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In the 17th National Rheumatology Diagnosis and Treatment New Progress Training Class, Professor Zhang Xuewu from Peking University People's Hospital shared "7+5" - 7 key contents of gout diagnosis and management in the 2022 National Institute of Health and Clinical Optimization (NICE) gout diagnosis and management [1] and 5 frontier gout issues worth paying attention to at the 2022 European Union Anti-Rheumatology Diseases (EULAR) Annual Meeting, reviewing the past and knowing the new.
7 points
▌ points 1: Symptoms and signs of gout
Unilateral or bilateral first metatarsophalal joint (MTP) appears rapidly (usually overnight) and is severely painful and accompanied by redness and swelling.
appears gout stone .
rapidly (usually overnight) in other joints other than MTP joints, such as the middle of the foot, the ankle joint , the knee joint , the hand, wrist joint, and the elbow joint.
For patients with joint pain, redness, swelling, and swelling, the possibility of suppurative arthritis , calcium pyrophosphate crystal deposition and inflammatory arthritis should be differentiated and evaluated.
If you are suspected of suffering from suppurative arthritis, you should refer you immediately according to local regulations.
Chronic gouty arthritis should be considered in patients with chronic inflammatory arthritis.
For patients with suspected gout, a medical history should be asked in detail and a physical examination should be conducted to evaluate symptoms and signs.
▌ Keywords 2: Diagnosis of gout
For patients with symptoms and signs of gout, blood uric acid level should be measured to clarify the clinical diagnosis [ blood uric acid level ≥360μmol/L (6mg/dl)]. If blood uric acid levels are below 360 μmol/L (6 mg/dl) during the onset and gout is strongly suspected, measurements of blood uric acid levels are repeated after at least 2 weeks of stable condition.
If the diagnosis of gout is still uncertain or not clear, joint extraction fluid can be considered for microscopic examination.
If the diagnosis of joint aspiration or gout is still unclear, X-ray, ultrasound or dual energy CT may be considered.
▌ Focus 3: Management of acute gout
Considering the patient's comorbidities, combined prescriptions and preferences, non-steroidal anti-inflammatory drugs (NSAID), colchicine or short-term oral glucocorticoid are used as the first-line treatment for gout attacks.
Consider adding a proton pump inhibitor to patients taking NSAID for gout attacks.
If NSAID and colchicine are contraindicated, intolerable or ineffective, intra-articular or intramuscular injection of glucocorticoids can be considered to treat gout attacks.
Unless NSAID, colchicine and glucocorticoids are contraindicated, intolerable or ineffective, interleukin-1 (IL-1) inhibitors should not be treated with interleukin-1 (IL-1) inhibitors. The use of IL-1 inhibitors must be guided by rheumatologists.
In addition to taking prescription medication, applying ice packs (cold therapy) on the lesion joints may help relieve pain.
After the onset of gout, follow-up should be considered and blood uric acid levels should be monitored.
provides information about gout to enhance patient teaching to help patients self-manage and reduce the risk of attack.
evaluates lifestyle and comorbidities (including cardiovascular risk factors and chronic kidney disease ).
reviews the drug and considers the risks and benefits of long-term uric acid-lowering treatment (ULT).
▌ Focus 4: Long-term management of gout
Provides ULT strategies for gout patients with different treatment goals, such as multiple or difficult-to-treat gout attacks, chronic kidney disease (CKD) stages 3 to 5, diuretic treatment, gout stones, and chronic gout arthritis.
For patients who have a first or subsequent gout attack but do not belong to the above conditions, they should be given compliance treatment and discuss ULT treatment with them.
ensures that patients understand the importance of ULT, and that ULT treatment is required even after blood uric acid levels reach the target, and is usually lifelong treatment.
ULT treatment begins at least 2 to 4 weeks after the onset of gout.If gout attacks are frequent, you can start using ULT during the attack.
▌ Key point 5: Blood uric acid level control target
Blood uric acid level control target should be less than 360μmol/L (6mg/dl).
Patients with gout stone or chronic gout arthritis and who continue to have frequent episodes despite blood uric acid levels below 360 μmol/L (6 mg/dl) may consider reducing the target blood uric acid level to 300 μmol/L (5 mg/dl).
▌ Focus 6: Uric acid-lowering therapy
When starting to target ULT, 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 ), allopurinol is recommended as the 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 the second-line treatment, considering the patient's comorbidities and preferences.
▌ Point 7: Prevent gout attack
When starting or deciding on ULT, the benefits and risks of taking medication to prevent gout attacks should be discussed with the patients.
For patients who choose to receive treatment when starting or deciding on ULT to prevent gout attacks, colchicine should be given when the target blood uric acid level is reached. If colchicine is contraindicated, intolerant, or ineffective, consider using low-dose NSAID or low-dose oral glucocorticoids.
