Slajd Hives Urticaria

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					Insect allergy
  Joanna Lange
• 0,4 % of the population in the USA;
• cross - sectional studies:
• 1 - 3% prevalence of systemic reaction;
• 9 - 32% sensitization to insect venoms;
• deaths to Hymenoptera stings –
  40/per year in the USA;
           Taxonomy of Hymenoptera
Family       Subfamily    Scientific name       Common
Apidae                    Apis mellifera        Honeybee
                          Bombus spp.           Bumblebee
                          Megabombus spp;.
                          Pyrobiombus spp.
                          Halictus spp.         Sweatbee
                          Dialictus spp.

Vespidae     Vespinae     Vespula spp.          Yellow jacket
                          Dolichovespula        Yellow hornet
                          maculata              White-faced
             Polistinae   Polistes spp.
                                                Paper wasp
Formicidae                Solenopsis invicta    Fire ant
                          Solenopsis richteri
                          Pogonomyrmex spp.     Harvester ant
Vespa crabro – European hornet
                                     Vespula rufa

                                 Paravespula germanica
         Vespa orientalis
Dolichovespula adulteriana   Polistes gallicus

   Dolichovespula media
                                Polistes nimpha
A cluster of honeybee.
   Paper wasp

Papernet wasp
       In central and northern Europe vespid (mainly Vespula spp.) and
honeybee stings are the most prevalent.
         In the Mediterranean area stings from Polistes and Vespula are
more frequent than honeybee stings.
        The stinger of honeybees usually remains in human skin.
       Bumblee-bees and vespids normally remove their stinger from the
human skin.
    Cross - reactivite among Hymenoptera

    APIDAE         APIS            BOMBUS




Venom biochemistry
                                             Venom biochemistry

• all venom allergens are proteins, and most are enzymes
  with molecular weights between 13,000 to 50,000D;

• with the exeption of mellitin from honeybee venom, the
  peptides of Hymenoptera venoms are nonallergic but are
  responsible for the toxic and pharmacologies acitvities of

• in addition to the proteins and peptides, Hymenoptera
  venoms contain vasoactive amines, such as – histamine,
  5-hydroxytryptamine, acetylocholine, dopamine and
                                             Venom biochemistry

• within the yellow jacket family there is strong cross -
  antigenicity and cross –allergenicity among venoms from V.
  maculifrons, V.germanica, V.vulgaris and V.flavopilosa;

• similar findings have been reported for the paper wasp

• there are rare individuals who react only to venom from one
  vespid species;

• there is little or no cross – reactivity between honeybee
  venom phospholipase A and vespid venom phospholipase A,
  whereas hyaluronidase from bee and vespid venom may
  cross - react.
                    Bee venom
                                                Venom biochemistry

Substances of lower molecular weight:
feromones, histamin -local toxity, dopamin, norepinephrine,
aminoacides, oligopeptides, fosfolipids, węglowodany;

Bigger peptides -1000-5000:
mellitin – membrane poisson; apamin - neurotoxin;
Peptide - MCD, tertiapine - liberator of histamin;
secapine; kardiopeptide – positive inotropic and chronotropic;

Enzymes - 10000 do 200000:
phospholipase A2 - membrane poisson – very high alergogenity;
hyaluronidase – high alergogenity; acid phosphatase;
alfa-glukosidase; esterases;

adolapin – pain relief, alergen C;
                                    Venom biochemistry

           Bombus venom

phospholipasa A2; hialuronidase; acid

  Immunological mimikra to bee venom
                                                Venom biochemistry

                  Vespa venom
•   histamin – higher than bee venom;
•   serotonin;
•   acetylocholin;
•   kinines;
•   mastoparan – degranulates mast cells;
•   hemolizyn - mellitin – like;
•   phospholipase A i B;
•   hialuronidases;
•   antigen 5;

    Allergens activity - phospholipases, hialuronidase i
    antigen 5;
Clinical presentation and
 pathogenesis of sting
                                      Clinical presentation

• venom hypersensitivity may be mediated
  by immunologic mechanisms (IgE or not-
  IgE), but also by non - immunological

• classification if the reaction:
•   normal local reaction;
•   large local reaction;
•   systemic toxic reaction;
•   systemic anaphzlactic reaction;
•   unusual reaction.
                                 Clinical presentation

       Normal local sting reaction

•   local reaction with pain;
•   erythema;
•   slight swelling around the sting side;
•   subside within 24 hours;
•   only a small sting reaction may be remain
    a visible for a few days.
                                Clinical presentation

    Large local sting reaction (LLR)
•   swelling exceeding a diameter of 10 cm
    last longer than 24 hours;
•   blisters may be rarely present;
•   sometimes swollen lymph glands;
•   great discomfort when symptoms
    prolonged few days;
                                    Clinical presentation

