Toxic epidermal necrolysis and Stevens-Johnson syndrome after COVID-19 infection and vaccination

Stevens-Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes; toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID-19 have been limited. We present a review of TEN/SJS after COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty-eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS-TEN overlap after COVID-19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID-19 vaccines can activate T-cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID-19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug-induced TEN/SJS. Treatments for post-infection and post-vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication.     

A review of toxic epidermal necrolysis management in Japan

Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25–50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA)-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%). The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA), while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN.     

亚洲人群HLA-B*1502等位基因与卡马西平引起SJS/TEN的关联性荟萃分析

目的 探讨亚洲人群人类白细胞抗原(HLA)-B*1502等位基因对卡马西平引起Stevens-Johnson综合征和中毒性表皮坏死松解症(Stevens-Johnson syndrome/toxic epidermal necrolysis,SJS/TEN)的影响.方法 检索Pubmed 、Embase、中国期刊网、万方和维普等数据库,按照纳入标准纳入有关HLA-B*1502等位基因与卡马西平引起SJS/TEN的病例对照研究,应用Review Manager 4.2和Stata 10.0进行荟萃分析.结果 共纳入10篇文献(10个病例对照研究),共计卡马西平引起的SJS/TEN患者208例,对照者829例.荟萃分析显示合并RR(95% CI)为10.95(8.30 ~ 14.45)(Z = 16.93,P < 0.000 01).结论 HLA-B*1502等位基因与卡马西平引起SJS/TEN存在明显关联.     

Lamotrigine and Stevens-Johnson Syndrome Prevention

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related—common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.     

中毒性表皮坏死松解型药疹的护理

目的：探讨中毒性表皮坏死松解型药疹(toxic epidermal necrolysis,TEN)的护理措施。方法：对9例TEN患者实施保护性隔离,在积极支持治疗的基础上,采用纳米银抗感染敷料联合无菌棉垫覆盖创面,安排特护确保基础护理、创面护理、病情观察到位。结果：9例患者均未发生创面感染,经过精心治疗护理原有感染创面治愈,8例痊愈出院未遗留疤痕,1例因多器官功能衰竭死亡。结论：在合理治疗的基础上,实施精心护理是提高TEN患者抢救成功率、降低创面感染、遗留疤痕等的重要策略。