CLINICAL REVIEW

Diagnosis and management of

Raynaud’s phenomenon
Follow the link from the
online version of this article
to obtain certified continuing
medical education credits

Beth Goundry, Laura Bell, Matthew Langtree, Arumugam Moorthy

Department of Rheumatology, Raynaud’s phenomenon is caused by episodic vasospasm

SOURCES AND SELECTION CRITERIA
University Hospitals of Leicester and ischaemia of the extremities in response to cold or
NHS Trust, Leicester LE1 5WW, UK We searched the Cochrane Library and PubMed (2001-11)
emotional stimuli, which result in a characteristic tripha- using the term “Raynaud’s”. Recommendations made at the
Correspondence to: A Moorthy
[email protected] sic colour change in extremities—usually fingers or toes— May 2011 conference “Raynaud’s phenomenon: new insights,
Cite this as: BMJ 2012;344:e289 from white, to blue, to red. Raynaud’s phenomenon may be new treatments” organised by the vascular medicine section of
doi: 10.1136/bmj.e289 primary, in direct response to stimuli, or secondary to an the Royal Society of Medicine were reviewed. We also consulted
underlying condition. In 10-20% of cases it may be the first published guidelines and information from the European League
presentation of, or may precede the onset of, a connective Against Rheumatism, Raynaud’s and Scleroderma Association,
tissue disease (such as scleroderma or mixed connective and Arthritis Research UK.
tissue disease), so that underlying causes must be ruled out.
Raynaud’s phenomenon is triggered by a change in Box 1 | Conditions associated with secondary Raynaud’s
temperature rather than simply exposure to cold. Patients phenomenon
can have attacks throughout the year—for example, if they Rheumatological
move from a warm environment to an air conditioned one, Systemic sclerosis (90% of patients with this condition have
stand in a cold wind (even on a relatively warm day), or Raynaud’s phenomenon)
hold a cold milk bottle.1 Mixed connective tissue disease (85%)
bmj.com A recent consensus statement on terminology produced Systemic lupus erythematosus (40%)
Previous articles in by the vascular medicine section of the Royal Society of Dermatomyositis or polymyositis (25%)
this series Medicine recommended abandoning the terms Raynaud’s Rheumatoid arthritis (10%)
ЖDiagnosis
Ж and syndrome and Raynaud’s disease because of the lack of Sjögren’s syndrome
management of Vasculitis
consensus on their use (Raynaud’s phenomenon: new
thalassaemia insights, new treatments. Conference organised by the Haematological
Polycythaemia ruba vera
(BMJ 2012;344:e228) Vascular Medicine Section of the Royal Society of Medi-
Leukaemia
ЖDiagnosis
Ж and cine. 2011 May). In this review we refer to primary and
Thrombocytosis
management of ANCA secondary Raynaud’s phenomenon. Recent advances in
Cold agglutinin disease (Mycoplasma infections)
associated vasculitis the management and treatment of this phenomenon have
Paraproteinaemias
(BMJ 2012;344:e26) followed on from the findings of randomised controlled Protein C deficiency, protein S deficiency, antithrombin III deficiency
trials of treatment strategies. We review observational stud-
ЖLaparoscopic
Ж Presence of the factor V Leiden mutation
ies, randomised controlled trials, systematic reviews, and Hepatitis B and C (associated with cryoglobulinaemia)
colorectal surgery
guidelines to provide an overview of the clinical presenta- Occlusive arterial disease
(BMJ 2011;343:d8029)
tion of Raynaud’s phenomenon, its risk factors, its diagno- External neurovascular compression, carpal tunnel syndrome,
ЖManaging
Ж infants who sis, and the current and potential treatments. and thoracic outlet syndrome
cry excessively in the first Thrombosis
few months of life Who gets Raynaud’s phenomenon? Thromboangiitis obliterans
(BMJ 2011;343:d7772) The prevalence of Raynaud’s phenomenon varies widely Embolisation
ЖManaging
Ж motion across countries and populations. Non-population based Arteriosclerosis
sickness studies of prevalence show that 3-12.5% of men and 6-20% Buerger’s disease
(BMJ 2011;343:d7430) of women report symptoms of Raynaud’s phenomenon. The
average age of onset is lower in women than in men, and
SUMMARY POINTS prevalence is higher in colder climates.2 Family history,
Raynaud’s phenomenon is caused by episodic vasospasm and ischaemia of the extremities, o­estrogen exposure, and emotional stress are commonly
particularly the digits, in response to cold or emotional stimuli associated with the phenomenon in women, whereas
Attacks comprise a colour change in extremities from white (ischaemia), to blue smoking and hand arm vibration syndrome (HAVS3) are
(deoxygenation), and then to red (reperfusion) more commonly implicated in men.2 Information from the
Primary Raynaud’s phenomenon is an exaggerated response to stimuli, with no known R­aynaud’s and Scleroderma Association states that sm­oking
underlying cause reduces body temperature by 1°C over 20 minutes.4
Secondary Raynaud’s phenomenon is usually caused by connective tissue disease and Many conditions have been associated with secondary
patients are more likely to develop tissue damage
Raynaud’s phenomenon (box 1), most notably systemic
Nifedipine is currently the only drug licensed for use in Raynaud’s phenomenon
sclerosis and mixed connective tissue disorders. An obser-
Key areas of ongoing research include a topical nitroglycerin and a rho kinase inhibitor
vational study of about 1500 people found that 89% of
(vasodilator)
Raynaud’s phenomenon was classified as primary and

