What is the management of an allopurinol (Zyloprim) reaction?

Management of Allopurinol Reaction

If a rash develops during allopurinol treatment, the medication should be discontinued immediately as skin reactions can be severe and potentially fatal. 1

Types of Allopurinol Reactions

Allopurinol reactions can manifest in several forms, ranging from mild to life-threatening:

• Mild reactions: Pruritic maculopapular skin eruptions
• Severe reactions:
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  • Stevens-Johnson Syndrome (SJS)
  • Toxic Epidermal Necrolysis (TEN)
  • Allopurinol Hypersensitivity Syndrome (AHS)

Immediate Management

1. Discontinue allopurinol immediately upon appearance of any rash 2, 1

2. Assess severity of the reaction:

   • Presence of fever, mucosal involvement, blistering
   • Laboratory evaluation: CBC with differential (check for eosinophilia), liver function tests, renal function
   • Vital sign monitoring

3. Supportive care based on severity:

   • For mild reactions: Antihistamines and topical corticosteroids
   • For severe reactions: Hospital admission, possibly ICU care with:
     • Fluid replacement therapy
     • Systemic corticosteroids (e.g., prednisolone 1 mg/kg/day) 2, 3
     • Consider cyclosporine for TEN 3
     • Wound care for skin lesions (polyhexanide and octenidine) 3
     • Multidisciplinary approach involving dermatology, critical care, and other specialties as needed

Risk Factors for Allopurinol Reactions

• Genetic factors: HLA-B*58:01 variant (particularly in Asian populations) 2, 4
• Renal impairment: Increases risk due to accumulation of oxypurinol 2, 1, 5
• Concomitant medications: Thiazide diuretics, ampicillin/amoxicillin 1, 5
• Recent initiation of therapy (reactions often occur within first few weeks) 2

Alternative Treatments

After an allopurinol reaction, future use of allopurinol is contraindicated. Alternative options include:

1. Febuxostat: Recommended for patients who cannot tolerate allopurinol; starting dose ≤40 mg/day 4
2. Probenecid: Consider when xanthine oxidase inhibitors are contraindicated 4
3. Rasburicase: For acute management of hyperuricemia, particularly in tumor lysis syndrome 2
4. Pegloticase: For severe debilitating chronic tophaceous gout 4

Prevention of Allopurinol Reactions

1. Genetic testing: Consider HLA-B*58:01 screening before initiating allopurinol in high-risk populations:

   • Koreans with CKD stage 3 or worse
   • All patients of Han Chinese and Thai descent 4

2. Appropriate dosing:

   • Start with low dose (100 mg daily)
   • Reduce dose by 50% or more in renal failure 2
   • Titrate slowly ("go low, go slow" approach) 2

Important Caveats

• Desensitization protocols exist but should only be attempted in specialized centers with experience in drug allergy management 6
• The mortality rate for allopurinol hypersensitivity syndrome can be as high as 25% 2
• Patients should be educated about the early signs of hypersensitivity reactions and instructed to seek immediate medical attention if they occur
• Cross-reactivity between allopurinol and its metabolite oxipurinol is common (up to 40%) 2

Long-term Follow-up

• Monitor for sequelae of severe reactions
• Provide clear documentation of the allopurinol reaction in the patient's medical record
• Consider medical alert bracelet for patients who experienced severe reactions
• Ensure alternative gout management strategies are implemented