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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 810-815

Assessment of enthesitis in the early spondyloarthropathy by ultrasonography combined with power Doppler


1 Department of Rheumatology, Physical Medicine and Rehabilitation, Faculty of Medicine Zagazig University, Zagazig, Egypt
2 Department of Rheumatology, Physical Medicine and Rehabilitation, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
3 Department of Radiodiagnosis, Physical Medicine and Rehabilitation, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission19-Dec-2017
Date of Acceptance03-Mar-2018
Date of Web Publication31-Dec-2018

Correspondence Address:
Samah S Yusef
Birket El Sabae, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_874_17

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  Abstract 


Objective
The aims were to assess prevalence of enthesitis among different subtypes of early spondyloarthropathy (SpA) and to evaluate specificity of entheseal involvement in such patients using ultrasonography and power Doppler.
Background
Enthesitis is one of the characteristic etiopathogenic manifestations of spondyloarthritis; however, in clinical practice, its presence often goes unnoticed. Ultrasound (US) can visualize most of the relevant enthesitis-associated pathologies such as bone erosions, calcification, bursitis, tendon structure, and thickness.
Patients and methods
A total of 80 patients with SpA with early disease duration and 20 controls (10 with mechanical low back pain and 10 with rheumatoid arthritis) of matched age and sex underwent ultrasonographic evaluation of entheses and were scored according to Madrid Sonographic Enthesitis Index. Patients were distributed as 36 patients with ankylosing spondylitis, 18 patients with reactive arthritis, and 26 patients with psoriatic arthritis.
Results
On clinical examination of entheses, 22.5% of the examined sites were abnormal as compared with US, which achieved higher sensitivity of 62.5%. Mean US score was significantly higher in patients with SpAs (22.6 ± 6.34) as compared with controls (P < 0.001). Elemental US lesions (calcification, Doppler, bone erosion, and bursae) also achieved significant difference between both groups (P < 0.003, 0.001, 0.003, 0.001, respectively). Disease duration but not human leukocyte antigen-B27 positivity had a significant correlation with the US score.
Conclusion
The entheses US score may be useful for improving the diagnostic accuracy of early SpA, which is difficult to diagnose.

Keywords: ankylosing spondylitis, enthesitis, power Doppler, spondyloarthropathy, ultrasonography


How to cite this article:
Elhewala AI, Soliman SG, Alsheraki DR, Mousa WA, Yusef SS. Assessment of enthesitis in the early spondyloarthropathy by ultrasonography combined with power Doppler. Menoufia Med J 2018;31:810-5

How to cite this URL:
Elhewala AI, Soliman SG, Alsheraki DR, Mousa WA, Yusef SS. Assessment of enthesitis in the early spondyloarthropathy by ultrasonography combined with power Doppler. Menoufia Med J [serial online] 2018 [cited 2019 Mar 21];31:810-5. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/810/248767




  Introduction Top


Spondyloarthropathies (SpA) are a group of inflammatory arthritis conditions that consist of ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), and arthritis/spondylitis associated with inflammatory bowel diseases. The association with human leukocyte antigen (HLA)-B27, peripheral joint involvement predominantly of the lower extremities, sacroiliitis, spondylitis, enthesitis, dactylitis, uveitis, enteric mucosal lesions, and skin lesions are the shared manifestations of the diseases[1].

Enthesitis is the term used to describe inflammation at tendon, ligament, or joint capsule insertions to bone. It thus applies to disease associated with the spondyloarthritides. The term ‘enthesopathy’, however, has a wider meaning and designates all pathological abnormalities of insertions including inflammatory changes, metabolic, and degenerative problems[2]. It has been demonstrated that entheseal inflammation is responsible for many of the symptoms, and explains the multitude of locations of pain in patients with SpA. For example, at an axial level, it is responsible for inflammatory back pain, sacroiliac pain, chest pain, and stiffness, and at a peripheral level, it is responsible for plantar fasciitis and Achilles tendinitis and is even implicated in the onychopathy of PsA[3].

