From the Guidelines
Allopurinol and Hypersensitivity Vasculitis
Allopurinol, a xanthine oxidase inhibitor commonly used to treat gout and hyperuricemia, can cause hypersensitivity vasculitis, a rare but potentially severe adverse reaction 1. This condition typically occurs within the first few months of treatment, often at doses ranging from 100 to 300 mg per day, and is characterized by inflammation of small blood vessels, resulting in symptoms such as:
- Palpable purpura
- Skin rash
- Arthralgias The exact incidence of allopurinol-induced hypersensitivity vasculitis is unknown, but it is considered a rare adverse event, estimated to occur in less than 1% of patients treated with this medication 1.
Risk Factors and Management
Certain populations, such as those with the HLA-B5801 haplotype, which is prevalent in Asian persons, including those of Han Chinese and Thai descent, and in Korean persons with stage 3 or worse chronic kidney disease, may have an increased risk for serious adverse effects with allopurinol, including hypersensitivity vasculitis 1. To minimize this risk, it is recommended to start with a low dose of allopurinol (no greater than 100 mg per day) and gradually titrate upwards, with regular monitoring for signs of hypersensitivity and other adverse events 1. Additionally, prior to initiation of allopurinol, rapid PCR-based HLA-B5801 screening should be considered as a risk management component in high-risk sub-populations 1.
Key Considerations
When prescribing allopurinol, it is essential to:
- Be aware of the potential for hypersensitivity vasculitis and other severe adverse reactions
- Monitor patients closely for signs of hypersensitivity, such as rash, pruritis, and elevated hepatic transaminases
- Adjust the dose accordingly, taking into account renal impairment and other risk factors
- Consider alternative treatments, such as febuxostat, in patients who are at high risk for allopurinol hypersensitivity reactions 1.
From the FDA Drug Label
Skin and Appendages: Erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), hypersensitivity vasculitis, purpura, vesicular bullous dermatitis, exfoliative dermatitis, eczematoid dermatitis, pruritus, urticaria, alopecia, onycholysis, lichen planus. In some instances a skin rash may be followed by more severe hypersensitivity reactions such as ... generalized vasculitis
Yes, allopurinol (Zyloprim) can cause hypersensitivity vasculitis 2, 2.
From the Research
Allopurinol and Hypersensitivity Vasculitis
- Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO) activity, has been associated with severe adverse reactions, including hypersensitivity vasculitis 3.
- Severe or life-threatening allopurinol adverse reactions, such as severe cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol hypersensitivity syndrome, occur less frequently but can be serious 3.
- A study found that one patient developed biopsy-confirmed cutaneous leukocytoclastic vasculitis while being treated with febuxostat, a non-purine analog inhibitor of XO, after previously experiencing severe allopurinol reactions 3.
- Other studies have reported on the efficacy and safety of febuxostat compared to allopurinol, but did not specifically mention hypersensitivity vasculitis as an adverse reaction 4, 5, 6.
- One study discussed the use of allopurinol in treating cardiac ischemia, but did not mention hypersensitivity vasculitis 7.
Key Findings
- Allopurinol can cause hypersensitivity vasculitis, although it is a rare adverse reaction 3.
- Febuxostat may be a safe alternative for patients who experience severe allopurinol reactions, including hypersensitivity vasculitis 3.
- Further research is needed to fully understand the relationship between allopurinol and hypersensitivity vasculitis.