What is the recommended dose of Intravenous Immunoglobulin (IVIG) for a patient with severe Stevens-Johnson syndrome?

IVIG Dosing for Stevens-Johnson Syndrome

For Stevens-Johnson syndrome, administer IVIG at a total dose of 2-3 g/kg divided over 3-5 consecutive days (typically 1 g/kg/day for 3 days), as higher total doses are associated with improved survival compared to lower-dose regimens. 1

Recommended Dosing Protocol

The optimal regimen is 1 g/kg/day for 3 consecutive days (total 3 g/kg), which has shown the best outcomes in retrospective analyses. 1 This high-dose approach significantly outperforms lower-dose protocols:

• Avoid the 0.4 g/kg/day for 4 days regimen (total 1.6 g/kg), which showed mortality rates of 42% in TEN patients 2, 1
• Meta-regression analysis demonstrates a strong inverse correlation between IVIG dosage and mortality (slope: -0.59, P = 0.009), with doses ≥2 g/kg significantly decreasing mortality 3
• Alternative acceptable regimen: 0.4 g/kg/day for 5 days (total 2 g/kg) 4, 5

Critical Timing Considerations

Initiate IVIG as early as possible after diagnosis while epidermal detachment is still progressing. 6 Earlier administration correlates with:

• Shorter time to complete healing (average 8.3 days when given early) 6
• Objective clinical response typically observed within 2 days of starting IVIG 6
• Better outcomes in patients treated within the first few days of hospital admission 7

Weight-Based Dosing Adjustments

Use ideal body weight or adjusted body weight for obese patients rather than actual body weight to prevent excessive dosing. 8 For patients with cardiac dysfunction, divide the total dose over 2 days to minimize fluid overload risk 8.

Pre-Administration Requirements

Before initiating IVIG, complete the following assessments 8:

• Check serum IgA levels to identify patients at risk for severe anaphylaxis; use IgA-depleted preparations if deficiency detected
• Evaluate renal function (serum creatinine, urine output)
• Assess thrombotic risk factors
• Review cardiac function, especially in patients with pre-existing cardiac disease
• Document history of previous infusion reactions

Premedication Protocol

Administer diphenhydramine and acetaminophen as standard premedication. 8 Consider adding corticosteroids (20 mg prednisone) for patients with prior infusion reactions 8.

Monitoring During Infusion

Administer IVIG over several hours and monitor renal function (urine output, serum creatinine) throughout the infusion. 8 Watch for:

• Common adverse effects: headaches, fever, chills, fatigue, nausea, blood pressure changes, tachycardia 8
• Serious complications: renal failure, thrombosis, aseptic meningitis, anaphylaxis 8

Important Evidence Caveats

Despite promising results in observational studies, the UK guidelines note that evidence quality remains limited (Level 3-4), with no randomized controlled trials demonstrating unequivocal benefit. 2, 1 Key evidence limitations include:

• Meta-analysis showed no overall survival benefit compared to supportive care alone (OR 1.00,95% CI 0.58-1.75) 1
• All available data comes from retrospective case series with significant ascertainment bias 2
• However, high-quality multidisciplinary supportive care remains the absolute priority regardless of specific interventions 2, 1, 9

Pediatric Considerations

Pediatric patients with SJS/TEN have significantly lower mortality than adults (0% vs. 21.6%), making IVIG a particularly attractive option in this population. 1 In pediatric series, IVIG at 1.5-2 g/kg as a single infusion shortened fever duration (8 vs. 14 days, p=0.06) and hospital stay (12 vs. 15 days) 7.

Combination Therapy Considerations

IVIG may be combined with systemic corticosteroids in refractory cases, though this approach lacks strong evidence. 4, 5 If combining therapies:

• Combination therapy (IVIG 0.4 g/kg/day × 5 days plus corticosteroids) showed a trend toward reduced mortality (SMR 0.85) but did not reach statistical significance 5
• Combination therapy significantly reduced time to arrested progression (P=0.019) and hospitalization time (P=0.043) 5
• Do not perform plasmapheresis immediately after IVIG administration, as it will remove the immunoglobulin 8

Clinical Pitfalls to Avoid

• Never use low-dose IVIG (<2 g/kg total) as it correlates with worse outcomes 1, 3
• Do not delay IVIG initiation while waiting for disease progression to arrest - IVIG is most effective when given during active epidermal detachment 6
• Ensure adequate supportive care is prioritized - IVIG is an adjunct, not a replacement for high-quality multidisciplinary management 2, 9