TUI LATAM IV Targeted Ultrasound Initiative Meeting Agenda

TUI LATAM IV
TARGETED ULTRASOUND INITIATIVE (TUI)
A Targeted Ultrasound Approach in Practice
Date: Saturday 08th - Sunday 09th October, 2016
Time: 09.00 – 17.15 (Saturday); 08.30 – 13.30 (Sunday)
Where: Renaissance São Paulo Hotel, São Paulo, Brazil

WELCOME AND INTRODUCTION
www.targetedultrasound.net
Paul Emery has received an honorarium from AbbVie to support his participation in the TUI LATAM meeting

Meeting objectives: Saturday
• To introduce final RA ultrasound algorithms for
using US in diagnosis, monitoring and remission
assessment
• To discuss implementing RA ultrasound algorithms
in clinical practice at national level
• To discuss and update on US training and
educational national initiatives during a TUI poster
session
• To discuss challenging cases in a `hands-on’ US
patient session

Meeting objectives: Sunday
• To discuss challenging cases in an interactive
session
• To review key clinical and ultrasonographic
challenges in PsA
• To introduce the TUI PsA programme
• To consider how US is used to assess PsA in clinical
practice

Anticipated meeting outcomes
• RA
• Support for using the RA ultrasound algorithms in clinical practice
• Support for assessing the impact of the RA ultrasound algorithms on clinical
decision-making
• PsA
• Suggestions for developing tools and resources to support using US evaluation in
PsA

Agenda: Saturday
09.30 – 10.15 When to use US in the RA patient pathway
Paul Emery
10.15 – 11.15 Ambassador feedback and RA ultrasound algorithms – discussion
Chaired by Maria Antonietta D’Agostino
11.15 – 11.45 COFFEE BREAK
11.45 – 13.00 Poster session
Introduced by Annamaria Iagnocco
13.00 – 14.00 LUNCH
14.00 – 16.00 Hands-on session
Introduced by Esperanza Naredo
16.00 – 17.15 Discussion feedback and next steps
Paul Emery

Agenda: Sunday
08.00 – 08.30 REGISTRATION
08.30 – 10.00 Challenging cases
Chaired by Peter Balint and Esperanza Naredo
10.00 – 10.15 COFFEE BREAK
10.15 – 10.30 Introduction to TUI PsA programme
Maria Antonietta D’Agostino
10.30 – 10.50 PsA: What are our greatest clinical challenges?
Paul Emery
10.50 – 11.10 PsA: What are our greatest ultrasonographic challenges?
Annamaria Iagnocco
11.10 – 12.00 PsA elementary lesions and interactive session
Chaired by Richard Wakefield and Maria Antonietta D’Agostino
12.00 – 12.30 TUI 2017 programme
Paul Emery

Acknowledgements
• Special thanks to Ieda Laurindo and Karina Bonfiglioli for
enabling the hands-on session with the participation of
their patients
• Thank you to AbbVie for continuing sponsorship
• Fabiola Spila, Maysa Arruda, Paulo Freitas (Abbvie Brasil)
• Abed Haddad, Nicolas Pokorny Anna Droggiti (Abbvie Global)
• Thank you to GE for supporting the hands-on session
• Paulo Pontes Araujo, Kallil Chebaro
• Thank you for completing the PsA survey

WHEN TO USE US IN THE RA PATIENT PATHWAY
Paul Emery

5.7
• Absence of specific guidance on how to
use ultrasound (US) to diagnose and
manage patients with inflammatory
arthritis hindered the optimal utilization
of US in clinical practice
• Produced five novel algorithms which
identify when US could be used to aid
diagnosis, inform assessment of
treatment response/disease and
evaluate stable disease state or
remission in patients with suspected or
established RA
• Pragmatic templates for using US at
certain time points of RA management
RA ultrasound algorithms
D'Agostino MA, Terslev L, Wakefield R, Østergaard M, Balint P, Naredo E,
Iagnocco A, Backhaus M, Grassi W, Emery P. Ann Rheum Dis. 2016 Aug 23. pii:
annrheumdis-2016-209646. doi: 10.1136/annrheumdis-2016-209646. [Epub
ahead of print] Review correspondence to PE

RA ultrasound algorithm 1 - diagnosis
Flow chart showing the ultrasound (US) evaluation in patients at risk of rheumatoid arthritis (RA). Purple rectangle denotes population of interest
(starting point); blue-green rectangles denote possible; Paths of the algorithm and red rectangle denotes final diagnosis. ACPA, anti-citrullinated
peptide antibody; ACR, American College of Rheumatology; EULAR European League against Rheumatism; RF, rheumatoid factor

