2. • Epidemiology
• Etiology
• Taxonomy
• Insect venom
• Clinical features
• Evaluation & Diagnosis
• Treatment and Prevention
• Predictors of risk for sting anaphylaxis
• Venom immunotherapy
Outline
3. • 56%-94% of adults worldwide have been stung a least once in their lifetime
• Can occur any age
• Only a weak correlation with other allergic conditions
• Most reactions are localized and self limited
- Large local reaction 5-25%
- Systemic reactions
>> Children 0.4-0.8%
>> Adults 3%
Epidemiology
Middleton'sEd8.
Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
4. • Stinging insects belong to the order Hymenoptera
• Sting apparatus is a modified ovipositor, only the female
insects can sting
• Almost sting primarily in defense of themselves and their nest
Etiology
Middleton'sEd8.
Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
6. FamilyApidae
• Feral honeybees often nest in natural hollows such as in trees
• Domestic honeybees : Rarely sting or swarm without considerable
provocation, mostly in defense of their nest and their queen
• "Sting autotomy"
Sting apparatus of the honeybee is barbed and breaks away
from the insect body when it remains in the skin after a sting
and leads to its death
Middleton's Ed 8.
Apis (Honeybee)
(ผึ้งน้ำหวาน)
7. • Unusual tendency to swarm
with little provocation and to
sting in large numbers
• Large numbers of stings at
one time can cause toxic
reactions --> Fatal to human
• Not found in Thailand
Middleton's Ed 8.
National Pest Management Association
8. Bombus (Bumblebee)
(ผึ้งหึ่ง)
• Not aggressive and do not usually sting
• Very uncommon causes of sting
• “fuzzy” appearing hair and loud buzzing sound
• Report to cause anaphylaxis during occupational exposure
especially in areas of higher exposure (e.g., greenhouse
workers)
• Found in Northern of Thailand
• Very limited cross-reactivity with honeybee sting reactions
Middleton's Ed 8.
Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
10. FamilyVespidae
Middleton's Ed 8.
Makoto Matsuura. The Social Biology Of Wasps.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
Provespa (ต่อนอนวัน)
• Typical nocturnal habits (peak:1-3 hr. after sunset)
• Nest in shrubs or trees
Thai : Provespa Barthelemyi
Provespa Anomala
11. • Use a wood pulp to construct nests that contain one or more
layers of comb, each of which contain a large number of cells,
attached in a vertical arrangement and usually are enclosed in
papier mâché outer layers
• Does not commonly autotomize, and vespids are able to
sting repeatedly
Vespa (Tropical Hornet)
(ต่อหัวเสือ)
Middleton's Ed 8.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
Thai : Vespa Affinis
Vespa Tropica
12. Polistes (Paper Wasp)
(ต่อกระดาษ)
• Narrow wasp waist and dangling legs when in flight
• Commonly build nests on human habitation
• Nest limited to single-layer of open cells with minimal outer covering
• Generally not aggressive but can sting readily when disturbed and can sting repeatedly
• Very commonly mistaken for a yellow jacket, as it is black, strongly marked with yellow
Thai : Polistes Sagitharius
Middleton's Ed 8.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
13. Vespula (Yellow Jacket)
• Scavengers
• Seek their food at picnics and in orchards, trashcans, and dumpsters
• Highly aggressive and sting for no apparent reason
• Nests are located in the ground or in cracks in buildings or
residential landscape materials
• Not found in Thailand
Middleton's Ed 8.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
14. Dolichovespula
(White-Faced & Yellow Hornet)
• Their sensitivity to vibration can initiate their defensive sting behavior
• Not found in Thailand
Middleton's Ed 8.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
15. FamilyFormicidae
• When they bite, they anchor by their mandibles and
pivot to administer multiple stings
• Unique lesions : "sterile pustules" within 24 hr. that can
become infected if excoriated or opened
Middleton's Ed 8.
วิภาดา ปาริยะประเสริฐ และนวลอนงค์ วิศิษฏสุนทร . โรคภูมิแพ้จากแมลงต่อย. ศิริราช 353-94.
