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PSORIATIC ARTHRITIS

Subclinical Entheseal Involvement in


Patients with Psoriasis: An Ultrasound Study
Marwin Gutierrez, MD,* Emilio Filippucci, MD,*
Rossella De Angelis, MD,* Fausto Salaffi, MD,* Giorgio Filosa, MD,
Santiago Ruta, MD, Chiara Bertolazzi, MD,* and Walter Grassi, MD*

Objectives: The main aim of the present study was to determine the prevalence of subclinical
entheseal involvement at lower limbs by ultrasound (US) in patients with psoriasis. The secondary
aim was to determine the interobserver reliability of the Glasgow Ultrasound Enthesitis Scoring
System (GUESS) and power Doppler (PD) technique in the assessment of enthesopathy.
Methods: The study was conducted on 45 patients with psoriasis and 45 healthy sex- and agematched controls. All patients with no clinical evidence of arthritis or enthesitis underwent an US
examination. All US findings were identified according to GUESS. The interobserver reliability
was calculated in 15 patients with psoriasis.
Results: A total of 450 entheses in 45 patients with psoriasis were evaluated by US. In 148 of 450
(32.9%) entheses, grayscale US found signs indicative of enthesopathy. In 4/450 (0.9%) entheses PD
signal was detected. In the healthy population, US found signs of enthesopathy in 38 of 450 (8.4%)
entheses and no PD signal was detected. The GUESS score was significantly higher in patients with
psoriasis than in healthy controls (P 0.0001). Both concordance correlation coefficient and unweighted values for US findings showed an excellent agreement (0.906 and 0.890, respectively).
Conclusions: Our results indicate that both grayscale US and PD findings indicative of enthesopathy were more frequent in patients with psoriasis. The US ability to detect signs of subclinical
enthesopathy should be the object of longitudinal investigations to define its value in predicting
the clinical onset of psoriatic arthritis.
2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 40:407-412
Keywords: ultrasound, psoriatic arthritis, psoriasis, enthesopathy, power Doppler

soriasis is 1 of the most common chronic inflammatory skin diseases, affecting approximately 1 to
3% of the worlds population. The prevalence of
psoriatic arthritis (PsA) among patients with psoriasis was
earlier reported as approximately 5 to 39% (1,2), the exact
percentage being unknown. Little is known about the
prevalence of entheseal involvement in patients with psoriasis (3). Some investigations indicate enthesis as the initial site of inflammation in spondyloarthropathies (SpA)

*Clinica Reumatologica, Universit Politecnica delle Marche, Jesi, Ancona, Italy.


Unit di Dermatologia, A. Murri Hospital, Jesi, Ancona, Italy.
Servicio de Reumatologa, Hospital Gral. San Martn de La Plata, Buenos Aires,
Argentina.
The authors have no conflicts of interest to disclose.
Address reprint requests to Marwin Gutierrez, MD, Clinica Reumatologica, Universit Politecnica delle Marche, Ospedale A. Murri, Via dei Colli, 52, 60035, Jesi,
Ancona, Italy. E-mail: dr.gmarwin@gmail.com.

0049-0172/11/$-see front matter 2011 Elsevier Inc. All rights reserved.


doi:10.1016/j.semarthrit.2010.05.009

(4), especially those of the lower limbs (5-7). The presence


of enthesopathy in patients with psoriasis may be underestimated due to its often oligosymptomatic clinical involvement.
Conventional radiography can demonstrate established bony erosions and spurs, but it gives little information about soft tissues, especially in the early phase of the
disease (8,9). Magnetic resonance imaging has the ability
to visualize both soft-tissue and bone marrow edema using multiplanar views, but it is mainly limited by high
cost (10,11).
There are a number of investigations describing the use
of ultrasonography (US) in identifying the features of
lower limb enthesitis in SpA (6,12-16). Moreover, US
was found able to reveal a high prevalence of abnormal
findings in asymptomatic entheses (14). The identification of enthesitis by US may precede by years its clinical
onset or, in general, the diagnosis of PsA.
407

