Allergisk rhinitt ARIA guidelines. Ola Storrø Spes. allmennmedisin, ph.d. Edda legesenter, Trondheim Førsteamanuensis, ISM, NTNU

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1 1 Allergisk rhinitt ARIA guidelines Ola Storrø Spes. allmennmedisin, ph.d. Edda legesenter, Trondheim Førsteamanuensis, ISM, NTNU

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3 3 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

4 4 Disposisjon Hva er allergisk rhinitt (AR)? Epidemiologi Patofysiologi Diagnose og differensialdiagnoser Beskrivelse og klassifisering av AR Behandling av AR

5 5 Hva er allergisk rhinitt? En inflammatorisk reaksjon Neseslimhinne, alltid involvert. Konjunktiva Bihuler (og tuba eustachi/mellomøre) Pharynx Inflammasjonen En IgEmediert respons mot et allergen (protein) Kompleks interaksjon mellom mange inflammatoriske mediatorer Flere typer immunceller er involvert (dendrittiske celler, T-celler, B- celler, mastceller, eosinofile leukocytter)

6 6 Rennende nese, rhinorrhoe Nesetetthet Sliming i halsen Kløe i nesen Nysing Sekundære helseeffekter (infeksjoner etc )

7 7 Patofysiologi 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.).

8 8 Patofysiologi Tidlig-fase mediatorer: Histamin, tryptase, chymase, kininer, og heparin. Mastcellen syntetiserer og frisetter leukotriener og prostaglandin D2 Symptomkaskade: 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

9 9 Patofysiologi I løpet av 4-8 timer: Mediatorindusert (interleukiner, cytokiner) tiltrekking og aktivering av inflammatoriske celler (nøytrofile, eosinofile, lymfocytter, makrofager). Sen-fase symptomer. 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

10 10 Epidemiologi Kumulativ prevalens 2010: 15% i Skandinavia 20% i England og USA. Stor variasjon internasjonalt. Stor variasjon i forkomst (I-land U-land) Betydelig økning de siste 30 år

11 11 The 12-month period prevalence (%) of self-reported asthma symptoms in year-olds (written questionnaire) for each ISAAC centre by country. The International Study of Asthma and Allergies in Childhood Steering Committee, The Lancet.Toxicology Letters Volumes , 28 December 1998, Pages

12 12 Livstidsprevalens av allergisk rinitt England 2006 (J R Soc Med1 September 2008 vol. 101 no )

13 13 Epidemiologi Morbiditet og mortalitet Sjelden livstruende (unntatt ved anafylaksi) Betydelig morbiditet. Store konsekvenser for hverdagen (fravær, arbeidskapasitet, nattesøvn osv.) Allergier sameksisterer med andre atopiske tilstander

14 14 Komorbiditet for allergiske sykdommer Journal of Allergy and Clinical Immunology, Volume 113, Issue 3, March 2004,

15 15 Diagnose av allergisk rhinitt 1. Sykehistorie og symptomer på recidiverende eller persisterende rhinitt 2. Atopisk komorbiditet (AD, astma) 3. Påvist sensitivisering (sige eller prikktest) 4. Utelukke andre årsaker til rhinitt

16 16 Diagnose av allergisk rhinitt 1. Sykehistorie og symptomer på recidiverende eller persisterende rhinitt og følgetilstander Rennende nese (rhinorrhoe) Tett nese Kløe Nysing Konjunktivitt, AD, astma, sinusitt, otitis media, søvnforstyrrelser, OSAS

17 17 Sykehistorie.. 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

18 18 Diagnose av allergisk rhinitt 2. Klinisk allergi

19 19 Diagnosis of Allergic Rhinitis 3. Påvisning av sensitivisering

20 20 sige versus prikktest sige Uavhengig av medikasjon Upåvirket av hudsykdom Enkel blodprøve, ingen spesialkompetanse Kvalitetskontrollert Relativt dyr test Prikktest Høyere sensitivitet Umiddelbare resultater Krever ekspertise for utføring og tolkning Billigere

21 21 sige versus prikktest Agreement of specific IgE and skin prick test in an unselected cohort of two-year-old children. Eur J Pediatr Mar;171(3): 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.

22 22 IgE antibody in the serum detection and diagnostic significance W. K. Dolen.Allergy, Volume 58, Issue 8, pages , August 2003 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..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.

23 23 Andre årsaker til rinitt hos barn Infeksjoner Virus, bakterier, Rhinosinusitt Fremmedlegeme i nesen Matallergi Non-allergisk rhinitt (NARES)

24 24 Konsekvenser av allergisk rhinitt Begrenser utfoldelse. Sosialt hemmende Søvnforstyrrelser Lærevansker Mye ØLI Assosiert med astma og atopisk dermatitt

25 25 Husk.. Spør rutinemessig etter symptomer på astma Lungeauskultering Vurder spirometri Vurder henvisning til allergologisk utredning

26 26 Spesifikk immunterapi (SIT / Reduserer mastcellers og basofile granulocytters evne til frigjøring av histamin og hyposensibilisering / allergivaksinering) 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.

27 27 Behandling av allergisk rhinitt Unngå allergener ved påvist allergi Medikamentell behandling Allergen immunotherapi (hyposensitivisering)

28 28 Behandling etter ARIA guidelines

29 29 Leukotrienantagonister Effektivitet Ekvipotent med H1-antagonister, men virker først etter 2-3 dager Reduserer nasal og pulmonal eosinofili Alternativ ved samtidig allergisk rhinitt og astma Sikkerhet God. Dyspepsi (ca. 2%)

30 30 Nasale steroider Mest potente antiinflammatoriske behandling Effektive mot alle nasale symptomer inklusive obstruksjon Bedre enn antihistaminer og leukotrienantagonister Førstelinjebehandling ved kron. allergisk rhinitt

31 31 Nasale steroider Generelt trygg behandling Bivirkninger Nasal irritasjon Epistaxis Septumperforasjon (ekstremt sjelden) Vekstretardasjon (sjelden/liten)

32 32 Miljøfaktorer 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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34 34 Konklusjon 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

35 35 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.

36 36 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.

37 37 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.

38 38 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.

39 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).

40 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).

41 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 H1- antihistamines rather than intranasal H1-antihistamines (conditional Recommendation / very low-quality evidence).

42 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 / high- Quality 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).

43 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.

44 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.

45 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.

46 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).

47 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).

48 48 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.