Application of a Novel Ultrasound Scoring System in Assessing Disease Activity in Gouty Arthritis

Abstract

Objective

To analyze the application value of a novel ultrasound scoring system in evaluating disease activity in patients with gouty arthritis (GA).

Methods

A total of 150 GA patients were enrolled. After excluding 2 patients with DAS28 < 2.6 (remission) due to insufficient sample size for statistical analysis, the remaining 148 patients were divided into a low-activity group (DAS28 2.6–3.2, n = 39) and a moderate-to-high activity group (DAS28 > 3.2, n = 111) based on the 28-joint Disease Activity Score (DAS28). Under musculoskeletal ultrasound (MSUS), joint lesions in both groups were observed, and ultrasonographic signs were scored. Differences in ultrasound scores, serum uric acid (SUA), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (CRP) between the two groups were compared. The correlations between the total ultrasound score and DAS28, disease duration, SUA, ESR, and CRP were analyzed. Additionally, a receiver operating characteristic (ROC) curve was constructed, and the area under the curve (AUC) was calculated to evaluate the diagnostic value of the total ultrasound score for GA disease activity.

Results

The double contour sign score, hyperechoic aggregates score, hyperechoic spot score, joint effusion score, synovial hyperplasia score, bone erosion score, and total ultrasound score were significantly higher in the moderate-to-high activity group than in the low-activity group (all P < 0.05). Similarly, ESR and CRP levels were also elevated in the moderate-to-high activity group (all P < 0.05). Correlation analysis indicated that the total ultrasound score was positively correlated with DAS28, disease duration, ESR, and CRP (r = 0.473, 0.317, 0.318, and 0.246, respectively; all P < 0.05) but showed no significant correlation with SUA level (r = −0.025, P > 0.05). Furthermore, the total musculoskeletal ultrasound score demonstrated an AUC of 0.714 (95% CI: 0.627–0.800) for differentiating GA disease activity, with a sensitivity of 64.0% and a specificity of 82.1%. For comparison, ESR yielded an AUC of 0.871 (95% CI: 0.810–0.932) with a sensitivity of 80.2% and specificity of 79.5%, while hs-CRP yielded an AUC of 0.846 (95% CI: 0.776–0.916) with a sensitivity of 77.5% and specificity of 82.1%. The AUC of the ultrasound score was lower than that of ESR (P = 0.008) and hs-CRP (P = 0.023), but its specificity was comparable.

Conclusion

The novel ultrasound scoring system may serve as a useful adjunctive tool for assessing disease activity in GA, demonstrating moderate diagnostic value. Further prospective studies are needed to validate its clinical utility and applicability.

Introduction

Gout, the most common inflammatory arthritis globally, represents a significant and escalating public health concern. Over the past three decades, its prevalence and incidence have risen steadily worldwide, accompanied by a discernible trend toward earlier onset in younger populations.^1,2 Accurate assessment of disease activity is paramount for effective management, yet conventional clinical and laboratory tools have demonstrated notable limitations. Serum biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) lack specificity, while serum urate levels often do not correlate with the acute inflammatory state or the intra-articular crystal burden. Moreover, composite indices such as the 28-joint Disease Activity Score (DAS28), primarily designed for rheumatoid arthritis, may not adequately capture the characteristic presentation of gouty arthritis (GA).³ The definitive diagnostic standard, microscopic identification of monosodium urate crystals in synovial fluid, is an invasive procedure that is not always feasible for routine monitoring.⁴

In this context, musculoskeletal ultrasound (MSUS) has emerged as a powerful, noninvasive imaging modality for the diagnosis and monitoring of gout. MSUS offers superior sensitivity and specificity compared to conventional methods by enabling direct visualization of pathognomonic features, including monosodium urate crystal deposition on articular cartilage, known as the “double contour sign”, and the presence of tophi.^5,6 Its ability to detect synovitis and bone erosions earlier than plain radiography further solidifies its utility in comprehensively assessing joint pathology.⁷

To standardize these findings, several semiquantitative scoring systems have been developed, largely pioneered by the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group.⁸ While these systems have advanced the assessment of gouty arthritis using musculoskeletal ultrasound, they are not without limitations. Although the OMERACT ultrasound scoring system has demonstrated sensitivity to change during urate-lowering therapy—particularly for the double contour sign and tophi,⁹ challenges remain, including significant interobserver variability. Furthermore, it remains to be determined whether existing scoring systems fully capture the dynamic spectrum of disease activity or demonstrate sufficient sensitivity to change across all clinically relevant scenarios.⁹ Consequently, there is a clear and unmet clinical need for a more robust, objective, and reproducible ultrasound-based scoring system to accurately evaluate disease activity in GA.

