Cutaneous Adverse Reaction After COVID-19 Vaccination

As coronavirus disease 2019 (COVID-19) spreads worldwide, various vaccines are being developed against the SARS-CoV-2 virus. These vaccines had to be developed in a relatively short period;therefore, they had to be manufactured using a method different from that of conventional vaccines. In addition, many people were vaccinated in a short period, and various side effects related to vaccination have been reported. In this article, we describe the injection site reactions and some unique skin reactions associated with COVID-19 vaccination, such as drug eruptions, bullous lesions, and foreign body reactions, with their possible causes. Copyright © 2022 by The Korean Society for Medical Mycology. All right reserved.

Histopathological Patterns of Cutaneous Adverse Reaction to Anti-SARS-CoV-2 Vaccines: The Integrative Role of Skin Biopsy.

The advent of vaccines represented a milestone to allow the slowing down and then containing of the exponential increase in ongoing infections and deaths of COVID-19. Since the first months of the vaccination campaign in various continents, there has been a certain number of reports of adverse events, including skin reactions. We conducted a systematic review, searching on PubMed, Web of Science, Scopus, and Cochrane Library for the words: COVID vaccine, dermatopathology, skin, eruptions, rash, cutaneous, BNT162b2 (Pfizer-BioNTech), ChAdOX1 (AstraZeneca), and mRNA-1273 (Moderna). A total of 28 records were initially identified in the literature search of which two were duplicates. After screening for eligibility and inclusion criteria, 18 publications were ultimately included. Various clinical cutaneous manifestations and histopathological patterns following vaccination have been described in literature. The most frequent clinical-pathological presentations were erythematous maculo-papular eruptions in different way of distribution with histopathological pictures mostly represented by interface changes and mixed peri-vascular and peri-adnexal cell infiltrate. Other presentations included new onset of pemphigoid bullous disease (n = 15), delayed T-cell-mediated hypersensitivity reaction (injection site reactions) (n = 10), purpuric skin rash (n = 13), mostly localized on the legs bilaterally and symmetrically with histological pictures characterized by extravasation of erythrocytes in the superficial and middle dermis, and other types of reactions. New studies with large case series and further literature reviews are needed to improve the clinical management of patients and optimize the timeline for carrying out histological biopsy for confirmatory, supportive, and differential diagnosis purposes.

Global prevalence and clinical manifestations of cutaneous adverse reactions following COVID-19 vaccination: A systematic review and meta-analysis.

Although vaccination is widely accepted as an effective method of preventing and controlling the COVID-19 pandemic, many people are concerned about possible cutaneous side-effects, which can delay or prevent them from being vaccinated. The objectives of this systematic review were to assess the global prevalence and clinical manifestations of cutaneous adverse reactions following COVID-19 vaccination. PubMed and Scopus databases were searched for articles published from 1 January 2019 to 31 December 2021, and reference lists for each selected article were screened. Case reports, case series, observational studies and randomized controlled trials that provided information on cutaneous adverse reactions following COVID-19 vaccines were included. A total of 300 studies were included in a systematic review of which 32 studies with 946 366 participants were included in the meta-analysis. The pooled prevalence of cutaneous manifestations following COVID-19 vaccination was 3.8% (95% CI, 2.7%-5.3%). COVID-19 vaccines based on the mRNA platform had a higher prevalence than other platforms at 6.9% (95% CI, 3.8%-12.3%). Various cutaneous manifestations have been reported from injection site reactions, which were the most common (72.16%) to uncommon adverse reactions such as delayed inflammatory reactions to tissue filler (0.07%) and flares of pre-existing dermatoses (0.07%). Severe cutaneous reactions such as anaphylaxis have also been reported, but in rare cases (0.05%). In conclusion, cutaneous adverse reactions are common, especially in those receiving mRNA vaccines. Most reactions are mild and are not contraindications to subsequent vaccination except for anaphylaxis, which rarely occurs. COVID-19 vaccination may also be associated with flares of pre-existing dermatoses and delayed inflammatory reactions to tissue filler. Patients with a history of allergies, pre-existing skin conditions or scheduled for filler injections should receive additional precounselling and monitoring. A better understanding of potential side-effects may strengthen public confidence in those wary of new vaccine technologies.

Histopathological analysis of skin reactions after coronavirus disease 2019 vaccination: Increment in number of infiltrated plasmacytoid dendritic cell.

Skin disorders are frequent adverse events after coronavirus disease 2019 (COVID-19) vaccination. However, the pathogenesis of these disorders is not fully understood. Here, we report a case series of cutaneous adverse events following COVID-19 vaccination, and the results of our investigation reveal the underlying mechanism. Case 1: a 47-year-old female developed a wheal, confined to the COVID-19 vaccination site, 2 days after her first injection. She was treated with topical steroids and oral antihistamines. Case 2: a 51-year-old female showed generalized petechial erythema accompanied by fever, genital bleeding, thrombocytopenia, liver dysfunction, and disseminated intravascular coagulation, 2 days after her second injection. She was diagnosed with vaccine-induced macrophage activation syndrome and treated with anti-inflammatory therapy. Immunohistological analysis of the skin eruption, in both these cases, showed infiltration of CD123+ BDCA2+ plasmacytoid dendritic cells (p-DC). Despite the distinctive clinical features in these two cases, this finding suggests that p-DC might be involved in different cutaneous adverse events after COVID-19 vaccination.

