A 55-Year-Old Man with Fever, Rash and Acute Kidney Injury after Starting Antibiotics
A 55-year-old man is admitted with 4 days of fever, a widespread maculopapular rash and reduced urine output. He was started on co-amoxiclav 10 days ago for a dental infection and allopurinol 3 weeks ago for asymptomatic hyperuricaemia (urate 560 micromol/L). Examination: temperature 38.6°C, BP 102/64 mmHg, HR 104. There is a diffuse erythematous rash with some targetoid lesions, facial oedema, and tender cervical lymphadenopathy. Bloods: creatinine 340 micromol/L (baseline 88), urea 18 mmol/L, eosinophils 1.6 x 10^9/L (0.04-0.4), ALT 210 U/L (10-40), platelets 98 x 10^9/L. Urinalysis: blood 2+, protein 2+, no nitrites; microscopy shows eosinophiluria and muddy brown casts.
1. What is the likely diagnosis, and which drug is the culprit? Justify your reasoning.
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The picture is a drug-induced systemic hypersensitivity reaction with acute kidney injury - most consistent with DRESS (drug reaction with eosinophilia and systemic symptoms) or a drug-induced tubulointerstitial nephritis (TIN) with a systemic component.
Supporting features:
- Fever, rash, facial oedema, lymphadenopathy - classic DRESS triad.
- Eosinophilia 1.6 x 10^9/L - marked, supports hypersensitivity.
- Hepatitis (ALT 210) - systemic organ involvement, typical of DRESS.
- AKI with eosinophiluria and muddy brown casts - acute interstitial nephritis with possible acute tubular injury.
- Timing: symptoms began 10 days after co-amoxiclav and 3 weeks after allopurinol - both are classic culprits. Allopurinol is the most notorious cause of DRESS and is a leading cause of drug-induced TIN; co-amoxiclav (beta-lactams) is also a common cause of TIN.
Culprit reasoning: Allopurinol is the more likely driver of a severe systemic reaction with hepatitis and eosinophilia, especially given the 3-week latency. However, co-amoxiclav cannot be excluded and both should be stopped. The temporal relationship with allopurinol and the severity of systemic features favour allopurinol as the primary culprit.
Differential: other causes of AKI with rash - sepsis (but no clear source, eosinophilia argues against), vasculitis (ANCA, complement), viral infection (EBV, HIV, hepatitis), and other drug reactions.
2. How would you confirm the diagnosis and manage this patient in the first 48 hours?
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Confirmation:
- Stop both culprit drugs immediately - this is both diagnostic and therapeutic.
- Skin biopsy if diagnosis is uncertain - shows interface dermatitis with eosinophils in DRESS; in TIN, renal biopsy shows interstitial infiltrate with eosinophils.
- Renal biopsy if the diagnosis is unclear or if there is no improvement after drug withdrawal - to distinguish TIN from ATN and guide steroid use.
- Exclude other causes: blood and urine cultures, viral screen (EBV, CMV, HIV, hepatitis), ANA/ANCA/complement, and review of all other medications.
First 48 hours:
- Stop allopurinol and co-amoxiclav - and avoid structurally related drugs (other beta-lactams, and importantly allopurinol's relative febuxostat should be avoided).
- Supportive care: IV fluids if hypovolaemic (cautious - he is not clearly volume-depleted), monitor urine output, correct electrolytes, and avoid nephrotoxins (NSAIDs, contrast, aminoglycosides).
- Corticosteroids: for DRESS with organ involvement, systemic corticosteroids (e.g. prednisolone 1 mg/kg/day) are indicated; for drug-induced TIN, steroids are used if there is no improvement after 3-5 days of drug withdrawal. In this patient with hepatitis and significant AKI, early steroids are reasonable.
- Monitor: renal function, LFTs, eosinophil count, and for signs of DRESS complications (myocarditis, pneumonitis, thyroiditis).
- Dialysis if refractory hyperkalaemia, acidosis, fluid overload or uraemic complications.
- Multidisciplinary input: dermatology and nephrology.
3. He recovers with a creatinine of 110 micromol/L. What long-term advice and monitoring are needed?
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Long-term advice:
- Permanent avoidance of allopurinol and documentation of the reaction in his records and on an allergy alert. Febuxostat should also be avoided because of cross-reactivity risk in severe allopurinol hypersensitivity.
- Avoid co-amoxiclav; use alternative antibiotics and document.
- Urate management: his hyperuricaemia was asymptomatic - guidelines do not recommend treating asymptomatic hyperuricaemia. If he later develops gout, use alternatives (e.g. febuxostat with caution, or uricosurics such as lesinurad/benzbromarone where available, or low-dose colchicine for flares). A rheumatology opinion is advisable.
- Renal follow-up: repeat creatinine and urinalysis; drug-induced TIN can leave residual CKD. Monitor blood pressure and avoid nephrotoxins.
- Hepatic follow-up: repeat LFTs until normal; DRESS can cause prolonged or relapsing hepatitis.
- DRESS sequelae: monitor for autoimmune sequelae (thyroiditis, type 1 diabetes, myocarditis) for up to 12 months - a recognised late complication.
- Patient education: carry an allergy card, inform all healthcare providers, and report any rash, fever or jaundice promptly.