Allergic Rhinitis Difficult To Allergic Rhinitis Difficult To Diagnose…...Diagnose…...

Easy To Easy To TreatTreat

Dr. Camelia CiacliDr. Camelia CiacliUniversitatea de Vest “Vasile Goldis” AradUniversitatea de Vest “Vasile Goldis” Arad

Spitalul Clinic Judetean AradSpitalul Clinic Judetean Arad

Clinica I MedicalaClinica I Medicala

OverviewOverview

History of allergy testingHistory of allergy testing Allergic rhinitisAllergic rhinitis

• DefinitionDefinition

• DiagnosisDiagnosis

• PathophysiologyPathophysiology Allergy testingAllergy testing

History of allergy testingHistory of allergy testing

18721872 pollen was identified as the pollen was identified as the causative factor for fall hay fever. causative factor for fall hay fever. Blakely Blakely performed first skin test with pollen performed first skin test with pollen extract.extract.

19121912 intradermal test by intradermal test by SchlossSchloss 19201920’s skin prick testing introduced by ’s skin prick testing introduced by

Lewis and Grant.Lewis and Grant. 19351935 Hansel began using serial dilution Hansel began using serial dilution

testing (1:5 dilution with endpoint testing) testing (1:5 dilution with endpoint testing) and Rinkel perfected serial endpoint and Rinkel perfected serial endpoint testing in the testing in the 19401940’s.’s.

Allergic RhinitisAllergic Rhinitis Inflammation to the mucosal Inflammation to the mucosal

lining of the nose caused by lining of the nose caused by inappropriate inappropriate hypersensitivity reaction to hypersensitivity reaction to an aeroallergen.an aeroallergen.

IgE mediated immune IgE mediated immune response, with mast cell response, with mast cell activation and release of activation and release of cytokinescytokines

Allergic rhinitisAllergic rhinitis Allergic rhinitis affects 20 to 40 million people in Allergic rhinitis affects 20 to 40 million people in

the United States annually, including the United States annually, including 10% to 30%10% to 30% of adults and up to of adults and up to 40%40% of children of children

Causes significant morbidityCauses significant morbidity Costs of continued medicationCosts of continued medication Most common chronic disease in United StatesMost common chronic disease in United States Decreased productivity Decreased productivity Lost work/school daysLost work/school days

• Accounts for three million missed work daysAccounts for three million missed work days

• Accounts for two million missed school days Accounts for two million missed school days

Significantly affects quality of life Significantly affects quality of life

So what do you do with a So what do you do with a suspected allergy patient?suspected allergy patient?

..

Family historyFamily history If both parents have allergies, their child has a 50% If both parents have allergies, their child has a 50%

chance of having the same problem.chance of having the same problem.

Past medical historyPast medical history In children, a history of recurrent otitis media, upper In children, a history of recurrent otitis media, upper

respiratory tract infection, asthma, chronic rashes, and respiratory tract infection, asthma, chronic rashes, and formula intolerance are suggestive of allergies.formula intolerance are suggestive of allergies.

identify other atopic conditions - hives, atopic identify other atopic conditions - hives, atopic dermatitis, allergic asthma, anaphylactic reactions dermatitis, allergic asthma, anaphylactic reactions

Inquire about the results of previous allergy tests and Inquire about the results of previous allergy tests and treatmenttreatment

SymptomsSymptoms

RhinorrheaRhinorrhea Cough/sneezingCough/sneezing Nasal congestionNasal congestion Post nasal dripPost nasal drip Nasal pruritisNasal pruritis Watery eyesWatery eyes General fatigueGeneral fatigue Diminished quality of lifeDiminished quality of life

Other Mucous Membrane Other Mucous Membrane ManifestationsManifestations

EyesEyes

conjunctival irritation, itching, erythema, & conjunctival irritation, itching, erythema, & tearing tearing

EarsEars

feeling of fullness in ears with popping feeling of fullness in ears with popping SinusesSinuses

pressure and/or pain over cheeks, forehead, pressure and/or pain over cheeks, forehead, or behind eyes or behind eyes

Systematic ManifestationsSystematic Manifestations

malaise, weakness, fatigue malaise, weakness, fatigue

any recent changes in the patient's any recent changes in the patient's Quality ofQuality of life life (eg, (eg, at home, in the workplace, in leisure activities, in at home, in the workplace, in leisure activities, in diet).diet).

