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Diagnosis of Insect Sting Allergy Indications for Venom

VIEWS: 112 PAGES: 28

									 Insect Sting Allergy and
  Venom Immunotherapy



      David B.K. Golden, M.D.
Johns Hopkins University, Baltimore
History of Reaction to Insect Stings
     (Skin Test Positive Patients)



      No reaction

      Large Local

      Cutaneous Systemic

      Anaphylaxis
             INSEC T ALLERGY CASE 1


   A 32 yea r old man with a his tory of seve re and

     prolonged swelling from previous insec t stings is

     stung on the leg. Aft er 15 minu tes he develops

     gene rali zed hives, swelling of lips and hands, with

     no throat tigh tness or dizz iness. Symp toms resolve

     after 1 hou r. The nex t day the E.D. treats his seve re

     leg s welling and discha rges him on antibio tics.



Severe swelling 24 hrs after a sting should be treated with:
A. Antibiotics       C. Antihistamine               E. Epinephrine
B. Prednisone        D. Venom immunotherapy
              INSEC T ALLERGY CASE 1b


   A 12 yea r old boy on the school cross -coun try track

     team is running in a wooded area when he is stung

     twice on the arm. Within 5 minu tes he develops

     throat tigh tness follo wed rapidly by gene rali zed

     hives and angioedema, di zz iness and dyspnea. He is

     helped back to school and met by pa ramedics who

     adminis ter epineph rine and tr anspo rt him to the

     eme rgency depa rt men t for prolonged obse rvation.
Venom immunotherapy:
A. Is not necessary (“He’ll outgrow it”)         B. Is dangerous
C. is only partially effective   D. Is forever   E. None of the above
Diagnosis of Insect Sting Allergy
(Indications for Venom Immunotherapy)



    • History

    • Venom Skin Test (RAST)

    • Natural History
Symptoms and Signs of Insect Sting Anaphylaxis
           in Adults and Children

                               Frequency (%)

    Symptoms or Sign        Adults    Children

    Cutaneous only            15        60

    Urticaria/angioedema      80        95

    Dizziness/hypotension     60        10

    Dyspnea/wheezing          50        40

    Throat tightness/         40        40
    Hoarseness

    Loss of consciousness     30         5
Epidemiology of Venom Allergy

• History of systemic reaction in 0.5%-3.0% of
  the population

• Positive venom skin test or RAST in 15%-25%
  of the population.

• Transient positive skin test or RAST may
  occur after uneventful sting.

• Presence of IgE venom antibody not
  necessarily predictive of clinical reactivity.
   Correlation of Yellow Jacket Venom
 RAST and Skin Tests (Golden - JAMA 1989)

                      Venom Skin Test
RAST (ng/L)       Positive        Negative

< 1 (negative)     9 (24%)        190 (89%)

≥ 1 (positive)    29 (76%)          23 (11%)

  1.0 - 1.9        8                 9
  2.0 - 2.9        5                 4
  3.0 - 4.9        4                 5
  ≥5.0            12                 5

Total             38               213
        History Positive Patients with
         Negative Venom Skin Tests

Possible explanations:

     Not true allergic reaction (no objective signs)

     Allergy “outgrown”

     Mastocytosis (~1 % of insect allergic patients)

     Not detected:
                     - Refractory period (anergy)
                     - RAST positive
           Diagnostic Venom Test Reactivity
             after Systemic Sting Reaction
           (Goldberg and Confino-Cohen; JACI 1997)


Time after sting        1 week      4 - 6 week        Any


Skin Test Positive       20 (53%)    15 (39%)        35 (92%)



RAST Positive            24 (63%)     8 (21%)        32 (84%)



Any Positive            30 (79%)      8 (21%)        38 (100%)
      Venom Skin Test / RAST in
History Positive Patients (Golden - JACI 2001)

Total history positive patients screened:       (N=307)

ST positive                208 (68%)

ST negative                  99 (32%)

     ST - neg/RAST neg               56 (57%)    (18%)

     ST - neg/RAST positive          43 (43%)

              RAST   1 - 3 ng/ml        36

              RAST   7 - 243 ng/ml       7
Diagnosis of Insect Allergy in Patients With
       Positive History (Systemic)

   Skin test positive            68%


   ST negative /
      RAST positive              14%


   ST neg / RAST neg /
      sting challenge positive   1%


   No sting allergy              17%
  Low Risk Sub-Groups of Patients With
       Positive Venom Skin Tests


                                    Risk of
Sting Reaction History          Systemic Reaction


Children - Cutaneous Systemic        10 %

Large Local                         5 - 10 %
Insect Sting Allergy in Children (1978 -1987)
   (Schuberth, Valentine, Kagey-Sobotka, Lichtenstein)


 History          N          Disposition of Patients


 Cutaneous       462         Untreated vs. VIT
 systemic                      • untreated     (n=352)
                               • treated (VIT) (n=110)

 Mod-severe      345          VIT advised
 systemic                       • untreated        (n=99)
                                • treated (VIT)   (n=246)

 Large Local     226          No VIT

 TOTAL           1033
        Summary Of Sting Reactions
       490 Stings in 180 Patients over 9 Yrs



100%
                  0.4%
                  10 %                 Severe SR
90%
80%                                    Mild SR
                  25%
70%                                    Large Local
60%                                    Normal
50%
40%               65%
30%
20%
10%
 0%
     Natural History of Large Local Reactions
                       Diagnostic Test      Sting Reaction
                      Skin Test    RAST    Systemic     LL

Graft et al
(J Ped 1984)          105/125               2/54      20/54
children               (84%)                (4%)      (37%)

