ABSTRACT
As a critical stage before psoriatic arthritis (PsA) onset, subclinical PsA provides an opportunity window for early diagnosis and intervention. This study aimed to describe the clinical and ultrasound characteristics of patients fulfilling the EULAR definition of subclinical PsA, and to explore the heterogeneity of arthralgia within this population. Patients fulfilling the EULAR definition of subclinical PsA, characterized by arthralgia and/or ultrasound evidence of synovial/entheseal inflammation without clinical synovitis, were enrolled in the Subclinical Psoriatic Arthritis Cohort of West China Hospital (SPAWCH) Cohort from January 2019 to December 2024. We collected clinical information, arthralgia features, and ultrasound findings, conducting a cross‐sectional analysis. Overall, 306 patients were included in the analysis. Among them, 84 (27.5%) had both arthralgia and ultrasound abnormalities (Group AU), 203 (66.3%) had isolated ultrasound abnormalities (Group IU), and 19 (6.2%) had isolated arthralgia (Group IA). Compared with the Group IU, patients in the Group AU were older (49.3 ± 13.7 vs. 43.5 ± 13.2 years, p = 0.001) and had a longer duration of psoriasis (17.7 ± 12.3 vs. 14.1 ± 9.8 years, p = 0.020). Additionally, the two main arthralgia types were activity‐related (60, 58.3%) and rest‐related (25, 24.3%). Rest‐related arthralgia was associated with prolonged arthralgia duration (p = 0.041), higher morning stiffness incidence (p = 0.031), and more prominent inflammatory characteristics (p = 0.001) compared to activity‐related cases. In this study, ultrasound abnormalities emerged as the dominant feature in patients meeting the EULAR definition of subclinical PsA. Notably, the coexistence of arthralgia and ultrasound abnormalities was associated with a longer duration of psoriasis. While activity‐related arthralgia was the most prevalent type, rest‐related arthralgia.
Keywords: arthralgia, psoriasis, psoriatic arthritis, subclinical, ultrasound
1. Introduction
Psoriasis is a common, chronic, inflammatory papulosquamous skin disease affecting over 60 million individuals worldwide [1]. Up to one‐third of patients with psoriasis develop psoriatic arthritis (PsA), a chronic and clinically heterogeneous inflammatory musculoskeletal disease [2]. Given the challenges in early diagnosis and suboptimal therapeutic outcomes for established PsA, there is growing interest in delaying or preventing the psoriasis‐to‐PsA transition [3, 4, 5].
The focus on this transition process has led to the conceptualization of distinct stages preceding clinical PsA. The 2023 European League Against Rheumatism (EULAR) guideline proposed a widely recognized three‐stage framework for psoriasis‐to‐PsA transition: individuals with psoriasis at higher PsA risk, subclinical PsA, and clinical PsA [6]. Specifically, EULAR defines subclinical PsA as psoriasis patients experiencing arthralgia and/or showing ultrasound evidence of synovial/entheseal inflammation but lacking clinical synovitis [6].
Subclinical PsA is considered a critical window for preventing the progression from psoriasis to PsA [7, 8] and has garnered growing interest among rheumatologists and dermatologists [9, 10]. Nevertheless, comprehensive characterization of this population remains limited, and distinctions between different subclinical PsA subgroups are insufficiently understood [11]. To address this gap, this study aims to describe the clinical, arthralgia, and ultrasound characteristics of patients meeting the EULAR definition of subclinical PsA, specifically comparing the three distinct patient groups (isolated arthralgia, isolated ultrasound abnormalities, and both). Furthermore, we will conduct a comprehensive investigation into the arthralgia features of these patients to enhance early identification for subclinical PsA. Together, these analyses may help better characterize the heterogeneity of this at‐risk population and improve its clinical interpretation.
2. Methods
2.1. Patient Enrollment and Study Design
This cross‐sectional study was based on the baseline data from the Subclinical Psoriatic Arthritis Cohort of West China Hospital (SPAWCH) database. The SPAWCH database was established in March 2024 and retrospectively included patients fulfilling the EULAR definition of subclinical PsA evaluated at West China Hospital between January 2019 and February 2024, with prospective enrollment thereafter. According to the 2023 EULAR criteria, subclinical PsA was defined as psoriasis patients with arthralgia and/or ultrasound evidence of synovial or entheseal inflammation, without clinical synovitis [6]. Based on this definition, eligible patients comprised those with: (1) the combination of arthralgia and imaging abnormalities, (2) imaging evidence of synovial and/or entheseal inflammation without arthralgia, or (3) isolated arthralgia without imaging abnormalities, provided that no clinical synovitis was detected on rheumatological examination. To ensure accurate classification, a stepwise approach was applied to define the study population. First, patients with clinically evident inflammatory arthritis were excluded. All participants were screened for typical features of inflammatory arthritis (such as joint swelling or other clinical signs suggestive of synovitis), and those fulfilling the CASPAR criteria were excluded, thereby ensuring that patients with definite PsA or other inflammatory arthritis were not included. Then among the remaining patients with psoriasis but without clinical evidence of inflammatory arthritis, musculoskeletal ultrasound examinations were systematically performed. Patients with ultrasound evidence of synovitis or enthesitis in the absence of clinical symptoms were classified as subclinical PsA. In addition, patients reporting arthralgia were referred for rheumatological assessment and, when necessary, underwent multidisciplinary team (MDT) evaluation involving dermatology, rheumatology, ultrasound, and radiology specialists to determine the nature of arthralgia. Mechanical injury, degenerative conditions (e.g., osteoarthritis), and other non‐inflammatory musculoskeletal causes were systematically evaluated and excluded. The remaining cases were considered to represent prodromal manifestations of PsA and were classified as subclinical PsA according to the EULAR definition.
