How do you diagnose Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)?

Diagnosis of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

The diagnosis of SJS/TEN requires a comprehensive clinical assessment, including detailed history of prodromal symptoms, skin biopsy for histopathological confirmation, and careful examination of skin and mucosal involvement to determine the extent of epidermal detachment.

Clinical Features and Initial Assessment

• Prodromal symptoms typically include fever, malaise, and upper respiratory tract symptoms that precede the eruption by several days 1
• Early symptoms include painful skin (a critical warning sign), mucosal involvement of eyes, mouth, nose, and genitalia leading to erosive and hemorrhagic mucositis 1
• Document the date when the rash first appeared and its progression 1
• Ask about symptoms indicating respiratory tract involvement: cough, dyspnoea, bronchial hypersecretion, and haemoptysis 1
• Inquire about symptoms of bowel involvement: diarrhoea and abdominal distension 1
• Record all medications taken over the previous 2 months, including over-the-counter and complementary therapies 1, 2

Physical Examination

• Look for target lesions (particularly atypical targets), purpuric macules, blisters, and areas of epidermal detachment 1
• Examine all mucosal sites for mucositis, blisters, and erosions 1
• Test for Nikolsky sign - epidermis peels away with minimal shearing force on lesional skin 1
• Record the extent of erythema and epidermal detachment separately on a body map 1
• Calculate percentage of body surface area (BSA) involved using the Lund and Browder chart 1
• Note that detachment should include both detached and detachable epidermis (Nikolsky positive areas) 1

Classification Based on Extent of Involvement

• SJS: Epidermal detachment less than 10% BSA plus widespread purple/red macules or flat atypical targets 1
• SJS-TEN overlap: Detachment or skin necrosis of 10-30% BSA plus widespread purpuric macules or flat atypical targets 1
• TEN: Detachment or skin necrosis greater than 30% BSA 1

Laboratory and Diagnostic Tests

• Full blood count, ESR, C-reactive protein, urea and electrolytes, magnesium, phosphate, bicarbonate, glucose, liver function tests, and coagulation studies 1, 2
• Chest X-ray 1
• Mycoplasma serology, particularly important in children and young adults 1
• Skin biopsy from lesional skin adjacent to a blister for histopathology 1, 2
• Second biopsy from periblister lesional skin for direct immunofluorescence to exclude immunobullous disorders 1, 2

Histopathological Features

• Variable epidermal damage ranging from individual cell apoptosis to confluent epidermal necrosis 1
• Epidermal changes associated with basal cell vacuolar degeneration and subepidermal vesicle or bulla formation 1
• Adnexal structures such as sweat ducts and hair follicles occasionally involved 1
• Mild, predominantly perivascular infiltrate of lymphocytes and histiocytes in the dermis, with small numbers of eosinophils in some cases 1

Differential Diagnosis

• Erythema multiforme major (EMM) - typically has typical targets or raised atypical targets predominantly on limbs and extremities; usually related to HSV rather than drugs 1
• Staphylococcal scalded skin syndrome (SSSS) - absence of mucosal involvement; more superficial level of skin cleavage 1, 3
• Immunobullous disorders - pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis 1, 3
• Acute generalized exanthematous pustulosis 1, 3
• Generalized bullous fixed drug eruption 1
• Bullous acute graft-versus-host disease 1

Risk Assessment

• Calculate SCORTEN (severity-of-illness score for toxic epidermal necrolysis) to predict mortality risk 2, 4
• Identify high-risk drugs: allopurinol, antibiotics (particularly sulfonamides), anticonvulsants, NSAIDs of the oxicam type 3, 5
• Consider genetic susceptibility factors, such as HLA-B*1502 association with carbamazepine-induced SJS in Han Chinese populations 4, 3

Important Pitfalls to Avoid

• Failure to promptly discontinue the culprit drug, which increases mortality risk 1, 2
• Neglecting eye care, which may result in permanent visual impairment 2, 6
• Overlooking infectious causes, particularly Mycoplasma pneumoniae in children and young adults 1, 2
• Misdiagnosing SJS/TEN as a less severe condition, delaying appropriate care 7, 5
• Failing to recognize respiratory infection-induced rash and mucositis, which can present with significant mucosal involvement but variable cutaneous involvement 1