diagnosis and management of hymenoptera sting

Diagnosis and management of

hymenoptera sting

Sadudee Boonmee,MD

Outline

Epidermiology of hymenoptera stings Clinical presentation Diagnosis Investigation Treatment

Most of them are glycoproteins of 10–50 kDa containing 100–400 amino acid- vasoactive amines (e.g. histamine, dopamine, norepinephrine)- acetylcholine- kinin

Venom allergen

Burning pain and itching

Diagnosis of Hymenoptera venom allergy Allergy 2005: 60: 1339–1349

50-140 mcg

10–31 mcg

1.7–3.1 mcg

2.4-5.0 mcg

4.2 to 17 mcg

Venom protein per sting

Apis species in Thailand

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Dwarf honey bee or Red dwarf honey bee ผึ้��งมิ้��มิ้ มิ้�ขนาดลำ าตั�วแลำะรั�งขนาด

เลำ�กชั้��นเด�ยว ท้�องปลำ�อง แรักสี�สี�มิ้ ปลำ�องตั�อไปจะ

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Apis species in Thailand Asiatic honey bee or Eastern honey bee ผึ้��ง

โพื่รังเอเชั้�ย มิ้�เขตัแพื่รั�กรัะจาย ในอ�ฟกาน�สีถึาน ปาก�สีถึาน

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Apis species in ThailandGiant bee ผึ้��งหลำวง มิ้�ขนาดลำ าตั�ว แลำะรั�งใหญี่�

ท้�&สี,ด สีรั�างรั�งเป!นรั%ปครั�&งวงกลำมิ้ชั้��นเด�ยว ไมิ้�มิ้�ท้�& ปกป'ด มิ้�กสีรั�างรั�งบนตั�นไมิ้�สี%ง ๆ ตัามิ้ชั้ายคาบ�าน

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ท้ว�ปเอเชั้�ยตัะว�นออกเฉี�ยงใตั�ข��นไปจนถึ�งจ�นตัอน ใตั� พื่มิ้�า ศัรั�ลำ�งกา เนปาลำ แลำะอ�นเด�ย

European honey bee or Western honey bee ผึ้��งโพื่รังฝรั�&ง หรั$อ ผึ้��งย,โรัป มิ้�

ขนาดใหญี่�กว�าผึ้��งโพื่รังไท้ย แตั�เลำ�กกว�าผึ้��ง หลำวง น�สี�ยไมิ้�ด,เหมิ้$อนผึ้��งหลำวง แลำะไมิ้�ท้��งรั�งง�าย

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VESPID SUBFAMILY VESPINAE

Tropical hornetVespa tropicana

ต้�อหลั4ม่

Asian giant hornetVespa mandarinia

ต้�อห�วเส์/อย�กษ"

Lesser banded hornet

Vespa affinis ต้�อห�วเส์/อบั�าน

Lesser nocturnal hornet Provespa anomala ต้�อนอนว�น

เลั-ก

รี�งต้�อห�วเส์/อบั�าน

Black-bellied hornet

Vespa basalis ต้�อเม่/องเหน/อ หรี/อต้�อห�ว

เส์/อท�องดี)า

VESPID SUBFAMILY POLISTINAE

แต้นท�องยาวแถบัเหลั/องSlender banded paper

แต้นใบัไม่�เลั-กparapolybia varia

แต้นวงเหลั/องropalidiamarginata

แต้นวงขาว Ropalidia sp.

รี�งแต้น

Ant

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เดลำ�น�วสี: 29-7-52

CROSS REACTIVITY

Double or even multiple positive- true double sensitization- cross-reactive

Cross-Reactivity

Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349

Cross-reactivity within the Apidae family- major allergens honeybees worldwide are very similar structure of the major allergen phospholipase A2 highly identical.

- Bumblebee PLA2 only 53% identical to honeybee immunologic cross-reactivity does exist.

Cross-Reactivity


Cross-reactivity within vespid venoms Cross-reactivity among vespids is strong

similarities of venom composition (identities up to 95%) - cross-reactivity within vespinae (Vespula, Vespa, and Dolichovespula) venoms- Cross-reactivity of the Vespinae with paperwasps (Polistes) is lower than cross-reactivity within the Vespinae

Cross-Reactivity


Cross-reactivity between venoms of Apidae and Vespidae

- hyaluronidase 50% sequence identity between honeybee and vespid venoms major cross reactive component

Cross-Reactivity


Double positive in vitro test can discreminated by skin test positive result more seen only to the venom which truly sensitized.