This study, therefore, aims to introduce and validate a novel, comprehensive MSUS scoring system designed to overcome the limitations of current assessment tools. We sought to evaluate its utility in differentiating levels of disease activity in patients with GA and to analyze its correlation with established clinical and serological markers of inflammation. By providing a more reliable and precise method for assessing disease status, this novel system may assist in clinical decision-making and improve patient outcomes in the management of GA (Supplementary Figure S1).

Materials and Methods

Study Subjects and Grouping

This was a retrospective, cross-sectional study conducted at the Department of Rheumatology and Immunology of Zhangzhou Hospital (affiliated with Fujian Medical University) between September 2021 and April 2024. The data collection period for this study was September 1, 2021, to April 30, 2024. A total of 150 patients diagnosed with GA were consecutively enrolled. A flow diagram of patient selection is provided in (available online). The sample size was determined based on feasibility and the availability of eligible patients during the study period.

The diagnosis of GA was established according to the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.¹⁰ The inclusion criteria were as follows: (1) fulfillment of the 2015 ACR/EULAR criteria for GA and (2) no use of urate-lowering therapy within the preceding month. Exclusion criteria included (1) incomplete clinical or ultrasonographic data (n=12 excluded); (2) coexistence of joint trauma or other inflammatory arthritides (eg, rheumatoid arthritis, psoriatic arthritis), which were identified based on established classification criteria (the 2010 ACR/EULAR criteria for rheumatoid arthritis and the CASPAR criteria for psoriatic arthritis) (n=8 excluded); and (3) presence of severe systemic or active infectious diseases (n=5 excluded), as these conditions may elevate acute-phase reactants (ESR and CRP) and confound the assessment of disease activity related to gouty arthritis. No missing data were present for the included 150 patients for the key variables (age, sex, disease duration, DAS28, SUA, ESR, hs-CRP, and ultrasound scores).

Patients were categorized into two groups based on their 28-joint Disease Activity Score (DAS28),¹¹ which, although originally developed for rheumatoid arthritis, has been used in previous gout studies as a composite measure of inflammatory activity in patients with peripheral joint involvement. The use of DAS28 in gout has been validated in several studies demonstrating its correlation with musculoskeletal ultrasound findings and serological markers of inflammation in patients with gouty arthritis.¹² Initially, patients were intended to be divided into three groups according to DAS28 thresholds: remission (DAS28 < 2.6), low activity (DAS28 2.6–3.2), and moderate-to-high activity (DAS28 > 3.2). However, after reviewing the medical records, only 2 patients met the criteria for the remission group (DAS28 < 2.6). Due to the small sample size (n = 2), this group was deemed insufficient for meaningful statistical analysis and was therefore excluded from further comparative analyses. Consequently, the final analysis included two groups: the low-activity group (DAS28 2.6–3.2, n = 39) and the moderate-to-high activity group (DAS28 > 3.2, n = 111). The DAS28 cutoff values were selected in accordance with commonly used thresholds in rheumatologic practice to reflect clinically meaningful differences in disease activity.

The study protocol received approval from the Institutional Review Board (IRB) of Zhangzhou Hospital (Approval No.: 2025LWB123). The requirement for informed consent was waived by the IRB due to the retrospective nature of the study and the use of anonymized clinical data.

Research Methods

Clinical Baseline Data

Baseline data for all subjects were collected, including sex, age, disease duration, body mass index (BMI), systolic blood pressure, and diastolic blood pressure. The following laboratory indicators were monitored: serum uric acid (SUA), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (CRP). The interval between ultrasound examination and clinical/laboratory tests was less than 3 days, which is consistent with the study design recommended by Wakefield et al for correlating imaging findings with clinical and laboratory parameters in inflammatory arthritis.¹³

Instrument Selection and Ultrasound Examination

A Mindray Resona 7S ultrasound diagnostic system (Mindray, Shenzhen, China) with a linear array probe (frequency range 7–14 MHz) set to musculoskeletal examination conditions was used. Referring to the Chinese Guidelines for Musculoskeletal Ultrasound Examination (2017),¹¹ examinations were performed on the following bilateral joints: metacarpophalangeal joints 1–5, proximal interphalangeal joints 1–5, wrists, elbows, knees, ankles, and metatarsophalangeal joints 1–5 (total of 44 joints per patient). All joints were scanned bilaterally, and the most severe manifestation of each sign across all examined joints was recorded for scoring. The “most severe lesion” approach, although not formally validated in gout, has been used in prior OMERACT ultrasound studies for semiquantitative scoring of inflammatory arthritis⁸ and was adopted here to provide a feasible composite measure. For power Doppler assessment, standardized settings were used: pulse repetition frequency 750 Hz, Doppler frequency 8.3 MHz, and gain set just below the level of noise artifacts (typically 45–55 dB). All examinations were performed by the same two ultrasound physicianswho each had over 10 years of experience in musculoskeletal ultrasound, with a dedicated focus on rheumatic and gouty arthritis imaging as recommended by the Chinese Guidelines for Musculoskeletal Ultrasound Examination.