BMJ | 11 FEBRUARY 2012 | VOLUME 344 37

 CLINICAL REVIEW

esis.8 Abnormalities of the blood vessel wall are thought to

be functional in primary Raynaud’s phenomenon and struc-
tural in secondary disease. Abnormalities of neural control
mechanisms are considered less likely to be important in
the pathogenesis of primary Raynaud’s phenomenon. Intra-
vascular factors—such as platelet activation, defective fibri-
nolysis, reduced red blood cell deformability, and increased
blood viscosity—are associated with secondary Raynaud’s
phenomenon, whereas white blood cell activation and oxi-
dative stress have been reported in primary and secondary
disease. The key to appropriate treatment lies in understand-
ing the underlying mechanism, but there is still some way

DR P MARAZZI/SPL
to go before a clear understanding is able to inform a gold
standard treatment.8

Fig 1 |  Raynaud’s phenomenon showing typical colour changes How are patients with Raynaud’s phenomenon assessed?
Raynaud’s phenomenon is diagnosed clinically.
11% as secondary.5 Around 12.5% of patients with Ray-
naud’s phenomenon develop scleroderma and 13.6% History
develop connective tissue diseases.6 Ask patients about the frequency and pattern of colour
changes, which stage(s) they experience, which digits are
What are the symptoms? affected, associated features such as pain and changes in
Patients with Raynaud’s phenomenon classically report sensation, what triggers an attack, and what relieves it.
intermittent triphasic changes in the colour of the extrem- A symptom diary can help to produce a clear picture of
ities (fingers, toes, nose, cheeks, and ears)—usually trig- attacks. Encourage patients to photograph the affected
gered by cold exposure or emotional stress—from white extremities during an attack.
(owing to vasoconstriction), to blue (tissue hypoxia), to A full systemic inquiry will detect secondary causes (box
red on rewarming (reperfusion) (figs 1 and 2). Colour 2). Key questions to ask include whether the patient has
changes are associated with tightness in the first two any evidence of a rash, photosensitivity, migraines, joint
stages and burning pain in the reperfusion stage. Not pains, ulcers, dysphagia, and xerostomia. Occupations
all of the three phases are needed to make a diagnosis.7 of note are those involving cold exposure and vibrating
Colour changes occur intermittently and tend to resolve tools. If employers do not help facilitate reduced exposure
when the digits are rewarmed. An attack may last for min- to vibrating tools, patients may be entitled to compensa-
utes to hours. Patients with secondary Raynaud’s phe- tion under the Control of Vibration at Work Regulations
nomenon are more likely to have severe disease, which, 2005.9 Ask about drugs that may predispose patients to
if left untreated, can progress to ulceration or gangrene the phenomenon or aggravate it: β blockers, vinyl chloride,
of extremities. chemotherapy, ergot derivatives, amphetamines, cocaine,
oestrogen (unopposed oestrogen replacement therapy, oral
What causes Raynaud’s phenomenon? contraceptives), clonidine, and sympathomimetics. Also
The pathophysiology of Raynaud’s phenomenon is poorly ask about current smoking because smoking aggravates
understood and is thought to differ between primary and the condition.
secondary disease. A recent review discussed pathogen- The Raynaud’s condition score (box 3) is an ordinal
score from 0-10 that measures the level of difficulty expe-
rienced by patients; it may help determine the impact of
the condition on the patient’s functioning.

