4. 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
5. Venom protein per sting 50-140 mcg 10–31 mcg 1.7–3.1 mcg 2.4-5.0 mcg 4.2 to 17 mcg Diagnosis of Hymenoptera venom allergy Allergy 2005: 60: 1339–1349
6. Apis species in Thailand Dwarf honey bee or Red dwarf honey bee ผึ้งมิ้ม มีขนาดลำตัวและรังขนาดเล็กชั้นเดียว ท้องปล้องแรกสีส้ม ปล้องต่อไปจะเป็นสีดำสลับสีเหลืองอ่อน มักสร้างรังอยู่บนกิ่งไม้ขนาดเล็ก และมีกิ่งไม้ปกปิด เพื่อป้องกันศัตรูพบเห็น ผึ้งมิ้มพบทั่วไปในประเทศไทย และทุกประเทศในเอเชียตะวันออกเฉียงใต้ขึ้นไปจนถึงจีนตอนใต้ www.maleang.com
16. Double or even multiple positive - true double sensitization - cross-reactive Cross-Reactivity Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
17. 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 Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
18. 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 Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
19. Cross-reactivity between venoms of Apidae and Vespidae - hyaluronidase50% sequence identity between honeybee and vespid venoms major cross reactive component Cross-Reactivity Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
20. 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 Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
21. 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 ; CurrOpin Allergy ClinImmunol 2008, 8:330–337 2. Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
22. Sensitization 9.3 – 27.8% ( positive skin test or detection of specific IgE in patients with no previous case history or both) Inchildren, inanunselectedItalianchildpopulationtheprevalenceofsensitization 3.7% Epidemiology 1.Epidemiology of insect-venom anaphylaxis ; CurrOpin Allergy ClinImmunol 2008, 8:330–337
23. 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 1.Epidemiology of insect-venom anaphylaxis ; CurrOpin Allergy ClinImmunol 2008, 8:330–337
25. 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 Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
27. 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
29. Local reaction 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)
30. Systemic 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
33. 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 1.Epidemiology of insect-venom anaphylaxis ; CurrOpin Allergy ClinImmunol 2008, 8:330–337
36. 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. Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
37.
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40. Elevated Baseline tryptase and mastocytosisอธิบายแต่ละอัน Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
41. 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) 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%)
42. 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
54. Tolerated stings after the first systemic reactionsDiagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
55. Demonstration of venom-specific immunoglobulin E Skin test - immediately available - greater discrimination between bee and wasp sensitization than serum-specific IgE to whole venom - correlate with history Investigations for hymenoptera venom allergy Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
56. 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 Investigations for hymenoptera venom allergy Diagnosis of Hymenoptera venom allergy ;Allergy 2005: 60: 1339–1349
57.
58. SPT and serum specific IgE not correlate with clinical, must be interpreted with clinical history
59. Double positivity (wasp and bee venom) 30%Investigations for hymenoptera venom allergy Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
60. Baseline tryptase : -patient with anaphylaxis to hymenoptera sting have an elevated ( ≥11.4 mg/L) baseline tryptase ‘mastocytosis’ spectrum investigations (bone marrow examination) Investigations for hymenoptera venom allergy Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
61. - Patients with baseline tryptase with or without systemic mastocytosis develop more severe(cardiovascular reactions) >normal baseline tryptase group Investigations for hymenoptera venom allergy Potier A, Lavigne C, Chappard D et al. Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase. Clin Exp Allergy 2009; 39:717–25.
62. Serum total specific IgE nonspecific 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 Investigations for hymenoptera venom allergy
63. Sting challenge test Untreated patients with or without a history of anaphylactic sting reactions, to identify who need immunotherapy. patients on maintenance VIT to identify who are not yet protected. performed 1 year or more after stopping VIT to monitor the duration of the protection by treatment, restricted to scientific studies
66. 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
67.
68. 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 parameter update 2011
70. The risk of non treatment includes the chance of future stings causing either mild reactions or life-threatening anaphylaxis, as well as impaired health-related quality of life. Prediction of risk on future stings is based primarily on the severity of the past reaction, the level of sensitivity measured by skin test or RAST, the age of the patient, and the degree of exposure David B.K Golden.J Allergy ClinImmunol 2005;115:439-47.
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72. 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
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75. 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.
78. VIT is generally not necessary for patients 16 years of age and younger who have experienced only cutaneous systemic reactions (C) Sting insect hypersensitivity : A practice parameter update 2011 Sting insect hypersensitivity : A practice parameter update 2011 N Engl J Med 2004;351:668-74.
79. 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) Sting insect hypersensitivity : A practice parameter update 2011
81. - 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. Diagnosis and management of hymenoptera venom allergy: BSACI guidelines Clinical & Experimental Allergy, 41, 1201–1220
82. 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% Sting insect hypersensitivity : A practice parameter update 2011
84. Selection of venom to be used in immunotherapy Honeybeeandbumblebeevenomsshowmarkedcross-reactivity Venomimmunotherapywithhoneybeevenomalonewillbesufficient. 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.
85. Selection of venom to be used in immunotherapy Cross-reactivityexistsbetweenthemajorvenomcomponentsofseveralvespids, particularlybetweenVespula, DolichovespulaandVespavenoms Most common therapy for vespid sensitivities is with the mixed vespid venoms 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.
86. Selection of venom to be used in immunotherapy Inthecaseofdouble-positiveteststohoneybeeandVespulaRAST-inhibitionassayswillhelptodistinguishbetweencross-reactivityanddoublesensitization Treatmentwithbothvenomsisonlyindicatedindocumenteddoublesensitization B. M. Bil, F. Rueff, H. Mosbech,F. Bonifazi, J. N. G. Oude-Elberink,the EAACI Interest Group on Insect Venom Hypersensitivity.Allergy2005;60:1459-70.
87. 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 Sting insect hypersensitivity : A practice parameter update 2011
88.
89. David B. K. Golden. AnneKagey-Sobotka.Lawrence M. LichtensteinJ Allergy ClinImmunol 2000;105:389.
90. Studies of immunotherapy with 100 mcg dose of individual venom have been associated with 75-95% efficacy ( Middleton’s allergy principle and practice 7 thadition ; 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 B. M. Bil, F. Rueff, H. Mosbech,F. Bonifazi, J. N. G. Oude-Elberink,the EAACI Interest Group on Insect Venom Hypersensitivity.Allergy2005;60:1459-70.
95. 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
96. 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