Professor Neil McHugh presentation for the Scleroderma Society and RSA 2015 joint annual conference

1. What is Raynaud’s
What is Scleroderma?
Neil McHugh, University of Bath and
Royal National Hospital for Rheumatic Diseases
Manchester June 2015

2. Raynaud’s disease
• De l'asphyxie locale et de la
gangrène symétrique des
extrémités.
• Discrete episodes of change in
colour, of the vasospastic type,
induced by cold exposure or
emotional stress
• Bilateral
• Normal pulsations in palpable
stress
Doctoral thesis, published
February 25, 1862.
Maurice Raynaud 1834-1881

3. What is Raynaud’s
• A sudden reversible colour change
• Digits turn white (ischaemia), blue
(deoxygenation), then red (reperfusion)
• Not all three colour changes necessarily
observed
• Fingers, whole hand, toes, tip of nose,
earlobe and tongue, affecting all
extremities if severe
• Precipitated by change in temperature
or emotional stress
• Associated with numbness, pain and
paraesthesia

4. Raynaud’s phenomenon (disease, syndrome)
• Primary Raynaud’s phenomenon
• A functional problem affecting small
blood vessels
• No evidence of an underlying disease
process
• Common affecting 15% female
population
• 10 million in UK have Raynaud’s
• ‘Benign’ – does not mean insignificant!

5. Raynaud’s phenomenon (disease, syndrome)
• Secondary Raynaud’s syndrome
• Much less common
• Often associated with an underlying
connective tissue disease such as
scleroderma
• May be other causes
• e.g. clots, medications, vibration, blood
disorders
• Needs specialist care

6. Helpful diagnostic tests
Infrared thermography Nailfold capillaroscopy
Blood tests

7. Classification criteria for Primary Raynaud’s
phenomenon
• Episodic attacks of acral pallor or
cyanosis
• Strong and symmetric peripheral
pulses
• No evidence of digital pitting scars,
ulceration, or gangrene
• Normal nailfold capillaries
• Negative antinuclear antibody test
• Normal ESR

8. Treatment of Raynaud’s phenomenon
• Vasodilators
• Calcium channel blockers
• Nitrate patches
• Serotonin inhibitors
• Serotonin re-uptake inhibitors
• PDE5 inhibitors
• a2-adrenergic blockers
• Vasodilatation and remodelling
• ACE inhibitors
• Angiotensin receptor blockers
• Prostocyclin analogues
• Endothelin receptor blockers
• Anti-oxidants
• Vitamin E, Vitamin C
• Probucol
Stop smoking
Keep warm
Ask

9. Scleroderma = Hard Skin

10. Scleroderma spectrum disorders
• Raynaud’s phenomenon
• Primary Raynaud’s phenomenon
• Autoimmune Raynaud’s phenomenon
• Systemic sclerosis (scleroderma)
• Limited cutaneous systemic sclerosis
• Diffuse cutaneous systemic sclerosis
• Systemic sclerosis sine scleroderma
• Scleroderma overlap syndromes
• Localised scleroderma
• Morphea
• Localised
• Generalised
• Linear scleroderma
• En coup de sabre
Digital ulceration

11. Limited cutaneous systemic sclerosis
• Formerly called CREST
• Calcinosis
• Raynaud’s
• oEsophageal disease
• e.g.relux, heartburn
• Sclerodactyly
• Telangiectasia
• 80 % of scleroderma cases
• Frequent Digital Ulceration
• Monitor for Pulmonary
Hypertension

12. Pulmonary Hypertension
• Increased blood pressure in pulmonary
artery on right side of the heart (in
contrast to ‘usual’ hypertension affecting
left side of the heart)
• May be a late complication especially in
limited cutaneous systemic sclerosis
• Important to detect early in order to
treat
• Annual lung function tests and
echogardiography
• Newer more effective treatments
available

13. Diffuse cutaneous systemic sclerosis
• 20% of cases of scleroderma
• Skin involvement may be
more widespread
• Watch for lung disease and
kidney complications

14. Digital Ulcers
• Occurs in more than 30% of patients
with SSc
• Recurrence rate of 50%
• Commonly fingertips, phalangeal
joints, toes, where skin is stretched,
and commonly with calcinosis
• Occur early in disease course
• 43% within first year of SSc (Hachulla J
Rheum 2007)
• 20% have 3 to 6 ulcers per episode

15. Digital ulcer – burden to patient
• Interfere with activities of daily living
• Restrict an individual's capabilities
• Impair hand function
• Impact on work opportunities and family commitments
• Increased disability, more pain and reduced QoL compared with
those without digital ulcers (Merkel 2002)
• Can be exquisitely painful with prolonged healing time

16. Epidemiology of scleroderma
• Prevalance 10-300 per million
• About 8000 cases in UK
• Female predominance (especially anti-centromere positive)
• Ethnic differences in subgroups
• Enviromental factors
• e.g. silica, bleomycin,vinyl chloride, organic solvents, epoxy resins
• Genetic factors
• e.g. MHC

17. Pathogenesis of scleroderma
Jimenez Ann Int Med 2004

18. Helpful diagnostic tests for scleroderma
Infrared thermography Nailfold capillaroscopy
Blood tests

19. Cold stress thermography and laser imaging
Laser speckle contrast imaging

20. Nailfold capillaroscopy
Early
pattern
Active
pattern
Late
pattern

21. Blood tests
‘It’s all in the blood’

22. Blood components

23. Antibodies circulate in blood
Anticentromere antibodies associated with limited cutaneous systemic sclerosis
Anti-Scl-70 antibodies associated with lung disease
Anti-RNAP antibodies associated with kidney disease

24. Autoantibody detection
Autoantibody Screening by Indirect Immunofluorescence
Hep-2 Hep-2 Hep-2Human neutrophil
Autoantibody identification by second technique
Immunodiffusion
ENA
anti-RNP
ELISA
anti-PR3 anti-centromere
Immunoblot Immunoprecipitation
Anti-fibrillarin
U3RNP

25. 2013 ACR/EULAR Classification criteria for SSc
Item Sub-item(s) Weight/score
Skin thickening of fingers of both
hands extending proximal to mcps
9
Skin thickening of fingers Puffy fingers 2
Sclerodactyly of fingers 4
Finger-tip lesions Digital tip ulcers 2
Fingertip pitting scars 3
Telangiectasia 2
Abnormal nailfolds 2
PAH +/- ILD 2
Raynaud’s phenomenon 2
SSc related autoantibodies ACA 3
Anti-topo 1
Anti-RNAP 3

26. And some of the Bath Team…