Stinging Insect Allergy

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					Stinging Insect Allergy
      Barnstable County
    Beekeepers Association
            April 12, 2011
 Bruce R. Gordon, MD, FACS, FAAOA
          Harvard Clinical Instructor
 President, American Academy of Otolaryngic
             Allergy, 2002-2003
Learn to :
• Understand sting reaction types
• Recognize responsible insects
• Understand risk factors
• Understand basic treatment of stings
• Understand when and how to immunize
• Understand when to stop immunotherapy
     Type of Reactions to Bees
• Contact allergy to propolis
• Respiratory allergy to hive dust and bee
• Asthma and anaphylaxis from royal jelly
• Sting reactions:
  – Toxic reactions
  – Local reactions
  – Systemic Anaphylacic reactions
    Bousquet J, Menardo JL, Michel FB. Allergy in beekeepers.
    Allergol Immunopathol (Madr). 1982;10(5):395-8.
     • 26.5% U.S. prevalence of venom sensitization
       (27.1% in Germany)
     • > 0.5 to 5% U.S. Severe insect sting allergy
     • > 40 deaths / year U.S. from insect stings
         – (does not include suspicious sudden deaths)

1.   Neugut AI, Ghatak AAT, Miller RRL. Anaphylaxis in the United States: an investigation into
     its epidemiology. Arch Intern Med. 2001;161(1):15-21.
2. Schäfer TT, Przybilla BB. IgE antibodies to Hymenoptera venoms in the serum are common
     in the general population and are related to indications of atopy. Allergy. 1996;51(6):372-7.
3. Valentine MD, Lichtenstein LM. Anaphylaxis and stinging insect hypersensitivity. JAMA
     1987; 258:2881-2885
           Sensitization Risk
              from Stings
• Frequent stings, especially < 2 mo.
  apart, sensitize
• Very frequent stings, > 50 / yr,
  desensitize (beekeepers)

  Pucci S, Antonicelli L, Bilo MB, Garritani MS, Bonifazi F.
  Shortness of interval between two stings as risk factor for
  developing Hymenoptera venom allergy. Allergy. 1994;49:894-6
   Types of Stinging Insects
Stinging insects are order Hymenoptera
  (membrane-winged insects)
• Apids (honeybees and bumblebees)
• Vespids (yellow jackets, wasps,
 hornets, and paper wasps)
• Formicids (ants, fire ants)
  Hymenoptera: Apids
   Risk of being Stung
• Domestic honeybees do not sting unless provoked
• Bumblebees are not aggressive & rarely sting, but
  use in greenhouses increases exposure
• Africanized hybrid honeybees, common in Mexico
  and South, are hostile, aggressive, and swarm
Africanized Bees 2009 Range
 is Barbed

• Bees leave their barbed stinger and
  venom sac implanted in their victim
• This distinguishes honeybee stings from
  all other stings: bumblebees, wasps, and
  ants have no barbs
Lewis,FS, Smith, LJ. What’s eating you? Bees, part 1. Cutis 2007;79:439-44
     Honeybee Sting Allergy
Honeybee venom is very sensitizing
 –More likely to react on re-sting
 –More likely to react during
  immunotherapy treatments
 –Less likely to be protected by
 –Less likely to stop immunotherapy
 Graft DF. Venom immunotherapy: when to start, when to stop
 Allergy Asthma Proc. 2000; 21:113-116
          Africanized Bee Stings
  • Africanized bees and domestic bees
    have identical venoms
  • Africanized bees are much more
    dangerous due to easy arousal,
    aggressive stinging, mass stings, and
    persistent pursuit of the victim

Lewis,FS, Smith, LJ. What’s eating you? Bees, part 1. Cutis 2007;79:439-44
Bumble Bee

• Ground nesting, < 200 bees per nest
• Stinger not barbed: stings repeatedly
• Not easily irritated: stings uncommon
   Vespids (Wasps)

• Yellow Jackets: ground nesting; very
  aggressive & swarm - stings cause skin
• Hornets, Wasps, and Paper Wasps : aerial
  nesting - in trees, roof overhangs, shutters,
  under shingles, in attics; not aggressive
  unless disturbed
   Formicids (Ants)
Imported Fire Ants found in SE
  and Gulf coast; will spread much
  further north & west from global warming
Ants bite, and deliver multiple stings in
  circular pattern; aggressive & swarm
  - attacks 6 - 60% of people living in an area
  during each year.
Harvester Ants (native fire ants) found in SW;
  stings painful, but fatalities rare
         Imported Fire Ant Range