Mauriello et al
(JACI 1984)         105/133       67/133    1/28      21/28
adults and children (79%)          (50%)    (4%)      (75%)

Golden et al
(JACI 1984)             38/52               5/52
adults                  (73%)               (10%)

Abrecht et al
(Clin Allergy 1980)     27/40     29/40
children and adults     (68%)     (73%)
Repeat Systemic Reaction In Sting Allergic Patients

        STUDY       (YEAR)       N     SYSTEMIC (%)
        GOLDEN         (1981)    115      75 (65%)

        HUNT           (1978)     23      19 (61%)

        SETTIPANE      (1979)   119       72 (61%)

        LANTNER        (1989)    18       11 (61%)

        REISMAN        (1992)    220     124 (56%)

        GALATAS        (1994)    27       13 (48%)

        PARKER         (1982)    16        7   (44%)

        DVORIN         (1984)    19        8   (42%)

        BLAAUW         (1985)    86       29 (39%)

        FRANKEN        (1994)    228      90 (39%)

        vanderLINDEN (1994)      324      96 (30%)

               TOTAL            1195     544 (46%)
    Risk of Systemic Reaction in
Untreated Skin Test Positive Patients

 Original Sting Reaction   Risk of Systemic Reaction

 Severity        Age        1 - 9 yrs    10 - 20 yrs

No reaction      Adult       17 %

Large local      All          10 %         10 %

Cutaneous        Child        10 %          5%
systemic         Adult        20 %         10 %

Anaphylaxis      Child       40 %          30 %
                 Adult       60 %          40 %
         INSEC T ALLERGY CASE HISTORY


A 28 yea r old man was stung by a yello w jacket and
rapidly developed gene ralized hives, dyspnea and
th roat tightness, follo wed by seve re dizziness with
nea r-unconsciousness.    He responded well to
eme rgency medical treatment. He was discha rged
with no specific recommendation      except fo r a
presc ription fo r an epineph rine injection device.

He presents to the alle rgist because his uncle died
from insect sting alle rgy and his family and docto rs
have told him the next sting   will su rely kill him.
Previous stings had caused no abno rmal reaction.
Controlled Trial of Venom Immunotherapy
                                          (Hunt et al, NEJM 1978)



   Trea tment                    Stung        System ic (%)


   Venom (n=19)                    18            1         (5%)*

   W B E (n=20)                    11            7         (64%)

   Placebo (n=20)                  12            7         (58%)
  * afte r crossover, tota l 1/55 = 2% on VI T (p<0.01 )
Venom Immunotherapy Treatment Protocols

                    Conservative    Moderate       Liberal


Regimen             Traditional    Modified Rush    Rush

Weeks to Mc           20 - 26           8            1


Dose (µg)               50            100           200


Maintenance (wks)       4             6-8            12
Dose Response of Venom Immunotherapy
(Rueff et al JACI 2001;108:1027-32.)
Premedication During Venom Immunotherapy

                                     Terfenadine    Placebo

Brockow et al (JACI 1997)

       Systemic during VIT            1/82 (1%)     6/39 (15%)

       Large Local during VIT        20/80 (24%)   17/39 (45%)

Muller et al (JACI 2001)

       Systemic during VIT            5/24 (21%)   13/23 (56%)

       Systemic to challenge sting    0/20          6/21 (28%)
Venom-IgE and Skin Test During
and After Venom Immunotherapy
        Discontinuing Venom Immunotherapy:
            Reported Studies and Criteria
Author                    Patients                                        Criteria

                                                                   Studied         Proposed
Graft (1984)               children                              5-7 years*          5 years
Urbanek (1985)             children                              RAST neg            RAST neg
Randolph (1986)            adults & children                     RAST neg           RAST neg
Keating (1991)             adults & children                     2-10 years*         5 years
Haugaard (1991)            adults                                 3-7 years*         3 years
Muller (1991)              adults & children                     3-10 years*         3 years*
Reisman (1993)             adults & children                       1-6 years         3+ years
Lerch (1998)               adults & children                     3-10 years*         5 years#
Golden (1998)              adults                                 5-7 years          5 years#

* Negative sting challenge included as criterion for discontinuation.
# Excluding patients with life-threatening history, honeybee allergy or systemic reaction during VIT.
     Discontinuing Venom Immunotherapy
                     (Lerch and Muller 1998)


                           N          Systemic       P
                      (pts/stings)    Reaction (%)

VIT Duration
   <50 months          118 pts        21 (18%)
   >50 months           82 pts         4 (5%)        0.007

Insect
    Honeybee           120 pts        19 (15.6%)
    Vespid              80 pts         6 (7.5%)      0.08

Time since D/C VIT
   1-2 years           444 stings     20 (4.5%)
   3-5 years           211 stings     30 (14%)       0.001
   6-7 years            64 stings      5 (8%)
    Discontinuing Venom Immunotherapy
                 (Golden et al JACI 2000)


                                       Systemic reaction

Venom Skin Test Positive                    10% / sting

Venom Skin Test Negative                    10% / sting

Off VIT 3 yrs (1 - 4 yrs)                   10% / sting

Off VIT 10 yrs (5 - 13 yrs)                 10% / sting

Cumulative risk (10 yrs)                    17%
               COLLABORATORS

Lawrence M. Lichtenstein
Anne Kagey-Sobotka
Robert G. Hamilton
Philip S. Norman
Timothy J. Craig
Denise C. Kelly
Kristin Chichester
Tina D. Grace


General Clinical Research Center (GCRC):
       Johns Hopkins Bayview, Baltimore, MD
       Penn State University, Hershey, PA

Funding: NIH AI08270 (L. M. Lichtenstein, P.I.)

								
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