Keynote presentation by Dr. Lorinda Chung MD at March 9, 2013 Cheri Woo Scleroderma Education Seminar in Tualatin, OR hosted by Oregon Chapter of the Scleroderma Foundation.

1. Skin Manifestations of
Scleroderma
Lorinda Chung, MD, MS
Stanford University School of Medicine
March 9, 2013

2. Overview
• Skin tightening
• Digital ulcers
• Paronychia
• Calcinosis
• Telangiectasias
• Hypo-/hyperpigmentation
• Lipodermatosclerosis

3. Scleroderma=hardening of the skin
• Localized Scleroderma
– Morphea
– Linear Scleroderma
• Systemic Sclerosis
– Diffuse
– Limited (CREST)
– Sine scleroderma
– Overlap Syndrome/MCTD

5. Systemic Sclerosis: Subsets
• Diffuse • Limited
– Skin thickening: face, – Skin thickening:
trunk, entire arms/legs, face, forearms, lower
hands and feet; tendon legs, hands and feet
friction rubs – Progressive dz following
– Rapid onset following RP: onset of RP
months to 3 yrs – Late internal organ dz
– Early internal organ dz – Association with anti-
– Association with anti-Scl-70 centromere Ab
Ab – 10-yr survival >70%
– 10-yr survival 40%

6. Systemic Sclerosis: CREST
• Calcinosis
• Raynaud’s
• Esophageal
Dysmotility
• Sclerodactyly
• Telangiectasias

7. Skin Thickening in Systemic
Sclerosis
• Modified Rodnan Skin Score
– Validated measure of skin thickening used in clinical trials
– Correlates with internal organ involvement and survival in diffuse
patients
– Thickening assessed in 17 body areas: face/neck, anterior
chest, abdomen and bilateral fingers, dorsal
hands, forearms, upper arms, feet, lower legs, and thighs
– Each area scored and summed for total score (0-51):
• 0=normal
• 1=mild thickening
• 2=moderate thickening, unable to move
• 3=hidebound, unable to pinch

8. Natural History of Skin Tightening in Systemic Sclerosis
Medsger Rheum Dis N Am 2003;29(2):255-73.

9. Different Rates of Skin Thickness Progression
in Anti-Scl70+ SSc Patients
Perera et al. Arthritis Rheum 2007;56(8):2740-6.

10. Rapid Skin Thickness Progression Associated with Poorer Survival
In Anti-Scl-70+ SSc Patients
Perera et al. Arthritis Rheum 2007;56(8):2740-6.

11. Potential Treatments for Skin
Tightening
• Anti-fibrotics: breakdown scar • Target growth factors
tissue or block collagen involved in scar tissue
production formation
– Halofuginone – Imatinib
– Antibody to Connective – Dasatinib
Tissue Growth Factor • Target T Cells/Cytokines
– Statins (Inflammatory cells)
– Pirfenidone (in trials for IPF) – Methotrexate
– Anti-transforming growth – IVIG
factor-beta antibody – Mycophenolate mofetil*
– LPA-1 receptor antagonist* – Cyclophosphamide
– Stem cell transplant*
• Target B Cells/AutoAb – Abatacept (CTLA4 Ig)**
– Rituximab**
– Anti-BLyS (LymphoStat-B)
– Anti-Interferon antibodies
– Anti-CD19 mAb (completed – Anti-IL-6 antibody**
trial)
*Ongoing clinical trials
**Clinical trials available or soon to be available at Stanford

12. Scleroderma Digital Ulcers
• Occur in up to 50% of patients with limited or
diffuse scleroderma.
• Can occur at tips of digits or overlying joints.
• Painful and heal slowly.
• Complications include:
– Functional disability and immobility
– Scarring and loss of distal tissue (ie. fingertip)
– Infection (osteomyelitis)
– Can progress to gangrene (dead tissue)
Chung and Fiorentino. Autoimmun Rev 2006;5:125-8.