Systemic anaphylactic reaction

• most often IgE - mediated;
• non - IgE mediated reaction - due to short term
  sensitising IgG or complement activation by IgG-
  venom complexes;
• most often symptoms appear within few minutes
  after the sting;
• recovering few hours after stinging;
  Classification of systemic reaction to
      insect sting by H.L. Mueller
Grade I     Generalized urticaria, itching, malaise and anxiety

Grade II    Any of the above plus two of more of the following:
            angioedema, chest constriction, nausea, vomiting,
            diarrhea, abdominal pain, dizziness

Grade III   Any of the above plus two of more of the following:
            dyspnea, whezzing, stridor, dysarthria, hoarsness,
            weakness, confusion, feeling of impending disaster

Grade IV    Any of the above plus two of more of the following: fall
            in blood pressure, collapse, loss of conciousness,
            incontinence, cyanosis
    Classification of systemic reaction modifide
        according to J. Ring and Messmer

Grade I     Generalized skin symptoms (e.g. flush, generalised
            urticaria, angioedema)

Grade II    Mild to moderate pulmonary, cardiovascular, and/or
            gastrointestinal symptoms

Grade III   Anaphylactic shock, loss of conciousness

Grade IV    Cardiac arrest, apnoea
                                             Clinical presentation

  Systemic toxic reaction

• toxic effect – phospholipase and
• after multiple – usually 50 -100 stings;
• symptoms: rhabdomyolisis, myocardial damage,
  hepatic dysfunction, intravascular haemolysis, acute
  renal failure, coagulation disorders with bleeding and
                                      Clinical presentation

  Unusual reaction

• serum sikness like symptoms with fever,
  arthralgias, urticaria, angioedema,
  lymphadenopathy and neurological symptoms;

• gromeluronephritis, acute allergic renal nephritis,
  haemolytic anemia, thrombocytopenia,
  myocarditis, Guillain-Barre sydrome
•   history;
•   skin tests;
•   in vitro tests;
•   allergen specific IgG;
•   baseline serum tryptase;
•   other in vitro tests
• Diagnostic tests should be done in all patients
  with a history of a systemic sting reaction to
  detect sensitisation;

• Diagnostic tests are not recommended in
  subjects with a history of large local reaction or
  no history of a systemic reaction;

• Testing comprises skin tests with Hymenophtera
  venoms and analysis of the serum for
  Hymenophtera venom-specific IgE;

• Stepwise skin testing with incremental venom
  concentrations is recommended;
• If skin prick tests are negative subsequently
  intradermal tests should be done;

• If diagnostic tests are negative they should be
  repeated several weeks later;

• If both skin tests and specific Ige stay negative
  additional in-vitro tests should be carried out;

• Serum tryptase should be analysed in patients
  with a history of a severe sting reaction
  Preventing insect stings and bites

• Avoid provoking insects whenever possible.

• Avoid rapid, jerky movements around insect hives or nests.

• Avoid perfumes and floral-patterned or dark clothing.

• Use appropriate insect repellants and/or protective clothing.

• Use caution when eating outdoors, especially with sweetened
beverages or in areas around garbage cans which often attract
    Examples of activities implying special risk
        for stings during warm season
• outdoor eating and drinking;
• barefoot walking;
• gardening (especially cutting hedges, flowers);
• picking fruit;
• outdoor sporting (especially with scanty outfit or
  open mouth);
• staying close to beehives when honey is
• removing vespid nests from attic or windows;
Yellow jacket and Vespa crabro nest
Emergency treatment
     Technic of proper removing of
              the stinger


         Removing of the stinger
                    First aid for minor reactions

• If the sting is from a honey bee, remove the stinger from the skin if it is still
           present. Carefully scrape the back of a knife or other thin straight-
           edged object across the stinger if the victim can remain still, and it is
           safe to do so. Otherwise, you can pull out the stinger with tweezers
           or your fingers, but avoid pinching the venom sac at the end of the
           stinger which will cause more venom to be released.

• Wash the site thoroughly with soap and water.

• Cover the site with a clean, cold compress or a clean, moist dressing to
         reduce swelling and discomfort.

• Over the next 24 to 48 hours, observe the site for signs of infection
         (such as increasing redness, swelling, pain).

• Sores from scratching can become infected. Keep bites clean and, to
          prevent infection, don't scratch.
                    First aid for serious reactions
 If the victim is having a severe reaction or the victim has been stung
 inside the mouth or throat, call immediately for emergency medical

•Check the victim’s airway, breathing, and circulation. If necessary, begin
rescue breathing and CPR.

•Reassure the victim. Try to keep him or her calm, as anxiety will worsen
the situation.

•Remove nearby rings and constricting items because the affected area
may swell.

