Toxic Epidermal Necrolysis

ICD-11

Synonyms

Lyell syndrome

Epidemiology

Rare disease 1-2 per 1 million. Higher risk in HIV/AIDS.

Definition

Severe drug-induced skin reaction characterised by death of the epidermis (keratinocyte necrosis) and marked mucosal erosions. Part of a spectrum, which ranges from SJS, where 30% of the BS is referred to as SJS-TEN-overlap syndrome.

Aetiology & Pathogenesis

Triggers are medications (typically antibiotics and antiepileptic drugs). Immunologically-induced apoptosis of keratinocytes cascading unchecked into massive epidermal destruction may be the pathogenic mechanism. Necrolysis by TNF alpha and gamma IFN. AnnexinA 1 promotes apotosis of keratinocyes. Increased miR-18 a-5p which is blocking antiapotopic action.

Signs & Symptoms

Starting with a confluent maculopapular exanthem without the classical E.e.m. like lesions, haemorrhagic blisters, epidermal necrosis followed by loss of sheets of epidermis; positive Nikolski's signs (Nikolski I: blisters induced by rubbing normal skin. Nikolski II: existing blisters extend with lateral pressure); usually severe periorificial mucosal erosions.

Localisation

Skin and mucosa.

Classification

Part of the Erythema multiforme –SJS/TEN complex as the maximal variant of the clinical cascade.

Laboratory & other workups

Check electrolytes, kidney and liver parameters, cardiac function.

Dermatopathology

Cytotoxic CD8 T-lymphocytes attacking the epidermal keratinocytes, but also mucous epithelia. Apoptosis and necrosis of cells. Disruption of epidermal / dermal connection. Bulla formation because of severe epidermal necrosis. Epidermal remnants separated from dermis with only sparse inflammatory infiltrate.

Course

More than 40 % complications. 30% mortality rate. More than 50% of TEN patients suffer from long-term sequelae.

Complications

Infection, electrolyte and fluid disturbances. Ophthalmic involvement incl. ectropium and synechia, phimosis, vaginal synechia. Scarring in esophagus and mouth mucosa.

SCORTEN evaluation essential.

Diagnosis

Clinical features and histology, showing necrolysis throughout all epidermal layers.

Differential diagnosis

Staphylococcal scalded skin syndrome, burns, erythema multiforme, Disseminated fixed drug eruption, pemphigus and pemphigoid variants and linear IgA disease.

Prevention & Therapy

Immediate referral to special dermatologic and intensive care center.

Aggressive burn therapy (fluid and electrolyte management, appropriate antibiotic coverage, warming measures), special supportive.

According to course and BS and mucosal involvement. Intravenous immunoglobulins, TNF alpha blockers. High dose ciclosporine and / or systemic corticosteroids. Ophthalmology review.

Special

Ophthalmologic consultations.

1.1.3.5 Toxic Epidermal Necrolysis