The SPAWCH database received ethical approval from the Biomedical Research Ethics Committee of the West China Hospital, Sichuan University (approval number 2024(1493)). Each participating patient signed an informed consent form.
2.2. Data Collection and Clinical Evaluation
All patients underwent detailed clinical interviews and examinations. Data were collected on the following domains. Regarding demographics and medical histories, we documented age, sex, surgical/trauma history, allergies, smoking/alcohol consumption, family history, and prior/current treatments. Comorbidities included tuberculosis/hepatitis B infection, malignancy, and others. Data on psoriasis characteristics, including psoriasis type, age of onset, disease duration, and skin/nail involvement, were collected. The Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA) were used to assess the severity of plaque psoriasis.
In terms of arthralgia patterns, we focused on joint sites (peripheral and axial joints), visual analog scale (VAS) score of arthralgia, and arthralgia features (e.g., symmetry, persistence, activity/rest‐related arthralgia). Activity‐related arthralgia was defined as pain that appeared or worsened during physical activity and was relieved by rest, whereas rest‐related arthralgia was defined as pain that occurred or worsened during rest, particularly at night or in the early morning. Arthralgia was further classified as inflammatory or non‐inflammatory based on whether the symptoms were predominantly worse in the morning and improved during the day [12]. We also recorded associated symptoms, particularly morning stiffness (duration and VAS score).
2.3. Ultrasound Examination
All patients underwent standardized musculoskeletal ultrasound examinations performed according to our institutional protocol, which aligns with the American Institute of Ultrasound in Medicine (AIUM) guidelines [13, 14, 15]. Scanned joints included: shoulders, elbows, wrists, metacarpophalangeal joints (MCP), proximal and distal interphalangeal joints (IP), hips, knees, ankles, and metatarsophalangeal joints (MTP). The analyzed tendons comprised: triceps, biceps, subacromial deltoid, common extensor tendons, finger flexor tendons, quadriceps, patellar, achilles, plantar fascia, and posterior tibial tendons. Ultrasound lesions were evaluated according to the OMERACT definitions of elementary lesions. Synovitis was defined as hypoechoic synovial hypertrophy accompanied by positive Power Doppler signal [16]. Enthesitis was defined as a hypoechoic and/or thickened enthesis within 2 mm of the bony cortex, with positive Power Doppler signal indicating active inflammation and possible erosions, enthesophytes, or calcifications as structural changes [17].
2.4. Statistical Analysis
Categorical data were summarized as counts (%), while continuous data were presented as mean ± SD (normal distribution) or median (IQR; non‐normal distribution). For comparisons between two groups, Student's t‐tests and Welch's t‐test were employed for normally distributed continuous variables with equal and unequal variances. The Wilcoxon's rank‐sum test was used for non‐normally distributed continuous variables. For comparisons across three groups, one‐way ANOVA and Welch's ANOVA were used for normally distributed continuous variables with equal and unequal variances. The Kruskal–Wallis H test was applied for non‐normally distributed continuous variables. Categorical variables were compared using chi‐square tests or Fisher's exact tests. A p‐value of less than 0.05 was considered statistically significant. Statistical analyses were performed using the R software (version 4.3.2).
3. Results
3.1. Overall Clinical Characteristics of Subclinical PsA
We included 306 patients fulfilling the EULAR definition of subclinical PsA, with detailed clinical characteristics presented in Table 1 and Figure 1. The cohort comprised predominantly males (male‐to‐female ratio was 1:0.44), and at the time of subclinical PsA diagnosis, the patients had a mean age of 45.0 (SD 13.4) years. 103 out of 306 patients reported arthralgia, with a mean VAS score of 3.4 (SD 2.1) and a mean arthralgia duration of 3.4 (SD 5.9) years. Musculoskeletal ultrasound revealed abnormalities in 287 patients (93.8%), synovitis (68.6%), and enthesitis (33.7%) were the most common findings.
TABLE 1.