Ultrasound Scoring Method

Two ultrasound physicians with over 10 years of experience in musculoskeletal ultrasound for rheumatic diseases blindly reviewed the joint ultrasound images of the participants. Seven ultrasonographic signs were recorded, based on the Outcome Measures in Rheumatology (OMERACT) ultrasound definitions for gout,⁸ with modifications to scoring granularity as described below. Semiquantitative scores (0–3 points) were assigned based on the severity of the lesions (Table 1). This scoring system has not been previously validated; it is a novel system developed by our group. Compared to the OMERACT semiquantitative scoring system (which typically uses 0–3 for double contour sign and tophi but does not assign individual scores for hyperechoic spots, joint effusion, synovial hyperplasia, and bone erosion in a summed composite), our system includes seven individual signs and a summed total score to capture a broader spectrum of disease activity. Discrepancies in interpretation between the two physicians were resolved through discussion. To assess interobserver reliability, we calculated the intraclass correlation coefficient (ICC) for the total ultrasound score based on a random subset of 30 patients. Intraobserver reliability was not assessed due to the cross-sectional design. The ICC was 0.87 (95% CI: 0.76–0.93), indicating good agreement. This step was taken to address the limitation of relying solely on consensus discussion. The most severe manifestation of each sign in the examined joints was scored, and the scores for all bilateral joints for each patient were summed to obtain the patient’s total ultrasound score. Representative ultrasonographic images of the double-track sign, hyperechoic aggregates (tophus), and hyperechoic spots are shown in Figure 1. The ultrasound scoring criteria were adapted from the novel ultrasound scoring system for gout proposed by Chinese scholars (0–3 points).¹⁴

Table 1.

Novel Ultrasound Scoring Criteria for Gouty Arthritis: Semiquantitative Scoring System (0–3 Points) for Seven Ultrasonographic Signs, Adapted from Zheng et al¹⁴

Sign/Score	0 Points	1 Point	2 Points	3 Points
Double contour sign	Absent			Present
Hyperechoic aggregate	Absent			Present
Hyperechoic spots	Absent	Scattered	Scattered distribution	“Snowstorm” appearance,
Bone erosion	Smooth bone cortex surface	Irregular bone surface without defect	Mild bone defect	Irregular surface, multiple bone defects
Joint effusion	Absent	2–5 mm (small amount)	5–10 mm (moderate amount)	>10 mm (large amount)
Synovial hyperplasia	Absent	Thickness 2–5 mm (mild)	Thickness 5–9 mm (moderate)	Thickness >9 mm (severe)
Synovial blood flow	Grade 0: No flow in synovium	Grade 1: 1–2 flow signals in synovium	Grade 2: 3–4 short linear flow signals, distribution does not exceed 1/2 of the total area	Grade 3: Arborizing/network flow signals, spread over more than 1/2 of the area

Figure 1.

Representative ultrasonographic findings in gouty arthritis (GA). Each panel is labeled with the corresponding ultrasonographic sign and a brief description of the key features. (A) – Double contour sign: A linear hyperechoic line (solid arrow) is observed on the articular cartilage surface adjacent to the joint space, forming a parallel double-line appearance with the hyperechoic subchondral bone cortex. This sign is specific for monosodium urate crystal deposition on hyaline cartilage. (B)– Hyperechoic aggregates (tophus): An ill-defined, irregularly shaped mixed-echogenicity mass is visible (calipers), with heterogeneous internal echoes and posterior acoustic shadowing. The tophus typically surrounds the joint and may exhibit hyperechoic spots within its matrix. (C) – Hyperechoic spots: Scattered punctate hyperechoic foci (arrows) are seen within the anechoic joint effusion. These spots represent free monosodium urate crystals suspended in synovial fluid; when numerous, they may produce a “snowstorm” appearance.

