Raynaud Phenomenon

Meet the patient

A 22-year-old woman's fingers go white, then blue, then red every time she reaches into the freezer aisle — bilateral, symmetric, all fingers, no ulcers, no scars, normal-looking nailfolds. Reassure her: this is primary Raynaud, benign, and a calcium-channel blocker is all she will ever need.[1]

Then the 52-year-old with a single non-healing fingertip ulcer, asymmetric attacks, and nailfold capillaroscopy showing giant tortuous megacapillaries and avascular dropout with a positive ANA. Do not reassure her — this is secondary Raynaud, the hand is announcing systemic sclerosis, and she needs a rheumatology work-up and aggressive vasodilation before she loses the digit.[7]

The two patients hold the entire topic: is this the benign symmetric form or the destructive structural form? Get that fork right and every dose, test and prognosis falls into place.[1]

White-blue-red, and reversible — the definition that does the work

Raynaud is reversible vasospasm; the reversibility is what separates it from a dead artery. The digit turns white (pallor) as the digital arteries close and flow ceases, then blue (cyanosis) as the trapped capillary blood deoxygenates, then red (hyperaemia) as the vessels snap open on rewarming and perfusion floods back. The whole sequence is fully reversible, with no residual — and that is the line that defines Raynaud and distinguishes it from fixed arterial occlusion.[1]

Attacks are triggered by cold or emotional stress, last minutes to a few hours, and end with throbbing pain and paraesthesiae as blood returns. The demarcation between the dead-white fingertip and the pink proximal finger is sharp — a clinical sign worth knowing for the viva.[1]

The mantra: white-blue-red, reversible; young and symmetric is primary, old or scarred is secondary — nailfold and ANA decide.[1]

Etymology for viva gold: named after Maurice Raynaud (1862), who proposed — wrongly — that the cause was sympathetic overactivity. The mechanism is far richer, but the eponym stuck, and "Raynaud disease" is still the term reserved for the primary, benign form.[1]

The one decision: primary or secondary

Nothing about Raynaud matters more than sorting the benign form from the destructive one — the entire prognosis and treatment ladder hangs off it. The fork rests on five axes: age of onset, symmetry, tissue loss, the nailfold capillaroscopy, and the autoantibody screen.[1]

[1] [1]

How common, and who gets it

Raynaud is one of the commonest vascular complaints in general practice — about 3 to 5 per cent of the population, climbing steeply in cold climates and in women. Primary Raynaud is overwhelmingly a young woman's disease (about 9 to 1), beginning in the teens or twenties, with a family history in roughly a quarter of first-degree relatives. Onset over 30 is itself a red flag — it shifts the prior toward secondary and forces the work-up.[1]

Occupational triggers matter and examiners love them. Vibrating tools (chainsaws, pneumatic drills, grinders) cause hand-arm vibration syndrome (HAVS, vibration white finger) — the commonest occupational secondary Raynaud — and the risk scales with cumulative vibration dose. Vinyl chloride, epoxy resin and frostbite are the rarer occupational causes.[1]

The prescribing trap: a beta-blocker given for comorbid hypertension or migraine in a Raynaud patient. Unopposed alpha-mediated vasoconstriction worsens attacks — switch to an ACE inhibitor, losartan or a rate-limiting agent. The same trap catches ergotamine, clonidine, triptans and sympathomimetics, and the bleomycin, cisplatin and vinblastine chemotherapy combination used in germ-cell tumour regimens.[1]

Why the finger shuts — the pathophysiology

A Raynaud attack is exaggerated vasoconstriction of the digital arteries to cold or stress — and the relative weight of the mechanisms differs between primary and secondary, which is why the two forms behave so differently.[1]

The neural mechanism — the cold-sensitive alpha-2C-adrenoceptor — dominates in primary Raynaud. This receptor sits inside the vascular smooth muscle cell at body temperature; on cooling, even by a few degrees, it translocates to the cell surface, sharply increasing the contractile response to sympathetic noradrenaline. Raised Rho-kinase activity then sensitises the myosin light chain to calcium and prolongs the spasm. The vessel wall is otherwise structurally normal — which is why primary Raynaud does not ulcerate.[1][2]

Secondary Raynaud adds endothelial dysfunction on top. The endothelium tips toward vasoconstriction: less nitric oxide and prostacyclin, more endothelin-1 and thromboxane A2. Endothelin-1 is a potent, long-acting vasoconstrictor whose levels are raised in systemic sclerosis and which drives both acute spasm and chronic structural narrowing. Sensory afferents that release calcitonin gene-related peptide (CGRP) — a powerful vasodilator — are impaired in systemic sclerosis, removing a key brake.[2]

