A Man With Acute Gouty Arthritis, Chronic Hyperuricemia, HLA-B58-01 Allele
In this video, Monica Richey, MSN, ANP-BC/GNP, discusses the clinical challenges and strategies in the management of a patient with acute gouty arthritis and chronic hyperuricemia, including the variant HLA-B*58:01 allele, which is strongly associated with severe cutaneous adverse reactions during treatment with allopurinol. This is part one of a two-part case presentation series on patients with gout.
Additional Resource:
- Dakkak M, Lanney H. Management of gout: update from the American College of Rheumatology. Am Fam Physician. 2021;104(2):209-210
Watch part two of this two-part case presentation series on patients with gout here..
For more gout content, visit the disease state hub..
TRANSCRIPTION:
My name is Monica Richey. I'm a nurse practitioner working in rheumatology for over 20 years. I currently work at Northwell Health on Long Island, New York.
Today, we're going to talk about gout, which is one of the most common diseases that we see in rheumatology. We're going to go over a couple of cases.
The first case is Mr Chen. He's 52 years old, he's of Chinese descendant, and he works as an office manager.
He has a medical history of hypertension and hyperlipidemia, and he was referred by his primary care physician because he's having episodes of severe pain, swelling, and redness over this right big toe. He reports that the pain starts suddenly, it worsens, and you know he has no idea what's going on.
He denies any recent trauma, no history of any accidents or anything, but he tells you that he has had similar episodes over the past few years. He used to have the episodes maybe once a year, now he started to have them maybe every couple of months, or so. He says the episodes come and go, sometimes he takes an anti-inflammatory to help and sometimes it just goes away after 5 or 7 days. He does not notice any triggers, but sometimes when he goes out with his family for dinner and he has seafood, he reports that sometimes he has an attack after that.
And he just takes either ibuprofen or Aleve help. There are a couple of clues right there that indicate that this is gout, right? The big toe is one of the biggest joints. The attacks comes and goes on their own. So, when you're taking the history, which is very important in rheumatology, you start to have some clues about what the diagnosis is going to be.
He has hypertension, which was diagnosed 10 years ago. He takes amlodipine 5 mg/d and he takes atorvastatin 20 mg/d for hyperlipidemia. He is not on diuretics. Has no history of diabetes or heart disease. His father also had gout, but he had no other significant family history. He does not smoke. He reports that he drinks about two to three drinks per week. He walks every day for about 30 minutes, so he exercises regularly. His diet is of rich vegetables, tofu, rice, and occasionally he consumes seafood and red meat.
His vital signs are normal, but he’s in moderate distress with pain. He comes to the office in a wheelchair because he cannot bear any weight on his feet. You have a feeling that this is gout because he has no shoes on. Usually, patients with gout show up with no shoes, maybe a sock.
Figure 1. The patient is referred to rheumatology by his primary care physician because he is having episodes of severe pain, swelling, and redness in this right big toe. He reports that the pain starts suddenly, and it worsens over time.
Sometimes a patient with gout will tell you that the pain is so severe that they want to cut their foot off. It's red, it's swollen. It affects the whole foot from the toe all the way up to the ankle, sometimes.
His big toe has a red-purple hue. That's usually another clue that this is gout. When you do the blood work, you see that the uric acid is about 8.5 mg/dL, which is elevated. I must point out that during a flare, about 60% of patients will have a low-to-normal uric acid. That is just because all the uric acid has moved from the bloodstream into the joint. But in his case, his uric acid was elevated. His serum creatinine was 1.0 mg/dL, so slightly elevated. The complete blood count was within normal limits.
He is of Chinese descent, and we are aware that some people of Asian descent cannot take allopurinol. I'm doing all of this in my head as I'm examining the patient. So, we usually check all patients of Asian descent for something called HLA-B58-01, which is a predisposition to have a severe reaction to allopurinol.
I’m planning to start him on a gout medication. I believe he has gout and chronic hypouricemia. True diagnosis of gout is done with fluid analysis, but in his case, it is extremely difficult and painful to take fluid out of the toe. You don't want to do that during a gout attack.
The knee is much easier to tap and send for analysis, but if it's in the toe and you have every single clue that this is gout, you can easily make the diagnosis of gout.
So, talking about the HLA-B58-01, it’s a genetic disposition to have a severe reaction to allopurinol. The variant HLA-B58-01 allele is strongly associated with severe cutaneous adverse reactions (SCAR) during treatment with allopurinol. This allele is most common among Asian subpopulations, notably in individuals of Korean, Han Chinese, or Thai descent.
