Value of ultrasound examination of the Leeds Enthesitis Index in assessment of disease activity in psoriatic arthritis

Methods: A total of 75 consecutive PsA patients diagnosed according to Classifi cation Criteria for Psoriatic Arthritis (CASPAR criteria) participated in the study. The LEI score was used to assess the enthesitis. All PsA patients underwent US assessment by the same sonographer who was blinded to the fi ndings of the clinical examination. Grey scale US imaging was used to assess the longitudinal and transverse planes of the 6 entheseal points of the LEI.

was designed for measuring enthesitis in PsA patients [11].
However, the specifi city of clinical enthesitis count is limited since the site of most entheseal points are near to joints and can be mistaken for tender points of fi bromyalgia and fi nding tenderness in these sites raise the possibility of false positive results [12].
Ultrasound (US) is a non-invasive tool with highly sensitivity to assess the presence of enthesitis [13]. Many US studies reported the high prevalence of subclinical enthesitis in patients with and without PsA [14][15][16].
However, these studies are limited by the incomplete assessment of PsA features by US with disease activity measures routinely used in RA [17]. This study aimed to determine the added value of the US assessment of enthesitis according to LEI over the clinical assessment in determination of PsA activity.

Subjects
A total of 75 consecutive PsA patients diagnosed according to Classifi cation Criteria for Psoriatic Arthritis (CASPAR criteria) [9], participated in the study. Patients were collected from the outpatient clinic of Rheumatology, in Saudi Arabia, during routine visit to the clinic. The protocol for this study was approved by the Institutional Research Board & the Ethical Committee.
Exclusion criteria for cases were rheumatoid arthritis, crystal induced arthritis, osteoarthritis, other seronegative spondyloarhrpathies and other active infl ammatory skin conditions. All patients were instructed to stop taking NSAIDs for at least 24 hours prior to assessments, to avoid the immediate masking effect of these medications. Prior to inclusion, the aim and the study procedures were explained to all participants who signed consent. This study was approved by the local ethics committee.

Clinical assessment
Patients were clinically assessed through full history taking in addition to both general and local examinations as well as review of their medical records. The LEI score was used to assess the enthesitis. Enthesitis was defi ned as tenderness at the enthesis site by applying pressure of around 4 kg/cm 2 (required to blanch the tip of fi ngernail of the examiner). LEI consists of assessment of tenderness at 6 sites: insertion of bilateral Achilles tendon, medial femoral condyles, and lateral humeral epicondyles. Tenderness at each site is measured on a dichotomous basis: 0 (not tender) and 1 (tender) [11].
PASDAS is a composite disease activity measurement for the psoriatic arthritis and it is based on patient (PtGA) and physician (PhGA) global VAS scores, tender (SJC66) and swollen (SJC68) joint counts, dactylitis and enthesitis, Physical Component Summary (PCS) scale of the Short Form 36 (SF-36), and CRP level [18]. In the current study, Minimal Disease Activity (MDA) on the PASDAS was a score of <1.9 [19].

US assessment
All PsA patients underwent US assessment by the same The scoring of all US fi ndings were either absent (score 0) or present (score 1) [20].
The US fi ndings were combined into 2 scores as follows: (1) Infl ammation score involves the sum of 4 items of vascularization, edema, bursitis and entheseal thickening (score range 0-4) and (2)

Ultrasound examination shows:
Marked oedema of the subcutaneous tissue.
Peritendinous oedema along the course of the planter fl exor tendon.
Thickening and oedema within and around insertion of the.
C. Healthy left tendoachilis tendon insertion, for comparison, yet mild erosions at its insertion noted.

Statistical analysis
Data were an alyzed using the SPSS v.20.0. Variables with continuous data expressed as mean ±SD while variables with categorical data expressed as number and percent. Variable with continuous data compared using the independent sample Student's t test while Variable with categorical data compared using the chi square test. Correlations were performed using the correlation co-effi cient test. ROC curve analysis was used to assess the ability of the total US infl ammation score in discrimination of patients with active PsA. Signifi cance was set at p value of <0.05.

Ultrasound examination shows:
A. Enthesophyte and Perientheseal soft tissue oedema.
B. Bursitis at insertion of tendoachilis tedon into calcaneum.  On the other hand the total damage score as well as the damage score at the 6-LEI points showed insignifi cant difference between the two groups.