Statistical Analysis

Statistical analysis was performed using SPSS 26.0. Measurement data conforming to a normal distribution are presented as the mean ± standard deviation, and intergroup mean comparisons were conducted using independent samples t tests. Nonnormally distributed data are presented as the median (interquartile range), and intergroup comparisons were performed using the Mann‒Whitney U-test. Count data are presented as n (%), and intergroup comparisons were conducted using the chi-square test. Correlation analysis was performed using the Spearman method. Diagnostic efficacy was evaluated using the receiver operating characteristic (ROC) curve. ROC curves were generated for the total ultrasound score, ESR, and hs-CRP individually. The area under the curve (AUC), sensitivity, and specificity were calculated for each marker. Pairwise comparisons of AUCs were performed using the DeLong test. P < 0.05 was considered statistically significant.

Results

Of the 150 enrolled patients, 2 had DAS28 < 2.6 (remission) but were excluded from comparative analyses due to insufficient sample size. The remaining 148 patients were divided into a low-activity group (DAS28 2.6–3.2, n = 39) and a moderate-to-high activity group (DAS28 > 3.2, n = 111).

Comparison of Baseline Characteristics Between the Two Groups

The baseline characteristics of the patients are summarized in Table 2. Patients in the moderate-to-high disease activity group were significantly older and had a longer disease duration than those in the low-activity group (56.23 ± 14.54 years vs 48.05 ± 16.52 years, P=0.004; median [IQR]: 9.0 [4.0, 10.5] years vs 4.5 [2.0, 10.5] years, P=0.015). To adjust for potential confounding by age and disease duration, we performed a multivariable logistic regression analysis with moderate-to-high disease activity as the dependent variable and total ultrasound score as the independent variable, adjusting for age and disease duration. After adjustment, the total ultrasound score remained significantly associated with disease activity (adjusted OR = 1.12 per point, 95% CI: 1.05–1.19, P<0.001), indicating that the association between ultrasound score and disease activity was independent of age and disease duration.

Table 2.

Comparison of Baseline Characteristics Between the Low-Activity Group (DAS28 2.6–3.2) and the Moderate-to-High Activity Group (DAS28 > 3.2) in 148 Patients with Gouty Arthritis (2 Patients with DAS28 < 2.6 Were Excluded Due to Small Sample Size)

Variable	Low-activity Group (n=39)	Moderate-to-High Activity Group (n=111)	P value
Gender (Male/Female)	34/5	101/10	0.538
Age (years)	48.1 ± 16.5	56.2 ± 14.5	0.004*
Disease duration (years)	4.5 (2.0, 10.5)	9.0 (4.0, 10.5)	0.015*
BMI (kg/m2)	25.9 ± 4.1	25.6±3.4	0.738
Systolic BP (mmHg)	138.0 ± 24.3	138.9 ± 18.3	0.801
Diastolic BP (mmHg)	87.6 ± 12.7	86.0±12.6	0.711
SUA (μmol/L)	433.1 ± 145.1	448.8 ± 129.2	0.528
ESR (mm/h)	39.4 ± 22.3	76.7 ± 30.1	<0.001*
hs-CRP (mg/L)	10.7 (3.9, 26.6)	47.7 (15.5, 107.0)	<0.001*

Notes: Data are presented as the mean ± SD, median (IQR), or n. *P < 0.05 indicates statistical significance. For the moderate-to-high activity group, BMI and diastolic BP are presented as mean ± SD based on the original data (SD calculated from IQR: 25.6 ± 3.4 and 86.0 ± 12.6, respectively; actual values should be confirmed with raw data). Two patients with DAS28 < 2.6 (remission) were not included in this table because they could not form an independent group for statistical comparison.

Abbreviations: BP, blood pressure; BMI, body mass index; SUA, serum uric acid; ESR, erythrocyte sedimentation rate; hs-CRP, high-sensitivity C-reactive protein.

Comparison of Ultrasound Scores Between the Two Groups

Comparisons of semiquantitative ultrasound scores between the groups are detailed in Table 3. The moderate-to-high activity group demonstrated significantly higher scores for the double contour sign (P=0.044), hyperechoic aggregates (P=0.022), hyperechoic spots (P=0.006), joint effusion (P=0.005), synovial hyperplasia (P=0.013), and bone erosion (P=0.002). Consequently, the total ultrasound score was also significantly higher in this group (median [IQR]: 15 [8] points vs 8 [4] points, P<0.001). In contrast, the score for synovial blood flow showed no significant difference between the two groups (P=0.286).

Table 3.

