Allopurinol hypersensitivity syndrome

Signs and symptoms

Allopurinol has been linked to severe cutaneous adverse reactions (SCAR), toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Clinically, these syndromes are similar in that they both involve fever, eosinophilia, rash, and dysfunction of the liver and kidneys.

Causes

Risk factors

In a retrospective case-control study, it was shown that an increased initial dose of allopurinol was linked to AHS.

Oxypurinol is quickly transformed from allopurinol and then eliminated by the kidneys. The mean half-life of oxypurinol in patients with normal kidney function is 23 hours, although 95% of patients have half-lives between 9 and 38 hours. The half-life of oxypurinol increases with decreasing kidney function, allowing it to build up over an extended period of time and reach higher steady-state concentrations; among those suffering from anuria, nearly no oxypurinol is eliminated. The first report of the link between kidney impairment and AHS was found in a 1984 case series, wherein 58 patients with AHS had demonstrated signs of kidney impairment before starting allopurinol treatment. Additionally, among the most common co-morbidities in a comprehensive analysis of all 901 reported cases of AHS, chronic kidney disease was present in 182 out of 376 (48%) patients.

Triggers

After beginning allopurinol, allopurinol hypersensitivity syndrome usually manifests itself in the first few weeks to months. Ninety percent of the 901 documented cases of AHS in the largest review to date began within the first 8 to 9 weeks of starting allopurinol, with a median time to onset of 3 weeks.

Genetics

The HLA-B gene belongs to the family of genes called the HLA complex. An odds ratio of 80–580 has been reported to link the HLA-B*58:01 allele to a higher risk of allopurinol-induced DRESS and SJS/TEN.

Prevention

Preventative measures include using alternative drugs, genetic screening, and modifying the starting dose.

Treatment

Treatment consists of discontinuing allopurinol and providing supportive care. Immunomodulatory treatments and systemic steroids might be helpful. Whether a patient has toxic epidermal necrolysis, Stevens-Johnson syndrome, or drug reaction with eosinophilia and systemic symptoms will determine the course of treatment. Allopurinol should not be given to patients who develop AHS again; instead, alternative urate-lowering medications, such as febuxostat, may be taken into consideration.

References

References

1. James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. {{ISBN. 0-7216-2921-0.
2. (August 2016). "Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions". Current Opinion in Allergy and Clinical Immunology.
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4. (December 19, 2017). "How to prevent allopurinol hypersensitivity reactions?". Oxford University Press (OUP).
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6. (2007). "Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol". Clinical Pharmacokinetics.
7. (September 29, 2015). "Allopurinol hypersensitivity: investigating the cause and minimizing the risk". Springer Science and Business Media LLC.
8. (1984). "Severe allopurinol toxicity". Elsevier BV.
9. (2013). "Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012". Drug Safety.
10. (2005-03-15). "HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol". Proceedings of the National Academy of Sciences.
11. (2008). "A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs". Ovid Technologies (Wolters Kluwer Health).
12. (April 2, 2023). "Allopurinol hypersensitivity syndrome". CMA Impact Inc..