Abstract
Background:
The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.
Methods:
Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts.
Results:
In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0–18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59–3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01–1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01–1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use.
Conclusions:
Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.
Keywords: Enthesitis, Psoriatic arthritis, Registry
Introduction
Psoriatic arthritis (PsA) is a chronic inflammatory disease that develops in up to 30% of patients with psoriasis. It is characterized by diverse clinical features including peripheral and axial arthritis, enthesitis, dactylitis, and nail dystrophy, leading to impaired function and reduced quality of life.[1] Enthesitis, the inflammation at the site of insertion of tendon and ligament into bone, is a hallmark manifestation of PsA and current knowledge supports the idea that enthesitis may be the primary event in PsA.[2,3] The importance of enthesitis in PsA is acknowledged by the inclusion of this clinical manifestation in the Classification Criteria for Psoriatic Arthritis (CASPAR).[4] Furthermore, enthesitis is approved by the Outcome Measures in Rheumatology (OMERACT) to be assessed as one of the core domains in all longitudinal studies and clinical trials on PsA.[5] Several physical examination measures of enthesitis, including the Leeds enthesitis index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC) index, and Maastricht ankylosing spondylitis enthesitis score (MASES), have been developed and proven reliable in its assessment.[6]
The prevalence of enthesitis in PsA has been reported to range from 19.5% to 65.7% in the US and Europe.[7,8] In an analysis from China, Yang et al[9] observed that enthesitis was present in 26.8% of PsA patients. The clinical features of enthesitis in patients with PsA have been reported in some Western countries.[7,8,10] However, data in China are very limited, hindering the comprehensive understanding of PsA in this region. The Chinese Registry of Psoriatic Arthritis (CREPAR) is a multi-center prospective registry based on the Chinese Rheumatism Data Center (CRDC). Data on enthesitis from the CREPAR have not been reported previously; thus, the present study aimed to determine the demographics, characteristics, and disease associations of enthesitis in Chinese patients with PsA.
Methods
Ethical approval
Ethical approval was obtained from the Peking Union Medical College Hospital Ethics Board (No. S-K1811). All patients provided informed consent before data collection.
Patients
The CREPAR, founded in December 2018, is a registry based on the CRDC, which was a clinical research and translational medicine platform under the aegis of the National Health Commission of the People's Republic of China and the national "12th 5-year Plan Period" of the 863 program. Patients in the CREPAR were recruited from 162 hospitals across 31 provinces in China, and their data were collected on each visit. All included centers were tertiary hospitals and researchers were experienced rheumatologists in the fields of PsA. Training programs were used to guide all investigators for clinical assessment and data input, and all centers used the same protocol-directed methods to provide a uniform evaluation and record data. Until June 2021, a total of 1074 patients with PsA according to the CASPAR registered in the CREPAR.[4] Patients who refused musculoskeletal examination were excluded.
Data collection
This was a cross-sectional study. Medical assessment and physical examination were performed by the study physicians in each participating center. Data were collected at the registry enrollment visit, which included demographic information (age, gender, body mass index [BMI], family history, onset age of psoriasis and PsA, and disease duration of PsA), clinical characteristics (clinical subtype including peripheral arthritis, axial involvement [based on the presence of inflammatory back pain according to the Assessment of SpondyloArthritis international Society 2009 criteria or diagnosis confirmed by rheumatologists],[11] dactylitis, enthesitis, nail disease, uveitis, and inflammatory bowel diseases [IBD]), laboratory tests including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and human leukocyte antigen (HLA)-B27, disease activity measures (swollen joint count [SJC], tender joint count [TJC], Psoriasis Area and Severity Index [PASI], Disease Activity in Psoriatic Arthritis [DAPSA], and Disease Activity Score 28-CRP [DAS28-CRP]), and treatment profiles (current use of non-steroidal anti-inflammatory drugs [NSAIDs], conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biological DMARDs [bDMARDs], and Janus kinase inhibitors [JAKi]).