17. Middleton's Ed 8.
Bilò Mb, Et Al. Allergy 2005; 60: 1339-49.
• Typically contain a mixture of 3 to 4 major proteins
• Contain active peptides, vasoactive substances and enzymes
• Common proteins shared amongst the various Hymenoptera species
• Major allergens primarily protein enzymes : phospholipase,
hyaluronidase, and acid phosphatase
- Glycoproteins of 10-50 kDa containing 100 – 400 amino acid residues
Insect venom
19. Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
Ollert M. Curr Allergy Asthma Rep (2015) 15: 26.
Apidae
Api m1
Api m2
Api m3
Api m7
20. Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
Vespidae
Ves v1
Ves v2
Ves v5
Phospholipases found in vespid venoms (PLA 1)
differ from those found in bee venoms (PLA 2)
21. Pesek Et Al. Allergy Asthma Immunol Res. 2013 May; 5(3):129-137.
Formicidae
Sol i1
Sol i3
22. • Hymenoptera deliver between 50 ng (fire ants) and 140 μg (honeybees)
of venom with each sting
- Honeybee : 50 - 140 µg of venom protein
- Bumblebee : 10 - 31 µg of venom protein
- Vespula : 1.7 - 3.1 µg of venom protein
Dolichovespula : 2.4 - 5.0 µg of venom protein
Polistes : 4.2 - 17 µg of venom protein
- Fire ant : 50 ng of venom protein
Venom Dose
Middleton's Ed 8.
Bilò Mb, Et Al. Allergy 2005; 60: 1339-49.
23. Between family
• Less common between honeybee and the other venoms
• Limited cross-reactivity exists between the antigens in
fire ant venom and the antigens in venoms of other
Hymenoptera
• Different insect families have almost no cross-reactivity
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Cross-reactivity
24. • Bumblebee show very limited cross-reactivity
with honeybee sting reactions
Apidae family
Vespidae family
• Extensive cross-reactivity in different genus
esp. hornet (vespa) and yellow jacket (vespula)
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Within family
Formicidae family • limited cross-reactivity
25. David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
27. • Classified as “local” or “systemic” in distribution and
an “immediate” or “delayed” time course
• Most insect stings are transient local reactions
- pain, swelling, and redness usually last from
a few hours to a few days and generally resolve
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Clinical features
28. • Limited to the area contiguous with the sting site
• Redness, Swelling, Itching and pain
• Late-phase, IgE-dependent reaction
• Increase in size for 24 to 48 hours
• Larger than 10 cm in diameter, and can
involve an entire extremity (crossing joint lines)
• Not dangerous except for potential local anatomic
compression, especially on the head, neck, tongue, or throat
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Local reaction
Large local reaction (LLR)
29. Systemic reaction (SR)
• Typically IgE mediated
• May present with a variety of symptoms, involving multiple organ
symptoms
1.) Cutaneous systemic reactions are limited to skin manifestations
2.) Anaphylaxis includes hypotension or involvement of at
least 2 organ systems
3.) Systemic toxic reaction
- Non-IgE mediated (anaphylatoid reaction) : onset < 24 hr.-6 days
- ex. Renal failure, rhabdomyolysis, DIC, N/V, diarrhea
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
30. Middleton's Ed 8.
Thomas B. Casale, Et Al. N Engl J Med 2014;370:1432-9.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
• Unusual reactions of unknown mechanisms are usually delayed (> 4 hr.) :
sickness-like reactions, encephalitis, peripheral and cranial neuropathies,
glomerulonephritis, myocarditis, and Guillain-Barré syndrome.
Kounis syndrome
(Allergic angina)
most
31. Brehler R, Et Al. Curr Opin Allergy Clin Immunol 2013, 13:360–364.
Matysiak J, Et Al. Ann Agric Environ Med. 2013; 20(4):875–879.