To prevent gout attacks, when starting or deciding on ULT, consider adding proton pump inhibitors to patients taking NSAID or glucocorticoids, and individual adverse events risk factors should also be considered.
Unless colchicine, NSAID and glucocorticoids are contraindicated, intolerable or ineffective, IL-1 inhibitors are not recommended to prevent gout attacks when starting or deciding on ULT. The use of IL-1 inhibitors requires guidance from rheumatologists.
5 Frontier Research
■ Frontier 1: What indicators are the risk factors for gout arthritis in patients with hyperuricemia?
A prospective metabolomics study in the UK [2] analyzed biological samples from 105,703 subjects (46% male, average age 57.2 years old) to determine that glycoprotein acetyl group is positively correlated with gout risk and is a novel gout biomarker, and its impact on risk prediction exceeds that of hematologic uric acid.
■ Frontier 2: What are the new understandings of the use of colchicine?
When studying the pathogenesis of JAK3-STAT5 signaling pathway involved in gout inflammation [3], researchers found that the phosphorylation levels of JAK3 and STAT5 and plasma IL-2 levels in PBMCs in the acute gout group were significantly higher than those in the normal subject group. The phosphorylation levels, IL-1β and IL-2 levels of JAK3 and STAT5 were significantly reduced after colchicine treatment, indicating that the IL2-JAK3-STAT5 signaling pathway is involved in the regulation of gout inflammation. Colchicine can treat gout inflammation by inhibiting the IL2-JAK3-STAT5 pathway, and JAK3 is expected to become a therapeutic target for acute gout inflammation. The significance of this study is that acute gout may get rid of the situation where only NSAID and hormones are available, avoid the annoying side effects of these two types of drugs, and provide more treatment options for high-risk patients. In addition, studies have shown that adverse cardiovascular outcomes in patients with calcium pyrophosphate deposition disease (CPPD) are associated with age, hypercholesterolemia, CKD and cardiovascular history, while intake of colchicine in patients with CPPD can reduce the risk of cardiovascular events, while methotrexate and hydroxychloroquine have not been observed.
■ Frontier 3: Advantages of hemostatic uric acid drugs combined with immunosuppressant
A randomized, double-blind , placebo-controlled multi-center trial observed the effect of methotrexate combined with pegylated enzyme in the treatment of refractory gout [5], where pegylated uricase can reduce serum uric acid (sUA) in these patients, but its remission rate is limited by antibiotic-resistant antibodies (ADA), thereby reducing the effect of lowering uric acid and increasing the risk of infusion reaction (IR). methotrexate can be used to prevent the development of biologic ADA.The results showed that the continuous uric acid reduction rate of PEGase + methotrexate combined treatment for 6 months was significantly higher than that of patients with PEGase + placebo, and there were no new safety issues at month 6, and the incidence of IR was significantly lower in patients with methotrexate.
■ Frontier 4: Effect of blood uric acid fluctuations on the treatment of gout arthritis
There was a study on the blood uric acid level of subjects aged 56.4±13.7 years (95.3% were males, with a course of 7.8±7.6 years). It decreased from the mean baseline 500 μmol/L to 311,500 μmol/L in 1 year and 324 μmol/L in 2 year. The recurrence rate of gout in the first year was 81.2% and the recurrence rate of year 2 was 26.0%, which indicated that serum uric acid fluctuations were related to gout recurrence .
■ Frontier 5: Cardiovascular effects of febustatt
Korean study analyzed the national health data from 2011 to 2019 [7], and included 160,930 febustatt users and 160,930 allopurinol users (average age 59.3 years, 79.6% were male). It was found that the cardiovascular safety of febustatt and allopurinol was similar, but compared with allopurinol, the all-cause mortality rate of febustatt was reduced by 16%, mainly due to the reduction of non-cardiovascular mortality.
Total
Conclusion
In the European and American perspectives, some details of gout diagnosis and treatment are still controversial, such as the timing of starting ULT treatment, and these disputes still need to be equal to the top of high-level evidence.
In addition, the new understanding brought by EULAR in 2022 also provides more confidence in the diagnosis and treatment of gout in the future, especially in terms of the use of febulista, South Korea's large cohort data is very worthy of reference for gout diagnosis and treatment in Asian countries.
References:
[1]Gout:diagnosis and management[J].Methods,2022.
[2]DOl:10.1136/annrheumdis-2022-eular.4213
[3]DOl:10.1136/annrheumdis-2022-eular.1202
[4]DOl:10.1136/annrheumdis-2022-eular.1715
[5]DOl:10.1136/annrheumdis-2022-eular.2949
[6]DOl:10.1136/annrheumdis-2022-eular.1135
[7]DOl:10.1136/annrheumdis-2022-eular.2910
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This article is first published丨Rheumatism and Immunization Channel in the medical community
Author of this article丨Guizhi
Review of this article丨Chen Xinpeng Associate Chief Physician
Editor-in-charge丨Carrier
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