SeveritySeverity does rhinitis interfere with work or school does rhinitis interfere with work or school

performance or playperformance or play Associated SymptomsAssociated Symptoms noisy or oronasal breathing, nasal voice, noisy or oronasal breathing, nasal voice,

hyposmia, repeated throat clearinghyposmia, repeated throat clearing Symptoms associated with chronicity Symptoms associated with chronicity

of rhinitisof rhinitis • Irritability Irritability

• Fatigue

• DepressionDepression

Physical ExaminationPhysical Examination ObservationObservation

Patients with allergic rhinitis frequently Patients with allergic rhinitis frequently have a characteristic facial appearance. have a characteristic facial appearance.

FaceFace

Facial grimacing and Facial grimacing and twitching caused by twitching caused by nasal itching in nasal itching in patient with allergic patient with allergic rhinitis. These are rhinitis. These are frequently repeated frequently repeated and easily noted and easily noted during patient during patient evaluation.evaluation.

Characteristic Characteristic adenoid-type facies adenoid-type facies in a patient with in a patient with long-standing long-standing allergic rhinitis. allergic rhinitis. Note the open Note the open mouth and gaping mouth and gaping habitus.habitus.

EyesEyes

Allergic shiners, (dark Allergic shiners, (dark discoloration below discoloration below the lower eyelids or the lower eyelids or dark circles beneath dark circles beneath the eyes) caused by the eyes) caused by venous stasis may be venous stasis may be present. present.

Patients may have Patients may have injected conjunctiva; injected conjunctiva; increased lacrimation; increased lacrimation; and long, silky and long, silky eyelashes.eyelashes.

NoseNose

The allergic salute The allergic salute is characteristic of is characteristic of children with children with allergic rhinitis and allergic rhinitis and nasal itching and is nasal itching and is usually noticed by usually noticed by parents.parents.

The nasal crease The nasal crease across the lower across the lower third of the nose third of the nose results from chronic results from chronic upward rubbing of upward rubbing of the nose with the the nose with the hand (allergic hand (allergic salute). to relieve salute). to relieve itching and open itching and open the nasal airway.the nasal airway.

Nasal Nasal ObstructionObstruction

Otoscope or Nasal Speculum Chronic Changes

INVESTIGATIONSINVESTIGATIONS

Nasal SecretionNasal Secretion for eosinophilia (>10-20%) for eosinophilia (>10-20%)

with Wright or with Wright or Eosin/Methylene Blue Eosin/Methylene Blue stains stains

SerumSerum

eosinophilia eosinophilia

elevated IgEelevated IgE

Eosinophilia on nasal smear from a patient with allergic rhinitis

Allergy TestsAllergy Tests

Gold standard Gold standard In Vivo - skin tests - In Vivo - skin tests -

immediate, delayed, skin immediate, delayed, skin brick testbrick test

In Vitro - Immunoassays – In Vitro - Immunoassays –

((Radio-allergo-sorbentRadio-allergo-sorbent ))RAST, CAP, ELISARAST, CAP, ELISA

Skin Prick TestsSkin Prick Tests

plastic lancet

Allergen solution

The procedure is painless

A specific Battery of Skin TestFirst Top ten Allergens (covering 90 % of the allergies)1- Dermatophagoides pteronyssinus (mite)2- Dermatophagoides farinae (mite)3- Cockroach4- 12 Grasses5- TreesTrees6- WeedsWeeds7-Molds8- Ambrosia artemisiifolia

9-Histamine10-Control Negative+ six other allergens can be added to cover 99 % of the allergies.

Indoor AllergensIndoor Allergens

Perennial allergens of Perennial allergens of importance are molds, house importance are molds, house dust, and animal danders.dust, and animal danders.

Although these allergens are Although these allergens are present throughout the year, present throughout the year, they tend to be more they tend to be more problematic during the problematic during the winter, when people spend winter, when people spend most of their time indoors.most of their time indoors.

