Fever, facial oedema, eosinophilia, and hepatitis after allopurinol
A 43-year-old woman started allopurinol 100 mg daily 4 weeks ago for asymptomatic hyperuricaemia. She presents with fever of 38.8°C, a widespread morbilliform eruption covering about 70% of her body surface area, facial oedema and tender cervical lymphadenopathy. There are no mucosal erosions and no blistering. Blood tests show eosinophils 1.8 × 10⁹/L (18%), ALT 210 U/L (baseline 24), creatinine 1.4 mg/dL (baseline 0.7), and atypical lymphocytes on the film. She has no history of gout. HLA-B*58:01 is positive. She is taking no other new medicines and has no prior drug allergies. She asks whether she can continue allopurinol at a lower dose and take an antihistamine.
1. What is the diagnosis and how would you assess severity? Why is this not SJS/TEN?
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The diagnosis is DRESS (drug reaction with eosinophilia and systemic symptoms), probably definite on the RegiSCAR score: fever, lymphadenopathy, eosinophilia, atypical lymphocytes, rash over more than 50% of body surface area, and liver and kidney involvement. The latent period of 4 weeks after starting allopurinol is typical. HLA-B*58:01 is a strong risk marker for allopurinol hypersensitivity.
This is not Stevens–Johnson syndrome or toxic epidermal necrolysis because there are no mucosal erosions and no epidermal detachment. SJS/TEN is a blistering disease with skin sloughing and prominent mucosal involvement; DRESS is a systemic hypersensitivity reaction with rash, eosinophilia, lymphadenopathy, and organ involvement. The facial oedema and hepatitis also favour DRESS. Severity should be assessed by the extent of organ involvement, especially liver and kidney function, and by monitoring for myocarditis, pneumonitis, and thyroiditis.
2. What is your immediate management, and how do you handle the allopurinol?
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I would stop allopurinol immediately and permanently, and document it as a severe adverse reaction. Lowering the dose is not acceptable because re-exposure can cause a more severe or fatal recurrence. I would give supportive care, monitor fluid balance and renal function, and start systemic corticosteroids, typically prednisolone 1 mg/kg/day, with a slow taper over 6–8 weeks because of the risk of rebound. Antihistamines alone are inadequate for a systemic reaction with hepatitis and renal impairment.
I would monitor for HHV-6 and CMV reactivation, which can cause fever and hepatitis flares, and check thyroid function, cardiac enzymes, and chest imaging if symptoms suggest myocarditis or pneumonitis. The patient should be reviewed frequently during the taper. If she develops mucosal erosions or blistering, the diagnosis must be reconsidered and urgent dermatology review arranged.
3. What is the long-term plan, including alternatives for hyperuricaemia?
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She should never receive allopurinol or oxypurinol again. I would explain the HLA-B*58:01 association and advise her to tell all future prescribers. Because she had asymptomatic hyperuricaemia, the original indication for allopurinol was questionable; asymptomatic hyperuricaemia is generally not treated with urate-lowering therapy unless there is gout, urate nephropathy, or another specific indication. If treatment is genuinely needed later, I would discuss febuxostat with caution, because cross-reactivity is possible but not absolute, or a uricosuric agent after specialist advice.
Long-term follow-up should include liver and kidney function, thyroid function, and blood counts for several months, because autoimmune sequelae such as thyroiditis and type 1 diabetes can occur after DRESS. I would also advise her to seek urgent care for fever, rash, mucosal lesions, or facial swelling. The key message is that this is a serious drug hypersensitivity, not a reason to adjust the dose of allopurinol.