Clinical characteristics of subclinical PsA patients.
| Variable | n = 306 |
|---|---|
| Age, mean (SD) | 45.0 (13.4) |
| Sex (male: female) | 1:0.44 |
| BMI, mean (SD) | 24.8 (3.8) |
| Family history of psoriasis, n (%) | 74 (24.2) |
| Family history of psoriatic arthritis, n (%) | 6 (2.0) |
| Drinking history, n (%) | 147 (48.0) |
| Smoking history, n (%) | 111 (36.3) |
| Surgery history, n (%) | 106 (34.6) |
| Trauma history, n (%) | 34 (11.1) |
| Psoriasis type | |
| Plaque psoriasis, n (%) | 296 (96.7) |
| Pustular psoriasis, n (%) | 1 (0.3) |
| Erythrodermic psoriasis, n (%) | 1 (0.3) |
| Palmoplantar pustulosis, n (%) | 4 (1.3) |
| Nail psoriasis, n (%) | 3 (1.0) |
| Onset of PsO, years, mean (SD) | 28.7 (14.0) |
| Disease duration of PsO, years, mean (SD) | 15.3 (10.7) |
| Nail lesions, n (%) | 104 (34.0) |
| PASI, mean (SD) | 4.9 (4.6) |
| BSA, mean (SD) | 6.5 (9.1) |
| Previous treatment | |
| Methotrexate, n (%) | 82 (26.8) |
| Acitretin, n (%) | 78 (25.5) |
| Phototherapy, n (%) | 76 (24.8) |
| TCM, n (%) | 149 (48.7) |
| Arthralgia (n = 103 a ) | |
| Arthralgia VAS, mean (SD) | 3.4 (2.1) |
| Duration of arthralgia, years, mean (SD) | 3.4 (5.9) |
| Triggers of arthralgia | |
| Activity‐related arthralgia, n (%) | 60 (58.3) |
| Rest‐related arthralgia, n (%) | 25 (24.3) |
| Weather‐related arthralgia, n (%) | 12 (11.6) |
| Symmetrical arthralgia, n (%) | 43 (41.7) |
| Intermittent arthralgia, n (%) | 94 (91.3) |
| Most severe symptoms present in the morning, n (%) | 16 (15.5) |
| Improvement of symptoms during the day, n (%) | 16 (15.5) |
| Morning Stiffness, n (%) | 19 (18.4) |
| Morning Stiffness VAS, mean (SD) | 4.0 (1.5) |
| Duration of morning stiffness, min, mean (SD) | 12.2 (9.1) |
Abbreviations: BMI, body mass index; BSA, body surface area; PASI psoriasis area and severity index; TCM traditional Chinese medicine; VAS visual analog scale.
103 patients include those with arthralgia.
FIGURE 1.
Clinical Characteristics of subclinical PsA patients. (A) comorbidities in subclinical PsA patients (n = 306); (B) peripheral joints with ultrasound changes in subclinical PsA patients (n = 287); (C) current treatment of subclinical PsA patients (n = 306); (D) peripheral joints with arthralgia in subclinical PsA patients (n = 103); (E) tendons with ultrasound changes in subclinical PsA patients (n = 287); (F) ultrasound changes of peripheral joints in subclinical PsA patients (n = 287). Percentages add up to more than 100% because some patients could exhibit more than one clinical feature simultaneously. CMJ, carpometacarpal joints; DIP, distal interphalangeal joints; IBD, inflammatory bowel disease; MCP, metacarpophalangeal joints; MTP, metatarsophalangeal joints; PIP, proximal interphalangeal joints; TCM, traditional chinese medicine.
3.2. Arthralgia Characteristics and Ultrasound Discrepancies Across Subclinical PsA Phenotypes
To stratify heterogeneity among patients in our cohort, we categorized them into three phenotypically distinct groups: (1) both arthralgia and ultrasound abnormalities (Group AU, n = 84, 27.5%), (2) isolated ultrasound abnormalities (Group IU, n = 203, 66.3%), and (3) isolated arthralgia (Group IA, n = 19, 6.2%) (Table 2).
TABLE 2.
Intergroup comparison in subclinical PsA.
| Variable | Group IA (n = 19) | Group IU (n = 203) | Group AU (n = 84) | p |
|---|---|---|---|---|
| Age, mean (SD) | 42.8 (10.6) | 43.5 (13.2) | 49.3 (13.7) | 0.002 |
| Sex (male: female) | 1:1.11 | 1:0.38 | 1:0.50 | 0.064 |
| BMI, mean (SD) | 24.1 (3.2) | 24.8 (3.6) | 25.5 (5.0) | 0.201 |
| Psoriasis type | ||||
| Plaque psoriasis, n (%) | 19 (100.0) | 197 (97.0) | 80 (95.2) | 0.732 |
| Pustular psoriasis, n (%) | 0 (0.0) | 0 (0.0) | 1 (1.2) | 0.337 |
| Erythrodermic psoriasis, n (%) | 0 (0.0) | 1 (0.5) | 0 (0.0) | 1.000 |
| Palmoplantar psoriasis, n (%) | 0 (0.0) | 3 (1.5) | 1 (1.2) | 1.000 |
| Nail psoriasis, n (%) | 0 (0.0) | 1 (0.5) | 2 (2.4) | 0.345 |
| Onset of PsO, years, mean (SD) | 25.3 (13.6) | 28.6 (13.5) | 29.8 (14.7) | 0.423 |
| Disease duration of PsO, years, mean (SD) | 16.46 (11.6) | 14.1 (9.8) | 17.7 (12.3) | 0.033 |
| Nail lesions, n (%) | 8 (42.1) | 63 (31.0) | 33 (39.3) | 0.301 |
