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Allergisk rhinitt
ARIA guidelines
Ola Storrø
Spes. allmennmedisin, ph.d.
Edda legesenter, Trondheim
Førsteamanuensis, ISM, NTNU
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Allergic Rhinitis and its Impact on Asthma (ARIA):
Achievements in 10 years and future needs
Journal of Allergy
and Clinical
Immunology
Volume 130, Issue
5, November 2012,
Pages 1049–1062
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Disposisjon
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Hva er allergisk rhinitt (AR)?
Epidemiologi
Patofysiologi
Diagnose og differensialdiagnoser
Beskrivelse og klassifisering av AR
Behandling av AR
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Hva er allergisk rhinitt?
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En inflammatorisk reaksjon
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Neseslimhinne, alltid involvert.
Konjunktiva
Bihuler (og tuba eustachi/mellomøre)
Pharynx
Inflammasjonen
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En IgE–mediert respons mot et allergen (protein)
Kompleks interaksjon mellom mange inflammatoriske mediatorer
Flere typer immunceller er involvert (dendrittiske celler, T-celler, Bceller, mastceller, eosinofile leukocytter)
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Rennende nese,
rhinorrhoe
Nesetetthet
Sliming i halsen
Kløe i nesen
Nysing
Sekundære
helseeffekter
(infeksjoner etc…)
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Patofysiologi
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Genetisk komponent i IgE-responsen
Allergisk sensitivisering- spesifikk IgE (sIgE)
sIgE adhererer til cellemembranen på mastceller I
nasalmucosa
Allergen (spesifikt protein) adhererer til IgE som gir
aktivering av mastcellen og frigjøring av mediatorer
(histamin o.a.).
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Patofysiologi
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Tidlig-fase mediatorer: Histamin, tryptase, chymase, kininer, og
heparin.
Mastcellen syntetiserer og frisetter leukotriener og
prostaglandin D2
Symptomkaskade:
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Nesettehet, nysing, kløe, tåreflod, tetthet/trykk i ørene , kløe i halsen
Øket mucøs sekresjon, øket vaskulær permeabilitet og plasmaexudasjon
Vasodilatasjon gir nesetthet og tetthet, sekresjon og trykk i bihulene
Sensorisk stimulering gir nysing og kløe
Alt dette skjer i løpet av minutter og kalles tidlig-fase reaksjon
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Patofysiologi
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I løpet av 4-8 timer:
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Sen-fase symptomer.
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Mediatorindusert (interleukiner, cytokiner) tiltrekking og aktivering
av inflammatoriske celler (nøytrofile, eosinofile, lymfocytter,
makrofager).
Likner tidlig fase, men med mindre sensorisk aktivering med
avtakende kløe og nysing. Økende tetthet og produksjon av mucus
Sen-fase symptomer kan vedvare over lang tid ved
fortsatt antigen stimulering
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Epidemiologi
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Kumulativ prevalens 2010:
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15% i Skandinavia
20% i England og USA.
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Stor variasjon internasjonalt.
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Stor variasjon i forkomst (I-land – U-land)
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Betydelig økning de siste 30 år
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The 12-month period prevalence (%) of self-reported asthma symptoms in 13–
14-year-olds (written questionnaire) for each ISAAC centre by country. The
International Study of Asthma and Allergies in Childhood Steering Committee, 1998. The Lancet.Toxicology Letters Volumes 102–
103, 28 December 1998, Pages 307–316
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Livstidsprevalens av allergisk rinitt
England 2006 (J R Soc Med1 September 2008 vol. 101 no.
9466-47)
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Epidemiologi
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Morbiditet og mortalitet
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Sjelden livstruende (unntatt ved anafylaksi)
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Betydelig morbiditet. Store konsekvenser for hverdagen (fravær,
arbeidskapasitet, nattesøvn osv.)
Allergier sameksisterer med andre atopiske tilstander
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Komorbiditet for allergiske sykdommer
Journal of Allergy and Clinical Immunology, Volume 113, Issue
3, March 2004,
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Diagnose av allergisk rhinitt
1.
2.
3.
4.
Sykehistorie og symptomer på
recidiverende eller persisterende rhinitt
Atopisk komorbiditet (AD, astma)
Påvist sensitivisering (sIgE eller prikktest)
Utelukke andre årsaker til rhinitt
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Diagnose av allergisk rhinitt
Sykehistorie og symptomer på recidiverende
eller persisterende rhinitt og følgetilstander
1.
