Allopurinol hypersensitivity syndrome

Other names| AHS
Allopurinol
Symptoms| Fever, Cutaneous Reaction, Eosinophilia, Acute Renal Failure.[1]
Treatment| Systematic Corticosteroids.[2]
Frequency| Rare

Allopurinol hypersensitivity syndrome (AHS) typically occurs in persons with preexisting kidney failure.[3]: 119 Weeks to months after allopurinol is begun, the patient develops a morbilliform eruption[3]: 119 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.[4] About 1 in 1000 patients receiving allopurinol are affected, and mortality rates have been reported to be between 20% and 25%.[5]

## Contents

* 1 Signs and symptoms
* 2 Causes
* 2.1 Risk factors
* 2.2 Triggers
* 2.3 Genetics
* 3 Prevention
* 4 Treatment
* 5 See also
* 6 References
* 7 Further reading
* 8 External links

## 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.[1]

## Causes

### Risk factors

In a retrospective case-control study, it was shown that an increased initial dose of allopurinol was linked to AHS.[6]

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.[7] 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.[8] 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.[9] 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.[10]

### 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.[8]

## 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.[2] Allopurinol should not be given to patients who develop AHS again; instead, alternative urate-lowering medications, such as febuxostat, may be taken into consideration.[5]

## See also

* Severe cutaneous adverse reactions
* List of cutaneous conditions

## References

1. ↑ 1.0 1.1 Stamp, Lisa K.; Barclay, Murray L. (December 19, 2017). "How to prevent allopurinol hypersensitivity reactions?". Rheumatology (Oxford University Press (OUP)) 57 (suppl_1): i35–i41. doi:10.1093/rheumatology/kex422. ISSN 1462-0324. PMID 29272508.
2. ↑ 2.0 2.1 Yaseen, Wid; Auguste, Bourne; Zipursky, Jonathan (April 2, 2023). "Allopurinol hypersensitivity syndrome". Canadian Medical Association Journal (CMA Impact Inc.) 195 (13): E483. doi:10.1503/cmaj.221575. ISSN 0820-3946. PMID 37011932.
3. ↑ 3.0 3.1 James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
4. ↑ "Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions". Current Opinion in Allergy and Clinical Immunology 16 (4): 339–45. August 2016. doi:10.1097/ACI.0000000000000286. PMID 27362322.
5. ↑ 5.0 5.1 Khanna, Dinesh; Fitzgerald, John D.; Khanna, Puja P.; Bae, Sangmee; Singh, Manjit K.; Neogi, Tuhina; Pillinger, Michael H.; Merill, Joan et al. (September 28, 2012). "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): 1431–1446. doi:10.1002/acr.21772. ISSN 2151-464X. PMID 23024028.
6. ↑ Stamp, Lisa K.; Taylor, William J.; Jones, Peter B.; Dockerty, Jo L.; Drake, Jill; Frampton, Christopher; Dalbeth, Nicola (2012). "Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposed safe starting dose of allopurinol". Arthritis & Rheumatism 64 (8): 2529–2536. doi:10.1002/art.34488. ISSN 0004-3591.
7. ↑ Day, Richard O; Graham, Garry G; Hicks, Mark; McLachlan, Andrew J; Stocker, Sophie L; Williams, Kenneth M (2007). "Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol". Clinical Pharmacokinetics 46 (8): 623–644. doi:10.2165/00003088-200746080-00001. ISSN 0312-5963. PMID 17655371.
8. ↑ 8.0 8.1 Stamp, Lisa K.; Day, Richard O.; Yun, James (September 29, 2015). "Allopurinol hypersensitivity: investigating the cause and minimizing the risk". Nature Reviews Rheumatology (Springer Science and Business Media LLC) 12 (4): 235–242. doi:10.1038/nrrheum.2015.132. ISSN 1759-4790. PMID 26416594.
9. ↑ Hande, Kenneth R.; Noone, Richard M.; Stone, William J. (1984). "Severe allopurinol toxicity". The American Journal of Medicine (Elsevier BV) 76 (1): 47–56. doi:10.1016/0002-9343(84)90743-5. ISSN 0002-9343. PMID 6691361.
10. ↑ 10.0 10.1 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. et al. (2013). "Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012". Drug Safety 36 (10): 953–980. doi:10.1007/s40264-013-0084-0. ISSN 0114-5916. PMID 23873481.
11. ↑ Hung, Shuen-Iu; Chung, Wen-Hung; Liou, Lieh-Bang; Chu, Chen-Chung; Lin, Marie; Huang, Hsien-Ping; Lin, Yen-Ling; Lan, Joung-Liang et al. (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 102 (11): 4134–4139. doi:10.1073/pnas.0409500102. ISSN 0027-8424. PMID 15743917. Bibcode: 2005PNAS..102.4134H.
12. ↑ Lonjou, Christine; Borot, Nicolas; Sekula, Peggy; Ledger, Neil; Thomas, Laure; Halevy, Sima; Naldi, Luigi; Bouwes-Bavinck, Jan-Nico et al. (2008). "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): 99–107. doi:10.1097/fpc.0b013e3282f3ef9c. ISSN 1744-6872. PMID 18192896.

