Early Signs of Stevens-Johnson Syndrome
The earliest warning signs of Stevens-Johnson Syndrome are a prodromal flu-like illness (fever, malaise, upper respiratory symptoms) followed by cutaneous pain and a painful rash that typically begins on the face, upper torso, and proximal limbs, accompanied by early involvement of mucous membranes (eyes, mouth, nose, genitalia). 1
Prodromal Phase (Days Before Rash)
- Fever, malaise, and upper respiratory tract symptoms precede the eruption by several days 1
- Sore throat may be an initial symptom 1
- Ocular inflammation can develop before skin signs appear 1
- This prodromal phase typically occurs 4-28 days after starting the culprit medication 2
Early Cutaneous Signs
Cutaneous pain is a prominent and critical early feature that should immediately alert clinicians to incipient epidermal necrolysis 1, 3. This is a key distinguishing feature that warrants urgent evaluation.
Initial Rash Characteristics:
- Atypical target lesions and/or purpuric macules are the earliest skin lesions 1, 3
- The rash begins on the upper torso, proximal limbs, and face, then spreads to the trunk and distal limbs 1, 3
- Lesions appear as dusky, dark red macules with a dark center surrounded by a pink ring 3
- Tender skin to touch is an early warning sign 1, 3
- Involvement of palms and soles is often prominent early 1, 3
Early Mucosal Involvement
Mucous membrane involvement of the eyes, mouth, nose, and genitalia is usually an early feature and may precede extensive skin involvement 1, 3:
- Purulent keratoconjunctivitis with eyelid edema in the eyes 1
- Painful oral erosions and mouth ulcers 1
- Genital mucosal involvement 1
- This erosive and hemorrhagic mucositis is a hallmark early sign 1
Critical Early Physical Findings
- Positive Nikolsky sign: Gentle lateral pressure on lesional skin causes the epidermis to slide over the dermis, though this is not specific to SJS 1, 4
- Skin shearing with minimal trauma 1
- Confluent erythema developing in affected areas 1
Important Clinical Pitfalls
Do not dismiss early symptoms as simple viral illness or drug rash. The combination of fever, painful skin, and mucosal involvement should trigger immediate suspicion 1.
Cutaneous pain out of proportion to visible findings is a red flag that distinguishes early SJS from benign drug eruptions 1, 3.
Differentiation from erythema multiforme major (EMM) is crucial: EMM has typical raised target lesions predominantly on limbs and extremities, while SJS has flat atypical targets more widely distributed on the torso and face 1, 3.
Immediate Action Required
If SJS is suspected, discontinue any potential culprit drug immediately 1. Common high-risk medications include sulfonamide antibiotics, anticonvulsants (carbamazepine, phenytoin, phenobarbital), allopurinol, NSAIDs of the oxicam type, and aminopenicillins 5, 6.
The FDA label for carbamazepine specifically warns that patients should report fever, sore throat, rash, ulcers in the mouth, easy bruising, or lymphadenopathy immediately, as these may signal serious reactions 7.
Early recognition within the first few days is critical, as lesions expand and coalesce rapidly, reaching maximum extent 5-7 days after disease onset 3.