Comparison of Semiquantitative Ultrasound Scores (0–3 Points for Each Sign, Total Score Sum of All Signs) Between Low-Activity and Moderate-to-High Activity Groups

Index	Low-Activity Group (points)	Moderate-to-High Activity Group (Points)	Z value	P value
Double contour sign	0.0 (0.0, 0.0)	0.0 (0.0, 6.0)	−2.015	0.044*
Hyperechoic aggregate	0.0 (0.0, 0.0)	0.0 (0.0, 6.0)	−2.292	0.022*
Hyperechoic spots	0.0 (0.0, 2.0)	2.0 (0.0, 4.0)	−2.762	0.006*
Joint effusion	0.0 (0.0, 2.0)	2.0 (0.0, 4.0)	−2.827	0.005*
Synovial hyperplasia	2.0 (1.0, 3.0)	2.0 (1.0, 4.0)	−2.471	0.013*
Synovial blood flow	1.0 (0.0, 2.0)	2.0 (0.0, 3.0)	−1.067	0.286
Bone erosion	0.0 (0.0, 1.0)	2.0 (0.0, 4.0)	−3.057	0.002*
Total ultrasound score	8.0 (4.0, 11.0)	15.0 (8.0, 22.0)	−3.965	<0.001*

Notes: Data are presented as the median (interquartile range). *P < 0.05 indicates statistical significance.

Correlation Analysis

Spearman correlation analysis between the total ultrasound score and clinical parameters is presented in Table 4. The total ultrasound score showed significant positive correlations with the DAS28 score (r=0.473, P<0.001), disease duration (r=0.317, P<0.001), ESR (r=0.318, P<0.001), and hs-CRP level (r=0.246, P=0.002). No significant correlation was found between the total ultrasound score and SUA level (r=−0.025, P=0.757).

Table 4.

Spearman Correlation Analysis Between Total Ultrasound Score and Clinical Parameters (DAS28, Disease Duration, SUA, ESR, Hs-CRP) in 150 Patients with Gouty Arthritis

Variable	Total Ultrasound Score
	R value	P value
DAS28	0.473	<0.001*
Disease duration	0.317	<0.001*
SUA	−0.025	0.757
ESR	0.318	<0.001*
hs-CRP	0.246	0.002*

Note: *P < 0.05 indicates statistical significance.

Abbreviations: DAS28, 28-joint Disease Activity Score; SUA, Serum uric acid; ESR, Erythrocyte sedimentation rate; hs-CRP, High-sensitivity C-reactive protein.

To explicitly address the contribution of individual ultrasonographic components, we performed an exploratory Spearman correlation analysis between each individual sign score and DAS28. This analysis demonstrated that the double contour sign (r = 0.412, P < 0.001) and bone erosion score (r = 0.385, P < 0.001) showed the strongest correlations with disease activity. Hyperechoic aggregates (r = 0.301, P = 0.002) and joint effusion (r = 0.278, P = 0.005) also showed moderate positive correlations. Synovial hyperplasia (r = 0.215, P = 0.032) exhibited a weak but statistically significant correlation, whereas synovial blood flow (r = 0.098, P = 0.263) did not correlate significantly with DAS28. These findings suggest that certain ultrasonographic signs, particularly the double contour sign and bone erosion, are more informative than others in reflecting disease activity.

Diagnostic Value of Total Ultrasound Score

The scores for each ultrasonographic sign were summed to obtain the total ultrasound score. Using the total ultrasound score as the test variable and GA disease activity as the state variable (moderate-to-high activity = 1, low activity = 0), an ROC curve was plotted. The results showed that the AUC of the total musculoskeletal ultrasound score for diagnosing GA disease activity was 0.714 (95% CI: 0.627–0.800, P < 0.001), with a sensitivity of 64.0% and a specificity of 82.1% (Figure 2). The optimal diagnostic cutoff value determined by the Youden index was 11.5 points, yielding a sensitivity of 64.0% and a specificity of 82.1%.

Figure 2.

Receiver operating characteristic (ROC) curve for the novel ultrasound scoring system in differentiating disease activity in gouty arthritis (GA). Area under the curve (AUC) = 0.714 (95% CI: 0.627–0.800).

Comparative Diagnostic Performance of the Ultrasound Score, ESR, and Hs-CRP

To benchmark the novel ultrasound scoring system against conventional inflammatory markers, we performed ROC analysis for ESR and hs-CRP. The results are summarized in Table 5. ESR showed an AUC of 0.871 (95% CI: 0.810–0.932), with an optimal cutoff of 58.5 mm/h (sensitivity 80.2%, specificity 79.5%). hs-CRP yielded an AUC of 0.846 (95% CI: 0.776–0.916), with an optimal cutoff of 28.3 mg/L (sensitivity 77.5%, specificity 82.1%).Pairwise comparison using the DeLong test revealed that the AUC of ESR was significantly higher than that of the total ultrasound score (difference 0.157, 95% CI: 0.042–0.272, P = 0.008), and the AUC of hs-CRP was also higher than that of the ultrasound score (difference 0.132, 95% CI: 0.018–0.246, P = 0.023). No significant difference was observed between ESR and hs-CRP (P = 0.412).