PsA occurs most commonly at an older age and with a longer duration of psoriasis. The most prevalent rheumatic manifestations are arthralgia, enthesitis, axial arthritis, sacroiliitis, and peripheral arthritis[4].

Ultrasound (US) has already proven higher sensitivity than clinical examination for detecting enthesitis and has revealed a high frequency of abnormalities in patients with subclinical enthesitis[5]. One major advantage of US is the ability to use power Doppler. Increased blood flow about diseased entheses indicates inflammation or neovascularity. However, it is important to realize that technical parameters need careful adjustment. Moreover, there are pitfalls to avoid, such as placing excessive probe pressure, which may collapse the underlying blood vessels[6].

This work aimed to evaluate sensitivity and specificity of enthesitis in early SpA using US combined with power Doppler.


  Patients and Methods Top


This case–control study was conducted on patients recruited from the Outpatient Clinic of Physical Medicine, Rheumatology and Rehabilitation Department, Menoufia University Hospital (May 2013–June 2015). Local approval was obtained from the ethical committee of our hospital. All individuals volunteered to participate after providing them with explanation of the procedure and the aim of the study and gave their informed consents.

A total of 80 patients with SpA diagnosed according to Assessment of Spondyloarthritis International Society criteria with early disease duration were selected[7]. The inclusion criteria included age less than 45 years and symptom duration between 3 and 24 months. Exclusion criteria were patients older than 45 years, disease duration more than 24 months, and patients with associated low back disorders such as congenital spine deformity, fracture, and malignancy. They were distributed as 36 patients with AS, 18 patients with ReA, and 26 patients with PsA. They were classified as having one of the previous subtypes as follows: (a) AS if they fulfilled modified New York criteria[8], (b) PsA if they fulfilled the classification criteria for psoriatic arthritis[9], (c) ReA if they had arthritis and recent evidence of infection.

A total of 20 controls were selected to match for both sex and age of the patients. They were distributed as 10 patients with mechanical low back pain (LBP) and 10 patients with rheumatoid arthritis (RA).

All patients with SpA underwent complete general and musculoskeletal examination with special emphasis on entheses clinical scoring according to Maastricht Ankylosing Spondylitis Enthesitis Score. Activity, and functional evaluations were measured according to Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index score, and for AS subtype, Stanford Health Assessment Questionnaire and visual analog scale. Full laboratory and radiological studies were performed for all patients, including erythrocyte sedimentation rate, C-reactive protein, antinuclear antibodies, rheumatoid factor, HLA-B27, radiography, and MRI for the pelvis and lumbosacral spine.

Patients and controls were examined by conventional gray-scale US and power Doppler using Hitachi EU 7000 (Hitachi High-Technologies, Hitachi-city, Ibaraki, Japan) machine, with a 5–13 MHz linear transducer. Examination was done by an experienced radiologist, who was blinded, that is, he was not aware if the patients were affected by rheumatologic disease. All participants were asked not to communicate with the US examiner.

Six bilateral entheseal sites were examined in each patient including proximal planter fascia, distal Achilles tendon, distal and proximal patellar ligament, distal quadriceps, and brachial triceps tendon. They were scored according to Madrid Sonography Enthesitis Index (MASEI) as follows: calcification (0–3), Doppler (0 or 3), tendon structure (0 or 1), tendon thickness (0 or 1), bursa (0 or 1), and erosion (0 or 3)[5].

