Allopurinol hypersensitivity syndrome explained

Allopurinol hypersensitivity syndrome
Synonyms:AHS
Symptoms:Fever, Cutaneous Reaction, Eosinophilia, Acute Renal Failure.
Treatment:Systematic Corticosteroids.
Frequency:Rare

Allopurinol hypersensitivity syndrome (AHS) typically occurs in persons with preexisting kidney failure.[1] Weeks to months after allopurinol is begun, the patient develops a morbilliform eruption or, less commonly, develops one of the far more serious and potentially lethal severe cutaneous adverse reactions viz., the DRESS syndrome, Stevens Johnson syndrome, or toxic epidermal necrolysis.[2] About 1 in 1000 patients receiving allopurinol are affected, and mortality rates have been reported to be between 20% and 25%.[3]

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.[4]

Causes

Risk factors

In a retrospective case-control study, it was shown that an increased initial dose of allopurinol was linked to AHS.[5]

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.[6] 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.[7] 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.[8] 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.[9]

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.[10]

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.[11] [12]

Prevention

Preventative measures include using alternative drugs, genetic screening, and modifying the starting dose.[7]

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.[13] Allopurinol should not be given to patients who develop AHS again; instead, alternative urate-lowering medications, such as febuxostat, may be taken into consideration.[3]

See also

Further reading

External links

Notes and References

  1. James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. .
  2. Wang CW, Dao RL, Chung WH . Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions . Current Opinion in Allergy and Clinical Immunology . 16 . 4 . 339–45 . August 2016 . 27362322 . 10.1097/ACI.0000000000000286 . 9183824 .
  3. Khanna . Dinesh . Fitzgerald . John D. . Khanna . Puja P. . Bae . Sangmee . Singh . Manjit K. . Neogi . Tuhina . Pillinger . Michael H. . Merill . Joan . Lee . Susan . Prakash . Shraddha . Kaldas . Marian . Gogia . Maneesh . Perez-Ruiz . Fernando . Taylor . Will . Lioté . Frédéric . Choi . Hyon . Singh . Jasvinder A. . Dalbeth . Nicola . Kaplan . Sanford . Niyyar . Vandana . Jones . Danielle . Yarows . Steven A. . Roessler . Blake . Kerr . Gail . King . Charles . Levy . Gerald . Furst . Daniel E. . Edwards . N. Lawrence . Mandell . Brian . Schumacher . H. Ralph . Robbins . Mark . Wenger . Neil . Terkeltaub . Robert . 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia . Arthritis Care & Research . Wiley . 64 . 10 . September 28, 2012 . 2151-464X . 10.1002/acr.21772 . 1431–1446. 23024028 . 2027.42/93740 . 16853635 . free .
  4. Stamp . Lisa K. . Barclay . Murray L. . How to prevent allopurinol hypersensitivity reactions? . Rheumatology . Oxford University Press (OUP) . 57 . suppl_1 . December 19, 2017 . 1462-0324 . 10.1093/rheumatology/kex422 . i35–i41 . 29272508 . free.
  5. Stamp . Lisa K. . Taylor . William J. . Jones . Peter B. . Dockerty . Jo L. . Drake . Jill . Frampton . Christopher . Dalbeth . Nicola . Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposed safe starting dose of allopurinol . Arthritis & Rheumatism . 64 . 8 . 2012 . 0004-3591 . 10.1002/art.34488 . 2529–2536 .
  6. Day . Richard O . Graham . Garry G . Hicks . Mark . McLachlan . Andrew J . Stocker . Sophie L . Williams . Kenneth M . Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol . Clinical Pharmacokinetics . 46 . 8 . 2007 . 0312-5963 . 10.2165/00003088-200746080-00001 . 623–644. 17655371 . 20369375 .
  7. Stamp . Lisa K. . Day . Richard O. . Yun . James . Allopurinol hypersensitivity: investigating the cause and minimizing the risk . Nature Reviews Rheumatology . Springer Science and Business Media LLC . 12 . 4 . September 29, 2015 . 1759-4790 . 10.1038/nrrheum.2015.132 . 235–242. 26416594 . 7273698 .
  8. Hande . Kenneth R. . Noone . Richard M. . Stone . William J. . Severe allopurinol toxicity . The American Journal of Medicine . Elsevier BV . 76 . 1 . 1984 . 0002-9343 . 10.1016/0002-9343(84)90743-5 . 47–56. 6691361 .
  9. Ramasamy . Sheena N. . Korb-Wells . Cameron S. . Kannangara . Diluk R. W. . Smith . Myles W. H. . Wang . Nan . Roberts . Darren M. . Graham . Garry G. . Williams . Kenneth M. . Day . Richard O. . Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012 . Drug Safety . 36 . 10 . 2013 . 0114-5916 . 10.1007/s40264-013-0084-0 . 953–980. 23873481 . 37362888 .
  10. Ramasamy . Sheena N. . Korb-Wells . Cameron S. . Kannangara . Diluk R. W. . Smith . Myles W. H. . Wang . Nan . Roberts . Darren M. . Graham . Garry G. . Williams . Kenneth M. . Day . Richard O. . Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012 . Drug Safety . 36 . 10 . 2013 . 0114-5916 . 10.1007/s40264-013-0084-0 . 953–980. 23873481 . 37362888 .
  11. Hung . Shuen-Iu . Chung . Wen-Hung . Liou . Lieh-Bang . Chu . Chen-Chung . Lin . Marie . Huang . Hsien-Ping . Lin . Yen-Ling . Lan . Joung-Liang . Yang . Li-Cheng . Hong . Hong-Shang . Chen . Ming-Jing . Lai . Ping-Chin . Wu . Mai-Szu . Chu . Chia-Yu . Wang . Kuo-Hsien . Chen . Chien-Hsiun . Fann . Cathy S. J. . Wu . Jer-Yuarn . Chen . Yuan-Tsong . HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol . Proceedings of the National Academy of Sciences . 102 . 11 . 2005-03-15 . 0027-8424 . 15743917 . 554812 . 10.1073/pnas.0409500102 . 4134–4139 . 2005PNAS..102.4134H . free .
  12. Lonjou . Christine . Borot . Nicolas . Sekula . Peggy . Ledger . Neil . Thomas . Laure . Halevy . Sima . Naldi . Luigi . Bouwes-Bavinck . Jan-Nico . Sidoroff . Alexis . de Toma . Claudia . Schumacher . Martin . Roujeau . Jean-Claude . Hovnanian . Alain . Mockenhaupt . Maja . A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs . Pharmacogenetics and Genomics . Ovid Technologies (Wolters Kluwer Health) . 18 . 2 . 2008 . 1744-6872 . 10.1097/fpc.0b013e3282f3ef9c . 99–107. 18192896 . 35512622 .
  13. Yaseen . Wid . Auguste . Bourne . Zipursky . Jonathan . Allopurinol hypersensitivity syndrome . Canadian Medical Association Journal . CMA Impact Inc. . 195 . 13 . April 2, 2023 . 0820-3946 . 10.1503/cmaj.221575 . E483. 37011932 . free . 10069920 .

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