   At Risk: Pacific Northwest, Arizona, Virginia

Tracy JM, Demain JG, Quinn JM et al. The natural history of exposure to the
imported fire ant (Solenopsis invicta). J Allergy Clin Immunol 1995; 95:824-828
Sting Risk Factors
            Risk Factors for Serious
               Sting Reactions 1
 Survey of 494 beekeepers:
      • 90% stung/year, 55% had >100 stings
      • 6.5% had serious reactions
      • Risks: having any kind of allergies,
      especially asthma, food allergies, or multiple
      kinds of allergies
Celikel S, Karakaya G, Yurtsever N et al. Bee and bee products allergy in Turkish beekeepers:
determination of risk factors for systemic reactions.
Allergol Immunopathol (Madr). 2006;34(5):180-4.
           Risk Factors for Serious
              Sting Reactions 2
 Survey of 1053 beekeepers:
     • annual stings/person 0-1000, average 58
     • 4.4% had serious reactions
     • Risks: current allergy symptoms, having
     allergies, years as beekeeper, stings in spring

 Münstedt K, Hellner M, Winter D, et al. Allergy to bee venom in beekeepers in Germany.
J Investig Allergol Clin Immunol. 2008;18(2):100-5
         Developing Bee Allergy in
             New Beekeepers
35 new beekeepers tested for 5 years:
  • 29% became venom sensitive
  • most within 12 months, all by 18 months
  • number of stings and presence of other
  allergies had no effect on developing sting
Kalogeromitros D, Makris M, Gregoriou S et al. Pattern of sensitization to honeybee
venom in beekeepers: a 5-year prospective study. Allergy Asthma Proc. 2006;27(5):383-7
         Predicting Risk of Serious
          Reaction in Beekeepers
78 beekeepers studied before being stung
Risks are:
  • pre-exposure high IgE blood test > 1 ku/L
  • allergic nasal, eye, or lung symptoms
  during hive work
  • less than 8 years beekeeping
  • prior serious sting reaction
 Annila IT, Annila PA, Mörsky P. Risk assessment in determining systemic reactivity
 to honeybee stings in beekeepers. Ann Allergy Asthma Immunol. 1997;78(5):473-7.
       Consecutive Stings increase
           Anaphylaxis Risk
 120 sting-allergic persons:
 • 59% of serious reactions occur when
 there was a prior sting within 2 months
 (p=0.0001 - highly significant)

Pucci S, Antonicelli L, Bilò MB et al. Shortness of interval between two stings as risk
factor for developing Hymenoptera venom allergy. Allergy. 1994;49(10):894-6.
                Fewer Stings increase
                  Anaphylaxis Risk
   176 sting-allergic beekeepers:
   • reaction risk is inversely correlated
   with annual number of stings

Bousquet J, Ménardo JL, Aznar R et al. Clinical and immunologic survey in beekeepers
in relation to their sensitization. J Allergy Clin Immunol. 1984;73(3):332-40.
 Types of Sting Reactions
• Immediate Allergic
   – Local, Large Local, Systemic
• Delayed Toxic (Non-Allergic)
   – Serum sickness, CNS demyelination,
     vascular thrombosis, glomerulonephritis,
     myocarditis, multi-organ failure, and death
   – Multiple stings required :
     LD50 (honeybee) > 500 stings

    Graft DF. Stinging insect hypersensitivity in children.
    Curr Opin Ped. 1996; 8:597-600
  for all

• Rapidly remove all bee venom sacs -
  envenomation is complete in one minute !
• Use your HIVE TOOL !
Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from
honeybee stings. J Allergy Clin Immunol. 1994;93(5):831-5.
            Toxic Sting Reactions
• Honeybees (especially Africanized) or Wasps
  (yellowjackets and hornets)
• Without treatment, > 20-200 wasp stings
  or > 150-1000 bee stings can be fatal
• Symptoms may not appear for hours to
  several days
• Go to the hospital immediately for any mass
  sting (call 911 !!!)