Calcifications were scored as 0 if absent, or 1 if a small calcification or ossification with an irregularity of enthesis cortical bone profile was seen. Calcifications were given a score of 2 if there was clear presence of enthesophytes, or if medium-sized calcifications were seen. They were classified as 3 if large calcifications were present. Bursitis was defined as a well-circumscribed, localized anechoic or hypoechoic area at the site of an anatomical bursa, which was compressible by the transducer. Bone erosion was defined as a cortical breakage with a step-down bone contour defect of in-longitudinal and transverse axes. Fascia and tendon thickness were measured at the point of maximal thickness on the bony insertion. The following criteria were used for abnormal structure thickness: quadriceps tendon thickness greater than 6.1 mm, proximal and distal patellar tendon greater than 4 mm, Achilles tendon greater than 5.29 mm, plantar aponeurosis greater than 4.4 mm, and triceps insertion greater than 4.3 mm. Structure was defined as pathological if loss of fibrillar pattern, hypoechoic aspect, or fusiform thickening of the enthesis occurred[10]. Each tendon was scanned in both the longitudinal and transverse planes.

Knee entheses were examined with the patient in the supine position and the knee flexed to 70°. The Achilles tendon and plantar aponeurosis were examined with the patient lying prone and the feet hanging over the edge of the table at 90° of flexion. The triceps insertion was examined with the arm flexed to 90°. The total possible score on both sides (12 entheses) was 136[5].

Statistical analysis

Data were statistically analyzed using an IBM personal computer with statistical package for the social sciences (SPSS) version 22 (SPSS Inc., Chicago, Illinois, USA). Quantitative variables were presented as mean, SD, and range. Qualitative variables, of parametric, were presented as number and percentage. Comparisons were performed using the χ2-test for qualitative variables; Student's t-test was used to compare two independent groups regarding quantitative variables. Pearson's correlation coefficients (r) were calculated for detection of parametric correlations, whereas Kruskal–Wallis correlation coefficients (r) were calculated for detection of nonparametric correlations between variables in one group. Receiver operating characteristic (ROC) curves were used to calculate different levels of sensitivity and specificity at every cut-off point. P values of less than 0.05 were considered significant and values less than 0.01 were considered highly significant.


  Results Top


This study included 80 patients with early SpA, with a mean age 31.9 ± 7.99 years and disease duration of 13.5 ± 5.73 months. Patients with SpA were further distributed as 36 patients with AS, 18 patients with ReA, and 26 patients with PsA. Moreover, 20 controls (10 with mechanical LBP and 10 with RA) of matched age and sex were included [Table 1].
Table 1: Demographic data of studied group

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On clinical examination of entheseal sites, inflammation in the form of tenderness and/or swelling was present in a total of 22.5% of examined sites as compared with US, which achieved higher sensitivity of 62.5% [Figure 1] and [Figure 2].
Figure 1: Number and percentage distribution of enthesitis in patients with spondyloarthritis (n = 80).

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Figure 2: Receiver operating characteristics curve for detection of the best cut-off point of ultrasound. The area under the curve was 0.743. There was highly significant difference in the area under the curve (P < 0.001).

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The mean erythrocyte sedimentation rate in SpA group was 32.1 ± 9.6 and C-reactive protein was 10.4 ± 4.8. Antinuclear antibodies and rheumatoid factor were negative in all patients with SpA. HLA-B27 positivity was found in 70%. The mean Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index were 3.61 ± 1.47 and 3.42 ± 1.24, respectively. Mean visual analog scale and Health Assessment Questionnaire were 3.97 ± 2.01 and 0.60 ± 0.83, respectively. Most patients in this study were not in active disease state [Table 2].
Table 2: Clinical, laboratory, radiological, and MRI findings in patients with spondyloarthropathy

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The US MASEI score in patients with SpA was as follows (mean ± SD): 22.4 ± 6.82 in AS, 24.6 ± 5.96 in ReA, and 24.6 ± 5.96 in PsA. There were no statistical differences in entheses scores between different diagnostic subtypes of patients with SpA in either total score or elemental lesions [Table 3].
Table 3: Differences between spondyloarthritis subtypes in total and elemental ultrasound Madrid Sonography Enthesitis Index score

