Introduction
Psoriasis is a quite common chronic, inflammatory immune-mediated skin disease affecting about 2% of the population [
1]. Psoriatic arthritis (PsA) is a member of the spondylarthropathy family and may be defined as an inflammatory arthropathy associated with psoriasis and usually negative for rheumatoid factor [
2]. Wright and Moll described the classification criteria in 1973 [
3]. The prevalence of psoriasis varies widely among populations in Norway and Russia; 5–10% of the population is affected while 0–0.3% of the West Africans or native Americans are affected [
4]. To our knowledge, no prevalence data in Arab countries are available. One study in Eastern Saudi Arabia showed that 5.3% of the new cases in a tertiary dermatology clinic had psoriasis, but no prevalence data are available [
5].
Among psoriasis patients, 7–42% may develop PsA [
6,
7]. The prevalence of PsA ranged between 0.056 and 0.28% in the USA in a large population study [
8].
Once the diagnosis of PsA has been established, treatment should be started to alleviate signs and symptoms, prevent future joint damage, and maximize quality of life (QOL) to improve the outcomes [
9]. Development of diagnostic and monitoring tools help to establish diagnosis for early disease control. Cutaneous manifestations of psoriasis mostly precede the onset of arthritis by an average of 10 years; however, in up to 14–21% of patients, arthritis develops prior to the occurrence of skin psoriasis [
10‐
13]. Several studies in psoriasis patients without clinical arthritis showed that a percentage had subclinical enthesopathy and synovitis. MRI is considered one of the sensitive radiological modalities. It has shown to be more sensitive than clinical examination in detecting synovitis and enthesitis, but unfortunately, MRI is not widely used in clinical practice due to its high cost and limited availability [
14]. With musculoskeletal ultrasound (MSUS), synovitis and enthesitis can also be detected, differentiating between inflammatory and non-inflammatory arthritis [
10]. Emad et al. revealed subclinical synovitis, enthesitis, and bone marrow edema changes in 48 psoriasis patients without psoriatic arthritis manifestations using MRI. In almost all (90/96), knees, bone marrow edema, enthesitis, and/or synovitis was found [
14].
The current multicenter study aimed to assess the presence of subclinical synovitis and enthesitis in psoriasis patients free from clinical arthritis or enthesitis, in comparison with healthy controls, followed by prospective follow-up of psoriasis patients to assess PsA incidence and study possible relation to baseline findings.
Discussion
Recently, MSUS has shown a great impact in the diagnostic era in musculoskeletal diseases, especially for detecting synovitis by using GSUS and PDUS [
22,
23], in the assessment of enthesitis [
24,
25] and tenosynovitis [
26] in different inflammatory arthritis. Several studies demonstrated MSUS abnormalities in joints of psoriatic arthritis patients as well as in patients with psoriasis who did not report pain or swelling at the time of clinical assessment [
10,
13,
27‐
29] with a conclusion that MSUS can proficiently identify subclinical inflamed areas in patients without clinical evidence on examination.
Preclinical phase of PsA can exist in psoriasis prior to the diagnosis of the disease, which is characterized by non-specific musculoskeletal symptoms, including fatigue and stiffness [
30], which may explain subclinical MSUS findings in our study.
In this study, we aimed to detect subclinical synovitis and enthesitis with MSUS in psoriasis patient free from rheumatic manifestation in comparison with healthy controls, with longitudinal prospective follow-up over 2 years to study PsA incidence and the relation between baseline findings and PsA development.
Subclinical synovitis and enthesitis were detected in 39.5% of patients and only in 10% of the control group. Freeston et al. had similar findings, in which MSUS showed power Doppler signals in 34.7% of the patients [
13]. The current study showed that PDUS, GSUS, subclinical synovitis, and enthesitis were of significantly higher incidence in psoriasis patients than in controls. In a cohort comparing psoriasis patients with and without musculoskeletal signs, the prevalence of MSUS synovitis in asymptomatic joints was 13% of joints, while controls showed synovitis in 1.3%, with a statistical significant difference [
10].
Scalp and nail psoriasis had been documented in different studies as risk factors for PsA [
31,
32]. However, in our study, there was no significant difference between different clinical varieties of psoriasis and GSUS, PDUS, or enthesopathy changes, which is in agreement with other studies [
10,
28].
Subclinical synovitis and enthesitis had been reported in various studies by different radiological modalities such as MSUS, MRI, and scintigraphy, without any clinical evidence of pain or swelling [
10‐
12,
14,
28,
33,
34]. Naredo et al. found a significantly higher prevalence of subclinical enthesitis and synovitis in psoriasis patients than in controls by MSUS [
8].
Some studies investigated CRP in psoriasis. It was remarkably higher in psoriasis patients than in healthy matched controls [
35]. These results were in agreement with ours. CRP levels are elevated in patients with psoriasis with or without PsA [
36]. Furthermore, our results showed remarkably higher CRP levels in patients with MSUS manifestations than those without (
P < 0.001). Higher baseline CRP levels in relation to positive MSUS findings and PsA development could be a sign of disease progression. Moreover, some studies showed that CRP levels were higher in PsA patients compared with psoriasis patients without arthritis [
37].
