key: cord-0951451-yy3kdm3d
authors: Balogun, M.; Millette, D.; Yip, V.; Chan, S.A.; Lee, P.; Gamal, N.; Hashim, N.; Phillips, D.; Walsh, M.; Trehan, P.; Hanna‐Bashara, L.; Abdullah, A.; Wernham, A.; Tso, S.
title: Phenotypic spectrum of serious cutaneous only adverse event following immunisation with COVID‐19 vaccines: a multi‐centre case series and literature review
date: 2021-11-08
journal: Clin Exp Dermatol
DOI: 10.1111/ced.15003
sha: 739b23c5f7d43bd99f88e8f41077a0dd3902c3a5
doc_id: 951451
cord_uid: yy3kdm3d

A phenotypic plethora of exclusively cutaneous adverse events following immunisation (AEFI) with COVID‐19 vaccines have been described. 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 United Kingdom launch a further booster phase of the COVID‐19 mass vaccination program due to concerns over waning immunity from initial vaccinations.

A phenotypic plethora of exclusively cutaneous adverse events following immunisation (AEFI) with COVID-19 vaccines have been described. 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 United Kingdom launch a further booster phase of the COVID-19 mass vaccination program due to concerns over waning immunity from initial vaccinations. This paper describes the phenotypic spectra of rare but serious cutaneous AEFI and explores the evidence underlying AEFI based on the literature and our multi-centre case series.

We used the World Health Organisation (WHO) definition for serious adverse event as 'any untoward medical occurrence that at any dose; results in death, life threatening, requires inpatient hospitalisation or its prolongation, or results in persistent of significant disability or incapacity.' 1 Our multi-centre case series included 21 patients between the ages of 21 and 83 with an 10 males and 11 females; with ethnicities including, 16 Caucasians; 3 South Asian; 1 Black and 1 Chinese, presenting with serious cutaneous only AEFI from February to August 2021. The phenotypic spectra of these AEFI is described in Table 1 together with supportive literature and relevant case histories. Table 1 describes affected patients' decisions (where known) on whether to receive further doses of COVID-19 vaccine and their outcome. Table 2 summarises 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 co-incidental presentation of an adverse event and temporal relation to vaccines received. Potential pathomechanisms leading to AEFI with COVID-19 vaccinations are described in figure 1. 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 immunisation programme).

We recommend clinicians carry out a personalised risk-benefit analysis, taking into consideration factors such as the risk of potential harm from contracting COVID-19 infection (risks increases 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

This article is protected by copyright. All rights reserved risks mitigation systems (described in figure 2 ), availability of antibody titre level testing services to determine adequacy of past immunisations, causality assessment of the previous AEFI (using the WHO-UMC system) 1 and patient preference. Figure 2 outlines our pragmatic but cautious consensus approach to considering potential management options for clinicians to utilise when counselling patients about future COVID-19 vaccines following a serious cutaneous AEFI. This should be in conjunction with a holistic approach with individualised risk-benefit analysis for each patient. Our recommendations will evolve as new evidence emerges over time. The options to be adopted by any clinician must be based on personalised risk-benefit analysis for individual patients with their fully informed consent. These recommendations represent the authors' current consensus viewpoint, which will change as higher level of scientific evidence, professional guidance or international consensus emerges. * denotes the clinician must ensure the vaccine offered does not contain excipients that has caused the adverse event;

% denotes mRNA vaccines such as Pfizer/BioNTech and Moderna vaccines contain similar excipients, PEG 200, and thus avoidance of vaccine from the same class if allergy to this excipient has been confirmed; @ denotes clinicians should consider referral to immunology department for consideration of intradermal prick testing prior to offering vaccination; + denotes risk mitigation systems may include a) neoadjuvant antihistamine and/or oral corticosteroid therapy; b) patients given a just-in-case prescription of antihistamine and/or oral corticosteroid therapy that they can initiate after AEFI; c) vaccination to take place at a specialist centre with resuscitation facilities; d) vaccination to take place on a weekday morning rather than towards evenings or weekends for ease of access to healthcare; e) provision of patient initiated follow ups services (such as telemedicine consultations, emergency telephone number) so that patients can be rapidly assessed. There is a lack of high-level scientific evidence examining the impact of neoadjuvant antihistamine and/or oral corticosteroid therapy on immune response following immunisation, thus, it is possible that neoadjuvant therapies may reduce or have no impact on the effectiveness of a vaccine.

This article is protected by copyright. All rights reserved Figure 2 shows the range of options considered by the authors as potentially appropriate for discussion with patients about whether to accept a further booster dose in the future. The options to be adopted by any clinician must be based on personalised risk-benefit analysis for individual patients with their fully informed consent. These recommendations represent the authors' current consensus viewpoint, which will change as higher level of scientific evidence, professional guidance or international consensus emerges. *denotes the clinician must ensure the vaccine offered does not contain excipients that has caused the adverse event; % denotes mRNA vaccines such as Pfizer/BioNTech and Moderna vaccines contain similar excipients, PEG 200, and thus avoidance of vaccine from the same class if allergy to this excipient has been confirmed; @ denotes clinicians should consider referral to immunology department for consideration of intradermal prick testing prior to offering vaccination; + denotes risk mitigation systems may include a) neoadjuvant antihistamine and/or oral corticosteroid therapy; b) patients given a just-in-case prescription of antihistamine and/or oral corticosteroid therapy that they can initiate after AEFI; c) vaccination to take place at a specialist centre with resuscitation facilities; d) vaccination to take place on a weekday morning rather than towards evenings or weekends for ease of access to healthcare; e) provision of patient initiated This article is protected by copyright. All rights reserved

follow ups services (such as telemedicine consultations, emergency telephone number) so that patients can be rapidly assessed. There is a lack of high-level scientific evidence examining the impact of neoadjuvant antihistamine and/or oral corticosteroid therapy on immune response following immunisation, thus, it is possible that neoadjuvant therapies may reduce or have no impact on the effectiveness of a vaccine.

This article is protected by copyright. All rights reserved Accepted Article

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