Raynaud phenomenon and digital ischaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Raynaud phenomenon is a clinical vasospastic response of fingers or toes to cold or emotional stress. Ask patients to describe the sequence, border, duration, trigger, pain and reversibility and to provide dated photographs when safe. Examine hands warm and cold-neutral for ulcers, pits, pulp loss, calcinosis, sclerodactyly, nailfold abnormalities and pulses. Primary disease is common and benign; secondary disease combines vasospasm with structural vessel injury and can threaten tissue.

The distinction is based on the whole phenotype rather than an ANA result. Later onset, asymmetry, prolonged painful attacks, thumb involvement, tissue injury or systemic features prompt FBC, renal and urine tests, inflammatory markers, ANA with phenotype-directed antibodies and nailfold capillaroscopy. If pulses are absent or a single territory is affected, evaluate large-vessel, embolic, compressive and occupational injury with duplex or angiographic imaging. A normal ANA does not override fixed ischaemia.

Non-drug management reduces sympathetic and endothelial stress: warm the core, layer clothing, pre-warm vehicles and rooms, avoid sudden temperature changes, stop smoking and protect fragile skin. Modified-release nifedipine is usually first oral therapy. Sildenafil, losartan, fluoxetine or other agents are selected when standard treatment is ineffective or poorly tolerated, but their evidence and indications differ. Severe systemic-sclerosis digital vasculopathy may require iloprost and ulcer-prevention strategies.

Critical digital ischaemia is an emergency. Provide warmth without direct burning heat, strong analgesia and rapid specialist assessment. Search for thrombosis, embolism, proximal obstruction, vasculitis, infection and systemic-sclerosis crisis. Intravenous prostanoid, nerve block, angiography, revascularisation or sympathectomy may be required. Debridement waits for perfusion and tissue demarcation unless infection mandates source control.

Key points

Raynaud phenomenon is episodic, sharply demarcated digital colour change triggered by cold or emotion; not every patient experiences all three white, blue and red phases.
Primary Raynaud is usually young-onset, symmetrical, thumb-sparing, reversible and non-ulcerating, with normal pulses, nailfolds and systemic assessment.
Secondary clues are later onset, severe pain, asymmetry, thumb involvement, ulcer or pit, abnormal nailfold capillaries, systemic features, absent pulses or relevant medicine and occupational exposure.
Critical ischaemia is persistent rather than episodic: rest pain, fixed pallor or cyanosis, numbness, ulcer progression or necrosis needs same-day care.
First-line care is whole-body warmth, gloves, rapid rewarming, smoking cessation, avoidance of vibration and review of beta blockers, stimulants, decongestants and other vasoconstrictors.
For troublesome uncomplicated attacks, modified-release nifedipine is the usual first oral medicine; titrate against attack burden, pressure, headache, oedema and reflux.
Sildenafil is a specialist next option for severe secondary Raynaud or digital ulcers; never combine it with nitrates or riociguat.
Intravenous iloprost is an urgent specialist treatment for severe refractory attacks, ulcer progression or threatened tissue, with continuous pressure and adverse-effect monitoring.
Use ANA, disease-specific antibodies and nailfold capillaroscopy when secondary disease is plausible, but pursue duplex or angiography when proximal or focal occlusion is suspected.
Antiplatelet and anticoagulant treatment is not routine for primary vasospasm; use it only for a defined thrombotic, embolic or vascular indication.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Primary vasospastic disease

Primary Raynaud commonly begins in adolescence or early adulthood, is symmetrical, lacks tissue injury and occurs without a structural vascular or systemic inflammatory disorder.

Connective-tissue vasculopathy

Systemic sclerosis is the strongest autoimmune association, while lupus, mixed connective-tissue disease, inflammatory myopathy, Sjogren disease and vasculitis can produce secondary attacks.

