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\begin{document}

\title{Fast gadolinium-based contrast agent challenge test searching for an
alternative contrast media}



\author[1]{Francisco Vega}%
\author[1]{Azahara Lopez-Raigada}%
\author[1]{Maria Victoria Mugica}%
\author[1]{Carlos Blanco}%
\affil[1]{Hospital Universitario de la Princesa}%


\vspace{-1em}



  
  \date{March 13, 2025}


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\sloppy


\textbf{Fast gadolinium-based contrast agent challenge test searching
for an alternative contrast media}

To the Editor,

Gadolinium-based contrast agents (GBCA) are used in contrast-enhanced
magnetic resonance imaging. Hypersensitivity reactions (HSR) to GBCA are
scarce, with an incidence of 0.07\% and a recurrence rate of 30\%, being
urticaria the most common presentation (91\%), with 0.52/10000 of severe
reactions reported\textsuperscript{1}. Recommendation of an alternative
GBCA without checking tolerance is dangerous, due to high
cross-reactivity between them\textsuperscript{2}. Moreover,
premedication is not enough\textsuperscript{1}, showing an overall rate
of breakthrough reactions of 39\%\textsuperscript{3}.

Allergy studies to achieve a safe recommendation in HSR to GBCA have
been performed. Negative predictive value of skin-tests to GBCA has been
estimated in 84\%\textsuperscript{1}. Therefore, more than 10\% of
patients could react using an alternative negative skin-tested GBCA, and
thus, good tolerance to GBCA should be confirmed through a drug
challenge-test (DCT)\textsuperscript{4}. These tests are usually
performed at graded administrations, and with observation periods
between doses\textsuperscript{1,5}. However, since GBCA is usually given
as a bolus during radiologic exams, DCT at slow rates cannot be
extrapolated to further administrations. Trying to avoid this
limitation, we study the tolerance of an alternative GBCA, by means of a
fast DCT, approaching the infusion rates used in clinical practice.

In accordance with the safety warnings to avoid linear GBCA, we have
only used the macrocyclic drugs gadobutrol (Gb) and gadoteric acid (Ga).
After obtaining signed informed consent from the patients, skin
pricktests (SPT) with undiluted macrocyclic GBCA commercial solutions
were done. When SPT at 20 min yielded negative results, intradermal
tests (IDT) with 1:10 dilutions were performed, with subsequent readings
at both 20 min and 24 hours.

A fast DCT with negative skin-tested GBCA was then performed, following
our methodology to study HSR to iodinated contrast media, previously
described elsewhere\textsuperscript{6}. Doses were 0.2 mg/kg for Ga and
0.1 mg/kg for Gb. First, one third of the total dose of Ga was
administered at a rate of 120 cc/hour and, immediately after, the
remaining 2/3 at 80 cc/hour. In case of Gb, infusion rates were half
those of Ga, i.e., 1/3 at 60 cc/hour and 2/3 at 40 cc/hour. Total
infusion time was 8 minutes for both of them. Well-tolerated GBCA was
finally recommended for subsequent examinations, and its tolerance was
recorded if it was used later.

Study results of sixteen patients that were enrolled are summarized in
Table 1. They were 12 women and 4 men, with median age of 45.5 years
(range 28-73). Adverse reactions to GBCA were immediate in 13 patients
(12 urticaria or exanthema, and 1 anaphylaxis), and delayed exanthema in
the remaining 3. Gb was involved in 11 reactions, and unknown GBCA in
the other 5. Most of the patients (14/16) had been previously exposed to
GBCA.

Median delay to perform the allergy study was 10 months (range 2-72
months). All skin-tests were negative, except in one patient who showed
an immediate positive SPT to Gb, which had been the GBCA involved in the
adverse reaction. In our study, we have estimated a negative predictive
value of skintests to GBCA of 89\%. DCT were negative in 14 patients (12
with Ga, and 2 with Gb). Finally, 15 out of 16 patients had an
alternative GBCA, avoiding the use of premedication. In fact, tolerance
has been confirmed in 7 of them in subsequent examinations.

Safety of our protocol has been confirmed because our 2 positive DCT
showed only mild reactions (delayed exanthema and immediate urticarial,
both with Ga), and also by including a patient with previous anaphylaxis
to GBCA.

