Keywords Achilles tendinopathy - psoriasis - psoriasis area and severity index - psoriatic
arthritis - shear-wave elastography - visual analog scale
Introduction
Psoriatic arthritis (PsA) is a form of chronic, inflammatory, seronegative, spondyloarthropathy
seen in up to 20% of patients with psoriasis.[1 ] Peripheral arthritis, spondylitis, enthesitis, and dactylitis are the common manifestations
of PsA[2 ] and achillodynia is frequently associated with it.[3 ] The psoriasis area and severity index (PASI) is an extensively used scoring system
for grading the severity of psoriasis. Patients are stratified based on the score
into mild (<7), moderate, (7–15)and severe categories (>15) and the progression of
the disease is monitored through it.[4 ]
Various imaging modalities used for assessment of PsA are plain radiography, gray
scale (GS) ultrasound, and magnetic resonance imaging (MRI). Utility of X-ray for
early diagnosis of PsA is minimal as soft tissue changes are not identified by it.[5 ]
[6 ]
[7 ] MRI is relatively expensive and time consuming. Conventional ultrasound (GS and
power Doppler [pD]) is routinely available, noninvasive, and affordable imaging modality
with high patient acceptability. Ultrasound findings suggestive of tendinopathy are
thickened tendon, hypoechoic echotexture, and increased signal on pD.[8 ]
[9 ]
[10 ] But studies have shown that the above-mentioned abnormalities are not characteristic
for tendinopathy.[11 ]
[12 ] Moreover, the usefulness of conventional ultrasound is limited as they lack sensitivity
in diagnosing tendinopathy.[13 ]
[18 ]
Many studies have shown a significant proportion of patients having subclinical enthesitis
in patients with psoriasis without arthritis.[3 ]
[19 ]
[20 ]
[21 ] Prompt diagnosis is important to prevent progression of the disease to irreversible
structural damage and tendon rupture.[22 ] It is important to identify enthesitis that is a marker for early disease to start
timely treatment.[5 ] Hence, there is importance of early diagnosis as well as objective assessment of
measuring the disease progression and treatment response. This has led to a need for
tools that allow earlier diagnosis of PsA and for identification of progressive structural
damage in tendons.
Shear-wave elastography (SWE) is a new technique that provides information on the
elastic properties of tissues. It generates the quantitative data in kilopascals (kPa)
by measuring the propagation velocity distribution of shear waves in tissues produced
by a focused acoustic push pulse.[23 ]
[24 ]
[25 ] It also provides qualitative data as color-coded images. These images are superimposed
on a GS ultrasound image. Harder tissues appear as red or yellow and softer tissues
appear blue or green. The efficacy of SWE has already been demonstrated by multiple
studies in liver, breast, prostate, and thyroid.[26 ]
[27 ]
[28 ]
[29 ]
[30 ]
[31 ]
[32 ] Tendinopathy is demonstrated by decreased tendon stiffness (kPa) in SWE.[13 ]
[33 ]
[34 ]
[35 ]
[36 ] Studies have shown SWE to be a valuable tool for diagnosing and monitoring tendinopathy.[33 ]
[37 ] Hence, the aim of the study was to establish the role of SWE in patients with PsA.
It was proposed to compare the accuracy of SWE with conventional ultrasound (GS and
pD) for diagnosing Achilles tendinopathy in patients with psoriasis with and without
arthritis and correlate the findings with clinical symptoms (achillodynia) and disease
severity score (PASI) in patients with psoriasis.
Materials and Methods
This was a prospective, observational study done in the Department of Radio Diagnosis
and Imaging, Postgraduate Institute of Medical Education and Research between August
2014 and November 2015. The ethical committee of the institute approved this study.
Written informed consent was taken from all the participants.
Inclusion Criteria
Patients diagnosed to have PsA according to classification criteria for psoriatic
arthritis[38 ] and presenting with achillodynia, regardless whether symptoms were unilateral or
bilateral, were included in the study as cases.
Exclusion Criteria
Patients with a history of metabolic disease, endocrine disease, and sports-related
injury or trauma were excluded from the study.
A standardized questionnaire was used on which demographic data and detailed history
of the disease characteristic of the study subjects were recorded. The study population
consisted of 50 patients. Among them, 28 were suffering from PsA and 22 were having
psoriasis without arthritis. Achilles tendon of both sides was examined regardless
of the symptoms. Hence, we examined 56 Achilles tendons in patients with PsA, which
were cases, and 44 Achilles tendons with psoriasis without arthritis were controls.
An experienced rheumatologist and dermatologist performed the clinical examination
and established the diagnosis. Visual analog scale (VAS) was used to score clinical
symptoms, achillodynia. The scale ranges from 0 to 10, where 10 implies maximum pain
and 0 implies no pain. The severity of the disease was assessed for all the patients
using PASI score.
