Fever and rash after a new antibiotic in a patient with renal impairment
A 45-year-old woman is admitted with 4 days of fever, a widespread maculopapular rash, and painful oral ulcers. She was started on allopurinol 300 mg daily 3 weeks ago for gout and also received a course of co-trimoxazole for a urinary tract infection 10 days ago. She has CKD stage 4 (eGFR 22 mL/min/1.73 m²). Examination: temperature 38.9°C, BP 102/64 mmHg, HR 110/min, widespread erythematous macules coalescing on the trunk, mucosal erosions in the mouth and conjunctival injection. Labs: WBC 3.1 ×10⁹/L, eosinophils 1.4 ×10⁹/L, ALT 180 U/L, creatinine 260 µmol/L (baseline 200), CRP 120 mg/L. Blood cultures are pending.
1. What is the most likely diagnosis and what is the immediate management priority?
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The picture - fever, widespread maculopapular rash with mucosal involvement (oral ulcers, conjunctival injection), eosinophilia, leucopenia, hepatitis, and renal impairment, with a new drug (allopurinol) started 3 weeks earlier - is highly suggestive of a severe cutaneous adverse reaction, most likely DRESS (drug reaction with eosinophilia and systemic symptoms) or Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of eosinophilia, hepatitis, and a maculopapular rather than bullous/necrotic rash favours DRESS, but mucosal involvement means SJS/TEN must be considered. Co-trimoxazole (a sulfonamide) is also a classic culprit and could be the trigger rather than allopurinol - both should be stopped.
Immediate priorities:
- Stop all suspect drugs - allopurinol and co-trimoxazole now. This is the single most important intervention.
- Assess severity and mucosal involvement - ophthalmology review for conjunctival involvement, and dermatology review; if there is epidermal detachment, manage as a burn-type patient in a specialised unit.
- Supportive care - fluids, wound care, analgesia, and monitoring for secondary infection. Avoid unnecessary new drugs.
- Do not start empiric antibiotics for the rash alone - but with fever, leucopenia, and mucosal breakdown, I would take cultures and consider broad-spectrum cover if there are signs of sepsis, while recognising antibiotics can worsen the reaction.
- Corticosteroids are controversial; in DRESS with organ involvement, systemic steroids are often used, but this should be a specialist decision.
I would also check for viral reactivation (HHV-6, CMV, EBV) which can drive DRESS, and monitor liver and renal function closely.
2. How does her CKD stage 4 change your drug dosing and monitoring over the next week?
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CKD stage 4 (eGFR 22) has several implications:
- Allopurinol - should have been dose-reduced in renal impairment (typically 100 mg daily or less with eGFR <30). The 300 mg dose likely contributed to the severity. Once she recovers, any urate-lowering therapy must be renally dosed and titrated to urate, with prophylaxis against flares.
- Co-trimoxazole - accumulates in renal impairment (trimethoprim raises creatinine and potassium, and can cause crystalluria); avoid or dose-reduce, and monitor potassium and creatinine.
- Any new drugs - avoid nephrotoxins (NSAIDs, aminoglycosides, contrast) and dose-adjust renally cleared drugs. If antibiotics are needed for sepsis, choose agents with renal dosing (e.g. adjusted beta-lactam) and monitor levels where relevant.
- Monitoring: daily renal function and electrolytes, liver function, FBC (eosinophils, neutrophils), and fluid balance. Watch for AKI on CKD - creatinine has already risen from 200 to 260.
- Steroids if used - no renal dose adjustment needed, but monitor glucose and blood pressure.
- Avoid re-exposure - document the allergy clearly (allopurinol and sulfonamides) and counsel the patient. Consider HLA-B*58:01 testing before any future allopurinol, given the severe reaction.
I would involve nephrology if renal function continues to deteriorate, and pharmacy for renal dosing of all medications.