Toxic Epidermal Necrolysis Post COVID Vaxx – First Reported Case

SJS/TEN represents a group of rare, severe, and potentially fatal delayed-type four-hypersensitivity reactions. Drugs are by far the most common cause of these conditions. However, SJS/TEN could be in very rare instances caused by vaccination [5]. The presentation starts with flu-like symptoms, followed by a painful rash that spreads and blisters. TEN lesions consist of targetoid lesions and purpuric macules with full-thickness epidermal necrosis, along with mucous membrane involvement.

TEN is considered a medical emergency that requires urgent medical intervention, whereby the offending agent if present should be discontinued immediately. The most involved sites in SJS/TEN are the face, palms, soles, and the presternal area of the torso. In addition, the genital, ocular, and buccal mucosa are commonly involved [8]. In SJS, less than 10% of the body surface area is involved, whereas in TEN, more than 30% of the body surface area is involved.

If the skin involvement is between 10% and 30%, it is considered as SJS-TEN overlap. The pathophysiology behind the development of SJS/TEN is believed to be drug-specific CD8+ lymphocytes, where these cytotoxic T cells release granulysin, granzyme B, and perforin – these enzymes lead to pores formation and activation of death cascade in the affected cells. In addition, tumor necrosis factor (TNF)-alpha and interferon-gamma are secreted in significant amounts by activated T cells, leading to Fas ligands overexpression and Fas-mediated keratinocyte death [9] (Figure 9).

COVID-19 vaccine is made of two components (excipients and virotopes). It has been hypothesized that the virotopes antigen, which is expressed on the keratinocyte surface, might lead to cytotoxic T lymphocyte activation and epidermal cells death [10, 11]. SJS/TEN is a clinical and histopathological diagnosis. On histopathology, there is necrosis of keratinocytes and dermal lymphocytic infiltrate with negative target immunofluorescent test.

Patients with TEN require supportive care such as discontinuation of the offending agent(s), intensive care or burn unit admission, fluid and electrolyte replacement, nasogastric tube feeding, or total parenteral nutrition along with pain and temperature control. Sepsis and organ failure are the most feared complication of TEN. TNF-alpha levels were shown to be elevated in skin biopsy specimens, blister fluid, and serum of TEN patients, encouraging the use of biologic therapy that utilizes anti-TNF-alpha action [12, 13].

In one of the studies, a single dose of etanercept (Enbrel, Immunex Corporation, Seattle, USA) 50 mg/mL subcutaneously seemed to modify the course of the disease where significant reduction of edema and stop of disease development was noticed in just 24 hours [14]. In recent years, TNF-alpha antagonists have been used, and the majority of cases exhibited significant improvement with lesion formation ceasing within two days and complete resolution occurring within 20 days.

Also, in SJS/TEN patients treated with etanercept, no severe side effects have been documented. In addition, as compared to individuals who were given corticosteroids, there was a lower rate of gastrointestinal hemorrhage and decreased granulysin and TNF-alpha expression levels [15]. Plasmapheresis, intravenous immunoglobulin (IVIG), and perhaps most promisingly TNF inhibitors such as etanercept are all treatment possibilities for vaccine-induced TEN [14].

However, the use of IVIG and high-dose systemic corticosteroids is still controversial [16]. Plasmapheresis is believed to work in TEN patients based on the premise of removing the drug, drug metabolite, or cytotoxic mediator from the circulation. However, one Swedish study found no benefit with plasmapheresis in eight patients when compared to patients in other studies who received equivalent support care but not plasmapheresis [17].

At this stage, there is insufficient data to justify the use of plasmapheresis above other adjunctive methods [18]. In a randomized controlled trial comparing the efficacy of etanercept and corticosteroids in SJS/TEN patients, etanercept was found to promote skin and oral mucosa healing and facilitate re-epithelialization [15]. To our knowledge, this is the first reported case of TEN secondary to the Pfizer COVID-19 vaccine.

There were two cases of SJS post-COVID-19 vaccine, in the first case, they did not mention the name or the dose of the vaccine that their patient had received [11]. However, in the second case, they mentioned that their patient developed SJS after he received the second dose of the Pfizer COVID-19 vaccine [19]. Our patient had a full recovery after receiving two doses of etanercept.

Conclusions

This instance highlights an extremely rare vaccine consequence. But the benefits greatly outweigh the risks in the present circumstances, therefore there should be no hesitation among the community to seek vaccination.

Therefore, as we report this case, we emphasize the rarity of the occurrence of this side effect, and given the circumstances, this should not influence the decision of taking the vaccine, nor add to the misconceptions out there.

In our case, we explained the pathophysiology behind the development of toxic epidermal necrolysis secondary to vaccination and we highlighted the successfulness of eternacept as a safe and fast treatment of this condition.

See more here: cureus.com

Header image: Seven Ponds Blog

PSI editor’s note: Because of the disturbing nature of the photorgaphs in the source article, we have not included any of them here, and used a generic header image.

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