•Use a special allergy first aid kit, if available. (Some people who have
serious insect reactions carry it with them.)

•If appropriate, treat the victim for signs of shock. Remain with the victim
until medical help arrives.
       Treatment of systemic reaction to Hymenoptera sting

Type of reaction Drug and dose                             Notes
Mild urticaria         Antihistamines oral or parenteral   Observe for at least 60

Urticaria, angioedema Check blood pressure and pulse       Patient must be kept
                      rate                                 under observation until
                      Establish an i.v. line with saline   symptoms completely
                      Antihistamines oral or parenteral    disappear
                      Corticosteroids oral or parenteral
                      In case of severe or progressive
                      Epinephrine (1mg/ml):
                      - Adults 0,30 – 0,50 mg i.m.
                      - Children 0,01 ml/kg i.m.
       Treatment of systemic reaction to Hymenoptera sting

Type of reaction Drug and dose                                Notes
Laryngeal oedema        Epinephrine by inhalation or i.m.     Intubation,
                                                              tracheotomy or
                                                              cricothyrotomy may be
                                                              needed in cases of
                                                              more severe laryngeal
Bronchial obstruction   Mild to moderate – beta2 –agonists    All patients with
                        by inhalation                         protracted respiratory
                        Severe - Epinephrine by inhalation    symptoms must be
                        beta2 –agonists (0,5 mg/ml) 1         hospitalized; those
                        year- 0,05 – 0,1 mg; 7 years- 0,2 -   with laryngeal oedema
                        0,4 mg; adults 0,25-0,5 mg            must be given
                                                              intensive medical care
                                                              as soon as possible
      Treatment of systemic reaction to Hymenoptera sting

Type of              Drug and dose                                   Notes
Anaphylactic shock   Epinephrine (1mg/ml):                           Hospitalization necessarz
                     - Adults 0,30 – 0,50 mg i.m.                    because of the risk of
                     - Children 0,01 ml/kg i.m.                      delazed anaphylaxis
                     May be repeated after 5-15 min.
                     Exeptionally i.v.
                     Place patient in supine position, oxygen 5-10
                     Check blood pressure and pulse rate
                     i.v.access, volume replacement
                     Antihistamines i.v. corticoids i.v.

                                                                     If epinephrine injections with
                     Dopamine or norepinephrine infusion             or without antihistamines and
                                                                     volume expansion fail to
                                                                     alleviate hypotension

                                                                     For refractory hypotension
                     Glucagone:0,1 mg/kg i.v (nausea, vomiting)      and bronchospasm in
                                                                     patients on beta-blokers
       Epinephrine - indications
• all with history of anaphylaxis or „ very sensitized”;

• those with hymenophtera allergy;

• with food allergy;

• in patients with anaphylaxis induced by exercises;
                                     Emergency treatment

• after a systemic reation, patients should be
  referred to an allergy specialist for evaluation of
  their allergy and if necessary VIT;
• i.m. epinephrine is regarded as a treatment fo
  choice for acute anaphylaxis;
• H1 – antihistamines alone or in combination with
  corticosteroids may be efective in mild to
  moderate, reactions confined to the skin and may
  support the value of treatment with epinephrine in
  full-blown anaphylaxis;
• untreated patients with a history of a systemic
  reaction are strongly advised to carry emergency
  kits containing injectable epinephrine for self
Proper using
 of EpiPen
 Remove the device from the
 plastic protective container.

Remove the grey cap from the
   fatter end of the device.
NB: This "arms the unit" ready
            for use
 Hold the EpiPen in your fist with clenched fingers wrapped around it
           (NB: there is nothing to "push" at the white end)

Press the black tip gently against the skin of the mid thigh, then start to
push harder until a loud "click" is heard. This means that the device has
                             been activated.

  Hold in place for 10-15 seconds (count "1 elephant, 2 elephants, 10
   elephants etc") while the adrenaline is injected under pressure.
               NB: The EpiPen "pop" is often quite loud.

      Remove the pen from the thigh; be careful with the needle
        that will now be projecting from the EpiPen when you
                        dispose of the device.
         Massage in the adrenalin. There may be some slight
                     bleeding at the injection site.

      Apply firm pressure with a cloth, tissue, clean handkerchief
                              or bandage.
               Record the time that the EpiPen was given.

                              Call for help.
   EpiPen Mistakes
   - what not to do!
          MISTAKE NUMBER 1

  The black tip contains the needle and
needs to be placed against the mid-thigh.
Holding the wrong end and injecting the
 thumb (blue line) is painful and not very
                effective ...