## Further reading

* Arellano, Félix; Sacristán, José A. (1993). "Allopurinol Hypersensitivity Syndrome: A Review". Annals of Pharmacotherapy 27 (3): 337–343. doi:10.1177/106002809302700317. ISSN 1060-0280. PMID 8453174.
* Lupton, George P.; Odom, Richard B. (1979). "The allopurinol hypersensitivity syndrome". Journal of the American Academy of Dermatology (Elsevier BV) 1 (4): 365–374. doi:10.1016/s0190-9622(79)70031-4. ISSN 0190-9622. PMID 159913.

## External links

* Allopurinol - Mayo Clinic
* Allopurinol - WebMD

Classification|

* ICD-11: NE60
* ICD-10: Y54.8
* ICD-10-CM: T50.4X5A
* ICD-9-CM: 995.29
* SNOMED CT: 702810006

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External resources|

* Scholia: Q4733137

* v
* t
* e

Drug reactions (Y40-Y59, E930-E949)

Adverse drug reaction/
drug eruption|

* antibiotics: Penicillin drug reaction
* Sulfonamide hypersensitivity syndrome
* Urticarial erythema multiforme
* Adverse effects of fluoroquinolones

* hormones: Steroid acne
* Steroid folliculitis

* chemotherapy: Chemotherapy-induced acral erythema
* Chemotherapy-induced hyperpigmentation
* Scleroderma-like reaction to taxanes
* Hydroxyurea dermopathy
* Exudative hyponychial dermatitis

* blood: Anticoagulant-induced skin necrosis
* Warfarin necrosis
* Vitamin K reaction
* Texier's disease

* anticonvulsant: Anticonvulsant hypersensitivity syndrome

* water-balance/acid-base: Allopurinol hypersensitivity syndrome

* pulmonary: Leukotriene receptor antagonist-associated Churg–Strauss syndrome

* vaccine: Eczema vaccinatum

* other specified agents: Adverse reaction to biologic agents
* Adverse reaction to cytokines
* Bromoderma
* Halogenoderma
* Iododerma
* Red man syndrome
* Methotrexate-induced papular eruption

* unspecified agent: Acute generalized exanthematous pustulosis
* Bullous drug reaction
* Drug-induced acne
* Drug-induced angioedema
* Drug-related gingival hyperplasia
* Drug-induced lichenoid reaction
* Drug-induced lupus erythematosus
* Drug-induced nail changes
* Drug-induced pigmentation
* Drug-induced pseudolymphoma
* Drug-induced urticaria
* Fixed drug reaction
* Stevens–Johnson syndrome
* Injection site reaction
* Linear IgA bullous dermatosis
* Toxic epidermal necrolysis
* HIV disease-related drug reaction
* Photosensitive drug reaction
* Serum sickness-like reaction

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