Objectives STINGING INSECT HYPERSENSITIVITY

STINGING INSECT
HYPERSENSITIVITY
Objectives
SHASHANK SHETH, MD
• To understand difference
between local and systemic
reactions to insect stings
• To identify indications for allergist
referral and testing for venom
allergy and immunotherapy
• To review signs/symptoms of
anaphylaxis
• To review acute management of
anaphylaxis
Case 1
Case 1
• RC is a 44 y/o male presented to
ER unresponsive
– Leaf blowing in the yard
– Felt a sting on his scalp and he
swatted the insect
– In 5 minutes, he had acute
shortness of breath
– Sat down and was found
unresponsive by daughter
• Daughter called 911
• EMS found pt unresponsive with
a BP of 70/40
• Treated with injectable
epinephrine on the field
– Started to improve
• Transferred to ER and given
antihistamines and steroids and
discharged home in a few hours
1
Case 1
• Never had angioedema or
urticaria
• PMH:
– Hypertension
• SH:
– Contractor
– No smoking or alcohol
• Venom skin test:
– Negative for honeybee
– + wasp (0.01); WFH (0.1); YH (0.1);
YJ (0.01)
Types of Insect Sting
Reactions
• Local
• Large local
• Systemic
– Anaphylaxis
– Toxic
Case
• Meds: quinapril /
hydrochlorathiazide
• PE: normal
• Serum tryptase – 7ng/ mL [2-10]
• Assessment:
– Anaphylaxis due to stinging insect
venom
• Plan:
– Venom IT
– Change to non- ACE – inhibitor
– Auto-injector of epinephrine
– Insect sting precautions
Local reactions
• Vast majority of insect stings
produce transient local reaction
that can last up to several days
and resolve without treatment
– Risk of future anaphylaxis is ~ 5%
• Treatment:
– Cold compresses
– antihistamines
2
Large Local Reactions
• Extensive local swelling extending
from the site of the sting
• Peaks in 24-48 hours; may last
one week
• Frequency: 5-15%
• IgE mediated late-phase reaction
– Risk of future anaphylaxis is 5% 10% 1
• Treatment: cold compresses,
antihistamines, and prompt use
of oral steroids
1 Green A, Reisman R, Arbesman C. Clinical and immunologic studies of
patients with large local reactions following insect stings. J Allergy
ClinImmunol 1980; 66:186-9.
3
Anaphylaxis
EPIDEMIOLOGY
• Vary from cutaneous to lifethreatening
• Can be biphasic or protracted
• Slower time of onset will reduce
chance of progression to a lifethreatening reaction 1
• Anaphylaxis from stinging insect
– At least 40 fatalities per year 1
• Potential life threatening systemic
reactions
– 0.4% – 0.8% of children 2
– 3 % of adults
• Possibly underrecognized
1 Lockey RF, Turkeltaub PC, Baird-Warren IA, et al. The
Hymenoptera venom study. I, 1979-82. J Allergy Clin Immunol
1988; 82: 370-81.
Risk of systemic reaction in untreated patients
with a history of sting anaphylaxis and positive
venom skin tests
Original Sting
reaction
Risk of
Systemic
Reaction
(%)
Risk of
Systemic
Reaction
(%)
Severity
Age
1-9 yr
10-20 yr
post-sting post-sting
No reaction
Adult
17
Large Local
All
10
10
Cutaneous
systemic
Child
10
5
Adult
20
10
Child
40
30
Adult
60
40
Anaphylaxis
1 Graft DF. Insect sting allergy. Med Clin North Am 2006; 90:211-32.
2 Bilo BM, Bonifazi F. Epidemiology insect venom anaphylaxis. Curr
Opinion Allergy Clin Immunol 2008;8:330-7.
Anaphylaxis - Signs /
symptoms
Cutaneous: flushing, pruritus, urticaria,
angioedema, and pilor erecti; pruritus
in unusual places (scrotum, vagina,
ear)
Cardiovascular: feeling of faintness,
syncope, chest pain, arrhythmia,
hypotension and shock
4
Anaphylaxis - Signs /
symptoms
Anaphylaxis - Signs /
symptoms
Respiratory
• Laryngeal: pruritus and “tightness” in
the throat, tongue or throat swelling
Other: periorbital pruritus, erythema,
(laryngeal edema), dysphagia,
and edema; conjunctival erythema
dysphonia and hoarseness/stridor,
and tearing; aura of impending
dry “staccato” cough
“doom,” seizures; lower back pain
• Lungs: shortness of breath, chest
and uterine contractions in women
tightness, cough, and wheezing
Treatment
• Venom Immunotherapy
• Carry Injectable epinephrine
– NO CONTRAINDICATION to
epinephrine in life-threatening
situation
• Lifestyle precautions
Immediate treatment
• Removal of stinger in first 10-20
seconds might prevent injection
of additional venom 1
• Flick or scrape
• Don’t grasp!
