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Tags : Insect Sting Allergy, Venom Immunotherapy, Diagnosis, Epidemiology

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Slide 1-

Insect Sting Allergy and Venom Immunotherapy David B.K. Golden, M.D. Johns Hopkins University, Baltimore
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History of Reaction to Insect Stings(Skin Test Positive Patients) No reaction Large Local Cutaneous Systemic Anaphylaxis
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Severe swelling 24 hrs after a sting should be treated with: A. Antibiotics C. Antihistamine E. Epinephrine B. Prednisone D. Venom immunotherapy
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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
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Diagnosis of Insect Sting Allergy(Indications for Venom Immunotherapy) History Venom Skin Test (RAST) Natural History
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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
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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.
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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
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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
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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%)
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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
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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%
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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 %
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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
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Summary Of Sting Reactions 490 Stings in 180 Patients over 9 Yrs
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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%)
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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%)
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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 %
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Controlled Trial of Venom Immunotherapy (Hunt et al, NEJM 1978)
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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
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Dose Response of Venom Immunotherapy(Rueff et al JACI 2001;108:1027-32.)
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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%)
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Venom-IgE and Skin Test During and After Venom Immunotherapy
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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.
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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%)
Slide 27-

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%
Slide 28-

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.)