<div>Basophil activation testing is useful for the evaluation of
life-threatening radiocontrast media anaphylaxis</div><div>Jamma Li, MBBS, MPhil (USyd)</div><div>Clinical Immunologist and Allergist</div><div>Department of Clinical Immunology and Allergy, Royal North Shore
Hospital, Reserve Road, St Leonards NSW 2065, Australia</div><div>University of Sydney, Sydney, Australia</div><div>Jamma.li@health.nsw.gov.au</div><div>Christopher Weir, PhD</div><div>University of Sydney, Sydney, Australia</div><div>Suran Fernando, MBBS, PhD</div><div>Department of Clinical Immunology and Allergy, Royal North Shore
Hospital, Reserve Road, St Leonards NSW 2065, Australia</div><div>University of Sydney, Sydney, Australia</div><div>Conflicts of interest: none</div><div>Funding source: none</div><div>Keywords: allergy, radiocontrast allergy, drug allergy, drug provocation
testing, drug challenge</div><div>Word Count: 582</div><div>Figures: 0</div><div>Tables: 2</div><div>To the Editor</div><div>The mechanism of immediate hypersensitivity reactions (IHR) to
radiocontrast media (RCM) is not fully elucidated (1, 2). Allergic
(IgE-mediated) mechanisms may account for &gt;50% of
life-threatening IHR, as detected by skin testing (ST) (3). Basophil
activation testing (BAT) may be useful for demonstrating allergic
sensitisation for severe RCM IHR as there is correlation with ST or drug
provocation testing (DPT) without the risk profile (3). ST is relatively
standardised compared to BAT. DPT is recommended only for ST-negative
RCM (3).</div><div>Our study focusses on the usefulness of BAT for evaluating
life-threatening RCM IHR and planning of safe subsequent RCM
administration. We sequentially recruited patients at a tertiary
institution in Sydney, Australia between July 1, 2019 and June 30, 2020.
All patients experienced symptoms consistent with Grade 3 or 4
anaphylaxis within 1 hour of RCM administration (4). Clinical
characteristics and mast cell tryptase levels were collected. Testing
was performed to RCMs available in our institution; iodixanol
(Visipaque, GE Healthcare Australia Pty Ltd, Sydney, Australia), iohexol
(Omnipaque, GE Healthcare Australia Pty Ltd), iopromide (Ultravist,
Bayer Australia Ltd, Sydney, Australia), meglumine iotroxate
(Biliscopin, Bayer Australia Ltd), and sodium diatrizoate and meglumine
amidotrizoate (Urografin, Bayer Australia Ltd). ST was performed to
EAACI guidelines (1). BAT was performed in line with our protocol (5) at
1:10000-1:10 dilutions. Results were expressed as percentage
upregulation above the negative control, and stimulation index (SI) for
CD63 and CD203c. If ST to Urografin was negative, the patient proceeded
to single-dose oral sodium diatrizoate 100mg and meglumine amidotrizoate
660mg DPT (Gastrografin 100mL, Bayer Australia Ltd) with no
premedication. Patients then proceeded to routine RCM administration for
contrast radiography, or 0.5ml/kg single-dose intravenous RCM challenge
with alternative suitable ST-negative RCM/s with no premedication.</div><div>Patient characteristics are shown in Table 1. Ten study patients were
enrolled, the culprit RCMs were iohexol (n=5), iopromide (n=2), and
amidotrizoate (n=1). Two patients did not have RCM anaphylaxis and
reserved as controls (RCM extravasation, and vasovagal syncope).
Findings are shown in Table 2. Six (75%) had significant change in mast
cell tryptase. Five (62.5%) had positive ST to the culprit RCM, all had
significant tryptase change. Using standard cut-offs for BAT of 5% and
10% upregulation for CD63 and CD203c respectively, and a SI
&gt;2.0 (5,6), there were 4 false positives to amidotrizoate,
and 1 to iohexol. Adjusting cut-offs to 10% and 15% reduced false
positives to 2 for amidotrizoate, and 0 for iohexol. BAT was positive to
the culprit RCM in 5 patients (62.5%), including 2 ST-negative
patients. Six of 8 (75%) were only positive to the culprit drug on ST
and BAT. Both control patients had negative ST and BAT. There was
significant lack of agreement between ST and BAT (P&lt;0.05)
(McNemar’s test).</div><div>Our case series centres on patients with life-threatening RCM IHR. Seven
of 8 (87.5%) had a positive ST or BAT suggesting that most Grade 3 or 4
anaphylaxis has an allergic mechanism. Also, the patient with negative
ST and BAT was evaluated remotely (1706 days from reaction). In this
study, BAT was a useful adjunct to ST as it identified an extra 2
patients with allergic IHR. BAT was not useful for amidotrizoate with a
significant false positive rate (29%).</div><div>Therefore, most life-threatening RCM IHRs may have an allergic
mechanism. This is significant, as in allergic IHR there may be less
cross-reactivity with other RCM. BAT may be a useful adjunct to ST to
demonstrate this allergic mechanism. Further study can optimise
performance characteristics of BAT, especially for amidotrizoate.</div><div>Contribution: JL, CW performed the experiments; J.L, CW, SF analysed the
results and constructed the tables; JL, CW and SF developed and designed
the research; JL wrote the paper.</div><div>1. Torres M, Trautmann A, Bohm I, et al. Practice parameters for
diagnosing and managing iodinated contrast media hypersensitivity.
Allergy 2021;76:1325-39.</div><div>2. Brockow K, Romano A, Aberer W, et al. Skin testing in patients with
hypersensitivity reactions to iodinated contrast media – a European
multicenter study. Allergy. 2009;64:234-41.</div><div>3. Clement O, Dewachter P, Mouton-Faivre C, et al. Immediate
Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study.
EClinicalMedicine 2018;1:51-61.</div><div>4. Ring J, Messmer K. Incidence and severity of anaphylactoid reactions
to colloid volume substitutes. Lancet 1977;1:466-9.</div><div>5. Li J, Best O, Rose M, Green S, Fulton R, Fernando S. Integrating
basophil activation tests into evaluation of perioperative anaphylaxis
to neuromuscular blocking agents. Br J Anaesth. 2019;123:e135-43.</div><div>6. Pinnobphun P, Buranapraditkun S, Kampitak T, Hirankarn N,
Klaewsongkram J. The diagnostic value of basophil activation test in
patients with an immediate hypersensitivity reaction to radiocontrast
media. Ann Allergy Asthma Immunol. 2011;106:387-93.</div><div>Table 1. Patient characteristics</div>