1 Schumacher MJ,
Tveten MS, Egen NB.
Rate and quantity of
delivery of venom
from honeybee stings.
J Allergy Clin
1994; 93; 831-35.
5
Immediate Treatment
• Aqueous epinephrine 1:1,000 is the
standard of care
• IM epinephrine if systemic reaction
Immediate Treatment
• H1 antihistamines: diphenhydramine
IM or IV
– Adults: 25 to 50 mg Children: 1-2
mg/kg
– Adults: 0.3ml to 0.5ml q5 minutes
up to 3 times
• H2 blockers p.o. or IV (ranitidine,
famotidine) – for epinephrine –
resistant hypotension or erythroderma
– Children: 0.01ml/kg body weight
q5 minutes up to 3 times
• Oxygen and bronchodilators
• Supine position
• Tourniquet
• Intravenous fluids or vasopressors as
needed for vascular collapse
• Depending upon the reaction,
consider PO or IV steroids
(prednisone)
Epinephrine
• IM in anterolateral thigh [83]
• Delayed use can lead to more
serious anaphylaxis or be
ineffective [85]
• NO contraindication in setting
of anaphylaxis
• Antihistamines and oral
corticosteroids are second
lines of treatment
WHEN IN DOUBT, INJECT
EPINEPHRINE
6
Outdated epinephrine loses efficacy
•
As time passes, percent of labeled dose and
epinephrine bioavailability are reduced.
•
•
Inadequate knowledge of epinephrine
• Healthcare professionals and patients have
inadequate knowledge about outpatient use.
Improper storage and exposure to sunlight and
- 76% of physicians are unaware that two auto-
heat increase degradation.
injector dose formulations exist
Degradation often occurs without a color
- Only 55% of patients at risk have in-date
change in the epinephrine solution.
auto-injectors on hand
- Only 30%-40% know how to use autoinjectors correctly
Simons FER et al. J Allergy Clin Immunol 2000;105:1025-30
Grouhi M et al. J Allergy Clin Immunol 1999; 104:190-3; Sicherer SH et al. Pediatrics
2000; 105:359-62;
Huang SW. J Allergy Clin Immunol 1998;102:525-6
Types of stinging insects
• Order Hymenoptera
– Apids
The PLAYERS
• Honeybees
• Bumblebees
– Vespids
NAME THAT STINGING
INSECT
• Yellow jackets
• White-faced and yellow-faced hornets
• Wasps
– Formicids
• Fire ants
7
Yellow jackets
• Nests in ground
• Yardwork,
farming,
gardening
• Wall tunnels,
crevices, hollow
logs
• Aggressive; sting
with minimal
provocation
• scavengers –
picnics, food and
drink
Hornets
• Large papermaiche nests in
trees or shrubs
– Extremely
aggressive
– Will chase
subjects for
some distance
before stinging
– Open beverage
containers
• Most common
cause in most
pasts of the US
Wasps
• Build
honeycomb
nests in shrubs
and under eaves
of houses or
barns
• In pipes on
playgrounds and
under patio
furniture
• Florida, Texas,
Louisiana
Insect identification
• Fire ant (red or
black)
– Build nests in
mounds of fresh
soil
– Aggressive
– Sting multiple
times in circular
fashion
– Sterile
pseudopustules
– Southern US
8
Fire ant
Apids (bees)
• Honeybees
– Leave a barbed stinger and attached
venom sac in the skin
• Occasionally with other insects too
– Nonaggressive away from hives
• Domestic honeybees
– Commercial hives
• Wild honeybees
– Tree hollows and old logs
– Stings on feet when barefoot on grass
Honeybee
• More sensitizing
• VIT less effective
• Higher risk of
reactions
• More severe
reactions
• Longer duration
VIT
• Africanized honeybees
– Hybrids between domestic and African
honeybees
– Attack in swarms; hostile and
aggressive
– Mexico and the South
9
Bumblebees
•
•
•
•
Different venom than honeybees
Less aggressive
In greenhouses
Requires specific testing
History
• How long ago did sting occur?
• How many stings occurred at the
same time?
