Ultrasonography in the Diagnosis and Management of Spondyloarthritis

Catherine J Bakewell, MD, RhMSUS

Intermountain Healthcare Salt Lake ClinicSalt Lake City, Utah

Overview

• MSUS is an excellent tool to study extraspinalmanifestations of spondyloarthropathy

– Use in Diagnosis of SpA

– Use in Monitoring and Treatment of Spa

• Ie. Scoring systems (GUESS)

• Unique features of SpA

– Dactylitis

• Future research and applications

What Can US Assess in SpA?

Peripheral Joints

Enthesis

Tendons

GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis)

Ultrasound in SpA

• Frequency of abnormal peripheral entheses is very high among SpA patients

• Abnormal entheses uniformly found in SpA, irrespective of disease type

• May be only manifestation of SpA in early disease

D’Agostino MA, Best Prac Res Clin Rheum; 20, 2006

Clinical Impact of Early Diagnosis

• Improved outcomes for patients with Rheumatoid arthritis well established.

• What about patients with Spondyloarthritis?

Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A

meta-analysis.Finckh A, Liang MH, van Herckenrode CM, de Pablo P

Arthritis Rheum. 2006 Dec 15; 55(6):864-72.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment

strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007;146:406–

15

Delayed diagnosis of PsA is associated with worse long-term outcomes

Association of clinical featuresa with >6 month delay in diagnosis

(univariate analysis model)

0123456789

1011

Erosions Number ofdeformed joints

(score)

Sacroiliitis Arthritis mutilans Functionaldisability

(HAQ score)

DMARD/anti-TNFfree

4.6 (2.5–8.2)

1.1 (1.0–1.1)2.3 (1.2–4.4)

10.6 (1.4–80.6)

2.2 (1.3–3.6)

0.4 (0.2–0.9)

Od

ds

rati

o (

95

% C

I)

***

****

*p<0.05; **p<0.01; ***p<0.001

*

*

Haroon M, et al. Ann Rheum Dis 2014 Feb 13.

doi: 10.1136/annrheumdis-2013-204858 [Epub ahead of print]

aClinical features recorded as percent, unless otherwise stated

DMARD, disease-modifying antirheumatic drug;

HAQ, health assessment questionnaire; OR, odds ratio

*

Enthesitis Clinical Evaluation

• Tenderness at enthesial insertion site

• MEI – 66 enthesis sites – most comprehensive

• Commonly used: more paired down versions such as LEI (Leeds Enthesitis Index) – 6 most commonly involved sites in PsA *

• Pitfall: overlap with FMS tenderpoints near lateral epicondyle, medial femoral condyle

• - Need for MSUS

*Healy 2008

2005Enthesopathy OMERACT Definition

• Tendon or ligament insertion into thecortical bone** which is abnormallyhypoechoic (loss of normal fibrillararchitecture) and/or thickened. Seen in 2 perpendicular planes and may exhibitDoppler signal and/or bone changes, including enthesophytes, erosions orirregularity.

** Occasionally may containhyperechoic foci consistent withcalcifications.

Lehtinen A, et al, Clin Exp Rheum 12;

1994.

D’Agostino MA, et al, Arth Rheum: 48,

2003.

Sturrock RD, Curr Rheum Rep; 11, 2009.

Falsetti P, et al, Mod Rheumatol; 19, 2009.

Wakefield RJ, et al. J Rheumatol. 2005;32:2485-2487

Achilles Tendon

Long Axis

McGonagle D. Arthritis Rheum. 1999;42:1080-1086.

Enthesitis

Calcaneus

Achilles Tendon

Enthesitis: Traditional View

OMERACT Definition: 2014

1. Hypoechogenicity and increased thickness of the tendon insertion– Lack of the homogeneous fibrillar pattern

– Increased thickness of the tendon/ligament/capsule insertion

2. Enthesophytes

3. Calcifications

4. Erosions—OMERACT definition

5. Doppler signal at enthesis~ <2 mm near the bony cortex– The Doppler signal must be at the enthesis, different from reflecting surface

artifact or nutrition vessel signal, with or without cortical irregularities, erosions or enthesophytes.

Terslev L, et al. Arthritis Care Res. 2014.

