In adult patients with Stevens‑Johnson syndrome or toxic epidermal necrolysis, does cyclosporine alone provide different outcomes compared with cyclosporine combined with systemic corticosteroids?

Cyclosporine Alone vs. Cyclosporine Plus Steroids in SJS/TEN

Use cyclosporine alone at 3 mg/kg/day divided into two doses for 7-10 days, followed by a taper, without adding systemic corticosteroids. The landmark Paris prospective study demonstrated zero deaths in 29 patients treated with cyclosporine monotherapy despite SCORTEN-predicted mortality of 2.75 deaths, and adding corticosteroids increases infection risk without proven additional benefit 1.

Evidence Hierarchy for Cyclosporine Monotherapy

Cyclosporine alone has the strongest mortality benefit:

• The prospective Paris study using cyclosporine 3 mg/kg/day for 10 days achieved 0% mortality versus SCORTEN-predicted 9.5% mortality 1
• Meta-analysis showed cyclosporine had a standardized mortality ratio (SMR) log of -0.88 (95% CI: -1.47, -0.29), indicating significant mortality reduction 2
• A separate meta-analysis confirmed cyclosporine significantly reduced mortality risk (SMR 0.320; 95% CI: 0.119-0.522; P=0.002) 3

Cyclosporine monotherapy provides superior clinical outcomes:

• Accelerates re-epithelialization compared to non-cyclosporine regimens 4
• Reduces length of hospital stay (13.0 vs 19.0 days, p=0.019) 4
• Decreases systemic infection rate (36.0% vs 71.4%, p=0.017) compared to non-cyclosporine treatment 4

Evidence Against Adding Corticosteroids

Corticosteroids lack proven benefit and carry significant risks:

• UK guidelines explicitly state there is no conclusive evidence that corticosteroids improve outcomes over conservative management (strength D, level 4 evidence) 1
• The primary concern is increased infection risk in patients who already have compromised skin barrier function 1, 5
• Retrospective EuroSCAR data showed benefit only in German patients but not French patients, highlighting inconsistent and unreliable evidence 1, 5
• Two deaths were specifically reported in patients treated with prednisolone 1

Combination therapy shows inferior results to cyclosporine alone:

• When corticosteroids plus immunoglobulins were combined, the SMR log was -0.56 (95% CI: -0.94, -0.19), which is numerically worse than cyclosporine monotherapy at -0.88 2
• No randomized controlled trials support corticosteroid use; all evidence derives from retrospective case series with major ascertainment bias 1

Recommended Cyclosporine Monotherapy Protocol

Standard dosing regimen:

• Initiate cyclosporine at 3 mg/kg/day divided into two doses 1
• Continue for 7-10 days at full dose 1
• Taper over an additional 7 days 1

Mechanism supporting monotherapy:

• Cyclosporine directly inhibits CD8+ T-cell activation and blocks cytotoxic T-cell-driven keratinocyte apoptosis, which is the primary pathologic mechanism in SJS/TEN 1, 6
• This targeted mechanism addresses the disease pathophysiology without the immunosuppressive burden of corticosteroids 6

Critical Clinical Pitfalls to Avoid

Do not add corticosteroids to cyclosporine:

• Adding steroids increases infection risk without demonstrated mortality benefit 1, 5
• The infection risk is particularly dangerous because corticosteroids blunt the febrile response, masking early signs of sepsis 5
• Patients already have compromised skin barrier function, making them highly vulnerable to infectious complications 1, 5

Monitor for cyclosporine-specific considerations:

• Cyclosporine is generally well tolerated with minimal adverse effects in SJS/TEN patients 3
• The drug specifically targets the pathologic mechanism without broad immunosuppression 1

Supporting Care Priorities

High-quality multidisciplinary supportive care remains the definitive priority regardless of immunomodulatory choice:

• Fluid and electrolyte management 1
• Meticulous wound care 1
• Infection prevention with daily smears of skin and mucous membranes 5
• Ophthalmology consultation for ocular complications 1