Algorithm 1: a) clinical synovitis seronegative
5.7
• 45-year-old male
• 2/12 month history of progressive pain in wrists, MCPJ
and PIPJ
• EMS – 60 mins
• Partial response to NSAID
• O/E:
• Tenderness of wrists, MCPJ/ PIPJ 2 + 3 bilaterally
• Swelling of right 2nd MCPJ
• Normal inflammatory markers
• Anti-CCP and RF negative

Algorithm 1: a) clinical synovitis seronegative US findings
• MCP 2, 3 PD2 +GS 3
• Erosion MCP 2
5.7

Early IA: Predictors in CCP/RF -ve patients
• Aim: To determine best predictors of persistence of hand IA – 12 months
• Method: 50 patients, <12 weeks, suspected IA, (EMS >60 mins), no DMARD
or steroid
– US scan: bilateral MCPJ, wrists: 12 J
• Results:
– All RF and CCP Ab patients developed RA (i.e. no added value for US)
– In CCP/RF negative patients
• Best predictors: PD ≥2, GS 3, US detected erosions
• Conclusions:
– Pre-test probability in seronegative group – 6%
– Post-test with one swollen and 1 CR erosion – 30%
– Post-test with PD ≥2, GS 3 and US erosion – 94%
Freeston JE, et al. Ann Rheum Dis 2010;69:417–419
CCP, cyclic citrullinated peptide; CR, conventional radiography; DMARD, disease-modifying anti-rheumatic drug; EMS, early morning stiffness; IA, idiopathic arthritis;
MCPJ; metacarpophalangeal joint; RF, rheumatoid factor

Algorithm 1: a) clinical synovitis seronegative US findings
• MCP 2,3 PD2 +GS 3
• Erosion MCP 2
• = very high chance of persistence: start MTX
• If US negative: likely self-limiting, give IM steroid
5.7

SEROPOSITIVE PATIENTS

Flow chart showing the ultrasound (US) evaluation in patients at risk of rheumatoid arthritis (RA). Purple rectangle denotes population of interest
(starting point); blue-green rectangles denote possible; Paths of the algorithm and red rectangle denotes final diagnosis. ACPA, anti-citrullinated
peptide antibody; ACR, American College of Rheumatology; EULAR European Leave against Rheumatism; RF, rheumatoid factor

Algorithm 1: b) at risk: arthralgia Ab +ve, NO clinical synovitis
5.7
• 38-year-old female
• 6/12 month history of progressive pain in wrists
• EMS - 10 mins; pain > stiffness
O/E:
• Hypermobile
• Puffiness bilateral UCJ; non tender
• CRP < 5, ESR 10mm/hr
• CCP Ab – 3.6 U/ml (N < 2.99)
• X-rays of hands and feet - normal

ACPA+ve selection model for primary care
• Tenderness of small joints present
• EMS ≥ 30 minutes
• High level RF and/or anti-CCP
Clinical
Rakieh C, Nam J, Hunt L; Emery Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal
symptoms: a prospective observational cohort study. ARD 2014
• 1
• 1
• 2

Model: secondary care
• Tenderness of small joints present
• EMS ≥ 30 minutes
• High level RF and/or anti-CCP
• Power Doppler present
• Shared epitope present
Clinical+Imaging+SE
•1
•1
•1
•1
•1

Aim:
To determine whether ultrasound can identify which anti-CCP antibody
positive patients with MSK symptoms and without clinical synovitis (CS)
progress to inflammatory arthritis (IA).

Predictive value of US in ACPA + patients with no clinical
synovitis
Nam J …….Emery P Ann Rheum Dis 2016
• 167 individuals >3000 joints scanned, 33% with PD signal
Progression to clinical synovitis
• PD = 0 5%
• PD = 1 16%
• PD = 2 55%
Risk of clinical swelling in a joint with PD signal >2
• 55% vs 4% Hazard Ratio= 31 (CI 16 to 63), p<0.001
Progression occurred earlier with PD ≥2
• median 7 vs 52 months

Algorithm 1: b) at risk: arthralgia Ab +ve, NO clinical synovitis
• Grade 2 Grey scale and Grade 2 PD in both ulnar carpal joints
• Mild erosive change of the ulna styloids bilaterally
Conclusion: grade 2 PD and erosions –changes risk from
low to moderate of progression to clinical arthritis

Algorithm 1: c) at risk: arthralgia Ab +ve, NO clinical synovitis
5.7
• 4 months ago, left shoulder pain; impingement
symptoms → injected
• Now c/o aching of wrists and stiffness in fingers
• CCP Ab 300U/ml
• Clinical examination of hands tender

Algorithm 1: c) at risk: arthralgia Ab +ve, NO clinical synovitis
• PD >1 in 2 MCPs
• SE +ve
• Changed risk of progression to clinical synovitis
from moderate to high

