Biologicals - internisten en angio oedeem.pdf · Basofielen activatie test Provocatie...
Transcript of Biologicals - internisten en angio oedeem.pdf · Basofielen activatie test Provocatie...
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Allergie en angio-oedeem
Paul van Daele
Snapperdagen Nijmegen
9 juni 2016
(potentiële)
belangenverstrengeling Geen / Zie hieronder
Voor bijeenkomst mogelijk
relevante relaties met
bedrijven
Bedrijfsnamen
Sponsoring of
onderzoeksgeld
Honorarium of andere
(financiële) vergoeding
Aandeelhouder
Andere relatie, namelijk
…
nvt
Disclosure belangen spreker
Disclosure belangen spreker
Allergie
Epidemiologie
Allergie is frequent voorkomend probleem
Ruim 1,2 miljoen Nederlanders gebruiken antiallergiemedicatie
Allergische rhinitis: 5-22% (bron: Allergy and Asthma Proc
21:367-370, 2000)
Lijkt toe te nemen (bron: Nationaal Kompas Volksgezondheid)
Allergie
Allergie
Inhalatie (bijv. huisstofmijt, pollen, huisdieren)
Voedselallergie (pinda, garnaal, kreeft)
Geneesmiddelenallergie (NSAID’s, antibiotica,
anaesthesiemiddelen)
Insecten allergie
Beroepsallergie
En allerlei rariteiten
Angio-oedeem
Urticaria
Maar naast type I ook
Type II: antistof gemedieerde cel-destructie
Maar naast type I ook
Type III: immuuncomplex gemedieerde reactie (Bijvoorbeeld
serumziekte)
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Maar naast type IV
Type IV: T-cel gemedieerd (ook wel delayed-type hypersensitivy)
Van mild
Tot zeer ernstig
Diagnostiek
Belangrijkste wapen in de diagnostiek Aanvullende diagnostiek
Specifiek IgE
Huidtesten
Plakproeven
Basofielen activatie test
Provocatie
Praktijkvoorbeelden
Rhinoconjunctivitis in de zomer
Braken en diarree en urticaria na broodje kip met pesto
Anafylaxie na wespensteek
Verdenking allergie voor amoxicilline
Angio-oedeem na het nemen van brufen
Dikke lippen na het eten van een appel
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Behandeling
Vermijden
Behandeling
Medicamenteus:
Antihistaminica
(lokale) corticosteroïden
(adrenaline)
Behandeling
Immunotherapie: Leonhardt Noon en John Freeman, Lancet 1911
Werkingsmechanisme immunotherapie
Immunotherapie
Subcutaan
sublingaal
Immunotherapie
Beschikbaar voor:
Huisstofmijt
Graspollen
Boompollen
Insecten
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Fig 2. Percentage of patients with changes in fluticasone dose steps after 2 years of therapy by comparison with baseline (P <
.05).
Stefan Zielen, Peter Kardos, Enzo Madonini
Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: A randomized controlled trial
Journal of Allergy and Clinical Immunology, Volume 126, Issue 5, 2010, 942–949
http://dx.doi.org/10.1016/j.jaci.2010.06.002
Kosten € 1.500 per jaar
Langdurig (3-5 jaar)
Immunotherapie voor voedingsmiddelen Immunotherapie
Trials voor
Melk
Eieren
Pinda
Hazelnoot
Dus wat is er dan aan nieuws? Omalizumab (anti-IgE)
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Fig. 1. Effect of treatment on ICS use.
William Busse, Jonathan Corren, Bobby Quentin Lanier, Margaret McAlary, Angel Fowler-Taylor, Giovanni Della Cioppa, Andre
van As, Niroo Gupta
Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma ☆ ☆☆
Journal of Allergy and Clinical Immunology, Volume 108, Issue 2, 2001, 184–190
http://dx.doi.org/10.1067/mai.2001.117880
astma
Fig. 2. Mean change from baseline in total asthma symptom scores and numbers of puffs of rescue medication (albuterol) per day.
William Busse, Jonathan Corren, Bobby Quentin Lanier, Margaret McAlary, Angel Fowler-Taylor, Giovanni Della Cioppa, Andre
van As, Niroo Gupta
Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma ☆ ☆☆
Journal of Allergy and Clinical Immunology, Volume 108, Issue 2, 2001, 184–190
http://dx.doi.org/10.1067/mai.2001.117880
astma
Urticaria Welke diagnostiek en wanneer?
Wanneer: na 6 weken
Welke diagnostiek:
Bloedbeeld
CRP/BSE
Urticaria Urticaria
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Behandeling?
Maurer M et al. N Engl J Med 2013;368:924-935.
Mean Weekly Symptom Scores.
En bij allergie?
Fig 1. Protocol flow chart.
