This is a presentation on Ultrasound and Systemic Sclerosis, and engaging presentation on new technologies and developments with scleroderma.

1. Ultrasound and Systemic
Sclerosis
Duncan F. Moore, MD, RhMSUS
Northwestern Scleroderma Program
October 21, 2023

2. Disclosures
• None
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3. 3

4. Objectives
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• Understand what ultrasound is and its advantages as type of imaging study.
• Describe the benefits of using ultrasound in the evaluation and management of
systemic sclerosis (SSc) and associated rheumatologic conditions.
• Identify limitations of ultrasound in the assessment non-musculoskeletal aspects
of SSc and how further research can help reduce these limitations.

5. What is ultrasound?
• Transducer generates inaudible
ultra high-frequency sound waves
-  Waves penetrate tissue
-  Reflected back with variable
intensity and deformation
based on what they are passing
through
-  Computer generates an
image
• Exam typically performed by an
ultrasound technician and
interpreted by a radiologist
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6. Why use ultrasound?
• Cheap
• Quick
• All patients can be examined
• Dynamic evaluation
• Can be performed at the point of
care by a physician
-  immediately impact care plan
-  guide procedures
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7. Why use ultrasound in systemic sclerosis?
• Detect and define musculoskeletal
disease manifestations
• Measure skin thickness
• Detect scleroderma-related lung disease
• Detect and target calcinosis
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8. Ultrasound in Systemic Sclerosis
• The physical exam of joints underneath thickened skin
can be difficult.
• Hand pain is common in SSc
- But frank inflammatory (autoimmune) arthritis is
thought of as uncommon in SSc
• However, in one 2012 study it was noted that while only
15% of SSc patients had synovitis on exam, 46% had
synovitis as determined by ultrasound exam1
• A 2020 study similarly noted 25% of patients with synovitis
on exam but 52% of patients with synovitis on ultrasound2
Detecting andDefining Musculoskeletal Disease Manifestations
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1. Elhai et al. Arthritis Care Res (Hoboken). 2012 Aug;64(8):1244-9.
2. Hubac et al. Joint Bone Spine. 2020 May;87(3):229-233.

9. Ultrasound in Systemic Sclerosis
• Hand pain is common in SSc
- Osteoarthritis (OA) often co-occurs with SSc
- In a 2021 study by Dr. Fairchild at Stanford1
• 49% of SSc patients had osteophytes (bone spurs
from OA)
• Noted high concordance of osteophytes with
joint swelling and tenderness, suggesting that
OA may be a significant contributor to joint pain
in SSc patients
• (~ 20% of SSc patients had inflammatory arthritis)
Detecting andDefining Musculoskeletal Disease Manifestations
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1. Fairchild et al. Semin Arthritis
Rheum. 2021 Aug;51(4):735-740.

10. Ultrasound in Systemic Sclerosis
• Hand pain is common in SSc
- Carpal tunnel syndrome can develop in early
scleroderma
- A 2011 case series describes ultrasound-guided
carpal tunnel “hydrodissection” and steroid
injection in 12 SSc patients1
•  improvement in pain 67% of patients and reduced
Raynaud’s and digital ulcers in 83% of patients
• “The mechanism may be a combination of…mechanical
freeing of entrapped arteries, nerves, and tendinous
structures and corticosteroid-induced reduction of
inflammatory vasospasm.”
Detecting andDefining Musculoskeletal Disease Manifestations
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1. DeLea et al. Clin Rheumatol. 2011 Jun;30(6):805-13.
Case courtesy of Maulik S Patel, Radiopaedia.org, rID: 21715
BruceBlaus, CC BY 3.0, via WikiMedia Commons

11. Ultrasound in Systemic Sclerosis
• Skin thickening assessment is highly variable
between examiners and even within serial
examination by the same physician.
• Numerous studies have reported ultrasound
measurement of skin thickness outcome
measure.
- Example: Trial of tofacitinib vs. methotrexate –
mean reduction of skin thickness at 52 weeks of
treatment was -0.31mm vs. -0.075mm (95% CI -
0.27 to -0.19, p < 0.001)1
• Multiple studies have reported excellent
inter-rater and intra-rater reproducibility.
Measuring Skin Thickness
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Li et al. Arthritis Res Ther. 2018 Aug 16;20(1):181
1. Karalilova et al. Rheumatol Int. 2021 Oct;41(10):1743-1753.

12. Ultrasound in Systemic Sclerosis
• However, standardization and validation are
lacking.
- What sites should be routinely measured?
- What ultrasound machine settings should
be used?
- What is the definition of normal vs.
abnormal skin thickness?
- What is the definition of a clinically-
meaningful change?
Measuring Skin Thickness
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Li et al. Arthritis Res Ther. 2018 Aug 16;20(1):181

13. Ultrasound in Systemic Sclerosis
• Santiago et al. (2022):
- “Ultrasound is a valid and reliable
tool for skin thickness
measurement in SSc but there
are significant knowledge gaps
regarding skin echogenicity
assessment by ultrasound…in
terms of feasibility, validity and
discrimination. Standardization of
image acquisition and analysis is
needed to foster progress.”
Measuring Skin Thickness
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• Santiago et al. (2019):
- “Published reports have strong
limitations and are highly heterogeneous,
hindering the evidence to support the
use of skin ultrasound assessment in
clinical practice. Further studies, with
modern devices and appropriate
methodology, are needed to establish the
real value of skin ultrasound assessment
in the early diagnosis and monitoring of
SSc patients.”
1. Santiago et al. Arthritis Care Res (Hoboken). 2019 Apr;71(4):563-574.
2. Santiago et al. Semin Arthritis Rheum. 2022 Feb:52:151954.