Here we present a prospective protocol to identify a safe alternative
GBCA, including DCT at high infusion rates. Further studies will be
necessary on this item/to check this.

\textbf{CONCLUSION}

Fast drug challenge-tests, approaching usual administration of contrast
media in radiological explorations, seems to be both effective and safe
in allergy studies of hypersensitivity reactions to gadolinium-based
contrast agents\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
\begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Patient}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Sex}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Medical History}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{GBCA}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{HSR}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Previous Contact}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Study delay (months)}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{ST}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{DCT}\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
\textbf{Subsequent Tolerance}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{1}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
45\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{2}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
66\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{3}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
48\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Digestive Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Exanthema (DY)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{4}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
66\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Exanthema (DY)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{5}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
38\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{6}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
50\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{7}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
47\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
60\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{8}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
40\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Digestive Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
11\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{9}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
44\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
\textbf{10}\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
35\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
Exanthema (DY)\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
\textbf{Ga} \textbf{POS (DY}) Gb NEG\strut
\end{minipage} & \begin{minipage}[t]{0.09\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{11}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
53\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Bone Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
20\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Gb POS}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{12}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
28\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Anaphylaxis\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
40\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{13}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
46\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Hematological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{14}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
41\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
22\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{15}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
44\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Gb\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Ga} \textbf{POS (IM)}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{16}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
73\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Neurological Ds\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Urticaria (IM)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Ga NEG\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Nk\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{REFERENCES}

1. Seta V, Gaouar H, Badaoui A, Franc\selectlanguage{ngerman}ès C, Barbaud A, Soria A. Low-dose
provocation and skin tests in patients with hypersensitivity to
gadolinium-based contrast agents. Clin Exp Allergy 2019;49:724-728.

2. Mankouri F, Gauthier A, Srisuwatchari W, et al. Hypersensitivity to
gadolinium-based contrast agents: A single-center retrospective analysis
over 7 years. J Allergy Clin Immunol Pract 2021;9:1746-9.e2

3. Walker DT, Davenport MS, McGrath TA, et al. Breakthrough
hypersensitivity reactions to gadolinium-based contrast agents and
strategies to decrease subsequent reaction rates: A systematic review
and meta-analysis. Radiology 2020;296(2):312-321.

4. Gallardo-Higueras A, Moreno EM, Muñoz-Bellido FJ, et al. Patterns of
cross-reactivity in patients with immediate hypersensitivity reactions
to gadobutrol. J Investig Allergol Clin Immunol 2021;31:504-506

5. Rodriguez-Nava G, Kesler AM, Carrillo-Martin I, Gonzalez-Estrada A.
Gadolinium-induced anaphylaxis with positive skin test results. Ann
Allergy Asthma Immunol. 2019;122:654-655

6. Vega F, Múgica MV, Bazire R, et al. Adverse reactions to iodinated
contrast media: Safety of a study protocol that includes fast full-dose
parenteral challenge tests searching for an alternative contrast media.
Clin Exp Allergy 2020;50:271-274.

\textbf{List of authors}

Francisco Vega, MD, Azahara Lopez-Raigada, MD, M. Victoria Múgica, MD
PhD, Carlos Blanco, MD PhD

\textbf{Institutional affiliation:}

Department of Allergy, Hospital Universitario de la Princesa. Instituto
de Investigacion Sanitaria Princesa (IIS-Princesa). Madrid. Spain

\textbf{Authors' contribution}

Francisco Vega conducted the prospective study, participated in all
stages of the study and wrote the first draft of the article.

Azahara Lopez-Raigada y M. Victoria Mugica collaborated to perform
skin-tests and drug challenge-tests.

Carlos Blanco coordinated the whole study

All authors have been involved in drafting the manuscript or revising it
critically for important intellectual content, and also, they have given
final approval of the version to be published.

\textbf{Funding}

The authors have no funding relationships to declare.

\textbf{Conflict of interest}

The authors declare that they have no conflicts of interest

\textbf{Ethical approval}

This protocol was approved by the Committee of Research and Ethics
``Comité de Ética de La Investigación con Medicamentos del Hospital
Universitario de la Princesa'' with the approval number 3396.

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