Anaphylaxie bei Immuntherapie

Transkript

1 Anaphylaxie bei Immuntherapie Peter Eng FMH Pädiatr. Pneumologie FMH Allergologie und klin. Immunologie Kinderspital Aarau und Luzern Löwenpraxis Luzern Immunoday Luzern,

2 Anaphylaxie bei Immuntherapie Fallvorstellung Anaphylaxie nach sublingualer Immuntherapie (SLIT) Anaphylaxie nach subkutaner Immuntherapie (SCIT) Häufigkeit systemisch allergischer Reaktionen Near fatal and fatal reactions Risikofaktoren für Anaphylaxien nach Immuntherapie Vorsichtsmassnahmen zur Prävention Behandlung

3 Samuel, 13-jährig Mittelschwere bis schwere Rhinokonjunktivitis pollinosa - Sensibilisierung auf Gräser- und Baumpollen Kein Asthma, nie akute Laryngotracheitis Beginn SCIT mit je 100% Gräser- und 100% Eschenpollen Extrakten 6h nach 5. sc-injektionen: akute Atemnot mit inspiratorischem Stridor Therapie: inhalatives Adrenalin, Antihistaminika und Corticosteroide po

4 Samuel, 13-jährig Beurteilung: SAR Grad 3 (gemäss WAO 2010*) nach SCIT (Spätreaktion) * Cox L et al. The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System JACI 2010;125:569-74

5 Rostrum Speaking the same language: The World Allergy Organization subcutaneous immunotherapy systemic reaction grading system Cox L et al. JACI 2010;125:569-74

6 Rostrum JACI 2013;132: Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language Giovanni Passalacqua, Carlos E. Baena-Cagnani, Jean Bousquet, Giorgio Walter Canonica et al.

7 Samuel, 13-jährig Beginn SLIT: 100% Gräserpollen und 100% Eschenpollen jeweils leichtes, kurz anhaltendes enorales Brennen nach Einnahme Nach Dosissteigerung auf Hälfte der Maximaldosierung: Nächtliches Aufwachen (6-8h nach SLIT) mit: ausgeprägter Dyspnoe und starkem inspiratorischem Stridor

8 Samuel, 13-jährig Wie weiter? Do it again! Bei gleicher Dosis erneut nächtlicher Laryngospasmus mit starker Dyspnoe, inspiratorischem Stridor Unter Xyzal, Spiricort per os, Adrenalininhalation rasch besser Abbruch der sublingualen Immuntherapie

9 Allergy 2009;64:963-4 Author's advice: 1) Not to start SLIT in patients with systemic SAR after SCIT 2) To take first dose of SLIT in doctor's office, 30 minutes observation

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11 Die Empfehlung, bei Patienten mit schweren Nebenwirkungen unter SCIT einen Wechsel auf eine SLIT vorzunehmen, kann nicht unterstützt werden, da eine Anamnese mit schweren systemischen Reaktionen nach subkutaner Applikation von Allergenen auch bei der SLIT einen Risikofaktor für potentiell schwere systemisch Reaktionen darstellt.

12 SLIT: 40 75% local reactions Especially during initiation and dose build-up phase 11 cases of non-fatal anaphylaxis published

13 Safety: special considerations Because the treatment is administered at home without direct medical supervision, patients should be provided with specific instructions regarding how to manage - adverse reactions - unplanned treatment interruptions

14 Some extracts are more likely to induce anaphylaxis or bronchospasm than others The efficacy of desensitising agents used in this country apart from the bee and vasp venoms remains in doubt.

15 82 confirmed fatalities from SCIT reported to surveillance committees SCIT related deaths per year in USA

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17 Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes fo the ACAAI and AAAAI Collaborative study David I Bernstein, Tolly Epstein et al Ann Allergy Asthma Immunol 2010;104: : introduction of a web-based prospective surveillance programme amongst members of AAAAI and ACAAI Monitoring annual incidences of SAR of varying severity related to SCIT and skin testing

18 JACI Pract 2014;2:161-7 Data gathered on 23.3 million injection visits From 2011: WAO classification system for SAR adopted: Grade 1 4 (very severe) and 5 (death)

19 JACI Pract 2014;2: fatality (2009) Declining since implementation of practice parameter guidelines introduced 2003 to mitigate risks associated with SCIT Annual incidence SAR 1:1000 sc Injections (stable) Incidence very severe (near fatal) Grade 4 SAR 1 : 1 Mio sc Injections (stable) severe airway compromise or upper airway obstruction with stridor or hypotension, with or without loss of consciousness