| PASI, mean (SD) | 2.9 (1.9) | 5.0 (4.6) | 5.2 (5.1) | 0.178 |
| BSA, mean (SD) | 3.4 (3.4) | 6.5 (8.4) | 7.1 (11.3) | 0.310 |
| Tendons with ultrasound changes | ||||
| Triceps tendon, n (%) | 47 (23.2) | 19 (22.6) | 1.000 | |
| Biceps tendon, n (%) | 22 (10.8) | 10 (11.9) | 0.956 | |
| Subacromial deltoid, n (%) | 19 (9.4) | 12 (14.3) | 0.310 | |
| Common extensor tendon, n (%) | 20 (9.9) | 20 (23.8) | 0.003 | |
| Flexor digitorum tendon, n (%) | 39 (19.2) | 9 (10.7) | 0.113 | |
| Quadriceps tendon, n (%) | 86 (42.4) | 50 (59.5) | 0.012 | |
| Patellar tendon, n (%) | 31 (15.3) | 26 (31.0) | 0.004 | |
| Achilles tendon, n (%) | 100 (49.3) | 43 (51.2) | 0.867 | |
| Plantar fascia, n (%) | 34 (16.8) | 18 (21.4) | 0.442 | |
| Posterior tibial tendon, n (%) | 3 (1.9) | 3 (3.6) | 0.363 | |
| Ultrasound changes | ||||
| Enthesitis, n (%) | 69 (34.0) | 33 (39.3) | 0.473 | |
| Synovitis, n (%) | 151 (74.9) | 60 (71.4) | 0.712 | |
| Bursitis, n (%) | 24 (11.8) | 9 (10.7) | 0.949 | |
| Bursal effusion, n (%) | 14 (6.9) | 8 (9.5) | 0.605 | |
| Tendinitis, n (%) | 1 (0.5) | 0 (0.0) | 1.000 | |
| Tenosynovitis, n (%) | 18 (8.9) | 4 (4.8) | 0.330 | |
| Tendon sheath effusion, n (%) | 52 (25.6) | 17 (20.2) | 0.413 | |
| Joint effusion, n (%) | 97 (47.8) | 46 (54.7) | 0.344 | |
| Bone erosion, n (%) | 9 (4.4) | 3 (3.6) | 1.000 | |
| Osteophyte, n (%) | 43 (21.2) | 25 (29.8) | 0.161 | |
| Enthesophyte, n (%) | 120 (59.1) | 61 (72.6) | 0.043 | |
| Nail dystrophy, n (%) | 67 (33.0) | 31 (36.9) | 0.619 | |
| PD signal of sacroiliac joint, n (%) | 8 (3.9) | 4 (4.8) | 0.751 | |
| Musculoskeletal symptoms | ||||
| Arthralgia, n (%) | 19 (100.0) | 84 (100.0) | ||
| Arthralgia VAS, mean (SD) | 3.7 (1.9) | 3.3 (2.1) | 0.403 | |
| Duration of arthralgia, years, mean (SD) | 2.0 (2.4) | 3.7 (6.4) | 0.048 | |
| Symmetrical pain, n (%) | 3 (15.8) | 40 (47.6) | 0.019 | |
| Intermittent pain, n (%) | 18 (94.7) | 74 (88.1) | 0.684 | |
| Triggers of arthralgia | ||||
| Activity‐related arthralgia, n (%) | 10 (52.6) | 50 (59.5) | 0.796 | |
| Rest‐related arthralgia, n (%) | 5 (26.3) | 20 (23.8) | 0.775 | |
| Weather‐related arthralgia, n (%) | 3 (15.8) | 9 (10.7) | 0.691 | |
| Most severe symptoms present in the morning, n (%) | 4 (21.1) | 12 (14.3) | 0.488 | |
| Improvement of symptoms during the day, n (%) | 4 (21.1) | 12 (14.3) | 0.488 | |
| Morning stiffness, n (%) | 3 (15.8) | 16 (19.1) | 1.000 | |
| Morning stiffness VAS, mean (SD) | 3.3 (1.5) | 4.1 (1.6) | 0.491 | |
| Duration of morning stiffness, min, mean (SD) | 18.3 (10.4) | 11.1 (8.7) | 0.351 | |
Abbreviations: AU, arthralgia and ultrasound abnormalities; BMI, body mass index; BSA, body surface area; IA, isolated arthralgia; IU, isolated ultrasound abnormalities; PASI, psoriasis area and severity index; VAS, visual analog scale.
Given that patients with ultrasound abnormalities constituted the majority of the subclinical PsA cohort and shared ultrasound‐detected musculoskeletal inflammation, comparative analyses were primarily focused on the AU and IU groups. Compared with the Group IU, patients in the Group AU were older (49.3 ± 13.7 vs. 43.5 ± 13.2 years, p = 0.001) and had a longer duration of psoriasis (17.7 ± 12.3 vs. 14.1 ± 9.8 years, p = 0.020). Furthermore, patients in the Group AU demonstrated significantly greater tendon involvement, including the common extensor tendon (p = 0.004), quadriceps tendon (p = 0.012), and patellar tendon (p = 0.004), along with higher enthesophyte prevalence (p = 0.043). In addition to imaging abnormalities, patients in the Group AU exhibited characteristic arthralgia features. The mean arthralgia VAS score was 3.3 ± 2.1, and the mean duration of arthralgia was longer than that in Group IA (3.7 ± 6.4 vs. 2.0 ± 2.4 years, p = 0.048). Nearly half of the patients reported symmetrical joint pain (47.6%), while arthralgia was predominantly intermittent and activity‐related. Morning stiffness was reported in a minority of patients and was generally of short duration. Patients with isolated arthralgia (Group IA) accounted for 6.2% (n = 19) of the cohort and exhibited a similar arthralgia pattern, although with a shorter mean duration (2.0 ± 2.4 years).