Species-specific recombinant major allergens- Api m 1( bee venom )- Ves v5 ( vespula )

Identifying true sensitization when dual positive.

Cross-Reactivity


Depending on the country’s climate Prevalence

- 56 – 94% are stung by insect in hymenoptera family at least once in their lifetime1 - In children prevalence rates are lower: questionnaires in several thousand girl and boy scouts in the USA and children in Europe resulted in a prevalence of only 0.15–0.3%.2

Epidemiology

1.Epidemiology of insect-venom anaphylaxis ; Curr Opin Allergy Clin Immunol 2008, 8:330–3372. Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349

Sensitization 9.3 – 27.8% ( positive skin test or detection of specific IgE in patients with no previous case history or both)

In children, in an unselected Italian child population the prevalence of sensitization 3.7%

Epidemiology

1.Epidemiology of insect-venom anaphylaxis ; Curr Opin Allergy Clin Immunol 2008, 8:330–337

Large local reaction (LLR) : 2.4-26.4%- In children is 19% - 38% in beekeepers

Systemic reaction - 0.3-7.5% (European)

- 0.5-3.3% ( USA)

- children in only 0.15–0.8 %. (USA and Europe)

Epidemiology


Anaphylactic shock was reported in 0.6– 42.8%

Fatal rate 0.03-0.48 per 100,000 inhabitants per year ( in USA and Europe )

40 to 85% of the subjects with fatal reactions after Hymenoptera stings had no documented history of previous anaphylactic reactions.

Epidemiology


Epidemiology in Thailand Thammasat : Occurrence rate of

anaphylaxis in ED;food 40%, drugs 36%, insects 5% Poachanukoon o, Asian Pac J Allergy Immunol. 2006 Jun-Sep;24(2-

3):111-6

Bunsawansong W, J Allergy Clin Immunol 2005; 115:S39

Siriraj : Incidence rate of anaphylaxis; drug35%, food28%, idiopathic15%, insect10%

Ramathibodi : Cause of anaphylaxis;food 41%, drugs 25%, insects 11.5%, radiocontrast media 4.2%, allergen extract 4.2% and blood products 2.1%

Direkwattanachai C, J Allergy Clin Immunol 2005; 115:S39

ANAPHYLAXIS IN ADMITED PATIENT A 5 YEARS EXPERIENCE IN CHONBURI HOSPITAL

The common causes of anaphylaxis was food (33%) and insect sting (29%).

Epidemiology in Thailand

Clinical Presentation

Most insect stings local reactions- Redness- Swelling- Itching and pain

Large local reaction (late phase IgE mediated)- increase in size for 24 to 48 hours,- swelling >10 cm in diameter contiguous to the site of the sting, and- 5 to 10 days to resolve

The risk of developing a SR after a LLR is relatively low (5–15%) (in adult & children)

Local reaction

Manifestations not contiguous with the site of the sting mild to lifethreatening.- cutaneous : urticaria and angioedema

- respiratory : bronchospasm, upper airway obstruction (eg, tongue or throat swelling and laryngeal edema)

- cardiovascular : arrhythmias ,coronary artery spasm hypotension and shock

- gastrointestinal : nausea, vomiting, diarrhea, and abdominal pain

- neurological :seizures

Systemic reaction

Non-allergic manifestations

No evidence that these are IgE mediated although the underlying mechanisms are not known.

Rare : under-recognized. Insect stings one quarter of all

anaphylactic deaths in the United Kingdom each year.

Average time from sting to death was 10–15min.

Fatal reaction


RISK FACTOR OF HYMENOPTERA

VENOM ALLERGY

The frequency of a systemic reaction is affected by the following factors

◦Time interval between sting: Risk for SRs increased by 58% if preceded by sting with in 2 month

: With increasing interval between stings

the risk declines steadily, but remains in range of 20–30% even after 10 years.

RISK FACTOR OF HYMENOPTERA VENOM ALLERGY

Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220

o Sensitization to venom : Ig E sensitization a riskfactor for subsequent SRs

o Severity of the preceding reaction

: After a large local reaction 5 -15% developSR when next stung.