Outdoor AllergensOutdoor Allergens

Seasonal allergens are primarily pollens. Seasonal allergens are primarily pollens. TreesTrees -- Spring pollen starting in early February -- Spring pollen starting in early February

through May - greatest levelsthrough May - greatest levels GrassesGrasses -- Primarily May and June but some -- Primarily May and June but some

continuing all summercontinuing all summer WeedsWeeds -- August through October -- August through October

INHALED ALLERGENS INHALED ALLERGENS ININ

OUR REGIONOUR REGION

MITES

Indoor Allergens

COCKROACHES

Oak Pollen - Most AbundantOak Pollen - Most Abundant

BERMUDA GRASS

Pollen Allergens

Short Ragweed-Short Ragweed-Ambrosia artemesiifoliaAmbrosia artemesiifolia

Giant RagweedGiant Ragweed

AMBROSIA ARTEMISIIFOLIA

Pollen Allergens

The nose is the part of the lung which isThe nose is the part of the lung which isaccessible to the finger accessible to the finger

L. Lichtenstein 1982L. Lichtenstein 1982

Particular from Piero della Francesca (modified)

United Airway DiseasesUnited Airway Diseases

gw41298

GWC 1998GWC 1998

Rhinitis is ubiquitous in allergic asthmatics.

Kapsali T et alKapsali T et al

JACI 1999

93% of asthmatics 93% of asthmatics have concomitant rhinitishave concomitant rhinitis

Rhinitis is a risk factor for asthmaRhinitis is a risk factor for asthmaThe Copenhagen Allergy StudyThe Copenhagen Allergy Study

Linneberg et al, Allergy 2002Linneberg et al, Allergy 2002

0

5

10

15

20

25

30in

cide

nce

of a

sthm

a (%

)

pollen animal mite

rhinitis at baseline

yes

no

• 734 subjects• 15-69 yr• Followed from 1990 to 1998

OR=8.1OR=18.9

OR=46.5

BHR was found in 24% to 40% of patients with active rhinitis(In the general population the BHR prevalence is 10-20%)

Di Lorenzo G. et al.“ Non-specific airway responsiveness in mono-sensitive Sicilian patientswith allergic rhinitis: its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season”Clin Exp Allergy 1997; 27: 1052-59

Ramsdale EH et al.“ Asymptomatic bronchial hyperresponsiveness in

rhinitis” J Allergy Clin Immunol 1985; 75: 573-577

Annesi I. et al. “ Relationship of upper airways disorders to FEV1 and bronchialhyperresponsiveness in an epidemiological study”Eur Respir J 1992; 5: 1104-1110

Inflammatory and mechanical factors of allergen induced bronchoconstrictionin mild asthma and rhinitis

E. Crimi, M. Milanese, S. Oddera. C. Mereu, G.A. Rossi, A. Riccio, G.W. Canonica V. Brusasco

J Appl Physiol 2001

Results (Biopsy)Results (Biopsy)

There were no significant differences in There were no significant differences in inflammatory cells numberinflammatory cells number between between rhinitis and asthma at baseline (P>0.5 rhinitis and asthma at baseline (P>0.5 for all comparisons)for all comparisons)

ASTHMATIC PATIENT AFTER BRONCHIAL SPECIFIC CHALLENGE

RHINITIC PATIENT AFTER BRONCHIAL SPECIFIC CHALLENGE

Airways response to allergen Airways response to allergen in rhinitis and asthmain rhinitis and asthma

WHAT MAKES THE DIFFERENCE?WHAT MAKES THE DIFFERENCE?

THE ALLERGEN DOSE!THE ALLERGEN DOSE!

A comparison of the airway responseA comparison of the airway responseto segmental antigen bronchoprovocationto segmental antigen bronchoprovocationin atopic asthma and allergic rhinitisin atopic asthma and allergic rhinitis

Becky Kelly E.Becky Kelly E.Busse W.W.Busse W.W.Jarjour N.N.Jarjour N.N.

J.A.C.I. 2003J.A.C.I. 2003

Segmental bronchial provocationinduces nasal inflammation inallergic rhinitis patients

Braunstahl G.J. et al.

