Abstract
Introduction: Venom immunotherapy (VIT) is highly effective and the treatment of choice for patients with a history of systemic anaphylactic reactions to a Hymenoptera sting. It has been assumed that VIT protocols with a rapid dose increase during the induction phase are associated with a higher frequency of systemic reactions (SR); however, study data addressing this issue are conflicting. Objective: The aim of this study was to compare the safety of 3 different Hymenoptera VIT protocols (half-day ultra-rush, 3-day rush, 3-week cluster). Methods: This retrospective 2-center study included 143 Hymenoptera venom-allergic patients, who underwent 147 VIT procedures during the years 2015–2018. Twenty cluster, 75 rush, and 52 ultra-rush VIT protocols were performed with honeybee (54 protocols) and wasp (93 protocols) venom. All documented side effects were classified into large local and SR (Ring and Messmer classification). Results: SR were observed during 11 (7.5%) VIT procedures and did not exceed severity grade II. SR occurred more frequently in cluster compared to accelerated protocols. This result was observed for both honeybee (cluster: 25%, rush: 8.7%, and ultra-rush: 15.8%) and wasp VIT (cluster: 12.5%, rush: 0%, and ultra-rush: 6.1%), though the differences were statistically significant only in the wasp VIT subgroup. Honeybee venom elicited more SR than wasp venom (14.8 and 3.2%, respectively, p = 0.01). The risk for SR did not depend on age, sex, concomitant antihypertensive medication, hypertryptasemia, or severity of the index sting reaction. Conclusion: Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster VIT protocols in our study.
References
1.
Muraro
A
, Roberts
G
, Worm
M
, Bilò
MB
, Brockow
K
, Fernández Rivas
M
, et al. Anaphylaxis: guidelines from the European academy of allergy and clinical immunology
. Allergy
. 2014 Aug
;69
(8
):1026
–45
. 2.
Bilò
MB
, Bonifazi
F
. The natural history and epidemiology of insect venom allergy: clinical implications
. Clin Exp Allergy
. 2009 Oct
;39
(10
):1467
–76
. 3.
Biló
BM
, Ruëff
F
, Mosbech
H
, Bonifazi
F
, Oude-Elberink
JN
; Hypersensitivity EIGoIV
. Diagnosis of hymenoptera venom allergy
. Allergy
. 2005 Nov
;60
(11
):1339
–49
. 4.
Turner
PJ
, Jerschow
E
, Umasunthar
T
, Lin
R
, Campbell
DE
, Boyle
RJ
. Fatal anaphylaxis: mortality rate and risk factors
. J Allergy Clin Immunol Pract
. 2017 Sep-Oct
;5
(5
):1169
–78
. 5.
Müller
U
, Helbling
A
, Berchtold
E
. Immunotherapy with honeybee venom and yellow jacket venom is different regarding efficacy and safety
. J Allergy Clin Immunol
. 1992 Feb
;89
(2
):529
–35
.6.
Ruëff
F
, Vos
B
, Oude Elberink
J
, Bender
A
, Chatelain
R
, Dugas-Breit
S
, et al. Predictors of clinical effectiveness of hymenoptera venom immunotherapy
. Clin Exp Allergy
. 2014
;44
(5
):736
–46
. 7.
Golden
DB
, Valentine
MD
, Kagey-Sobotka
A
, Lichtenstein
LM
. Regimens of hymenoptera venom immunotherapy
. Ann Intern Med
. 1980 May
;92
(5
):620
–4
.8.
Malling
HJ
, Djurup
R
, Søndergaard
I
, Weeke
B
. Clustered immunotherapy with yellow jacket venom. Evaluation of the influence of time interval on in vivo and in vitro parameters
. Allergy
. 1985 Jul
;40
(5
):373
–83
.9.
Tarhini
H
, Knani
J
, Michel
FB
, Bousquet
J
. Safety of venom immunotherapy administered by a cluster schedule
. J Allergy Clin Immunol
. 1992 Jun
;89
(6
):1198
–9
.10.
Birnbaum
J
, Ramadour
M
, Magnan
A
, Vervloet
D
. Hymenoptera ultra-rush venom immunotherapy (210 min): a safety study and risk factors
. Clin Exp Allergy
. 2003 Jan
;33
(1
):58
–64
.11.
Brehler
R
, Wolf
H
, Kütting
B
, Schnitker
J
, Luger
T
. Safety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections
. J Allergy Clin Immunol
. 2000 Jun
;105
(6 Pt 1
):1231
–5
.12.
Berchtold
E
, Maibach
R
, Müller
U
. Reduction of side effects from rush-immunotherapy with honey bee venom by pretreatment with terfenadine
. Clin Exp Allergy
. 1992 Jan
;22
(1
):59
–65
.13.
Ruëff
F
, Przybilla
B
, Biló
MB
, Müller
U
, Scheipl
F
, Aberer
W
, et al. Predictors of side effects during the buildup phase of venom immunotherapy for hymenoptera venom allergy: the importance of baseline serum tryptase
. J Allergy Clin Immunol
. 2010 Jul
;126
(1
):105
–11.e5
. 14.
