Why are corticosteroids and cyclosporine used in Stevens‑Johnson syndrome and toxic epidermal necrolysis?

Why Corticosteroids and Cyclosporine Are Used in SJS-TEN

Corticosteroids and cyclosporine are used in SJS-TEN based on their theoretical mechanisms to inhibit inflammation and lymphocyte-mediated keratinocyte destruction, though the evidence supporting their use is weak and conflicting, with high-quality supportive care remaining the definitive priority. 1

Rationale for Corticosteroid Use

Theoretical Mechanism

• Corticosteroids aim to inhibit the inflammatory cascade early in disease progression, with proponents emphasizing the importance of high-dose therapy given early to suppress the immune-mediated epidermal destruction. 1
• The pathophysiology involves cytotoxic T-cell mediated keratinocyte apoptosis through Fas-FasL interaction and release of perforin, granzyme B, and granulysin, which corticosteroids theoretically suppress. 2, 3

Evidence Supporting Use

• Retrospective EuroSCAR data showed lower mortality in German patients (but not French patients) treated with corticosteroids compared to supportive care alone, highlighting significant geographic inconsistencies. 1, 4
• High-dose pulsed IV protocols (dexamethasone 100 mg or 1.5 mg/kg for 3 days, or methylprednisolone 1000 mg for 3 consecutive days) showed decreased mortality compared to SCORTEN predictions in small case series. 1
• A meta-analysis suggested potential survival benefit with glucocorticosteroids, though this was significant in only one of three statistical analyses across 96 studies with 3,248 patients. 4, 5

Critical Concerns Against Use

• The primary concern is increased infection risk in patients who already have compromised skin barrier function, with opponents emphasizing that systemic corticosteroids may increase sepsis risk. 1, 4, 6
• Two deaths were reported in patients treated with prednisolone in retrospective case series. 4, 6
• The UK guidelines explicitly state there is no conclusive evidence to demonstrate benefit of any intervention over conservative management, with strength of recommendation D and level of evidence 4. 1, 4

Rationale for Cyclosporine Use

Theoretical Mechanism

• Cyclosporine provides effective inhibition of lymphocyte function, specifically blocking CD8+ T-cell activation, which directly targets the pathogenic mechanism of cytotoxic T-cell mediated keratinocyte destruction. 1, 3
• This immunomodulatory action reduces epidermal destruction without the broad immunosuppressive effects of corticosteroids. 3

Evidence Supporting Use (Stronger Than Corticosteroids)

• A landmark study from Paris showed 29 patients treated with cyclosporine 3 mg/kg daily for 10 days had zero deaths despite SCORTEN-predicted mortality of 2.75/29, representing a dramatic reduction in expected mortality. 1, 4
• Direct comparison studies demonstrate superiority over corticosteroids: mean re-epithelialization time was 14.54 days with cyclosporine versus 23 days with corticosteroids (P=0.009956), and mean hospital stay was 18.09 versus 26 days (P=0.02597). 7
• Meta-analysis of 9 studies with 358 patients revealed significant mortality reduction with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119-0.522; P=0.002). 8
• Cyclosporine was generally well tolerated with minimal adverse effects or increased infection risk, despite patients being critically ill. 8

Dosing Protocol

• Standard regimen: 3 mg/kg daily in divided doses for 7-10 days, then tapered over another 7 days. 1, 7

Critical Clinical Pitfalls

Evidence Quality Limitations

• No randomized controlled trials exist for either agent—all evidence comes from retrospective case series with major ascertainment bias, low patient numbers, and variation in timing/nature of intervention. 1, 4
• The UK guideline development group found the data of insufficient quality to make specific recommendations either for or against active interventions. 1
• There is lack of consensus even among experienced clinicians managing SJS-TEN. 1

Practical Decision-Making

• If immunomodulation is pursued despite weak evidence, cyclosporine appears to have stronger supporting data and better safety profile than corticosteroids, with multiple studies showing mortality benefit and faster re-epithelialization without increased infection risk. 7, 5, 8
• Corticosteroids carry documented infection concerns and conflicting efficacy data, making them a less favorable choice when immunomodulation is considered. 4, 6
• High-quality multidisciplinary supportive care (fluid/electrolyte management, wound care, infection prevention, ophthalmology consultation) remains the definitive priority regardless of immunomodulatory therapy chosen. 1, 9

When to Consider These Agents

• Rapidly progressive disease with high SCORTEN scores may warrant consideration of cyclosporine over corticosteroids based on comparative evidence. 7, 8
• If corticosteroids are used despite guidelines, employ shortest possible duration (7-10 days) with rapid tapering and intensive infection monitoring. 6
• TNF-α inhibitors (etanercept) represent an emerging alternative, with one series showing 0% mortality despite 50% SCORTEN-predicted mortality. 1, 4