Vetter RS, Visscher PK, Camazine S. Mass envenomations by honey bees and wasps.
West J Med. 1999;170(4):223-7.
       Allergic Reactions
        to Insect Stings
1. Local: pain, redness at site
2. Large Local: swelling of extremity
3. Systemic: generalized, involves any
   symptoms at a remote site from the
   sting. These may quickly be life
              Immediate Therapy
                 for Stings

     • Local reaction: ice, antihistamine
Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from
honeybee stings. J Allergy Clin Immunol. 1994;93(5):831-5.
              Immediate Therapy
                 for Stings

  • Large Local reaction: ice, antihistamine,
    prescription prednisone
Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from
honeybee stings. J Allergy Clin Immunol. 1994;93(5):831-5.
              Immediate Therapy
                 for Stings

• Systemic reactions: give epinephrine & treat
  for anaphylaxis. Call 911 !!!
Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from
honeybee stings. J Allergy Clin Immunol. 1994;93(5):831-5.
      Systemic Reactions
• Treat immediately !
• If you think of epinephrine, USE IT !
• Epinephrine 1:1000 (0.01ml/kg)
  = 0.3 ml adult, 0.15 ml child.
  Inject into muscle !
• Be ready to Re-Treat. Epinephrine
  may only last 5-10 minutes.
Systemic Reactions

• Epinephrine is required more than
  once in 35% of anaphylaxis cases
• Most insurance companies cover
  dual packs of epinephrine
  injectors.      Buy them !
 Korenblat P, Lundie MJ, Dankner RE, Day JH. A retrospective study of epinephrine
 administration for anaphylaxis: how many doses are needed?
 Allergy Asthma Proc. 1999;20(6):383-6.
• Caution after
removing safety cap
- don’t inject hand
• Swing hard
• Inject right
through your clothes
• Hold against leg &
count slowly to 10
   After Giving Epinephrine
• CALL 911
• Keep giving Epinephrine, as often
  as needed to control symptoms
• If patient has asthma, USE THEIR
• If available, give oral
  Antihistamine and Oxygen
       Facts to Remember
Clinical History - helps with treatment
 Important to Identify:
• what kind of insect
• type of reaction
• severity of reaction
• ? progression of this reaction over time
• ? worse compared to last sting
     What Insect Was it ?
• Winged / flying eliminates Fire Ants
• Stinger left in skin : Honeybee
• Nest location : ground favors Yellow
 Jacket (bumble bee less common)
• Large size: favors Hornet
• Narrow waist: not a bee or bumblebee
 Insects to Test 1
• About 90% of stings are from Wasps
• Always test Yellow Jacket
  (most aggressive, most likely to sting)
• If Wasp or Hornet is likely, test all local
• If Africanized bees are local, test Honeybee
  Pérez-Pimiento AJ, González-Sánchez LA, Prieto-Lastra L, et al. Anaphylaxis to
  hymenoptera sting: study of 113 patients. Med Clin (Barc). 2005;125(11):417-20.
Which Insects to Test 2
• If stinger found, test Honeybee
• When unsure, test Honeybee & Yellow
• If stung by Bumblebee (large bee), test
  for Honeybee and Bumblebee
• If poor history, test all local species
 Why to do In Vitro (Blood) Tests
• IgE:
   – To identify culprit insect ( may be falsely
    negative in 15-20%)
   – To determine degree of sensitivity
   – To differentiate toxic and allergic Rxn
   – For Safety, prior to Skin Testing
• IgG :
   – To check progress of desensitization
 Reisman RE. Stinging Insect Allergy. Med Clin NA 1992; 76:883-894
        Why to do Skin Tests

• If blood test is negative, and suspicion of
 allergic reaction is high
• if immunotherapy is needed, skin test
 must precede beginning treatment
              Bee-Venom Allergy
             without positive Tests
• In very rare patients with classic bee
sting anaphylaxis history, blood tests and
skin tests may both be negative.
• If an in-hospital sting challenge is
positive, immunotherapy is indicated.