14. Scleroderma Digital Ulcers
Causes
• Vasospasm (RP)
• Vasculopathy
• Thrombosis (Clot)
• Calcinosis (Limited)
• Repeated trauma
• Tight skin overlying
joints

15. Scleroderma Vascular Disease

16. Scleroderma Digital Ulcers
• Risk Factors
– Male sex
– Presence of pulmonary arterial hypertension
– Severe involvement of the esophagus
– Diffuse skin involvement (only when PAH present)
– Young age at onset of RP
– Elevated sedimentation rate
Sunderkotter et al. Br J Dermatol 2009;160:835-43.

17. Scleroderma Digital Ulcers

18. Kahaleh Rheum Dis Clin N Am 2008;34:57-71.

19. Algorithm for the treatment and prevention of digital ulcers in systemic sclerosis.
DU present
NO YES
DU in past Multiple & severe DU
NO YES NO YES
Avoid cold, stress, trauma* Statins Hydrocolloid occlusion Prostacyclins (IV/SQ)
Smoking cessation* CCB OTC pain meds Anticoagulants
Treat RP PDE5-inhibitors Wound care Cilostazol/pentoxifylline
CCB ET-receptor Treat infections Narcotics
-adrenergic blockers blockers Hi dose CCB Wound care
Nitrates PDE5-inhibitors Treat infections
ACE-inhibitors ET-receptor blockers Consider digital or cervical
ARB Cilostazol sympathectomy
SSRI
ASA*
Statins
* All patients should be educated to avoid cold, stress, trauma, and nicotine. Aspirin 81mg daily should be considered for all patients who do
not have a contraindication.
DU=digital ulcers; RP=Raynaud’s phenomenon; CCB=calcium channel blockers; ACE=angiotensin converting enzyme; ARB=angiotensin II
receptor blocker; SSRI=selective serotonin reuptake inhibitor; ASA=aspirin; PDE5=phosphodiesterase-5;
ET=endothelin; OTC=over the counter; IV=intravenous; SQ=subcutaneous.

20. Paronychia
• Skin infection that occurs
around the nails, presenting
as painful, red, swollen area
around the nail.
• Usually caused by breach in
skin barrier.
• Infection can be due to
bacteria, yeast, or fungus.
• Prevalence and incidence in
scleroderma patients
unknown.

21. Paronychia
• Treatment • Prevention
– Acute – Minimize exposure to
• Antibiotics wet environment
• Possible incision/drainage – Avoid trauma to nails or
– Chronic fingertips
• Antifungal medication – Bring your own tools to
• Topical corticosteroids nail salons
– Do not trim cuticles or
use cuticle removers
– Use aquaphor or
vaseline around cuticles

22. Calcinosis
• Calcium deposits under the skin.
• Can occur in limited or diffuse skin disease, usually a sign of damage.
• Common locations: hands, arms, elbows, knees, trunk
• Can be nodular or plaque-like

23. Calcinosis
• Assessment of calcinosis:
• X-rays: lesions on extremities
• CT: lesions on trunk/plaque-like lesions
• Ultrasound: experimental

24. Calcinosis: Treatments
• Not very effective: warfarin, probenecid,
colchicine, alendronate
• Some efficacy: calcium channel blockers,
minocycline (especially if inflammation
present)
• Often successful: surgical removal
– Not all lesions are accessible for surgery
– Can recur

25. Telangiectasias
• Small dilated blood vessels near the surface of the skin.
• Matted or square-like appearance in patients with scleroderma.
• Can be seen in limited or diffuse disease, usually a sign of damage.
• Common locations: hands/fingers, oral mucosa, face, chest, arms
• Others: over joints, periungual (around nail)

26. Telangiectasias

27. Telangiectasias
• Clinical Associations:
– Older age
– African-Americans less likely to develop
– Former or current smoking
– Longer disease duration
– Increased risk for pulmonary arterial hypertension
Shah et al. J Rheumatol 2010;37(1):98-104.