Grading of systemic reactions
Grading Muller Ring & Messmer
I
Generalized urticaria, periorbital edema, itching,
malaise, anxiety
Cutaneous manifestations
(flushing, pruritus, urticaria, angioedema)
II
Angioedema or
two or more of following:
chest/throat tightness, nausea,vomiting
Mild respiratory, CV, GI
(Rhinorrhea, hoarseness, dyspnea,
tachycardia, BP change, arrhythmia)
III
Dyspnea, wheezing, or stridor or
two or more of following:
dysphagia, dysarthria, hoarseness, weakness,
confusion, feeling of impending diaster
Severe multisystem involvement
(Laryngeal edema, bronchospasm,
anaphylaxis, cyanosis, shock, collapse)
IV
Hypotension, collapse, loss of consciousness,
incontinence, cyanosis
Cardiac arrest
32. Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
Evaluation & Diagnosis
• Diagnosis requires a clear, thorough medical history
• Quite high sensitization rate (positive tests to hymenoptera venom
but with a negative history)
• However, people with a clear documented history of a venom
reaction can have negative tests, and occasionally testing can be
positive to both honey bee and wasp venom
33. • Diagnosis of insect sting allergy rests on the history as the primary
evidence
- Nature and timing of stings in the past
- Time course of the reaction
- All associated symptoms and treatments
- Number of stings and the location on the body (systemic or local reactions)
- Concurrent medications : β-adrenergic blocking agents, ACEIs
(contribute significantly to the severity of the anaphylactic reaction)
- Underlying disease : heart disease
- Medications used for treatment of the reaction
Clinical history
Middleton's Ed 8.
34. Identity of the culprit insect :
- notoriously unreliable part of the history
- location and timing of the sting or the location of the nest
may suggest the type of insect
Middleton's Ed 8.
35. • In Vivo
- Skin prick test (SPT)
- Intradermal test (ID)
- Sting challenge
• In Vitro
- sIgE : RAST
- Serum tryptase
- Basophil activation test (BAT)
Middleton's Ed 8.
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
Diagnostic tests
Purpose
1.) Confirm allergic sensitization
2.) Define the risk of future systemic
reaction to stings (Candidates VIT)
36. Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
• Should be performed at least 2 weeks after a sting reaction,
ideally 1–2 months later in case of false negatives due to a refractory
period after a sting
• Sensitivity : SPT < ID
• Increasing doses in 10-fold increments of venom traditionally have
been used for either SPT or ID
SPT & ID (Apid, Vespid)
SPT : Start 1.0 µg/mL (max 100 µg/mL)
ID : Start 0.001-0.01 µg/mL (max 1 µg/mL)
If >1.0 mcg/ml : nonallergenic ingredients can cause nonspecific reaction (False positive)
38. Tracy Et Al. Curr Opin Allergy Clin Immunol 2015, 15:358–363.
• Difficulty in collecting all species for the yellow-jacket and paper wasp
venom mixes, not all lots contain every species
Thailand
(Freeze-dried venom)
40. Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
Rutcharin Potiwat. Asian Pac J Allergy Immunol 2015;33:267-75.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016
SPT & ID (Fire Ant)
• Imported fire ant whole-body extract
• Screening SPT : 1:1000 (w/v) of imported fire ant WBE
• Intradermal skin test :
- initial concentrations of approximately 1 x 10-6 (1:1 million) wt/vol.
- increased by increments until a positive response is elicited or a
maximum concentration of 1 x 10-3 (1:1,000) or 2 x 10-3 (1:500) wt/vol
42. • ID skin test
- Inconsistency in the description of the technique and interpretation
- No definitive studies to suggest any specific intradermal technique
to be superior for determining specific IgE for venom
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
North America,
Europe, and many
countries
United Kingdom
ALK
(manufacture)
Method
Injection of 0.02 -
0.03 mL of venom
to produce a bleb
of 3 mm
Injection of 0.03 mL
of venom to raise a
bleb of 3 to 5 mm.