: After Systemic reaction 40–60% developSR when next stung.

o Insect : Bee venom > vespid for systemic reaction on next sting.

o Bee keeper : Frequently stung < 15-25 sting per year high risk of SR > 200 sting per year protected

o Atopy : Venom allergy not common in atopic individual

The severity of a systemic reaction

o Age : Major SR in pediatric cutaneous Adult Cardiovascular

o Underlying Cardiac and respiratory disorder

o Elevated Baseline tryptase and mastocytosis อธุ์�บายแตั�ลำะอ�น


Nature of the symptoms of initial insect sting anaphylaxis is related to the risk and severity of subsequent sting reactions

re-stings were analyzed in 220 patients (venom anaphylaxis + did not receive VIT )

The incidence of a reaction after re-sting was 56% in the total group, was more frequent in adults (74%) than in children (40%)

Natural history of insect sting allergy: Relationship of severity of symptoms of initial sting anaphylaxis to re-sting reactionsMD Robert E. Reisman (J Allergy Clin Immunol 1992;90:335-9)

When re-sting reactions did occur, symptoms was similar to initial sting reaction.

The observations suggest that patients with mild to moderate symptoms probably do not require VIT

Natural history of insect sting allergy: Relationship of severity of symptoms of initial sting anaphylaxis to re-sting reactionsMD Robert E. Reisman (J Allergy Clin Immunol 1992;90:335-9)

DIAGNOSIS

Detailed history

o Date of sting reactionso Severity of symptomso Interval between sting and the onset of symptomo Progression of reactiono Emergency treatmento Sting siteo Retained or removed stingero Environment and activities before stingo Risk factors of severe reactiono Risk factors for repeated re-stingso Tolerated stings after the first systemic reactions

Investigations for hymenoptera venom allergy


Demonstration of venom-specific immunoglobulin E

1. Skin test - immediately available - greater discrimination between bee and wasp sensitization than serum-specific IgE to whole venom- correlate with history



SPT with standardized venom extracts (0.01–100 mcg/mL) with both bee and wasp venoms

If SPT negative but strong clinical history intradermal testing (IDT)- concentrations 0.001- 1mcg/mL venom- volume 0.03 mL of the extract- patients with Hx of severe anaphylaxis lower starting

SRs reported during skin testing



2. Serum-specific IgE- level of ≥ 0.35 kU/L positive- SPT and serum specific IgE not correlate

with clinical, must be interpreted with clinical history

- Double positivity (wasp and bee venom) 30%



Baseline tryptase :- patient with anaphylaxis to

hymenoptera sting have an elevated ( ≥11.4 mg/L) baseline tryptase ‘mastocytosis’ spectrum investigations (bone marrow examination)



- Patients with baseline tryptase with or without systemic mastocytosis develop more severe(cardiovascular reactions) >normal baseline tryptase group


Potier A, Lavigne C, Chappard D et al.Cutaneous manifestations in Hymenopteraand Diptera anaphylaxis: relationshipwith basal serum tryptase. ClinExp Allergy 2009; 39:717–25.

Serum total specific IgEnonspecific total serum IgE of > 250 kU/L is more likely to indicate asymptomatic sensitization

BAT (Basophil activation test) research tool Surface expression of CD63/203c is used as

a surrogate for basophil activation. BAT correlates well with serum-specific IgE


Sting challenge test 1. Untreated patients with or without a

history of anaphylactic sting reactions, to identify who need immunotherapy.

2. patients on maintenance VIT to identify who are not yet protected.

3. performed 1 year or more after stopping VIT to monitor the duration of the protection by treatment, restricted to scientific studies

Management

1.Treatment of acute reaction

Provision of management plan- Treatment plan :antihistamine used, self-injectable adrenaline, supine posture with legs raised.- Children liaison with the school- Patients with previous SRs wear a medical alert bracelet.

2. Prevention

Patients who have had a systemic reaction from an insect sting and have venom-specific IgE antibodies

The goals of VIT 1) prevent systemic reactions and 2) alleviate patients’ anxiety related to insect stings.

3.Venom immunotherapy

Stinging insect hypersensitivity: A practice parameterupdate 2011

Theodore M.Freeman. N Engl J Med2004;351:1978-84.

David B.K Golden. J Allergy Clin Immunol 2005;115:439-47.

The risk of non treatment includes the chance of futurestings causing either mild reactions or life-threateninganaphylaxis, as well as impaired health-related quality oflife. Prediction of risk on future stings is based primarilyon the severity of the past reaction, the level of sensitivitymeasured by skin test or RAST, the age of the patient, andthe degree of exposure

Prospective studies have shown that patients 16 years of age and younger who have experienced cutaneous systemic reactions without other allergic manifestations have approximately a 10% chance of having a systemic reaction if re-stung. If a systemic reaction does occur, it is likely to be limited to the skin, with less than a 5% risk of a more severe reaction and less than a 1% risk of life-threatening anaphylaxis.

Indications for venom immunotherapy in children

Between 1978 and 1985,diagnosed allergic reaction to insect stings in 1033 children, of whom 356 received venom immunotherapy

telephone and mail between January 1997 and January 2000, to determine the outcome of stings that occurred in the period from 1987 through 1999.