3.3. Rest‐Related Arthralgia Indicates Severe Inflammatory Characteristics
Based on emerging evidence linking arthralgia patterns to early PsA development [6, 12], we stratified patients by arthralgia characteristics: activity‐related (n = 60) versus rest‐related (n = 25) (Table 3). We observed that patients with rest‐related arthralgia had a significantly longer duration of arthralgia (p = 0.041), a higher prevalence of morning stiffness (p = 0.031), and were more likely to exhibit the following patterns: most severe symptoms present in the morning (p = 0.001) and improvement of symptoms during the day (p = 0.001).
TABLE 3.
Comparison of activity‐related and rest‐related arthralgia in subclinical PsA.
| Variable | Activity‐related arthralgia (n = 60) | Rest‐related arthralgia (n = 25) | p |
|---|---|---|---|
| Duration of arthralgia, year, mean (SD) | 2.1 (3.7) | 3.5 (4.5) | 0.041 |
| Arthralgia VAS, mean (SD) | 3.1 (2.0) | 3.6 (1.7) | 0.181 |
| Symmetrical arthralgia, n (%) | 25 (42) | 14 (56) | 0.227 |
| Intermittent arthralgia, n (%) | 6 (10) | 1 (4) | 0.668 |
| Weather‐related arthralgia, n (%) | 1 (2) | 6 (24) | 0.002 |
| Most severe symptoms present in the morning, n (%) | 3 (5) | 12 (48) | 0.001 |
| Improvement of symptoms during the day, n (%) | 2 (3) | 12 (48) | 0.001 |
| Morning stiffness, n (%) | 9 (15) | 9 (36) | 0.031 |
| Morning stiffness VAS, mean (SD) | 3.7 (1.9) | 4.2 (1.2) | 0.516 |
| Duration of morning stiffness, min, mean (SD) | 9.4 (5.7) | 15.2 (11.5) | 0.201 |
| Peripheral joint involvement | |||
| Shoulder joint, n (%) | 6 (10) | 4 (16) | 0.471 |
| Elbow joint, n (%) | 3 (5) | 2 (8) | 0.628 |
| Wrist joint, n (%) | 6 (10) | 3 (12) | 0.719 |
| MCP, n (%) | 3 (5) | 1 (4) | 0.999 |
| DIP (finger), n (%) | 5 (8) | 3 (12) | 0.688 |
| PIP (finger), n (%) | 5 (8) | 3 (12) | 0.688 |
| Hip joint, n (%) | 0 (0) | 2 (8) | 0.084 |
| Knee joint, n (%) | 28 (47) | 10 (40) | 0.573 |
| Ankle joint, n (%) | 6 (10) | 5 (20) | 0.287 |
| MTP, n (%) | 5 (8) | 0 (0) | 0.315 |
| PIP (toe), n (%) | 0 (0) | 0 (0) | 0.999 |
| DIP (toe), n (%) | 3 (5) | 3 (12) | 0.353 |
| Achilles tendon, n (%) | 6 (10) | 0 (0) | 0.173 |
| Axial joint involvement | |||
| Cervical vertebrae, n (%) | 3 (5) | 1 (4) | 0.999 |
| Thoracic vertebrae, n (%) | 1 (2) | 1 (4) | 0.504 |
| Lumbar vertebrae, n (%) | 8 (13) | 4 (16) | 0.742 |
| Sacral vertebrae, n (%) | 0 (0) | 0 (0) | 0.999 |
| Coccygeal vertebrae, n (%) | 0 (0) | 0 (0) | 0.999 |
Abbreviations: DIP distal interphalangeal joints; MCP metacarpophalangeal joints; MTP metatarsophalangeal joints; PIP, proximal interphalangeal joints; VAS, visual analog scale.
4. Discussion
This study profiles multifaceted characteristics of patients fulfilling the EULAR definition of subclinical PsA in a large cohort, revealing near‐universal subclinical inflammation by ultrasound, significantly surpassing the number of patient‐reported arthralgia. Importantly, phenotypic stratification identified patients with concurrent arthralgia and ultrasound abnormalities (Group AU) as a distinct subgroup, which exhibit longer psoriasis duration and more severe tendon/entheseal involvement. Activity‐related arthralgia was the predominant type of arthralgia among patients with subclinical PsA, whereas rest‐related arthralgia was associated with longer arthralgia duration, higher morning stiffness incidence, and more prominent inflammatory characteristics.
