What are the diagnostic criteria and management strategies for a patient with suspected Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), presenting with recent medication use, fever, skin lesions, and mucous membrane involvement?

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

Diagnose SJS/TEN primarily through clinical recognition of painful skin lesions with epidermal detachment plus mucous membrane involvement, confirmed by skin biopsy showing full-thickness epidermal necrosis, and immediately discontinue all suspected culprit drugs. 1

Clinical Diagnostic Criteria

Essential Clinical Features

The diagnosis rests on identifying the characteristic triad: painful skin lesions, mucous membrane involvement, and recent drug exposure (typically 4-28 days prior). 1, 2

• Skin findings: Look for purpuric macules, flat atypical targets, flaccid blisters, and areas of epidermal detachment that extend with lateral pressure (positive Nikolsky sign) 1
• Mucous membrane involvement: Examine all mucosal sites for erosive and hemorrhagic mucositis affecting eyes (purulent keratoconjunctivitis with eyelid edema), mouth (painful erosions requiring nasogastric feeding), nose, and genitalia—this is an early diagnostic hallmark 1, 3
• Prodromal symptoms: Document fever, malaise, upper respiratory symptoms, sore throat, skin pain, and sore eyes/mouth occurring before rash onset 1, 2

Disease Classification by Extent

Classify disease severity by percentage of body surface area (BSA) with epidermal detachment, NOT erythema: 1

• SJS: <10% BSA epidermal detachment 4, 5
• SJS/TEN overlap: 10-30% BSA detachment 5
• TEN: >30% BSA detachment 4, 5

Required Diagnostic Workup

History Taking

Obtain a detailed drug timeline for ALL medications taken in the previous 2 months, including over-the-counter and complementary therapies, documenting exact start and stop dates. 1

• Identify the index date (first symptom onset) and calculate latency period from drug initiation 1
• Document any previous drug hypersensitivity reactions 1
• Assess drug notoriety for causing SJS/TEN (high-risk drugs include allopurinol, sulfonamide antibiotics, anticonvulsants like carbamazepine and lamotrigine, NSAIDs of oxicam type) 4, 6
• Consider mycoplasma infection, particularly in children and young adults with predominantly mucous membrane involvement 1, 3

Physical Examination

Record vital signs, oxygen saturation, and baseline body weight, then systematically examine all skin and mucosal surfaces. 1

• Map the extent of erythema AND epidermal detachment separately on a body chart using the Lund and Browder method 1
• Include detachable epidermis (Nikolsky-positive areas) in your detachment calculation—this figure has prognostic value, not the erythema extent 1
• Examine for respiratory symptoms (cough, dyspnea, bronchial hypersecretion) and bowel involvement (diarrhea, abdominal distension) 1

Laboratory Investigations

Order the following mandatory tests immediately: 1

• Full blood count, ESR, C-reactive protein, urea and electrolytes, magnesium, phosphate, bicarbonate, glucose, liver function tests, coagulation studies 1, 7
• Mycoplasma serology 1
• Chest X-ray 1
• Swabs from lesional skin for bacterial and candidal culture 1, 7

Histopathological Confirmation

Perform two skin biopsies to confirm diagnosis and exclude mimics: 1

• First biopsy: Take from lesional skin just adjacent to a blister and send for routine histopathology—look for full-thickness epidermal necrosis with confluent keratinocyte apoptosis, basal cell vacuolar degeneration, subepidermal vesicle formation, and mild perivascular lymphocytic infiltrate 1, 4
• Second biopsy: Take from periblister lesional skin and send unfixed for direct immunofluorescence to exclude immunobullous disorders (pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus) 1

Critical Differential Diagnoses to Exclude

Actively rule out these conditions that can mimic SJS/TEN: 1

• Erythema multiforme major: Typical target lesions on extremities, less severe mucositis, usually HSV-associated 1
• DRESS syndrome: Prominent eosinophilia (>700/μL), lymphadenopathy, milder or absent mucosal involvement, morbilliform rash, 2-6 week latency 3
• Staphylococcal scalded skin syndrome: Occurs in children, no mucosal involvement, superficial epidermal split on histology 4, 6
• Acute generalized exanthematous pustulosis (AGEP): Sterile pustules, no mucosal involvement 1, 4
• Generalized bullous fixed drug eruption: History of recurrence in same sites 1

Immediate Management Actions Upon Diagnosis

Once SJS/TEN is suspected, initiate these actions simultaneously with diagnostic workup: 1, 7

• Discontinue ALL potential culprit drugs immediately—this is the single most important intervention 1, 7
• Calculate SCORTEN within first 24 hours to predict mortality risk 7, 6
• Transfer patients with >10% BSA detachment to specialized burn unit or ICU with experience managing SJS/TEN 7, 4
• Establish IV access through non-lesional skin and commence fluid resuscitation if clinically indicated 1, 7
• Insert nasogastric tube if oral intake inadequate 1, 7
• Insert urinary catheter when urogenital involvement causes dysuria or retention 1, 7
• Arrange ophthalmology consultation within 24 hours 7
• Organize photographs documenting lesion type and extent 1

Common Diagnostic Pitfalls

• Delayed recognition: Early SJS/TEN may resemble viral exanthem or simple drug rash—maintain high suspicion with any painful rash plus mucositis in patient on high-risk medications 1, 2
• Confusing erythema with detachment: Only epidermal detachment percentage (including Nikolsky-positive areas) determines disease classification and prognosis, not erythema extent 1
• Missing mycoplasma etiology: Consider mycoplasma-induced SJS especially in children with predominantly mucous membrane involvement and minimal skin lesions 1, 3
• Overlooking drug timeline: The 5-28 day latency window from drug initiation is most typical; shorter latency suggests previous exposure to same drug 1
• Failing to examine all mucosal sites: Genital and ocular involvement may be missed without systematic examination, leading to preventable long-term complications 1, 3