Allopurinol hypersensitivity syndrome

Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome A review. Ann Pharmacother 1993 27 337-343. 

The major side effects of allopurinol are skin rash, urticaria, leukopenia, GI problems, headache, and increased frequency of acute gouty attacks with the initiation of therapy. An allopurinol hypersensitivity syndrome characterized by fever, eosinophilia, dermatitis, vasculitis, and renal and hepatic dysfunction occurs rarely but is associated with a 20% mortality rate. 

Lupton GP, Odom RB. The allopurinol hypersensitivity syndrome. J Am Acad Dermatol 1979 l(4) 365-74. 

Vazquez-Mellado J, Guzman Vazquez S, Cazarin Barrientos J, Gomez Rios V, Burgos-Vargas R. Desensitisation to allopurinol after allopurinol hypersensitivity syndrome with renal involvement in gout. J Clin Rheumatol 2000 6 266-8. 

Singer JZ, Wallace SLThe allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality. Arthritis Rheum 1986 29 82-87. 

Vanderstigel M, Zafrani ES, Deyone JL, et al. Allopurinol hypersensitivity syndrome as a cause of hepatic fibrin granulomas. Gastroenterology 1986 90 188-190. 

Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. The major side effects of allopurinol are skin rash, leukopenia, occasional gastrointestinal toxicity, and increased frequency of acute gouty attacks with the initiation of therapy. An allopurinol hypersensitivity syndrome characterized by fever, eosinophilia, dermatitis, vasculitis, and renal and hepatic dysfunction is a rare side effect, but is associated with a 20% mortality rate. ... 

To reduce the risk of developing the allopurinol hypersensitivity syndrome, some experts believe that the dose of allopurinol should be adjusted based on the patient s creatinine clearance. 

Major limitations of the use of allopurinol are allergy, hypersensitivity syndromes, hepatotoxicity, bone marrow suppression, nonspecific central nervous system and gastrointestinal side effects. Skin rash occurs in 2% and Steven-Johnson syndrome, although rare, may occur. The latter can cause life-threatening major organ system failure. 

Adverse reactions to allopurinol, particularly toxic epidermal necrolysis and a hypersensitivity syndrome, are reputed to be more common in patients taking thiazides, but evidence to support this is hard to find (SEDA-11, 198) (SEDA-13,188). 

The cutaneous reaction caused by allopurinol is predominantly a pruritic, erythematous, or maculopapular eruption, but occasionally the lesion is urticarial or purpuric. Rarely, toxic epidermal necrolysis or Stevens-Johnson syndrome occurs, which can be fatal. The risk for Stevens-Johnson syndrome is limited primarily to the first 2 months of treatment. Because the rash may precede severe hypersensitivity reactions, patients who develop a rash should discontinue allopurinol. If indicated, desensitization to allopurinol can be carried out starting at 10—25 fjbg/day, with the drug diluted in oral suspension and doubled every 3—14 days until the desired dose is reached. This is successjul in approjdmately half of patients. Oxypurinol is available for compassionate use in the U.S. for patients intolerant of allopurinol. The safety of oxypurinol in patients with severe allopurinol hypersensitivity is unknown it is not recommended in this setting. 

Fathallah N, Ben Salem C, Slim R, Kaabia N, Letaief A, Bouraoui K. Fatal allopurinol-induced hypersensitivity syndrome associated with pancreatic abnormalities. J Clin Rheumatol 2010 16(4) 170-1. 

ACE INHIBITORS ALLOPURINOL Risk of serious hypersensitivity with captopril and enalapril Uncertain. Both drugs can cause hypersensitivity reactions Warn patients to look for clinical features of hypersensitivity and Stevens-Johnson syndrome... 

Allopurinol is contraindicated in patients who have exhibited serious adverse fffects or hypersensitivity reactions to the medication, and in nursing mothers and children, except those with malignancy or certain inborn errors of purine metabolism (e.g., Lesch-Nyhan syndrome). Allopurinol generally is used in complicated hyperuricemia (see above), to prevent acute tumor lysis syndrome, or in patients with hyperuricemia post-transplantation. If necessary, it can be used in conjunction with uricosuric agents. 

Three cases of Stevens-Johnson syndrome (one fatal) and two cases of hypersensitivity have been attributed to the use of captopril with allopurinol. Anaphylaxis and myocardial infarction occurred in one man taking enalapril when given allopurinol. The combination of ACE inhibitors and allopurinol may increase the risk of leucopenia and serious infection, especially in renal impairment. 

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