Frequency of entheses abnormalities in clinical versus US examination in the 6-LEI points
A signifi cant correlation was identifi ed between PASDAS with the LEI score (r=0.280, p=0.015) ( Figure 2) and with the total US infl ammation score (r=0.332, p=0.004) (Figure 3).
However, no signifi cant correlation was found between the PASDAS and the total US damage score (r=0.007, p=0.951).

ROC curve analysis
The analysis of ROC curve revealed that the total US infl ammation score >10 at the 6-LEI points can differentiate patients with active from those with MDA PsA (AUC=0.717) ( Figure 4). As shown in Table 3     many composite measures of disease activity in PsA were in use; however, PASDAS has a better ability to identify patients with MDA from those with higher disease activity [18].
Enthesitis is common feature in PsA [21]. In the present study, the 6-LEI points were examined clinically and by US in the same day. Clinical examination had revealed 170/450 entheses tender locations, meanwhile 306/450 entheses abnormalities were detected by US examination. These fi ndings indicate that 136 locations had subclinical enthesitis.
Previous studies revealed signifi cant discrepancy of infl ammation between US and clinical fi ndings in rheumatic diseases [22,23] which is in keeping with our results.. Subclinical Sonographic enthesitis prevalence in PsA patients and in patients with psoriasis without arthropathy was high in many previous studies [14][15][16]. De Filippis et al. [24], found entheseal abnormalities in 25% of the psoriasis patients detected by US and not by clinical examination. Also in agreement with the fi ndings of the present study, Acquacalda et al., found US enthesitis in 25.9% of the psoriasis patients without musculoskeletal symptoms.
In the present study, the most common site of entheseal involvement was the Achillis tendon. Similar fi nding was reported by Galluzzo et al., [25], who found that 71% of the PsA patients had US features of tendon involvement with the Achilles tendon is the most frequent sites of enthesopathic involvement in PsA (11 tendons in 6 patients), producing heel pain, and diffi culty walking. Similarly, D'Agostino et al., [26], found that the most frequent site of enthesopathy in PsA is the Achilles tendon.
Perrotta et al., [27], reported that PDUS detected structural and infl ammatory abnormalities of enthesis in early PsA patients. However, in the current study, in agreement with results of study of Ahmed et al., [28], no PDUS entheseal signals were detected in PsA patients.
In the current study, PASDAS is signifi cantly correlated with clinical LEI score in PsA patients and strongly correlated with the total US infl ammation score at the 6-LEI points (p=0.015 and p=0.004 respectively). Ahmed et al. [28], reported a direct signifi cant correlation between PASDAS score and the clinical LEI score in active PsA patients. Similar fi ndings were reported by the study of Girolomoni and Gisondi [29], who reported that patients with severe clinical psoriasis outcome had a signifi cantly higher US score (measured by Glasgow Ultrasound Enthesitis Scoring System) and is correlated with higher disease activity. Moreover, Aydin et al., [30], reported that psoriatic patients (with or without arthritis) had shown higher infl ammation-related enthesopathy scores and the PsA patients had higher US enthesopathy scores than psoriatic patients with arthritis.
However, Ash et al., [31], found no link between the severity of psoriasis and enthesitis was evident. The discrepancy could be explained by the fact that Ash et al. enrolled psoriatic patients with nail changes but with no evident arthritis.
Although the mechanism of enthesitis in PsA still not fully understood, the roles of environmental, mechanical stress, immunologic and genetic factors were proposed. Gisondi et al., [14], proposed the role of increased mechanical stress on the entheses of the lower limbs as a cause of enthesitis particularly in obesity which is also associated with increased levels of pro-infl ammatory cytokines and systemic infl ammation.
McGonagle et al., [32], also suggested that enthesitis arises at sites of compression and high shear forces, resulting from an interaction between micro-trauma, mechanical stress, and variably in mechanisms of tissue repair leading to infl ammation.
In the present study, ROC curve analysis showed that the total US infl ammation score >10 at the 6-LEI points can decimate patients with active from those with MDA PsA patients (AUC=0.717) with good accuracy. Future studies can assess the validity of this score in the detection of the PsA patients with active disease at this cut-off point or can generate more accurate cut-off point in studies with lager PsA population.

Conclusion
US examination of 6-LEI points is an accurate method to assess entheseal abnormalities and is signifi cantly correlated to disease activity in PsA patients.