Phenotypic spectrum of serious cutaneous-only adverse event following immunization with COVID-19 vaccines: a multicentre case series and literature review.

Dear Editor,

A phenotypic range of exclusively cutaneous adverse events following immunization (AEFI) with COVID‐19 vaccines has been reported. Currently, there is no formal consensus on advice given to affected individuals pertaining to their subsequent COVID‐19 vaccines, which is increasingly pertinent as countries such as the UK launch a further booster phase of the COVID‐19 mass vaccination programme, owing to concerns over waning immunity from initial vaccinations. We describe the phenotypic spectrum of rare but serious cutaneous AEFI and explore the evidence underlying AEFI, based on the literature and our multicentre case series. We used the World Health Organization (WHO) definition for serious adverse event as ‘any untoward medical occurrence that at any dose: results in death, is life‐threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity’.

This multicentre case series (Table S1, , , , , , , , , , , , , ) comprised 21 patients (10 men, 11 women; aged 21–83 years) with ethnicities reported as White British (n = 16), South Asian (n = 3), Black (n = 1) and Chinese (n = 1), who presented with serious cutaneous‐only AEFI during the period February–August 2021.

The phenotypic spectrum of these AEFI is described in Table S2 together with supportive literature and relevant case histories. Table S1 describes the affected patients' decisions (where known) on whether to receive further doses of COVID‐19 vaccine and their outcome. Table S3 summarizes the literature on the estimated prevalence of cutaneous AEFI from COVID‐19 vaccination (of all severities) and the outcomes when subsequent COVID‐19 vaccination has been accepted.

A key attributing factor to the lack of global consensus regarding clinical guidance on subsequent dose of COVID‐19 vaccine following serious cutaneous AEFI from COVID‐19 vaccination is the difficulty in distinguishing between causation and coincidental presentation of an adverse event and the temporal relation to any vaccines received. Potential pathomechanisms leading to AEFI with COVID‐19 vaccinations are described in Table S4.

Serious cutaneous AEFI remain exceedingly rare as demonstrated from supporting literature. However, we could not identify high‐level scientific evidence (i.e. Level 1–3) to guide clinicians and patients on how to make informed decisions on whether to accept their subsequent dose (if eligible as part of a local immunization programme). We recommend that clinicians should carry out a personalized risk–benefit analysis, taking into consideration factors such as the risk of potential harm from contracting COVID‐19 infection (risks increase with age and certain types of comorbidities), efficacy and risk profile of locally available COVID‐19 vaccines (risk profile may differ between vaccines and patient groups), local availability of risk mitigation systems (described in Table S5), availability of antibody titre level testing services to determine adequacy of past immunizations, causality assessment of the previous AEFI (using the WHO–Uppsala Monitoring System) and patient preference. Table S5 outlines our pragmatic but cautious consensus approach to considering potential management options for clinicians to use when counselling patients about future COVID‐19 vaccines following a serious cutaneous AEFI. This should be in conjunction with a holistic approach with individualized risk–benefit analysis for each patient. Our recommendations will evolve as new evidence emerges over time.

Table S1. Multicentre case series (n = 21).

Table S2. Phenotypic spectra of serious cutaneous‐only adverse events following immunization with COVID‐19 vaccines.

Table S3. Summary of the literature on the prevalence of cutaneous adverse events following immunization with COVID‐19 vaccination, and the outcome of those who accepted a subsequent dose of the vaccine.

Table S4. Possible pathomechanisms underlying cutaneous adverse events following immunization with COVID‐19 vaccination.

Table S5. The range of options we consider as potentially appropriate for discussion with patients about whether to accept a further booster dose in the future.

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