Enthesitis was defined as the presence of at least one tender entheseal site. The standardized assessment method for each entheseal site was to use the thumb or index finger and apply about 4 kg/cm2 of pressure (enough to blanch the finger about a fifth of the way from the tip of the fingernail); participants were then asked if they felt any pain to ascertain the presence/absence of enthesitis.[6] The index for evaluating enthesis used in this study was the MASES, which primarily evaluated pain at axial sites, as well as the SPARCC and LEI indices, which evaluated at peripheral sites.[12–14] Axial sites include the spine, chest wall, and pelvis entheses.[15] The MASES assesses tenderness at the following enthesitis sites: bilateral first and seventh costochondral joints, posterior superior iliac spines, anterior superior iliac spines, iliac crests, insertion of the Achilles tendon into the posterior surface of the calcaneus, and the fifth lumbar spinous process. The SPARCC enthesitis index was evaluated at 16 sites: bilateral supraspinatus insertion, lateral and medial epicondyles, greater trochanter, quadriceps insertion, inferior patella, tibial tubercle, Achilles tendon insertion, and plantar fascia insertion (the inferior patella and tibial tuberosity were considered one site because of their anatomical proximity). The LEI consists of six sites: bilateral lateral epicondyles, medial femoral condyles, and Achilles tendon insertion sites. Achilles tendon insertion was included in all enthesitis indices.
Statistical analysis
Analyses were based on observed data with no imputation of missing data. Descriptive statistics were performed with frequencies and percentages for categorical variables and means and standard deviation (SD) for quantitative variables. Means and percentages of enthesitis at individual sites were calculated among the patients with any assessment of entheses. Comparisons of descriptive data between groups were performed using the Student's t-test or the Mann–Whitney U test. Categorical data were compared using the chi-squared or Fisher's exact test. A P-value of <0.05 was considered statistically significant. Multivariable logistic regression analysis was used to assess the demographic and clinical factors associated with enthesitis, where the dependent variable was presence or absence of enthesitis. Variables with P <0.1 in the univariate analysis were included in the multivariable logistic regression analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated. Before the construction of a multivariable model, collinearity diagnostics were determined using the variance inflation factor, and variables were accordingly removed from the final model (variance inflation factor >10). We also compared our results with four previous large cohort studies. SPSS (version 24.0; IBM Corp., Armonk, NY, USA) was used for all statistical analyses.
Results
Demographics, clinical characteristics, disease activity assessment, and treatment in patients with and without enthesitis
A total of 1074 patients had at least one visit registered in the CREPAR during the years 2018–2021, of which 1031 (96.0%) patients had a record of entheseal assessment and enthesitis was positive in 308 (28.7%) patients. As shown in Table 1, 47.4% of the 308 patients were female, and the mean age was 43.1 ± 12.8 years. Furthermore, the mean BMI was 24.4 ± 5.6 kg/m2. A total of 102 patients (33.1%) reported a family history of psoriasis or PsA. Besides, the onset ages of psoriasis and PsA were 30.0 ± 13.2 years and 36.9 ± 13.1 years, respectively. PsA courses having a duration of >5 years were reported in 134 (43.5%) patients. Compared with those without enthesitis, patients with enthesitis were younger, exhibited an earlier onset both in psoriasis and inflammatory arthritis, and reported a higher proportion with a duration of PsA over 5 years (all P <0.05).
Table 1.
Demographics, clinical characteristics, disease activity assessment, and treatment in PsA patients with and without enthesitis.