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Rennende nese (rhinorrhoe)
Tett nese
Kløe
Nysing
Konjunktivitt, AD, astma, sinusitt, otitis media,
søvnforstyrrelser, OSAS
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Sykehistorie..
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Varighet, sesonvariasjon, døgnvariasjon
Triggere (obs: vasomotorisk rhinitt)
Arvelig disposisjon. Foredre og søsken
Miljømessige forhold (røyking, hund, katt..)
Infeksjoner (særlig barndom)
Yrkesanamnese
Konsekvenser av tilstanden for funksjon og
livskvalitet
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Diagnose av allergisk rhinitt
2.
Klinisk allergi
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Diagnosis of Allergic Rhinitis
3.
Påvisning av sensitivisering
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sIgE versus prikktest
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sIgE
Uavhengig av
medikasjon
Upåvirket av
hudsykdom
Enkel blodprøve, ingen
spesialkompetanse
Kvalitetskontrollert
Relativt dyr test
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Prikktest
Høyere sensitivitet
Umiddelbare
resultater
Krever ekspertise
for utføring og
tolkning
Billigere
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sIgE versus prikktest
Agreement of specific IgE and skin prick test in an unselected cohort of
two-year-old children.
Eur J Pediatr. 2012 Mar;171(3):479-84. Epub 2011 Sep 30.Rø AD, Saunes M,
Smidesang I, Storrø O, Oien T, Moen T, Johnsen R.
CONCLUSION: In young children total IgE is of limited value when
evaluating allergy-related disorder. The lack of agreement among the
positive tests of the sIgE and SPT for some allergens imply that these tests
should not be used interchangeably, and both tests should probably be
used complementarily when diagnosing atopic sensitization in small
children.
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IgE antibody in the serum – detection and diagnostic
significance
W. K. Dolen.Allergy, Volume 58, Issue 8, pages 717–723, August 2003
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Thus, it has traditionally been taught that the result of any test for specific IgE –
immunoassay or skin test – will not in and of itself determine whether the patient
has symptoms of IgE-mediated allergic hypersensitivity upon allergen exposure,
and in and of itself determine treatment. For these reasons, it is not possible to
define a normal range for specific IgE immunoassays.
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….increasing experience with modern quantitative assay technology
suggests that in at least some clinical situations, higher levels of
specific IgE are more likely to be clinically relevant. Lower levels may or
may not be relevant.
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Andre årsaker til rinitt hos barn
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Infeksjoner
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Virus, bakterier,
Rhinosinusitt
Fremmedlegeme i nesen
Matallergi
Non-allergisk rhinitt (NARES)
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Konsekvenser av allergisk rhinitt
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Begrenser utfoldelse. Sosialt hemmende
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Søvnforstyrrelser
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Lærevansker
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Mye ØLI
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Assosiert med astma og atopisk dermatitt
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Husk…..
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Spør rutinemessig etter symptomer på astma
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Lungeauskultering
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Vurder spirometri
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Vurder henvisning til allergologisk utredning
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Spesifikk immunterapi (SIT /
hyposensibilisering / allergivaksinering)
• Reduserer mastcellers og basofile granulocytters evne til frigjøring av histamin og
andre mediatorer ved allergenstimulering.
• Påvirker IgE syntesen (langsiktig senkning av IgE nivå etter forbigående stigning).
• Indikasjoner
– Bi og vepseallergi:
SIT skal tilbys barn og voksen med generelle reaksjoner som
omfatter respirasjons- og sirkulasjonsorganene og kan tilbys voksne med generell
reaksjon i form av urticaria
– Tre- og gresspollenallergi:
SIT kan tilbys der pasientet ikke oppnår tilstrekkelig
symptomlindring ved optimal sanerende og medikamentell beh., der pasienter med
rhinoconjunktivitt begynner å få bronkial hyperreaktivitet/astma, for å redusere risiko for
utvikling av astma hos barn med rhinokonjunktivitt og for å redusere risiko for
sensibilisering mot flere allergener
– Hunde-katte- og middallergi:
SIT kan tilbys ved manglende symptomkontroll ved
eksponeringsreduserende tiltak og har behov for regelmessig steroidbehandling.
NB – pos. prikktest og spes. IgE.
Helst monoallergi.
