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People's Hospital Professor Zhang Xuewu explained the progress of gout diagnosis and treatment, and the wonderful content should not be missed.
Recently, the 9th Children's Rheumatism and Immunization Summit Forum and the 15th National Children's Rheumatism and Immunization Disease Study Class were held online recently. Rheumatologists and pediatricians from all over the country discussed and collided with academic sparks at the meeting. Professor Zhang Xuewu of Peking University People's Hospital explained the progress of gout diagnosis and treatment, and introduced the diagnosis and treatment of gout in a comprehensive way, from the trend of youthfulness of hyperuricemia and the clinical manifestations of gout to the latest NICE gout guidelines and the EULAR conference on issues of much-attended gout in the field of gout.
The trend of rejuvenation of hyperuricemia
Gout is a metabolic arthritis caused by high uric acid and is a disease that must be taken seriously. Hyperuricemia, as the early stage of gout, is currently defined as: under normal purine diet, two fasting blood uric acid >420 μmol/L (adults, regardless of male or female). When the blood uric acid level exceeds the saturation of the joint monosodium urate and precipitates and deposits in the peripheral joints and surrounding tissues, it is called gout.
In China, the prevalence of gout reaches 1.6%, and the number of patients exceeds 22 million. However, due to the blind spots and misunderstandings in gout diagnosis and treatment, and the racial differences in gout diagnosis and treatment plans, the current situation of gout diagnosis and treatment in my country is still worrying.
Recent studies have shown that the incidence of hyperuricemia is showing a tendency toward rejuvenation. A survey of more than 20,000 freshmen from a university in Beijing from 2015 to 2017 showed that the prevalence of hyperuricemia was shocking, with the incidence of hyperuricemia in men reaching 37%, and the incidence of hyperuricemia in women also reached 12.8%.
However, the result was questioned. Some experts believe that freshmen in colleges and universities have experienced the cruel college entrance examination, with few activities, excessive and irregular diet, which may have a promoting effect on hyperuricemia. Therefore, more than 10,000 college graduates were investigated, and the results showed that there was no significant difference in the prevalence of hyperuricemia, with the incidence of hyperuricemia in men being 34%, and the incidence of hyperuricemia in women being 10.7%.
Professor Zhang Xuewu pointed out that hyperuric acid is the basis of gout and hypertension, so it is crucial for children to identify and deal with hyperuricemia.
Figure 1: Prevalence of 23497 newborn hyperuricemia from 2015 to 2017
Figure 2: Prevalence of HUA for 12839 graduates from 2015 to 2017
clinical manifestations of gout
Professor Zhang Xuewu pointed out that gout patients often have a process from asymptomatic hyperuricemia, acute gout arthritis, intermittent attack period, chronic gout arthritis to gout kidney disease. Gout patients experience "it's really painful" during the acute gout arthritis period, but there are no symptoms during the attack interval, and it is easy to "forget the pain when the scar is healed", which causes many patients to have complications of gout. Gout patients are often accompanied by coronary heart disease , cerebrovascular and hypertension diseases, and about 25% of gout patients die from vascular and heart accidents.
Figure 3: Progress of gout
2022NICE Gout Guidelines Overview
In June 2022, the UK National Institute of Health and Clinical Optimization (NICE) released the diagnostic and management guide for gout [1].
This article mainly covers the diagnosis and management of gout, and provides guidance and suggestions on the diagnosis of gout, management of gout attacks, and long-term management and referral.
Literature screenshot
▌ Symptoms and signs
1. Any of the following conditions may indicate gout:
unilateral or bilateral first metatarsorophalal joint (MTP) appears rapidly (usually overnight) and is severely painful and accompanied by redness and swelling;
gout stone .
2. Gout usually occurs rapidly (usually overnight). In addition to the MTP joint, other joints can also experience severe pain, redness, swelling or swelling quickly, such as the middle of the foot, ankle joint , knee joint , hand, wrist joint, elbow joint .
3. For patients with joint pain, redness, swelling, and swelling, the possibility of suppurative arthritis , calcium pyrophosphate crystal deposition and inflammatory arthritis should be evaluated.
4. If you are suspected of suffering from suppurative arthritis, you should refer you immediately according to local regulations.