Zidarn M, Kosnik M, Drinovec I. Anaphylaxis after Hymenoptera sting without detectable
specific IgE. Acta Dermatovenerol Alp Panonica Adriat. 2007 ;16(1):31-3.
     Management of Proven
     Stinging Insect Allergy
Insect Avoidance
  – Caution during outdoor activities
    • Look for nests on ground, roofs
  – Extra care in Picnic areas
    • Orchards, trash containers, soda cans, fruit
  – Wear shoes, long sleeves, pants, gloves
  – Avoid fragrances, bright colors
  – Use protective suit, veil, & gloves when
    working with bees
Management of
Stinging Insect
• Epinephrine kits
  – Kits must be with you to be useful
    • epinephrine stability is poor with oxygen,
      light, & heat ( replace kits as needed )
  – Practice epinephrine use
  – Always call 911 after epinephrine
• Antihistamines & corticosteroids are
  OK to use AFTER epinephrine
        Management of
    Stinging Insect Allergy
Venom Immunotherapy
  (Allergy Shots) - should be
  considered in all persons who:
• have a positive history of one or
  more Systemic Reactions to stings
• have a positive diagnostic test
• are likely to be re-stung
Who Needs Immunotherapy ?
Only 25 - 50% of patients repeat Systemic
  Reactions when re-stung
• risk increases with repeat stings,
  especially if close together in time
• higher risk for occupational exposure
• higher risk for asthmatics
• highest risk if Circulatory Shock occurs
• clinical judgement required
        Immunotherapy Results
• Treatment effectiveness is 97% (Wasps)
  or 80% (Honeybees)
• About 20% have mild reactions due to
  treatment, usually early in therapy
• Rare patients (0.7 %) require
  epinephrine during therapy
 1. Mosbech H, Muller U. Side-effects of insect venom immunotherapy:
 results from an EAACI multicenter study. Allergy 2000; 55:1005-1010
 2. Muller UR. Duration of venom immunotherapy. J Allergy Clin Immunol.
 1997; 95:271-272
       Immunotherapy Results
146 sting immunotherapy cases, at 6.5
years after beginning treatment.
  • High Risk of re-sting (41%)
  • Most had improved quality of life
  (90% had less fear and fewer changes
  in lifestyle on immunotherapy)
Roesch A, Boerzsoenyi J, Babilas P. et al. Outcome survey of insect venom allergic
patients with venom immunotherapy in a rural population.
J Dtsch Dermatol Ges. 2008;6(4):292-7.
      Immunotherapy Results
181 sting immunotherapy cases, 1 - 27
years after at least 3 years of treatment.
   • High Risk of re-sting (55%)
   • Most had only local reactions (92%)
   • Systemic reactions (8% ) were milder
   than before treatment

Hafner T, DuBuske L, Kosnik M. Long-term efficacy of venom immunotherapy.
Ann Allergy Asthma Immunol. 2008 100(2):162-5.
     Benefits of Immunotherapy
           for Beekeepers
459 bee-allergic patients:
  • 14% were beekeepers, and 10% were
  beekeeper’s family members
  • beekeepers vs non-beekeepers: there
  was no difference in results of
  • beekeepers had less problems with IT
  • most beekeepers continued beekeeping
  with immunotherapy protection
      Eich-Wanger C, Müller UR. Bee sting allergy in beekeepers.
      Clin Exp Allergy. 1998;28(10):1292-8.
Repeated Stings may increase
     Reaction Severity
40 sting allergy immunotherapy cases,
after at least 3 years of treatment, were
then re-stung more than once.
   • 83% remained desensitized
   • 17% had progressively more severe
   reactions with each subsequent sting (like
   people never treated with immunotherapy)
 Hafner T, DuBuske L, Kosnik M. Long-term efficacy of venom immunotherapy.
 Ann Allergy Asthma Immunol. 2008 100(2):162-5.
        Lab Check on Immunity
   IgG and IgE can be measured in blood.
   • If protective immunity is occurring:
       – IgE should decrease
       – IgG should increase
   • Higher venom doses can be used if
     standard doses do not work
1. Valentine MD, Lichtenstein LM. Anaphylaxis and stinging insect hyper-
sensitivity. JAMA 1987; 258:2881-2885
2. Bosquet J, Muller UR, Drebord S, et al. Immunotherapy with Hymenoptera
venoms. Allergy 1987; 42:401-413
Difficulty with Immunization
• In rare patients, it is impossible to
increase the venom dose high enough
to produce good immunity, without
triggering unacceptable reactions
• Most people with this problem can
now be helped with anti-IgE
 Anti-IgE and Immunotherapy
   Where immunotherapy reactions
   prevented administering adequate
   venom doses, adding anti-IgE
   (omalizumab, Xolair) resulted in
   success in 7 reported cases

Galera C, Soohun N, Zankar al. Severe anaphylaxis to bee venom immunotherapy:
efficacy of pretreatment and concurrent treatment with omalizumab.
J Investig Allergol Clin Immunol. 2009;19(3):225-9..
When to Stop Bee Immunotherapy
• After 5 years, before stopping maintenance
  injections, measure blood IgE and IgG
   – IgE should drop to 0
   – IgG should be > 5 mg / ml
• How likely is this person to be restung ?
• How severe was the last sting reaction ?
• Are there any treatment side effects ?
• Weigh the pros and cons carefully
• Avoidance techniques should always
  be employed
• Emergency epinephrine should
  always be with you
• Accurate diagnosis is critical
• Immunotherapy is highly effective,
  but treatment failures still can occur
Happy, Safe, Beekeeping !

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