Utilization of allopurinol has increased in tandem with the growing prevalence of gout globally. Although ahs is rare, the number of patients with gout requiring allopurinol is high, and there are sufficient overall cases of ahs to warrant consideration of preventive measures. Allopurinol for asymptomatic hyperuricemia associated with. Allopurinol hypersensitivity syndrome is a rare but lifethreatening adverse effect of allopurinol therapy. How to prevent allopurinol hypersensitivity reactions.
Combining febuxostat with nsaid does not result in a significant increase in adverse events. For this reason all patients who develop a cutaneous reaction to allopurinol should discontinue the drug. Allopurinol hypersensitivity is primarily mediated by dose. Describe the effect of the starting dose of allopurinol on the risk for allopurinol hypersensitivity syndrome in patients with gout. Indications for allopurinol therapy in all cases were asymptomatic hyperuricaemia. However, even a mild rash may be a harbinger of allopurinol hypersensitivity tumor lysis syndrome. Drug hypersensitivity reactions dhr are clinically and functionally heterogeneous.
People taking allopurinol should be advised to inform their doctor immediately if they develop any type of skin reaction while being treated with allopurinol. Hirtminkowski regionalspital emmental ag burgdorf background. More detailed information about the symptoms, causes, and treatments of allopurinol hypersensitivity syndrome is available below. Prescribers should take care when prescribing allopurinol to highrisk populations, the authors caution. T1 allopurinolhypersensitivity vasculitis and liver damage.
Although allopurinol hypersensitivity syndrome, a severe cutaneous adverse reaction, is less common, affecting 0. Allopurinol induced drug reactions with eosinophilia and systemic symptoms dress is a severe illness related to hypersensitivity syndrome characterized by fever, skin rash, lymph node. Dress syndrome is a special variant of hypersensitivity reaction dress. Drug reaction w eosinophilia and systemic symptoms dihs drug induced hypersensitivity syndrome begins 2. If you continue browsing the site, you agree to the use of cookies on this website. Fatal allopurinol hypersensitivity syndrome after treatment of. The aim of this study is to document the clinical presentation of allopurinol hypersensitivity syndrome in a local. Rasburicase is a potent recombinant form of urate oxidase, which can metabolize uric acid to the more highly soluble compound allantoin. Allopurinol hypersensitivity syndrome ahs is a disorder involving multiple organs. T1 allopurinol hypersensitivity vasculitis and liver damage. Includes apoallopurinol side effects, interactions and indications. For the treatment of severe delayedtype drug hypersensitivity, such. Allopurinol hypersensitivity syndrome a preventable adverse.
Allopurinol is the most common cause of dress syndrome in. The risk of development of allopurinol hypersensitivity syndrome is related to the level of oxypurinol metabolite of allopurinol. Full text dress syndrome associated with allopurinol. The time period from using the culprit agent to onset of the drug reaction ranged from 6 to 90 days. Gout treatment dosage affects risk for hypersensitivity syndrome. The accumulation of oxypurinol leads to tissue damage with development of antibodies against tissue components and formation of immune complexes. Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs as this could result in more serious hypersensitivity reactions including stevensjohnson syndrome and toxic epidermal necrolysis see section 4.
An 80 year old man started treatment with 300 mg allopurinol a day for asymptomatic hyperuricaemia. Severe hypersensitivity reactions associated with allopurinol. Allopurinol hypersensitivity syndrome a preventable adverse reaction. Side effects and interactions of the xanthine oxidase. Allopurinol hypersensitivity syndrome ahs was first reported by lang 4 in 1979, and diagnostic criteria were established in 1986 5. Two patients developed fever, dermatitis, renal insufficiency, and eosinophilia, three and five weeks after beginning therapy with allopurinol. The clinical, laboratory, and histologic findings were compatible with a severe hypersensitivity reaction. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or stevenjohnson syndrome and lethal toxic epidermal. Detachment of the skin affects less than 10 % of bsa. Discontinuation of allopurinol did achieve the ultimate goal of palliative care, which was to make the patient as comfortable as possible. Allopurinol hypersensitivity syndrome singapore medical journal. Allopurinol is the most common cause of dress syndrome in hungarian patients. Jun 29, 2015 furthermore, febuxostat appears to induce hypersensitivity syndrome less frequently than allopurinol, and is well tolerated by most ahs patients 34,36.
