Current and future treatment option for Systemic Sclerosis
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Transcript of Current and future treatment option for Systemic Sclerosis
Current and future treatment options for SSc
Dr Victoria Flower
Rheumatology Specialty Registrar
RNHRD, Bath
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
Systemic Sclerosis
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
Raynaud’s phenomenon
• Cold, white/blue red
• Painful hands and reduced fine movement during attacks
Endothelium
• Aim to dilate the blood vessels to improve blood flow and warmth to fingers
Raynaud’s phenomenon
• Nifedipine*
• Iloprost
• Bosentan
• Sildenafil
• Reduce frequency and severity of attacks
• Heal ulcers
• Reduce new ulcers occurring
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
Raynaud’s phenomenon
• Digital ulcers
• Infection
• Antibiotics as well as dilating treatments
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
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
Progressive Diffuse or lung disease
Maintenance
Induction Cyclophosphamide
Lung, heart, progressive skin
Methotrexate
Skin, arthritis, muscle
inflammation
Mycophenolate, Azathoprine
Predominantly lung disease
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
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
Calcinosis
• Treat infection
• Unfortunately no targeted treatments for calcium deposits
• Sometimes surgery but avoid if possible
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
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
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
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
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
Lungs Symptoms: 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
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
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 group SSc Research Foundation
Rituximab, Abatacept, Tocilizumab Autologous Stem cell transplant
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