It is theorized that CD8+ immune cells become overactive by stimulation from drugs or drug metabolites. CD8+ T cells then mediate keratinocyte cell death through release of a number of molecules, including perforin, granzyme B, and granulysin. Other agents, including tumor necrosis factor alpha and Fas ligand, also appear to be involved in TEN pathogenesis. Diagnosis
The diagnosis of TEN is based on both clinical and histologic findings. Early TEN can resemble non-specific drug reactions, so clinicians should maintain a high index of suspicion for TEN. The presence of oral, ocular, and/or genital mucositis is helpful diagnostically, as these findings are present in nearly all patients with TEN. The Nikolsky sign (a separation of the papillary dermis from the basal layer upon gentle lateral pressure) and the Asboe-Hansen sign (a lateral extension of bullae with pressure) are also helpful diagnostic signs found in patients with TEN.Given the significant morbidity and mortality from TEN, as well as improvement in outcome from prompt treatment, there is significant interest in the discovery of serum biomarkers for early diagnosis of TEN. Serum granulysin and serum high-mobility group protein B1 (HMGB1) are among a few of the markers being investigated which have shown promise in early research. Histology
Definitive diagnosis of TEN often requires biopsy confirmation. Histologically, early TEN shows scattered necrotic keratinocytes. In more advanced TEN, full thickness epidermal necrosis is visualized, with a subepidermal split, and scant inflammatory infiltrate in the papillary dermis. Epidermal necrosis found on histology is a sensitive but nonspecific finding for TEN.
Skin usually regrows over two to three weeks; however, recovery can take months and most are left with chronic problems. Signs and symptoms
Prodrome
TEN ultimately results in extensive skin involvement with redness, necrosis, and detachment of the top (epidermal) layer of the skin and mucosa. Before these severe findings develop, people often have a flu-like prodrome, with a cough, runny nose, fever, decreased appetite and malaise. A history of drug exposure exists on average 14 days (ranging from 1–4 weeks) prior to the onset of symptoms, but may result as early as 48 hours if it is a reexposure. Skin findings
Initial skin findings include red-purple, dusky, flat spots known as macules that start on the trunk and spread out from there. These skin lesions then transform into large blisters. The affected skin can then become necrotic or sag from the body and peel off in great swaths. Mucosal findings
Nearly all people with TEN have oral, eye and genital involvement as well. Painful crusts and erosions may develop on any mucosal surface. The mouth becomes blistered and eroded, making eating difficult and sometimes necessitating feeding through a nasogastric tube through the nose or a gastric tube directly into the stomach. The eyes can become swollen, crusted, and ulcerated, leading to potential blindness. The most common problem with the eyes is severe conjunctivitis. Complications
Those who survive the acute phase of TEN often develop long-term complications affecting the skin and eyes. Skin manifestations can include scarring, eruptive melanocytic nevi, vulvovaginal stenosis, and dyspareunia.