Injection of 0.05 mL
of venom
Interpretation
- wheal 3 - 5 mm. >
negative control
- with appropriate
surrounding
erythema
- wheal 3 mm. >
negative control
- at 20 minutes
- wheal 5 - 10 mm
and erythema
11 - 20 mm
43. Negative skin test
• Patients with a convincing history but negative skin test results
may consider
- Refractory period of anergy : skin tests should be repeated
after 4 to 6 weeks
- Confounding medicine
- Not used culprit insect
- Maybe non-IgE mediated
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
" If skin test results are negative in a patient with a clear history of
systemic sting reaction, further testing (in vitro testing, repeat skin
testing , or both) should be performed, as well as basal serum tryptase "
44. Middleton's Ed 8.
Golden. Immunol Allergy Clin North Am. 2007 May ; 27(2): 261–Vii.
• Skin test results for individual venoms can vary over a short period,
and identification of all sensitivities requiring treatment may require
skin testing on 2 separate occasions
• The strongest skin tests often occur in patients who have had
only large local reactions and have a very low risk of anaphylaxis
" If negative skin test results and a convincing history of anaphylaxis
should be further investigated with serologic testing, and if results
remain negative, the skin tests should be repeated after 3 - 6 months "
45. • Sensitivity of venom sIgE is generally lower than ID
• sIgE increased in days-week maximum 2-3 week after sting than
gradually decrased
• Perform for "Whole body extract" or "Components" (Natural or
Recombinant components)
- Natural venom extracts can lead to clouding of the diagnostic
process secondary to cross-reacting carbohydrate determinants
(CCDs) ex. HBV, YJV
sIgE
Middleton's Ed 8.
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
46. Ollert M, Et Al. Curr Allergy Asthma Rep (2015) 15: 26.
Cross-reactivity carbohydrate
determinants (CCD)
• In insects, the relevant CCD epitope is defined by an
alpha-1,3-linked fucose residue at the innermost N-
acetylglucosamine of the carbohydrate core structure
47. Ollert M, Et Al. Curr Allergy Asthma Rep (2015) 15: 26.
Brehler R, Et Al. Curr Opin Allergy Clin Immunol 2013, 13:360–364.
• IgE antibodies with specificity for the alpha-1,3-fucose epitope are
responsible for approximately 75 % of double sensitizations to HBV
and YJV
• Clinical relevance of these IgE antibodies appears to be rather low
Insect
MMF3F6: represents a typical structure
Plant
48. Brehler R, Et Al. Curr Opin Allergy Clin Immunol 2013, 13:360–364.
Matysiak J, Et Al. Ann Agric Environ Med. 2013; 20(4):875–879.
• IgE antibodies reacting with bee and wasp venom (Double sensitivity)
could be detected in about 30–50% may be due to 3 causes
(1) independent sensitization to both venoms (rare)
(2) cross-reactive IgE antibodies against to common protein
Hyaluronidase (Api m2 & Vas v2) or dipeptidylpeptidase
(Api m5 & Vas v3)
(3) cross-reactive IgE antibodies against CCD
Double sensitive to bee & wasp
49. Darío Antolín-Amérigo, Et Al. Curr Allergy Asthma Rep (2014) 14:449.
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
• Api m 1 (major honeybee allergen) : low sensitivity
• Ves v 1 & Ves v 5
- Ves v 5 : good diagnostic performance
- Ves v 5 & Ves v 1 : sensitivity was significantly increased
• Pol d 1 & Pol d 5
• Crucial especially when the stinging insect was not identified
and when skin tests and specific IgE to the native allergens are
unsuccessful for the identification
Recombinent marker allergen
50. MUXF3 : glycan from bromelain is commercially available
Darío Antolín-Amérigo, Et Al. Curr Allergy Asthma Rep (2014) 14:449.
52. • Cannot performed skin test
• Disconcordant between history and skin test
- sIgE test is positive in 10% of patients with negative skin test results
• Double sensitization
- 50% of allergic reaction to honey bee or vespulae had positive both
diagnostic test (homology in the hyaluronidase enzymes) ,
CRD can help to identify true culprit insect
Middleton's Ed 8.