| Variables | Patients with enthesitis | Patients without enthesitis | t/z/ χ 2-value | P-value |
|---|---|---|---|---|
| (N = 308) | (N = 723) | |||
| Demographics | ||||
| Age (years) | 43.1 ± 12.8 | 45.3 ± 12.9 | 2.507* | 0.012 |
| Female | 146 (47.4) | 327 (45.2) | 0.411† | 0.521 |
| BMI (kg/m2) | 24.4 ± 5.6 | 24.5 ± 6.1 | 0.166* | 0.868 |
| Family history | 102 (33.1) | 196 (27.1) | 3.793† | 0.051 |
| Onset age of PsA (years) | 36.9 ± 13.1 | 40.0 ± 13.0 | 3.550* | <0.001 |
| Onset age of psoriasis (years) | 30.0 ± 13.2 | 32.4 ± 13.4 | 2.486* | 0.013 |
| Course of PsA (>5 years) | 134 (43.5) | 265 (36.7) | 4.277† | 0.039 |
| Clinical characteristics | ||||
| Dactylitis | 135 (43.8) | 323 (44.7) | 0.062† | 0.803 |
| Nail disease | 197 (64.0) | 449 (62.1) | 0.319† | 0.572 |
| Uveitis | 19 (7.0) | 29 (4.3) | 2.842† | 0.092 |
| IBD | 12 (4.4) | 31 (4.6) | 0.021† | 0.886 |
| Peripheral arthritis | 281 (91.2) | 638 (88.2) | 1.995† | 0.158 |
| Axial involvement | 169 (55.0) | 253 (35.0) | 35.841† | <0.001 |
| HLA-B27 positive | 73 (23.9) | 138 (19.4) | 2.727† | 0.099 |
| ESR (mm/1 h) | 20.0 (10.0, 42.0) | 20.0 (9.0, 39.0) | -1.167‡ | 0.243 |
| CRP (mg/L) | 9.1 (3.2, 23.7) | 7.0 (2.5, 18.7) | -2.550‡ | 0.011 |
| Disease activity assessment | ||||
| PASI | 1.6 (0.0, 7.8) | 0.3 (0.0, 3.7) | -3.645‡ | <0.001 |
| SJC66 | 4.0 (1.0, 9.0) | 2.0 (0.0, 7.0) | -3.199‡ | 0.001 |
| TJC68 | 4.0 (1.0, 10.0) | 2.0 (0.0, 7.0) | -5.272‡ | <0.001 |
| DAS28-CRP | 3.7 (2.6, 4.7) | 3.2 (2.4, 4.1) | -4.275‡ | <0.001 |
| DAPSA | 21.8 (13.4, 36.3) | 15.8 (8.7, 26.2) | -5.761‡ | <0.001 |
| Treatment | ||||
| NSAIDs | 142 (46.1) | 266 (36.8) | 7.833† | 0.005 |
| Glucocorticoid | 33 (10.7) | 66 (9.1) | 0.626† | 0.429 |
| csDMARDs | 211 (77.6) | 481 (80.0) | 0.689† | 0.407 |
| MTX | 170 (62.5) | 399 (66.4) | 1.248† | 0.264 |
| LEF | 45 (16.5) | 116 (19.3) | 0.946† | 0.331 |
| SASP | 33 (12.1) | 47 (7.8) | 4.183† | 0.041 |
| bDMARDs | 104 (38.2) | 207 (34.4) | 1.175† | 0.278 |
| TNFi | 85 (31.3) | 164 (27.3) | 1.442† | 0.230 |
| IL-17i | 19 (7.0) | 43 (7.2) | 0.008† | 0.928 |
| JAK inhibitors | 18 (6.6) | 32 (5.3) | 0.580† | 0.447 |
Data are presented as n (%), mean ± standard deviation, or median (Q1, Q3);*t value; †χ2 value; ‡z value. bDMARDs: Biological DMARDs; BMI: Body mass index; CRP: C reactive protein; csDMARDs: Conventional synthetic disease-modifying antirheumatic drugs; DAPSA: Disease Activity in Psoriatic Arthritis; DAS28-CRP: Disease Activity Score 28-CRP; ESR: Erythrocyte sedimentation rate; HLA-B27: Human leukocyte antigen; IBD: Inflammatory bowel diseases; IL-17i: Interleukin-17 inhibitors; JAK: Janus kinase inhibitors; MTX: Methotrexate; NSAIDs: Non-steroidal antiinflammatory drugs; PASI: Psoriasis Area and Severity Index; PsA: Psoriatic arthritis; SASP: Sulfasalazine; SJC: Swollen joint count; TNFi: Tumor necrosis factor inhibitors; TJC: Tender joint count.
In terms of clinical characteristics and disease activity, patients with enthesitis had a higher percentage of axial involvement (55.0% [169/308] vs. 35.0% [253/723], χ2= 35.841, P <0.001) and greater disease activity as reflected by greater TJC, SJC, higher CRP, PASI, DAS28-CRP, and DASPSA scores (all P <0.05) than those in the group without enthesitis. The prevalence of other PsA manifestations including peripheral arthritis, dactylitis, nail disease, uveitis, and IBD was an approximately comparable percentage in the two groups. As for laboratory results, 73 (23.9%) were HLA–B27 positive in patients with enthesitis, which was higher than that in patients without enthesitis (138, 19.4%). ESR was also higher in the group with enthesitis. However, these indicators did not reach statistical significance.