Occlusive, occupational and medicine causes

Atherosclerosis, emboli, thoracic outlet disease, hypothenar-hammer injury, vibration, frostbite, smoking, stimulants, beta blockers and selected chemotherapy can impair digital flow.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Exaggerated vasoconstriction
Cold or emotional sympathetic activation causes excessive digital arterial and arteriolar constriction, reducing flow and producing sharply demarcated pallor and cyanosis.
2
Reperfusion response
Vessel relaxation restores oxygenated flow, causing erythema, throbbing, paraesthesia and warmth; the familiar white-blue-red sequence is helpful but not required.
3
Structural microangiopathy
Secondary disease adds endothelial injury, intimal proliferation, capillary loss and thrombosis, making attacks more prolonged and capable of ulceration or gangrene.
4
Critical tissue oxygen failure
Persistent severe hypoperfusion crosses from episodic vasospasm to ischaemic nerve and tissue injury, requiring rapid vasodilation and correction of an occlusive cause.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Primary attack pattern

Brief symmetrical cold-triggered episodes reverse fully with warming and occur without ulcer, abnormal pulse, nailfold change or systemic symptom.

Scleroderma-spectrum pattern

Puffy fingers, sclerodactyly, telangiectasia, pits, ulcers, reflux or abnormal capillaroscopy with Raynaud suggests systemic-sclerosis-spectrum disease.

Fixed digital ischaemiaRed flag

Persistent rest pain, non-blanching pallor or cyanosis, paraesthesia, pulp loss or necrosis indicates threatened tissue rather than ordinary vasospasm.

Proximal occlusive patternRed flag

A single hand, absent pulse, bruit, pressure asymmetry or acute continuous symptoms suggests embolus, thrombosis, thoracic outlet or arterial injury.

Medicine or occupational pattern

Temporal association with stimulants, beta blockers, chemotherapy, vibrating tools, repetitive hypothenar trauma or cold work may reveal a modifiable cause.

Red flags requiring action

Pain or colour change that does not reverse with warming, new sensory loss, weakness, ulceration or black tissue requires urgent digital-ischaemia care.
Absent or asymmetric upper-limb pulses, major inter-arm pressure difference or acute onset suggests embolic, thrombotic or large-vessel obstruction.
New Raynaud after age thirty, severe asymmetry, thumb involvement, abnormal nailfolds, puffy or tight skin, inflammatory features or systemic illness suggests secondary disease.
Fever, purulence, spreading erythema or rapidly progressive pain around an ulcer requires infection and osteomyelitis assessment alongside perfusion care.
Pregnancy with severe vasculopathy, hypertension or renal symptoms requires specialist review before changing vasoactive or renin-angiotensin medicines.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
History, pulses and vascular examinationFirst step
Why
Separate episodic small-vessel vasospasm from fixed digital or proximal arterial disease.
Interpretation and limitations
Document temperature, refill, Allen test, wounds, all upper-limb pulses and bilateral pressures; absent flow or neurological change demands urgent imaging.
02
Nailfold capillaroscopy
Why
Identify structural scleroderma-spectrum microangiopathy in secondary Raynaud assessment.
Interpretation and limitations
Giant capillaries, haemorrhage, capillary loss and abnormal repair support secondary CTD; trauma and other autoimmune disease require expert context.
03
FBC, ESR or CRP, renal profile and urinalysis
Why
Screen systemic inflammation, cytopenia and organ involvement when secondary disease is plausible.
Interpretation and limitations
Normal markers do not exclude systemic sclerosis; anaemia, eosinophilia, renal change or haematuria redirects the diagnostic pathway.
04
ANA and phenotype-directed autoantibodies
Why
Support connective-tissue classification after history and examination indicate meaningful pre-test probability.
Interpretation and limitations
Select centromere, topoisomerase-I, RNA-polymerase-III, RNP, dsDNA or myositis tests from phenotype; isolated ANA does not prove secondary disease.
05
Duplex ultrasound
Why
Assess suspected proximal stenosis, occlusion, embolic source or thoracic-outlet flow abnormality.
Interpretation and limitations
Normal large-vessel flow does not exclude microvascular disease; focal abnormality may require CTA, MRA or catheter angiography for intervention planning.
06
Angiography for threatened tissue
Why
Define treatable digital and proximal anatomy when revascularisation, thrombolysis or surgery is being considered.
Interpretation and limitations
Choose CTA, MRA or catheter angiography with vascular specialists, balancing resolution, kidney function and the need for immediate intervention.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Acrocyanosis

Persistent painless symmetrical blue discoloration without episodic pallor, ulceration or clear reperfusion favours acrocyanosis rather than Raynaud phenomenon.

