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The hot content that has attracted much attention in the field of gout in 2022 will be explained in one article!

 Last Update: 2022-10-21
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Professor Zhang Xuewu of Peking University People's Hospital explained the progress of the diagnosis and treatment of gout, and the wonderful content should not be missed
.

Recently, the 9th Children's Rheumatic Immunity Summit Forum and the 15th National Pediatric Rheumatic Immune Disease Study Class were recently held
online.
Rheumatologists and pediatricians from all over the country discussed and collided academic sparks
at the conference.
Professor Zhang Xuewu of Peking University People's Hospital explained the progress of the diagnosis and treatment of gout, from the younger trend of hyperuricemia, the clinical manifestations of gout, to the latest NICE gout guidelines, and the EULAR conference gout field of gout to introduce the diagnosis and treatment
of gout.

The younger trend 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 the normal purine diet, the fasting blood uric acid > 420μmol/L twice a day (adults, regardless of male or female).

When the blood uric acid level exceeds the monosodium urate saturation of the joint and precipitates and deposits in the peripheral joints and surrounding tissues, it is called gout
.

In China, the prevalence of gout is 1.
6%, with more than 22 million
people.
However, due to blind spots and misunderstandings in gout diagnosis and treatment, and racial differences in gout diagnosis and treatment plans, the current situation of gout diagnosis and treatment in China is still worrying
.

Recent studies have shown that the incidence of hyperuricemia is showing a younger trend
.
A survey of more than 20,000 freshmen in a university in Beijing from 2015 to 2017 showed that the prevalence of hyperuricemia was alarming, with the incidence of hyperuricemia reaching 37% in men and 12.
8%
in women.

But the results have been questioned, and some experts believe that college freshmen have experienced a brutal college entrance examination, with low activity, excessive and irregular diet, which may promote hyperuricemia
.
Therefore, more than 10,000 college graduates were surveyed, 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 also being 10.
7%.

Professor Zhang Xuewu pointed out that hyperuricemia is the basis of gout and hypertension, so for children, the identification and treatment of hyperuricemia is very important
.

Fig.
1: The prevalence of hyperuricemia in 23,497 neonates from 2015 to 2017 Fig.
2: Clinical manifestations of gout in 12,839 cases of
HUA
prevalence among graduates from 2015 to 2017 Professor Zhang Xuewu pointed out that gout patients often have a process
from asymptomatic hyperuricemia, acute gouty arthritis, intermission period, chronic gouty arthritis to gout nephropathy.
Gout patients in the acute gouty arthritis period experience "pain is really fatal", and there are no symptoms during the attack interval, easy to "heal the scar and forget the pain", which makes many patients have gout complications, gout patients often accompanied by coronary heart disease, cerebrovascular and hypertension and other diseases, about 25% of gout patients die of vascular and heart accidents
.

Figure 3: Progression of gout Overview of the 2022NICE Gout Guidelines In June 2022, the National Institute for Health and Care Excellence (NICE) published guidelines for the diagnosis and management of
gout ^[1].

This article mainly covers the diagnosis and management of gout, and provides guidance and recommendations for the diagnosis of gout, the management of gout attacks, and long-term management and
referral.

Literature screenshot
▌ Symptoms and signs
1.
The presence of any of the following conditions may indicate gout:

Rapid onset (usually overnight) severe pain with redness and swelling in the unilateral or bilateral first metatarsophalangeal joint (MTP);
Tophi
.

2.
Gout usually occurs rapidly (usually overnight), in addition to MTP joints, other joints can also quickly appear severe pain, redness or swelling, such as the middle of the foot, ankle, knee joint, hand, wrist, elbow joint
.

3.
For patients with joint pain, redness, swelling and swelling, it is necessary to evaluate the possibility
of septic arthritis, calcium pyrophosphate crystal deposition and inflammatory arthritis.

