This document discusses Raynaud's phenomenon and its link to systemic sclerosis. It begins with an overview of Raynaud's phenomenon, including its causes stemming from problems with blood vessel function. It then discusses systemic sclerosis and how Raynaud's phenomenon is more complex and can lead to worse issues when associated with sclerosis, like skin thickening and lung/organ problems. The document covers treatments aimed at improving blood vessel function and managing symptoms. It emphasizes the need for early, aggressive treatment of Raynaud's in sclerosis patients to potentially slow disease progression and prevent complications.

1. Dr John Pauling
BMedSci MRCP (Rheum) PhD
Consultant Rheumatologist, Royal National Hospital for Rheumatic Diseases, Bath, UK
Visiting Senior Lecturer, University of Bath, UK
Raynaud’s phenomenon in systemic
sclerosis:
Why do the blood vessels stop working
properly and how can we treat this?

2. • “What is Raynaud’s phenomenon?”
• “Why do the blood vessels stop working properly?”
• “What is the link with systemic sclerosis?”
• “Friends say they have Raynaud’s too but my
Raynaud’s seems worse. Are they the same?”
• “How can I / WE manage treat these problems?”
www.rnhrd.nhs.uk
What I will try to cover over next 30 minutes or so

3. Raynaud’s phenomenon
Maurice Raynaud (1834 – 1881)
De l'asphyxie locale et de la
gangrène symétrique des
extrémités.
Doctoral thesis, published February
25, 1862.

4. 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

5. Causes of Raynaud’s phenomenon
Muscle in blood
vessel wall
The “endothelium”
The inside of blood vessel
filled with blood cells
Nerves supplying muscle
• Overactivity of nerves supplying muscle
in vessel wall
• Muscles in the vessel wall contract
leading to narrowing of the blood vessel
or “vasoconstriction”
• Increased production of molecules
which promote “vasoconstriction” by the
endothelium e.g. ET-1
• Reduced production of molecules which
promote relaxation of the vessel wall
and “vasodilation” e.g. NO
• Production of molecules which promote
“vasoconstriction” e.g. serotonin from
platelets
• Activation of receptors in vessel wall
which promote vasoconstriction e.g. AT
II receptors
EXPOSURE TO COLD
AT II
AT II
AT II
AT II
AT II

6. www.rnhrd.nhs.uk
Systemic sclerosis (SSc) / Scleroderma

7. Blood vessel abnormalities in Systemic sclerosis
• Startin 1846
Scottish girl, 18 years old “contraction of the right arm”
Ulcers formed “around the nails and joints of the fingers which healed
gradually, but left the sort of contraction as existed in the right hand
and arm”. “fingers contracted into the palm”
“My poor sister is now never off the sofa….so dreadfully reduced by
low fainting fits… followed by hours of exhaustion; her stiffness, too,
increases, so soon she will become a piece of bone”
• Thomas Barlow (1845-1945) 1888 (Royal Free Hospital)
A women who for 5 years had suffered during the winter with hard
yellowish patches on the extremities, which subsided on the return of
spring. Ultimately the fingers were permanently altered in that the
extremeties became cold, hard, somewhat unsensitive and decidedly
atrophied. The last phalanges were contracted in a state of semi-
flexion….The patient was liable to crises from time to time during which
the finger reddened and became painful, then ulceration occurred and
tardy cicatrisation with loss of substance. After each crisis the affected
digit became a little more atrophied and deformed than before. There
was no trace of scleroderma in other parts of the body’

8. www.rnhrd.nhs.uk
Another way of approaching systemic sclerosis
Systemic sclerosis
Blood vessel abnormalities
Fibrosis / scar
tissue
Inflammation
Fatigue??

9. www.rnhrd.nhs.uk
A Simpler way of approaching scleroderma
Systemic sclerosis
Blood vessel abnormalities
Fibrosis / Scar
tissueInflammation
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??

10. www.rnhrd.nhs.uk
Is Raynaud’s phenomenon in systemic sclerosis actually
Raynaud’s phenomenon?
A healthy arteriole
(primary RP)
Systemic sclerosis

11. 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

12. 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

13. 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

14. 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

15. 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
Body attempts to
make new blood
vessels

16. 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
Skin thickening
Scarring of lungs
Gastrointestinal
dysmotility
Body attempts to
make new blood
vessels

17. 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
Skin thickening
Scarring of lungs
Gastrointestinal
dysmotility
Body attempts to
make new blood
vessels
A WINDOW OF OPPORTUNITY

18. Promote patient self-management
• Stop smoking
• Keep warm (even uncomfortably so)
• Be prepared
• Keep skin moist and clean
• Nail care
• Hand exercises
• Do not attempt DIY surgery
• Report new ulcers on fingers and toes immediately
(a scleroderma emergency)

19. “Natural” remedies for Raynaud’s phenomenon
• Not strong “evidence” to support treatments
• Biofeedback training
• Low level laser therapy
• Nutritional supplements e.g. cinnamon, vitamin
B3 (niacin)
• Ginkgo biloba (Maidenhair tree)
• Potential for interactions with conventional
treatments of systemic sclerosis e.g. anti-
platelets, azathioprine (so bring along to clinic
appointments and tell your clinician).

20. Drug treatment targets in Raynaud’s phenomenon
Muscle in blood
vessel wall
The “endothelium”
The inside of blood vessel
filled with blood cells
Nerves supplying muscle
• Directly prevent vascular muscle cells
contracting e.g. nifedipine, amlodipine
• Prevent nerve stimulation of vascular muscle
e.g. prazosin
• Prevent stimulation of AT II receptors in vessel
wall e.g. losartan
• Block action of molecules released by
endothelium which promote “vasoconstriction”
e.g. bosentan
• Enhance action of molecules released by
endothelium which promote “vasodilation” e.g.
sildenalfil (viagra)
• Block the release of molecules from blood cells
which cause vasoconstriction e.g. fluoxetine
(prozac)
• Inject molecules that make blood vessel
muscles relax e.g. iloprost
AT II
AT II
AT II
AT II
AT II

21. Side effects to watch out for
• Some side effects are common to all drugs and may
necessitate coming off treatment e.g. nausea, rash etc.
• Side effects generally evidence of treatment
effectiveness (relating to dilated blood vessels)
• Headaches
• Light-headedness if blood pressure drops too low
• Side effects less of a problem if you gradually build
dose allowing body to get used to drug
• Unusual not to identify treatments to suit patient and
improve symptoms

22. • Raynaud’s phenomenon is complex and caused by a
multitude of factors
• Sometimes requires multiple treatments
• Raynaud’s even more complex in systemic sclerosis and can
result in progressive damage to the blood vessels
• Early aggressive treatment might slow disease progression in
systemic sclerosis
• Finger ulcers in SSc should be considered a Rheumatological
Emergency and there should be an open door policy for
patients for DU assessment/management
www.rnhrd.nhs.uk
Conclusions

23. “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