Ultrasound in SpA

• Hallmark of inflammatory peripheral enthesitis is vascularization at cortical bone insertion as seen by power doppler

• Detection of any vascularized enthesis by PDUS has good sensitivity/specificity for dx SpA

• Technique is sensitive to change: disappearance of vascularization with anti TNF Rx and reappearance with relapse

D’Agostino MA, Best Prac Res Clin Rheum; 20, 2006.

Achilles Enthesitis

Hypoechogenecity

and

increased thickness

Vascularity

within

body of tendon

GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis)

Achilles Enthesitis

D'Agostino MA, et al. Arthritis Rheum. 2003;48(2):523-533.

Doppler Signal at

Enthesis

Achilles Enthesitis

Calcaneal Erosion

GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis)

Erosions

Codo

Insertional Irregularities

Enthesophytes

Enthesitis: Bone Abnormalities

GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis)

Enthesitis Scoring Systems

Glasgow Ultrasound Enthesitis Scoring: GUESS

*Most frequently used Scoring system available

US examination at the following 5 sites:

• Superior pole of patella (quadriceps insertion)• Inferior pole of patella (patellar ligament origin)• Patella ligament insertion at tibial tuberosity• Achilles tendon• Plantar aponeurosis

Scoring on US: bursitis, tendon thickness, enthesophyte and bone erosion

Balint PV et al, Ann Rheum Dis; 61, 2002.

Hatemi G, et al, Arth Rheum; 58, 2008

D’Agostino MA, ibid* Gandjbakhch et al Arthritis Research and Therapy 2011

Madrid Sonographic Enthesis Index (MASEI)

Examination done bilaterally• Inferior pole of calcaneus: plantar aponeurosis enthesis• Superior pole of calcaneus: Achilles tendon enthesis• Tibial tuberosity: distal patellar ligament enthesis• Inferior pole of patella: proximal patellar ligament enthesis• Superior pole of patella: quadriceps tendon enthesis• Olecranon tuberosity: triceps tendon enthesis

Score: tendon structure and thickness, bursitis 0 or 1; power dopplerand erosion 0 or 3; calcification 0 to 3

Value >18 cut off point with sensitivity 83%, specificity 83%

De Miguel E, et al, Ann Rheum Dis; 68, 2009.

Clinical Application

• MASEI can differentiate between healthy patients, patients with psoriasis, and patients with PsA.

– Cut off of >= 20 used for calculation

– Sensitivity 30%

– Specificity of 95% to differentiate PsA from PsO

• No significant difference was found in patients with BMI > 30

Eder L et al. J Rheum. 2014 Mar;41(3):466-72

BMI and Enthesitis Scoring

• The GUESS score, which primarily analyzes lower body entheses, has been correlated with BMI, and an association between the thickness of the Achilles tendon and BMI has previously been noted.[Balint 2002, Gisondi 2008]

• May not apply for any patient with BMI > 30!

Glasgow Ultrasound Enthesitis Scoring System (GUESS)

Superior pole of the patella—quadriceps tendon enthesis• Quadriceps tendon thickness ≥6.1 mm

• Suprapatellar bursitis

• Superior pole of patella erosion

• Superior pole of patella enthesophyte

Inferior pole of the patella—proximal patellar ligament enthesis• Patellar ligament thickness ≥4 mm

• Inferior pole of patella erosion

• Inferior pole of patella enthesophyte

Tibial tuberosity—distal patellar ligament enthesis• Patellar ligament thickness ≥4 mm

• Infrapatellar bursitis

• Tibial tuberosity erosion

• Tibial tuberosity enthesophyte

Superior pole of the calcaneus—Achilles tendon enthesis• Achilles tendon thickness ≥5.29 mm

• Retrocalcaneal bursitis

• Posterior pole of calcaneus erosion

• Posterior pole of calcaneus enthesophyte

Inferior pole of the calcaneus—plantar aponeurosis enthesis• Plantar aponeurosis thickness ≥4.4 mm

• Inferior pole of calcaneus erosion

• Inferior pole of calcaneus enthesophyte

Suprapatellar Longitudinal• Suprapatellar bursitis

• Superior pole of patella erosion

• Superior pole of patella enthesophyte

• Quad tendon thickness ≥6.1 mm

Quad tendon

Patella

FemurUSSONAR

Suprapatellar bursitis

• Abnormal hypoechoic or anechoic intraarticular material that is compressible and displaceable, without Doppler signal.