20 17 fatal reactions 16 after sc-allergen injection 1 after skin testing Scratch 90 food allergens in a female patient with uncontrolled asthma (FEV1 36%)

21 80 % whithin 30 minutes after injection 20 % later (outside office)

22 age range: 5-81 years 2 children with asthma (5 and 12 y) 12% of fatal reactors: allergic rhinitis 88%: asthmatics 60% not controlled asthma 50% FEV1 < 70%

23 Fatalities and use of epinephrine: 33% of fatalities: administration of epinephrine too late > 5 minutes 30% of fatalities: administration of epinephrine subcutaneously instead of im or iv

24 Risk factors for fatal reaction following SCIT: Uncontrolled asthma (38-92%) High allergen dosis during peak pollen season (29-41%) Prior SAR to SCIT (28-42%) Delayed or not given epinephrine (7-18%)

25 Risk factors for fatal reaction following SCIT: Dosing or administration errors (6-27%) Inadequate waiting times after injections (6-13%) Late SAR (after 30 min) (6-18%) Administration in medically unsupervised settings (4-18%) Concommittant beta blocker use (0-13%)

26 AIT should not be initiated in patients with poorly controlled asthma symptoms. Asthma control has to be assesssed at each injection visits JACI 2010;127:1:S1-S55

27 Dose adjustment during pollen seasons associated with fewer SAR Grade 3 or 4 (p<.001) JACI Pract 2014;2:161-7

28 LESSONS TO REDUCE FUTURE NUMBER OF FATAL OR NEAR-FATAL REACTIONS TO SCIT FATALITIES 80%: not controlled asthma 50%: FEV1 < 70% 20%: late reactions (> 30 ) Bernstein DI et al. JACI 2004;113: RECOMMENDATIONS Withold SCIT if asthma is not well controlled Assess asthma before injection (spirometrie, PF) Extend waiting period to in high risk patients Dispense self-injectable epinephrine in high risk patients

29 LESSONS TO REDUCE FUTURE NUMBER OF FATAL OR NEAR-FATAL REACTIONS TO SCIT FATALITIES 18%: at home / unsupervised clinic 30-50%: inadequate epinephrine administration Bernstein DI et al. JACI 2004;113: RECOMMENDATIONS SCIT only in fully equipped clinic / practiced by trained staff mg epinephrine i.m. immediately after begin of respiratory or CV symptoms Repeat epinephrine 2x, if no response, to i.m. => i.v. infusion

30 JACI 2004;113: Use patient specific vials Standardised dosing sheets Triple check to make sure the correct patient is receiving the correct injection

31 Im Einzelfall ist gemeinsam mit dem verordnenden Arzt über die unter Umständen notwendige Fortführung der Therapie mit Beta-Blockern zu entscheiden.

32 JACI 2009;123: (23%) reactions were biphasic No biphasic reaction in children All biphasic reaction were significantly less severe compared with initial reaction Non of the biphasic reaction required second epinephrine dose

33 TREATMENT OF ANAPHYLAXIS (1) 1. Rapid assessment of patient, remove exposure to trigger 2. Adrenaline i.m mg/kg 3. Place patient on the back, lower extremities elevated 4. Oxygen 5. i.v.-line and volume: saline or colloid 20 ml/kg i.v. 6. Antihistaminics i.v. (Clemastine 0.05 mg/kg) 7. Corticosteroids i.v. (Hydrocortisone 2 mg/kg) 8. Admission for monitoring (1) Simons E et al. World Allergy Organisation guidelines: for Assessment and Management of Anaphylaxis.J Allergy Clin Immunology 2011;593.e1-22.

34 Premedication with H1 antihistamine effective in patients with recurrent LR or mild SAR Insufficient evidence that antihistamines can effectively prevent near-fatal or fatal anaphylactic reactions* * US practice parameter JACI 2011

35 Omalizumab Fewer SAR to AIT in 248 patients with uncontrolled asthma (1) Prevention of anaphylaxis during VIT (2) Reduces SAR in OIT to multiple foods (3) (1) JACI 2010;125:383 (2) JACI 2014;133:937 (3) Allergy Asthma Clin Immunol 2014;10:7

36 AIT: Perspective for improving safety Production of AIT extracts which are less allergenic while retaining potential for tolerance induction Use AIT in facilities equipped for resuscitation Educate staff, follow recommendations SLIT: first dose administered under medical supervision Calderon et al. Curr opin Allergy Clin Immunol 2014;14:316