Anaphylactic Reaction Requiring Epinephrine in a 10-Year-Old
Patient Undergoing Peanut Challenge While on Dupilumab Therapy
Peanut is one of the most frequent elicitors of anaphylaxis in
childhood1. Reactions occur commonly in two organ
systems and often involve the lower respiratory tract or the
cardiovascular system2, requiring an intramuscular
administration of epinephrine3. Many patients with
peanut allergy also suffer from other atopic diseases, especially atopic
dermatitis (AD), which is a predisposing factor for the development of
food allergy4. In recent years, new therapeutic
modalities for AD have been developed: Dupilumab, a monoclonal antibody
against interleukin-4-receptor-α, has been approved since 2017 and can
now be used in infants with severe AD from 6 months of
age5. Beyond its therapeutic success in AD, dupilumab
is also used in the therapy of severe asthma and eosinophilic
oesophagitis6,7. Its mechanism is based on the
blockade of the interleukin-4 and interleukin-13 signalling pathways and
thereby modulating two central cytokines in the Th2-mediated immune
response5. The extent to which the expression of
interleukin-4 and interleukin-13 has an influence on IgE-mediated food
allergies is largely unexplored, but interleukin-4-expression seems to
play a role in peanut allergy8. Dupilumab has an
influence on peanut-specific and Ara h 2-specific IgE, which decrease
significantly during therapy9. However, the clinical
significance remains unclear. It can be hypothesized that patients will
no longer exhibit severe reactions to food. A clinical trial assessing
the efficacy and safety of dupilumab in children with peanut allergy as
monotherapy or as adjunct to oral immunotherapy has been completed, but
the results have not yet been published (NCT03793608 and NCT03682770,
respectively).
The case of a 10-year-old male patient reported below shows that despite
dupilumab and low peanut- and Ara h 2-specific IgE levels under this
therapy, an anaphylactic reaction requiring the administration of
epinephrine was elicited. The patient has suffered from severe AD since
infancy. He has been treated with dupilumab subcutaneously every four
weeks since May 2022, with a significant improvement of his disease.
Basic therapy is still given twice daily, and tacrolimus 0.03% is
applied topically to erythematous areas. With known sensitization to
house dust mites, birch and grass pollen, the patient also suffers from
allergic rhinoconjunctivitis and allergic asthma, which was treated with
a combination preparation of inhaled corticosteroid and long-acting
beta-agonist until May 2022. His therapy for asthma could be
discontinued under dupilumab.
Furthermore, he has a clinically relevant hen’s egg allergy, which could
be confirmed by an oral hen’s egg provocation at 5 years of age. With
known sensitization to hazelnut and peanut with a maximum value of
peanut-specific IgE of 21.4 kU/l in 2016 with a total IgE of 730 kU/l,
an elimination diet has been practiced since infancy. An emergency kit
including an adrenaline autoinjector, an antihistamine and a
corticosteroid was already available. In order to evaluate the clinical
relevance of peanut and hazelnut sensitization for the first time, the
patient was admitted in September 2023 for a double-blind,
placebo-controlled food challenge (DBPCFC) with peanut and hazelnut.
The patient’s admission status was unremarkable except for the skin
findings; the atopic dermatitis presented with dry integument, partly
crusty, slightly erythematous efflorescences on the extremities and
retroauricularly, hands lichenified. The findings resulted in a SCORAD
of 41 points. Total IgE and specific IgE against hen’s egg, peanut and
hazelnut, as well as their components on admission are shown in table 1.
The DBPCFC was performed following the PRACTALL
recommendations10. During the peanut challenge, an
objective reaction occurred after the 5th dose (300 mg peanut protein)
with generalised urticaria, repetitive cough, dyspnoea and a systolic
blood pressure drop of 18 mmHg. Adrenaline was administered
intramuscularly and clemastine and prednisolone intravenously. During
the challenge with hazelnut and placebo, all doses could be administered
without reactions, so that we assumed clinical tolerance to hazelnut but
peanut allergy with anaphylactic reaction. Before discharge, knowledge
about the use of emergency medication was checked again and the family
received detailed nutritional counselling.
Dupilumab is a highly effective biologic for the treatment of moderate
to severe atopic dermatitis and severe asthma5,6. Our
patient also showed significant improvement in eczema and asthma.
Dupilumab also lowers food-specific IgE antibodies9.
However, the clinical impact of the suppression is unclear. In our case,
despite very low specific IgE antibodies to peanut and its components,
the patient showed an anaphylactic reaction to peanut requiring
treatment with epinephrine. Even though this is only a first case report
and data from controlled studies are still pending, this case shows that
clinical relevance should in any case be checked in a controlled setting
despite reduced and low peanut IgE levels so that emergency measures can
be initiated immediately in case of provocation.
Key words: anaphylaxis, dupilumab, epinephrine, peanut allergy, food
allergy
Seda Symank, Hannes Krüger, Kirsten Beyer, MD
Department of Pediatric Respiratory Medicine, Immunology and Critical
Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
Acknowledgements: We would like to sincerely thank the patient and his
family for permission to write this report, and Susanne Schwarz and
Saskia Albroscheit for performing the DBPCFC.
Conflicts of interest: Kirsten
Beyer has received honoraria outside of this case report from Aimmune
Therapeutics, Bencard, Danone/Nutricia, DBV, Hycor, Infectopharm,
Mabylon, Meda Pharma/Mylan, Nestle, Novartis and ThermoFisher, as well
as research funding from Aimmune, ALK, Danone/Nutricia, DBV
Technologies, Hipp, Hycor, Infectopharm and Novartis.
All other authors declare no conflicts of interest.
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Table 1: Laboratory results on admission