N Engl J Med 2004;351:668-74.

N Engl J Med 2004;351:668-74.

VIT is generally not necessary for patients 16 years of age and younger who have experienced only cutaneous systemic reactions (C)

N Engl J Med 2004;351:668-74.

Sting insect hypersensitivity : A practice parameter update 2011


Adults who have experienced only cutaneous manifestations to an insect sting are generally considered candidates for VIT, although the need for immunotherapy in this group of patients is controversial. (D)


The New England Journal of Medicine ;1994

- VIT usually not indicated for sting-induced cutaneous SRs but may be considered in

raised baseline tryptase age likelihood of future stings (bee keeping, or occupational exposure) effect on QOL patient preference morbid conditions.


VIT is generally not necessary in patients who have experienced only large local reactions to stings but might be considered in those who have frequent unavoidable exposure. (B)

The risk of systemic reaction in patients with a history of large local reactions in most studies is no more than 5% to 10%


Venom immunotherapy reduces large local reactions to insect stings(J Allergy Clin Immunol 2009;123:1371-5.)

Selection of venom to be used in immunotherapy Honey bee and bumblebee venoms show

marked cross-reactivity

Venom immunotherapy with honeybee venom alone will be sufficient.

B. M. Bil, F. Rueff, H. Mosbech,F. Bonifazi, J. N. G. Oude-Elberink,the EAACI Interest Group on Insect Venom Hypersensitivity. Allergy 2005;60:1459-70.

Selection of venom to be used in immunotherapy Cross-reactivity exists between the major

venom components of several vespids, particularly between Vespula, Dolichovespula and Vespa venoms

Most common therapy for vespid sensitivities is with the mixed vespid venoms


Selection of venom to be used in immunotherapy

In the case of double-positive tests to honey bee and Vespula RAST-inhibition assays will help to distinguish between cross-reactivity and double sensitization

Treatment with both venoms is only indicated in documented double sensitization


VIT should usually be continued for at least 3 to 5 years. Although most patients can then safely discontinue VIT, some patients might need to continue VIT for an extended period of time or indefinitely. (C)

Duration of VIT


o SR to re-sting discontinuing VIT were reported on only 4.8% of 82 patients with a VIT duration of ≥50 months as opposed to 17.8% of 118 with a VIT duration of 33–49 months

Duration of VIT

The evaluation of the common diagnostic methods of hypersensitivity for bee and yellow jacket venom by means of an in-hospital insect sting.

J Allergy Clin Immunol 1985;75:556–562.

David B. K. Golden. Anne Kagey-Sobotka.Lawrence M. Lichtenstein J Allergy Clin Immunol 2000;105:389.

Studies of immunotherapy with 100 mcg dose of individual venom have been associated with 75-95% efficacy

( Middleton’s allergy principle and practice 7 th adition ; p 1012)

In prospective uncontrolled studies with sting provocation tests during immunotherapy 0–9% of vespid-allergic individuals but around 20% of bee venom-allergic patients still reacted to the challenge.

Efficacy of VIT


Safety 3-12% of patients have treatment-induced

systemic reactions that generally are mild and occur in the early phases of VIT

The large local reactions that occur in 25% of children and 50% of adults, usually at doses about 20-30 mcg

Pretreatment with antihistamines reduces VIT reactions and may improve the efficacy of VIT

Honeybee-sensitive patients have more reactions to VIT (41% versus 25%) than those on vespid VIT

David F. Graft. Med Clin N Am 2006;90:211-32

Protocal schedules for VIT in US

-Build up dose injected VIT 1-2 time/wk (21 wk)-Start concentration 0.1-1mcg/ml- Maintenain dose 100 mcg/ml - US FDA approved every 4 wk-Duration of IT for 3-5 year

Protocal schedules for VIT in UK

-Build up injected VIT every 1 wk ( 12 wk)-Maintenance 100 mcg/ml every 4-8 wk - Duration 3 year (recommented ), mostly receive 3-5 years

Rush

Ultrarush

symptoms of initial insect sting is related to the risk and severity of subsequent sting reactions

Systemic Reaction after subsequence more frequent in adults ( 60 %) than in children (40%)

The risk of systemic reaction in patients with a history of large local is no more than 5% to 10%

Take home message

Patients who have had a systemic reaction from an insect sting and have venom-specific IgE antibodies candidate for VIT

VIT is generally not necessary for patients 16 years of age and younger who have experienced only cutaneous systemic reactions

Take home message

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