Oct 22, 2014 allopurinol is an effective uratelowering drug that is well tolerated by the majority of patients. Allopurinol use and risk of fatal hypersensitivity reactions. Allopurinol 4hydroxypyrazolo 3, 4dpyrimidine is a potent inhibitor of uric acid synthesis commonly prescribed for the treatment of gout and other hyperuricemic states 1, 2. Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Clinical symptoms typically appear 57 days after the initiation of treatment. The risk for hypersensitivity syndrome from a specific gout treatment increased as the starting dose corrected for egfr, increased. Diagnosis is challenging because the extent of skin involvement does not always correlate with the extent of internal organ involvement and therefore early recognition of symptoms is vital to minimize morbidity and mortality. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, stevensjohnson syndrome, and toxic epidermal necrolysis. Dosage adjustment might have reduced the occurrence or severity of the rash. We describe a 61yearold male patient who was treated with allopurinol and developed fever, a skin rash, eosinophilia and severe renal and liver dysfunction. The records of 8 patients with the al lopurinol hypersensitivity syndrome evaluated at the. Allopurinolhypersensitivity vasculitis and liver damage. Allopurinol hypersensitivity syndrome typically occurs in persons with preexisting kidney failure 119 weeks to months after allopurinol is begun, the patient develops a morbilliform eruption. Sangheon cho, kyungup min and hyeryun kang, an effective strategy to prevent allopurinolinduced hypersensitivity by hla typing.
Prevention and treatment view in chinese 2 mgkg daily on days 1 to 3 plus oral allopurinol 300 mg daily on days 3 to 5, or allopurinol alone 300 mg daily on days 1 to 5. Combining this interstitial nephritis with the clinical findings of fever, skin rash. Food and drug administration, silver spring, maryland. Terms such as mononucleosislike syndrome and febrile muco. Describe risk factors for and clinical features of allopurinol hypersensitivity syndrome in patients with gout who are receiving allopurinol. The frequencies of obesity, chronic kidney disease ckd, hypertension, type 2 diabetes, dyslipidaemias, cardiac diseases including coronary heart disease, heart failure and atrial fibrillation, stroke and peripheral arterial. The term hypersensitivity syndrome hss has long been used in different ways to. Febuxostat can be given to patients who are renally impaired or have allopurinol hypersensitivity syndrome.
Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Allopurinol hypersensitivity syndrome ahs is a severe and sometimes lifethreatening adverse drug reaction. This exposes more patients to the risk of allopurinol hypersensitivity ah, a rare adverse reaction characterised by a spectrum of cutaneous reactions and systemic manifestations. Allopurinol hypersensitivity syndrome in patients with hematological. In rare instances, the rash may progress to stevens johnson syndrome. The overall risks of allopurinol use remain unclear. Gout treatment dosage affects risk for hypersensitivity. Dihs drug induced hypersensitivity syndrome begins 2. Risk of fatal hypersensitivity reactions with allopurinol. Find patient medical information for allopurinol oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Allopurinol hypersensitivity syndrome in patients with.
Although the prevalence of this syndrome is thought to be low, more than 100 cases have been reported since 1970. Patients with reported allopurinol hypersensitivity syndrome were mostly middleaged men with hypertension andor renal failure, receiving excessive doses of allopurinol primarily for asymptomatic hyperuricaemia. The allopurinol hypersensitivity syndrome sciencedirect. Serious allopurinolrelated adverse events for example, allopurinol hypersensitivity syndrome ahs are rare, but are associated with high morbidity and mortality. In allopurinol hypersensitivity, kidney disease with reduced. The literature accompanying the prescription is replete with warnings that skin reactions can be severe and sometimes fatal, and that treatment should be discontinued immediately if a rash develops. Other involvement such as gastrointestinal bleeding is common. Patients with chronic renal impairment and concomitant diuretic use, in particular thiazides, may be at increased. Chemical structures of allopurinol and febuxostat 3.
Allopurinol oral interactions with other medication. The most frequent allergic reaction to allopurinol is a skin rash. Pdf allopurinol hypersensitivity syndrome in patients. Pdf allopurinol hypersensitivity syndrome in patients with. Each scored white tablet contains 100 mg allopurinol and the inactive ingredients lactose, magnesium stearate, potato starch, and povidone. Jul 20, 20 allopurinol is the primary therapy for the management of chronic gout. Diagnosis is challenging because the extent of skin involvement does not always correlate with the extent of internal organ involvement and therefore early recognition of. Gout medication treatment patterns and adherence to standards of care from a. B5801 screening in severe allopurinol hypersensitivity syndrome. Classification of drug hypersensitivity into allergic, pi, and pseudo. Two of the patients recovered following therapy with corticosteroids. Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, an initial allopurinol dose of more than 100 mgd, renal or cardiovascular comorbidities, and use of allopurinol for asymptomatic hyperuricemia. Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death.