408

The main aim of the present study was to determine the


prevalence of subclinical entheseal involvement at lower
limbs by US in patients with psoriasis. The secondary
aims were to determine the interobserver reliability of the
Glasgow Ultrasound Enthesitis Scoring System (GUESS)
(6) and power Doppler (PD) technique in the assessment
of entheseal involvement and to evaluate the correlation
between GUESS and other clinical parameters.
MATERIALS AND METHODS
Patients
A total of 47 patients were referred from the dermatologist with a definite diagnosis of psoriasis to be included in
the study. Two patients were excluded since tenderness
was found by the rheumatologist at the Achilles enthesis.
The study was conducted on 45 patients with psoriasis
and 45 healthy sex- and age-matched controls, recruited
from January 2008 to February 2009. The body mass
index (BMI) median; CI 95% for the median; SD were as
follows: 24.2; 22.6 to 24.9; 3.66 for psoriatic patients,
and 24.4; 23.4 to 24.7; 1.5 for healthy controls. Both
patients and healthy controls underwent a clinical examination by both an expert dermatologist (G.F.) who
scored the Psoriasis Area and Severity Index (PASI), and
by an expert rheumatologist (R.D.A.) who recorded tenderness elicited by pressure, mobilization, and contraction against resistance of the corresponding entheses, to
confirm the absence of entheseal involvement. Patients
with a diagnosis of psoriasis and without any clinical evidence of arthritis or enthesitis underwent an US examination of lower limbs. Exclusion criteria were as follows:
clinical evidence of arthritis, age 18 years, BMI 30,
peripheral neuropathy of lower limbs, history of recent
severe trauma at entheses scanned, or knee or ankle surgery and corticosteroid injection of the examined structures, or any systemic treatment for psoriasis in the previous 3 months before the beginning of the study.
Study Design
The study was conducted according to the Declaration of
Helsinki and local regulations. Ethical approval for the
study was obtained from the local Ethics Committee and
informed consent was obtained from both patients and
healthy controls.
All US examinations were performed by an experienced sonographer (M.G.) blinded to clinical data in a
darkened room. Patients and healthy subjects underwent
US assessments at random and were asked not to talk
about their clinical condition with the US examiner. To
assess interobserver reliability, in 15 patients with psoriasis, US examinations were performed independently by a
second investigator with less than 1 year of experience in
musculoskeletal US (S.R.) under the same scanning conditions of the experienced sonographer. Before the study,
the investigators reached a consensus on the US scanning
technique to adopt and on US findings to interpret.

Subclinical entheseal involvement in patients with psoriasis

US Assessment
US examinations were performed at the Rheumatology
Department of the Universit Politecnica delle Marche,
using a MyLab 70 XVG (Esaote Biomedica, Genoa, Italy)
equipped with a 6- to 18-MHz broadband linear transducer.
The following 5 entheses were scanned bilaterally:
quadriceps insertion into the upper pole of the patella,
patellar tendon insertion into the lower pole of the patella
and into the tibial anterior tuberosity, and Achilles tendon and plantar aponeurosis insertion into the calcaneal
bone.
Multiplanar US examinations of the quadriceps and
patellar entheses were performed with the patient in the
supine position with lower limbs extended. The Achilles
tendon and the proximal plantar aponeurosis were examined with the patient lying prone with the feet hanging
over the edge of the examination table at 90 of flexion
(17). Each enthesis was scanned in grayscale to detect
morphostructural changes and subsequently with PD
technique to detect abnormal blood flow.
All US findings indicative of enthesopathy according to
GUESS (6) were investigated and documented in both
transverse and longitudinal views (from proximal to distal
and from medial to lateral aspects of the entheses). These
include the following: entheseal thickness of tendon, bursitis, bony erosions, and enthesophytes. Entheseal thickness was measured at the point of maximal thickness 2
mm proximal to the bony insertion (normal value of
thickness for each enthesis are represented in the table 1).
Bursitis was defined as a well-circumscribed, localized anechoic or hypoechoic area at the site of an anatomical
bursa and which was compressible by the transducer (18).
Bone erosion was defined as a cortical interruption with a
step-down contour defect and enthesophyte was defined
as a step-up bony prominence at the end of normal bone
profile. Blood flow was examined in each enthesis using
PD, the settings of which were standardized with a pulse
repetition frequency of 750 KHz and a Doppler frequency between 9.1 and 11.1 MHz. The presence of the
PD was considered positive if found within the tendon 2
mm proximal to the bony insertion and not at the body of
the tendon or at the bursal level. Particular attention was
paid on not compressing the tissues under examination to
avoid the blanching of PD signal due to the transducer
pressure (19).
Statistical Analysis
Statistical analysis was performed using MedCalc, version
9.5.1 for Windows XP (Microsoft Corp., Redmond,
WA). Standard descriptive results were expressed as median and 95% confidence intervals for the median. A 2
test was used to compare the distribution of PD US technique among different groups. P values less than 0.05
were considered statistically significant. The interobserver
agreement was calculated using a kappa () test (un-