Cutaneous adverse reactions to coronavirus vaccines: A Saudi nationwide study.

The coronavirus vaccine was developed to help overcome the COVID-19 crisis. This study aimed to identify the cutaneous side effects secondary to Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines in the general population of Saudi Arabia and to list the risk factors for the development of cutaneous side effects. This cross-sectional study was conducted in 2021, self-administered surveys were distributed electronically through social media, and telephonic interviews were conducted with a sample size of 1000 participants. Data analysis was performed using Statistical Package for the Social Sciences. A total of 1021 patients (229 male and 722 female) aged 12 years or older were included. While 833 participants were medically free, 188 had chronic illnesses. While 802 participants were not taking any medications, 219 were taking medications regularly. Oxford-Astra Zeneca and Pfizer BioNTech vaccines were administered to 319 and 702 participants, respectively. One-hundred and twenty-five participants previously had COVID-19 infection and 407 were exposed to a PCR positive case of COVID. Six hundred and fifty-nine patients (64.5%) reported experiencing injection site reactions: 606 (59.4%) had injection site pain, 168 (16.5%) had injection site swelling, and 107 (10.5%) had injection site redness. Only 51 patients (5%) experienced cutaneous side effects after injection. A significant association was found between chronic illnesses and cutaneous side effects post-vaccine (9% vs. 4.1%; p value = 0.005). Patients on medications showed a higher rate of symptoms (8.2% vs. 4.1%; p value = 0.005). Age, gender, vaccine types, and history of COVID-19 infection were not significantly associated with cutaneous side effects post-vaccine.

Cutaneous reactions to COVID-19 vaccines: A review.

Background: The increasing number of reports on cutaneous reactions following COVID-19 vaccination has led to growing concerns among certain groups. Objective: We reviewed the published reports of cutaneous lesions after COVID-19 vaccination. Methods: We conducted a literature search for original and review articles published between January 1, 2020, and September 27, 2021. Results: Eleven cutaneous reactions associated with COVID-19 vaccines were determined; the most prevalent reactions were local injection site reactions, delayed local reactions, urticaria, angioedema, and morbilliform eruptions. There were more reports on skin reactions following the administration of messenger RNA-based vaccines than on those following the administration of adenoviral vector or inactivated whole-virus vaccines, in part, due to their higher administration rate. Most reported skin reactions occurred after the first vaccine dose. Limitations: A reporting bias could not be excluded, and skin biopsy results were not available for most included individuals. Moreover, given that the included trials focused on vaccine efficacy, there was a lack of details concerning cutaneous reactions and participant information. Conclusion: Not all cutaneous reactions observed after COVID-19 vaccination are hypersensitivity reactions. Different cutaneous reactions may reflect underlying immune responses to the vaccines. A large majority of COVID-19 vaccination reactions were mild and self-limiting, and people should be encouraged to complete their vaccination regimen.

Critical Review of Gaps in the Diagnosis and Management of Drug-Induced Liver Injury Associated with Severe Cutaneous Adverse Reactions.

Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI associated with SCARs. Interestingly, alleles HLA-B*58:01 and HLA-A*31:01 are associated with both adverse reactions. However, there is no consensus about the criteria used for the characterization of liver injury in this context, and the different thresholds for DILI definition make it difficult to gain insight into this complex disorder. Moreover, current limitations when evaluating causality in patients with DILI associated with SCARs are related to the plethora of causality assessment methods and the lack of consensual complementary tools. Finally, the management of this condition encompasses the treatment of liver and skin injury. Although the use of immunomodulant agents is accepted for SCARs, their role in treating liver injury remains controversial. Further randomized clinical trials are needed to test their efficacy and safety to address this complex entity. Therefore, this review aims to identify the current gaps in the definition, diagnosis, prognosis, and management of DILI associated with SCARs, proposing different strategies to fill in these gaps.

A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?

BACKGROUND: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most Serious Cutaneous Adverse Reaction (SCAR) often with a fatal outcome. Coronavirus Disease (COVID-19) is caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV2) and is an emergent pandemic for which no cure exist at the moment. Several drugs have been tried often with scant clinical evidence and safety. CASE PRESENTATION: Here we report the case of 78-years-old woman with cardiometabolic syndrome and COVID-19. A multidrug regimen including others hydroxychloroquine, antibiotics, dexamethasone and paracetamol, low-molecular-weight-heparin and potassium canrenoate was started. After almost 3 weeks, the patient started to display a violaceous rash initially involving the flexural folds atypical targetoid lesions and showing a very fast extension, blister formation and skin detachments of approximately 70% of the total body surface area and mucous membranes involvement consistent with toxic epidermal necrolysis (TEN). The ALDEN algorithm was calculated inserting all drugs given to the patient in the 28 days preceding the onset of the skin manifestations. The highest score retrieved was for hydroxychloroquine. Other less suspicious drugs were piperacillin/tazobactam, ceftriaxone and levofloxacin. CONCLUSIONS: To our knowledge, this is the first case of TEN in a patient suffering from COVID-19 probably associated with hydroxychloroquine. Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.