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
sIgE benefit in patients
The level of sensitivity (skin test or serum IgE) is correlated
with the frequency but not the severity of the reaction
53. Golden. J Allergy Clin Immunol 2005;115:439-47.
• Venom skin tests and venom-specific IgE assays correlate imperfectly
sIgE negative in 20% of skin test–positive
skin test negative in 10% of persons with elevated IgE antibodies
55. Matysiak J, Et Al. Ann Agric Environ Med. 2013; 20(4):875–879.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
Darío Antolín-Amérigo, Et Al. Curr Allergy Asthma Rep (2014) 14:449.
Can be useful in
• In cases of negative skin tests and negative specific IgE
results or discrepancies in these tests
• Monitoring of VIT results
" Routine use of BAT in evaluating Hymenoptera sensitive
patients is not recommended "
• Remains to be standardized in terms of methodology
and interpretation
56. • Should be done : severe
anaphylaxis
• Evaluation : Mastocytosis
or mast cells diseases
• Predict : Severity of
systemic reaction to sting
Serum tryptase
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
57. Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Mast cell disorders
• Insect stings are the most common
cause of anaphylaxis in mastocytosis
• 25% of insect sting anaphylaxis --> have elevated baseline serum tryptase
• 2% mastocytosis --> insect sting anaphylaxis
58. Middleton's Ed 8.
Rueff Et Al. J Allergy Clin Immunol 2009;124:1047-54.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
• If the serum tryptase is elevated
(>11.4 ng/ml) bone marrow biopsy
should be considered
• Tryptase concentrations manifest a
significant correlation with severity
of clinical symptoms, especially
with a decrease in blood pressure
in the main arteries
59. Sting challenge
• Sting challenge is the most specific diagnostic test, but unethical
and impractical
• Recommended by some to better select those patients who need VIT
Middleton's Ed 8.
Agache Et Al. Allergy 70 (2015) 355–365.
Www.Eaaci.Org
Absolute contraindication
- Pregnancy
- Acute inflammatory disease
- Severe or uncontrolled cardiovascular or respiratory disease
- Treatment with beta-blockers
60. • Low negative predictive value (NPV) : A single negative challenge
sting does not preclude anaphylaxis to a subsequent sting
• Less reliable with vespids than with honeybees
Middleton's Ed 8.
Agache Et Al. Allergy 70 (2015) 355–365.
Www.Eaaci.Org
Limitation
• Same species as the one that
provoked the reaction
• Sting has to be confirmed by the
development of a wheal and flare
reaction and by the characteristic
burning pain
• After the sting challenge, all patients
have to be observed for at least 2 hr
in the hospital
61. D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
62. • Ice pack, elevation of the afftected limb
• Oral antihistamines
• Large local reactions, especially head and neck
- Oral corticosteroid 40-60 mg of prednisone 5 days
(steroids should be started within few hours of sting in patients
with known history of large local reactions)
- Analgesic : NSAIDs
• Antibiotics are not necessary
Treatment of acute reactions
Local & Large local
Middleton's Ed 8.
63. • Urticaria may respond to antihistamines alone
• Anaphylactic reactions require epinephrine injection IM (1:1000)
0.01 mg/kg (max 0.3 mg in children, 0.5 mg. in adult)
• Patients who have history of rapid onset or very severe systemic
reactions may treatment immediately after the sting
• Hypotension should be supine with legs raised
• Delay in the use of epinephrine has contributed to fatal reactions
• Some individuals with anaphylactic shock are resistant to epinephrine
- Patients taking β-blocker medications Rx Glucagon
Middleton's Ed 8.
Systemic reactions
64. • Anaphylaxis requires patient education before discharge
• Use of self-injectable epinephrine requires consistent instruction
and follow-up
• Referred for an allergy consultation : For VIT
• Preventive treatment : effective measures to avoid insect stings
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Patient education
Pitfall
• Patients often fail to carry the injector with them
• Delay using when they have a reaction
65. Prevention
• Avoid eating outdoors
• Avoid flowering plants
• Avoid drinking from straws, cans,
or bottles outdoors
• Remove fallen fruit or pet feces
• Cover trash cans
• Watch for nests in bushes or in the
ground when mowing
• Avoid going barefoot outdoors
• Avoiding fragrances
• Avoiding brightly colored or floral
clothing
• Using insect repellants
• Running; flailing the arm
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Effective Ineffective
66. Predictors of risk for
sting anaphylaxis
Natural history
• Prognosis for affected patients is based on the understanding
of the natural history of the condition including clinical factors
and biologic markers
• Future sting will cause an allergic reaction depends on the history
and immunologic status of the patient
Middleton's Ed 8.