Multimodal ultrasound was done on all the participants bilaterally that included high-resolution
GS ultrasound, pD, and SWE. Care was taken to conduct the study in each participant
in the same order with the same standardized settings and parameters on a Supersonic
Imagine's Aixplorer ultrasound machine, which was equipped with a linear array probe
SL14–5 probe (5–14 MHz). Every patient followed a standardized positioning protocol.
The tendon was kept in a relaxed state with the patient in prone posture and the foot
hanging freely beyond the examination table. A single operator performed all the scans
to remove interobserver variability.
Multimodal ultrasound of Achilles tendon was done in the longitudinal plane from the
origin at the musculotendinous junction to its point of insertion at the calcaneus.
Achilles tendon was evaluated at the level of the medial malleolus for the distal
third, at the level of mid-calf for the middle third, and at the musculotendinous
junction for the proximal third and three representative images were taken. The criteria
for normal tendon thickness were taken according to a study done by Aydin et al.[39 ] The cutoff values were 3.7 mm for females and 4.8mm for males. The abnormal GS ultrasound
findings included thickened tendon and hypoechoic echotexture. Next pD of the whole
tendon was performed. Any neovascularization was considered abnormal. The results
of both GS ultrasound and pD were dichotomized into normal or abnormal.
In the same sitting, SWE was performed on the three representative images at the proximal,
middle, and distal thirds of the Achilles tendon. Dual screen was used to generate
elastograms showing GS ultrasound image with an overlying elastogram. For recording,
the SWE data a standard region of interest (ROI) with a diameter of 1 mm was taken.
We had taken proper precaution to place the ROI in the tendon and avoid surrounding
soft tissue to avoid minimizing errors in the kPa values. Both qualitative (color
maps) and quantitative data (measured in kPa) were recorded. The color maps were coded
from blue for components with least strain (i.e., softest) to red for those with greatest
strain (i.e., hardest). The criteria for normal SWE values in Achilles tendon were
taken by following two previous multicenter studies.[40 ]
[41 ] These studies calculated the mean elasticity of normal Achilles tendon to be >300kPa.
Statistical Analysis
The statistical analysis was performed using Statistical Package for Social Sciences
(SPSS Inc., Chicago, Illinois, United States, version 16.0 for Windows). All the quantitative
variables were calculated using mean and measures of dispersion (standard deviation
and standard error). For comparing the categorical and continuous variables in the
demographic and clinical data of the study groups, chi-squared test and Mann–Whitney
U test, respectively, were used. Covariance analysis was done to look for any confounding
effect of age or gender. Pearson's correlation was used to look for any association
between duration of arthritis, VAS, PASI with quantitative SWE values. Log regression
analysis was done to see for any correlation between VAS and qualitative SWE data
(color). The statistical significance was set at p ≤ 0.05.
Result
The study population consisted of 50 subjects (mean age: 38.3 ± 19.1 years). Among
them, 28 (mean age: 40.6 ± 9.7 years) patients were suffering from PsA and 22 (mean
age: 38.2 ± 12.2 years) patients were having psoriasis without arthritis. Hence, a
total of 100 Achilles tendons were evaluated that fulfilled the inclusion criteria.
Of these 56 (56%) were patients with PsA presenting with achillodynia, which were
taken as cases, and 44 (44%) patients with psoriasis without arthritis were control.
The mean score value of the pain in the leg and heel perceived by patients on a VAS
was 3.5 ± 1.7. The mean score value of PASI in the study population, cases and control,
was 4.5 ± 3.4, 5.2 ± 3.7 and 3.7 ± 2.8, respectively.
Demographic details of patients and clinical symptoms are given in [Table 1 ]. No statistically significant difference was seen in the demographic data in between
the groups.
Table 1
Demographic data, history, and clinical symptoms
All (n = 100)
Cases (n = 56)
Control (n = 44)
Mean age (years)
38.3 ± 19.1
40.6 ± 9.7
38.2 ± 12.2
Men
58 (58%)
24 (42.86%)
34 (77.27%)
Women
42 (42%)
32 (57.14%)
10 (22.72%)
Duration of psoriasis (years)
8.5 ± 6.6
7.3 ± 4.7
9.9 ± 8.3
Duration of treatment (years)
4.5 ± 5.8
4.0 ± 3.4
5.2 ± 7.9
Duration of arthritis (years)
_
2.5 ± 2.5
_
Mean of VAS (Achillodynia)
_
3.5 ± 1.7
_
PASI
4.5 ± 3.4
5.2 ± 3.7
3.7 ± 2.8
Abbreviations: PASI, psoriasis area and severity index; VAS, visual analog scale.
