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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