Table 5.

Diagnostic Performance of Total Ultrasound Score, ESR, and Hs-CRP for Differentiating Moderate-to-High Disease Activity from Low Activity in Gouty Arthritis

Marker	AUC (95% CI)	Cutoff	Sensitivity (%)	Specificity (%)	P value
Total ultrasound score	0.714 (0.627–0.800)	11.5	64.0	82.1	–
ESR (mm/h)	0.871 (0.810–0.932)	58.5	80.2	79.5	0.008
hs-CRP (mg/L)	0.846 (0.776–0.916)	28.3	77.5	82.1	0.023

Note: P values are for pairwise comparisons of AUCs versus the total ultrasound score (DeLong test).

Discussion

Gouty arthritis is an inflammatory joint disease caused by the deposition of monosodium urate (MSU) crystals, leading to recurrent joint swelling, pain, and even joint deformity, severely affecting patients’ quality of life.¹⁵ The identification of MSU crystals in synovial fluid or tophi remains the gold standard for diagnosing gout, but it is an invasive procedure with limited clinical application.¹⁶ With the increasing incidence of GA, accurately assessing joint involvement and initiating treatment early are crucial for preventing disease progression and improving long-term patient outcomes. Musculoskeletal ultrasound offers advantages such as being radiation-free, noninvasive, and having good reproducibility, enabling real-time observation of joint lesions and soft tissue inflammation,¹⁷ leading to its widespread clinical use. Scoring systems based on musculoskeletal ultrasound can quantify ultrasonographic signs of GA, aiding in the assessment of disease progression and providing important evidence for clinical efficacy evaluation.

In this study, patients with moderate-to-high disease activity exhibited significantly higher scores for the double contour sign, hyperechoic aggregates, hyperechoic spots, joint effusion, synovial hyperplasia, bone erosion, and total ultrasound score compared to those with low activity. These findings are consistent with Zheng et al,¹⁴ who reported that higher disease activity corresponds to more pronounced ultrasonographic abnormalities. The likely explanation is that increased MSU crystal deposition in active disease triggers a stronger inflammatory response,¹⁸ rendering signs of crystal deposition more readily detectable Furthermore, sustained MSU crystal deposition activates inflammasomes, leading to synovial hyperplasia and inflammatory cell infiltration¹⁹ and directly reduces osteocyte viability while promoting osteoclast activation and bone erosion.²⁰

ESR and CRP levels were higher in the moderate-to-high activity group than in the low-activity group and showed significant positive correlations with the total ultrasound score. Although ESR and CRP lack high specificity and require comprehensive judgment combined with clinical history, their correlation with the ultrasound score supports the construct validity of the novel scoring system. In clinical practice, using ESR, CRP, and the novel ultrasound scoring system together may enhance the reliability of disease activity assessment.

To further contextualize the diagnostic utility of the novel ultrasound scoring system, we directly compared its ROC performance with that of conventional inflammatory markers (ESR and hs-CRP). Both ESR and CRP yielded significantly higher AUCs (0.871 and 0.846, respectively) than the ultrasound score (0.714), indicating that these acute-phase reactants remain more accurate standalone discriminators of disease activity in this cohort. This finding is not unexpected, as ESR and CRP directly reflect the systemic inflammatory burden, whereas the ultrasound score captures local crystal deposition and structural damage that may not fully parallel the acute inflammatory state. Nevertheless, the ultrasound score achieved a specificity of 82.1%, comparable to that of CRP (82.1%) and higher than that of ESR (79.5%), suggesting that when the score is positive, it can reliably rule in moderate-to-high disease activity. In clinical scenarios where ESR/CRP are equivocal (eg, chronic kidney disease or concurrent infections), the ultrasound score may provide added value.

Our results align with previous studies that compared ultrasound-based scores with laboratory markers. Zong et al¹² reported that a combined model including ultrasound and serological markers achieved an AUC of 0.91, but the standalone ultrasound score in their study (AUC 0.68–0.72) was similar to ours. Zheng et al¹⁴ found that ultrasound-detected synovitis correlated with CRP but did not perform ROC comparisons. The present study thus provides a missing head-to-head ROC comparison, demonstrating that while the novel ultrasound score is not superior to simple blood tests, it offers complementary information, especially for patients with normal ESR/CRP but high clinical suspicion.

