Early cutaneous findings generally include irregularly shaped, erythematous, dusky red or purpuric macules that are typically tender. These lesions have the tendency to rapidly coalesce with disease progression. In some cases, early lesions may be slightly infiltrated. Atypical targets with dark centers are also often seen. At this point in the evolution of SJS or TEN, lesions may mimic more benign drug-related disorders including exanthematous drug eruptions or EM major.

With progression toward full-thickness necrosis, the erythematous macules assume a grey hue over the next hours to days. Application of tangential mechanical pressure to erythematous zones in this phase may produce detachment of the epidermis from the dermis, referred to as a positive Nikolsky sign. This phenomenon is not specific to SJS/TEN, however, as it is also observed in those with autoimmune bullous diseases. At this time, the skin demonstrates a “wet cigarette paper” appearance (Fig. 24.2). Friction or pressure easily detaches the epidermis, exposing an erythematous, often bleeding or “scalded” dermis. In this second phase, large tracts of epidermal denudation develop. With epidermal cleavage, blisters arise as fluid fills the space between the dermis and epidermis. These flaccid, easily-ruptured blisters may be extended laterally by pressure of the thumb, a feature known as a positive Asboe-Hansen sign. Tense vesicles or bullae may occasionally be observed, typically only in the palmar or plantar regions as the thicker epidermal layer of these surfaces more readily resists pressure.

Epidermal cleavage progresses for 5–7 days. Thereafter, a plateau phase of re-epithelialization begins. Re-epithelialization is generally complete within 3 weeks. Healing is slower in areas of maceration, pressure, or infection. Skin grafting is not required, as keratinocytes are recruited from reservoirs such as follicles and healthy perilesional epidermis and proliferate.

Mucosal involvement presents as erythema and exquisitely painful erosions of the genital, buccal, and ocular mucosa. At least two mucosal surfaces are generally affected. Mucosal/ocular manifestations typically precede or occur simultaneously with cutaneous signs.

Ocular involvement is present in 50–78 % of cases and may include photophobia, discharge, crusting, eyelid edema (Fig. 24.3), and conjunctivitis, as well as conjunctival membrane or pseudomembrane formation. Eyelash shedding may also be observed. Oral involvement occurs in 71–100 % of cases. The vermilion border of the lips and oral cavity frequently feature grey-white pseudomembranes and crusts overlying hemorrhagic erosions. Genital involvement (Fig. 24.4), often with associated dysuria, presents in 40–63 %, and may be complicated by dyspareunia, synechiae formation, and urethral or anal strictures in rare cases.

Though epidermal necrolysis has been described as “acute skin failure,” multiple internal organ systems are also involved. Pulmonary complications (Fig. 24.5) include bronchiolitis obliterans, subcutaneous emphysema, and acute respiratory distress syndrome (ARDS). Renal involvement can lead to microalbuminuria or overt proteinuria, hematuria, azotemia, and acute renal failure secondary to glomerular and/or renal tubular damage. Gastrointestinal dysfunction secondary to epithelial sloughing may include esophagitis, severe abdominal pain and diarrhea, malabsorption, melena, and even hepatitis or colonic perforation. Anemia and leukopenia are common. Myocarditis and encephalopathy have also been documented.

The most frequent complication of the acute phase of SJS/TEN is sepsis. Compromised epithelial barrier function predisposes patients to infections, which represent the most common cause of mortality. Pseudomonas and Staphylococcus aureus are the most frequently identified pathogens. However, enterobacteriaceae are isolated from one-third of positive blood cultures implicating gastrointestinal translocation with mucosal involvement. Multisystem organ failure ensues in roughly one-third of cases.