M. Gutierrez et al.

409

Table 1 Distribution of the Morphostructural Changes in the Study Population


Bursitis
Entheseal Thickness
(patients/healthy (patients/healthy
controls)
controls)
Quadriceps enthesis (n)
Proximal patellar enthesis (n)
Distal patellar enthesis (n)
Achilles enthesis (n)
Plantar aponeurosis
enthesis (n)
Totalb

Enthesophyte
(patients/healthy
controls)

Bone Erosion
(patients/healthy
controls)

9/7
21/5
31/3
9/3
3/0

0/0
0/0
0/0
4/1
0/0

20/6
10/5
8/0
27/8
1/0

0/0
0/0
2/0
3/0
0/0

73/18

4/1

66/19

5/0

6.1 mm
4 mm
4 mm
5.29 mm
4.4 mm

aNormal
bTotal

values of the entheseal thickness.


value of abnormalities of patients with psoriasis and healthy subjects is 148 and 38, respectively.

weighted for dichotomous scoring) and concordance correlation coefficient (CCC) and illustrated by Bland and
Altman plots. A value of 0 to 0.20 was considered poor,
0.21 to 0.40 fair, 0.41 to 0.60 moderate, 0.61 to 0.80
good, and 0.81 to 1.00 excellent, whereas a value of more
than 0.8 for the CCC was considered significant. Correlation between GUESS score and covariates (psoriasis duration, BMI, and PASI) was compared using Spearmans
rank correlation coefficient ().
RESULTS
A total of 450 entheseal sites in 45 patients with psoriasis
were examined by US. In 148 of 450 (32.9%) entheseal
sites, grayscale US found at least 1 sign indicative of enthesopathy. The entheseal site with the highest number of

signs of enthesopathy was the Achilles enthesis (43/450)


(9.5%), followed by distal patellar enthesis (41/450)
(9.1%), proximal patellar enthesis (31/450) (6.9%),
quadriceps enthesis (29/450) (6.4%), and plantar aponeurosis enthesis (4/450) (0.9%). In 4/450 (0.9%) entheses (2 in the Achilles enthesis, 1 in the quadriceps enthesis,
and 1 in the distal patellar enthesis), PD signal was detected. Figures 1 and 2 show the normal US findings at
the investigated entheseal sites and the US features most
representative of enthesopathy, respectively.
In the healthy population, US found at least 1 sign
indicative of enthesopathy in 38 of 450 (8.4%) entheseal
sites (P 0.0001). In this group, the entheseal sites with
the highest number of US signs of enthesopathy were the
quadriceps enthesis (13/450) (2.8%) and the Achilles en-

Figure 1 Representative US images of the normal entheseal insertions on longitudinal scan. Note the typical fibrillar echotexture
of tendon and its sharp margins (arrowheads). (A) Quadriceps enthesis (q). (B) Proximal patellar enthesis (pp). (C) Distal patellar
enthesis (dp). (D) Plantar aponeurosis enthesis (pa). (E) Achilles enthesis (ac). US images were obtained with a 6- to 18-MHz
linear transducer using a MyLab 70 XVG US system (Esaote Biomedica, Genoa, Italy). p patella; t tibia; st sub cutaneous
soft tissue; ca calcaneous bone.