Algorithm 1: d) at risk: Ab +ve, clinical synovitis
• 45-year-old female, c/o inflammatory hand pain for 8 weeks
• EMS – 45 mins
• 50% response to NSAIDs which she continues to take:
• Mild swelling in Right 2 MCPJ
• Investigations:
• Serology: RF+ and ACPA –ve, CRP 12 mg/dl
• X-rays hand and feet - normal
• Insufficient to make diagnosis of RA
• When clinical synovitis present can use imaging to define number of
affected joints

US findings
• Total synovitis scores
GS = 9
PD = 5
Combined = 9
• Ultrasound Report
• Synovitis scores
R 2 MCPJ GS 3, PD 3
R 2 PIPJ GS 1, PD 0
R 3 PIPJ GS 1, PD 0
L 2 MCPJ GS 2, PD 2
L 2 PIPJ GS 1, PD 0
L 3 PIPJ GS 1, PD 0
One erosion R 2 MCP
Mild OA – PIPJ
No evidence of crystal disease
6 joints
Score 6 = RA, Rx MTX)

Flow chart showing the ultrasound (US) evaluation in patients who fulfil American College of Rheumatology (ACR)/European League
Against Rheumatism (EULAR) criteria. Purple rectangle denotes population of Interest (or starting point); blue-green rectangles denote
possible paths of the algorithm and red rectangle denotes final diagnosis.

• 3-month history of pain in wrists, hands, knees and ankles
O/E
• EMS = 120 mins
• Swollen 4 MCPJ and 4 PIPJ, both knees and 2 MTPJ
• CRP – 40 mg/dl
• X-rays – no erosions
Algorithm 2: a) patients who fulfil EULAR/ACR criteria

Algorithm 2: patients who fulfil EULAR/ACR criteria
Grey scale 2-3 and PD≥ 2 synovitis in both wrists, 4 MCPJ and 3
PIPJ and 5 MTPJ
Mild erosive change on lateral aspect of one 5th MTPJ
Conclusion: Polyarticular inflammation with marked PD and
early erosive change = poor prognosis for aggressive therapy

• 6-month history of pain in wrists, hands, knees and ankles
• O/E
• EMS = 20 mins
• Swollen 4 MCPJ and 4 PIPJ, CRP<5 mg/dl
• RF positive
• X-rays – no erosions
Algorithm 2: b) patients who fulfil EULAR/ACR criteria

• No significant synovitis GS<2 and small effusion of MCP2
• Changes diagnosis –not RA
Algorithm 2: b) patients who fulfil EULAR/ACR criteria
US findings

RA ultrasound algorithm 3 – therapeutic response
Flow chart showing the ultrasound (US) evaluation of therapeutic response in patients with rheumatoid Arthritis (RA) starting
csDMARDs or bDMARDs. Purple rectangle denotes population of interest (or) starting point); red text denotes csDMARDs; blue text
denotes bDMARDs; blue-green rectangles denote possible paths of the algorithm; red rectangle denotes proposed path for
csDMARDs population and blue rectangle denotes proposed path for bDMARDs.

Algorithm 3: initial assessment: csDMARD good response
US no PD
• Continue therapy
US significant PD
• What was baseline synovitis?
• If improved, continue therapy?
• If no change, escalate therapy
• With bDMARD continue therapy, as will not erode?

Algorithm 3: initial assessment : csDMARD poor response
US no significant PD
• If improved continue therapy
• If no change think of pain therapy
US significant PD
• Change/escalate therapy

RA ultrasound algorithm 4 – loss of response
Flow chart showing the ultrasound evaluation in patients with rheumatoid arthritis with loss of treatment Response (both
conventional synthetic or biological disease-modifying anti-rheumatic drugs). Purple Rectangle denotes population of
interest (or starting point) and blue-green rectangle denote possible paths of the algorithm.

Algorithm 4: loss of response
US significant PD
• Change/escalate therapy
US no significant PD
• If improved continue therapy but improve pain relief
• If no change think of pain therapy

RA ultrasound algorithm 5 – low disease
activity/remission
Flow chart showing the ultrasound evaluation in assessing remission or low disease activity in patients with
rheumatoid arthritis. Purple rectangle denotes population of interest (or starting point) and blue-green
rectangle denote possible paths of the algorithm.

Algorithm 5 – low disease activity/remission
• 56-year-old woman seropositive RA for 7 years
• In remission with MTX and TNF alpha blocker (DAS28< 2.1) for 12
months
• No tender joints but 1 swollen wrist with limited ROM
• No morning stiffness, CRP< 5 mg/l
• Tapering biological treatment
• Would you taper biological treatment?
• Would US aid decision?

