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