68. David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Clinical markers Laboratory markers
Very severe previous reaction
Insect species
No urticaria/angioedema
Age (>45), Gender (male)
Medications (ACE inhibitors)
Multiple or sequential stings
acetylhydrolase
Venom skin test
Venom-specific IgE
Basal serum tryptase
Platelet activating factor (PAF)
Angiotensin converting enzyme
(ACE)
Predictors of risk of systemic reaction to insect sting
69. Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
Venom immunotherapy
• Treatment of choice for prevention of systemic allergic reactions
to insect stings but it requires careful selection of patients
70. • All patients who have experienced a systemic allergic reaction to
an insect sting and who have specific IgE to venom allergens
- reduces the risk of a subsequent systemic sting reaction to
as low as 5% compared with up to 60% in untreated patients
• High risk patients : patient with mastocytosis, or an increased basal
serum tryptase level
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Indication for VIT
72. Change in practice parameter 2016
VIT
Optional
• VIT is generally not required for patients > 16 years of age who have
experienced only cutaneous systemic reactions
• Sting challenge studies suggest that these patients are very unlikely to have
severe anaphylactic reactions to subsequent stings
(Recommendation: C)
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
73. (1) Prevent systemic reactions
(2) Alleviate patients' anxiety related to insect stings
(with improved quality of life)
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Goals of VIT
Only large local reactions to stings that VIT is generally not necessary
(low risk of a systemic reaction 4-10%) , but might be considered in
those who have frequent unavoidable exposure for quality of life reason
74. • Malignancy
• Severe asthma
• Immunological conditions
• Chronic heart and lung disease
• Severe hypertensions
• Drug: beta blockers, tricyclic antidepressants,
monoamine oxidase inhibitors, ACEIs
• Initiation during pregnancy
(though maintenance can be continued in pregnancy)
Contraindications
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
75. • 95-100% effective in preventing systemic reactions to stings
- maintenance dose of 300 μg of mixed vespid venoms
• 75-95% efficacy
- 100 μg dose of individual venoms
(i.e., honeybee, yellow jacket, or Polistes wasp)
• Fire ant IT using wholebody extracts has been reported to be
reasonably safe and effective
• Repeat sting reactions usually are milder than pretreatment reactions
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Efficacy
95% to 100% effective in preventing
systemic reactions to stings
76. Failure of VIT
• Associated with
- abnormal basophil activation test responses
- underlying mastocytosis
Middleton's Ed 8.
77. Safety
Middleton's Ed 8.
Darío Antolín-Amérigo, Et Al. Curr Allergy Asthma Rep (2014) 14:449.
• Adverse reactions to VIT are no more common than reactions
during inhalant allergen immunotherapy
• Systemic symptoms occur in 5-15% (Most are mild)
- Severe systemic reactions to injections --> underlying mast cell
disease
• LLR to venom injections ~ 50% of patients, esp. dose 20 - 50 μg
- LLR to venom injections not predicted systemic reactions
78. Risk factors for side effect during IT
Darío Antolín-Amérigo, Et Al. Curr Allergy Asthma Rep (2014) 14:449.
79. • Antihistamines
- Reduce local and systemic reactions
• Leukotriene modifier
- Reduce LLR
• Recurrent systemic reactions to VIT: rush VIT, or omalizumab
Pre-medication
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
80. • Need only contain a single venom if the culprit is definitively
known
• Recombinant venom allergens has been able to resolve dual
sensitivity that may be due to CCD
• Mixed vespid efficacy > single vespid
• Therapy with yellow jacket or mixed vespid venoms can protect against
wasp stings
Venom species
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
81. • Increasing the maintenance dose up to 200 mcg per dose has
been effective in achieving protection in patients who had sting
reactions while receiving a 100-mcg maintenance dose of VIT
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Venom Dose
• Initial dose of up to 1 mcg
Increase to maintenance dose of at least 100 mcg of each venom
(equivalent to 2 honeybee stings : 50 mcg per sting)
• Children might be effectively treated with a maintenance dose of 50 mcg.
