Allopurinol, an analogue of hypoxanthine, which inhibits xanthine oxidase, is an effective urate lowering drug that has been the cornerstone in the treatment of hyperuricaemia and gout for decades. Allopurinol is a xanthine oxidase inhibitor and a widely used medication for gout. An immune reaction to the ingestion of a drug called allopurinol. Frequently, the rash can involve ulcers of the mouth, throat. In most patients, the drug is well tolerated, however, about 2% of treated patients develop a skin rash. Symptoms of allopurinol hypersensitivity syndrome including 6 medical symptoms and signs of allopurinol hypersensitivity syndrome, alternative diagnoses, misdiagnosis, and correct diagnosis for allopurinol hypersensitivity syndrome signs or allopurinol hypersensitivity syndrome symptoms. A rare but potentially fatal adverse event is allopurinol hypersensitivity syndrome ahs.
Fatal allopurinolinduced hypersensitivity syndrome associat. Jun 29, 2015 furthermore, febuxostat appears to induce hypersensitivity syndrome less frequently than allopurinol, and is well tolerated by most ahs patients 34,36. Allopurinol hypersensitivity syndromescar occurs early after starting allopurinol. There is reluctance from many prescribers of allopurinol, most of whom are general practitioners, to increase the dose above 300 mgday despite advice in the product information that supports a maximum dose of 900 mgday. More detailed information about the symptoms, causes, and treatments of allopurinol hypersensitivity syndrome is available below. The allopurinol hypersensitivity syndrome unpecessary morbidity and mortality joyce 2. Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Patients who have developed a severe reaction to allopurinol should not be restarted on the drug. Allopurinol is a xanthine oxidase inhibitor that works by. Pdf lesson of the week fatal allopurinol hypersensitivity. Moreover, high starting doses of allopurinol might increase the risk of serious adverse reactions including drug hypersensitivity syndrome with rash, eosinophilia and systemic symptoms dress. Episodes of hypersensitivity to the drug are not rare. Rasburicase is a potent recombinant form of urate oxidase, which can metabolize uric acid to the more highly soluble compound allantoin. Hypersensitivity syndromes are rare but can be fatal.
Use of allopurinol for the treatment of asymptomatic hyperuricemia has also become common, due to a series of reports demonstrating. Allopurinol is used to prevent or lower high uric acid levels in the blood. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, and worsened renal function. Objective to assess the risk of hypersensitivity reactions hsrs with allopurinol and febuxostat in a populationbased study. Serious skin rashes hypersensitivity syndrome, stevens johnson syndrome, toxic epidermal necrolysis have been reported in patients taking allopurinol. A severe form of this with a generalized exanthem, fever and liver involvement has been termed the allopurinol hypersensitivity syndrome ahs. Our observation suggests that allopurinol toxicity should be considered as an additional cause of. Allopurinol is one of the drugs commonly known to cause stevensjohnson syndrome and toxic epidermal necrolysis, two lifethreatening dermatological conditions.
Allopurinol is a xanthine oxidase inhibitor widely used to control plasma uric acid levels. Zyloprim allopurinol dose, indications, adverse effects. 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. Historical risk factors for ahs include renal insufficiency and diuretic use3, and because the syndrome can prove fatal. After diagnosis of an allopurinol hypersensitivity syndrome, allopurinol was stopped. Unnecessary morbidity and mortality singer, joyce z wallace, stanley l. Allopurinol hypersensitivity syndrome, although rare, is a significant concern for physicians who use the drug to lower serum uric acid in patients with gout. People taking allopurinol should be advised to inform their doctor immediately if they develop any type of skin reaction while being treated with allopurinol. Tissue damage is due to cytotoxic t cells and cytokine release. Under treatment with heavily dosed steroids and antihistamines, the liver. 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. Unnecessary morbidity and mortality the allopurinol hypersensitivity syndrome.