• How much time between sting and
onset of symptoms
• Where on the body did the sting
occur?
• Ask about all potential systemic
symptoms.
• Which insect was it?
• How was the reaction treated?
• Any delayed symptoms?
• Previous stings and reactions?
• Any stings subsequent to the
reaction?
Diagnosis of Stinging
Insect Allergy
Insect venom skin testing
• Stings are painful and patients are
almost always aware that sting
occurred
• Criteria
• Done by allergist that is trained and
qualified in diagnosis and treatment
of insect allergy
• Technique
– History of a sting that resulted in a
systemic reaction (even if remote
history)
• Risk of anaphylaxis may persist for
decades 1
– Evidence of venom specific IgE
• Skin testing
• in vitro serum specific IgE
– Prick at 100 mcg/mL (optional)
– Intradermal ( Q 20 minutes)
•
•
•
•
0.001 mcg
0.01 mcg
0.1 mcg
1.0 mcg
- careful about irritant reactions
above this
• Very rare systemic reactions to skin
test
1 Golden DB, Breisch NL, Hamilton RG, et al. Clinical and entomological factors
influence the outcome of sting challenge studies. J Allergy Clin Immunol 2006;
117:670.
10
Screening at large not
indicated
• Up to 27% of general adult
population has venom specific IgE
– Not sufficient to predict that patient
is high risk for future systemic
reactions
Golden DB, Marsh DG, Kagey-Sobotka A, et al. Epidemiology of
insect venom sensitivity. JAMA 1989; 262:240.
VENOM TESTING NOT
INDICATED:
• No sting history
• Only local reactions
• Family history but no personal
history
• Possible exception:
– Unavoidable exposure and frequent
large local reactions which are
disabling
11
Diagnostic Testing
• Venom
– Yellow jacket, white-faced hornet,
yellow hornet, wasp and honeybee
– Available for skin testing and
immunotherapy
• Whole body extract
– Fire ant
• Positive intradermal skin test at a
concentration of less than or
equal to 1.0 mcg/ mL
Diagnostic Testing
• Any patient that is a candidate for
VIT
• If negative skin test and
convincing history such as airway
or CV compromise, then need to
repeat ST or do in vitro IgE testing
before ruling out VIT as an option
1
• Tests may be falsely negative
within first few weeks after a
sting
1 Golden DBK, Tracy JM, Freeman TM, Hoffman DR. AAAAI
Insect Committee. Negative venom skin tests results in patients
with histories of systemic reaction to a sting. J Allergy Clin
Immunol 2003; 112: 495-8.
Diagnostic Testing
• Rarely, (< 1 % of patients with a
convincing history of systemic
reaction) patient can have
anaphylaxis from subsequent
sting after negative skin and in
vitro test
– Consider underlying systemic
mastocystosis
Diagnostic Testing
• Approximately 30-60% of patients
with history of systemic reaction
to a sting and have + SPT or in
vitro test will have a systemic
reaction when restung
• No correlation between size of
skin test or concentration of
extract and severity of allergy
12
In vitro testing
• Skin tests are preferred
• Up to 20% with positive skin test
have undetectable serum specific
IgE
• Recent studies:
– 10-20% of patients with negative
skin test have positive in vitro when
using highly sensitive assays
Indications for VIT
• Any age with systemic reactions
beyond cutaneous manifestations
– extremely effective
– Reduces risk of subsequent reaction
to < 5 %
– Reactions that occur are usually
milder
• NOT INDICATED for children with
systemic cutaneous
manifestations
• Large local reactions - maybe ??
Mastocytosis
• Clonal expansion of mast cells
resulting in severe and recurrent
anaphylaxis
• Consideration in those with
severe insect sting reactions
• Workup:
– Baseline serum tryptase
– Bone marrow biopsy
Children are not miniadults
• Children <17 y/o with only skin
manifestations have ~ 10% of
systemic reaction if re-stung
– Usually limited to skin
– < 5% chance of more severe
reaction
– < 1 % chance of life-threatening
anaphylaxis
Golden DBK, Kagey-Sobotka A, Norman PS, Lichtenstein LM.
Outcomes of allergy to insect stings in children with and
without venom immunotherapy. N Eng J Med; 2004; 351:
668-74.
13
Large local reactions
• Risk of systemic reaction to a
future sting is 5-10 %
• Vast majority do not need to be
tested
• New evidence that VIT may
reduce the size and duration of
LLR
– May be useful in those at risk for
unavoidable or frequent reactions 1
Golden DBK, Kelly D, Hamilton RG, Craig TJ. Venom
immunotherapy reduces large local reactions to insect stings. J
Allergy Clin Immunol 2009: 123:1371-5.