            MISTAKE NUMBER 2

 Unless the grey cap is removed (blue line),
  the EpiPen will NOT work, no matter how
              hard you push ...
               MISTAKE NUMBER 3

   This photograph is more subtle. The patient is
    pressing the white end very hard (blue line),
assuming there is a "button" at the white end. There
                        is not!
  Unless pressure is exerted at the black end, the
 EpiPen will not work. By all means rest the thumb
 on the white end, but you must exert pressure on
         the black tip into the thigh as well.
                          First aid kit

    30 €
                                          40 €

                               35 €

                                                 Epi Mate
                                                  35 €

                                           Venom immunotherapy

• in persons who have expirience a systemic reaction to
  an insect sting and who have postive skin test (prick or
  intradermal) at concentration 1 mcg/ml or less;

• medical indications are strongest in adults – untreated
  individuals – 50-60% of risk of systemic reaction if stung

• large local reactions – only a small risk of anaphylaxix
  after future stings
                                          Venom immunotherapy

    Contra indications:

• autoimmunologic diseases;
• tumors;
• immunological deficiences;
• children younger than 5 years;
• insufficiences of heart, hepatic problems, nephrological
  problems, epilepsy;
• psychiatric problems;
• diseases in which adrenalin is conrtaindicated (e.g.
  pcheochromocytoma, thyreoid tumors);
Indication to the immunotherpy (by Bousquet) in
              patients above 15 year

Clinical    Skin tests   IgE        Qualification
reaction                            for IT
Systemic         +             +           +
Systemic         +             -          +
Systemic         -             +      disussion
Systemic         -             -           0
Local          + or -      + or -          0
Indication to the immunotherpy (by Bousquet) in
          patients younger than 15 year

Clinical    Skin tests   IgE        Qualification
reaction                            for IT
Systemic         +             +           +
Systemic         +             -          +
Systemic          -            +      disussion
Systemic          -            -           0
Generalized      +             +      usually 0
Local          + or -      + or -          0
Even skin tests are positive or specific IgE
 are positive, no immunotherapy in such

• no systemic or large local reactions;

• only slight large local reaction;

• systemic reactions were late;
                                    Venom immunotherapy

• it is possible to reach the targeted maintance
  dose (100 mcg/ml) in 2 or 3 days, 6 hours or
  even 31/2 hourse;

• local swelling, erythema or even anaphylactic
  reactions – those schedules unacceptable for
  some persons;

• if monthly maintance doses of venom have been
  tolerates fo 6 months, the interval between
  injections can be lenghted to 6 to 8 weeks or 8
  to 12 weeks;
                                  Venom immunotherapy
• generally well tolerated;

• 12% of persons have allergic reactions during
  the bulid – up doses of 1 to 50 mcg/ml and some
  in the maintance dose of 100 mcg;

• more apt to occur with honeybee or wasp

• if a patient experiences a systemic reaction
  during bulid-up phase, the next dose should be
  reduced by 50%
Bitting insect allergy
        Selected biting insects reported to cause human
                        allergic reactions
Order            Family                  Genus

Hemiptera        Reduvidiidae            Triatoma (kissing or cone-
                                         nose bug)
                 Cimicidae (bed bugs)    Cimex
Diptera          Culicidae (mosquitos)   Culex
                 Simuliidae (blackfly)   Cnephia
                 Tabanidae               Tabanus (horsefly)
                                         Chrysops (deerfly)

Siphonaptera     Pulicidae               Ctenocephalides (cat or
                                         dog flea)
  Triatoma (Kissing bug, Cone – nose bug)

• feed by sucking the blood of vertebrate animals;

• bites are painless;

• allergens derived from salivary glands of insect;

• immunotherapy with T.protracta salivary gland
  extract has provided clinical protection from
  Triatoma bite – induced anaphylaxis in a small
  number of individuals;
Culicidae (Mosquitoes)
 • severe local reactions;

 • anaphylacitic reactions are anegdotal;

 • cutaneous reactions may be mediate by
   IgE antibodies to mosquito salivary
  Tabanidae (Horsefly, Deerflies)
• females suck blood, whereas males feed on plant juices,
  nectar or other nourishing liquids;

• Horseflies are cosmopolitan and are pests of both human
  and animals;

• their bite is painful, and they make a deep wound with a
  considerable flow of blood;

• systemic reactions have been noted after deerfly bites and
  IgE antibodies to deerfly antigens have been demonstrated
  by leukocyte histamine release assays and passive skin
           Other biting insects

• only two case reports of allergic reactions after
  bites from bed bugs (Cimex spp.);

• blackfly bites may cause large local reactions and
  induce specific IgE antibodies;

• severe systemic reactions to blackfly bites are
        Inhalant insect allergy
• rhinitis, conjunctivitis, and asthma can develop
  as the result of allergic sensitivity to scales,
  hairs, and emanations of a variety of insects;

• symptoms are typical of inhalant allergy caused
  by other activities to polens and danders;

• a number of insects may cause occupational
  asthma (e.g. coackroaches)

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