Sir, a relationship between allopurinol hypersensitivity syndrome ahs and viral infections, especially with human herpes virus hhv6, has been suspected since the first report of ahs in 1970 1. Allopurinol oral route description and brand names mayo. Relation between adverse events associated with allopurinol. Sep 15, 2005 allopurinol, an analogue of hypoxanthine, which inhibits xanthine oxidase, is an effective urate lowering drug that has been the cornerstone in the treatment of hyperuricaemia and gout for decades.
We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of ahs. Additional contraindications not in the us labeling. The hlab5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity syndrome and sjsten. A 46yearold man was treated by allopurinol for asymptomatic hyperuricemia. Jan 17, 2020 dress also known as drug hypersensitivity syndrome has been reported. Pustular drug hypersensitivity syndrome due to allopurinol. Symptoms can include liver and kidney damage, stevensjohnson syndrome, and toxic epidermal necrolysis.
Allopurinol hypersensitivity syndrome symptoms, diagnosis. Allopurinol hypersensitivity syndrome in patients with hematological. 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. Risk factors for allopurinol hypersensitivity included female sex, age 60 years or.
Allopurinol hypersensitivity syndrome, a severe form of cutaneous adverse reaction. Allopurinol hypersensitivity syndrome as a cause of hepatic. Serious and life threatening adverse events such as the allopurinol hypersensitivity syndrome ahs are rare. Furthermore, febuxostat appears to induce hypersensitivity syndrome less frequently than allopurinol, and is well tolerated by most ahs patients 34,36. Allopurinol is an effective uratelowering drug that is well tolerated by the majority of patients. The allopurinol hypersensitivity syndrome george p. Gout treatment dosage affects risk for hypersensitivity syndrome. A high uric acid level can cause gout or gouty arthritis joint pain and inflammation. Allopurinol is one of the drugs commonly known to cause stevensjohnson syndrome and toxic epidermal.
Allopurinol hypersensitivity syndrome scar occurs early after starting allopurinol. Allopurinol is a rare but well known cause of acute liver injury that has features of a hypersensitivity reaction and can be severe and even fatal. Oct 22, 2014 allopurinol is an effective uratelowering drug that is well tolerated by the majority of patients. Allopurinol hypersensitivity syndrome has clinical peculiarities that distinguish it from hypersensitivity syndrome caused by other drugs. Methods we used the 5% medicare beneficiary sample. Regarding the potential implications of our findings in other populations, allopurinol is a common drug that is associated with severe cutaneous adverse reactions in different ethnic groups, including asians and europeans. Physician ignores patients allergic reaction to allopurinol. Nov 01, 2019 the allopurinol hypersensitivity assay, or hlab58. Asymptomatic hyperuricaemia and allopurinol induced toxic epidermal necrolysis.
Allopurinol hypersensitivity syndrome ahs was first reported by lang 4 in 1979, and diagnostic criteria were established in 1986 5. Drug hypersensitivity syndrome is a delayed t cell mediated reaction. Allopurinol hypersensitivity syndrome ahs is an idiosyncratic cellmediated hypersensitivity to allopurinol1 characterized by a diffuse morbilliform rash which can evolve into exfoliative dermatitis, eosinophilia, worsening renal function, and fever2. Describe risk factors for and clinical features of allopurinol hypersensitivity syndrome in patients with gout who are receiving allopurinol. Starting dose is a risk factor for allopurinol hypersensitivity syndrome. The syndrome is potentially lifethreatening and fatal. Severe hypersensitivity reaction to allopurinol or any component of the formulation canadian labeling. Hlab5801 testing to prevent allopurinol hypersensitivity. There is a genetic predisposition to drug hypersensitivity syndrome. The allopurinol hypersensitivity syndrome, which occurs in about 1 in patients prescribed allopurinol, includes stevensjohnson syndrome, toxic epidermal necrolysis, and dress.