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There was a highly significant difference in the value of total US score in patients with SpA and the non-SpA control group (mean ± SD: 22.6 ± 6.34 and 15.5 ± 4.76, respectively; P < 0.001). Moreover, elemental US lesions (calcification, Doppler, bone erosion, and bursae) achieved significant difference between both groups (P = 0.003, 0.001, 0.003, and 0.001, respectively), being higher in patients with SpA [Table 4].
Table 4: Ultrasound score in spondyloarthritis and nonspondyloarthritis groups

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US validity was determined by ROC curves showing that a value of 21 was established as the best cut-off point to differentiate between cases and controls. At this cut-off point, the MASEI achieved a sensitivity of 60%, specificity of 85%, positive predictive value of 94, and negative predictive value of 35. The area under the curve was 0.743 [Table 5].
Table 5: Diagnostic validity of Madrid Sonography Enthesitis Index in spondyloarthropathy

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  Discussion Top


In this study, clinically detected enthesitis was much lower than enthesitis detected by US, explained by the fact, that many enthesitis are asymptomatic. This low sensitivity of clinical examination is in agreement with Balint et al.[11] and Ezzat et al.[12].

Our study showed that there were no statistically significant differences in US entheses scores between different diagnostic subtypes of patients with SpA in either total MASEI score or elemental lesions. This comes in agreement with de Miguel et al.[13], who found no statistical differences in the MASEI score among diagnostic SpA subtypes or presentation patterns (axial, peripheral, or mixed) for the global MASEI score or for any elemental lesions. Similar findings were also reported by D'Agostino et al.[14].

In this study, the total value of the US MASEI score revealed highly significant statistical difference between patients with SpA and non-SpA control group. Elemental US lesions in the form of calcification, Doppler, erosions, and bursae also achieved significant difference between both groups, being higher in patients with SpA. D'Agostino et al.[15] demonstrated that the involvement of lower extremity entheses in patients with SpA is common and more frequent than in controls with mechanical LBP or RA. They also reported that the frequency of entheseal vascularity was greater in patients with SpA compared with controls, and that RA erosive entheseal changes start close to bursal spaces, only in entheses close to synovial spaces[15]. Similarly Ezzat et al.[12] found that enthesis US score was significantly higher in patients with SpA as compared with controls; tendon thickness, enthesophytes, and bursitis were significantly higher in patients with SpA than controls. Moreover, de Miguel et al.[13] reported that the mean MASEI score was significantly higher in patients with SpA as compared with controls, and the mean calcification, Doppler, and erosion achieved statistical significance.

Hamdy et al.[16] included 50 patients with psoriasis and 20 healthy controls and found a highly significant difference between groups in terms of the total MASEI score, tendon structure, bursa, erosion, calcification, and power Doppler signal scores (higher in psoriasis group).

In this work to explore the validity of the MASEI in SpA, ROC curves were determined. As a result, a value of 21 was established as the best cut-off point to differentiate between cases and controls. The MASEI achieved a sensitivity of 60% and specificity of 85% at this cut-off point.

A common problem in clinical rheumatologic practice is to differentiate primary (SpA-related) enthesitis from mechanical/dysmetabolic enthesopathy and/or enthesopathy in the course of other inflammatory (RA, connective tissue diseases) or degenerative (osteoarthritis) diseases. Previous studies clearly showed differences of US enthesis findings between patients with SpA, RA, and mechanical back pain[15].

The validity of the score depends on the 12 entheses, because a smaller number or unilateral exploration reduces the area under the curve of the score. It was the number of elemental lesions rather than the presence or absence of the lesions that discriminated between SpA and controls. The value of the index is not that it diagnoses patients with a sensitivity of 60% and a specificity of 85%, rather its greatest importance is in developing an US score that can be used in early SpA, which is difficult to diagnose, with significant delay in diagnosis, and the ability of the score to classify patients and controls correctly. This was also confirmed by de Miguel et al.[17] who applied the MASEI on patients with early SpA and showed that the proposed index had a similar utility in the preradiographic stage of this disease to that in established disease.