1. Wakefield J Rheum 2005;32:2485-7

Suprapatellar long

OA, suprapatellar trans

USSONAR

Infrapatellar Long-Proximal

• Assess the origin of the ligament at the patella

• Patellar ligament thickness ≥4 mm

• Inferior pole of patella erosion

• Inferior pole of patella enthesophyte

Patella

Patellar ligament

A. Nelson

• Patellar ligament thickness ≥4 mm

• Infrapatellar bursitis

• Tibial tuberosity erosion

• Tibial tuberosity enthesophyte

Patellar ligament

Tibial tuberosityFat pad

Infrapatellar Long-Distal

A. Nelson

Infrapatellar Transverse

• May demonstrate fluid in the infrapatellar bursae

Patellar ligament

Tibia

MEDIAL

Deep infrapatellar bursa area

A. Nelson

Infrapatellar Enthesitis

Longitudinal Transverse

Ankle – Posterior Longitudinal

Kager’s Fat Pad

Calcaneus

• Achilles tendon thickness ≥5.29 mm

• Retrocalcaneal bursitis

• Posterior pole of calcaneus erosion

• Posterior pole of calcaneus

enthesophyte

Images: Kohler, M

Achilles Enthesopathy/Enthesitis

Retrocalcaneal bursitis

Images: Kohler, M

Plantar Longitudinal

Plantar fascia

calcaneus

• Plantar aponeurosis thickness ≥4.4 mm

• Inferior pole of calcaneus erosion

• Inferior pole of calcaneus enthesophyte

Images: Kohler, M

Long Axis Short Axis

Enthesopathy Plantar Fascia

GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis)

US for Enthesopathy• 35 SpA patients

• Mean GUESS Score = 6.9

(total possible =36)

• Abnormality detected by US in 56% of sites and by clinical exam in 22%

• 2011 Tinazzi et al: GUESS score predictive of subsequent PsA (PsOcohort) 9.5 vs 6.6

• Eder 2012 Average GUESS for HC 4.4 vs. 8.9 for PsA, 5.6 for PsO

1. Balint Ann Rheum Dis 2002;61:905-10; Tinazzi J Rheumatol 2011; 38:2691-2; Eder Arthritis Rheum 2012;64:S582

Clinical Relevance

“The identification of enthesitis in patients with psoriasis is becoming increasingly significant, because studies have suggested that higher enthesitis scores detected by the GUESS system, and the involvement of joints using both greyscale and power Doppler US signals is predictive of the development of PsA in patients with psoriasis.”

Delle Sedie A, Riente L. Psoriatic arthritis: what ultrasound can

provide us. Clin Exp Rheumatol. 2015 Sep-Oct;33(5 Suppl 93):S60-5

MASEI and PsA damage

• Higher MASEI score associated with more peripheral joint damage and a greater chance of patients developing joint ankyloses and/or arthritis mutilans.

• Also associated with greater axial damage, thus demonstrating the importance of not only diagnosing a patients with PsA, but also identifying patients with enthesitis.

Polachek A, Gladman DD, Cook RJ, Chandran V, Eder L. The Association Between

Sonographic Enthesitis and Radiographic Damage in Psoriatic Arthritis [abstract]. Arthritis

Rheumatol. 2016; 68 (suppl 10).

Where we are Currently

• A proper US index for enthesitis could be used to diagnose early PsA and thereby improve patient outcomes.

• Currently, no index exists that accounts for the Delphi exercise update to the OMERACT definition for enthesitis, and no consensus for the best index has been reached.[Micu 2016]

Micu MC, Fodor D. Concepts in monitoring enthesitis in patients with spondylarthritis--the role of musculoskeletal ultrasound. Med Ultrason. 2016 Mar;18(1):82-9.

Case

• 35 yof presents with 4 mo of swelling of her right thumb

• Interfering w her time at the gym

• Does have history of psoriasis

Images

Images

Extensor Tendinosis/Paratenonitis Flexor Tenosynovitis

Dactylitis

• Characteristic feature of SpA

• Painful or relatively assx chronically swollen digit

• Occurs in 16 – 48 % of PsA patients

• May be sole manifestation

• Ddx: TB, Syphilis, Gout

Olivieri, I et al J Rheumatol 2007

Taylor W et al Arthritis Rheum 2006

Dactylitis Old Concepts

Predominantly flexor tenosynovitisOlivieri 1996, Kane 1999, Wakefield 2000

Dactylitis

Kaeley G. Curr Rheumatol Rep. 2011;13:338-345.