For treatment, patients with enthesitis were more likely to use NSAIDs compared to those without enthesitis (χ2=7.833, P = 0.006). The proportion of patients receiving csDMARDs, including methotrexate and leflunomide, remained insignificantly different between the two groups. However, a greater proportion of patients with enthesitis received sulfasalazine than patients without enthesitis (χ2=4.183, P = 0.041). Besides, bDMARDs usage was observed to be slightly higher in the enthesitis group than in the non-enthesitis group, of which TNF inhibitors were the most used, and the rates of IL-17 inhibitors were approximately equal in both groups. However, these differences were not statistically significant.
Enthesitis characteristics
Among the 308 patients with enthesitis at the time of enrollment, the average number of enthesitis sites was 3.3 ± 2.8 (range: 1.0–18.0). More than half of the patients (53.6%) had 1 or 2 tender entheseal sites (73 and 92 patients, respectively), 86 (27.9%) patients had 3 or 4 sites, and the rest (57, 18.5%) had between 5 and 18 tender sites.
The distribution and prevalence of enthesitis sites according to the MASES, SPARCC, and LEI indices are given in Table 2. The most common enthesitis site was iliac crest (left 88 [28.6%]; right 82 [26.6%]; bilateral 78 [25.3%]), followed by anterior superior iliac spine (left 84 [27.3%]; right 70 [22.7%]; bilateral 65 [21.1%]) and first costo-condral (left 63 [20.5%]; right 61 [19.8%]; bilateral 55 [17.9%]) when using MASES, while the top three tender entheseal sites were plantar fascia (left 40 [13.0%]; right 38 [12.3%]; bilateral 30 [9.7%]), Achilles tendon insertion (left 25 [8.1%]; right 23 [7.5%]; bilateral 17 [5.5%]), and lateral epicondyles (left 18 [5.8%]; right 18 [5.8%]; bilateral 11 [3.6%]) according to the SPARCC index. When assessed by LEI, the more common enthesitis sites were Achilles tendon and lateral epicondyles, and the medial femoral condyles (left 14 [4.5%]; right 14 [4.5%]; bilateral 7 [2.3%]) was the third. It can be seen that the prevalence of axial entheseal sites was higher than that of peripheral sites.
Table 2.
Distribution of enthesitis in patients with PsA.
| Enthesitis sites | Left | Right | Bilateral |
|---|---|---|---|
| SPARCC | |||
| Supraspinatus | 11 (3.6) | 15 (4.9) | 9 (2.9) |
| Medial epicondyle | 7 (2.3) | 5 (1.6) | 3 (1.0) |
| Lateral epicondyle | 18 (5.8) | 18 (5.8) | 11 (3.6) |
| Greater trochanter | 5 (1.6) | 7 (2.3) | 5 (1.6) |
| Superior pole of the patella | 8 (2.6) | 8 (2.6) | 4 (1.3) |
| Inferior pole of patella or tibial tuberosity | 10 (3.2) | 13 (4.2) | 10 (3.2) |
| Achilles tendon | 25 (8.1) | 23 (7.5) | 17 (5.5) |
| Plantar fascia insertion to calcaneum | 40 (13.0) | 38 (12.3) | 30 (9.7) |
| MASES | |||
| First costo-condral | 63 (20.5) | 61 (19.8) | 55 (17.9) |
| Seventh costo-condral | 44 (14.3) | 39 (12.7) | 35 (11.4) |
| Anterior superior iliac spine | 84 (27.3) | 70 (22.7) | 65 (21.1) |
| Posterior superior iliac spine | 43 (14.0) | 42 (13.6) | 35 (11.4) |
| Iliac crest | 88 (28.6) | 82 (26.6) | 78 (25.3) |
| Achilles tendon | 25 (8.1) | 23 (7.5) | 17 (5.5) |
| Lumbar fifth spinous process | – | – | 57 (18.5) |
| LEI | |||
| Lateral epicondyles | 18 (5.8) | 18 (5.8) | 11 (3.6) |
| Medial femoral condyles | 14 (4.5) | 14 (4.5) | 7 (2.3) |
| Achilles tendon | 25 (8.1) | 23 (7.5) | 17 (5.5) |
Data were presented as n (%). LEI: Leeds enthesitis index; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; PsA: Psoriatic arthritis; SPARCC: Spondyloarthritis research consortium of Canada. –: Not applicable.