4.
If septic arthritis is suspected, it should be referred immediately according to local regulations
.

5.
For patients with chronic inflammatory joint pain, chronic gouty arthritis
should be considered.

6.
For patients suspected of gout, a detailed medical history should be asked and a physical examination should be performed to evaluate the symptoms and signs
.

▌ Diagnosis

In patients with signs and symptoms of gout, blood uric acid levels should be measured to confirm the clinical diagnosis [blood uric acid levels ≥ 360 micromol/L (6 mg/dl)], and repeat blood uric acid levels after at least 2 weeks of stabilization if blood uric acid levels
are below 360 micromol/L (6 mg/dl) during an attack and gout is strongly suspected.
If the diagnosis of gout remains unclear, joint aspiration and microscopic examination of joint fluid
may be considered.
If joint aspiration is not possible or the diagnosis of gout remains uncertain, imaging of the affected joint with X-ray, ultrasound, or dual-energy computed tomography CT imaging may be considered
.

▌ Management of acute gout

Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or short courses of oral corticosteroids are first-line treatment for gout attacks, taking into account comorbidities, medications being taken, and preferences
.
In patients with gout who are taking NSAIDs for gout attacks, consider increasing the use of proton pump inhibitors
.

▌ Long-term management of gout

Allopurinol or febuxostat should also be considered as first-line therapy when performing urate-lowering (ULT) therapy
.
Allopurinol is recommended as first-line therapy
in patients with gout with severe cardiovascular disease such as previous myocardial infarction or stroke, or unstable angina.
If the target serum uric acid level is not reached or first-line therapy cannot be tolerated, allopurinol or febuxostat is used as second-line therapy
, taking into account patient comorbidities and preferences.
The goal of blood uric acid level control should be <360 μmol L (6 mg/dl).
<b10> For patients with tophi or chronic gouty arthritis, and for patients with persistent and frequent attacks despite blood uric acid levels < 360 micromol/L (6 mg/dl), consider lowering the blood uric acid level target to <b12><300</b12> micromol/L (5 mg/dl).

▌ Prevention of gout attacks For the prevention of gout attacks
at the beginning of ULT, colchicine should be added, and if colchicine is contraindicated, intolerant or ineffective, consider low-dose NSAIDs or low-dose oral corticosteroids
.

Interpretation of the issues of concern in the field of gout in the EULAR meeting In the EULAR annual meeting in 2022, experts from various countries shared the results
of large-scale epidemiological studies on the use of high uric acid, gout and gout 。 What indicators are risk factors for the onset of gouty arthritis in patients with hyperuricemia? What is the cardiovascular protective effect of colchicine? What are the advantages of blood lowering urate-lowering drugs combined with immunosuppressants? Cardiovascular effects of febuxostat? Professor Zhang Xuewu summarized and explained
these problems.

■ Risk factors
for goutiness and arthritis in patients with hyperuricemiaSerum uric acid levels are the strongest known causal predictors of clinical gout, but only about 20% of long-term hyperuricemia will develop into gout, which prompts the need for additional biomarkers for risk prediction and stratification
.

A prospective metabolomics study in the United Kingdom involving 105703 participants through metabolomics analysis ^[2] found that at 10.
4 years of follow-up, glycoprotein acetyl (GlycA) was positively associated with the risk of gout attacks, that is, GlycA is a novel gout biomarker
.

GlycA is new to gout, although this pro-inflammatory biomarker has predicted the risk of other cardiometabolic inflammatory phenotypes, unrelated
to CRP.
These findings may provide insight into the pathogenesis of metabolic inflammation in gout, have implications for risk prediction, even beyond serum uric acid, but require further investigation
by broader metabolome analysis and validation cohorts.

■ Blood uric acid lowering drugs combined with immunosuppressants
oral urate lowering treatment refractory gout patients have few treatment options
.
PEG uricase reduces serum uric acid in these patients, but response rates are limited by antimicrobial antibodies (ADA), which reduces urate-lowering effect and increases the risk of
infusion reactions (IR).
Because methotrexate (MTX) is commonly used for rheumatoid arthritis and to prevent the development of ADA against biologics, the combination of MTX with pegylase in patients with refractory gout is of interest
.

