key: cord-0984359-8c26nrdg
authors: Leong, Paul; Al-Harrasi, Mohammed; Carr, Beau; Leahy, Elizabeth; Bardin, Phillip G.; Barnes, Sara
title: Vocal cord dysfunction/inducible laryngeal obstruction(s) mimicking anaphylaxis during SARS-CoV-2 (coronavirus) vaccination
date: 2022-03-05
journal: J Allergy Clin Immunol Pract
DOI: 10.1016/j.jaip.2022.02.025
sha: b5211b90e947d59d15b57107caaf9d7da9ccb045
doc_id: 984359
cord_uid: 8c26nrdg

nan

concern for anaphylaxis but these symptoms are also characteristic of vocal cord 21 dysfunction/inducible laryngeal obstruction(s). We report the first case series of VCD/ILO occurring in 22 the context of SARS-CoV-2 (coronavirus) vaccination. 23

The Brighton Collaboration anaphylaxis definition includes symptoms of respiratory distress, 26 tachypnoea, hoarse voice, stridor, and a sensation of throat closure (1) . These features significantly 27 overlap with manifestations of vocal cord dysfunction/inducible laryngeal obstruction(s) (VCD/ILO), a 28 disorder characterised by intermittent laryngeal obstruction(2). We have recently proposedcardinal 29 VCD/ILO phenotypes, including 'incident-associated VCD/ILO' which may be linked to vaccination(3). 30

This Clinical Communication details the first case series of SARS-CoV-2 (coronavirus) vaccination-31 related VCD/ILO in ten consecutive individuals who were initially labelled as having only anaphylaxis. 32

The study received ethics authorisation from Monash Health (QA/80480/MonH-2021-289442). 33

In the local health-care setting individuals receive coronavirus vaccination in primary care, hospital 34 clinics or vaccine hubs. Following a provisional diagnosis of anaphylaxis to SARS-CoV-2 vaccine, 35

individuals are referred to a subspecialist vaccine reaction assessment service located at a tertiary 36 care hospital (Monash Health). After initial assessment by a specialist allergist/immunologist, a second 37 dose of the same brand of SARS-CoV-2 vaccine may be administered under supervision in the 38 allergy/immunology clinic. 39

During March 2021 to December 2021, 149 people were assessed in the vaccine reaction clinic. Details 40 of ten consecutive symptomatic individuals who generated a strong clinical suspicion for VCD/ILO are 41 reported here. Median age was 33 years (interquartile range (IQR) 31-54) and all were female. 42

Notably, eight of the ten patients reported a history of "anaphylaxis" (penicillin, foods, and insect 43 venoms), with six having been treated with epinephrine prior to receiving SARS-CoV-2 vaccination. A 44 history of asthma was present in six patients and four had a history of anxiety or depression. 45

Seven of the ten (7/10) reactions after a first dose of vaccine occurred following Pfizer-BioNTech 19/AZD1222) vaccine. Symptoms included dyspnoea in all cases, a sensation of throat closure (8/10), 48 wheeze were present in 2/10 patients. In 6/10 patients, symptoms began within 30 minutes of the 50 dose. All patients presented to an Emergency Department (ED), and a provisional diagnosis of 51 anaphylaxis was made by the treating physicians in all cases. 52

One individual had Brighton diagnostic certainty level 1 anaphylaxis with rapid onset of facial and 53 upper airway angioedema, hypotension, and elevated tryptase (22 micrograms/litre, upper limit of 54 normal 11.4 micrograms/litre). This patient was admitted to hospital, respiratory syncytial virus was 55 detected and subsequent inpatient laryngoscopy performed in the intensive care unit for non-56 resolving stridor demonstrated obvious inspiratory vocal cord adduction indicating VCD/ILO. In the 57 other patients laryngoscopy was not performed and symptomatic treatment was administered leading 58 to symptom resolution. 59

Following specialist allergist assessment, nine of the ten individuals, including the patient with 60 anaphylaxis, received a second dose of the same vaccine that caused their reaction in a monitored 61 hospital setting. Symptoms recurred in 8/9 patients who received the second vaccination and clinical 62 findings mirrored the initial reactions. All occurred within 30 minutes of vaccine administration with a 63 sensation of throat closure in 8/9, tachypnoea in 7/9, stridor in 2/9, wheeze in 2/9 and hoarse voice 64 in 1/9 patients. One patient fulfilled a Brighton diagnostic certainty level 3 case definition of and was administered another vaccine (Moderna mRNA-1273).In summary, in ten individuals initially 74 diagnosed with anaphylaxis after SARS-CoV-2 vaccination, the initial diagnosis may have been correct 75 in a small minority with only two cases meeting Brighton criteria for anaphylaxis. There are important caveats. Definitive VCD/ILO was only directly visualised in five patients but 93 symptoms in the other five cases were typical of VCD/ILO. This is not unexpected since VCD/ILO is reassurance, breathing strategies such as panting to facilitate glottic aperture opening, continuous 98 positive airway pressure, and benzodiazepines(4). In the longer term, speech-behavioral therapy is 99 designed to regain laryngeal control. 100

In conclusion, clinicians should be aware that VCD/ILO can mimic anaphylaxis, and that the two 101 conditions may overlap. Differentiation of anaphylaxis from VCD/ILO is critical in the setting of 102 vaccination, especially during the ongoing pandemic since diagnosing an individual with vaccine-103 related anaphylaxis has critical implications for future vaccination and their ability to benefit from this 104 important treatment. 105

Anaphylaxis: 108 Case definition and guidelines for data collection, analysis, and presentation of immunization 109 safety data. Vaccine

Diagnostic Criteria for the Classification of Vocal Cord Dysfunction

Middle airway obstruction: phenotyping vocal 113 cord dysfunction/inducible laryngeal obstruction(s) to progress diagnosis and management

Laryngeal Dysfunction: Assessment and Management 116 for the Clinician

Inducible laryngeal 118 obstruction: an official joint European Respiratory Society and European Laryngological Society 119 statement