5. For patients with chronic inflammatory arthritis, chronic gouty arthritis should be considered.
6. For patients with suspected gout, the medical history should be asked in detail and the physical examination should be performed to evaluate the symptoms and signs.
▌Diagnosis
For patients with symptoms and signs of gout, blood uric acid levels should be measured to clarify the clinical diagnosis [health uric acid level ≥360 μmol/L (6 mg/dl)]. If blood uric acid levels are less than 360 μmol/L (6 mg/dl) during the onset, and gout is strongly suspected, blood uric acid levels will be measured repeatedly after the condition is stable for at least 2 weeks.
If the diagnosis of gout is still unclear, joint puncture and microscopy can be considered.
If joint aspiration cannot be performed or the diagnosis of gout is still uncertain, consider using X-ray, ultrasound or dual-energy computed tomography CT imaging to perform imaging examination of the affected joints.
▌ Management of acute gout
Nonsteroidal anti-inflammatory drugs (NSAID), colchicine or short-term oral glucocorticoid are the first-line treatment options for gout attacks, and the patient's comorbidities, medications being taken and preferences should be taken.
Gout patients who are taking NSAID to treat gout attacks, consider increasing the use of proton pump inhibitors.
▌ Long-term management of gout
When uric acid reduction (ULT) treatment, allopurinol or febulista should also consider the patient's comorbidities and preferences.
For gout patients with severe cardiovascular diseases (such as previous myocardial infarction or stroke , or unstable angina pectoris >, allopurinol is recommended as first-line treatment.
If the target blood uric acid level is not reached or cannot tolerate first-line treatment, allopurinol or febuxstat will be used as second-line treatment if the patient's comorbidities and preferences are considered.
blood uric acid level control target should be <360>
▌▌ Preventing gout attacks
Colchicine should be added to prevent gout attacks when starting ULT. If colchicine has contraindications, intolerance or ineffectiveness, consider using low-dose NSAID or low-dose oral corticosteroids.
EULAR conference
Additional issues in the field of gout in the field of high-profile
EULAR conference Interpretation of the field of gout
EU in 2022 During the LAR annual meeting, experts from various countries shared the research results of large-scale epidemiological on high uric acid, gout and gout medication. Which indicators are the risk factors for gout arthritis in patients with hyperuricemia? What is the cardiovascular protection effect of colchicine? The advantages of hypothermic uric acid drugs combined with immunosuppressant ? The cardiovascular impact of febulista? Professor Zhang Xuewu summarized and explained these issues.
■ Risk factors for gout arthritis in patients with hyperuricemia
serum uric acid levels are the strongest causal predictor of clinical gout, but only about 20% of long-term hyperuricemia develops gout, which prompts people to need additional biomarker for risk prediction and stratification.
A prospective metabolomics study in the UK with 105,703 participants through metabolomics analysis [2], found in 10. During a 4-year follow-up, glycoprotein acetyl group (GlycA) was positively associated with gout onset risk, i.e. GlycA is a novel gout biomarker.
GlycA is new to gout, although this pro-inflammatory biomarker has predicted the risk of other cardiac metabolic inflammatory phenotypes, not associated with CRP. These findings may provide in-depth understanding of the pathogenesis of gout metabolic inflammatory dysfunction, affecting risk prediction, even beyond serum uric acid, but require further investigation through a broader metabolomic analysis and validation cohort.
■ lowering uric acid drug combined with immunosuppressant
oral lowering uric acid treatment for patients with gout who have few treatment options. Pegylated uricase reduces serum uric acid in these patients, but the remission rate is limited by antibiotic-resistant antibodies (ADA), which reduces the uric acid-lowering effect and increases the risk of infusion reaction (IR). Because methotrexate (MTX) is commonly used in rheumatoid arthritis and prevents the development of ADA against biological agents, it is of interest to use MTX with pegylated enzymes in patients with refractory gout.
A randomized, double-blind , multi-center, controlled trial was conducted on the safety/effectiveness of MTX combined with pegylated enzyme therapy in a randomized, [3]. The study included 100 gout patients in the PEGase + MTX group and 52 in the PEGase + placebo (PBO) group. It was found that the 6-month response rates of the main focus of the MTX and PBO groups were 71% vs 38.5%, respectively, while the infusion reactions in the PBO group (30.6%) were more common than those in the MTX group (3.1%).