Diffuse

Soft Tissue

Swelling

Synovitis

Contralateral

Normal ToePlantar

Tenosynovitis

Content Validity

Bakewell CJ, et al. J Rheumatol. 2013;40(12):1951-1957.

Ultrasound MRI

Year 2006 2006 1999 1996 2008 2008 2002 1997 1996 1995

Fournie Ribes Kane Olivieri Healy Olivieri Olivieri Olivieri Olivieri Jevtic

Definition or description of dactylitis NA Y† Y Y Y Y Y Y Y NA

Probe frequency (MHz) slice thickness 13.5 13.5 7-10 7.5 NA 3-5 mm 3-5 mm 3-7 mm 3-7 mm 3 mm

Elementary components

Soft tissue thickening Desc NA Desc Meas* NA NA NA Meas* Meas* Desc

Soft tissue edema Desc NA NA NA Desc Desc Desc Desc NA NS

Flexor tendon tenosynovitis Desc Desc Meas Meas Desc Desc Desc Meas Meas NA

Extensor tendon inflammation, thickening NA NA NA Meas* Desc Desc Desc Meas Meas* NA

Nail plate abnormalities NA NA NA NA NA NA NA NA NA NA

Nail bed / matrix abnormalities NA NA NA NA NA NA NA NA NA NA

Joint synovitis Desc Desc Desc Desc* Desc Desc Desc Desc Desc Desc

Bone-extraarticular osteoproliferaion Desc Desc NA+ NA NA NA NA NA NA NA

Bone-intraarticular osteoproliferaion Desc Desc NA NA NA NA NA NA NA NA

Erosions Desc Desc NA‡ NA Desc NA NA NA NA NA

Collateral ligament abnormalities NA NA NA NA Desc NA NA NA NA Desc

Bone edema NA†† NA†† NA†† NA†† Desc Desc* Desc NA NA Desc*

Sesamoid abnormalities / sesamoiditis Desc Desc NA NA Desc NA NA NA NA NA

Plantar / palmar plate abnormalities NA NA NA NA Desc NA NA NA NA NA

Ultrasound / MRI Definition of Dactylitis

or of Its Elementary Components Demonstrated by Study

Nail Changes

Normal Nail Bilayer

Obliteration of nail bilayer and

increased nail bed thickness

Fibers of extensor tendon

merge with proximal nail matrix

Images: GRAPPA, Kaeley, G

Palmar Plate Inflammation

Metacarpal Head - MH

Base of proximal phalange - Pb

Palmar Plate - PP

Volar recess - R

Volar Recess MCP JointPP

MH

Pb

R

Images: GRAPPA, Kaeley, G

Differentiation of Inflammatory Arthritis

• Early RA vs PsA: Dorsal MCP involvement

– 2.5% of patients with RA

– 54.1% of patients with PsA

Zabotti A, Salvin S, Quartuccio L, De Vita S. Differentiation between early rheumatoid and early psoriatic

arthritis by the ultrasonographic study of the synovio-entheseal complex of the small joints of the hands.

Clin Exp Rheumatol. 2016 May-Jun;34(3):459-65.

Enthesitis Images (Finger DIP/Dorsal)

** *

DP

MP

MP = Middle phalanx, DP = Distal phalanx,

* = Enthesophyte at Extensor tendon insertion onto distal phalanx, ** = enthesopathy of extensor

tendon (thickened, hypoechogenic, loss of fibrillar architecture)

BMI and Enthesitis Cont

• US indices should focus more on the smaller, peripheral joints commonly affected in PsAand not expected to be affected by BMI.

Zabotti A, Salvin S, Quartuccio L, De Vita S. Differentiation between early rheumatoid and

early psoriatic arthritis by the ultrasonographic study of the synovio-entheseal complex of

the small joints of the hands. Clin Exp Rheumatol. 2016 May-Jun;34(3):459-65.

New role: Axial evaluation?

• Sacroiliitis and spondylitis: may be a future role for contrast enhanced color doppler of SI joints

1. Klauser A, et al, Arth Rheum; 61, 2009.

Summary

• Sonography depicts extraspinal manifestations of spondyloarthropathy

– Synovitis, erosions, osteoproliferation

– Enthesitis—including ultrastructural changes of surrounding tissues

– Power Doppler allows detection of vascularity without use of contrast

Thank you!