Imaging abnormalities are commonly recognized predictors of subsequent PsA progression [18, 19]. Notably, our study reveals that 93.8% of patients fulfilling the EULAR definition of subclinical PsA demonstrate ultrasound abnormalities, two‐thirds of whom present isolated ultrasound abnormalities. This high prevalence should be interpreted within the context of a selected population already meeting the EULAR definition of subclinical PsA, rather than as an estimate for the general psoriasis population. Within this selected population, the predominance of ultrasound abnormalities highlights the importance of imaging in identifying subclinical musculoskeletal inflammation that may not be clinically apparent.
The EULAR task force highlights that patients with both arthralgia and ultrasound abnormalities present a particularly high short‐term risk [6]. In line with this concept, our cross‐sectional analysis showed that patients with both arthralgia and ultrasound abnormalities exhibited several clinical and imaging features that have previously been linked to PsA development. Compared with patients with isolated ultrasound abnormalities, patients with both arthralgia and ultrasound abnormalities had more frequent ultrasound‐detected abnormalities at the extensor, quadriceps, and patellar tendons, and previous studies have suggested that entheseal involvement, particularly at the quadriceps and patellar tendons, may be associated with subsequent PsA development and has been incorporated into predictive ultrasound models [14, 15]. In addition, patients with both arthralgia and ultrasound abnormalities had a significantly longer duration of psoriasis than patients with isolated ultrasound abnormalities, which is also a well‐recognized risk factor for PsA development [19, 20]. These findings suggest that patients with both arthralgia and ultrasound abnormalities may present a distinct clinical and imaging phenotype characterized by features aligned with previously reported risk factors for PsA progression.
According to the 2023 EULAR framework, patients with concomitant arthralgia and imaging abnormalities, isolated imaging abnormalities, and isolated arthralgia are all included within the spectrum of subclinical PsA. Importantly, this concept represents a heterogeneous continuum rather than a uniform disease stage [21, 22, 23, 24, 25]. In this context, isolated arthralgia can be interpreted as a potential early manifestation within the PsA continuum. Evidence from longitudinal and prospective studies indicates that the development of PsA is often preceded by a prolonged period of nonspecific musculoskeletal symptoms in patients with psoriasis [12], and psoriatic arthralgia has been recognized as a key feature of this prodromal phase [26, 27, 28]. From a dermatology practice perspective, recognizing isolated arthralgia is clinically relevant, as joint symptoms may precede clinically apparent PsA and prompt early referral, closer monitoring, or further imaging assessment.
Noteworthy, contrasting with typical rest‐related arthralgia in established PsA patients [2] this study found activity‐related arthralgia was significantly more common than rest‐related arthralgia in subclinical PsA. We observed that rest‐related arthralgia was associated with longer arthralgia duration, higher morning stiffness incidence, and a more inflammatory profile than activity‐related arthralgia. These findings raise the possibility that different patterns of arthralgia may reflect distinct clinical phenotypes within the spectrum of subclinical PsA. Given that prolonged pain duration, morning stiffness and rest‐related arthralgia are commonly recognized features of inflammatory joint disease, these findings suggest that patients with rest‐related arthralgia may have a higher inflammatory burden [29, 30, 31]. In contrast, activity‐related arthralgia may represent a less inflammatory presentation within the spectrum of subclinical PsA. Similar to our findings, previous studies have suggested that subclinical PsA may initially present with non‐specific musculoskeletal symptoms, with some patients subsequently developing more inflammatory manifestations [12]. However, given the cross‐sectional design of the present study, a temporal relationship between different arthralgia patterns cannot be established. Therefore, activity‐related arthralgia may warrant clinical attention as a potential early or less inflammatory manifestation within the subclinical PsA spectrum, although longitudinal studies are needed to clarify its role in disease progression.
This cross‐sectional study has several limitations. First, the data originate solely from an Asian population, while racial differences should be further examined. Second, although we clinically assessed both peripheral and axial arthralgia, our imaging evaluation was limited to peripheral joints via ultrasound. Future studies should include imaging of axial joints to establish a comprehensive imaging profile of subclinical PsA. Third, longitudinal studies are essential to determine progression risk factors to clinical PsA, with particular attention to correlating arthralgia type and locations with imaging abnormalities. Finally, the concept of “subclinical PsA” remains evolving and has not yet been fully standardized. Therefore, classifications based on existing frameworks, including the EULAR definition, have inherent limitations in distinguishing subclinical PsA from other causes of musculoskeletal symptoms [6]. Although a structured multidisciplinary diagnostic approach was applied to improve specificity, residual confounding from alternative causes of arthralgia cannot be entirely excluded, particularly in patients with overlapping or early‐stage musculoskeletal conditions. Thus, our findings should be interpreted within the current EULAR framework of subclinical PsA and the broader risk continuum of psoriasis‐to‐PsA transition.
In conclusion, this study provides a comprehensive characterization of patients fulfilling the EULAR definition of subclinical PsA, highlighting near‐universal ultrasound‐detected inflammation. Consequently, it underscores the critical role of ultrasound examination in early screening. Notably, the predominance of activity‐related arthralgia suggests a potential early disease phase, whereas rest‐related arthralgia is associated with a more inflammatory profile. These findings may contribute to the early identification of patients at increased risk of PsA and support further research into preventive strategies.
