient was pregnant or
breast feeding.
2. Specific inclusion criteria for the PNAR group: a history of persistent
rhinitis for at least 2 years, negative skin prick test and
serum specific IgE to perennial aeroallergens, negative intradermal
skin test to DP, and fulfilling the exclusion criteria for
idiopathic rhinitis outlined in the ARIA1 and Rijswijk reviews.9
3. Specific inclusion criteria for the PAR group: history of persistent
rhinitis 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 NAPTDP
and no evidence of treatment with immunotherapy during
the previous 10 years.
4. Inclusion criteria for the CG: age 18-70 years, healthy, no
allergic or nasal diseases, no pregnancy or lactation, negative
skin prick test, negative serum specific IgE to aeroallergens,
and negative NAPT-DP.

Local Allergic Rhinitis

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