De Miguel et al.[5] showed that ROC curves established an US score of 18 as the best cut-off point for differentiation between SpA cases and healthy controls. The sensitivity and specificity were 83.3 and 82.8%, respectively. This higher sensitivity and specificity (as compared with our results) may be related to different control groups. In our study, an inflammatory control with RA was included. In addition, their patients with SpA were diagnosed according to ESSG criteria with significant delay in diagnosis and did not represent an early group[5].

The current study conceded with another study by de Miguel et al.[13], where a cut-off point of greater than 20 points achieved a specificity of 83.3% and a sensitivity of 53.1%.

The choice for the cut-off point depends on whether the test objective is for a very sensitive test to detect mostly diseased individuals or for a very specific test to rule out the disease in mostly healthy individuals. An ideal test would have 100% sensitivity and specificity. However, this is rarely possible, and as sensitivity increases, specificity often decreases.

A limitation in this study is that the study population was not matched for BMI, a factor that might influence the enthesis score. Subsequent studies matched for BMI might be more informative.

It should be noted that US alone is not sufficient to make the diagnosis of SpA. However, when used in a clinical setting with more signs or symptoms, the US results might be decisive.


  Conclusion Top


A systematic US study of peripheral entheses could be useful in the diagnostic process of patients with early SpA, which is often confusing.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, et al. The Assessment of Spondyloarthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70:25–31.  Back to cited text no. 1
    
2.
Mata Arnaiz MC, de Miguel Mendietab E. Usefulness of ultrasonography in the assessment of peripheral enthesis in spondyloarthritis. Reumatol Clin 2014; 10:113–119.  Back to cited text no. 2
    
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5.
De Miguel E, Cobo T, Muñoz-Fernández S, Naredo E, Usón J, Acebes JC, et al. Validity of enthesis ultrasound assessment in spondyloarthropathy. Ann Rheum Dis 2009; 68:169–174.  Back to cited text no. 5
    
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Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of Spondyloarthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009; 68:777–783.  Back to cited text no. 7
    
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Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27:361–368.  Back to cited text no. 8
    
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11.
Balint PV, Kane D, Wilson H, McInnes IB, Sturrock RD. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 2002; 61:905–910.  Back to cited text no. 11
    
12.
Ezzat Y, Gaber W, Abd El-Rahman SF, Ezzat M, El Sayed M. Ultrasonographic evaluation of lower limb enthesis in patients with early spondyloarthropathie. Egypt Rheumatol 2013; 35:29–35.  Back to cited text no. 12
    
13.
De Miguel E, Munoz-Fernadez S, Castillo C, Cobo-Ibanez T, Martin-Mola E. Diagnostic accuracy of enthesisultrasound in the diagnosis of earlyspondyloarthritis. Ann Rheum Dis 2011; 70:434–439.  Back to cited text no. 13
    
14.
D'Agostino MA, Aegerter P, Bechara K, Salliot C, Judet O, Chimenti MS, et al. How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography. Ann Rheum Dis2011; 70:1433–1440.  Back to cited text no. 14
    
15.
D'Agostino MA, Said-Nahal R, Hacquard-Bouder C, Brasseur JL, Dougados M, Brebaan M. Assessment of peripheral enthesitis in the spondyloarthropathies by ultrasonography combined with power Doppler. Arthritis Rheum 2003; 48:523–533.  Back to cited text no. 15
    
16.
Hamdy M, Omar G, Elshereef R, Ellaban AS, Amin M. Early detection of spondyloarthropathy inpatients with psoriasis by using the ultrasonography and magnetic resonance. Eur J Rheumatol 2015; 1:10–15.  Back to cited text no. 16
    
17.
De Miguel E, Cobo T, Muñoz Fernández S, Steinerova M, Martín-Mola E. Value of ultrasound in the study of early spondyloarthropathies. Ann Rheum Dis 2007; 66:394–398.  Back to cited text no. 17
    


    Figures

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