This hypersensitivity syndrome was first named after many different terms. The literature accompanying the prescription is replete with warnings that skin reactions can be severe and sometimes fatal, and that treatment should be discontinued immediately if. Physician ignores patients allergic reaction to allopurinol. Most of the allopurinol is rapidly oxidized to oxypurinol, its major metabolic product 3, which in turn is a potent inhibitor of the enzyme xanthine oxydase. Dress syndrome drug rash with eosinophilia and systemic symptoms is a severe drug reaction with an estimated mortality of up to 10% largely due to multiorgan dysfunction. It is a xanthine oxidase inhibitor which is administered orally. Hypogammaglobulinemia as an early sign of druginduced. In patients with renal or cardiovascular comorbidities, allopurinol use for asymptomatic hyperuricemia was associated with statistically significant increased risk of hypersensitivity reactions and mortality. Severe cutaneous adverse reactions scars include syndromes such as drug. Isolated cases of cholestatic jaundice, hepatic necrosis, granulomatous hepatitis, and hepatomegaly have also been reported. Recent euroscar studies demonstrated that allopurinol is the leading cause of stevensjohnson syndrome sjs and toxic epi.
Severe cutaneous reactions requiring hospitalization are rare but occurred 10 times more often among patients beginning allopurinol treatment, and most often in the first 180 days of use. Blacks, asians at higher risk for allopurinolrelated skin reactions. Allopurinol is the primary therapy for the management of chronic gout. Hypersensitivity syndromes are rare but can be fatal.
About europe pmc funders joining europe pmc governance roadmap outreach. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. In patients with renal or cardiovascular comorbidities, allopurinol use for asymptomatic hyperuricemia was associated with statistically significant increased risk of. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol. Allopurinol hypersensitivity syndrome ahs, a rare but potentially fatal adverse reaction in patients beginning allopurinol therapy for gout, might be largely avoided by keying the starting dose to kidney. Febuxostat is funded by the pbs for patients with chronic gouty arthritis or chronic tophaceous gout not just hyperuricaemia who have a documented history of allopurinol hypersensitivity syndrome, intolerance to allopurinol necessitating permanent discontinuation or a medical contraindication to allopurinol. Allopurinol is an effective uratelowering drug that is well tolerated by the majority of patients. Allopurinolinduced drug reactions with eosinophilia and systemic. An immune reaction to the ingestion of a drug called allopurinol.
Impact of comorbidities on gout and hyperuricaemia. Rash is thought to occur in 2% of people taking allopurinol. Allopurinol hypersensitivity syndrome a preventable. The use of allopurinol has infrequently been associated with asymptomatic elevations of serum transaminase and alkaline phosphatase levels. Allopurinol, a widelyprescribed uratelowering drug, is well tolerated in most patients. Allopurinol desensitization with a 2 weeks modified. However, about 2% of treated patients develop a skin rash. Be careful when prescribing allopurinol to black and asian gout patients. Cutaneous rash and fever were the most common clinical findings. Allopurinolinduced dress syndrome is associated with significant mortality, and. Furthermore, febuxostat appears to induce hypersensitivity syndrome less frequently than allopurinol, and is well tolerated by most ahs patients 34,36. Allopurinol may cause hypersensitivity reactions, especially skin rashes, are the most common adverse reactions, occurring in approximately 3 percent of patients. In the same time period, the rate of hypersensitivity conditions attributed to allopurinol also increased significantly. N2 fever, skin rash, renal failure and liver disease developed in 3 patients 3 to 4 wk after treatment with allopurinol was begun.
Although allopurinol hypersensitivity syndrome, a severe cutaneous adverse. Allopurinol hypersensitivity syndrome symptoms, diagnosis. Discontinue at first sign of allergic reactions first sign of rash, vasculitis, or stevensjohnson syndrome, drug rash with eosinophilia and systemic symptoms dress andor generalized vasculitis, irreversible hepatotoxicity. Allopurinol desensitization with a 2 weeks modified protocol. Earn cme credits at your convenience with our free online activities.
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