Structural vessel disease is the hallmark of secondary Raynaud — and the reason it ulcerates. Repeated spasm and endothelial injury drive intimal fibrosis, luminal narrowing and obliterative vasculopathy, best seen at the nailfold where capillaries become dilated, tortuous, bushy megacapillaries and ultimately drop out into avascular areas. That narrowing — not the spasm — causes ulcers, pitting scars and gangrene, and it is why nailfold capillaroscopy is the single best discriminator between the two forms.[2][7]

Deep dive — the colour sequence mapped to physiology

White (pallor) = arterial closure, blood flow ceases, the digit is ischaemic. Blue (cyanosis) = the small volume of trapped capillary blood deoxygenates. Red (hyperaemia) = reflex reopening of the arteriovenous anastomoses on rewarming, with throbbing pain and paraesthesiae. The whole sequence is fully reversible — that reversibility defines Raynaud and separates it from fixed occlusion. In the secondary rheological forms (cryoglobulinaemia, hyperviscosity, antiphospholipid syndrome), red-cell and platelet aggregates, cryoproteins and microthrombi add an intravascular component to the ischaemia independent of spasm.[1]

The causes of secondary Raynaud — the COLDER rule

When it is secondary, run the COLDER list before you reach for the cream. It sweeps the connective tissue diseases, the occupational and drug causes, the large-vessel and embolic lesions, and the rheological states — and it is the structure the viva wants.[1]

[1]

The classic trap: labelling secondary Raynaud as primary and discharging the patient — missing early systemic sclerosis. About 5 to 20 per cent of patients first called 'primary' later evolve into a connective tissue disease, most often systemic sclerosis within 2 to 5 years. Defend yourself with nailfold capillaroscopy and ANA at baseline, and re-review — that combination is what catches the converters.[1][7]

The clinical picture — the attack and the pattern

The attack is the clinical unit of Raynaud. Cold or emotional stress triggers bilateral, symmetric blanching of the fingers, followed by cyanosis and then hyperaemia on rewarming — minutes to a few hours, with numbness then throbbing pain on reperfusion. The demarcation between the ischaemic white tip and the pink proximal finger is characteristically sharp.[1]

The primary pattern is the 22-year-old in the freezer aisle: bilateral, symmetric, all fingers (thumbs often spared), sometimes the toes and occasionally ears, nose, tongue or nipples; fully reversible, under an hour, no tissue damage, normal nailfold, negative ANA.[7]

The secondary pattern is older, asymmetric or unilateral, may spare fingers — and crucially shows tissue damage: digital pulp ulcers, pitting ice-pick scars, dystrophic or lost nails, and in severe disease critical ischaemia and gangrene. Hunt for the underlying disease, especially systemic sclerosis: look for sclerodactyly (tight, shiny, thickened fingers), telangiectasia, calcinosis cutis and digital pitting scars — the components of CREST (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia), the limited cutaneous subset that is anti-centromere positive.[1]

The vascular trap: asymmetric, pulseless, unilateral Raynaud with absent radial or ulnar pulse, arm claudication, a subclavian bruit or blood-pressure asymmetry is large-vessel occlusive disease — atherosclerosis, Takayasu, Buerger, subclavian stenosis, thoracic outlet — not vasospasm. Image the vessels (arterial Doppler, CT or MR angiography) before you reach for a CCB; nailfold capillaroscopy alone will miss the proximal lesion.[1]

Two mimics to keep separate. Chilblains (perniosis) are pruritic or painful erythematous-violaceous swellings hours after cold — no triphasic change, no reversible white phase. Acrocyanosis is persistent, painless blue-purple discoloration of hands and feet — no paroxysmal pallor. Neither is true vasospasm; warming (and nifedipine for recurrent chilblains) is enough.[1]

Differential — name the cause before you treat it

The differential splits into the connective tissue diseases, the non-CTD causes, and the cold acrosyndromes that merely mimic Raynaud.[1]

[1]

Clinical and bedside assessment — one purpose

The assessment has one job: decide primary or secondary, and if secondary, find the cause. The diagnosis of Raynaud itself is clinical — the triphasic change is elicited from the history; cold challenge is rarely needed.[1]

History. Fix the age of onset (under 30 favours primary; over 30 favours secondary), the symmetry, the triggers (cold, stress, vibration, drugs), the duration and frequency, and any tissue damage — ulcers, pitting scars, gangrene. Take a careful occupational and drug history (vibrating tools, vinyl chloride; beta-blockers, ergotamine, chemotherapy, stimulants) and ask for connective tissue disease features: skin thickening, dysphagia or heartburn, dry cough and exertional dyspnoea, arthritis, rashes, dry eyes or mouth, and a family history of autoimmune disease.[1]

