1. Current and future treatment
options for SSc
Dr Victoria Flower
Rheumatology Specialty Registrar
RNHRD, Bath

2. Systemic Sclerosis
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits

3. Systemic Sclerosis

4. Raynaud’s Phenomenon
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits

5. Raynaud’s phenomenon
• Cold, white/blue red
• Painful hands and
reduced fine movement
during attacks

6. Endothelium
• Aim to dilate the
blood vessels to
improve blood flow
and warmth to
fingers

7. Raynaud’s phenomenon
• Nifedipine*
• Iloprost
• Bosentan
• Sildenafil
• Reduce frequency and
severity of attacks
• Heal ulcers
• Reduce new ulcers
occurring

8. Raynaud’s Phenomenon
Nifedipine
• Tablet three
times a day
• Blood
pressure
• Dizziness
Iloprost
• Intravenous
• In hospital
• Nausea
• Diarrhoea
• Muscle cramp
• Headaches/jaw
pain
• blood pressure
• Flushing
• Expensive
Bosentan
• Dizzy
• Flushing
• Liver tests
• May reduce OCP
• Rarely
haemoptysis

9. Raynaud’s phenomenon
• Digital ulcers
• Infection
• Antibiotics as well as
dilating treatments

10. Scleroderma
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits

11. Limited cutaneous SSc
• If no lung disease then manage symptoms
• Treat Raynaud’s / ulcers/ infection
• Hand therapy
• Monitor
• Early sausage swelling of fingers may benefit from
low dose steroids & antihistamines

12. Progressive Diffuse or lung disease
Maintenance
Induction
Cyclophosphamide
Lung, heart,
progressive skin
Methotrexate
Skin, arthritis,
muscle
inflammation
Mycophenolate,
Azathoprine
Predominantly
lung disease

13. Cyclophosphamide
What is it?
• Also used for other
conditions as well – lupus,
vasculitis
• Intravenous injection (4-6
‘cycles’)
• Takes up to 6 weeks to work
• Live vaccines ✗
• Annual Pneumovax ✓
Side effects:
• Nausea is common
• Haemorrhagic cystitis
• Monitor for white blood
cells dropping and infection
• Fertility/contraception

14. Methotrexate
What is it?
• Used for many
Rheumatological conditions
• Once a week
• Anti-folate
• Weekly folic acid supplement
• Monthly blood test monitoring
• Takes up to 12 weeks to work
• Live vaccines ✗
• Annual Pneumovax ✓
Side effects:
• Mouth ulcers
• Nausea
• Hair thinning (usually
minor)
• Blood count
• Liver function tests
• Rarely lung inflammation

15. Calcinosis
• Treat infection
• Unfortunately no
targeted treatments for
calcium deposits
• Sometimes surgery but
avoid if possible

16. Arthritis – joint pain and swelling
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits
Hydroxychloroquine, Methotrexate and Mycophenolate mofetil

17. Hydroxychloroquine
• “Plaquenil”
• Takes up to 12 weeks to work
• Usually well tolerated with few side effects
Side effects:
• Skin rash
• Can exacerbate psoriasis
• Indigestion
• Headaches
• Rarely visual problems 1 in 2000

18. Upper Gastrointestinal problems
Oesophageal
dysmotility
Difficulty swallowing
Painful swallow
Indigestion and acid
reflux
GORD
PPIs to reduce acid
Prokinetics
Thrush
Antibiotics -
Fluconazole
Delayed emptying of
stomach
Bloating,
Early satiety
Wind
Prokinetics –
domperidone,
metoclopramide

19. Lower Gastrointestinal problems
Reduced movement
(peristalsis) of small bowel
Bloating, wind and constipation
Laxatives
Diarrhoea
Loperamide
Bacterial overgrowth
Rotated antibiotics
Reduced absorption of nutrients
Nutritional advice & supplements
Rarely TPN

20. Systemic Sclerosis lung disease
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits

21. LungsSymptoms:
Short of breath
Cough
Chest pain
Fatigue
Ankle swelling
Fibrosis:
Cyclophosphamide
Mycophenolate mofetil
Azathioprine
Steroids
Aim to improves symptoms,
breathing tests and QoL
Pulmonary hypertension:
Warfarin, water tablets
Bosentan
Sildenafil
Iloprost (as an inhaler)
Epoprostinol (as a continuous infusion)
Improves exercise tolerance, day to day symptoms and function, improves heart pressure

22. Kidney – Scleroderma renal crisis
High Blood pressure
Frothy urine
Persistent headache
Blurred vision
Ankle swelling
Short of breath
ACEI - lower BP
Improves survival and reduces
need for long term dialysis.
Dialysis
Steroids in SSc:
Monitor BP, urine dipstick and kidney blood test
Avoid high dose steroids if at risk of SRC

23. The future for Systemic Sclerosis
Autoimmune
•Immune system produces cytokines
•Inflammation
Overproduction of Collagen
•Scar tissue forms, thickening of soft
tissues
Blood vessel damage
•Reduces blood flow to tissues
causing damage
•Encourages calcium deposits
EULAR SSc Trials and
Research Group - EUSTAR
Canadian SSc
research groupSSc Research Foundation
Rituximab, Abatacept, Tocilizumab
Autologous Stem
cell transplant

24. References
(1)Thompson AE, Shea B, Welch V, Fenlon D, Pope JE. Calcium-channel blockers for Raynaud’s phenomenon in systemic
sclerosis. Arthritis Rheum 2001;44:1841–7.
(2) Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, et al. Iloprost and cisaprost for Raynaud’s phenomenon in
progressive systemic sclerosis. Cochrane Database Syst Rev 1998;(2):CD000953. doi: 10.1002/14651858.CD000953.
(3) Rademaker M, Cooke ED, Almond NE, Beacham JA, Smith RE, Mant TG, et al. Comparison of intravenous infusions of
iloprost and oral nifedipine in treatment of Raynaud’s phenomenon in patients with systemic sclerosis: a double blind
randomised study. BMJ 1989;298:561–4.
(4) Scorza R, Caronni M, Mascagni B, Berruti V, Bazzi S, Micallef E, et al. Effects of long- term cyclic iloprost therapy in
systemic sclerosis with Raynaud’s phenomenon. A randomized, controlled study. Clin Exp Rheumatol 2001;19:503–8.
(5) Wigley FM, Seibold JR, Wise RA, McCloskey DA, Dole WP. Intravenous iloprost treatment of Raynaud’s phenomenon
and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 1992;19:1407–14.
(6) Wigley FM, Wise RA, Seibold JR, McCloskey DA, Kujala G, Medsger TA Jr, et al. Intravenous iloprost infusion in
patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind
study. Ann Intern Med 1994;120:199–206.
(7) Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, et al. Continuous intravenous
epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized controlled trial.
Ann Intern Med 2000;132:425–34.
(8) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and
Research group (EUSTAR) O Kowal-Bielecka,1 R Landew ́e,2 J Avouac,3 S Chwiesko,1 I Miniati,4 L Czirjak,5
P Clements,6 C Denton,7 D Farge,8 K Fligelstone,9 I F ̈oldvari,10 D E Furst,6 U M ̈uller- Ladner,11 J Seibold,12 R M
Silver,13 K Takehara,14 B Garay Toth,15 A Tyndall,16
G Valentini,17 F van den Hoogen,18 F Wigley,19 F Zulian,20 Marco Matucci-Cerinic,4 and the EUSTAR co-authors