Disease association
Univariate analyses indicated 14 variables with P-values<0.1. Based on the results, these variables were included in the multivariable regression models to identify factors related to enthesitis. The DAPSA was not included in the model because of its co-linearity [Supplementary Tables 1 and 2, http://links.lww.com/CM9/B495]. The following three features were found independently associated with enthesitis: axial involvement (OR: 2.21, 95% CI: 1.59–3.08, P <0.001), PASI (OR: 1.03, 95% CI: 1.01–1.04, P = 0.002), and DAS28-CRP (OR: 1.25, 95% CI: 1.01–1.55, P = 0.037) [Table 3].
Table 3.
Multivariable analysis in PsA patients with enthesitis.
| Variables | OR | 95% CI | P-value |
|---|---|---|---|
| Age | 1.00 | 0.96–1.04 | 0.967 |
| Family history | 1.15 | 0.80–1.64 | 0.452 |
| Onset age of PsA | 0.98 | 0.95–1.02 | 0.417 |
| Onset age of psoriasis | 1.00 | 0.98–1.02 | 0.814 |
| Course of PsA (>5 years) | 0.97 | 0.59–1.61 | 0.914 |
| Uveitis | 1.40 | 0.70–2.79 | 0.338 |
| Axial involvement | 2.21 | 1.59–3.08 | <0.001 |
| PASI | 1.03 | 1.01–1.04 | 0.002 |
| SJC66 | 1.00 | 0.98–1.03 | 0.796 |
| TJC68 | 1.01 | 0.98–1.04 | 0.525 |
| HLA-B27 positive | 0.97 | 0.64–1.47 | 0.881 |
| CRP | 1.00 | 0.99–1.00 | 0.173 |
| DAS28-CRP | 1.25 | 1.01–1.55 | 0.037 |
CI: Confidence interval; CRP: C reactive protein; DAS28-CRP: Disease Activity Score 28-CRP; HLA-B27: Human leukocyte antigen; OR: Odds ratio; PASI: Psoriasis Area and Severity Index; PsA: Psoriatic arthritis; SJC: Swollen joint count; TJC: Tender joint count.
Comparison of main characteristics of PsA patients with enthesitis in several large cohorts
Table 4 provides published data related to enthesitis in PsA cohorts in the US,[7] Denmark,[8] Canada,[16] and Turkey,[10] and we compared these with our data. The prevalence of enthesitis varied widely among different studies: 19.5% in the US, 65.7% in Denmark, and 28.7% in between in China. These discrepancies can be attributed to the different enthesitis indices used: MASES in Turkey, SPARCC in Denmark, Canada, and the US, and all by us. The distribution was somewhat higher in men than in women in Chinese and Canadian patients, but lower in Turkish and American patients. Besides, Chinese patients had a lower BMI (24.4 kg/m2) compared to patients in other countries (28.6–31.6 kg/m2). The disease duration of Chinese patients was 6.2 years, longer than that in Denmark and Turkey, but shorter than that in Canada and the US. Moreover, participants in China had the highest rate of positive HLA-B27 (23.9% vs. 14–18.7%). The prevalence of dactylitis ranged between 13.1% and 19%, except in China, where the prevalence was higher (43.8%). As for the involved entheseal sites, the most common site was Achilles tendon insertion in Denmark, Canada, and Turkey, whereas it was lateral epicondyles in the US; however, in China, iliac crest was more common. In terms of treatment, more than two-thirds of Chinese patients received csDMARDs (77.6%) compared to 14% of Canadian, 17.5% of Danish, and 21.7% of American patients. In addition, bDMARDs were used in over a third of patients in China (38.2%), compared to 34% of Canadian patients, and were more prevalent in 61.5% of American patients.
Table 4.
