What is Raynaud’s phenomenon? What is
Scleroderma? What is the link?
Dr John Pauling
BMedSci MRCP (Rheumatology) PhD
Consultant Rheumatologist
RNHRD
Thank you for joining us to celebrate world
scleroderma day (29th June)
Relaxed morning with opportunities for
questions and answers
Opportunity to meet the team from
RNHRD
Opportunity to meet the teams from the
major UK national scleroderma charities
www.rnhrd.nhs.uk
Welcome
Thank you for the support of the UK
Raynaud’s and Scleroderma charities in
facilitating this event
www.raynauds.org.uk
www.sclerodermasociety.co.uk
Other avenues are available to patients
with Raynaud’s and Scleroderma needing
support
• “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
www.rnhrd.nhs.uk
Systemic sclerosis (SSc) / Scleroderma
www.rnhrd.nhs.uk
Another way of approaching systemic sclerosis
Systemic sclerosis
Blood vessel abnormalities
Fibrosis / scar
tissue Inflammation
Fatigue??
www.rnhrd.nhs.uk
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
www.rnhrd.nhs.uk
Is Raynaud’s phenomenon in systemic sclerosis actually
Raynaud’s phenomenon?
A healthy arteriole Systemic sclerosis
www.rnhrd.nhs.uk
Evaluating Raynaud’s phenomenon (microvascular imaging)
Thermal Imaging
Healthy nailfold capillaries (as is found in
primary Raynaud’s phenomenon)
Systemic sclerosis
www.rnhrd.nhs.uk
So how does this all link together? “The Vascular Hypothesis”
www.rnhrd.nhs.uk
Theories on the link between inflammation, vascular
abnormalities and fibrosis
Damage to
lining 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
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
www.rnhrd.nhs.uk
Another way of looking at it - Normal wound repair
• 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