TITLE: REMISSION OF A CASE OF MULTIPLE HYMENOPTERA
STINGS-ASSOCIATED CHRONIC URTICARIA DURING VENOM IMMUNOTHERPY
AUTHORS: Dubini Marco 1, Pravettoni Valerio2, Rivolta Federica 2, Segatto
Giulia 1, Asero Riccardo 3, Nicola
Montano 1
1 – Allergy and Clinical Immunology Residency,
2 – General Medicine, Immunology and Allergology Unit, IRCCS Foundation
Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
3 – Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano,
Milan, Italy.
Corresponding Author: Marco Dubini,
marco.dubini@unimi.it,
via Pace 9 20122 Milan, Italy.
KEYWORDS : chronic urticaria; venom immunotherapy;
immunotherapy; venom allergy; Hymenoptera venom allergy.
INTRODUCTION
Chronic Urticaria (CU) is defined as the appearance of wheals,
angioedema or both for more than 6 weeks due to known or unknown causes.
Urticaria affects about 15-20% of the population once or more during a
lifetime and 0.5–1.0% suffer from CU. So far, IgE-mediated mechanisms
and the relevance of external allergens in CU have not been fully
clarified. 1
CASE REPORT
We report a case of 34-year-old man with CU that appeared after a grade
I Mueller reaction to Hymenoptera sting and remitted during venom
immunotherapy (VIT), after months of unsuccessful therapy for CU.
He had a negative history of allergic and autoimmune diseases, and
previous anaphylactic episodes, only a familiar history of intolerance
to Aspirin and a personal history of gastroesophageal reflux disease,
not requiring any therapy at that moment. He referred the first sting at
the age of 20 by an unidentified insect and experienced a normal local
reaction (smaller than diameter). Afterwards, about one year before our
examination, he was stung by a vespid, and again experienced a normal
local reaction. Two months later, about 20 minutes after receiving
multiple stings by a wasp swarm, itching hives developed all over his
body. At the local hospital intravenous methylprednisolone acetate and
intramuscular chlorphenamine were administered, with complete regression
in 24 hours. The day after, though, he manifested satellite
lymphadenitis, which regressed in 5 days with steroid cream. Three weeks
later, migrant generalized urticarial lesions started, showing
spontaneous short-lived wheals not in relation to foods or drugs,
physical agents or exercise. At our facility, routine blood tests were
normal, except for mild leucopenia, which was already known before
urticaria occurred; basophil and eosinophil counts were normal. Other
causes of CU, such as acute or chronic infections and thyroid gland
disorders, were excluded. Plasma levels of D-Dimer and acute phase
reactants were normal. Autologous serum skin test excluded the presence
of functional autoantibodies. Skin tests with common inhalant and food
allergens (, ), Apis mellifera ( , ) and Polistes
dominula () venoms were negative. Vespinae venoms tested positive, bothVespula spp (ALK -Abelló) and Vespa crabro(Anallergo), at concentration of 0.1 μg/mL. Specific IgE tested positive
for vespid venoms, respectively 5.46 kU/L for Vespula spp , 0.47
kU/L V. crabro , 0.69 kU/L P. dominula . Analysis of the
venom-specific component revealed rVes v 5 (6.17 kU/L), rVes v 1
(< 0.10 kU/L), and rPol d 5 (1.07 kU/L). Total IgE level was
132 kU/L and serum baseline tryptase 7 mcg/mL. Notably, after skin tests
with vespid venoms the patient suffered from an exacerbation of
urticaria on his hips and thighs. Baseline assessment of disease
activity with the urticaria activity score (UAS) showed a scarce control
with oral antihistamine. Then he started oral prednisone, reaching the
daily lowest effective dose of 5 mg. After three months, CU symptoms
partially improved, and he agreed to start VIT because of the impairment
of his quality of life. Venom-specific immunotherapy was started withVespula spp extract (ALK -Abelló) according to a 6-week
cluster schedule with weekly incremental doses of venom extract
subcutaneously, until a maintenance dose of 100,000 standard quality
units (SQ-U/ml) was reached. During the up-dosing phase, the patient
remained under antihistamines therapy, because urticaria was still
present. The achieved maintenance dose (100,000 SQ-U/ml) was then given
every 4–6 weeks. During the up-dosing phase and maintenance treatment
minor side-effects such as local flushing and mild itching were reported
and tolerated, and a worsening of the urticarial lesions occurred the
day after each VIT injections. Nevertheless, after few months of VIT
both pruritus and wheals improved gradually, and after ten months
urticaria suddenly remitted and antihistamines were stopped. At present
CU symptoms have not recurred and the patient continues VIT (almost 5
years so far).
DISCUSSION
The hypothesis behind urticaria progression can be explained from
several perspectives. First, vespid sting and urticaria onset could be
coincidental and CU remitted spontaneously with VIT exerting no effect
on its course. In fact, in most cases, CU is a self-limiting disorder,
persisting for 2-5 years. 2 Moreover, Hymenoptera
sting causes acute urticaria and in the literature no report of CU after
Hymenoptera sting can be found.
Alternatively, CU progression, from onset to remission, might be
associated with some specific effects of venom allergens, from sting to
VIT. Supporting this hypothesis, we observed a clear-cut association
between exposure to venom allergens and urticaria symptoms. In fact,
type I allergy is a rare cause of CU, but should be considered in
patients with intermittent symptoms. 3 Examples of CU
treated with allergen immunotherapy (AIT) can be found in literature.
Immunotherapy with sweat extract has been reported to be successful in
the treatment of cholinergic urticaria, presumably due to the induction
of tolerance to endogenous allergens. 4 Sublingual
immunotherapy with latex extract showed efficacy in patients with
latex-induced urticaria. case of seasonal urticaria due to grass
pollinosis was treated successfully with desensitization.6 House dust mite allergy has been hypothesized as a
pathogenic factor in CU, and some patients have benefited from AIT.
study reported an improvement in CU symptoms using AIT with Giardia’s
antigen preparation. 8
Moreover, besides its specific effects, AIT exerts some non-specific
effects. AIT changes basophil and mast cell homeostasis and reduces the
skin sensitivity not only to specific allergens, but also to histamine
and non-specific mast cell stimuli. Immunologic changes induced during
the course of AIT include reduced mast cell and basophil activity and
degranulation. After a few months, AIT produces a decrease in tissue
mast cell, both connective and mucosal, in innate type 2 lymphocytes and
eosinophil counts as well as in the release of their mediators.9,10 As a matter of fact, reduced immune cells
reactivity could contribute significantly to the improvement of
urticaria symptoms, even if they have not been related to venom
allergens. Therefore, in our patient VIT might have played a positive
role, increasing the sensitivity threshold to non-specific stimuli.
CONFLICT OF INTEREST
The authors certify that there is no conflict interest with any
financial organization regarding the material discussed in the
manuscript.
AUTHOR CONTRIBUTIONS
VP and FR provided the patient data regarding the allergic disease; MD
and VP wrote the manuscript; RA and GS made contributions to
interpretation of data. All authors critically read and approved the
final manuscript.
ETHICS STATEMENT
All procedures were in accordance with the ethical standards of the
responsible committee on human experimentation (institutional and
national) and with the Helsinki Declaration of 1975, as revised in 2013.
Informed written consent was obtained from the patient.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
ORCID
Marco Dubini iD http://orcid.org/0000-0003-1760-783X
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