Comparison of the PsA cohorts evaluating enthesitis.
| Variables | CREPAR | Mathew et al[8] | Polachek et al[16] | Mease et al[7] | Sunar et al[10] |
|---|---|---|---|---|---|
| Country | China | Denmark | Canada | The United States | Turkey |
| Date | 2018–2021 | 2010–2020 | 2008–2014 | 2013–2018 | 2018–2019 |
| No. of patients | 1074 | 1037 | 803 | 2003 | 1130 |
| No. enthesitis positive, n (%) | 308 (28.7) | 681 (65.7) | 281 (34.9) | 391 (19.5) | 251 (22.2) |
| Age (years) | 43.1 ± 12.8 | 46.8 ± 13.1 | 49.0 ± 12.7 | 52.7 ± 12.6 | – |
| Male, n (%) | 162 (52.6) | 268 (39.4) | 151 (54) | 146 (37.0) | – |
| Disease duration (years) | 6.2 ± 7.3 (mean) | 2.34 ± 5.58 (mean) | 11.4 ± 11.3 (mean) | 7.0 ± 8.0 (mean) | 3 (median) |
| BMI (kg/m2) | 24.4 ± 5.6 | 28.6 ± 5.9 | 30.0 ± 6.4 | 31.6 ± 7.0 | 29.12 ± 4.72 |
| HLA-B27 positive, n (%) | 73 (23.9) | 56 (18.7) | 40 (14) | – | – |
| Dactylitis, No. (%) | 135 (43.8) | – | 52 (19) | 55 (14.1) | 33 (13.1) |
| Measure of enthesitis | SPARCC + MASES + LEI | SPARCC | SPARCC | SPARCC | MASES |
| No. of affected entheseal sites | 3.3 ± 2.8 | 2.5 ± 3.2 | 2.03 ± 1.6 | 3.9 ± 3.0 | – |
| Three most common tender entheseal sites | Iliac crest (28.6%), anterior superior iliac spine (27.3%), first costochondral joint (20.5%) | Achilles tendon insertion (24.4%), lateral epicondyle (22.2%), plantar fascia (17.1%) | Achilles tendon insertion (24.2%), plantar fascia (20.8%), and lateral epicondyles (17.2%) | Lateral epicondyles (23.8%), greater trochanter (20.0%), medial epicondyles (17.8%)* | Achilles insertion (39.6), lumbar fifth spinous process (36.5), first costochondral sites (27.6) |
| csDMARD, n (%) | 211 (77.6) | 119 (17.5) | 40 (14) | 85 (21.7) | – |
| bDMARD, n (%) | 104 (38.2) | 15 (2.2) | 95 (34) | 240 (61.5) | – |
bDMARDs: Biological DMARDs; BMI: Body mass index; CREPAR: Chinese Registry of Psoriatic Arthritis; csDMARDs: Conventional synthetic disease-modifying antirheumatic drugs; HLA-B27: Human leukocyte antigen; LEI: Leeds enthesitis index; MASES: Maastricht ankylosing spondylitis enthesitis score; PsA: Psoriatic arthritis; SPARCC: Spondyloarthritis Research Consortium of Canada. *The prevalence of enthesitis at each site is listed as a total percentage of the left and right affected sites in the original paper; here we take the half. –: Not available.
Discussion
In this study, we described the clinical characteristics of enthesitis in patients with PsA in China and compared our data with those from other large published cohort studies. To our knowledge, this is the largest scale and the first multi-center study that reported on data from a wide group of patients with PsA from almost all regions of China, and the population is highly representative.
Our study demonstrated that nearly one-third of patients with PsA experienced enthesitis at enrollment. Moreover, patients with enthesitis were younger and had higher rates of axial involvement as well as higher disease activity than those without enthesitis. Previous studies of PsA cohorts have reported similar observations.[10,16–18] As for treatment, current recommendation for enthesitis is to go from NSAID directly to bDMARD or targeted synthetic DMARD therapy based on the lack of evidence for the effectiveness of csDMARDs.[19] However, only 38.2% of patients with enthesitis were receiving biologic agent therapy in this study, significantly lower than csDMARDs, due to the small number of targeted drugs covered in the reimbursement plan in China. These findings indicate the big unmet need for the appropriate treatment of PsA in the country. In addition, compared to the results of other cohort studies, Chinese patients showed unique characteristics. The heterogeneity could be partly attributed to the patients' disease onset profile, differences in the enthesitis indices used, ethnic differences, and variations in the number of patients included in the studies. However, these comparative studies have cross-sectional designs, and a long-term longitudinal follow-up study that captures the effects over time is necessary.