Examination (look, feel, move)

Examination may be tailored according to clues from the
history.
In the hands look for colour changes, nail bed changes,
JOHN RADCLIFFE HOSPITAL/SCIENCE PHOTO LIBRARY

and skin integrity. Sclerodactyly, flexion deformities, tendon

friction rubs, and calcinosis are seen in systemic sclerosis.
Digital ulcerations (fig 3) are not normal and always
reflect secondary Raynaud’s phenomenon; they should
prompt careful examination for other signs of connective
tissue disease and referral to a specialist.
Feel for peripheral pulses. Synovitis suggests an inflam-
matory arthropathy.
Move all joints and assess for pain and contracture.
In the face look for a malar rash, non-scarring alo-
Fig 2 |  Severe Raynaud’s phenomenon showing colour changes and digital ulceration pecia, and oral ulcers, which may suggest systemic lupus

38 BMJ | 11 FEBRUARY 2012 | VOLUME 344

 CLINICAL REVIEW

e­rythematous, and for tightening of the skin, which is indic-

ative of systemic sclerosis.
Identify any dry skin, telangiectasia, and the salt and pep-
per appearance of hyperpigmentation and hypopigmenta-
tion, which are indicative of systemic sclerosis. Also look for
livedo reticularis, which suggests systemic lupus erythema-
tous or antiphospholipid syndrome.
Assess for arrhythmias, especially atrial fibrillation and
murmurs, which provide evidence of thromboembolic dis-
ease (or rarely Libman-Sacks endocarditis). Pulmonary
fibrosis suggests systemic sclerosis.

Box 2 | Distinguishing primary and secondary Raynaud’s Fig 3 |  Digital ulcer in severe Raynaud’s phenomenon
phenomenon Investigations
Primary disease Patients with primary Raynaud’s phenomenon do not rou-
Younger age (<30, but can be any age) tinely need blood tests.
Female Patients with a clinical suspicion of secondary Raynaud’s
Genetic component (30% have an affected first degree phenomenon should have a full blood count to look for
relative3) anaemia and lymphopenia, which suggest an underlying
No symptoms/signs of underlying disease autoimmune disease; immunology tests for antinuclear
No tissue necrosis or gangrene antibodies (ANA), extractable nuclear antibodies (ENA), anti
Normal nail fold capillaries Scl-70 (topoisomerase I), anti-Ro (SS-A), and anti-La (SS-B);
Normal erythrocyte sedimentation rate inflammatory markers such as erythrocyte sedimentation
Negative antineutrophil antibodies rate and plasma viscosity. Negative results cannot exclude
Secondary disease a secondary cause.
Older age (>30, but can be any age) Patients with unilateral signs should have a chest radio-
Less common (10-20%) graph to look for a cervical rib compressing the bronchial
Symptoms and signs of underlying disease and cephalic vascular branches. Perform magnetic reso-
Tightness of finger skin; more severe pain nance imaging if thoracic outlet syndrome is suspected.