14. Ultrasound in Systemic Sclerosis
Detecting SSc-Related LungDisease
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Gargani et al. Rheumatology (Oxford). 2022 Apr 18;61(SI):SI56-SI64.
• 2020 review article1:
- “Despite a great deal of work
supporting the potential role of
LUS for the assessment of ILD-
SSc, much remains to be done
before validating its use as an
outcome measure in ILD-SSc.”
- Insufficient evidence for
criterion validity, reliability, and
sensitivity to change.
1. Gutierrez et al. J Rheumatol. 2020 Jul 1;47(7):991-1000.

15. Ultrasound in Systemic Sclerosis
Detect andTarget Calcinosis
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Boutry et al. Eur Radiol. 2007 May;17(5):1172-80.
• 2022 case series1:
- Five patients with calcinosis
cutis
- Treated with ultrasound-
guided intralesional sodium
thiosulfate injections
- Ultrasound was used to
confirm response to
treatment
1. Tubau et al. J Ultrasound. 2022 Dec;25(4):995-1003.

16. Summary
• Ultrasound is a quick, affordable, accessible, and highly-versatile diagnostic
modality.
• In rheumatologic conditions, including systemic sclerosis, point-of-care
ultrasound can inform the clinical exam and assessment during the clinic visit.
• Inflammatory arthritis is under-diagnosed in systemic sclerosis.
• Osteoarthritis is common in systemic sclerosis and a large contributor to hand
pain.
• Ultrasound guidance can improve performance of challenging procedures in SSc
like carpal tunnel injection and calcinosis injections.
• Ultrasound assessment of skin thickening and interstitial lung disease in systemic
sclerosis requires further standardization and assessment of clinical utility.
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17. References
1. Elhai M, Guerini H, Bazeli R, Avouac J, Freire V, Drapé J-L, et al. Ultrasonographic hand features in systemic sclerosis and correlates with clinical, biologic, and radiographic
findings. Arthritis Care Res (Hoboken) 2012;64:1244–1249.
2. Hubac J, Gilson M, Gaudin P, Clay M, Imbert B, Carpentier P. Ultrasound prevalence of wrist, hand, ankle and foot synovitis and tenosynovitis in systemic sclerosis, and
relationship with disease features and hand disability. Joint Bone Spine 2020;87:229–233.
3. Fairchild R, Horomanski A, Sharpless L, Chung M, Li S, Hong J, et al. Ultrasound evaluation of the hands and wrists in patients with systemic sclerosis: Osteophytosis is a major
contributor to tender joints. Semin Arthritis Rheum 2021;51:735–740.
4. DeLea SL, Chavez-Chiang NR, Poole JL, Norton HE, Sibbitt WL, Bankhurst AD. Sonographically guided hydrodissection and corticosteroid injection for scleroderma hand. Clin
Rheumatol 2011;30:805–813.
5. Li H, Furst DE, Jin H, Sun C, Wang X, Yang L, et al. High-frequency ultrasound of the skin in systemic sclerosis: an exploratory study to examine correlation with disease activity
and to define the minimally detectable difference. Arthritis Res Ther 2018;20:181.
6. Karalilova RV, Batalov ZA, Sapundzhieva TL, Matucci-Cerinic M, Batalov AZ. Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic
sclerosis, evaluated by ultrasound. Rheumatol Int 2021;41:1743–1753.
7. Santiago T, Santiago M, Ruaro B, Salvador MJ, Cutolo M, Silva J a. P da. Ultrasonography for the Assessment of Skin in Systemic Sclerosis: A Systematic Review. Arthritis Care Res
(Hoboken) 2019;71:563–574.
8. Santiago T, Santos E, Ruaro B, Lepri G, Green L, Wildt M, et al. Ultrasound and elastography in the assessment of skin involvement in systemic sclerosis: A systematic literature
review focusing on validation and standardization - WSF Skin Ultrasound Group. Semin Arthritis Rheum 2022;52:151954.
9. Gutierrez M, Soto-Fajardo C, Pineda C, Alfaro-Rodriguez A, Terslev L, Bruyn GA, et al. Ultrasound in the Assessment of Interstitial Lung Disease in Systemic Sclerosis: A Systematic
Literature Review by the OMERACT Ultrasound Group. J Rheumatol 2020;47:991–1000.
10. Gargani L, Romei C, Bruni C, Lepri G, El-Aoufy K, Orlandi M, et al. Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung
disease screening. Rheumatology (Oxford) 2022;61:SI56–SI64.
11. Boutry N, Hachulla E, Zanetti-Musielak C, Morel M, Demondion X, Cotten A. Imaging features of musculoskeletal involvement in systemic sclerosis. Eur Radiol 2007;17:1172–
1180.
12. Tubau C, Cubiró X, Amat-Samaranch V, Garcia-Melendo C, Puig L, Roé-Crespo E. Clinical and ultrasonography follow-up of five cases of calcinosis cutis successfully treated with
intralesional sodium thiosulfate. J Ultrasound 2022;25:995–1003.
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18. Questions?