Funding
This work was supported by the Department of Science and Technology of Sichuan Province under the Sichuan Provincial Science and Technology Program (Grant No. 2024NSFSC1628).
Ethics Statement
The study was approved by the ethics committee of West China Hospital, Sichuan University (approval number 2024 (1493)) and performed in accordance with the Helsinki declaration of 1964 and its later amendments. Each participating patient signed an informed consent form. No identifying information of participants was included in the manuscript.
Conflicts of Interest
The authors declare no conflicts of interest.
Contributor Information
Wei Yan, Email: yanweihappyhappy@163.com.
Lingyan Zhang, Email: zhangling-yan1982@163.com.
Wei Li, Email: liweihx_hxyy@scu.edu.cn.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1. Griffiths C. E. M., Armstrong A. W., Gudjonsson J. E., and Barker J. N. W. N., “Psoriasis,” Lancet 397 (2021): 1301–1315. [DOI] [PubMed] [Google Scholar]
- 2. Ritchlin C. T., Colbert R. A., and Gladman D. D., “Psoriatic Arthritis,” New England Journal of Medicine 376 (2017): 957–970. [DOI] [PubMed] [Google Scholar]
- 3. Ogdie A. and Scher J. U., “Prevention of Psoriatic Arthritis: The Next Frontier,” Lancet Rheumatology 5 (2023): e170. [DOI] [PubMed] [Google Scholar]
- 4. McGonagle D. G., Zabotti A., Watad A., et al., “Intercepting Psoriatic Arthritis in Patients With Psoriasis: Buy One Get One Free?,” Annals of the Rheumatic Diseases 81 (2022): 7–10. [DOI] [PubMed] [Google Scholar]
- 5. De Marco G., Zabotti A., Baraliakos X., et al., “Characterisation of Prodromal and Very Early Psoriatic Arthritis: A Systematic Literature Review Informing a EULAR Taskforce,” RMD Open 9 (2023): e003143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Zabotti A., De Marco G., Gossec L., et al., “EULAR Points to Consider for the Definition of Clinical and Ultrasound Features Suspicious for Progression From Psoriasis to Psoriatic Arthritis,” Annals of the Rheumatic Diseases 82 (2023): 1162–1170. [DOI] [PubMed] [Google Scholar]
- 7. Singla S., Putman M., Liew J., and Gordon K., “Association Between Biological Immunotherapy for Psoriasis and Time to Incident Inflammatory Arthritis: A Retrospective Cohort Study,” Lancet Rheumatology 5 (2023): e200–e207. [DOI] [PubMed] [Google Scholar]
- 8. Gisondi P., Bellinato F., Targher G., Idolazzi L., and Girolomoni G., “Biological Disease‐Modifying Antirheumatic Drugs May Mitigate the Risk of Psoriatic Arthritis in Patients With Chronic Plaque Psoriasis,” Annals of the Rheumatic Diseases 81 (2022): 68–73. [DOI] [PubMed] [Google Scholar]
- 9. Liu Z., Chen J., Zhou K., et al., “Effectiveness of Biologics on Synovitis and Enthesitis Using Musculoskeletal Ultrasound Assessment in Subclinical Psoriatic Arthritis: A 12‐Week Observational Real‐World Study,” Journal of the American Academy of Dermatology 94 (2025): 41–47. [DOI] [PubMed] [Google Scholar]
- 10. Mehta S., Xiong G., Metko D., Abdi P., McMullen E., and Alhusayen R., “Subclinical Synovitis Among Patients With Psoriasis Without Musculoskeletal Involvement: A Systematic Review and Meta‐Analysis,” JAMA Dermatology 161 (2025): 966–969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Elnady B., Shaarawy N. K., Dawoud N. M., et al., “Subclinical Synovitis and Enthesitis in Psoriasis Patients and Controls by Ultrasonography in Saudi Arabia; Incidence of Psoriatic Arthritis During Two Years,” Clinical Rheumatology 38 (2019): 1627–1635. [DOI] [PubMed] [Google Scholar]
- 12. Zabotti A., Fagni F., Gossec L., et al., “Risk of Developing Psoriatic Arthritis in Psoriasis Cohorts With Arthralgia: Exploring the Subclinical Psoriatic Arthritis Stage,” RMD Open 10 (2024): e004314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. American College of Radiology (ACR); Society for Pediatric Radiology (SPR); Society of Radiologists in Ultrasound (SRU) , “AIUM Practice Guideline for the Performance of a Musculoskeletal Ultrasound Examination,” Journal of Ultrasound in Medicine 31 (2012): 1473–1488. [DOI] [PubMed] [Google Scholar]
- 14. Wang Y., Liu N., Zhang L., et al., “Ultrasound‐Based Detection of Inflammatory Changes for Early Diagnosis and Risk Model Construction of Psoriatic Arthritis,” Rheumatology (Oxford) 63 (2024): 2776–2780. [DOI] [PubMed] [Google Scholar]