Digital ischaemia (digital pitting scars, ulceration, or gangrene) Specialist investigations performed in secondary care
Abnormal nail fold capillaries include infrared thermography, laser Doppler flowmetry,
Raised erythrocyte sedimentation rate portable radiometry, and digital plethymography, all of
Positive antineutrophil antibodies or anti-extractable nuclear which highlight a pattern of changes consistent with scle-
antigen antibodies roderma (box 4). The results of these are often analysed
together with a cold stimulation test, which measures the
Box 3 | Raynaud’s condition scorew7 response of the digits to cooling and rewarming. Digits usu-
The patient is asked about the frequency, duration, and severity ally rewarm in less than 15 minutes, but in Raynaud’s phe-
of attacks to arrive at a single score expressed on a scale of 0-10 nomenon this phase is longer than 20 minutes.
(0=patient not handicapped by attacks; 10=patient extremely Refer patients with suspected secondary disease for capil-
handicapped). laroscopy if possible because ophthalmoscopy (20× magnifi-
Questions cation, dermatoscope 10× magnification) can miss capillary
How many attacks have you had today? changes. The gold standard method is videocapillaroscopy
How long did they last? (200× magnification, or a biomicroscope). A patient with pri-
How much pain, numbness, or other symptoms have you had mary Raynaud’s phenomenon will have regular disposition
today? of capillary loops along the nail bed. In contrast, patients
How much has Raynaud’s affected the use of your hands today? with secondary disease will have architectural disorgani-
sation, giant capillaries, haemorrhages, loss of capillaries,
Box 4 | Specialist secondary care investigations angiogenesis, and avascular areas (“scleroderma pattern,”
Infrared thermography seen in 95% cases of systemic sclerosis).10 Around 80% of
Detects infrared energy emitted from skin, converts it to patients with Raynaud’s phenomenon, scleroderma antibod-
temperature, and displays an image of temperature distribution ies, and a scleroderma pattern on capillaroscopy will develop
Laser Doppler flowmetry scleroderma after 15 years, but if capillaroscopy is normal
A non-invasive continuous measure of microcirculatory blood flow the likelihood of developing scleroderma is almost nil.6
that uses monochromatic light emitted from a low power laser Capillaroscopy is now part of the new definition for early
Portable radiometry systemic sclerosis proposed by the European League Against
Measures the temperature at the centre of the whorl of the Rheumatism (EULAR).11
palmar aspect of each fingertip
Digital plethymography When and who to refer?
Air pressures that occur in a sensing cuff applied to the finger Most patients can be managed in primary care. However,
are amplified and filtered to make it possible to measure arterial referral (usually to a rheumatologist) should be consid-
blood flow
ered if:

BMJ | 11 FEBRUARY 2012 | VOLUME 344 39

CLINICAL REVIEW

•   The diagnosis is in doubt cessation may help to reduce the severity but not occur-
•   A secondary cause is suspected rence of the condition.14
•   The cause is thought to be job related (refer to Ginkgo biloba has been investigated over the past 10
occupational health services) years. A double blind placebo controlled trial found a
•   The patient is aged under 12 years 56% reduction in the frequency of attacks in established
•   Digital ulcerations are present Raynaud’s phenomenon (compared with a 27% reduction
•   The symptoms are poorly controlled, despite in the placebo group).15 Another randomised multicentre
appropriate conservative management. flexible dose open trial found a 31% reduction compared
with 50.1% for nifedipine, suggesting that Ginkgo may not
How is Raynaud’s phenomenon treated? be as effective as nifedipine.16 However, given that Ginko
The first step in managing Raynaud’s phenomenon in had no adverse effects and was well tolerated, further
primary care is lifestyle modification. Such advice can be research may be worthwhile.
given to patients while awaiting investigations and referral
to secondary care if an underlying cause is suspected. Most Drug treatments
people with primary Raynaud’s phenomenon respond Several randomised controlled trials are under way that
well to lifestyle measures and need no further treatment. may lead to an increase in the number of treatments for
Patients with secondary Raynaud’s phenomenon require Raynaud’s phenomenon. However, to date, no guidelines
treatment of the underlying disorder, which entails referral have been published on the medical treatment of Ray-
to secondary care. naud’s phenomenon. We discuss drugs that are currently
used off-label in the treatment of this condition and which
Non-drug based treatments the clinician may consider using on a case by case basis,
Conservative approaches to treatment aim to reduce expo- taking care to balance evidence on efficacy versus toxi­
sure to triggers, such as cold and emotional stress. city. It is also important to review prescription drugs that
Advise the patient to try to keep warm, perhaps by using ag­gravate symptoms.
hand and feet warmers, which are commercially available.
The frequency and severity of attacks can be reduced by Vasodilators
avoiding dramatic changes in environmental temperature Calcium channel blockers—Non-cardioselective dihydropy-
and taking steps to reduce occupational cold exposure. ridine calcium channel blockers are most widely used in
Vasodilation can be increased during attacks by rotating the treatment of Raynaud’s phenomenon. Nifedipine pro-
the arms in a windmill pattern, placing the hands under motes relaxation of vascular smooth muscle cells and leads
warm water or in a warm body fold such as the axilla, to vasodilatation. A meta-analysis of randomised control-
and performing the swing-arm manoeuvre (raising both led trials found that nifedipine (10-20 mg three times
arms above the shoulders and forcefully swinging them daily) reduced the number of attacks by 2.8-5.0 a week
across the body to generate a force that promotes blood and reduced their severity by 33%. However, effects may be
flow distally to the fingers).12 Another simple tip is to avoid short lived, and longer acting calcium channel blockers or
carrying bags by the handles, which impairs circulation amlodipine and diltiazem may be needed.17 Unfortunately,
to the fingers.4 There is little objective evidence to suggest patients commonly report troubling adverse effects such
that any nutritional supplement benefits patients with as hypotension, flushing, headache, and tachycardia, so
the condition. Minimising stress through general relaxa- alternative treatments have been researched.
tion techniques may be of benefit. Biofeedback has been Topical nitrates—A randomised controlled study of 33
a popular treatment, but a recent Cochrane review found patients found that topical glyceryltrinitrate applied to the
it to be no more effective than sham biofeedback.13 Sup- dorsum of the finger resulted in digital vasodilatation with
port groups can provide helpful tips and guidance on self fewer systemic side effects than with oral nitrates.18 Two
management. A prospective study showed that smoking large recent randomised controlled trials of MQX-503, a
new formulation of nitroglycerin, applied to the affected
TIPS FOR THE NON-SPECIALIST finger found that it reduces the severity of Raynaud’s phe-
Examine patients with troublesome Raynaud’s phenomenon nomenon, but not the duration or frequency of attacks.19  20
carefully, looking for an underlying condition, although 80-90% Evidence on topical nitrates is limited, but the results of
will have no identifiable cause current trials may provide more robust evidence of efficacy.
Offer conservative management options to everyone, even Prostaglandins—Prostaglandins have vasodilatory and
those awaiting referral or investigations; these include antiproliferative effects, and they inhibit platelet aggrega-
avoidance of stress and cold, smoking cessation, and ensuring tion. Their side effects are similar to those of calcium chan-
that extremities are kept warm nel blockers. The European League Against Rheumatism
Nifedipine is the only drug licensed for use; other effective recommends prostaglandins when calcium channel block-
treatments are used off-label and are best prescribed by a ers have failed.21 Most published studies have focused on
specialist the use of intravenous iloprost. A randomised open label
Refer patients with possible underlying disease, those who
single centre study and a 2009 Cochrane review found that
present with ulceration or signs of ischaemic digits, and those iloprost reduces the frequency and severity of attacks.22  23
whose symptoms do not improve on treatment with a calcium A randomised study found cyclic use to be beneficial in
channel blocker to a specialist terms of patient adherence and quality of life.24 However,
two randomised controlled trials found that iloprost was