Duration of VIT
• 3-5 years, ideally 5 years
– Despite persistent positive SPT, 8090% will not have a systemic reaction
after 3-5 yrs of VIT (44-52)
• NO test to predict risk of relapse
• Risk is lower with 5 yrs vs. 3 yrs 1
• Consider indefinite IT
– h/o severe anaphylaxis with shock or
LOC
– High risk profession or hobbies
– Honeybee allergy
– Elevated tryptase
– Systemic reactions to VIT
– Anxiety from risk of IT
Lerch E, Muller U. Long term protection after stopping venom
immunotherapy. J Allergy Clin Immunol 1998; 101: 606-12.
14
VIT protocol
• Shots administered once a week
– Start with beginning dose 0.1 mcg
– Increase to maintenance dose of
100 mcg of each venom
• Interval at maintenance
– 4 to 6 weeks
– Some continue at 6-8 weeks
Alternate protocols for
VIT
• Rush
– 3 weeks
– Beekeepers and military
– No increase risk in reaction rate
• Ultra-rush
– 1 day
– Hospital based
Adverse Reactions to VIT
• Systemic: 3-12%
– Mild and easily treatable
– Dose adjustment
• Large Local: 25 % children, 50 %
adults
– Pretreat with antihistamine or
montelukast
– No dose adjustment necessary
15
Relative Contraindications
• Beta-blockers
– Risk of VIT is less than beta-blockers
• ACE – inhibitors
– Recent retrospective study showed
increase of more severe anaphylaxis
[142]
Rx for auto-injectable
epinephrine
• High risk
– Near fatal
reactions
– Systemic
reactions during
VIT
– Severe
honeybee
allergy
– Underlying
medical
conditions
– Frequent
unavoidable
exposures
• Low Risk
– Large local
reactions or
systemic
cutaneous
reactions
– Maintenance VIT
– s/p 5 yrs of VIT
Assessment of VIT
Avoidance measures
• Decrease is venom specific IgE to
insignificant levels
• Conversion to negative skin test
• Neither test is required and there
have been relapses despite a
negative skin test
• Venom specific IgG has no
predictive value for discontinuing
VIT
• Have trained professionals
remove known or suspected nests
in immediate vicinity of patient’s
home
• Avoid wearing brightly colored or
flowery prints or strong scents
• Avoid walking outside barefoot or
with open toes
• Wear long pants, long sleeves,
socks, shoes, hats, work gloves
when working outdoors
16
Avoidance measures
Toxic Reactions
• Be cautious near bushes, eaves,
and attics
• Avoid garbage containers and
picnic areas
• Keep insecticides for stinging
insects readily available
• Avoid eating or drinking outdoors
and be cautious in areas where
food and beverages are being
served
• Nonallergic reaction from venom
components
• Cytotoxic reaction from multiple
stings (>100)
Mosquito Bite Reactions
Normal reaction
• Immunologic reaction to proteins
in mosquito saliva
• Very common
• Immediate wheal and flare that
peak at 20 min
• Delayed itchy indurated papules
peak at 24 hours and subside in 710 days
• 5 stages of reactivity evolve over
months and years
– Normal Reaction
– Large Local Reaction
– Systemic reaction
– shock
– acute renal failure
– ARDS
– rhabdomyolysis
17
Large local reactions
(Skeeter Syndrome)
• Itchy or painful areas of redness,
warmth, swelling and induration
• 2 – 10+ cm areas
• Develop within hours, progress over
8-12 hours and resolve in 3- 10 days
• Possible low grade fever or malaise
• Can affect entire side of face or
extremity
• May interfere with drinking, eating,
seeing or normal use of arm or leg
Skeeter Syndrome
• May be hard to differentiate
between secondary bacterial
infection from scratching
• Timing is key
– LLR occur within hours
– Infection takes days
Systemic reactions
•
•
•
•
•
Very rare
Generalized urticaria
Asthma flare
Anaphylaxis
Serum sickness
• Treatment
– Antihistamines
– Topical or systemic glucocorticoids
18
Take home points
• Be educated in avoidance of
stinging insects
• Carry epinephrine auto-injector
and be instructed in appropriate
indications and administration
• Undergo testing for IgE antibodies
to insect venom
• Initiate immunotherapy if test
results are positive
• Consider carrying medical
identification tag
19