DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)
This patient has DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), a potentially life-threatening hypersensitivity reaction to allopurinol that requires immediate drug discontinuation. 1
Clinical Presentation
The triad of lymphadenopathy, eosinophilia, and elevated liver enzymes (including bilirubin) following recent allopurinol initiation is pathognomonic for DRESS syndrome. The FDA drug label explicitly describes this syndrome as characterized by:
- Fever, severe and profuse skin rash
- Elevated eosinophil counts and lymphadenopathy (as in this patient)
- Multi-organ pathologies, particularly hepatic and renal systems (manifesting as cholestatic jaundice, hyperbilirubinemia, elevated transaminases) 1
The syndrome is potentially life-threatening and fatal, with symptoms typically developing approximately 1 week after initiating allopurinol, though longer latency periods (up to 8 weeks) have been documented 1, 2.
Immediate Management Algorithm
Step 1: Discontinue allopurinol immediately - The FDA label is unequivocal: "ALLOPURINOL TABLETS SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR OTHER SIGNS WHICH MAY INDICATE AN ALLERGIC REACTION" 1. In severe reactions with fever, eosinophilia, and hepatic involvement, this becomes even more critical.
Step 2: Initiate systemic corticosteroids - Multiple case reports demonstrate successful treatment with corticosteroids (typically IV methylprednisolone or hydrocortisone), with clinical improvement occurring within 3-7 days 3, 2, 4, 5.
Step 3: Monitor for multi-organ involvement - Check:
- Hepatic function (transaminases, bilirubin, alkaline phosphatase)
- Renal function (creatinine, BUN) - acute kidney injury with interstitial nephritis is common 2
- Cardiac, pulmonary, and gastrointestinal systems
- Complete blood count with differential (eosinophilia, atypical lymphocytosis)
Step 4: Consider HHV-6 reactivation testing - Viral reactivation, particularly HHV-6, is part of the syndrome and may guide treatment duration 2.
Critical Pitfalls
Renal impairment significantly increases risk - Even patients with stable renal function from previous donor nephrectomy (not intrinsic kidney disease) remain at elevated risk 3. The incidence of hypersensitivity reactions is increased in patients with decreased renal function, particularly when combined with thiazides 1.
Avoid other potentially hypersensitivity-inducing drugs during acute phase - One case demonstrated severe exacerbation when teicoplanin was administered during active DRESS syndrome 4. Do not introduce new medications with high hypersensitivity potential until complete resolution.
Delayed progression despite drug discontinuation - Some patients experience worsening organ involvement (particularly renal failure requiring dialysis) even after stopping allopurinol and initiating corticosteroids 2, 6. Close monitoring for 4-6 weeks is essential.
Mortality Risk
DRESS syndrome carries significant mortality risk - one case series reported death from multiple organ failure at day 24 despite treatment 6. The syndrome includes risks of hepatic necrosis, necrotizing angiitis, vasculitis, and irreversible hepatotoxicity 1.
Diagnostic Confirmation
Use the RegiSCAR scoring system to confirm diagnosis 7. The combination of:
- Recent drug exposure (allopurinol within 1-8 weeks)
- Eosinophilia (>1,000/μL or >10%)
- Lymphadenopathy
- Hepatic involvement (elevated transaminases, bilirubin)
- Skin rash
...provides high diagnostic certainty for DRESS syndrome.