Anaphylactic Shock Due to Allergy to Macrogol 4000 Contained in SonoVue<sup>&reg</sup>

Abstract

SonoVue® (Bracco; Milan, Italy) is an ultrasound contrast medium which contains polyethylene glycol (PEG) or macrogol, an excipient responsible for severe allergic reactions, especially through the parenteral route, and widely used, especially in the health field. We present an adult patient who experienced an IgE-mediated anaphylactic shock due to macrogol contained in SonoVue®, as demonstrates the skin tests realized. The allergy study has been useful in our case because it has guided us in the preventive measures to advice to the patient, who has to avoid not only SonoVue® but also other products that contain macrogol. We consider this case of interest because it is an allergic adverse reaction to SonoVue® in which its excipient, macrogol, has acted like the allergen responsible. We have to add SonoVue® to the list of the products that contain macrogol in their composition and keep in mind the possible allergenic capacity of this excipient for suspecting its responsibility, especially in those patients with multiple drug allergy and/or reactions to products of different natures like ultrasound gels, topical products (e.g. toothpastes, antiseptics, sunscreens, etc.), plasma expanders and others.

Immediate hypersensitivity to polyethylene glycols in unrelated products: when standardization in the nomenclature of the components of drugs, cosmetics, and food becomes necessary

“…Since its development, PEG polymers held a reputation for safety, nevertheless from mild to life-threatening immediate-type hypersensitivity reactions have been reported, with clinical manifestations ranging from generalized urticaria to anaphylactic shock [2–5]. Awareness about the allergenic potential of these polymers is minimal due to the non-standardization of their nomenclature, inadequate labelling of products containing PEGs, and the lack of suspicion as the agents responsible of such reactions.…”

Immediate Hypersensitivity Reactions Caused by Drug Excipients: A Literature Review

“…Anaphylaxis with SonoVue, which contains macrogol 4000: SPTs to SonoVue and macrogols 3350 and 4000 were positive [21].…”

“…glycol/macrogol undiluted [21]; 4000 0.1% [42]; 3350 0.01 to 10% and undiluted [43,63]; 6000 undiluted [45]; 4000 0.01% [46]; 4000 0.1 to 10% [66]; 400 (Escitalopram) 20 mg/mL, 3350 (Micralax 1.18 g/mL), 4000 (Casenglicol) 254 mg/mL, 400/6000 (Stada metformin) 170 mg/mL [69]; 6000 0.01% [72]; 400, 4000 and 6000 0.01 to 100 mg/mL [76] Poly(oxyethylene)-poly 0.01% [72] (oxypropylene) glycol Polysorbate 20…”

Anaphylaxis associated with the mRNA COVID-19 vaccines: Approach to allergy investigation

“…Literature data regarding PEG-associated anaphylaxis confirmed by skin testing, oral challenge, and/or the detection of specific IgE antibodies to PEG, suggest the importance of IgE-mediated mechanisms for some hypersensitivity reactions [ [9] , [10] , [11] , [21] , [22] , [23] , [24] , [25] ]. Positive skin reactions were more frequent with high MW PEGs (>4000), independently of the PEG MW in the culprit product.…”

“…The MW and dose thresholds are not known, but it is likely that patients have an individual reactivity-threshold for both dose and MW. An IgE-related mechanism is further supported by positive basophil activation and basophil histamine release tests, and suppression of histamine release through the utilization of omalizumab (anti IgE monoclonal antibodies) and both mono- and dimeric fractions of PEGs [ [24] , [25] , [26] , [27] ]. Recently, a study was published by Zhou and colleagues [ 28 ] who developed a Dual Cytometric Bead Assay for anti-PEG IgG, IgM, and IgE; samples for PEG-associated anaphylaxis cases were positive for anti-PEG IgE, confirming the long-considered hypothesis of IgE-mediated type 1 hypersensitivity.…”