410

Subclinical entheseal involvement in patients with psoriasis

Figure 2 Representative US findings indicative of enthesopathy on longitudinal scan. (A) Presence of abnormal PD signal to the
bony insertion of distal patellar enthesis. (B) Enthesophyte at Achilles enthesis level (curved arrow). (C) Thickening of the plantar
aponeurosis enthesis (6.1 mm). The vertical white line indicates the exact point where the measurement was obtained. (D) Deep
retrocalcaneal bursitis (asterisk) at the Achilles enthesis level. dp distal patellar enthesis; ac Achilles enthesis; pa plantar
aponeurosis enthesis; t tibia; st subcutaneous soft tissue; ca calcaneous bone. US images were obtained using a MyLab
70 XVG US system with a 6- to 18-MHz linear transducer and Doppler frequency of 9.1 MHz.

thesis (12/450) (2.7%), followed by the proximal patellar


enthesis (10/450) (2.2%), the distal patellar enthesis (3/
450) (0.6%), and the plantar aponeurosis enthesis (0/
450) (0%). No PD signal was detected in healthy controls.
Table 1 provides the distribution of the morphostructural changes obtained in both the patients with psoriasis
and the healthy controls at different entheseal levels.
The GUESS score was significantly higher in patients
with psoriasis than in healthy controls (P 0.0001). No
statistically significant correlation was found between the
GUESS score and the psoriasis duration ( 0.088; P
0.556), the BMI ( 0.209; P 0.165), and the PASI
( 0.094; P 0.532). The presence of PD signal was
found more frequently in the entheses of patients with
psoriasis compared with healthy controls (P 0.0001).
One hundred fifty entheses of 15 patients with psoriasis
were examined by 2 investigators. Both CCC and unweighted values for the examined parameters showed
excellent agreement (0.906 and 0.890, respectively). The
values between the 2 investigators for the single abnormalities (thickness, bursitis, enthesophytes, and bone erosions) were 0.820, 0.990, 0.795, and 0.990, respectively.
Moreover, the CCC of the thickness was 0.845. Figure 3
shows the distribution of the entheseal thickness measurements by the 2 investigators, according to Bland and Altman plot.

High-resolution US has been shown to be of value in


revealing subclinical joint and tendon inflammation
in patients with chronic arthritis (24,25). Its sensitivity in
the detection of enthesitis has been demonstrated in patients with SpA (6,12-15). Thus, we decided to investigate the ability of US to identify entheseal involvement in
patients with psoriasis without any clinical sign of musculoskeletal system involvement. A similar study has been
recently conducted by Gisondi and coworkers (26), using
only grayscale US with a lower frequency probe (15
MHz). The present investigation was performed in a
higher number of patients using a latest generation US
system equipped with a probe frequency reaching 18
MHz and very high-frequency PD.
There is evidence supporting the issue that PD strongly
improves US accuracy in the assessment of enthesitis

DISCUSSION
Enthesitis has been indicated as a distinctive pathologic
condition affecting patients with PsA (20). Because radiographs are not sensitive enough for the detection of early
signs of entheseal involvement (8,9,21,22), US may be
considered as an alternative imaging technique in the diagnosis of enthesopathy (21-23).

Figure 3 Distribution of the entheseal thickness measurements by the 2 investigators (M.G. and S.R.) on the Bland
and Altman plot.