We usually avoid allopurinol in these populations because I've seen some patients who are prescribed allopurinol and eventually develop DRESS syndrome. So, we really want to check that right from the beginning. If you ever see a patient who is of Asian descent, you want to send that lab as soon as possible.
I started the patient on colchicine twice a day for 5 days, and then I decreased it to BID just to try to decrease some of his pain and swelling and stop the attack. So, colchicine is your number one drug if there is no kidney involvement. And given that his symptoms were present for at least 5 years, his uric acid was 8.5, and I cannot use allopurinol. I started him on febuxostat, 40 mg/d. And usually what we do is once we start and any medications to lower the uric acid, we leave patients on both the medications, either allopurinol or febuxostat with colchicine, daily until the uric acid reaches six because they're likely to flare when you're trying to lower that uric acid.
So be that a month, a month and a half, if there are no contraindications to colchicine, you're going to keep that patient taking both medications until you recheck after 6 weeks. If the uric acid is below six, you start to taper off colchicine very quickly. You can tell the patients to start taking colchicine every day, then every other day, every 2 days, and then just come off the colchicine slightly. I am not one of those providers that tell you just stop colchicine because sometimes they can flare, so I slowly pulled the colchicine out just by tapering off. So, as I said, I started him off at febuxostat where we checked his uric acid after 6 weeks, but his uric acid was still elevated to 6.5 mg/dL.
The gout was still hanging around after 8 weeks, so I increased the dose of the febuxostat so we can pull him out of the colchicine quickly. And then after another 4 weeks, I checked it again, it was five, and then I was able to taper off the colchicine. So, that's our case number one.
Now we’ll go over the importance of lifestyle modification is to all patients. I have some patients who decide they’re going to control gout with diet. Sometimes it's possible and sometimes it's not. So dietary counseling is very important for all of our patients. It’s also important for them to stay hydrated. I usually tell all my patients not to eat seafood, no red meat, and no alcohol. It can be difficult sometimes depending on the patient's culture and obviously dietary preferences, but this is like the initial step on getting gout under control. And then hydration is very important. A liter to two liters of water daily will help dissolve the uric acid and help your kidneys get rid of the uric acid. Obviously, we always talk about exercise and weight management.
Talking about the worst foods for gout: high fructose corn syrup is one of the worst. It can cause gout, and we here consume a lot of high fructose syrup, and sometimes we don't even know that it’s in the food but it’s there. Any patient with gout should be counseled to look at the ingredients and see if there's any high fructose corn syrup. Beer and alcohol are out. Gamey meats, red meats, and liver are not allowed, as well as seafood, shrimp, and anchovies. So those are the worst foods for patients with gout.
The best foods for gout are actually cherries and anything that has high levels of vitamin C, so oranges and clementines. Coffee is actually good for people with gout, believe it or not, and skim milk, as well as water. So those are important counseling that we should do with all of our patients with gout.
The American College of Rheumatology has come up with some guidelines in 2020 and obviously the first-line options for our patients with gout is xanthine oxidase inhibitors. Allopurinol will be the first-line therapy unless there is a contraindication. And the special consideration is to always check for this HLA-B58-01 in all patients of Asian descent. I'm repeating myself, but this is really important.
And then the second-line therapy is febuxostat. And allopurinol is even recommended in patients who have kidney disease. There is no problem. I work a lot with nephrologists, and they all say let's start with allopurinol unless there are any other contraindications.
Probenecid is used for people who have either allergy to allopurinol or febuxostat. I currently have a patient on probenecid because she's highly allergic to both medications. We started at 100mg once or twice daily, and we can increase as the patient tolerates and as you see the uric acid decreasing, right?
And then pegloticase is for people with really tophaceous gout. This is our next case, just giving you a hint. That is an intravenous medication, so that is really our last case scenario. If allopurinol and febuxostat fail and you cannot use probenecid, then pegloticase is your next choice.
The take-away message on this case is really check HLA-B28-10. I know this is the fifth time I'm saying this, but it's important to know this about patients of Asian descent. Febuxostat over probenecid is recommended for those patients with HLA-B58-01.
Then, target uric acid. Patients are always asking “why are you always checking the uric acid?” Because the target is to be less than 6. And really at 5, you stop flares.
And then ACR also recommends if patients are in any kind of blood pressure medication for them to be on losartan vs other thiazide diuretics because they can also trigger gout. And then in any patient with gout, fenofibrate is contraindicated because that will make gout even worse. So, switch to losartan if you can, and then avoid thiazides and avoid fenofibrates.