Toxic Epidermal Necrolysis Post COVID-19 Vaccination – First Reported Case

Authors: Mohamad BakirHanan AlmeshalRifah AlturkiSulaiman ObaidAreej Almazroo

Published: August 16, 2021


Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of acute, delayed-type hypersensitivity reactions that affect the skin and the mucous membranes. Medications are the culprit cause of these disorders in addition to infections and in very rare instances vaccinations. We report a case of TEN in a 49-year-old woman with no previous medical history. The disorder developed one week after receiving the first dose of COVID-19 vaccine with no other identifiable causes. The patient received two doses of tumor necrosis factor-alpha inhibitor (etanercept) and she stopped developing new lesions after two days of the initial dose; complete healing was observed after 22 days and no side effects were observed in our patient. This case demonstrates an extremely rare complication to the COVID-19 vaccine. The benefits of receiving the COVID-19 outweigh the potential risk. 


Toxic epidermal necrolysis (TEN) is a rare immune-mediated, life-threatening skin reaction characterized by blistering and extensive epidermal detachment of more than 30% of body surface area. The incidence is estimated to be 0.4 to 1.9 cases per million population per year worldwide and an estimated mortality rate of 25% to 35% [1, 2]. Medication is usually the cause of TEN (e.g., certain antibiotics and antiepileptics) [3]. Vaccination-induced Stevens-Johnson syndrome (SJS)/TEN is rare, with less than twenty reported cases in the published literature, with the measles vaccine being reported to cause both SJS and TEN, varicella, smallpox, anthrax, tetanus, and influenza vaccines were reported to cause SJS alone, and MMR (measles, mumps, rubella), hantavirus and meningococcal B vaccines were reported to cause TEN [4, 5, 6]. The patient usually develops a fever and other flu-like symptoms one to three weeks after being exposed to medication followed by painful erythematous to purpuric skin lesions that tend to coalescence. Next erosions and vesiculobullous lesions and epidermal detachment over wide body surface area develop. Mucous membranes are also involved, and the patient develops oral ulcers, vaginal ulcers, and possible acute conjunctivitis [7]. In this paper, we report a case of TEN following the administration of the Pfizer COVID-19 vaccine (Pfizer, Inc., New York, USA).

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Pathological findings in organs and tissues of patients with COVID-19: A systematic review

Authors: Sasha Peiris 1 2Hector Mesa 3Agnes Aysola 4Juan Manivel 5Joao Toledo 1 2Marcio Borges-Sa 6Sylvain Aldighieri 1 2Ludovic Reveiz 2 7


Background: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

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Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study

Authors: Brandon Michael Henry1 Cheruiyot2, Stefanie W Benoit3,4, Fabian Sanchis-Gomar5,6 Lippi7, Justin Benoit8 Correspondence to Dr Brandon Michael Henry, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA;


Background The mechanism by which SARS-CoV-2 triggers cell damage and necrosis are yet to be fully elucidated. We sought to quantify epithelial cell death in patients with COVID-19, with an estimation of relative contributions of apoptosis and necrosis.

Methods Blood samples were collected prospectively from adult patients presenting to the emergency department. Circulating levels of caspase-cleaved (apoptosis) and total cytokeratin 18 (CK-18) (total cell death) were determined using M30 and M65 enzyme assays, respectively. Intact CK-18 (necrosis) was estimated by subtracting M30 levels from M65.

Results A total of 52 COVID-19 patients and 27 matched sick controls (with respiratory symptoms not due to COVID-19) were enrolled. Compared with sick controls, COVID-19 patients had higher levels of M65 (p = 0.046, total cell death) and M30 (p = 0.0079, apoptosis). Hospitalised COVID-19 patients had higher levels of M65 (p= 0.014) and intact CK-18 (p= 0.004, necrosis) than discharged patients. Intensive care unit (ICU)-admitted COVID-19 patients had higher levels of M65 (p= 0.004), M30 (p= 0.004) and intact CK-18 (p= 0.033) than hospitalised non-ICU admitted patients. In multivariable logistic regression, elevated levels of M65, M30 and intact CK-18 were associated with increased odds of ICU admission (OR=22.05, p=0.014, OR=19.71, p=0.012 and OR=14.12, p=0.016, respectively).

Conclusion Necrosis appears to be the main driver of hospitalization, whereas apoptosis and necrosis appear to drive ICU admission. Elevated levels CK-18 levels are independent predictors of severe disease, and could be useful for risk stratification of COVID-19 patients and in assessment of therapeutic efficacy in early-phase COVID-19 clinical trials.

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