40 BMJ | 11 FEBRUARY 2012 | VOLUME 344

 CLINICAL REVIEW

ONGOING RESEARCH
Endothelin receptor antagonists (bosentan)—Endothe-
lin is a potent vasoconstrictor of vascular smooth muscle
Trials are currently testing rho kinase inhibitors as a method of cells. Among its other actions, bosentan exerts a consistent
vasodilation
effect on vasculature. The Randomized Placebo-controlled
MQX-503 (nitroglycerin) shows potential in reducing the Investigation of Digital Ulcers in Scleroderma (RAPIDS-1
severity of Raynaud’s phenomenon
and 2) trials have shown that the number of new digital
Preliminary reports suggest that botulinum toxin A improves ulcers in patients with secondary Raynaud’s phenomenon
symptoms, reduces the frequency of attacks, and improves the
decreased significantly when treated with bosentan.21 The
healing of digital ulcers
European League Against Rheumatism recommends its use
Oral phosphodiesterase type 5 inhibitors may be effective in
when symptoms are refractory to treatment with calcium
patients with severe and disabling Raynaud’s phenomenon,
although further studies are needed
channel blockers and prostaglandins.
Serotonin reuptake inhibitors—The exact role of sero-
tonin reuptake inhibitors in the treatment of Raynaud’s
only slightly better than nifedipine,25 and because ilo- phenomenon is not yet clear. These agents block the
prost is more expensive, the European League Against uptake of serotonin, which is a vasoconstrictor. A pilot
R­heumatism has advised that nifedipine should remain the study of 53 patients showed that fluoxetine reduces the
first line drug for patients with Raynaud’s phenomenon. severity and frequency of attacks compared with nifed-
A double blind multicentre placebo controlled study and ipine in primary Raynaud’s phenomenon. Its effect in sec-
randomised double blind study found that orally admin- ondary Raynaud’s phenomenon was less pronounced.w1
istered prostaglandins are less effective than intravenous A Cochrane review of a small number of studies con-
ones, although higher doses may confer benefit.21 Research cluded that another serotonin reuptake inhibitor, ketan-
is currently ongoing into the use of treprostinil, an oral serin, was not beneficial in the treatment of Raynaud’s
pr­ostaglandin analogue. phenomenon.w2 This agent may have a role in patients
Phosphodiesterase type 5 inhibitors (sildenafil, tadala- who cannot tolerate other drugs because of hypotension,
fil, and vardenafil)—Phosphodiesterase type 5 breaks but more research is needed.
down cGMP in endothelial cells. Inhibition of this enzyme Botulinum toxin A—Botulinum toxin A blocks vasocon-
increases the amount of cGMP available to promote vascu- striction and, although there are no blinded placebo trials
lar smooth muscle relaxation and blood flow. A randomised to date, preliminary reports have suggested that it can
double blind placebo controlled fixed dose crossover study improve symptoms, decrease frequency of attacks, and
and two case series found a decrease in the frequency and improve healing of digital ulcers.w3 w4
severity of attacks in patients treated with oral sildenafil but
not tadalafil compared with placebo. These inhibitors also Others
have a favourable effect on the Raynaud’s condition score Statins—After the observation that statins affect endothe-
and ulcer healing.26‑28 The benefits of these orally delivered lial function, a 2008 randomised trial compared
and well tolerated drugs suggest that they may be an effec- atorvastatin and placebo in patients with Raynaud’s phe-
tive treatment for patients with severe and disabling Ray- nomenon associated with systemic sclerosis. Treatment
naud’s phenomenon, although further studies are needed. with atorvastatin reduced the number of digital ulcers
Antioxidants—N-acetylcysteine acts as a vasodilator via compared with placebo. Endothelial markers of activation
modulation of the vasodilator adrenomedullin. A recent also improved compared with placebo.w5
observational study found that it decreases the frequency Aspirin—Although there is no firm evidence to support
and severity of attacks. The number of digital ulcers and its use in patients with Raynaud’s phenomenon, daily
ulcer healing also improved.29  30 aspirin is commonly prescribed for patients who have no
contraindications.
Inhibitors of vasoconstriction
Angiotensin receptor antagonists—A randomised control- Does surgery have a role in treatment?
led trial suggested that losartan reduces the frequency and For a small number of patients with severe and disabling
severity of attacks to a greater extent than nifedipine.31 The symptoms surgical intervention may be considered.
European League Against Rheumatism recommends its use, Surgical interventions include arterial reconstruction,
but this is an informal recommendation because of the lack peripheral sympathectomy, embolectomy, and ulcer
of sufficient evidence. d­ebridement, or a combination of techniques.
Angiotensin converting enzyme inhibitors—These drugs Cervical sympathectomy is no longer recommended
are no longer recommended since a randomised double because observational studies showed that it was not
blind placebo controlled trial found that they do not reduce effective in the long term and that side effects were
digital ulcers or the frequency or severity of attacks.32 intolerable—patients often needed digital amputation.
α1 adrenoceptor blockers—Limited low level evidence A therapeutic study with grade III evidence study found
from a randomised double blind placebo controlled cross­ that digital artery (palmar) sympathectomy can lead to
over study of 24 patients suggests that prazosin may reduce complete healing and a decrease in the number of ulcers,
the frequency but not the severity of attacks compared with although it is a highly specialised procedure and this ben-
placebo. However, prazosin is rarely used in the treatment efit is not seen for chronic digital ischaemia.w6 Decom-
of Raynaud’s phenomenon because its potential adverse pression arteriolysis and arterial reconstruction can be
effects outweigh any benefit.33 performed at the same time.