28. Shah et al. J Rheumatol 2010;37(1):98-104.

29. *12.4X increased odds of PAH for every 10-point increase in telangiectasia score (p=0.01)
Shah et al. J Rheumatol 2010;37(1):98-104.

30. Telangiectasias: Treatment
• 585 nm flashlamp pulsed dye laser
– 1-4 treatments in 8 scleroderma patients
– No scarring or pigmentary changes post-treatment
– Did not recur during follow-up of 6 months to 2
years
Ciatti et al. J Am Acad Dermatol 1996;35:487-8.

31. Ciatti et al. J Am Acad Dermatol 1996;35:487-8.

32. Telangiectasias: Treatment
• Intense pulsed light
– 17 patients underwent 3 monthly treatments
• 3 patients withdrew: hyperpigmentation, facial edema,
hand blistering
– Follow-up at 1, 6, and 12 months after last treatment
– Perfusion as measured by laser doppler imaging was
decreased at 1 and 6 months, but not maintained to 12
months.
– 12/16 patients with follow-up photographs were improved
or much improved at 1 and 6 months.
Murray et al. Brit J Dermatol 2012;167:563-9.

33. BASELINE 1 MONTH
Murray et al. Brit J Dermatol 2012;167:563-9.

34. Hypo-/Hyperpigmentation
• Change in the pigment of skin due to
unknown cause
– Salt and pepper appearance
• Common locations: chest, lower extremities,
back, hands, arms, face

35. Salt and Pepper

36. Lipodermatosclerosis
• Fat inflammation that can be seen with
chronic leg edema and autoimmune diseases
• Cause in scleroderma is unknown

37. LIPODERMATOSCLEROSIS
• Chronic inflammation and
fibrosis of skin and SQ
tissue of the lower legs
causing a bound-down
appearance.
• Can be plaque or
surrounding entire lower
leg.
• Also known as
hypodermitis
sclerodermaformis and
sclerosis panniculitis.

38. Lipodermatosclerosis: Inverted
champange bottle appearance

39. Lipodermatosclerosis
• Prevalence in SSc unknown and may be
associated with anti-phospholipid antibodies
• Related to venous insufficiency—71% with
associated edema
• Obese, middle-aged women
• Initially painful and redhyperpigmented,
bound-down skin
• ~13% associated with ulceration
Miteva et al. Dermatol Ther 2010;23(4):375-88.

40. Lipodermatosclerosis: Treatments
• Compression stockings
• Stanozolol/Danazol
– Synthetic/modified testosterone derivative that
breaks up scar tissue
• Intralesional steroids
• Pentoxifylline
– Decreases sludging of blood
• Excision
– For non-healing ulcers
• Topical capsaicin
Miteva et al. Dermatol Ther 2010;23(4):375-88.

41. Summary
• Scleroderma is characterized by skin tightening
but the extent and rate differs among patients.
• Digital ulcers and paronychia are related to the
abnormal blood vessels in patients with
scleroderma and poor wound healing.
• Calcinosis, telangiectasias, and hypo-
/hyperpigmentation in scleroderma are signs of
damage in the skin that need further study and
better treatments.

42. Stanford Scleroderma Center
FACULTY CLINICAL TRIALS
David Fiorentino (Dermatology) • Tocilizumab for diffuse skin dz
Glenn Rosen (Pulmonary) – < 5 years of skin tightening
Roham Zamanian (Pulmonary) • Macitentan for digital ulcers
Howard Chang (Dermatology) – New or worsened ulcer in past
month
Linda Nguyen (Gastroenterology) • Rituximab for SSc-APAH
Mark Nicolls (Pulmonary) – On PAH drugs for > 3 months
William Robinson (Immunology) COORDINATORS
Amanda Foster: amfoster@stanford.edu
James Chang (Hand/Vascular) 650-721-7147
Francois Haddad (Cardiology) Val Scott (PAH): valval@stanford.edu
650-725-8082