Mosbech
H
, Müller
U
. Side-effects of insect venom immunotherapy: results from an EAACI multicenter study. European academy of allergology and clinical immunology
. Allergy
. 2000 Nov
;55
(11
):1005
–10
.15.
Youlten
LJ
, Atkinson
BA
, Lee
TH
. The incidence and nature of adverse reactions to injection immunotherapy in bee and wasp venom allergy
. Clin Exp Allergy
. 1995 Feb
;25
(2
):159
–65
.16.
Ring
J
, Messmer
K
. Incidence and severity of anaphylactoid reactions to colloid volume substitutes
. Lancet
. 1977 Feb 26
;1
(8009
):466
–9
.17.
Lockey
RF
, Turkeltaub
PC
, Olive
ES
, Hubbard
JM
, Baird-Warren
IA
, Bukantz
SC
. The hymenoptera venom study. III: safety of venom immunotherapy
. J Allergy Clin Immunol
. 1990 Nov
;86
(5
):775
–80
.18.
Boyle
RJ
, Elremeli
M
, Hockenhull
J
, Cherry
MG
, Bulsara
MK
, Daniels
M
, et al. Venom immunotherapy for preventing allergic reactions to insect stings
. Cochrane Database Syst Rev
. 2012 Oct 17
;10
:CD008838
. 19.
Roll
A
, Hofbauer
G
, Ballmer-Weber
BK
, Schmid-Grendelmeier
P
. Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy
. J Investig Allergol Clin Immunol
. 2006
;16
(2
):79
–85
.20.
Sturm
G
, Kränke
B
, Rudolph
C
, Aberer
W
. Rush hymenoptera venom immunotherapy: a safe and practical protocol for high-risk patients
. J Allergy Clin Immunol
. 2002 Dec
;110
(6
):928
–33
.21.
Rzany
B
, Przybilla
B
, Jarisch
R
, Aberer
W
, Dietschi
R
, Wüthrich
B
, et al. Clinical characteristics of patients with repeated systemic reactions during specific immunotherapy with hymenoptera venoms. A retrospective study
. Allergy
. 1991 May
;46
(4
):251
–4
.22.
Birnbaum
J
, Charpin
D
, Vervloet
D
. Rapid hymenoptera venom immunotherapy: comparative safety of three protocols
. Clin Exp Allergy
. 1993 Mar
;23
(3
):226
–30
.23.
Bożek
A
, Kołodziejczyk
K
. Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy
. Hum Vaccin Immunother
. 2018 Feb 1
;14
(2
):288
–91
.24.
Rosman
Y
, Confino-Cohen
R
, Goldberg
A
. Venom immunotherapy in high-risk patients: the advantage of the rush build-up protocol
. Int Arch Allergy Immunol
. 2017
;174
(1
):45
–51
. 25.
Patella
V
, Florio
G
, Giuliano
A
, Oricchio
C
, Spadaro
G
, Marone
G
, et al. Hymenoptera venom immunotherapy: tolerance and efficacy of an ultrarush protocol versus a rush and a slow conventional protocol
. J Allergy
. 2012
;2012
:192192
. 26.
Ruëff
F
, Przybilla
B
. Ultrarush immunotherapy in patients with hymenoptera venom allergy
. J Allergy Clin Immunol
. 2001 May
;107
(5
):928
–9
.27.
Roumana
A
, Pitsios
C
, Vartholomaios
S
, Kompoti
E
, Kontou-Fili
K
. The safety of initiating hymenoptera immunotherapy at 1 microg of venom extract
. J Allergy Clin Immunol
. 2009 Aug
;124
(2
):379
–81
. 28.
Sturm
GJ
, Varga
EM
, Roberts
G
, Mosbech
H
, Bilò
MB
, Akdis
CA
, et al. EAACI guidelines on allergen immunotherapy: hymenoptera venom allergy
. Allergy
. 2018 Apr
;73
(4
):744
–64
. 29.
Bernstein
JA
, Kagen
SL
, Bernstein
DI
, Bernstein
IL
. Rapid venom immunotherapy is safe for routine use in the treatment of patients with hymenoptera anaphylaxis
. Ann Allergy
. 1994 Nov
;73
(5
):423
–8
.30.
Quercia
O
, Rafanelli
S
, Puccinelli
P
, Stefanini
GF
. The safety of cluster immunotherapy with aluminium hydroxide-adsorbed honey bee venom extract
. J Investig Allergol Clin Immunol
. 2001
;11
(1
):27
–33
.31.
Čerpes
U
, Arzt-Gradwohl
L
, Schrautzer
C
, Koch
L
, Bokanovic
D
, Laipold
K
, et al. Simultaneous up-dosing of bee and vespid venom immunotherapy is safe
. Allergy
. 2020
;75
(3
):721
–3
.© 2020 S. Karger AG, Basel
2020
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