Change in practice parameter 2016
82. Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
Schedules Different in Build-up phase
1.) Build-up
1.) Traditional/ conventional : 4-6 mo.
2.) Modified rush/ cluster : 6-8 wk.
3.) Rush : 2-7 days
4.) Ultra-rush : < 2 days
85. Patella V, Et Al. Journal Of Allergy Volume 2012.
Ultrarush Rush
Unlike inhalant allergen IT, the more rapid regimens of VIT appear
to have the same or greater safety as the traditional regimen
86. 2.) Maintenance
• Onset of protection with VIT is quite rapid
• Sting challenge studies : protective is reached after an 8-week
build-up regimen
Every 4 weeks for 12-18 months
Every 6 weeks for 12-18 months
then Every 8 weeks
Middleton's Ed 8.
D.B.K. Golden / Ann Allergy Asthma Immunol 111 (2013) 84-89.
12-week interval may be effective for extended maintenance
treatment after 4 years of routine therapy
87. • Repeat skin tests or immunoassays : every 2-3 years
• SPT
- After 5 years : negative < 20%
- After 7–10 years : negative 50–60%
(although most remain positive by RAST)
• Venom-specific IgE antibody levels
- level rises during the first months of therapy
- returns to baseline after 12 months
- declines steadily during maintenance treatment
(even after therapy is stopped and after a sting)
Maintenance evaluation
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
88. • Venom-specific IgG antibodies
- marker of clinical efficacy
- good PPV but poor NPV
- confirm protective levels after initial therapy
(especially honeybee or single venoms)
- considered protective: ≥ 3 μg/mL during the first 4 years
Maintenance evaluation
Middleton's Ed 8
Ludman And Boyle. Journal Of Asthma And Allergy 2015:8 75–86.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
90. Duration
• Early studies : recommended 3 years (results included patients with
up to 10 years of treatment)
• Subsequent studies : 5 years of was associated with better
suppression of allergic sensitivity and lower risk of relapse
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Change in practice parameter 2016
• 5 years is better than 3 years
• Longer treatment recommended in high-risk patients; 3 years may be sufficient in children
Better for 5 years
92. Risk of relapse after discontinuing VIT
• No specific tests to
distinguish which patients
will relapse after stopping
VIT
• Relapse
- 5 years < 3 years of VIT
- younger children < adults
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
93. Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Maybe need longer than 5 years
• Honeybee allergy
• Had systemic reactions to an injection or sting during VIT
• Elevated baseline serum tryptase levels
• Very severe sting reactions before treatment
94. • Mastocytosis
- recommend VIT for life
- efficacy of VIT is less than optimal in mastocytosis patients, they
should continue to carry 2 epinephrine injectors
• Patients who are not willing to accept the 10%- 20% chance of
reaction to a subsequent sting
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Long-term extension of VIT
95. Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
• The decision to stop immunotherapy can involve consideration
of several factors by the patient and physician
(1) severity of the initial reaction
(2) basal serum tryptase
(3) frequency of exposure
(4) presence of concomitant disease and medications
(5) effect of such action on work and leisure activities
(6) the patient's preferences
96. • Natural history of fire ant allergy is not as well described
• But clear need for effective IT
• IT using WBE : effective but no placebo-controlled trials
• The dosage maintenance schedule is less well defined
- most experts recommend maintenance dose : 0.5 mL ,1:100 wt/vol
- some experts : 0.5 mL , 1:10 wt/vol
• Duration is still uncertain, because discontinuation led to relapse
• Most allergists consider stopping after specified period (usually 3-5 years)
or only when skin test or in vitro test become negative
Middleton's Ed 8.
David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
Fire Ant immunotherapy
98. David B.K. Golden, Et Al. Stinging Insect Hypersensitivity. Practice Parameter 2016.
50 mcg., 3 years