M. Gutierrez et al.

(12,14,27,28). In the present study a lower mean value of


GUESS score was found both in patients with psoriasis
and in healthy controls, probably related to differences in
age and BMI of the recruited subjects. Further differences
in the results obtained regard evidence of bone erosions,
not detected in the study by Gisondi and coworkers (26),
and found in 4 of our patients (0.9%).
Our results indicate that both grayscale US and PD
findings were more frequent in patients with psoriasis
than in age- and sex-matched healthy controls. The absence of PD in healthy controls suggests a very high specificity of this imaging technique. This provides evidence
for performing US examination in patients with psoriasis
especially at Achilles insertion in the calcaneal bone,
which represents the most frequently involved enthesis at
US assessment. Similar findings were reported by Ozcakar
and coworkers and De Simone and coworkers (29,30).
The prevalence of sonographic findings indicative of
enthesopathy is not homogeneously distributed in the 5
entheses examined, enthesophytes being more frequently
found at Achilles enthesis and entheseal thickening at the
proximal and distal patellar entheses. A possible explanation may be related to both mechanical and local anatomic factors. For instance, the relatively low prevalence
of pathologic US findings at the plantar fascia level may be
due to the presence of a thicker layer of both skin and
subcutaneous tissue overlying the fascia, which may decrease the US sensitivity.
A limitation of the present study is related to the dichotomous way to report the US findings in terms of
presence/absence. In this way very small and focal irregularities of the new bone formation had the same value of
high and multiple enthesophytes. Further, despite trying
to ensure blinding of the sonographer to clinical data,
psoriatic plaques affecting the skin overlying the entheses
of the lower limbs could be visualized by US.
The US ability to detect signs of subclinical enthesopathy should be the object of longitudinal investigations to
define its value in revealing subclinical PsA. Ongoing follow-up of the patients recruited in the present study will
provide further information regarding the predictive
value of US findings in the development of the PsA.
REFERENCES
1. Leonard DG, ODuffy JD, Rogers RS. Prospective analysis of
psoriatic arthritis in patients hospitalized for psoriasis. Mayo Clin
Proc 1978;53:511-8.
2. Ibrahim G, Waxman R, Helliwell PS. The prevalence of psoriatic
arthritis in people with psoriasis. Arthritis Rheum 2009;61:
1373-78.
3. Filippis LG, Caliri A, Lo Gullo R, Bartolone S, Miceli G, Cannav SP, et al. Ultrasonography in the early diagnosis of psoriasisassociated enthesopathy. Int J Tissue React 2005;27:159-62.
4. McGonagle D, Khan MA, Marzo-Ortega H, OConnor P, Gibbon W, Emery P. Enthesitis in spondyloarthropathy. Curr Opin
Rheumatol 1999;11:244-50.
5. Olivieri I, Barozzi L, Padula A, De Matteis M, Pavlica P. Clinical
manifestations of seronegative spondylarthropathies. Eur J Radiol
1998;27:3-6.