We used the MASES, SPARCC, and LEI indices together in our study because they allowed for enthesitis assessment at both peripheral and axial sites and demonstrated reliability in PsA.[6,20,21] In our study, we observed a higher prevalence of axial sites compared with peripheral sites, suggesting that axial sites may be an important area of focus. Although some evidence suggests that enthesitis in lower sites is more common due to mechanical loading,[22] the prevalence of Achilles tendon insertion among patients with PsA in our cohort was lower than that reported in most previous studies. Considering that many of the entheseal points used in the enthesitis assessment tools are also trigger points of fibromyalgia, we do not exclude the possibility that the prevalence of enthesitis in axial sites has been overcalled due to concomitant fibromyalgia. Additionally, although the researchers involved in the present study regularly received training to optimize the accuracy of their evaluations, it is also possible that human error by individual researchers may have led to the underdiagnosis of enthesitis in Achilles tendon. However, Mease et al[7] found that the presence of clinical enthesitis was associated with worse PsA disease severity, regardless of enthesitis location. Advanced imaging techniques such as ultrasound and magnetic resonance imaging (MRI) are currently considered more sensitive than clinical examination.[23] Ultrasound can be used to visualize morphostructural and vascular abnormalities indicative of entheseal inflammation, and it has been proven to be reliable for the evaluation of peripheral entheses in PsA.[24] Conversely, MRI allows for a comprehensive assessment of enthesitis at both peripheral and axial levels. Guo et al[25] found that enthesitis was more commonly detected by whole-body MRI than by clinical assessment in patients with spondyloarthritis.
Our study found that frequent axial involvement, high PASI, and DAS28-CRP were associated with enthesitis. Similarly, previous studies have revealed that high disease activity is correlated with enthesitis.[16,26] This finding has important implications for clinical practice, emphasizing the significance underlying the identification and assessment of the manifestations. Additionally, Polachek et al[27] noted that enthesitis measured by ultrasound showed a correlation with more axial damage measured by X-rays. In spondyloarthritis (SpA) patients with enthesitis, significantly more inflammatory axial symptoms have been found than patients without enthesitis.[26] In this study, we also found that axial involvement is associated with enthesitis. One probable reason is that the inflammation in spondylitis is located at the entheses, where the ligaments attach to the vertebrae.[28] Alternatively, the higher proportion of axial involvement in our cohort may also be responsible for this result. Apart from the different genetic backgrounds,[29,30] the use of different definitions may lead to a higher percentage of axial involvement. In our study, axial involvement was defined as the presence of inflammatory back pain or physician-confirmed axial PsA (axPsA) with limited imaging information. However, the presence of inflammatory back pain does not necessarily indicate the presence of inflammation and may present as a manifestation of a mechanical back issue.[31] Currently, there is no agreed-upon classification or diagnostic criteria for axial PsA; thus, a definition is urgently needed to facilitate research and clinical recognition.
Some study limitations should be noted. First, as a multi-center study, although the training programs were used to guide all investigators for clinical assessment and data input, inconsistency between the evaluation results of different researchers is inevitable. Second, due to the incomparability of the results from different centers, our study did not provide imaging information. Third, no data were available on fibromyalgia and central sensitization, which could be significant confounders of clinical enthesitis.
In conclusion, clinical enthesitis is a common condition in Chinese patients with PsA, and patients with enthesitis had an earlier age of onset both in psoriasis and arthritis, reported a higher proportion with PsA duration over 5 years, and had a higher percentage of axial involvement. Besides, more frequent axial involvement, as well as higher PASI and DAS28-CRP, were associated with enthesitis. It is important to evaluate both peripheral and axial sites for a comprehensive assessment of enthesitis.
Funding
This study was supported by a grant from the National Basic Research Program of China (973 Program) (No. 2014CB541801).
Conflicts of interest
None.
Supplementary Material
Footnotes
How to cite this article: Yang F, Lu CF, Liu HL, Dou L, Wang YH, Li HB, Duan XW, Wu LJ, Wang YF, Zhang XY, Xu J, Su JM, Xu D, Zhao JL, Wu QJ, Li MT, Leng XM, Zeng XF. Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR). Chin Med J 2023;136:951–958. doi: 10.1097/CM9.0000000000002646
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