ALLERGIA a VELENO di IMENOTTERI

Elisa Meucci

S.Capretti

F. Fassio

MCL. Iorno

A. Radice

D. Macchia

SOS Allergologia Immunologia Clinica

Nuovo San Giovanni di Dio (Firenze)

SOC Allergologia Immunologia Toscana Centro

Dipartimento Specialistiche Mediche

The frequency of anaphylaxis has been estimated to be 50–2000

episodes per 100,000 persons, with a lifetime prevalence of 0.05%–

2.0%.

Attacks of anaphylaxis lead to the death of 0.65%–2.0% of sufferers

Castells J All Clin Immunol 2017

●Hymenoptera stings are among the most

frequent causes of anaphylaxis

● responsible for an annual fatality rate in Europe

of approximatively 200 individuals

Incidence of anaphylaxis with circulatory symptoms: a

study over a 3-year period comprising 940,000

inhabitants of the Swiss Canton Bern.

Helbling A, Hurni T, Mueller UR, Pichler WJ.

Clin Exp Allergy. 2004

Clin Exp Allergy 2009

•Older age

•Insect type (honey bee, european hornet)

•Pre-existing disease: cardiovascolar disease, asthma

•Drugs: particularly b-blockers,

angiontensin-converting enzyme inhibitors

•Sting site (head)

•Mast cell disease, elevated baseline serum tryptase

concentration

Comparison of the robustness and functionality

of three adrenaline auto-injectors

●The Adrenaline Auto-injectors (AAI) currently available in Europe Jext®,

EpiPen®, and Anapen® are designed to deliver a single dose of 0.15 mg

(pediatric) or 0.3 mg (adult) adrenaline in a sterile solutio im into the vastus

lateralis muscle of the thigh.

Schwirtzs J of Asthma and Allergy 2012

• ACTIVATION FORCE

• TEMPO D’INIEZIONE e VOLUME

• ESPOSIZIONE DELL’ AGO

• PERFORMACE DELL ‘ AAI in GELATINA

• DISTRIBUZIONE nella GELATINA

Comparison of the robustness and functionality

of three adrenaline auto-injectors

Schwirtzs J of Asthma and Allergy 2012

MEAN exposed needle:

15,6 mm jext

15,02 mm epipen

7,6 mm anapen

Allergy 2016

Allergy 2016

QUANDO PRESCRIVERE 2 AUTOINIETTORI?

• Mastocitosi

• Precedente episodio near-fatal

• Precedente necessità di più di una dose di

adrenalina

• Obesità

• Lontananza da un punto di soccorso

JACI 2013

PRIMO LIVELLO•Anamnesi•Test cutanei•IgE specifiche sieriche•TriptasiSECONDO LIVELLO•CRD•RAST inibizioneALTRI TEST: BAT, immunoblotting, liberazione d’istamina

Diagnosi di allergia al veleno di Imenotteri

CRD in hymenoptera venom allergy

EAACI Molecular Allergology User’s Guide 2016

Molecular diagnostics with recombinant marker allergens is able to exclude ‘false-positive’ test results due to IgE directed against CCDs or homologous allergens present in venom extracts and to uncover IgE sensitizations to allergens that are underrepresented, labile, degraded, or masked in venom extracts.

Double sensitization• the majority of crossreactivities between honeybee and vespid venom can be attributed to

clinically irrelevant IgE antibodies that are directed against cross-reactive

carbohydrate determinants (CCDs)

This is of particular importance, as most Hymenoptera venom allergens are

glycoproteins with one or more of such carbohydrate structures

In insects the relevant CCD epitope is defined by an alpha-1,3-linked fucose residue at the

innermost N-acetylglucosamine • highly immunogenic because they are not present in

mammals and can induce the production of specific

IgG and IgE antibodies.

• No CLINICAL RELEVANCE

CRD in bee venom allergy

CRD in vespid venom allergy

Indicazioni alla immunoterapia

Journal of Asthma and Allergy 2015; 8:75-86

Allergy 2015

Aeberhard et al, J Investig Allergol Clin Immunol 2017

Specific Immunotherapy in Hymenoptera Venom Allergy and

concomitant Malignancies. A retrospective follow-up focusing on

efficacy and safety.

In case of concomitant malignancies VIT has been considered contraindicated

Wohrl et al Int Arch Allergy Immunol 2011

EAACI position paper 2015

• 42 of a total of 1,495 patients with VIT were diagnosed with cancer either before

VIT (25 subjects), during VIT (16 subjects) or after VIT (one subject)

• overall incidence of cancer was 1.1 %. This number of affected patients is lower

than in the general Swiss population (2.2 %).

• Among 25 patients with known malignancies at the start of VIT, it results safe in

stable cancer disease

• It is safe to resume VIT after cancer treatment has been conducted.

• The impact of the cancer, or its treatment, seems not to reduce the immunologic

response to VIT

ESTRATTI acquosi, depot, purificati

DOSE 50-100-200 mcg

BUILD-UP tradizionale, cluster, rush, ultrarush

TIMING della SOMMIN. primo anno ogni 4 sett.

secondo anno ogni 6

terzo anno ogni 8

quarto anno ogni 10

dal quinto in poi ogni 12

Venom immunotherapy (VIT) in Hymenoptera

venom allergy is an established treatment with

an efficacy rate of 75-80 % in bee venom and

over 90 % in Vespula venom allergic patients

EAACI Interest Group on Insect Venom Hypersensitivity.

Prevention and treatment of Hymenoptera venom allergy:

guidelines for clinical practice. Allergy 2005

The anxiety that some patients feel about LLRs may be

initiated by friends and even physicians concerned about

the risk of fatal systemic reactions to subsequent stings

(‘the next one will kill you’).

2016

the risk of anaphylaxis 5–15% from several studies,

but all of them studied very small numbers of patients and

most of them were retrospective.

epinephrine prescription to patients with LLRs gives

patients the impression that there is significant risk of

anaphylaxis, even when they are told that the risk is

‘minimal’. Prescription of epinephrine is not benign and is

associated with impaired quality of life

Large local reactions

“

Severino MG et al JACI 2008Golden BK et al. JACI 2009

Triptasi persistentemente elevata

Diagnosi : biospsia cutanea+o - BOM

Prurito, flushing, orticaria

Anafilassi (imenotteri/ farmaci/alimenti)

Sincope/palpitazioni

Osteoporosi, fratture vertebrali

Cefalea, difficoltà di concentrazione Depressione, insonnia

Diarrea, crampi addominali, gastrite

Stimoli fisici- calore- freddo- pressione- sfregamentoFattori emozionali- stress- ansiaFarmaci

- acido acetilsalicilico- antinfiammatori non steroidei- morfina e rilassanti muscolari utilizzati nell’anestesia generale, anestetici locali- beta-blocccanti, alfa-adrenergici e antagonisti dei recettori colinergici- polimixina-B, anfotericina-B- interferon-alfa- molecole ad alto peso molecolare come il destranoMezzi di contrasto iodati

Punture di insetti (imenotteri, ditteri)AlcoolAlimenti Esami endoscopici/ Interventi chirurgici

Fino all’8% dei pazzienti con grave reazione allergica a puntura d’imenottero è

affetta da mastocitosi

Alcuni pazienti vengono dignosticati soltanto a causa della gravità della reazione

dopo puntura di imenotteri

Questi pazienti hanno della caratteristiche diverse dagli altri pazienti con mastocitosi

e ci si chiede se sia un’entità patologica a se stante.