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Behandling av allergisk rhinitt
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Unngå allergener ved påvist allergi
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Medikamentell behandling
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Allergen immunotherapi (hyposensitivisering)
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Behandling etter ARIA guidelines
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Leukotrienantagonister
Effektivitet
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Ekvipotent med H1-antagonister, men virker først etter
2-3 dager
Reduserer nasal og pulmonal eosinofili
Alternativ ved samtidig allergisk rhinitt og astma
Sikkerhet
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God. Dyspepsi (ca. 2%)
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Nasale steroider
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Mest potente antiinflammatoriske behandling
Effektive mot alle nasale symptomer inklusive
obstruksjon
Bedre enn antihistaminer og
leukotrienantagonister
Førstelinjebehandling ved kron. allergisk rhinitt
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Nasale steroider
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Generelt trygg behandling
Bivirkninger
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Nasal irritasjon
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Epistaxis
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Septumperforasjon (ekstremt sjelden)
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Vekstretardasjon (sjelden/liten)
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Miljøfaktorer
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Sanere?
Kjæledyr?
Skal vi sanere eller eksponere?
Forskjell på sensitivisering og klinisk allergi
Hvis allergi er påvist skal allergen i størst mulig grad
unngås
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Konklusjon…
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Allergisk rhinitt er veldig vanlig og gir betydelig
morbiditet
Adekvat og korrekt behandling gir betydelig
symptomlindring og bedring av livskvalitet
Miljømessige forhold er av stor betydning og
gjenstand for betydelig forskningsaktivitet
Komorbiditet er svært vanlig og krever stor
oppmerksomhet
ARIA guidelines, “united airways”
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1. Should exclusive breast-feeding be used in infants
to prevent allergy?
Recommendation. We suggest exclusive
breast-feeding for at least the first 3 months for all infants
irrespective of their family history of atopy (conditional recommendation
low-quality evidence).
Values and preferences. This recommendation places a
relatively high value on the prevention of allergy and asthma and a
relatively low value on challenges or burden of breast-feeding in
certain situations.
Remarks. The evidence that exclusive breast-feeding for at
least the first 3 months reduces the risk of allergy or asthma is not
convincing, and the recommendation to breast-feed exclusively is
conditional.
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2. Should antigen avoidance diet be used in pregnant or
breast-feeding women to prevent development of
allergy in children?
Recommendation. For pregnant or breast-feeding women, we suggest no antigen
avoidance diet to prevent development of allergy in children (conditional
recommendation / very low-quality evidence).
Underlying values and preferences. This recommendation
places a relatively high value on adequate nourishment of
mothers and children and a relatively low value on very uncertain
effects on the prevention of allergy and asthma in this setting.
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5. Should infants and preschool children avoid exposure
to pets at home to reduce the risk of developing
allergy or asthma?
Recommendation. In infants and
preschool children, we suggest no special avoidance of exposure to
pets at home (conditional recommendation / low-quality evidence).
Underlying values and preferences. This recommendation
places a relatively high value on possible psychosocial
downsides of not having a pet and relatively low value on
potential reduction in the uncertain risk of developing allergy and/
or asthma.
Remarks. Clinicians and patients may reasonably choose an
alternative action considering circumstances that include other
sensitized family members.
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9. Should patients with allergy to animal dander
avoid exposure to these allergens at home?
Recommendation.
In patients with AR caused by animal dander, we recommend avoiding
exposure to these allergens at home (strong recommendation / very lowquality evidence).
Underlying values and preferences. This recommendation places a
relatively high value on potential reduction of symptoms of AR and a
relatively low value on psychosocial downsides of not having a pet or the
inconvenience and cost of environmental control measures.
Remarks. On the basis of a biological rationale, there is little doubt that
total avoidance of animal allergens at home, and probably also marked
reduction in their concentration, can improve symptoms, despite the
paucity of published data to substantiate this statement.
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13. Should oral H1-antihistamines be used in preschool
children with other allergic diseases for the prevention
of wheezing or asthma?
Recommendation. In infants with atopic dermatitis and/or family history of
allergy or asthma (at high risk of developing asthma), we suggest clinicians
do not administer and parents do not use oral H1-antihistamines for the
prevention of wheezing or asthma (conditional recommendation
/ very low-quality evidence).
Underlying values and preferences. This recommendation places a
relatively high value on avoiding side effects of oral H1-antihistamines in
infants and a lower value on the very uncertain reduction in the risk of
developing asthma or wheezing.
Remarks. The recommendation not to use oral H1-antihistamines
in these infants refers only to prevention of asthma or wheezing. The
guideline panel did not consider other conditions in which
these medications may be commonly used (eg, urticaria).
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14. Should intranasal H1-antihistamines be used for
treatment of AR?
Recommendation.