One of our patients had erosions with synovitis on the second and fifth right MCP, who developed frank PSA later during follow-up. PsA may develop erosions early, although other observational cohorts stated that PSA patients usually have sustained progressive radiographic damage over time [
38,
39]. In addition, erosions documented at the first visit were associated with mortality risk in PsA [
40]. Silent erosive joints were documented as not uncommon in Italian patients, who go on to develop a clinically manifested PsA [
41]. Ultrasound-detected features of inflammation in the form of grayscale ultrasound and power Doppler activity are associated with the abnormal blood flow of active inflammation in patients with PSA [
42].
Up to our knowledge, this is the first Saudi prospective study conducted on psoriasis patients with and without abnormal MSUS, to assess the incidence of PsA among them, and to study the relation of this incidence to the baseline MSUS findings. In our study, the annual incidence of PsA among Saudi psoriasis patients was 4.3%; our incidence is slightly higher than in Eder et al. study [
31], in which the annual incidence was 2.7–3.2% over 8-year follow-up stud. This difference could be related to different ethnic groups. We have noticed that newly diagnosed PsA patients had higher baseline CRP levels with increased prevalence of baseline MSUS subclinical enthesitis, synovitis with higher GSUS, PDUS scores rather than psoriasis patients without PsA (Table
6).
When using clinical assessment several studies estimated the prevalence of PsA in patients with plaque psoriasis. In a systematic review, the point prevalence of PsA among psoriasis patients ranged from 7 to 26% [
43]. Mease et al. sought to estimate PsA prevalence in patients with plaque psoriasis in 34 dermatology centers in 7 European and North American countries. Of 949 patients evaluated, 285 (30%) had PsA (95% confidence interval 27–34) based on rheumatologists’ assessment [
44]. Villani et al. looked for the prevalence of newly diagnosed PsA in patients with psoriasis at the time they seek medical care. In a review study, seven epidemiological studies and five studies on PsA screening questionnaires were found. The prevalence of undiagnosed PsA was 15.5% (varying from 4,2% - 33.6%) when all studies were considered and 10.1% when only epidemiological studies were considered [
45]. In a recent Brazilian multicenter study a total of 524 patients with PsA followed in dermatology settings, were evaluated by a rheumatologist. A diagnosis of PsA was documented in 175 patients (33%), of whom 49% were newly identified by the rheumatologist [
46].
When using MRI for diagnosis of PsA, the figures are higher. In a cross-sectional and longitudinal analysis, Faustini et al. showed that in 55 psoriasis patients free from musculoskeletal manifestations using MRI of the hands, 47% had at least one inflammatory lesion [
47]. Emad et al. detected subclinical synovitis, enthesitis, and/or bone marrow edema changes in 48 psoriasis patients without psoriatic arthritis manifestations using MRI even in 90 out of 96 knees [
14].
Our findings are in agreement with another longitudinal study [
48], in which high enthesitis, GSUS, and PDUS synovitis scores can predict PSA development in psoriasis patients.
Psoriatic arthritis (PsA) increases the disease burden associated with psoriasis by further diminishing quality of life (QOL), increasing health care costs and cardiovascular risk, and potentially causing progressive joint damage [
49]. The presence of PsA influences psoriasis treatment by increasing overall disease complexity and, within the framework of current guidelines and recommendations, requiring the use of conventional disease-modifying anti-rheumatic drugs or TNFα inhibitors in order to prevent progressive joint damage. Despite its important impact, PsA is still under-diagnosed in dermatology practice. Dermatologists are well positioned to recognize and treat PsA, given that it characteristically presents, on average, 10 years subsequent to the appearance of skin symptoms. Regular screening of psoriasis patients for early evident joint symptoms should be incorporated into daily dermatologic practice [
49,
50]. Early detection and treatment of PsA are of great importance for the patients as these are usually associated with rapid response, regression of radiographic damage, and improved QOL [
9,
10,
48,
49,
51]. A collaboration between dermatologists and rheumatologists is greatly needed to establish earlier PsA diagnoses and adequate multidisciplinary management [
46,
47,
50].
It is still controversial whether we should treat subclinical synovitis with DMARDs like methotrexate or leflunomide or biologicals. In general, close follow-up is recommended until clinical synovitis is seen. When persistent active subclinical synovitis is seen, one may consider to start these treatments depending on the severity of the complaints. By early treatment, it may be possible to prevent structural damage. Treatment of patients with early PsA who had higher CRP values shows good efficacy [
52].
The strength of our study is that it is a case-controlled study and conducted in a hardly studied ethnic group of Saudi citizens. Almost all relevant joints and entheses were investigated and the follow-up was almost complete. But this study also has some limitations. NSAIDs intake over the counter was not registered, while it can be considered one of the PsA treatments, which might have influenced our results. The fact that it was conducted in one ethnic group only means that the findings cannot be generalized. Although it is one of the largest series of patients published, the sample size is not sufficient to make the results of the incidence generalizable to other settings.
The objective nature of the diagnostic tool used in the study (MSUS) and the plausibility of its findings all support the validity of the conclusions based on this study. Still, longer duration longitudinal studies with larger sample size are needed to confirm our results regarding the incidence of new cases.
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