Multimodal ultrasound (GS, pD, SWE) was done in all the patients and results are shown
in [Table 2 ] and images are shown in [Fig. 1A–F ]. The number of abnormal tendons identified by multimodal ultrasound was shown in
[Table 3 ]. Ultrasound was also performed in few healthy volunteers for reference ([Fig. 2A, B ]) but was not included in the data analysis.
Table 2
Measurement of tendon thickness and SWE values
Whole tendon
Proximal third
Middle third
Distal third
Cases
Control
Cases
Control
Cases
Control
Cases
Control
Mean thickness (mm)
2.4 ± 0.6
2.5 ± 0.5
1.7 ± 0.8
1.6 ± 0.4
2.3 ± 0.8
2.5 ± 0.8
3.1 ± 0.8
3.4 ± 0.5
Mean SWE (kPa)
265.8 ± 90.6
413.6 ± 136.2
202.2 ± 87.3
367.5 ± 172
285.4 ± 143.8
438.3 ± 178.8
310.0 ± 175.8
434.9 ± 166.7
Difference in SWE values between cases and control
150.1kPa
171.2kPa
145.8kPa
133.2kPa
Abbreviations: kPa, kilopascal; mm, millimeter; SWE, shear-wave elastography.
Fig. 1 Sagittal gray scale (GS) ultrasound, power Doppler (pD), and shear-wave elastography
(SWE) images of the Achilles tendon in patients with psoriatic arthritis (PsA). Dual-screen
was used showing GS ultrasound image with an overlying elastogram. Images of the proximal
third part of the Achilles tendon; (A ) pD image showing no color flow; (B ) dual-screen SWE image showing color elastogram with circle representing the region
of interest (ROI) where elastic modulus kilopascal (kPa) was measured with mean elastic
modulus measuring 186.1kPa. Images of the middle third part of the Achilles tendon;
(C ) pD image showing no color flow; (D ) dual-screen SWE image showing color elastogram with circle ROI where elastic modulus
kPa was measured with mean elastic modulus measuring 137.7kPa. Images of the distal
third part of the Achilles tendon; (E ) pD image showing no color flow; (F ) dual-screen SWE image showing color elastogram with circle representing the ROI
where elastic modulus kPa was measured with mean elastic modulus measuring 132.8kPa.
Color ranges from blue (softer) to red (stiffer).
Table 3
Results of multimodal ultrasound (abnormal tendons identified)
All (n = 100)
Cases (n = 56)
Control (n = 44)
GS
12 (12%)
12 (21.43%)
0
pD
2 (2%)
2 (3.57%)
0
GS + pD
13 (13%)
13 (23.21%)
0
SWE value (kPa)
71 (71%)
53 (94.6%)
18 (40.9%)
Abbreviations: GS, gray scale; kPa, kilopascal; pD, power Doppler; SWE, shear-wave
elastography.
Fig. 2 Sagittal gray scale (GS) ultrasound and shear-wave elastography (SWE) images of the
Achilles tendon in a healthy volunteer. Dual-screen was used showing GS ultrasound
image with an overlying elastogram. Images of middle third part of the Achilles tendon,
(A ) dual-screen SWE image showing color elastogram with circle representing the region
of interest (ROI) where elastic modulus kilopascal (kPa) was measured with mean elastic
modulus measuring 373.8kPa. Images of distal third part of the Achilles tendon, (B ) dual-screen SWE image showing color elastogram with circle representing the ROI
where elastic modulus kPa was measured with mean elastic modulus measuring 738.8kPa.
Color ranges from blue (softer) to red (stiffer).
Association between SWE Values and Duration of Arthritis
There was negative correlation seen between duration of arthritis and SWE values with
r -value for proximal, middle, and distal third part of the Achilles tendon being −0.34
(p < 0.001), −0.28 (p < 0.001), and −0.26 (p < 0.001), respectively.
Association between SWE and Clinical Symptom (VAS)
There was negative correlation seen between VAS and SWE values with r -value for proximal, middle, and distal third part of the Achilles tendon being −0.47
(p < 0.001), −0.38 (p < 0.001), and −0.35 (p < 0.001) ([Fig. 3 ]), respectively. Log regression analysis between VAS and qualitative SWE data (color)
was showing significant correlation with a R
2 value 6.8 (p < 0.001).
Fig. 3 Relationship between clinical symptom, visual analog scale (VAS) and elastic modulus,
kilopascal (kPa) values of distal third part of Achilles tendon (L3) in patients with
psoriatic arthritis. Pearson's correlation: r = −0.35; p < 0.001, suggesting a significant negative correlation.