Remission post TNFi discontinuation
Relapse-free period predicted only by US
Time after discontinuation of biologics (months)
DAS28 GS score PD score
Iwamoto T, Ikeda K, et al. Arthritis Care Res 2014

CHALLENGING CASES
Chaired by Esperanza Naredo and Peter Balint
Esperanza Naredo and Peter Balint have received honoraria from AbbVie to support their participation in the TUI LATAM meeting

CHALLENGING CASES – CASE 1
Presented by Oscar Sedano
ECOSERMEDIC, Lima, Peru

Case 1: clinical history
• 45-year-old male diagnosed with
psoriasis of 15 years evolution
• Referred for arthralgia in knees, ankles
and feet
• Clinical examination: no synovitis,
enthesis, painful knees and heels
- nail lesions in 3rd/4th finger of the hands
• ultrasound - 5 enthesis and nails
Images courtesy of Oscar Sedano

Case 1: ultrasound nails GS

Case 1: ultrasound nails GS & PD
healthy control
EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Ann Rheum Dis 2015;74:1327
PsA

Case 1: ultrasound nails PD

Case 1: differential diagnosis
onychomycosis viral warts
melanoma trauma

Case 1: ultrasound nails RA

Case 1: ultrasound nails scleroderma
18 Mhz 22 Mhz

Case 1: ultrasound nails & microvasculature

Case 1: conclusions
• Nail involvement is present and predicts PsA
• US is useful for diagnosis, monitoring, evaluating
microvasculare involvement, enthesitis and
differential diagnosis
• Ultrasound PsA should
include nail studio in
clinical practice

Presented by Karina Bonfiglioli
University of São Paulo - FMUSP

Case 2: clinical picture and history
• MCN, 66 years, female, caucasian
• RA since 2006, RF- /anti-CCP-
• Multiple changes in therapy due to toxicity
• Good response to anti-TNF in monotherapy
• etanercept since 2014
• Co-morbidities: hypertension

Case 2: history
• Feb 2016: frequent flares
• arthritis in both knees, ankles and feet
• Using intramuscular bethmethasone (self-medication),
after feeling better for about 1 month, new flare
• US for evaluation of RA activity and probably drug switch

Case 2: 3rd MTF (right)
Images courtesy of Karina Bonfiglioli

Case 2: right knee

Case 2: follow up
• Seric uric acid: 9.7
• Treatment with alopurinol and colchicine (peptic ulcer,
contraindication for NSAIDs)
• Patient had no new episodes of arthritis and remains in
clinical remission (DAS 2.3)

Case 2: discussion points
• Long-standing RA, presenting flares during anti-TNF
monotherapy: first impression was secondary failure,
leading to a switch in biological therapy
• US presented an unexpected diagnosis, that entirely
changed the clinical approach

CHALLENGING CASES - CASE 3
Presented by José Alexandre Mendonça
Pontifical Catholic University of Campinas

Case 3: introduction
• The association of ocular disorders and psoriatic
arthritis was first reported in 1976 by Lambert and
Wright in a study of 112 patients
• Ocular inflammation was noted in 35 (31.2%) patients
Lambert JR, Wright V. Eye inflammation in psoriatic arthritis. Ann Rheum Dis. 1976; 35: 354–356; Paiva ES, Macaluso DC, Edwards A, Rosenbaum JT.
Characterisation of uveitis in patients with psoriatic arthritis. Ann Rheum Dis. 2000; 59 (1):67-70

Case 3: introduction - vitritis images
Mendonça J.A. Ultrasound Color histogram assessment allows better view of echotexture damage. Brazilian Journal Rheumatology 2014
http://dx.doi.org/10.1016/j.rbr.2014.12.016
• Ultrasound colour histogram
assessment allows better view of
echotexture damage
Images courtesy of J.A. Mendonça

Case 3: introduction - vitritis images
Image courtesy of J.A. Mendonça
Mendonça J.A. Ultrasound Color histogram assessment allows better view of echotexture damage.
Brazilian Journal Rheumatology 2014 http://dx.doi.org/10.1016/j.rbr.2014.12.016

Case 3: introduction – vitritis images
Images courtesy of J.A. Mendonça

Case 3: clinical history
• Patient, 28 years, male, soccer player
• Previously diagnosed with psoriasis
• Referred to the rheumatology service due to arthralgia
(inflammatory characteristics) in his right knee and ankle
• Diagnosis of psoriatic arthritis
• Ophthalmological examination without changes
• Referred to ultrasound for assessment of joint and eye

Case 3: vitritis detected in the left eye, with
free inflammatory bodies
Image courtesy of J.A Mendonça

Case 3: vitritis detected in the left eye, with
free inflammatory bodies

Case 3: right knee ultrasound examination detected
enthesitis with intense Doppler signal at the
proximal insertion of the patellar tendon

Case 3: effusion in right ankle

Case 3: conclusion
• Ocular ultrasound may be an important diagnostic tool
for suspected cases of sub-clinical ophthalmologic
involvement in psoriatic arthritis

