What is Raynaud’s phenomenon? What is Scleroderma? What is the link?
Dr John Pauling BMedSci MRCP (Rheumatology) PhD
Consultant Rheumatologist
RNHRD
• “What is Raynaud’s phenomenon?” • “What is scleroderma?” • “How do these conditions affect the body?” • “What are antibodies important with this?” • “Friends say they have Raynaud’s too but my Raynaud’s seems worse. Are they the same? • “How are all these problems linked?” • “What causes scleroderma?” • “How can understanding the development of scleroderma help guide treatment?”
www.rnhrd.nhs.uk
What I will try to cover over next 30 minutes or so
Raynaud’s phenomenon
Maurice Raynaud (1834 – 1881)
De l'asphyxie locale et de la gangrène symétrique des
extrémités.
Doctoral thesis, published February 25, 1862.
Initial ischaemia
Pallor
Cyanotic phase
Blue
Hyperaemic phase
Red / purple
Clinical features of Raynaud’s phenomenon
• Usually affects fingers
• Can affect toes, thumbs, nipples, nose, earlobes
• Episodes precipitated by cold exposure and emotional stress
• Episodes accompanied by pain +/- numbness
• “Primary” in the majority of cases (excellent prognosis)
• “Secondary” forms rare e.g. systemic sclerosis but not to be missed
'The head was completely withered, of a uniform shade of bronze, the nose was as thin as a knife-blade; the lips had almost disappeared. Two tiny hands of the same bronze colour slowly moved their fingers up and down like little sticks. And the face seemed all the more awesome to me because I could see that a smile was striving to appear on it, to cross its metallic cheeks - and yet could not spread.'
With a shock, after the woman had said, “Master, don't you recognize me?”, he realizes that she is Lukeria, who ten years before had been 'the greatest beauty among all the servants in our house, tall, buxom, white-skinned and rosy-cheeked.
Turgenev Living Relic 1874
Sketches from a Hunter's Album
Scleroderma
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Systemic sclerosis (SSc) / Scleroderma
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Another way of approaching systemic sclerosis
Systemic sclerosis
Blood vessel abnormalities
Fibrosis / scar tissue
Inflammation
Fatigue??
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A Simpler way of approaching scleroderma
Systemic sclerosis
Blood vessel abnormalities
Fibrosis / Scar tissue Inflammation
Raynaud’s phenomenon Pulmonary arterial hypertension Scleroderma renal crisis
Skin thickening Lung fibrosis Gastrointestinal problems Bowel problems
Antibody formation Inflammation in muscles Inflammation in joints
Fatigue??
www.rnhrd.nhs.uk
Subsets of systemic sclerosis (limited versus diffuse cutaneous SSc)
Limited cutaneous SSc (lcSSc) • More vascular problems • Relatively mild skin
involvement • Digital ulcers • Telangiectasia • Calcinosis • Late pulmonary arterial
hypertension in minority of patients
Diffuse cutaneous SSc (dcSSc) • More scar tissue problems • More widespread skin
involvement • Lower bowel problems • Scar tissue in lungs
Antinuclear autoantibodies
Anticentromere Anti-DNA Anti-topoisomerase Anti-nucleolar
Antibody subsets in scleroderma
RNAP
Topo-I
Centromere
Lung fibrosis
Diffuse subtype (fibrosis)
Limited subtype (vascular)
Overlap features (inflammatory features)
Kidney
Th RNP
RNAP II
U3RNP
U1RNP Pm-Scl
PAH
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Is Raynaud’s phenomenon in systemic sclerosis actually Raynaud’s phenomenon?
A healthy arteriole Systemic sclerosis
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Evaluating Raynaud’s phenomenon (microvascular imaging)
Thermal Imaging
Healthy nailfold capillaries (as is found in primary Raynaud’s phenomenon)
Systemic sclerosis
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Theories on the link between inflammation, vascular abnormalities and fibrosis
Damage to lining of blood vessels
Antibodies Viruses Toxins e.g. solvents
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Theories on the link between inflammation, vascular abnormalities and fibrosis
Damage to lining of blood vessels
Intermittent Raynaud’s attacks
Destruction of blood vessels
Antibodies Viruses Toxins e.g. solvents
www.rnhrd.nhs.uk
Theories on the link between inflammation, vascular abnormalities and fibrosis
Damage to lining of blood vessels
Intermittent Raynaud’s attacks
Complications Destruction of blood vessels
Antibodies Viruses Toxins e.g. solvents
Persistent Raynaud’s symptoms Digital ulcers Pulmonary arterial hypertension Scleroderma Renal crisis
www.rnhrd.nhs.uk
Theories on the link between inflammation, vascular abnormalities and fibrosis
Damage to lining of blood vessels
Intermittent Raynaud’s attacks
Body recognises tissue damage
Complications Destruction of blood vessels
Reduced oxygen and nutrient supply to tissues
Antibodies Viruses Toxins e.g. solvents
Persistent Raynaud’s symptoms Digital ulcers Pulmonary arterial hypertension Scleroderma Renal crisis
Body attempts to make new blood vessels
www.rnhrd.nhs.uk
Theories on the link between inflammation, vascular abnormalities and fibrosis
Damage to lining of blood vessels
Tissue fibrosis
Intermittent Raynaud’s attacks
Body recognises tissue damage
Wound healing cells activated
Complications Destruction of blood vessels
Reduced oxygen and nutrient supply to tissues
Antibodies Viruses Toxins e.g. solvents
Persistent Raynaud’s symptoms Digital ulcers Pulmonary arterial hypertension Scleroderma Renal crisis
Skin thickening Scarring of lungs Gastrointestinal dysmotility
Body attempts to make new blood vessels
• We spent much of the 20th Century identifying the many different features and subtypes of systemic sclerosis
• We are now beginning to better understand the triggers of systemic sclerosis and what happens on a cellular/molecular level to cause progression of the disease
• Early identification and management of blood vessel abnormalities in scleroderma may help to prevent late complications of scleroderma
• Emphasizes the importance of keeping warm, stopping smoking etc.
• A lot of work still to do to understand the disease and develop a cure
• The horizon looks very promising as this knowledge is being translated into potentially effective treatments to halt the progression and reverse complication of scleroderma
www.rnhrd.nhs.uk
What does all this mean for patients with systemic sclerosis?
“The captive” 1940
• Nazi’s presented his work as evidence of “Degenerate Art”
• Fled to Switzerland 1933
• Diagnosed with SSc in 1935
• Died of cardiac complications 5 years later
Paul Klee (1879-1940)
“Death and Fire” 1940
The bars are thought to represent the restrictive effect of being trapped by his cutaneous fibrosis
His face is etched with the letters “Tod” meaning death in German