- 15. Wang Y., Zhang L., Yang M., et al., “Development of a Predictive Model for Screening Patients With Psoriasis at Increased Risk of Psoriatic Arthritis,” Dermatology and Therapy 12 (2022): 419–433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Bruyn G. A., Naredo E., Damjanov N., et al., “An OMERACT Reliability Exercise of Inflammatory and Structural Abnormalities in Patients With Knee Osteoarthritis Using Ultrasound Assessment,” Annals of the Rheumatic Diseases 75 (2016): 842–846. [DOI] [PubMed] [Google Scholar]
- 17. Terslev L., Naredo E., Iagnocco A., et al., “Defining Enthesitis in Spondyloarthritis by Ultrasound: Results of a Delphi Process and of a Reliability Reading Exercise,” Arthritis Care & Research 66 (2014): 741–748. [DOI] [PubMed] [Google Scholar]
- 18. Naredo E., Möller I., de Miguel E., et al., “High Prevalence of Ultrasonographic Synovitis and Enthesopathy in Patients With Psoriasis Without Psoriatic Arthritis: A Prospective Case‐Control Study,” Rheumatology (Oxford) 50 (2011): 1838–1848. [DOI] [PubMed] [Google Scholar]
- 19. Zabotti A., Bandinelli F., Batticciotto A., et al., “Musculoskeletal Ultrasonography for Psoriatic Arthritis and Psoriasis Patients: A Systematic Literature Review,” Rheumatology (Oxford) 56 (2017): 1518–1532. [DOI] [PubMed] [Google Scholar]
- 20. Garcia‐Salinas R., Magri S., Mareco J., et al., “Arthralgia With Risk of Progression to Psoriatic Arthritis: Role of Clinical Assessments and Ultrasound as Prognostic Factors,” Rheumatology (Oxford) 64 (2025): 2550–2556. [DOI] [PubMed] [Google Scholar]
- 21. Ciccia F., Gandolfo S., Caporali R., and Scher J. U., “Understanding the Spectrum From Preclinical Psoriatic Arthritis to Early Diagnosis of the Disease,” Lancet Rheumatology 7 (2025): e208–e211. [DOI] [PubMed] [Google Scholar]
- 22. Errichetti E. and Zabotti A., “Biologics in Prevention of Psoriasis to Psoriatic Arthritis Transition: The Need of Prospective Analyses and Stratification According to Time‐Related Risk Factors,” Dermatology and Therapy 14 (2024): 1–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Aronovich A., Novikov I., and Pavlovsky L., “Do Biologic Treatments for Psoriasis Lower the Risk of Psoriatic Arthritis? A Systematic Review,” American Journal of Clinical Dermatology 24 (2023): 865–873. [DOI] [PubMed] [Google Scholar]
- 24. Rosenthal Y. S., Schwartz N., Sagy I., and Pavlovsky L., “Incidence of Psoriatic Arthritis Among Patients Receiving Biologic Treatments for Psoriasis: A Nested Case‐Control Study,” Arthritis and Rheumatology 74 (2022): 237–243. [DOI] [PubMed] [Google Scholar]
- 25. Acosta Felquer M. L., LoGiudice L., Galimberti M. L., Rosa J., Mazzuoccolo L., and Soriano E. R., “Treating the Skin With Biologics in Patients With Psoriasis Decreases the Incidence of Psoriatic Arthritis,” Annals of the Rheumatic Diseases 81 (2022): 74–79. [DOI] [PubMed] [Google Scholar]
- 26. Eder L., Polachek A., Rosen C. F., Chandran V., Cook R., and Gladman D. D., “The Development of Psoriatic Arthritis in Patients With Psoriasis Is Preceded by a Period of Nonspecific Musculoskeletal Symptoms: A Prospective Cohort Study,” Arthritis and Rheumatology 69 (2017): 622–629. [DOI] [PubMed] [Google Scholar]
- 27. Simon D., Tascilar K., Kleyer A., et al., “Association of Structural Entheseal Lesions With an Increased Risk of Progression From Psoriasis to Psoriatic Arthritis,” Arthritis and Rheumatology 74 (2022): 253–262. [DOI] [PubMed] [Google Scholar]
- 28. Faustini F., Simon D., Oliveira I., et al., “Subclinical Joint Inflammation in Patients With Psoriasis Without Concomitant Psoriatic Arthritis: A Cross‐Sectional and Longitudinal Analysis,” Annals of the Rheumatic Diseases 75 (2016): 2068–2074. [DOI] [PubMed] [Google Scholar]
- 29. Zabotti A., McGonagle D. G., Giovannini I., et al., “Transition Phase Towards Psoriatic Arthritis: Clinical and Ultrasonographic Characterisation of Psoriatic Arthralgia,” RMD Open 5 (2019): e001067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Ribeiro A. L. and Eder L., “From Psoriasis to Psoriatic Arthritis: Ultrasound Insights Connecting Psoriasis With Subclinical Musculoskeletal Inflammation and the Path to Psoriatic Arthritis,” Current Rheumatology Reports 26 (2024): 235–247. [DOI] [PubMed] [Google Scholar]
- 31. Zuliani F., Zabotti A., Errichetti E., et al., “Ultrasonographic Detection of Subclinical Enthesitis and Synovitis: A Possible Stratification of Psoriatic Patients Without Clinical Musculoskeletal Involvement,” Clinical and Experimental Rheumatology 37 (2019): 593–599. [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.