Symptoms of Stevens-Johnson Syndrome
Stevens-Johnson syndrome presents with a prodrome of fever, malaise, and upper respiratory symptoms, followed by painful skin lesions (purpuric macules or flat atypical targets), multisite erosive mucositis (eyes, mouth, nose, genitalia), and epidermal detachment affecting less than 10% of body surface area. 1, 2
Prodromal Phase (Precedes Skin Eruption by Several Days)
- Fever (often extremely high) 1, 2, 3
- Malaise and general unwellness 2
- Upper respiratory tract symptoms (sore throat, cough) 1, 2
- These "flu-like" symptoms typically begin 4-28 days after drug exposure 4
Early Warning Signs
Cutaneous pain is a prominent early feature that should immediately alert clinicians to incipient epidermal necrolysis 1, 2. This painful skin sensation often precedes visible skin changes and is a critical diagnostic clue.
Ocular inflammation may develop before skin signs appear 1, 2. In fact, acute conjunctivitis occurs before or simultaneously with skin eruptions in the majority of cases 3.
Mucosal Involvement (Usually an Early Feature)
Involvement of mucous membranes leads to erosive and hemorrhagic mucositis affecting 1, 2:
- Eyes: Conjunctivitis, pseudomembrane formation, erosions
- Mouth: Painful erosions, hemorrhagic crusting of lips
- Nose: Erosions, crusting
- Genitalia: Erosions, pain with urination (dysuria)
All patients who remember details report oral and ocular involvement 3. This multisite mucositis is a defining characteristic that distinguishes SJS from other blistering disorders.
Cutaneous Manifestations
Initial Skin Lesions
The earliest skin lesions are 2:
- Atypical target lesions (flat targets with dark red center surrounded by pink ring)
- Purpuric macules (dark red, flat lesions)
Distribution Pattern
- Initial sites: Upper torso, proximal limbs, and face 2
- Progression: Spreads to trunk and distal limbs
- Palms and soles involvement is often prominent 2
Progressive Skin Changes
- Lesions expand and coalesce over 5-7 days 2
- Large areas of confluent dusky erythema develop 1, 2
- Tender skin with positive Nikolsky sign: Gentle lateral pressure causes epidermis to slide over dermis 1, 2
- Flaccid bullae form as necrotic epidermis separates from dermis 1, 2
- Epidermal detachment results in denuded dermis that exudes serum, bleeds easily, and becomes secondarily infected 1, 2
Defining Characteristic: Extent of Epidermal Detachment
SJS is defined by epidermal detachment (both detached and detachable epidermis) of less than 10% body surface area plus widespread purpuric macules or flat atypical targets 1, 2.
Common Pitfalls to Avoid
Do not confuse with erythema multiforme major (EMM): EMM has typical raised target lesions predominantly on extremities, patients are constitutionally well, and it doesn't progress to widespread necrolysis 1, 2. The distinction matters because EMM is usually HSV-related while SJS is typically drug-induced.
Do not dismiss early symptoms: The combination of high fever, painful skin, and acute conjunctivitis occurring before or with skin eruptions—especially with oral and nail involvement—strongly indicates SJS/TEN onset 3.
Recognize that pustular lesions can rarely occur: While uncommon, neutrophilic infiltration into blisters may create pustule-like eruptions in SJS 5, which could lead to diagnostic confusion with acute generalized exanthematous pustulosis (AGEP).
Systemic Symptoms to Assess
Beyond skin and mucosa 2:
- Respiratory: Cough, dyspnea, bronchial hypersecretion, hemoptysis
- Gastrointestinal: Diarrhea, abdominal distension
- Constitutional symptoms persist throughout acute phase
The clinical presentation is striking enough that diagnosis relies primarily on recognizing this constellation of symptoms, though histopathology confirms the diagnosis by showing full-thickness epidermal necrosis with keratinocyte apoptosis 1.