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J Investig Allergol Clin Immunol 2019; Vol. 29(5): 378-398

© 2019 Esmon Publicidad


Usefulness of the Basophil Activation Test in the

Diagnosis of Hypersensitivity to Amiodarone

Vílchez Sánchez F


, Lluch Bernal M


, González Muñoz M



Marques Mejías MA


, Quirce S


, Cabañas Moreno R



Department of Allergy, Hospital La Paz Institute for Health

Research (IdiPaz), Madrid, Spain


Department of Immunology, Hospital La Paz, Madrid, Spain


CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 378-379

doi: 10.18176/jiaci.0404

Key words:

Amiodarone. Allergy. Immediate hypersensitivity. Basophil

activation test.

Palabras clave:

Alergia a amiodarona. Hipersensibilidad inmediata.Test

de activación de basófilos.

Amiodarone is a class III antiarrhythmic agent that

inhibits outward potassium channels. It also has class I

sodium channel–blocking effects, class II antiadrenergic

effects, and class IV calcium channel–blocking effects and is

widely prescribed owing to its efficacy in the management of

ventricular and supraventricular arrhythmia [1].

Although prolonged use of amiodarone may cause

numerous adverse effects (affecting the thyroid gland, liver,

lungs, eyes, and skin), hypersensitivity reactions to amiodarone

are rare. Moreover, few case reports include a thorough allergy

work-up (anaphylaxis confirmed with determination of mast

cell tryptase levels and skin testing [2], angioedema confirmed

with positive oral challenge results [3,4], and amiodarone-

induced hypersensitivity pneumonitis confirmed with positive

results in skin testing and basophil degranulation tests [5]).

We report the first 2 cases of immediate amiodarone

hypersensitivity reaction with a positive basophil activation

test (BAT) result. An anaphylactic reaction was recorded

in 1 of the cases.

A48-year-old man was referred to our allergy department

after experiencing an anaphylactic reaction in the operating

room. An intravenous injection of amiodarone (50 mg) to treat

atrial fibrillation was followed immediately by a decrease in

blood pressure (60/40 mmHg), oxygen desaturation (<90%),

and rash all over his body. The patient had also received

treatment with etomidate, fentanyl, and rocuronium to induce

anesthesia for cholecystectomy.

He was treated with methylprednisolone 100 mg,

hydrocortisone 100 mg, and infusion of noradrenaline at

30 mL/h. The symptoms of anaphylaxis resolved gradually.

Tryptase levels were as follows: 4.79 µg/L when the

anaphylaxis occurred, 4.6 µg/L 2 hours later, and 1.47 µg/L

on the following day.

The medical history revealed dilated cardiomyopathy,

hypothyroidism, and permanent atrial fibrillation. Nevertheless,

the patient had no history of allergy. Negative results were

recorded in the skin prick test with an anaphylaxis panel

(including latex, panallergens, and the most allergenic food)

and prick and intradermal tests with etomidate, fentanyl, and


In an attempt to clarify the underlying mechanism and the

culprit agent, BATwas performed with etomidate (1-100 µg/mL),

fentanyl (1-100 µg/mL), rocuronium (5-500 µg/mL), and

amiodarone before skin tests for safety reasons owing to the

severity of the initial reaction.

The BAT methodology is detailed elsewhere [6-8].

Briefly, 100 µL of heparinized blood was incubated with

20 µL of intravenous amiodarone (0.2, 0.1, and 0.01 μg/mL)

for 15 minutes at 37ºC. Negative and positive controls were

included by incubating the blood without the drug and with

20 μL (10 mg/mL) of anti-IgE (BD Bioscience), respectively.

Basophil activation was determined by CD63 upregulation

using flow cytometry (FACSCanto II, BD Bioscience) for

the identification and quantification of alterations in specific

activation markers on the basophil surface membrane (using

CD63/CD123/Anti-HLA-DR, BD Bioscience). At least

400 basophils were acquired. The results are expressed as the

percentage of CD63-positive basophils and the stimulation

index (SI, that is, the ratio of the percentage of activated

basophils after stimulation to the percentage of activated

basophils in negative controls). The result is considered

positive when the percentage of basophils activated after

stimulation with the drugs was 5% or more and the SI >3 [7].

BAT was positive with intravenous amiodarone (37%

activation) (Figure), with an SI of 5.11 at an amiodarone

concentration of 0.1 mg/mL (SI of 1 in the control) and 13.6


Basophil activation with intravenous amiodarone. Bars represent

the percentage of CD63-positive basophils after incubation with

amiodarone (0.2, 0.1, and 0.01 mg/mL).









Patient 1

Patient 3

Basophil Activation, %

0.2 mg/mL

0.1 mg/mL

0.01 mg/mL