Presented by Karina Bonfiglioli
University of São Paulo - FMUSP

Case 4: introduction to Chikungunya fever
• Chikungunya fever (CF): arboviruses 1
• Polyartralgia is the main clinical feature
• Can become chronic (>3 months)
• 10 to 60% up to 3 - 5 years 2
• South America: Epidemic since 2013
• Brazil, 2016: 137,808 cases until June 3
1. Emilie Javelle, Anne Ribera, Isabelle Degasneet et al. Specific Management of Post-Chikungunya Rhematic Disorders: A
Retrospective Study of 159 Cases in Reunion Island from 2206-2012. PLOS Neglected Tropical Diseases; 2. Pineda C, Muñoz-Louis
R, Caballero-Uribe CV, Viasus D. Chikungunya in the Region of the Americas. A challenge for Rheumatologists and Health Care
Systems. Colin Rheumatol 2016 aura 24; 3. Boletim epidemiológico 2016;47(20)

Case 4: history
• MS, female, 45 years old, resident in north east of
Brazil (Bahia)
• No previous rheumatic conditions
• Presented with fever (38˚C) and acute, disabling
polyarthralgia in March 2016
• After acute illness, polyarthralgia persisted
• US evaluation in July/2016 (four months)

Case 4: flexor tenossynovitis 3 MCF D

Case 4: arthritis

Case 4: other observed findings
• Enthesitis
• Carpal tunnel syndrome
• Erosions??

CHALLENGING CASES - CASES 5, 6, 7
Presented by Esperanza Naredo
Esperanza Naredo has received an honorarium from AbbVie to support her participation in the TUI LATAM meeting

Case 5: history
• 45-year-old, previously healthy male
• Pain and swelling at the medial
aspect of the left elbow
• Cut in finger 3 days ago
Image courtesy of Esperanza Naredo

Case 5: US findings
• US: medial aspect of the elbow, sonographic palpation +
US diagnosis?
Images courtesy of Esperanza Naredo

Case 5: US findings
• US: medial aspect of the elbow, sonographic palpation +
US diagnosis? reactive lymphadenopathy

Case 6: history
• 65-year-old RA male, MTX 20 mg/w, clinical remission
• Motion and nocturnal pain in left shoulder over the
previous month

Case 6: US findings
• US left shoulder, SE tendon trans/long and
bicipital groove trans
US diagnosis? US-guided aspiration:
haemorrhagic fluid Images courtesy of Esperanza Naredo

Case 6: US findings
• US left shouder, SE tendon long and bicipital
groove trans
Diagnosis? Bronchogenic carcinoma with
bone metastasis

Case 7: history
• 76-year-old female with hand OA
• Severe inflammatory pain in both shoulders with marked
functional limitation over the previous 2 weeks
• Increased ESR (50 mm/1st h) and CRP (2.0,normal 0-0.5
mg/dL)
• Normal blood count and biochemistry
• Negative RF and ACPA

Case 7??
• Differential diagnosis?
RA? PMR?

Case 7: US shoulders
Image courtesy of Esperanza Naredo

Case 7: US wrist and knee

Case 7: US-guided aspiration of SASD bursa
synovial fluid
• 40,000 white blood
cells/mm3
• Negative culture
• Microscopic
identification of CPPD
crystals

Case 7: ??
• Diagnosis?
CPPD

INTRODUCTION TO THE TUI PSORIATIC ARTHRITIS PROGRAMME
Maria Antonietta D’Agostino
Maria Antonietta D’Agostino has received an honorarium from AbbVie to support her participation in the TUI LATAM meeting

TUI is a pragmatic educational programme
• TUI concept = US should be a standard outcome measure in RA
Wakefield et al. ARD 2012 71(6):799-803
D’Agostino et al. Ann Rheum Dis 2016
DRIVING CHANGE TARGETING
UNMET NEED
AUDIT TO SHOW
BENEFIT

TUI achievements so far
• Engagement in national activities
Global Network of National TUI Ambassadors
• Practical Support via website training resources and clinical
practice tools www.targetedultasound.net
Global Education and Resource Platform:
Tools for Clinical Practice, Training Materials
• TUI Concept Paper, TUI Statements, RA
Ultrasound Algorithms
Promoted Understanding of MSUS Role and
Application in Clinical Practice

Setting the scene
Considerable
logic and big
demand for
ultrasound
TUI
A pragmatic,
educational approach
to promote US as a
standard outcome in
RA
Several achievements so far:
- Educational programmes
- Statements
- Network of ambassadors
- Algorithms
Need for:
• Implementing this
approach to other
inflammatory
diseases:
• Psoriatic Arthritis
• SpA

Why TUI PsA?
Better classification of
the disease
Introduction of effective
therapies
Increase in demand for
efficient tools in PsA
Increased research
effort within imaging
Better dissemination
of US and better
applicability
PsA