Erythromelalgia

Burning red hot extremities triggered by warmth and relieved by cooling has the opposite thermal pattern and may accompany a myeloproliferative disorder.

Acute arterial occlusion

Sudden continuous pain, pallor, pulselessness, sensory or motor change indicates embolic or thrombotic limb ischaemia rather than a self-limited vasospastic attack.

Chilblains and cold injury

Persistent itchy or painful inflammatory lesions after cold exposure, blistering or tissue freezing indicates perniosis or frostbite, which follows a different injury course.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line classificationSeparate primary from secondaryFirst stepFirst lineEpisodic cold- or stress-induced digital colour change is reported without current fixed ischaemia.

1Document onset, symmetry, thumb involvement, phases, duration, pain, reversibility, ulcers, systemic symptoms, medicines, smoking, work and vibration exposure.
2Examine pulses, pressures, skin, nailfolds, joints and connective-tissue signs; reserve antibodies and capillaroscopy for a secondary phenotype.
3Diagnose primary Raynaud only when examination and trajectory are reassuring, and give return advice for persistent pain, asymmetry, ulcer or systemic change.

02Preferred symptom treatmentProtect first, then vasodilatePreferredReversible attacks impair function despite trigger reduction and warming.

1Optimise whole-body warmth, gloves, skin care, smoking cessation and removal of avoidable vasoconstrictors or vibration.
2Start modified-release nifedipine and titrate to benefit while monitoring pressure, dizziness, oedema, headache and reflux.
3AlternativeIf ineffective or not tolerated, refer severe secondary disease for sildenafil or another specialist alternative rather than uncontrolled polypharmacy.

03Ischaemia escalationRescue threatened tissueEscalationPain or colour becomes fixed, sensation falls, an ulcer progresses or necrosis appears.

1Provide same-day hospital assessment, warmth, analgesia, infection review and duplex or angiography for thrombosis or proximal occlusion.
2Begin specialist intravenous iloprost and optimise oral vasodilation, avoiding nitrates with PDE5 inhibitors and monitoring continuous pressure.
3Coordinate vascular intervention, digital sympathectomy, wound care, antibiotics for proven infection and delayed debridement according to perfusion.

04Systemic disease routeUse Raynaud as an organ clueAbnormal nailfolds, puffy or tight skin, inflammatory symptoms, weakness or organ features accompany attacks.

1Request phenotype-directed serology and baseline blood, renal, urine, lung and cardiac assessment without delaying care for a threatened digit.
2Refer rheumatology and route ILD, PAH, renal-crisis, myositis or vasculitis findings to the corresponding urgent organ pathway.
3Continue vascular prevention while disease-modifying treatment addresses the systemic process; immunosuppression alone does not reliably restore fixed flow.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Usual first oral vasodilator for troublesome primary or secondary Raynaud after non-drug protection is optimised; the Raynaud indication is off-label for many UK modified-release products.

Nifedipine modified release

Give 30 mg by mouth once a day initially. According to attack response, blood pressure and the selected modified-release product, raise the dose, commonly to 60 mg once daily.

Monitor headache, flushing, ankle oedema, tachycardia, dizziness and reflux; reduce or stop for symptomatic hypotension. Review CYP3A4 interactions, pregnancy and gastrointestinal obstruction risk for the selected product, and do not crush modified-release tablets.

PDE5 inhibition augments digital flow when calcium-channel blockade is inadequate; Raynaud and digital-ulcer use is separate from its licensed pulmonary-hypertension indication.

Sildenafil

For severe secondary Raynaud or digital ulceration, a common specialist off-label regimen is 20 mg orally three times daily, titrated only within the vascular or systemic-sclerosis plan.

