How to manage exfoliation in a patient with erythroderma, a history of gout, and currently taking febuxostat (febuxostat)?

Management of Exfoliative Erythroderma in a Patient Taking Febuxostat

Immediately discontinue febuxostat and do not rechallenge, as this patient has developed a severe cutaneous adverse reaction that requires permanent cessation of the offending medication. 1, 2

Immediate Management of Erythroderma

• Hospitalize the patient for initial evaluation and treatment, as exfoliative dermatitis is a serious skin disorder requiring intensive monitoring and supportive care 1
• Maintain temperature control, as extensive skin involvement impairs thermoregulation 1
• Replace lost fluids and electrolytes due to increased transepidermal water loss 1
• Prevent and treat secondary bacterial infections, which are common complications 1
• Maintain skin barrier function with emollients and appropriate wound care 2
• Provide sedative antihistamines for symptomatic relief 2
• Consult nutrition services for assessment, as protein and caloric losses can be significant 2

Diagnostic Workup for Erythroderma

• Obtain multiple skin biopsies if the etiology remains uncertain after initial evaluation, as this enhances diagnostic accuracy 2
• Conduct a thorough search for underlying malignancy, particularly cutaneous T-cell lymphoma, which may not manifest for months or years after onset of erythroderma 1
• Review all medications the patient is taking, as drug reactions are among the most common causes of exfoliative dermatitis 1, 2

Febuxostat and Severe Cutaneous Reactions

The risk of severe cutaneous reactions with febuxostat exists, though it appears lower than with allopurinol. One documented case in the literature describes a patient who developed exfoliative erythroderma on allopurinol and subsequently developed biopsy-confirmed cutaneous leukocytoclastic vasculitis on febuxostat 3. This demonstrates potential cross-reactivity or independent hypersensitivity reactions to febuxostat in patients with prior severe allopurinol reactions.

• Among patients with prior cutaneous reactions to allopurinol, approximately 9% developed skin reactions to febuxostat, compared to 2.5% without prior allopurinol reactions 4
• The risk of skin reaction with febuxostat is moderately increased in patients with a history of cutaneous adverse events with allopurinol, though this does not definitively support cross-reactivity 4

Alternative Urate-Lowering Therapy After Recovery

Once the erythroderma has resolved and the patient is stable, alternative urate-lowering therapy options include:

• Consider allopurinol desensitization if the patient has no history of severe cutaneous reactions to allopurinol and cannot be treated with other oral urate-lowering agents 5
• Uricosuric agents (probenecid) may be appropriate if the patient does not have known renal calculi or moderate-to-severe chronic kidney disease 6
• Pegloticase (intravenous biologic) for refractory cases where oral agents are contraindicated 5

Critical Pitfalls to Avoid

• Never rechallenge with febuxostat after a severe cutaneous reaction, as this can result in life-threatening recurrence 3, 1
• Do not assume the erythroderma is solely drug-related without investigating for underlying malignancy, particularly cutaneous T-cell lymphoma 1
• Do not manage erythroderma on an outpatient basis, as complications including sepsis, fluid/electrolyte imbalances, and hypothermia require hospital-level monitoring 1
• When considering alternative urate-lowering therapy after recovery, ensure adequate prophylaxis with colchicine (dose-adjusted for renal function) or low-dose NSAIDs for 3-6 months to prevent gout flares 7, 6

Prognosis

• The long-term prognosis is generally good in patients with drug-induced erythroderma once the offending agent is discontinued 1
• The course tends to be remitting and relapsing in idiopathic cases 1
• Prognosis in cases associated with malignancy depends on the outcome of the underlying malignancy 1