We suggest intranasalH1- antihistamines in adults with
seasonal AR (conditional recommendation / low-quality evidence) and in
children with seasonal AR (conditional recommendation / very low-quality
evidence). In adults and children with persistent AR, we suggest
that clinicians do not administer and patients do not use intranasal
H1-antihistamines until more data on their relative efficacy and
safety are available (conditional recommendation / very lowquality
evidence).
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15. Should newer oral H1-antihistamines versus
intranasal H1-antihistamines be used for treatment of
AR?
Recommendation.
We suggest new-generation oral H1-antihistamines rather than intranasal
H1-antihistamines in adults with seasonal AR (conditional
recommendation / moderate-quality evidence) and in adults with persistent
AR (conditional recommendation / very low- quality evidence). In children
with intermittent or persistent AR, we also suggest new-generation oral H1antihistamines rather than intranasal H1-antihistamines (conditional
Recommendation / very low-quality evidence).
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16. Should oral leukotriene receptor antagonists be
used for treatment of AR?.
Recommendation. We suggest oral leukotriene receptor antagonists in
adults and children with seasonal AR (conditional recommendation / highQuality evidence) and in preschool children with persistent AR (conditional
recommendation / low-quality evidence).
In adults with persistent AR, we suggest that clinicians do not administer
and patients do not use oral leukotriene receptor antagonists (conditional
recommendation / high-quality evidence).
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17. Should oral leukotriene receptor antagonists
versus oral H1-antihistamines be used for treatment
of AR?
Recommendation. We suggest oral H1-antihistamines
over oral leukotriene receptor antagonists in patients with
seasonal AR (conditional recommendation j moderate-quality evidence)
and in preschool children with persistent AR
(conditional recommendation / low-quality evidence).
Underlying values and preferences. This recommendation
places a relatively high value on avoiding resource expenditure.
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19. Should intranasal glucocorticosteroids versus
oral H1-antihistamines be used in patients with AR?
Recommendation. In patients with seasonal AR, we suggest intranasal
glucocorticosteroids over oral H1-antihistamines in adults (conditional
recommendation / low-quality evidence) and in children (conditional
recommendation / very low-quality evidence).
In patients with persistent AR, we suggest intranasal glucocorticosteroids
over oral H1-antihistamines in adults (conditional recommendation /
moderate-quality evidence) and in children (conditional recommendation /
low-quality evidence).
Underlying values and preferences. This recommendation
places a relatively high value on the likely higher efficacy of
intranasal glucocorticosteroids. In many patients with strong
preference for the oral versus intranasal route of administration,
an alternative choice may be reasonable.
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20. Should intranasal glucocorticosteroids versus
intranasal H1-antihistamines be used in patients with
AR?
21. Should intranasal glucocorticosteroids versus
oral leukotriene receptor antagonists be used for
treatment
of AR?
In both questions: We recommend intranasal glucocorticosteroids!
Underlying values and preferences. This recommendation
places a relatively high value on efficacy of intranasal
glucocorticosteroids and a relatively low value on their rare
adverse effects.
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23. Should intramuscular glucocorticosteroids be
used for treatment of AR?
Recommendation. In patients with AR, we recommend that clinicians do
not administer intramuscular glucocorticosteroids (strong recommendation
/ low quality evidence).
Underlying values and preferences. This recommendation places a
relatively high value on avoiding possible side effects of a single or multiple
injections of intramuscular glucocorticosteroids and relatively low value on
their efficacy and convenience of use.
Remarks. Possible side effects of intramuscular glucocorticosteroids
may be far more serious than the condition they are
supposed to treat (ie, AR).
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45. Should leukotriene receptor antagonists be used
for treatment of asthma in patients with AR and
asthma?
Recommendation. In patients with AR and
asthma, we recommend inhaled glucocorticosteroids over oral
leukotriene receptor antagonists as a single controlling medication
for asthma (strong recommendation / moderate-quality
evidence).
In patients with AR and asthma who prefer not to use or cannot
use inhaled glucocorticosteroids or in children whose parents do
not agree to use inhaled glucocorticosteroids, we suggest oral
leukotriene receptor antagonists for treatment of asthma (conditional
recommendation / moderate-quality evidence).
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Concluding remarks…..
The strengths of these guidelines are the transparent, evidencebased
approach to the development of recommendations and the
consideration and explicit description of the values and preferences
that influenced the recommendations.
It is crucial that these recommendations should never be seen as
dictates. No recommendation can take into account all of the often
compelling unique features of individual clinical circumstances.
Thus, nobody charged with evaluating clinicians’ actions should
attempt to apply these recommendations by rote or in a blanket
fashion.