Never combine with nitrates or riociguat. Review hypotension, cardiac disease, renal or hepatic impairment, pregnancy, CYP3A4 interactions and visual, hearing or prolonged-erection adverse effects.

Licensed prostacyclin-analogue treatment for severe Raynaud with progressive trophic injury and a specialist rescue option for threatened ischaemic tissue.

Intravenous iloprost

Start 0.5 nanograms/kg/min intravenously and increase every thirty minutes by 0.5 to the maximum tolerated 1.5–2 nanograms/kg/min; infuse for six hours daily on five consecutive days in a monitored unit.

Monitor pressure and pulse at each increase; headache, flushing, nausea, hypotension, arrhythmia and bleeding occur. Reduce initial titration in dialysis or severe hepatic impairment. Pregnancy and breast-feeding are contraindications, and effective contraception is required during treatment.

Off-label alternative with modest Raynaud evidence in selected patients, especially when another renin-angiotensin indication exists.

Losartan

When nifedipine is unsuitable, specialists may start 25 mg orally once daily and increase to 50 mg once daily according to pressure and symptom response.

Monitor pressure, creatinine and potassium; stop before pregnancy, avoid in bilateral renal-artery stenosis and apply sick-day guidance during dehydrating illness.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Digital ulcer and infection

Repeated ischaemia breaks fingertip and periungual skin, causing severe pain, delayed healing, cellulitis, osteomyelitis and functional loss.

Gangrene and amputation

Fixed vasculopathy, thrombosis or missed large-vessel disease can cause irreversible necrosis requiring debridement, sympathectomy, revascularisation or amputation.

Medicine-related hypotension

Combined calcium-channel, PDE5 and prostanoid vasodilation can cause syncope, headache, oedema and organ hypoperfusion without careful titration.

Missed systemic disease

Treating attacks alone can delay recognition of systemic-sclerosis lung, renal and pulmonary-vascular disease or another connective-tissue complication.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use an attack diary or photographs to track frequency, duration, pain, trigger and recovery and review function rather than colour alone.
At each secondary-disease review inspect every fingertip, pits and ulcers, check pulses and pressure and document infection or tissue progression.
Monitor blood pressure, dizziness, oedema and interactions after each vasodilator start or titration and reconcile nitrates before sildenafil.
Repeat systemic-sclerosis lung, PAH, renal and cardiac surveillance at the risk-based interval when capillary or antibody findings support it.
For ulcers record dimensions, perfusion, pain, exudate, culture only when infected and healing trajectory; investigate bone involvement if deep or persistent.
Revisit smoking, work vibration, cold exposure, contraception and pregnancy before medicine escalation.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Three colours are not mandatory

A sharply demarcated cold-triggered pallor or cyanosis with reperfusion can be Raynaud even when the complete textbook sequence is absent.

Warm the person

Core cooling triggers digital sympathetic constriction, so body layers and environmental planning often matter more than gloves alone.

Fixed pain changes the diagnosis

An uncomplicated attack reverses; persistent rest pain and sensory change indicate tissue oxygen failure and an emergency vascular question.

Capillaroscopy predicts context

Structural capillary loss and repair points toward scleroderma-spectrum vasculopathy but does not itself measure current digital perfusion.

Ulcers have two problems

Healing requires adequate flow and management of pressure, trauma and infection; antibiotics cannot correct ischaemia and vasodilators cannot drain pus.

11Common pitfallsFrequent interpretation and management errors.

01
Reassuring a patient with persistent pain or numbness because previous episodes were labelled Raynaud.
02
Calling disease primary despite an ulcer, absent pulse, abnormal capillaroscopy or systemic-sclerosis features.
03
Ordering broad antibodies for every cold hand while omitting pulses, occupational exposure and medicine review.
04
Combining sildenafil with nitrate treatment and causing profound hypotension.
05
Treating a necrotic or infected digit only with outpatient calcium-channel blockade.
06
Using anticoagulation for ordinary vasospasm without a demonstrated thrombotic or embolic indication.