PsA has a heterogeneous clinical appearance
• And, accordingly, imaging findings can vary
spinal
Manifestations
peripheral
articular
manifestations
peripheral
enthesitis
manifestations
dactylitis
cutaneous
manifestations
SKIN
NAILS
McInnes I.B. Clin Exp Rehumatol 2016;34(Suppl.98):S9-S11

PsA which lesions to target?
PsA: why US?
• Joint?
• Enthesis?
• Dactylitis?
• Extra-articular sites?
Images courtesy of Maria Antonietta D’Agostino

US spectrum in PsA
Are all adapted for the purpose?
What is the goal of TUI in PsA?
Images courtesy of Maria Antonietta D’Agostino

Current status of US in PsA
• US can detect inflammatory and structural lesions
• Skin, enthesis and peritenon seem specific features
• Potential for improvement of PsA management
Kaeley GS Curr Rheumatol Rep 2011 Aug;13(4):338-45, Gutierrez M, et al. Clin Rheumatol 2015 Aug 23 [Epub ahead of print], Coates L et al, Best Pract Res Clin
Rheumatol 2012 Dec;26(6):805-22, Grassi W and Gutierrez M J Rheumatol Suppl 2012 Jul;89:39-43

Proposed role of US in PsA management
Making/confirming
a diagnosis
evaluating
disease activity
VERIFYING
RESPONSE/ADJUSTING
THERAPY
CONFIRMING REMISSION
+
REMISSION
Predicting
successful medication
de-escalation
+

Initial promising data: US for making
a diagnosis/confirming PsA
• Patient with
psoriasis
• PsA?
2) symptomatic
patients
3) early arthritis
1) at risk patients (?)
• Patients with
arthralgia

Initial promising data: US for monitoring PsA
2) Verifying
response
3) Confirming
remission and successful
medication de-escalation
and progression
1) Evaluating
disease activity

Open questions
• Which lesions should we target by US?
• Should we use a composite scoring system ?
• Should we propose a standardized approach? mannequin?
• Time points of evaluation (minimal time point)
• Define minimal level of activity/normality
• Threshold in remission
• Threshold of sub-clinical activity
• Educational needs

TUI PsA Programme
• To extend the principles of the TUI RA programme to a
TUI PsA programme
• TUI PsA vision: to use US to improve the outcome of
patients with PsA through better defining treatment
response and disease state

TUI PsA programme objectives
• Share the ultrasonographic
challenges in PsA
• Discuss which lesions are targeted
with US in clinical practice
• Based on ambassador feedback from 2016 TUI
Programme and PsA survey, work on achieving
consensus for a standardized US approach:
• Which lesions to target?
• How to detect them?
• How many target lesions?
• PsA Patient Pathways for diagnosis, disease and
treatment monitoring, remission evaluation
• Stimulate and develop educational activities around PsA
Today’s focus 2017 onwards focus

TUI is a pragmatic educational programme
TUI Concept: promoting ultrasound as a standard outcome in inflammatory
arthritis
TUI PsA: developing tools and resources to aid ultrasound assessment
targeting
unmet need
target lesions patient
pathways
audit to show
benefit
TUI PsA: developing tools and resources to aid ultrasound assessment

TUI PsA: WHAT ARE OUR GREATEST CLINICAL CHALLENGES?
Paul Emery

Psoriatic arthritis: a complex disease
• Peripheral arthritis
• Polyarthritis
• Oligo-arthritis
• SpA
• Axial
• Enthesitis
• Extra-articular
• Nails
• Skin
McInnes I.B. Clin Exp Rehumatol 2016;34(Suppl.98):S9-S11

Clinical remission concept key questions
• How appropriate are the various remission definitions for the
different disease phenotypes (e.g. peripheral and axial disease,
enthesitis and dactylitis)?
• Pros/cons of the different definitions of clinical remission in
psoriatic arthritis (PsA) What is the most appropriate definition
of clinical remission from (a) the physician’s and (b) the
patient’s perspective?
• Responsiveness of remission criteria according to different
disease phenotypes and stages of disease

1. Individualised to the patient
• Perfect for every patient
• Takes into account their:
• Disease manifestations
• Past disease history
• Past treatment
• Personal opinions
• Isn’t this normal care?
• What measure can you
use?
• Does disease get missed?