Lynda C. Schneider, Rima Rachid, Jennifer LeBovidge, Emily Blood, Mudita Mittal, Dale T. Umetsu
A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients
Journal of Allergy and Clinical Immunology, Volume 132, Issue 6, 2013, 1368–1374
http://dx.doi.org/10.1016/j.jaci.2013.09.046
Resultaat
start eind
Kosten
5 injecties: € 2071,03
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En is er nog meer?
Angioedema
Angioedema
self-limited
localized subcutaneous (or submucosal) swelling
which results from extravasation of fluid into interstitial tissues.
in isolation
accompanied by urticaria
as a component of anaphylaxis.
It is not only the face
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Epidemiology
US: 80.000 – 112.000 ED/annually
18% of ED for angioedema results in hospital admission
Hospitalization rate: 4:100.000 persons
Lifetime prevalence 7.4%
Underlying cause identified in 20-40%
Academic Emergency Medicine 2014;21:469–484 © 2014 by the Society for Academic Emergency Medicine
Acta Derm Venereol 2012; 92
Mast cell driven
Bradykinin
Unknown/cytokine driven
Pathophysiology: Mast cell induced angioedema Pathophysiology: Mast cell induced angioedema
Pathophysiology: bradykinin induced angioedema Pathophysiology: bradykinin induced angioedema
Inhibition of bradykinin degradation
Increased bradykinin production
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Pathophysiology: bradykinin induced angioedema Pathophysiology: bradykinin induced angioedema
ACE inhibitors
-
ACE inhibitor induced angioedema
Prevalence 0.1-2.2%
About 1/3 of angioedema cases on the ER
50% within one week of start treatment
Relatively often involvement gastro-intestinal tract
Figure 3
The Lancet 2012 379, 474-481DOI: (10.1016/S0140-6736(11)60935-5)
Copyright © 2012 Elsevier Ltd Terms and Conditions
Increased bradykinin production HAE
Three types
Type I: low concentration of C1-inh
Inherited
aquired
Type II: functionally abnormal C1-inh
Type III: estrogen dependent
20% mutation in FXII
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HAE
Prevalence: 1-50 / 100.000 persons
Median attack frequency: 1 / 45 dagen
Annual cost per patient (without treatment): 42.000 – 92.000 $
HAE
Increased attack risk
Physical and emotional stress
ACE inhibitor use
Exposure to estrogens
Why and how to make a difference
Why?
Different treatment approach
Different approach in prevention
How
By careful anamnesis
By looking at the skin
Sometimes by laboratory analysis
Urticaria
Urticaria pigmentosa Erythema marginatum
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What laboratory analyses should be performed
Tryptase
C4
(C1-inhibitor)
Concentration
Activity
Differential diagnosis
Peri-orbital contact dermatitis
Infection (cellulitis)
Auto-immune disease
Superior vena cave syndrome
Differential diagnosis
Madke, Bhushan Sevakram; Ghia, Deepti; Gadkari, Reshma; &
Nayak, Chitra. (2012). Cheilitis granulomatosa (Miescher
granulomatous macrocheilitis) with trisomy 21. Dermatology
Online Journal, 18(6).
Treatment angioedema
In general
Focus on vital signs
Examination of the airways, skin and abdominal regions
Consider flexible fiberoptic laryngoscopy
Treatment: mast cell mediated
Life threatening:
Secure airway
Epinephrine + actions taken below
Not life-threatening
H1-receptor antagonist
H2 receptor antagonist
Corticosteroids
Usually relatively quick response
Treatment bradykinin associated angioedema
Life threatening
C1-inhibitor
Plasma derived
Conestat alfa (recombinant C1-esterase inhibitor)
Icatibant (bradykininereceptor type 2 antagonist)
Ecallantide (plasma kallikreine inhibitor)
FFP
(epinephrine)
Corticosteroid / H1-receptor blockers?
Not life-threatening
Wait and see
Consider phrophylactic treatment
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Primary Outcome in the Trial of C1 Inhibitor Therapy for Acute Attacks of Angioedema.
Zuraw BL et al. N Engl J Med 2010;363:513-522
.Estimated median time to the onset of unequivocal relief: 2 hours in the C1
inhibitor group vs. 4 hours in the placebo group
(estimated success rate ratio: 2.41; 95% CI: 1.17 to 4.95; P=0.02)
Cost of treatment
Plasma derived C1-inhibitor
Per 500 IE: € 770
Usually 1000 IE per attack
Median attack frequency: 8 / year
Total cost: > €12,000
Treatment in ACE inhibitor induced angioedema
Mean time (hours) until complete resolution of symptoms in the 8 patients treated with
icatibant and in a historical group of patients receiving standard therapy with
methylprednisolone and clemastine.
Prophylaxis
When to give prophylaxis
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Prophylaxis
Androgens
Danazole (max 200 mg/day)
Stanazole (2 mg/day)
Cyklokapron (max 4,5 g/day)
C1-inhibitor