Association between SWE Values and Severity Score (PASI)
There was a significant negative correlation seen between PASI and mean elastic modulus
and elastic modulus of distal third part of the Achilles tendon in cases with r -values being −0.29 (p - < 0.05) and −0.41 (p < 0.001), respectively ([Fig. 4 ]). Overall when the entire cohort was taken into consideration, there was a significant
negative correlation between PASI and elasticity modulus of the distal third part
of the Achilles tendon with r -0.27 (p < 0.05), ([Fig. 5 ]).
Fig. 4 Relationship between disease severity score, psoriasis area and severity index (PASI),
and elastic modulus, kilopascal (kPa) values of distal third part of Achilles tendon
(L3) in patients with psoriatic arthritis. Pearson's correlation: r = −0.41; p < 0.001, suggesting a significant negative correlation.
Fig. 5 Relationship between disease severity score, psoriasis area and severity index (PASI)
and elastic modulus, kilopascal (kPa) values of distal third part of Achilles tendon
(L3) in the entire cohort. Pearson's correlation: r = -0.27; p = < 0.05, suggesting a significant negative correlation.
Discussion
In this study, we evaluated the efficacy of SWE for the assessment of morphologic
and elastic alterations in Achilles tendons in patients with psoriasis with and without
arthritis. This study provides evidence that SWE can be a dependable tool to detect
and quantify the degree of tendinopathies.
This study showed a significant negative correlation between duration of arthritis,
VAS and PASI with elastic modulus. Hence, we can propose that as the severity of the
PASI scores increases, there was a decrease in elastic modulus indicating softening
of tendons. Similarly, as the duration of arthritis was increasing in patients with
PsA, there was a decrease in elastic modulus. With severe clinical symptoms, VAS,
there was a decrease in elastic modulus. In the study done by Dirrichs et al,[33 ] they also found similar findings with SWE improving the diagnostic accuracy and
helped monitor treatment. The changes in the elastic modulus in abnormal tendons were
due to the microscopic alterations in the tendon due to the disruption of the collagen
fibers, fluid accumulation between fibers, and proliferation of noncollagenous matrices.[42 ]
[43 ] To our knowledge, there have been no reported studies in literature, comparing SWE
and PASI.
The lesser number of abnormalities identified by GS ultrasound and pD might be due
to the fact that most of the patients included in the study were having chronic disease
and were on treatment. Hence, they would have reduced inflammation, which in turn
generates lesser pD signal. This effect was also demonstrated by other studies.[44 ]
[45 ] Although tendon abnormalities in patients with PsA can be identified with GS ultrasound,
this method alone is not reliable to detect subclinical alterations. Loss of fiber
integrity may be depicted well with SWE with greater sensitivity than GS ultrasound.
This inability to detect tendinopathy in a significant number of cases can be overcome
by the use of SWE. SWE can also rate the degree of tendon impairment by their quantitative
values, which was also substantiated in previous study.[33 ]
Hence, from the above discussion we could say that SWE was successful in identifying
more abnormal tendons in patients with PsA as compared with GS ultrasound. In addition,
some subclinical elastic alterations in the form of softened Achilles tendon in psoriasis
patients without arthritis were also identified in the control. This suggests that
subclinical elastic alterations may be far more common than earlier thought. These
alterations were unidentifiable by GS ultrasound or pD. The findings were similar
to the study done by Dirrichs et al.[33 ] Hence, we could propose that changes in the elastic properties occur early in the
inflammatory process of the tendon, which is unidentifiable by routine GS ultrasound
but identified only by SWE. The clinical significance of it is abundant as in equivocal
cases if not identified early, degenerative changes in collagen structure, which soften
and weaken the tendon, can eventually lead to tear or spontaneous rupture of the tendon.
Moreover, by using SWE, tendon structure and integrity can be assessed that are actually
clinically significant and help monitor progression or regression of the disease.
This can help us in better appreciation of the disease process and aid us in staging
the altered elastic properties of the tendon.
The limitation of our study was that no histopathological correlation or MRI was done
to confirm the SWE detected lesions. However, histological correlation with elastography
was previously evaluated in a study done by Klauser et al.[10 ] Second, we could not assess the intraobserver variability. However, they have already
been evaluated in earlier studies.[46 ]
[47 ] Third, the operator was not blinded to the clinical symptoms of the patient.
In conclusion, SWE can be a novel biomarker in assessing Achilles tendinopathy in
patients with psoriasis. Our study has shown that SWE can better diagnose tendinopathy
compared with conventional ultrasound. Early identification of the abnormality can
prevent the progression of the disease and morbidity to the patient in the form of
tendon rupture. Further studies should be done to evaluate the significance of altered
elastic modulus in Achilles tendon in patients of psoriasis without arthritis with
a prospective study in a large study population. Further evaluation should be done
whether treatment should be changed on encountering altered elastic modulus in the
Achilles tendon and whether the patients benefited from the changed treatment. We
hope that our findings will lead to further research in PsA using SWE.