AJRCCM 2000 161:2051

Segmental Segmental Bronchoprovocation in Allergic Bronchoprovocation in Allergic Rhinitis Patients Affects Mast Rhinitis Patients Affects Mast Cell and Basophil Numbers in Cell and Basophil Numbers in Nasal and Bronchial MucosaNasal and Bronchial Mucosa

Braunstahl GJ et al.Braunstahl GJ et al.AJRCCM 2002 AJRCCM 2002

Correlation between nasal and bronchial Correlation between nasal and bronchial eosinophilseosinophils

Study of whether nasal mucosal inflammation exists in asthma regardless of the presence of allergic rhinitis in atopic subjects 20 to 66 years of age.

Adapted from Gaga M et al Clin Exp Allergy 2000;20:663-669.

40

35

30

25

20

15

10

5

0

Asthmaticnasalnasal

mucosaeosinophils

0

r=0.851, p<0.001

Asthmatic bronchialbronchial mucosa eosinophils5 10 15 20 25 30

(n=17)

EXPERIMENTAL EVIDENCE PROVIDED EXPERIMENTAL EVIDENCE PROVIDED BY THE NASAL MODELBY THE NASAL MODEL

Symptomfree patients sensitized and Symptomfree patients sensitized and exposed to perennial allergens have exposed to perennial allergens have always a weak inflammatory infiltrate and always a weak inflammatory infiltrate and a weak ICAM-1 expression, even when a weak ICAM-1 expression, even when they are symptom-freethey are symptom-free: :

MINIMAL PERSISTENT INFLAMMATION-MINIMAL PERSISTENT INFLAMMATION-MPIMPI

Ciprandi et al. Ciprandi et al. JACI 1995JACI 1995

GP722000

Rhinitis Asthma

NATURAL HISTORY

THE NATURAL HISTORY OF ASTHMA?THE NATURAL HISTORY OF ASTHMA?

ASTHMAASTHMA

REMODELLINGREMODELLINGFUNCTION DECLINEFUNCTION DECLINE

HYPERRESPONSIVENESSVIRAL INFECTIONS

GENETICS ENVIRONMENTATOPY

RHINITISRHINITIS

TIMETIME

“ “ TREATING THE TREATING THE ALLERGIC PATIENTALLERGIC PATIENT::

THINK GLOBALLY,THINK GLOBALLY,TREAT GLOBALLYTREAT GLOBALLY ” ”

Passalacqua G. Passalacqua G. & &

Canonica G.W.Canonica G.W.Allergy. 2002Allergy. 2002

NoseNose BronchiBronchi

Inhaled CSsInhaled CSsNasal CSsNasal CSs

AntihistaminesAntihistamines

L.ong Acting. L.ong Acting. 2s2s

allergen avoidance-education

specific immunotherapy

Antileukotrienes

United Airways Disease United Airways Disease Passalacqua et al.Passalacqua et al. Curr.Op.All.& Clin.ImmunolCurr.Op.All.& Clin.Immunol 20012001

A few global facts and figures for two common allergic diseases, asthma and rhinitis:

Country Year costs calculated

Population(2010)

Disease Direct costs* Indirect costs** Total costsestimated

Australia 2007 23 million All allergies A$1.1 billion A$8.3 billion A$9.4 billion

Finland 2005 5.3 million All allergies €468 million €51.7 million €519.7 million

South Korea

2005 50 million AsthmaAllergic Rhinitis

US $1.78 billionUS $266 million

Israel 7.5 million Asthma US $250 million

Mexico 2007 103 million Asthma US $35 million

USA 20072005

310.2 million AsthmaAllergic Rhinitis

US $14.7 billionUS $11.2 billion

US $5 billionUp to US $9.7

billion

US $19.7 billionUp to $20.9

billion

* Direct costs: Expenditure on medications and health care provision** Indirect costs: Cost to society from loss of work, social support, loss of taxation income, home modifications, lower productivity at work, etc

Source: WAO White Book on Allergy (Member Society Reports)

The economic burdenof allergy

Final RemarksFinal Remarks

Recommendations

1- Patients with persistent rhinitis should be evaluated for asthma

2- Patients with persistent asthma should be evaluated for rhinitis

3- A strategy should combine the treatment of upper and lower airways in terms of efficacy and safety