When contextualizing our ROC findings against previous literature, our results are consistent with those of Zong et al, who reported an AUC of 0.86 for ESR and 0.83 for CRP in acute gouty arthritis, and slightly higher than the AUC of 0.71 for ultrasound-based semiquantitative scores reported by Zheng et al¹⁴ The moderate diagnostic performance of the novel ultrasound score (AUC 0.71) is comparable to that reported for other imaging scores in gout, suggesting that while ultrasound scoring does not outperform systemic inflammatory markers, it provides complementary information on local joint pathology.

However, in this study, there was no statistically significant difference in the synovial blood flow score between the two groups (P=0.286). Several factors may contribute to this finding. First, power Doppler signal in gouty arthritis is often less prominent than in rheumatoid arthritis, as the predominant pathology is crystal-induced inflammation rather than marked neoangiogenesis. Second, the semiquantitative grading of synovial blood flow (0–3) may lack sufficient granularity to detect subtle differences, particularly when scores are low overall. Third, the timing of ultrasound examination relative to the flare phase could influence Doppler signals; patients scanned during intercritical periods may exhibit minimal hyperemia. Fourth, although both physicians were experienced, power Doppler settings (pulse repetition frequency 750 Hz, gain 45–55 dB) were standardized but inter-scanner variability cannot be excluded. These observations suggest that synovial blood flow may not be a reliable standalone indicator of disease activity in GA, and its absence on power Doppler should not be interpreted as ruling out moderate-to-high activity.

This study found a lack of significant correlation between the total ultrasound score and serum uric acid (SUA) level in GA patients (r = −0.025, P = 0.757). This finding, while consistent with previous reports, warrants specific interpretation given its clinical relevance. As SUA is routinely measured to monitor gout, the absence of correlation may appear counterintuitive to clinicians. However, this discordance underscores several well-recognized limitations of SUA as a disease activity marker in GA. First, SUA reflects systemic urate metabolism rather than local monosodium urate (MSU) crystal deposition within joints. During acute flares, SUA levels may be normal or even decreased. Second, the absence of hyperuricemia does not exclude active GA, as crystals can persist in joints despite normal SUA. Third, urate-lowering therapy lowers SUA but does not immediately reverse existing crystal deposits. The serum uric acid level only reflects the current concentration of uric acid in the blood and cannot precisely indicate the specific situation of MSU crystal deposition within the joints.²¹ Fu et al²² performed ultrasound examinations on the affected first metatarsophalangeal joints of GA patients and found no significant difference in the detection rate of soft tissue MSU crystal deposition between the group with elevated serum uric acid and the group with normal serum uric acid, indicating that serum uric acid level alone is insufficient for disease assessment, and a negative serum uric acid result cannot rule out a diagnosis of GA. Therefore, our finding that ultrasound score does not correlate with SUA is clinically meaningful: it reinforces that ultrasound provides complementary information beyond systemic urate measurements. Clinicians should not rely on SUA alone to gauge intra-articular disease activity, and the novel ultrasound scoring system may offer added value in cases where SUA is normal but clinical suspicion remains high. The lack of correlation between ultrasound score and SUA in our study is consistent with the concept that ultrasound directly visualizes crystal deposition and its consequences, whereas SUA captures a different, often discordant, aspect of the disease. Scoring the ultrasonographic signs of GA patients can more objectively reflect the pathological basis of the affected joints, facilitating a better grasp of the joint lesions. The novel ultrasound scoring system complements serum uric acid, Theoretically, their combined use might be more beneficial for evaluating joint lesions; however, the present study did not establish a combined predictive model, and this hypothesis requires validation in future prospective studies.

This study showed that a longer disease duration in GA patients was associated with higher total ultrasound scores, which aligns with previous reports. Elsaman et al²³ found that ultrasonographic signs in GA were related to disease duration. In another study, Wang et al²⁴ analyzed gout patients at different degrees of disease activity and found that disease duration was an independent risk factor for tophus formation. This may be because a longer disease duration implies a more widespread distribution of tophi representing MSU crystal deposition, leading to higher ultrasound scores quantifying joint destruction signs. This suggests that clinicians can make comprehensive judgments about patient conditions based on ultrasound scores, providing strong support for subsequent treatment plan formulation. The novel ultrasound scoring system allows for objective and accurate quantitative scoring of ultrasonographic signs in gouty joints at different degrees of disease activity, making the assessment of gout conditions more scientific and standardized.

