Americans of Asian and African descent have much higher risk than white and Hispanic Americans of developing rare but severe, sometimes life-threatening skin reactions to thegoutdrug allopurinol (Zyloprim), according to a new study published recently inSeminars in Arthritis & Rheumatism.
These two skin reactions, called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), cause flu-like symptoms, a widespread rash, and large portions of the upper layer of skin (including mucus membranes) to blister and detach. They can also damage other major organs. SJS and TENS, which are believed to be different manifestations of the same disorder, are usually caused by a reaction to a drug (including acetaminophen [Tylenol] and certain antibiotics).
别嘌呤醇能减少体内尿酸的产生，是痛风和高尿酸血症最常用的一线治疗方法;它已经存在了50年。
The risk of developing SJS/TENS for Asian Americans who take allopurinol is 12 times greater than for white and Hispanic Americans; for African Americans, it’s 5 times greater.
Still, these reactions are uncommon even among higher-risk groups, emphasizes study author Hyon Choi, MD, PhD, professor of medicine at Harvard Medical School and director of the Gout and Crystal Arthropathy Center at Massachusetts General Hospital in Boston, .
Choi博士说，不管患者的种族是什么，SJS/TEN，如果它会发生，几乎总是在用别嘌呤醇治疗的前三到六个月发生，这是最常用的降低尿酸水平的痛风药物，所以已经服用一段时间的人不必担心这些反应。
Race and Risk
Dr. Choi and his colleagues looked at U.S. hospitalization records from 2009 to 2013, with 5 million to 8 million admissions per year, and found only 606 cases of SJS/TEN. But when they looked more closely, they found many more cases of the serious reactions among Americans of Asian and African descent than one would expect, given the racial makeup of the general U.S. population. Of the SJS/TEN patients, for example, 27% were Asian American, 26% were African American and 29% were white. Asian Americans, African Americans and whites, however, make up 5%, 12%, and 67%, respectively, of the U.S. population.
To put it another way, says Dr. Choi, approximately 1 in 4,000 whites, 1 in 740 African Americans, and 1 in 340 Asian Americans taking allopurinol will develop a severe reaction. (The number of SJS/TENs cases linked to allopurinol use among Hispanics during the study period was too low to report, meaning they are unlikely to have a higher risk than Asian, African, or white Americans.)
It’s almost certainly the presence of an allele (a variant form of a gene) called HLA-B*5801 causing these race-related increases in risk, says Dr. Choi. Experts have known for some time that Asians are more likely to carry the allele; about 7.4% of Asian Americans do, compared with 4% of African Americans and 1% of both white and Hispanic Americans.
The American College of Rheumatology (ACR) in 2012 updated its gout management guidelines to recommend screening for the allele in patients of Asian descent before starting allopurinol, which accounts for 96% of all urate-lowering drug use in the Unites States. Dr. Choi, who was a co-author of the ACR guidelines, expects the findings of the recent study to prompt rheumatologists to expand screening for the allele, a simple blood test that costs about $150. He now screens all of his Asian-American and African-American patients before beginning allopurinol therapy. If they test positive for the allele, Dr. Choi begins therapy with one of the handful of alternative urate-lowering drugs, such as probenecid or febuxostat (Uloric).
Increasing Safety
People with gout typically take allopurinol long-term. Taking it regularly is the key to lowering uric acid levels, which can reduce frequency and severity of gout attacks. “This information will allow us to use allopurinol in a safer way and, if patients perceive better safety, they may be more likely to use it and therefore be better treated,” says Dr. Choi. Even though SJS/TEN is uncommon, some patients can be understandably reluctant to take a drug that can cause frightening and potentially fatal side effects, he says. About 30% of patients die from these reactions, and those who survive can have long-term kidney and eye damage.
“The presence of this allele is a major risk factor for SJS/TEN. I would hope that, if we can predict the risk of this reaction more precisely by screening for this allele and identifying other known risk factors, such as poor kidney function, we can bring the probability of developing this to almost zero,” Dr. Choi says.
目前的研究“证实了我们所知道的亚洲人与别嘌呤醇相关的SJS/TEN的风险，并为我们提供了关于非洲裔美国人风险的新信息，这将帮助医生为特定的患者选择最好的药物，避免造成伤害，”位于安娜堡的密歇根大学医学助理教授Puja Khanna医学博士说。康纳博士也是2012年ACR痛风指南的合著者，但没有参与这项研究。
“One important message I see for patients who are newly diagnosed with gout is that it could be wise to have a discussion with your doctor about your ethnic background,” she says. “Sometimes doctors aren’t comfortable asking, and it may not always be obvious that someone is one-eighth Han Chinese, for example, and therefore might have a higher risk of having this allele than their appearance suggests.”
肯纳博士说，这种等位基因检测呈阳性的人确实有一些替代治疗方案，但肯定需要更多口服降低尿酸的药物。“目前有几种(新的治疗方法)正在研发中，但由于别嘌呤醇对大多数人都有效，而且这些反应很少见，所以新药的研发过程很缓慢。”
Author: Emily Delzell for the Arthritis Foundation