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ACI 170411
EDITORIAL
CURRENT
OPINION Drug allergy/hypersensitivity in adults and children
Bernard Yu-Hor Thong a and Miguel Blanca b
The increasing use of computed tomography (CT)
and MRI as imaging modalities is often necessary to
delineate abnormalities in internal organs and struc-
tures. Iodinated contrast media (ICM) hypersensi-
tivity [1] is a potential adverse reaction that patients
undergoing CT scans may develop. In patients who
subsequently require repeat contrasted scans, diag-
nostic skin testing for the culprit and alternative
ICM may be considered [2], provided alternatives
are available within the region/country. Skin testing
for alternatives is not a universally agreed procedure
[3] given that not all ICM hypersensitivity reactions
are IgE-mediated. There is strong evidence that non-
immediate reactions can be T-cell-mediated [4,5].
For T-cell-mediated responses, skin test sensitivity is
not optimal either for establishing the diagnosis of
a T-cell-mediated reaction or for assessing cross-
reactivity when we look for alternatives. Where
no alternative ICM are available, MRI may be used
as an, albeit more expensive, alternative. However,
MRI may in fact not be the diagnostic imaging
modality of choice in certain clinical situations such
as bony structures. In addition, hypersensitivity
to Gadolinum-based contrast agents (GBCAs),
although infrequent, can still be potentially serious
and life-threatening. The review by Fok and Smith
(pp. 000–000) looks at the pathomechanisms, risk
factors, diagnostic modalities, and management of
patients with GBCA hypersensitivity reactions. In a
recent clinical practice guideline from Spain [6],
both ICM and GBCA hypersensitivity reactions were
reviewed, with the appropriate recommendations
and treatment algorithms suggested.
Drug provocation tests (DPTs) or drug chal-
lenges are an important diagnostic modality for
many allergists and immunologists managing adults
and children. In the last decade, many groups
including the European Network on Drug Allergy
have written clear guidelines on the utility, indica-
tions, contraindications, and when/ how to carry
out DPT [7]. DPTs are sometimes necessary when in-
vivo or in-vitro tests are not sufficient in ruling in or
ruling out the drug as a cause of the allergy. None-
theless, there are methodological issues in carrying
our DPT in adults in contrast to children. Desensi-
tization is a therapeutic modality for patients with
IgE-mediated drug allergy, where temporary toler-
ance to the culprit drug is achieved by small
1528-4050 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
incremental doses of the drug [8]. It has also been
shown to be effective in nonimmediate reactions,
although the mechanisms remain unclear [9]. This
term has also been used in the achievement of
temporary tolerance to nonallergic drug hypersen-
sitivity reactions such as NSAID hypersensitivity
reactions. ‘Provocation tests’ remain often confused
with ‘desensitization’ as protocols may look similar.
Aspirin hypersensitivity alone is estimated to
affect 0.3–2.5% of the general population. However,
the prevalence of NSAID hypersensitivity among
patients with underlying diseases such as asthma
and chronic urticaria is much higher, affecting up to
25 and 30%, respectively [10]. Phenotyping hyper-
sensitivity reactions in children are also becoming a
subject of interest as drugs such as ibuprofen, para-
cetamol and in some countries pyrazolones, and
diclofenac are widely used. In children, the main
phenotypes appear to be nonallergic NSAID hyper-
sensitivity, single NSAID-induced urticaria/angioe-
dema or anaphylaxis and single NSAID-induced
delayed reactions (SNIDR) [11–13]. Risk factors for
NSAID hypersensitivity in children and adolescents
include atopy, family history of atopy, and multiple
NSAID hypersensitivity [14]. It is not known why
some become tolerant over time. Among children
who are single NSAID reactors, the majority are
single NSAID-induced urticaria/angioedema or ana-
phylaxis and, even though to a lesser extent, SNIDR.
SNIDR are T-cell-mediated and occur much less
often in children than in adults. As viral exanthems
in childhood often mimic SNIDR especially when
NSAIDs are administered concomitantly, DPTs are
often required when the child is older to establish
NSAID tolerance [15].
Coronary artery disease (CAD) and cerebro-
vascular disease are an important cause of morbidity
and mortality among adults especially with the
rising prevalence of type 2 diabetes mellitus,
a
Department of Rheumatology, Allergy and Immunology, Tan Tock Seng
Hospital, Singapore, Singapore and bHospital Civil, Laboratorio de
Investigacion, Malaga, Spain
Correspondence to Bernard Yu-Hor Thong, Department of Rheumatol-
ogy, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tan Tock
Seng, Singapore 308433. E-mail: bernard_thong@ttsh.com.sg
Curr Opin Allergy Clin Immunol 2017, 17:000–000
DOI:10.1097/ACI.0000000000000382
www.co-allergy.com
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ACI 170411
Drug allergy
hypertension, hyperlipidemia, and obesity. Aspirin
desensitization [16] has emerged as an important
method of rendering long-term tolerance in patients
with NSAID hypersensitivity reactions, majority of
whom have nonimmunologically mediated hyper-
sensitivity. Whereas high-dose desensitization with
300–625 mg/day was previously described for refrac-
tory chronic rhinosinusitis with nasal polyposis, the
low dose 75–100 mg/day desensitization protocol is
now used extensively in patients with CAD, especi-
ally following percutaneous coronary intervention
where dual antiplatelet therapy is often needed for
3–18 months to prevent in-stent thrombosis.
Cortellini (pp. 000–000) provide an extensive
review of the topic in this journal. In the multicenter
study by the European Academy of Allergy Asthma
and Clinical Immunology’s (EAACI) Drug Interest
Group on Challenge and Desensitization Procedures
with Aspirin in CAD, the group risk-stratified
patients where a diagnostic aspirin challenge is
recommended versus those where desensitization
should directly be considered.
In recent years, there has been increasing interest
in diagnostic and management issues in paediatric
drug allergy, including antibiotic allergy, DPTs [17]
and Stevens–Johnson syndrome/toxic epidermal
necrolysis [18]. As in adults, hypersensitivity reac-
tions to chemotherapeutic agents is not uncommon
in children, although the spectrum of childhood
cancers and hence type of culprit drugs are different
from those in adults. Cernadas (pp. 000–000) dis-
cusses this topic and highlights two key points:
platinum compounds, L-asparaginase and metho-
trexate are the most common causes; and rapid
desensitization allows patients with HSRs to chemo-
therapy to be treated with first-line chemotherapy.
Acknowledgements
None.
Financial support and sponsorship
None.
2 www.co-allergy.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Conflicts of interest
The authors declare no conflicts of interest.
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