The safety/efficacy of MTX in combination with peglase therapy for sustained reduction of uric acid response ^{was conducted in} a randomized, double-blind, multicenter, controlled trial [3] in 100 patients with gout in pegylase + MTX and 52 in pegylase + placebo (PBO), The 6-month response rate for the main focus of MTX versus PBO was found to be 71% vs.
38.
5%, respectively, while infusion reactions were more common
in the PBO group (30.
6%) than in the MTX group (3.
1%).

This study showed that the rate of sustained urate-lowering response for 6 months was significantly higher
in patients treated with peglase + MTX compared with PEGDASE + PBO combination.
No new safety concerns were identified by the 6th month, and the incidence of infusion reactions was significantly lower
in patients with simultaneous use of MTX.

Professor Zhang Xuewu pointed out that the use of urate-lowering drugs and immunosuppressants has reduced side effects and prolonged efficacy, which has clinical application prospects
.

■ Cardiovascular protective effect
of colchicine Even if guidelines recommend long-term use of urate-lowering drugs (such as allopurinol, febuxostat) to urate-lowering therapy in patients with gout, the maintenance of urate-lowering in real life is still not ideal
.
Colchicine is often used in patients with gout to reduce the incidence
of gout attacks at the start of urate-lowering therapy.
Studies have shown that colchicine is associated
with a reduced risk of cardiovascular events.

In a study investigating the effect of colchicine therapy on atherosclerosis-related cardiovascular outcomes in patients with CPPD disease (^{CPPD) [4]}, 305 patients with CPPD with a mean follow-up of 3.
9±2.
7 years found that adverse cardiovascular outcomes in patients with CPPD were associated with age, hypercholesterolemia, chronic kidney disease, and history of cardiovascular disease.
Intake of colchicine in patients with CPPD reduces the risk of cardiovascular events, while methotrexate and hydroxychloroquine are not related
.

Professor Zhang Xuewu pointed out that colchicine, NSAIDs, and glucocorticoids can be used to prevent gout attacks, and colchicine can be the first choice
in reducing cardiovascular risk.

■ Febuxostat trapped in the vortex of cardiovascular safety is associated with an increased risk of cardiovascular disease due to gout, and a CARES study published in the New England Journal in 2018 showed that febuxostat may increase the time of cardiovascular death in gout patients, which directly led to the FDA's black box warning for febuxostat

。
This year, a large-scale Korean cohort study spanning nine years again compared the cardiovascular safety of febuxostat versus allopurinol in patients with gout ^[5]. , 2011-2019, including 160,930 febuxostat users and 160,930 allopurinol users, showed similar cardiovascular safety in febuxostat and allopurinol users, but found a 16% reduction in all-cause mortality compared with allopurinol, mainly due to a reduction
in non-cardiovascular mortality.

Professor Zhang Xuewu pointed out that the study is long, large, and Asian ethnic research, and the results are contrary to the previous New England CARES study, once again pushing febuxostat to the "forefront", and its cardiovascular disease safety aspects are still worthy of attention
.

Expert profile
Professor Zhang Xuewu Peking University People's Hospital

Professor, Chief Physician, M.
D.
, Ph.
D.
, Rheumatology and Immunology, Clinical Immunology Center/Institute of Rheumatology, Peking University People's Hospital
National Standing Committee Member of Rheumatology Branch of Chinese Medical Association
Standing Committee Member of Beijing Rheumatology Branch of Chinese Medical Association
Member of the National Standing Committee of the Rheumatology Branch of the Chinese Medical Doctor Association and Secretary General of the Osteoporosis Group
Vice Chairman of Beijing Rheumatology Branch of Chinese Medical Doctor Association
National Standing Committee Member of Bone and Joint and Rheumatology Branch of 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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