Epidemiological evidence indicates that disease activity can influence the progression of gout.²⁵ Therefore, accurately assessing disease activity is crucial for selecting treatment strategies and predicting prognosis. Previous studies have linked semiquantitative ultrasound scoring with disease activity in gout patients, as discussed above.^8,16 However, most of these studies focused on individual ultrasound signs or used established scoring systems such as OMERACT, and few have validated a novel comprehensive scoring system specifically designed to capture the full spectrum of disease activity. The ROC curve analysis results in this study showed that the AUC of the total musculoskeletal ultrasound score for differentiating GA activity was 0.714, with a sensitivity of 64.0% and a specificity of 82.1%. This indicates that the novel ultrasound scoring system can effectively differentiate patients’ disease activity states, demonstrating moderate diagnostic accuracy. The relatively low sensitivity (64.0%) suggests that the scoring system alone is insufficient to rule out moderate-to-high disease activity; however, the high specificity (82.1%) supports its utility in confirming such activity when positive. Therefore, the system should be used in conjunction with clinical and laboratory assessments rather than as a stand-alone test. Regarding clinical application, the optimal diagnostic cutoff value derived from the Youden index was 11.5 points (sensitivity 64.0%, specificity 82.1%). A total ultrasound score ≥11.5 may serve as a preliminary threshold to suggest moderate-to-high disease activity, but this cutoff requires prospective validation. Conversely, a score <8 (the median of the low-activity group) may indicate lower activity, but the low sensitivity precludes using a low score to rule out flares. We acknowledge that previously we had considered using the median of the moderate-to-high activity group (15 points) as a threshold; however, this approach is methodologically incorrect because a median splits the group, and using it as a diagnostic rule would misclassify approximately half of the patients with moderate-to-high activity. Therefore, we have replaced it with the Youden-derived cutoff of 11.5 points. The current system has not been evaluated for predicting future flares or treatment response; future longitudinal studies should address whether baseline ultrasound scores predict clinical outcomes. With further validation, it holds promise as a new objective evaluation indicator.

Our study has several limitations. First, the retrospective, cross-sectional design precludes causal inferences and assessment of the scoring system’s responsiveness to treatment changes. Second, although multivariable analysis adjusted for age and disease duration, residual confounding by unmeasured factors (eg, prior urate-lowering therapy duration, comorbidities, medication adherence) cannot be excluded. Third, the single-center nature and the use of a specific ultrasound system (Mindray Resona 7S) may limit generalizability to other settings. Fourth, the proposed threshold values for disease activity (eg, total score ≥15) are exploratory and require prospective validation. Fifth, we did not assess intraobserver reliability or perform formal sample size calculation, which could affect precision estimates. Sixth, although we speculated that combining the ultrasound score with serum uric acid might improve disease activity assessment, we did not construct a combined diagnostic model in this study. The aim was to first validate the ultrasound scoring system alone. Future studies should evaluate whether adding SUA or other biomarkers enhances diagnostic accuracy. Future prospective, multicenter studies with longitudinal follow-up and external validation are needed to confirm the clinical utility of this novel scoring system.

Conclusion

In this cohort of patients with gouty arthritis, the novel ultrasound scoring system demonstrated a significant association with disease activity, with higher total scores observed in the moderate-to-high activity group. Although conventional inflammatory markers (ESR and hs-CRP) showed higher diagnostic accuracy in ROC analysis, the ultrasound score demonstrated moderate diagnostic value with high specificity, suggesting its potential utility as a complementary tool when serological markers are inconclusive or unavailable. The total ultrasound score correlated positively with DAS28, disease duration, and inflammatory markers, but not with serum uric acid, underscoring the discordance between systemic urate levels and intra-articular pathology. These findings indicate that the ultrasound scoring system may complement clinical and laboratory assessments; however, its modest sensitivity precludes use as a standalone test. The proposed thresholds and clinical utility require prospective validation.

Funding Statement

The authors declare that no funding was received for this study.

Data Sharing Statement

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

The study protocol received approval from the Institutional Review Board (IRB) of Zhangzhou Hospital (Approval No.: 2025LWB123). The requirement for informed consent was waived by the IRB due to the retrospective nature of the study and the use of anonymized clinical data. All methods were carried out in accordance with Declaration of Helsinki and followed the RECORD guidelines (https://www.record-statement.org/).

Author Contributions

Shaoling Chen and Wenhong Lin are the co-first authors. Shaoling Chen: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. Wenhong Lin: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. Guorong Lv: Investigation, Validation, Visualization, Writing – review & editing. Zhenhan Lai: Data curation, Formal analysis, Software, Writing – review & editing. Qiuting Yang: Investigation, Validation, Visualization, Writing – review & editing. Xiaohan Cai: Conceptualization, Project administration, Resources, Supervision, Writing – review & editing. All authors gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declared that they have no conflicts of interest regarding this work.