What is the role of Intravenous Immunoglobulin (IVIG) in the treatment of patients with Steven Johnson Syndrome (SJS), particularly those with severe cases or significant mucosal involvement?

IVIG in Stevens-Johnson Syndrome

IVIG is not recommended as standard first-line therapy for Stevens-Johnson syndrome, as high-quality evidence shows no mortality benefit compared to supportive care alone, though it may be considered in severe or steroid-unresponsive cases, particularly in the context of immune checkpoint inhibitor-induced disease. 1

Evidence Against Routine IVIG Use

The British Journal of Dermatology guidelines explicitly recommend against using IVIG as standard therapy for SJS based on robust meta-analysis data. 1 The pooled evidence demonstrates:

• No survival benefit: Meta-analysis showed an odds ratio for mortality of 1.00 (95% CI 0.58-1.75; P = 0.99) when comparing IVIG to supportive care alone 1
• Overall mortality rate of 19.9% in patients with TEN and SJS-TEN overlap treated with IVIG, showing no statistical improvement over supportive care 1
• Level 3-4 evidence quality, which is insufficient to support routine use 1

When IVIG May Be Considered

Immune Checkpoint Inhibitor-Induced SJS

IVIG or cyclosporine may be considered specifically in severe or steroid-unresponsive cases of immune checkpoint inhibitor-induced SJS/TEN. 2 This represents a distinct clinical scenario where:

• The underlying mechanism is T-cell immune-directed toxicity 2
• First-line treatment is IV methylprednisolone 1-2 mg/kg 2
• IVIG serves as second-line therapy when steroids fail 2

Combination Therapy Context

If IVIG is used, it should be combined with corticosteroids rather than used as monotherapy. 3, 4, 5 Evidence supporting combination therapy includes:

• Reduced recovery time by 1.63 days (95% CI: 0.83-2.43, P < 0.001) when IVIG combined with corticosteroids versus corticosteroids alone 4
• Greater benefit in Asian populations (2.19 days reduction, 95% CI: 1.41-2.97, P < 0.001) and TEN specifically (2.56 days, 95% CI: 0.35-4.77, P = 0.023) 4
• IVIG monotherapy showed worse outcomes than supportive care in pediatric Mycoplasma-associated SJS, with longer hospital stays and more febrile days 6

Dosing Protocol When Used

If IVIG is administered, high-dose regimens (total 2-3 g/kg) show better outcomes than low-dose protocols. 1, 7 Specific dosing:

• Standard protocol: 1 g/kg/day for 3 consecutive days (total 3 g/kg) 1
• Alternative protocol: 400 mg/kg/day for 5 consecutive days (total 2 g/kg) 3, 5
• Low-dose regimens (0.4 g/kg for 4 days) showed unfavorable outcomes with 42% mortality 1, 7

Population-Specific Considerations

Pediatric patients treated with IVIG had significantly lower mortality than adults (0% vs. 21.6%, P = 0.01), suggesting age may modify treatment response. 1, 7 However, this does not override the lack of overall mortality benefit in meta-analyses. 1

Ocular Outcomes

There is no robust evidence that IVIG improves ocular outcomes when given in the acute phase of SJS/TEN. 1 Standard ophthalmologic care remains essential regardless of systemic therapy choice. 8

Safety Profile

IVIG may be safer than systemic corticosteroids regarding infection risk, but carries its own adverse effects: 1, 7

• Headache and aseptic meningitis 1
• Thromboembolic events 1, 7
• Renal dysfunction 1, 7
• Anaphylaxis 1

Recommended Treatment Algorithm

The priority is high-quality supportive care as the foundation of treatment. 1, 7, 8 The algorithmic approach:

1. Immediately discontinue all suspected causative drugs - this is the single most critical intervention 8
2. Transfer to burn unit or ICU with multidisciplinary team 8
3. Initiate comprehensive supportive care: fluid management, wound care, infection prevention, mucosal care, pain control, nutrition 8
4. For standard drug-induced SJS: Supportive care alone is appropriate 1
5. For immune checkpoint inhibitor-induced SJS (Grade 3-4):
   • Start IV methylprednisolone 0.5-1 mg/kg (Grade 3) or 1-2 mg/kg (Grade 4) 2
   • Add IVIG or cyclosporine only if steroid-unresponsive 2
6. If IVIG is used: Administer high-dose (2-3 g/kg total over 3-5 days) in combination with corticosteroids 1, 7, 4

Critical Pitfalls to Avoid

• Do not use IVIG as routine first-line monotherapy - evidence shows no benefit and possible harm compared to supportive care 1, 6
• Do not use low-dose IVIG protocols - doses below 2 g/kg total are associated with worse outcomes 1, 7
• Do not delay transfer to specialized centers while pursuing immunomodulatory therapies 8
• Do not neglect supportive care fundamentals - these remain the cornerstone regardless of adjunctive therapies 1, 8