2. DAPSA: PsA specific but only joints
• Quick
• Feasible
• Easy to calculate
• Accounts for most of
disease for most people
• Continuous score,
response measure and cut
offs for disease states
• Sensitive to change
• What about
• Skin and nail psoriasis
• Enthesitis
• Dactylitis
• Axial disease
• Skin excluded due to PsA
cohort
• Cut offs based only on
physician opinon
• Current measure needs
CRP (delay)
TJC + SJC + Pt pain VAS + Pt global VAS + CRP or ESR = DAPSA
Schoels et al, Ann Rheum Dis. 2015 Aug 12. [Epub ahead of print]

3. MDA: PsA specific but global
• Pretty quick and feasible
• Flexible on individual
measures
• Accounts for nearly all
disease for most people
• No bloods required
• Correlates well with Pt opinion
• Used in T2T study
• Modified versions (MDAjts,
MDA-6 and MDA-7)
• Only a measure of disease
state, not continuous
• Requires joints, skin and
enthesis exam
• Could allow active joint
disease
Coates LC, et al. Ann Rheum Dis 2010;69(1):48-53; Coates et al J Rheum 2016;43:371–5

4. PASDAS/CPDAI: PsA specific but global
• Feasible (just)
• Accounts for nearly all disease
for most people
• Measure of disease activity,
response measures and
disease states
• PASDAS developed on real life
treatment decisions
• Disease states based on phys
and pt opinion
• Bit slower
• CPDAI not evidence based
• Requires joints, (skin) and
enthesis exam
• Need SF36 (PASDAS)
• Need online
calculator
(PASDAS)
• Need CRP
(PASDAS)
Phys global, Pt global, SF36-PCS, SJC, TJC, enthesitis, dactylitis, CRP = PASDAS
Peripheral joints, skin, enthesitis, dactylitis, axial disease all 0-3 = CPDAI
Helliwell et al ARD. 2013 Jun;72(6):986-91; Mumtaz et al ARD. 2011 Feb;70(2):272-7
PASDAS Improve >2 1-2 <1
Final score
<2.3
2.3-4.7
>4.7

5. RAPID: Not PsA specific
• Very quick
• All done by patient
• Feasible
• Highly sensitive to change
• No bloods required
• Questions not
specific to PsA and
all MSK not skin
• No specific physician
exam at all
(objectivity)
• Cut offs not validated
yet in PsA
Patient pain VAS + Patient global VAS + Function = RAPID3
Pincus et al Bull NYU Hosp Jt Dis. 2009;67(2):211-25

Hierarchy of potential measures
PASDAS
Pt global
Pt pain
Function
Joints and entheses
Dactylitis
Inflammatory marker
Phys global
MDA
Pt global
Pt pain
Function
Joints and entheses
Skin
RAPID3
Pt global
Pt pain
Function

PsA remission remaining questions
• Which target should we choose?
• Minimal level of activity/normality?
• Impact of disease duration on the likelihood of achieving
certain targets?
• Which dosing strategy should we apply?
• What is importance of sub-clinical synovitis/enthesitis?

0.87
-0.51 -0.44
-2
-1
0
1
2
n=95 n=116 n=95
All patients
0.28
-1.29 -1.24
-2
-1
0
1
2
n=54 n=57 n=48
MTX at BL
(all patients) 1.64
0.25 0.38
-2
-1
0
1
2
n=41 n=59 n=47
Achieving MDA associated with reduced radiographic
progression at Week 256 in the GO-REVEAL study
116
MeanSHSscore
* *****
Without MTX at BL
(all patients)
***
never achieved MDA achieved MDA ≥3 consecutive visits achieved MDA ≥4 consecutive visits
*p<0.005 vs never achieved MDA; **p<0.01 vs never achieved MDA
***p<0.0001 vs without MTX at baseline
SHS, PsA-modified Sharp–van der Heijde Score Kavanaugh A, et al. ACR 2013;#341

WHAT CAN IMAGING OFFER IN PSORIATIC ARTHRITIS?

Making a diagnosis in Psoriatic DISEASE
• Patient with psoriasis
1) At risk patients (?)
2) Symptomatic
patients
• Patients with pain/ arthralgia
3) Early arthritis • PsA?

PsO without MSK symptoms
Naredo et al. Rheumatology 2011 Oct;50(10):1838-48

PsO and pain: PsA vs fibromyalgia
Marchesoni A, et al Journal of Rheumatology 2012 Jul;89:29-31

PsO +MSK diagnosis: predictors of damage
Miedany Y, et al Clin Rheumatol 2015;34:307-313

PsO +MSK diagnosis: Early PsA vs RA
Iagnocco A, et al. Joint Bone Spine 2012;:323-334
• PDUS evaluation of enthesitis in psoriatic arthritis

PsO +MSK diagnosis: sub-clinical inflammation
Freeston J, et al. Arthritis Care Research 2014;66:432-9
• 75% of patients with early PsA have sub-clinical disease
• Median no. of joints involved: 3
• wrist, knee and MCPs

PsO +MSK monitoring: enthesitis
Naredo E, et al. J Rheumatol 2010 Oct;37(10):2110-7
Doppler ++++