Jun 15, 2010 allopurinol hypersensitivity syndrome, although rare, is a significant concern for physicians who use the drug to lower serum uric acid in patients with gout. It is also used to prevent or lower excess uric acid levels caused by cancer medicines or in patients with kidney stones. It is characterized by rash, fever, and internal organ involvement. Frequently, the rash can involve ulcers of the mouth, throat, nose, genitals and conjunctivitis red and swollen eyes. We report a case of fatal allopurinolinduced hypersensitivity syndrome associated with acute pancreatitis. Dress also known as drug hypersensitivity syndrome has been reported. Breastfeeding mothers and children except those with cancer therapyinduced hyperuricemia or leschnyhan syndrome. How to prevent allopurinol hypersensitivity reactions. Incidence of allopurinol hypersensitivity syndrome ahs. Allopurinol hypersensitivity syndrome ahs is a severe drug reaction. Fatal allopurinol hypersensitivity syndrome after treatment. The most frequent allergic reaction to allopurinol is a skin rash.
Although allopurinol hypersensitivity syndrome, a severe cutaneous adverse. Allopurinol hypersensitivity syndrome, a severe form of cutaneous adverse reaction, is associated with significant mortality and morbidity. Successful febuxostat desensitization in a patient with. Recent euroscar studies demonstrated that allopurinol is the leading cause of stevensjohnson syndrome sjs and toxic epi. The allopurinol hypersensitivity syndrome sciencedirect. Describe the effect of the starting dose of allopurinol on the risk for allopurinol hypersensitivity syndrome in patients with gout. Dosage adjustment might have reduced the occurrence or severity of the rash. The aim of this study is to document the clinical presentation of allopurinol hypersensitivity syndrome in a local.
Renal dosing of allopurinol results in suboptimal gout care. Allopurinol is contraindicated in patients with a known hypersensitivity to allopurinol, including previous occurrence of skin rash or serious rash. Pdf allopurinol, an analogue of hypoxanthine, which inhibits xanthine oxidase. A defect in the way the liver metabolises drugs may be responsible.
Hypersensitivity reactions with allopurinol and febuxostat. The janus faces of allopurinolallopurinol hypersensitivity. Reactivation of human herpesvirus 6 hhv6, the cause of roseola or. Introduction allopurinol is a widelyprescribed uratelowering agent. We describe a 61yearold male patient who was treated with allopurinol and developed fever, a skin rash, eosinophilia and severe renal and liver dysfunction.
Febuxostat hypersensitivity the journal of rheumatology. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol. Allopurinol hypersensitivity syndrome ahs is a severe and sometimes lifethreatening adverse drug reaction. The frequency of the hla b5801 allele varies widely between ethnic populations. We used multivariableadjusted cox regression analyses to compare the hazard ratio hr of. Skin rash is a frequently reported adverse reaction in patients receiving allopurinol. Discontinuation of allopurinol did achieve the ultimate goal of palliative care, which was to make the patient as comfortable as possible. Sep 29, 2015 starting dose is a risk factor for allopurinol hypersensitivity syndrome. Allopurinol hypersensitivity syndrome is a severe adverse reaction characterized by rash, fever, and internal organ involvement. Patients receiving allopurinol are at risk of developing the allopurinol hypersensitivity syndrome, an immunologic reaction to the drug, characterized by multiple abnormalities such as fever, rash, decreased renal function, hepatocellular injury, leukocytosis, and eosinophilia. It has been reported that symptoms may develop in approximately 1 week from initiating allopurinol therapy, but longer latency periods have also been reported. Allopurinol desensitization with a 2 weeks modified protocol. The aim of this study was to document the clinical presentation of allopurinol hypersensitivity in a local population, examine the indications for uratelowering therapy and to identify. Allopurinol use and risk of fatal hypersensitivity reactions.
Rash is thought to occur in 2% of people taking allopurinol. Gout medication treatment patterns and adherence to standards of care from a. Allopurinol hypersensitivity syndrome singapore medical journal. Although allopurinol hypersensitivity syndrome, a severe cutaneous adverse reaction, is less common, affecting 0. The use of allopurinol only for accepted indications and in dosages adjusted for a patients renal function may be the only.
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