BMJ | 11 FEBRUARY 2012 | VOLUME 344 41

 CLINICAL REVIEW

7 Wigley F. Raynaud’s phenomenon. N Engl J Med 2002;347:1001-8.

ADDITIONAL EDUCATIONAL RESOURCES 8 Herrick AL. Pathogenesis of Raynaud’s phenomenon. Rheumatology
(Oxford) 2005;44:587-96.
Resources for healthcare professionals 9 Health and Safety Executive. Control of vibration at work regulations 2005.
Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati www.hse.gov.uk/vibration/hav/regulations.htm.
I, Czirjak L. EULAR recommendations for the treatment of 10 Herrick AL, Cutolo M. Clinical implications from capillaroscopic analysis
in patients with Raynaud’s phenomenon and systemic sclerosis. Arthritis
systemic sclerosis: a report from the EULAR Scleroderma Trials Rheum 2010;62:2595-604.
and Research group (EUSTAR). Ann Rheum Dis 2009;68:620-8 11 Avouac J, Mogavero G, Guerini H, Drapé J, Mathieu A, Kahan A, et al.
Raynaud’s and Scleroderma Association (www.raynauds. Predictive factors of hand radiographic lesions in systemic sclerosis: a
prospective study. Ann Rheum Dis 2011;70:630-3.
org.uk/images/stories/PDF/hpbooklet2011.pdf)—Contains 12 Bakst R, Merola JE, Franks AG Jr, Sanchez M. Raynaud’s phenomenon:
information on Raynaud’s phenomenon and scleroderma for pathogenesis and management. J Am Acad Dermatol 2008;59:633-53.
patients and healthcare professionals 13 Malefant D, Catton M, Pope JE. The efficacy of complementary and
alternative medicine in the treatment of Raynaud’s phenomenon: a literature
Herrick A. Raynaud’s phenomenon. Curr Treat Options review and meta-analysis. Rheumatology (Oxford) 2009;48:791-5.
Cardiovasc Med 2008;10:146-55 14 Suter LG, Murabito JM, Felson DT, Fraenkel L. Smoking, alcohol
consumption, and Raynaud’s phenomenon in middle age. Am J Med
Levien TL. Advances in the treatment of Raynaud’s 2007;120:264-71.
phenomenon. Vasc Health Risk Manage 2010;6:167-77 15 Muir AH, Robb R, McLaren M, Daly F, Belch JJ. The use of Ginkgo biloba
in Raynaud’s disease: a double-blind placebo-controlled trial. Vasc Med
Baumhäkel M, Böhm M. Recent achievements in the 2002;7:265-7.
management of Raynaud’s phenomenon. Vasc Health Risk 16 Choi WS, Choi CJ, Kim KS, Lee JH, Song CH, Chung JH, et al. To compare
Manage 2010;6:207-14 the efficacy and safety of nifedipine sustained release with Ginkgo
biloba extract to treat patients with primary Raynaud’s phenomenon
Bakst R, Merola JE, Franks AG Jr, Sanchez M. Raynaud’s in South Korea; Korean Raynaud study (KOARA study). Clin Rheumatol
phenomenon: pathogenesis and management. J Am Acad 2009;28:553-9.
Dermatol 2008;59:633-53 17 Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s
phenomenon: a meta-analysis. Rheumatology (Oxford) 2005;44:145-50.
Resources for patients 18 Anderson ME, Moore TL, Hollis S, Jayson MI, King TA, Herrick AL. Digital
Raynaud’s and Scleroderma Association (www.raynauds.org. vascular response to topical glyceryl trinitrate, as measured by laser
Doppler imaging, in primary Raynaud’s phenomenon and systemic
uk)—Information for patients and healthcare professionals sclerosis. Rheumatology (Oxford) 2002;41:324-8.
Arthritis Research UK (www.arthritisresearchuk.org)— 19 Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S. MQX-
503, a novel formulation of nitroglycerin, improves the severity of
Information leaflets for patients Raynaud’s phenomenon: a randomized, controlled trial. Arthritis Rheum
Patient.co.uk (www.patient.co.uk/health/Raynaud’s- 2009;60:870-7.
Phenomenon-(Cold-Hands).htm)—Information for patients on 20 Belch J, Fiorentino D, Denton C, Herrick A, Sule S, Steen V, et al. MQX-503,
a novel topical nitroglycerin formulation, improves severity of symptoms
Raynaud’s phenomenon associated with Raynaud’s phenomenon [abstract]. Arthritis Rheum
Health and safety executive (www.hse.gov.uk/vibration/hav/ 2008;58(9 suppl):S622.
21 Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati I, Czirjak L.
index.htm)—Information on claiming compensation for hand EULAR recommendations for the treatment of systemic sclerosis: a report
and arm vibration syndrome from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann
International scleroderma network (www.sclero.org)— Rheum Dis 2009;68:620-8.
22 Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells GA, et al. Iloprost and
Comprehensive information on Raynaud’s phenomenon, cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis.