411
6. Balint PV, Kane D, Wilson H, McInnes IB, Sturrock RD. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 2002;61:905-10.
7. McGonagle D, Wakefield RJ, Tan AL, DAgostino MA, Toumi
H, Hayashi K, et al. Distinct topography of erosion and new bone
formation in achilles tendon enthesitis: Implications for understanding the link between inflammation and bone formation in
spondylarthritis. Arthritis Rheum 2008;58:2694-9.
8. Calin A, Mackay K, Santos H, Brophy S. A new dimension to
outcome: application of the Bath Ankylosing Spondylitis Radiology Index. J Rheumatol 1999;26:988-92.
9. Resnick D, Niwayama G. Entheses and enthesopathy. Anatomical, pathological, and radiological correlation. Radiology 1983;
146:1-9.
10. Kenny JB, Hughes PL, Whitehouse GH. Discovertebral destruction in ankylosing spondylitis: The role of computed tomography
and magnetic resonance imaging. Br J Radiol 1990;63:448-55.
11. McGonagle D, Gibbon W, OConnor P, Green M, Pease C,
Emery P. Characteristic magnetic resonance imaging entheseal
changes of knee synovitis in spondylarthropathy. Arthritis Rheum
1998;41:694-700.
12. De Miguel E, Cobo T, Muoz-Fernndez S, Naredo E, Uson J,
Acbes JC, et al. Validity of enthesis ultrasound assessment in spondylarthropathy. Ann Rheum Dis 2009;68:169-74. doi 10.1136/
ard.2007.084251.
13. Alcalde M, Acebes JC, Cruz M, Gonzlez-Hombrado L, HerreroBeaumont G, Snchez-Pernaute O. A sonographic enthesitic index of lower limbs is a valuable tool in the assessment of ankylosing spondylitis. Ann Rheum Dis 2007;66:1015-9.
14. DAgostino MA, Said-Nahal R, Hacquard-Bouder C, Brasseur JL,
Dougados M, Breban M. Assessment of peripheral enthesitis in the
spondylarthropathies by ultrasonography combined with power
Doppler: A cross-sectional study. Arthritis Rheum 2003;48:523-33.
15. Lehtinen A, Taavitsainen M, Leirisalo-Repo M. Sonographic
analysis of enthesopathy in the lower extremities of patients with
spondylarthropathy. Clin Exp Rheumatol 1994;12:143-8.
16. Borman P, Koparal S, Babaoglu S, Bodur H. Ultrasound detection of entheseal insertions in the foot of patients with spondyloarthropathy. Clin Rheumatol 2006;25:373-7.
17. Backhaus M, Burmester GR, Gerber T, Grassi W, Maschold KP,
Swen WA, et al. Group for Musculoskeletal Ultrasound in the
EULAR Standing Committee on International Clinical Studies
including Therapeutic Trials. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis 2001;60:641-9.
18. Van Holsbeeck M, Introcaso J. Sonography of bursae. Musculoskeletal ultrasound. St. Louis (MO): Mosby Year Book; 1991. p.
91-121.
19. Joshua F, de Carle R, Rayment M, Bryant C, Shnier R, Edmonds
J, et al. Power Doppler blanching after the application of transducer pressure. Australas Radiol 2005;49:218-21.
20. McGonagle D, Conaghan PG, Emery P. Psoriatic arthritis: A
unified concept twenty years on. Arthritis Rheum 1999;42:
1080-6.
21. Evangelisto A, Wakefield R, Emery P. Imaging in early arthritis.
Best Pract Res Clin Rheumatol 2004;18:927-43.
22. Kane D, Pathare S. Early psoriatic arthritis. Rheum Dis Clin
North Am 2005;31:641-57.
23. Tan AL, McGonagle D. Imaging of seronegative spondyloarthritis. Best Pract Res Clin Rheumatol 2008;22:1045-59.
24. Wakefield RJ, Green MJ, Marzo-Ortega H, Conaghan PG, Gibbon WW, McGonagle D, et al. Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease.
Ann Rheum Dis 2004;63:382-5.
25. Kane D, Balint PV, Sturrock RD. Ultrasonography is superior to
clinical examination in the detection and localization of knee joint
effusion in rheumatoid arthritis. J Rheumatol 2003;30:966-71.
26. Gisondi P, Tinazzi I, El-Dalati G, Gallo M, Biasi D, Barbara SM,
et al. Lower limb enthesopathy in patients with psoriasis without

412
clinical signs of arthropathy: A hospital-based case-control study.
Ann Rheum Dis 2008;67:26-30.
27. Kiris A, Kaya A, Ozgocmen S, Kocakoc E. Assessment of enthesitis in ankylosing spondylitis by power Doppler ultrasonography.
Skeletal Radiol 2006;35:522-8.
28. Kane D. The role of ultrasound in the diagnosis and management
of psoriatic arthritis. Curr Rheumatol Rep 2005;7:319-24.

Subclinical entheseal involvement in patients with psoriasis


29. Ozcakar L, Cetin A, Inanici F, Kaymak B, Gurer CK, Kolemen F.
Ultrasonographical evaluation of the Achilles tendon in psoriasis
patients. Int J Dermatol 2005;44:930-2.
30. De Simone C, Guerriero C, Giampetruzzi AR, Costantini M,
Di Gregorio F, Amerio P. Achilles tendinitis in psoriasis: Clinical and sonographic findings. J Am Acad Dermatol 2003;49:
217-22.