Management of Febuxostat-Induced Erythroderma
Immediately discontinue febuxostat and do not rechallenge the patient with this medication. Erythroderma represents a severe cutaneous adverse reaction that can progress to life-threatening complications if the offending drug is not stopped promptly 1.
Immediate Management Steps
Discontinue Febuxostat
- Stop febuxostat immediately upon recognition of erythroderma to prevent progression to more severe complications including DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) 1
- Do not attempt rechallenge with febuxostat, as severe cutaneous reactions can recur with greater intensity 1, 2
- One documented case exists of a patient who developed exfoliative erythroderma with allopurinol and subsequently developed biopsy-confirmed cutaneous leukocytoclastic vasculitis when switched to febuxostat, demonstrating potential cross-reactivity in severe hypersensitivity reactions 2
Assess for DRESS Syndrome
- Check for fever, elevated liver enzymes, acute kidney injury, and eosinophilia 1
- DRESS syndrome has been documented with febuxostat and requires immediate recognition 1
- Monitor for systemic involvement including hepatic, renal, and hematologic abnormalities 1
Alternative Urate-Lowering Therapy
Switch to Allopurinol (if no prior severe reaction)
- Allopurinol is recommended as first-line urate-lowering therapy for most patients with normal to mildly impaired renal function 3
- Start at 100 mg daily and titrate by 100 mg every 2-5 weeks to achieve target serum uric acid <6 mg/dL 3, 4
- Provide mandatory anti-inflammatory prophylaxis with colchicine 0.5-0.6 mg once or twice daily for at least 3-6 months when initiating therapy 3, 4
Consider HLA-B*5801 Testing
- For patients of Southeast Asian descent, obtain HLA-B*5801 testing before starting allopurinol due to increased risk of severe hypersensitivity reactions 4
- Allopurinol is associated with DRESS syndrome and severe cutaneous adverse reactions, particularly in patients carrying the HLA-B*5801 allele 3
Alternative Options if Allopurinol Contraindicated
- Consider uricosuric agents (probenecid) if no history of nephrolithiasis and adequate renal function 3
- Pegloticase may be considered as third-line therapy in refractory cases with failure of oral urate-lowering therapy 3
Critical Pitfalls to Avoid
- Never rechallenge with febuxostat after erythroderma, as this can result in more severe reactions including vasculitis 1, 2
- Do not assume febuxostat is safe in patients with prior allopurinol hypersensitivity reactions—while febuxostat is often recommended as an alternative, severe cutaneous reactions can still occur 1, 2
- Ensure anti-inflammatory prophylaxis is provided when initiating any new urate-lowering therapy to prevent acute gout flares 3, 4
- Monitor closely during the first weeks of any new urate-lowering therapy for signs of hypersensitivity reactions 1, 2
Long-Term Gout Management
Target Serum Uric Acid Levels
- Maintain serum uric acid <6 mg/dL for all gout patients 3, 4
- Consider target <5 mg/dL in patients with tophi until complete crystal dissolution occurs 5
- Monitor serum uric acid every 2-5 weeks during dose titration, then every 6 months once at target 5, 4