When does the skin rash typically appear in Stevens-Johnson syndrome?

When Does the Skin Rash Appear in Stevens-Johnson Syndrome?

The skin rash in Stevens-Johnson syndrome typically appears within 7 to 21 days after starting the causative drug, though it can develop as early as a few days or occasionally take several weeks. 1

Timeline of Clinical Presentation

Prodromal Phase (Before Rash)

• An "influenza-like" prodromal illness precedes the rash, characterized by fever, malaise, upper respiratory tract symptoms, sore throat, and general discomfort 2, 3
• This prodromal phase typically lasts 1-3 days before skin manifestations appear 2
• Constitutional symptoms can occur without the rash initially, making early diagnosis challenging 2

Rash Onset and Progression

• The rash typically begins on the face and chest (trunk), then spreads to other areas 2, 4
• Initial lesions present as painful erythematous macules or atypical target lesions that rapidly progress 4, 1
• The palmoplantar areas (palms and soles) are usually spared, which is an important distinguishing feature 4
• Macular lesions become purplish and progress to epidermal detachment with flaccid blisters that converge and break 4

Temporal Relationship to Drug Exposure

• The median time from drug initiation to cutaneous eruption is approximately 11 days for nevirapine-induced SJS/TEN, with two-thirds of cases occurring during the initial dosing period 2
• The average timeframe across all causative drugs is 7 to 21 days after starting the offending medication 1
• In some cases, symptoms may appear within the first week of therapy 2

Critical Clinical Features at Presentation

Mucosal Involvement

• Mucosal involvement occurs in almost all patients and may precede or accompany the skin rash 1
• The most frequently affected sites are the oropharynx (mouth ulcers), followed by eyes (conjunctivitis/iritis) and genitourinary tract 2
• Painful mucosal erosions are a hallmark feature 2

Rash Characteristics

• The rash manifests as a macular exanthema with "atypical targets" focusing on face, neck, and central trunk 5
• Lesions show rapid confluence and a positive Nikolsky's sign (epidermal detachment with lateral pressure) 4, 5
• Lesions may continue to erupt in crops for as long as 2 to 3 weeks 2

Important Clinical Pitfalls

Don't Miss Early Warning Signs

• Patients may seek care before the rash appears, presenting only with prodromal symptoms 2
• The presence of painful skin, sore eyes, or mouth ulcers should raise immediate suspicion even before widespread rash develops 2
• Constitutional symptoms (fever, malaise) combined with a new medication started within the past 3 weeks should trigger heightened vigilance 2, 1

Document the Index Date

• The "index date" is defined as when the patient developed the first symptom or sign (sore throat, rash, skin pain, sore eyes/mouth), not necessarily when the full rash appeared 2
• This distinction is critical for determining the causative drug, as the culprit is typically started 7-21 days before the index date 1

Medication History is Essential

• Record all medications taken over the previous 2 months, including over-the-counter and complementary/alternative therapies 2
• Note any brand switches or medication errors, as these can be relevant 2
• High-risk drugs include sulfonamides, anticonvulsants (carbamazepine, phenytoin), allopurinol, NSAIDs, and certain antibiotics 4, 5, 3

Immediate Actions When SJS is Suspected

• Discontinue any potential culprit drug immediately upon suspicion—do not wait for confirmatory testing 2, 1
• The course of the disease is often rapid and fatal, making early drug withdrawal the most important intervention 4
• Prompt referral to an appropriate medical center (burn unit or intensive care unit) is mandatory 1, 3