This study showed that the continuous uric acid reduction rate of 6 months of pegylated enzyme + MTX combined treatment was significantly higher than that of patients with combined pegylated enzyme + PBO treatment. No new safety issues were found by month 6, and the incidence of infusion reactions in patients with MTX was significantly lower.
Professor Zhang Xuewu pointed out that the use of uric acid-lowering drugs and immunosuppressants has reduced side effects, extended the efficacy, and has clinical application prospects.
■ The cardiovascular protection effect of colchicine
Even though the guidelines recommend that patients with gout use uric acid-lowering drugs (such as allopurinol and febulista) for a long time, the maintenance of uric acid-lowering in real life is still not ideal. Colchicine is often used in gout patients to reduce the incidence of gout attacks at the beginning of uric acid-lowering treatment. Studies have shown that colchicine is associated with a reduced risk of cardiovascular events.
A study explored the effect of colchicine therapy on cardiovascular outcomes related to atherosclerosis in patients with pyrocalcium phosphate deposition disease (CPPD). [4] was included. 305 patients with CPPD were included. The average follow-up was 3.9±2.7 years. It was found that adverse cardiovascular outcomes in patients with CPPD were related to age, hypercholesterolemia, chronic kidney disease and cardiovascular disease history. Intake of colchicine in patients with CPPD can reduce the risk of cardiovascular events, while methotrexate and hydroxychloroquine were not related to this.
Professor Zhang Xuewu pointed out that when preventing gout attack, colchicine, NSAIDs, and glucocorticoids can be used. In terms of reducing cardiovascular risks, colchicine can be the first choice.
■ Febulista, which is deeply trapped in the cardiovascular safety vortex,
Because gout is related to an increased risk of cardiovascular disease, a CARES study published in the New England Journal of China showed that febulista may increase the time of cardiovascular death in gout patients, which directly led to a black box warning of FDA for febulista.
This year, a large-scale cohort study in South Korea spanned 9 years, comparing the cardiovascular safety of gout patients with febustat and allopurinol . [5]. From 2011 to 2019, 160,930 febustat users and 160,930 allopurinol users were included. The results showed that the cardiovascular disease safety of febustat and allopurinol users were similar, but it was found that compared with allopurinol, the allopurinol mortality rate of febustat was reduced by 16%, mainly due to the reduction of non-cardiovascular disease mortality.
Professor Zhang Xuewu pointed out that this study has been a long time, is a large number, and is an Asian ethnicity study. The results are contrary to the previous New England CARES study, which once again pushed febulista to the forefront, and its cardiovascular disease safety is still worthy of attention.
Expert Profile
Professor Zhang Xuewu
Peking University People's Hospital
Professor of the Clinical Immunization Center/Rheumatology and Immunization Institute of Peking University People's Hospital, Chief Physician, Doctoral Supervisor
Rheumatology Branch of Chinese Medical Association National Standing Committee
Chinese Medical Association Beijing Rheumatology Branch National Standing Committee
Chinese Medical Association Beijing Rheumatology Branch National Standing Committee
Chinese Medical Association Beijing Rheumatology Branch Standing Committee Member
National Standing Committee Member of the Rheumatology Branch of the Chinese Medical Association and Secretary-General of the Osteoporosis Group
Vice Chairman of the Beijing Rheumatology Branch of the Chinese Medical Association
National Standing Committee Member of the Bone and Joint and Rheumatology Branch of the Chinese Rehabilitation Medical Association
References:
[1]Gout:diagnosis and management—summary of NICE guidance,BMJ 2022;378
[2]http://dx.doi.org/10.1136/annrheumdis-2022-eular.4213
[3]http://dx.doi.org/10.1136/annrheumdis-2022-eular.2949
[4]http://dx.doi.org/10.1136/annrheumdis-2022-eular.1715
[5]http://dx.doi.org/10.1136/annrheumdis-2022-eular.2910
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Source of this article丨Rheumatism and Immunization Channel of the Medical World
Author of this article丨Zhou Zhici
Review of this article丨Zhang Xuewu Professor
Editor-in-charge丨Orange
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