particularly when related to scleroderma; includes recent Cochrane Database Syst Rev 2000;2:CD000953.
evidence based references, photographs, patient stories, and tips 23 Kawald A, Burmester GR, Huscher D, Sunderkotter C, Riemerkasten G. Low
versus high-dose iloprost therapy over 21 days in patients with secondary
Raynaud’s phenomenon and systemic sclerosis: a randomized, open,
In chronic ulceration and in critical digital ischaemia, single-center study. J Rheumatol 2008;35:1830-7.
24 Milio G, Corrado E, Genova C, Amato C, Raimondi F, Almasio PL, et al.
surgical debridement may reduce the need for amputa- Iloprost treatment in patients with Raynaud’s phenomenon secondary
tion if osteomyelitis develops. to systemic sclerosis and the quality of life: a new therapeutic protocol.
Rheumatology 2006;45:999-1004.
Contributors: All authors contributed equally to the writing of this article. AM
25 Scorza R, Caronni M, Mascagni B, Berruti V, Bazzi S, Micallef E. Effects of
and BG are guarantors. Thanks to April Lauren Rose Goundry (fourth year long-term cyclic iloprost therapy in systemic sclerosis with Raynaud’s
medical student), who helped to edit and proofread this review article. phenomenon: a randomized, controlled study. Clin Exp Rheumatol
Funding: No special funding received. 2001;19:503-8.
26 Herrick AL. Modified-release sildenafil reduces Raynaud’s phenomenon
Competing interests: All authors have completed the ICMJE uniform disclosure attack frequency in limited cutaneous systemic sclerosis. Arthritis Rheum
form at www.icmje.org/coi_disclosure.pdf (available on request from the 2011;63:775-82.
corresponding author) and declare: no support from any organisation for the 27 Schiopu E, Vivien M, Impens A, Rothman J, McCloskey D, Wilson J,
submitted work; no financial relationships with any organisations that might et al. Randomized placebo-controlled crossover trial of tadalafil in
have an interest in the submitted work in the previous three years; no other Raynaud’s phenomenon secondary to systemic sclerosis. J Rheumatol
relationships or activities that could appear to have influenced the submitted 2009;36:2264-8.
work. 28 Shenoy P, Kumar S, Lalan KJ, Choudhary C, Singh U, Misra R, et al. Efficacy
of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator
Provenance and peer review: Not commissioned; externally peer reviewed. therapy: a double-blind randomized cross-over trial. Rheumatology
Patient consent obtained. (Oxford) 2010;49:2420-8.
29 Rosato E Borghese F, Pisarri S, Salsano F. Long-term therapy with NAC,
1 Reynaud’s and Scleroderma Association. Coping with Raynaud’s. www.
in patients with SSc, has a durable effectiveness on ischemic ulcers and
raynauds.org.uk/raynauds/coping-with-raynauds.
Raynaud’s phenomenon. Clin Rheumatol 2009;28:1379-84.
2 Fraenkel L. Raynaud’s phenomenon: epidemiology and risk factors. Curr
30 Sambo P, Amico D, Giacomelli R, Matucci-Cerinic M, Salsano F, Valentini G,
Rheumatol Rep 2002;4:123-8.
et al. Intravenous N-acetylcysteine for treatment of Raynaud’s phenomenon
3 Palmer K, Griffin M, Syddall H, Pannett B, Cooper C, Coggon D. Prevalence
secondary to systemic sclerosis: a pilot study. J Rheumatol 2001;28:2257-
of Raynaud’s phenomenon in Great Britain and its relation to hand
62.
transmitted vibration: a national postal survey. Occup Environ Med
31 Dziadzio M, Denton CP, Smith R, Howell A, Blann A, Bowers E, et al. Losartan
2000;57:448-52. therapy for Raynaud’s phenomenon and scleroderma. Arthritis Rheum
4 Reynaud’s and Scleroderma Association. Digital ulcers. www.raynauds.org. 1999;42:2646-55.
uk/component/content/article/138. 32 Gliddon A, Dore C, Black CM, McHugh N, Moots R, Denton CP, et al.
5 Riera G, Vilardell M, Vaqué J, Fonollosa V, Bermejo B. Prevalence of Prevention of vascular damage in scleroderma and autoimmune Raynaud’s
Raynaud’s phenomenon in a healthy Spanish population. J Rheumatol phenomenon. Arthritis Rheum 2007;56:3837-46.
1993;20:66-9. 33 Wollershiem H, Thien T, Fennis J, Van Elteren P, Van’t Laar A. Double-blind,
6 Koening M, Joyal F, Fritzler M, Roussin A, Abrahamowicz M, Boire C, et al. placebo-controlled study of prazosin in Raynaud’s phenomenon. Clin
Autoantibodies and microvascular damage are independent predictive Pharmacol Ther 1986;40:219-25.
factors for the progression of Raynaud’s phenomenon to systemic sclerosis.
Arthritis Rheum 2008;58:3902-12. Accepted: 05 January 2012

42 BMJ | 11 FEBRUARY 2012 | VOLUME 344