PsO +MSK monitoring: PDUS Target
Baseline
Images courtesy of M. Gutierrez8 weeks

TUI PsA: WHAT ARE OUR GREATEST ULTRASONOGRAPHIC
CHALLENGES?
Annamaria Iagnocco
Annamaria Iagnocco has received an honorarium from AbbVie to support her participation in the TUI LATAM meeting

Ultrasound in PsA: target lesions
• enthesitis
• paratenonitis
• fascitis
• synovitis
• bursitis
• tenosynovitis
• dactylitis
• bone abnormalities:
• erosions
• osteoproliferation
• nail
• skin
• subcutaneous tissue
peripheral (joint & peri/extra-articular)

US IN ENTHESITIS

Enthesis
5.7
• The region where a tendon, ligament, or joint capsule is
attached to the skeleton
Image courtesy of EULAR
4 consecutive areas:
• dense fibrous connective tissue
• uncalcified fibrocartilage
• calcified fibrocartilage
• bone
fibrous enthesis
fibrocartilaginous enthesis
Enthesitis associated with SpA is typically
located at the fibrocartilaginous attachments
EULAR Online MSUS Course

PDUS of enthesis
5.7
Images courtesy of Annamaria Iagnocco

Enthesitis is a landmark of SpA
structural changes
at entheses
• enthesophytes
• intratendinous calcification
• fissuring
• cell clustering
• fibrillation
• delamination of fibrocartilage
• necrosis
• cyst formation
• inflammatory cell infiltration
• lining cell hyperplasia
• formation of synovial villi
inflammatory changes
in the synovial
component of the SEC
Benjamin et al AR, 2007

Enthesitis is a landmark of SpA
• US may detect more enthesitis than clinical examination
• PD signal at bony attachment is typical of inflammatory enthesitis
tendinitis
enthesitis
bursitis
D’Agostino et al A&R 2002, D’Agostino et al A&R 2003, D’Agostino et al A&R 2009, D’Agostino et al ARD 2011, De Miguel et al A&R
2009, De Miguel et al ARD 2009, De Miguel et al ARD 2011
Image courtesy of Annamaria Iagnocco

How to define enthesitis by US? OMERACT US enthesitis
task force
• thickening of tendon insertion into the
bone (<2mm)
• hypoechogenicity of tendon insertion
• Doppler activity (i.e. hypervascularity) of
tendon insertion
• enthesophytes
• calcifications
• erosions

PDUS & enthesitis
Inflammatory abnormalities:
• hypoechogenicity
• thickening
• Doppler (entheseal pathological vascularization)
Structural damage lesions:
• erosions
• enthesophytes
• calcifications
• entheseal changes/local inflammatory activity/structural lesions

PDUS & structural damage
Inflammatory abnormalities (entheses)
• hypoechogenicity
• thickening
• Doppler (entheseal pathological vascularization)

PDUS & enthesitis

Enthesitis

Elbow CET enthesitis

Plantar fascitis

PDUS in enthesitis: structural damage
Structural damage (entheses)
• erosions
• enthesophytes
• calcifications

PDUS in enthesitis: structural damage

Enthesitis & structural damage

US IN SYNOVITIS, BURSITIS, TENOSYNOVITIS AND DACTYLITIS

PsA: pathological characteristics
synovial inflammation
• synovitis
• tenosynovitis
• bursitis
paratenonitis
structural damage
• bone erosions
• osteoproliferation

PDUS in PsA: synovitis & paratenonitis and also

US in PsA: bony cortex abnormalities
osteoproliferation
erosions

PsA: joint abnormalities by PDUS
synovitis
osteoproliferation
erosions

synovitis
osteoproliferation
erosions

OMERACT US elementary lesions of active dactylitis
• superficial oedema – anechoic areas within subcutaneous tissues
• soft tissue thickening
• nail plate bilayer obliteration, nail bed thickening and nail bed
hypervascularity
• tenosynovitis
• profundus enthesitis – abnormalities insertion and vascularity
• collateral ligament thickening, hypervascularity
• synovitis
Bakewell CJ, et al. OMERACT Ultrasound Task Force. J Rheumatol 2013 Dec;40(12):1951-7

PsA: dactylitis

PsA: Baker’s cyst
Image courtesy of Annamaria Iagnocco

Nail changes
Loss of nail bilayer and
increased nail bed and extensor
tendon thickness
Normal tri-laminar
appearance
Fibers of extensor tendon
merge with proximal nail matrix
Images courtesy of M.A. D’Agostino and S. Aydin

PsA: What are our greatest US challenges?
• Detection and scoring of inflammatory abnormalities
• Assessment of structural damage
• role in early?
• US evaluation: which lesions for which purpose?
• diagnosis
• follow-up
• responsiveness
• disease activity/remission

TUI LATAM IV Targeted Ultrasound Initiative Meeting Agenda

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