Overview 

A potentially fatal illness, which is characterised by widespread exfoliation of the mucous membrane and epidermis that may result in sepsis and mortality, is Toxic epidermal necrolysis(TEN). In the majority of cases, TEN is due to an immune reaction to certain types of medications.¹ TEN and Stevens–Johnson Syndrome (SJS) are dermatologic conditions usually described as extensive necrolysis and scraping of epidermal tissue. These conditions are known to have common pathology and are categorised based on the involvement of body surface area(BSA).² SJS involves less than 10% and TEN involves 30% of BSA.¹

Epidemiology, etiology and pathophysiology of  toxic epidermal necrolysis (TEN)

TEN and SJS are rare conditions, and the rate of incidence varies by location. In the United States, 1.9 per million adults per year are affected by TEN and the death rate is greater in 30% of cases.^{1, 2} TEN can be due to various factors such as vaccines, infections(mycoplasma pneumoniae, hepatitis A and human herpesvirus 7), medications, tumours (lung cancer and hepatocellular carcinoma)and in some cases idiopathic(exact cause cannot be ruled out).¹ Medication that are mainly associated with TEN include antiepileptic drugs (like Phenytoin, clorazepate, zonisamide, carbamazepine, lamotrigine and valproate,  rufinamide),^{1, 3} antibiotics such as chloramphenicol, quinolones, penicillins and sulfonamides),⁴ piroxicam and oxybutazone NSAID and in antiviral agents (abacavir and oseltamivir) and allopurinol. In the case of  Vaccines, the meningococcal vaccine is associated with the development of TEN.^{1, 5} Most recently, in patients with COVID-19, TEN is reported due to medications during the treatment period or the viral infection.^{6, 7} The pathophysiology of toxic epidermal necrolysis is mainly unknown. Recent developments show that most of the individuals with TEN have aberrant drug metabolism, and epidermal cell death is due to cell-mediated cytotoxic reaction against keratinocytes,⁸ which are the primary cells of the epidermis that provide immunological and physical barrier against external surroundings.⁹

Clinical criteria for diagnosis of Toxic epidermal necrolysis (TEN)

Clinical manifestations involved in TEN are

• Fever 
• malaise
• Sore throat
• Cough 
• Cutaneous and mucosal involvement showing erythematous macules or lesions  
• Positive Nikolsky sign 
• Sheet of Stripped epidermis 

Most commonly, fever and flu-like symptoms can be seen from one to three days, followed by cutaneous involvement. Individuals will experience subsequent cutaneous and mucosal involvement, which usually manifests as erythematous macules or unusual target lesions on the trunk that develop into confluent erythema regions with dark centres and flaccid blisters.^{10, 2} TEN can be of two forms one with macules(spots) and one without macules(rare) but associated with widespread erythema.¹¹

The characteristic feature of TEN is the detachment of skin involving more than 30% of BSA.SJS/TEN overlap is seen if the skin detachment is between 10%and 30%.^{1, 2 11} TEN with macules involve >30% of skin detachment, atypical target lesions, there is no involvement of raised lesions and distributed in the trunk region, while TEN without macules involve >10%of skin detachment, none of targeted and raised lesion and distribution is same as TEN with macules.¹¹ Up to 80% of cases include two or more mucosal surfaces, and the great majority of patients have mucosal involvement.² With little pressure, blistering and epidermis separation at the dermal-epidermal junction might occur. All across the skin and mucosa, epidermal detachment can happen, but it usually affects the respiratory and ocular epithelium.¹⁰ The most common issue is with the mouth, and in up to 100% of cases, it leads to mouth sores and ulcers. Eye problems are also quite common, and they can be as bad as complete skin loss on the eye surface or redness of the eye lining. It is key to see an ophthalmologist soon to stop long-term harm to your eyes. Although the degree of gynecologic involvement varies, up to 77% of female patients.²

Nikolsky's sign can be used as a clinical diagnostic test for toxic epidermal necrolysis(TEN). The phenomenon known as Nikolsky's sign (Clinical Nikolsky's sign) occurs when tangential pressure is applied to the skin or mucosa that appears to be normal, to the perilesional skin or mucosa, or to the affected skin or mucosa using the thumb or fingerpad. This causes a shearing force that separates the upper layers of the epidermis from the lower epidermis, resulting in the formation of blisters. In TEN, a positive pseudo-Nikolsky sign can be observed.¹²

Complications of TEN include respiratory compromise, sepsis due to a breakdown of the skin barrier. People who have weakened immune systems, such as those who have HIV, cancer, or other illnesses, are more likely to get TEN. Comorbidities and advanced age are linked to higher mortality rates.¹⁰

Laboratory test for the diagnosis of toxic epidermal necrolysis

There aren’t any specific blood tests that can diagnose Toxic Epidermal Necrolysis (TEN). However, a basic set of tests—like a complete blood count, erythrocyte sedimentation rate, coagulation studies, and assessments of urea, electrolytes, and liver function-plays an important role. These tests help guide supportive treatment, monitor organ function, and provide insight into the overall prognosis. It’s common to find anaemia and low lymphocyte counts in patients with TEN, and a drop in neutrophil counts can signal a worse outlook. Keeping the coagulation profile and blood count within normal ranges is especially important for patients with extensive mucosal damage since abnormalities could raise the risk of serious bleeding, particularly from the gastrointestinal tract. In some cases, blood or blood product transfusions might be necessary to manage these risks¹.

Prognosis of TEN

Prognosis of TEN can be determined using scale Severity of Illness Score for Toxic Epidermal Necrolysis(SCROTEN) scale, which is most commonly used for determining the prognosis of TEN/SJS.² Several studies have confirmed that this is an efficient technique. This scale gives a total score of 7. Mortality risk exceeds 90% when five points or more are added together. A cutoff limit for sensitivity and specificity assessment was established as SCORTEN greater than four.¹³ If only one risk factor is present, a patient's mortality score may be 3.2%; if five or more risk factors are present, it may be >90%.¹

SCROTEN ( Severity of illness score for Toxic epidermal necrolysis) scale

Summary 

Early identification and providing treatment are necessary in case of Toxic Epidermal Necrolysis (TEN) patients. Along with providing a proper treatment and counselling session regarding the disease, its prognosis, complications, and lifestyle management play an important role in the improvement of patients' overall health-related quality of life. To improve the current prognostic diagnosis of TEN, it’s important to thoroughly investigate the underlying causes of mortality. So that many cases can be treated during the early stages.