Examination. Inspect the hands for sclerodactyly, digital pulp pitting scars, active ulcers, telangiectasia, calcinosis and nailfold abnormalities. Palpate the peripheral pulses (radial, ulnar, brachial, subclavian) and listen for a subclavian or carotid bruit; check blood pressure in both arms (asymmetry suggests subclavian or Takayasu). Survey the skin (malar rash of SLE, Gottron papules of dermatomyositis, morphea plaques), the chest (basal crackles of ILD, loud P2 and right ventricular heave of PAH), the joints and the abdomen.[7]

Nailfold capillaroscopy at the bedside. Place a drop of immersion oil on the proximal nailfold of the fourth finger and examine with a dermatoscope, an ophthalmoscope at the plus-40 diopter setting, or a USB microscope at roughly 10 to 200 times magnification. Normal nailfolds show neat, parallel, hairpin-shaped capillary loops of uniform size and density. Secondary Raynaud shows the scleroderma pattern: dilated, tortuous, giant (mega) capillaries, bushy capillaries and avascular dropout areas with microhaemorrhages. A normal nailfold in a young woman with symmetric attacks supports primary; an abnormal nailfold mandates an autoantibody screen and surveillance for systemic sclerosis.[1][7]

Investigations — the two tests that matter

Two tests decide whether isolated Raynaud will become systemic sclerosis: nailfold capillaroscopy and an ANA. A young patient with classical primary features needs little more than reassurance; any feature of secondary disease triggers the panel below.[1]

The core screen (every suspected secondary case):[1]

• Full blood count, ESR and CRP — anaemia of chronic disease; a raised ESR argues against uncomplicated primary Raynaud and for inflammation.
• Urea, electrolytes, creatinine, LFTs — baseline organ function and a platform for later drugs.
• Creatine kinase — myositis overlap.
• Thyroid function — autoimmune thyroid disease coexists with autoimmune Raynaud.
• Immunoglobulins, complement, rheumatoid factor, cryoglobulins and antiphospholipid antibodies — where the history suggests hyperviscosity, cryoglobulinaemia or antiphospholipid syndrome.
• Hepatitis B, C and HIV serology — when cryoglobulinaemia or vasculitis is suspected.

[1]

Autoantibodies. ANA is the screen; a positive ANA with an abnormal nailfold is the strongest predictor of evolution to systemic sclerosis. If ANA is positive, request the scleroderma-specific antibodies: anti-centromere (limited or CREST), anti-Scl-70 or anti-topoisomerase I (diffuse SSc and ILD), anti-RNA polymerase III (renal crisis) and anti-U1-RNP (MCTD). Add anti-dsDNA and anti-Smith (SLE), anti-Ro or La (Sjogren, neonatal lupus) and anti-Jo-1 and the anti-synthetases (inflammatory myopathy) as the picture dictates.[1][2]

Nailfold capillaroscopy — the single best discriminator. Beyond the bedside dermoscope, nailfold video-capillaroscopy is the gold standard, reproducible enough to monitor progression. The Cutolo classification describes three sequential scleroderma patterns:[7]

• Early — few giant capillaries, preserved architecture, little dropout; the window where Raynaud may be the only feature of systemic sclerosis.
• Active — frequent giant and megacapillaries, microhaemorrhages, moderate capillary loss; the most recognisable pattern at diagnosis.
• Late — severe avascular dropout, loss of normal architecture, bushy (ramified) capillaries, few giants left; late, severe disease that predicts digital ulcers.

[1]

Abnormal nailfold plus positive ANA is the combination that predicts progression from isolated Raynaud to definite systemic sclerosis, and it is now embedded in the ACR or EULAR 2013 classification criteria — where abnormal nailfold capillaries and Raynaud each score points alongside pitting scars, telangiectasia, PAH or ILD and the SSc-autoantibodies.[5][7]

Organ screen in suspected systemic sclerosis. Once secondary Raynaud is confirmed, stage the underlying disease: pulmonary function tests (a fall in DLCO is the earliest sign of ILD or PAH), high-resolution CT chest for interstitial lung disease, echocardiogram for pulmonary arterial hypertension and pericardial effusion, ECG, right heart catheterisation if PAH is suspected, renal function and blood pressure monitoring for scleroderma renal crisis, and gastrointestinal studies (manometry, endoscopy) for dysmotility and reflux.[1]

Vascular imaging for the atypical or asymmetric case. Digital pulse volume recording or photoplethysmography confirms whether arterial flow is present; arterial Doppler ultrasound, CT or MR angiography excludes proximal large-vessel disease (subclavian stenosis, thoracic outlet, Buerger, embolus, Takayasu). Cold challenge and thermography are research tools.[1]

Self-test — which two results best predict progression to systemic sclerosis?

Abnormal nailfold capillaroscopy (giant capillaries, dropout) PLUS a positive ANA, especially with anti-centromere or anti-Scl-70. This combination is built into the ACR or EULAR 2013 criteria and is the basis for early surveillance of pre-scleroderma Raynaud.[5][7]

Critical digital ischaemia — the rheumatological emergency

Raynaud is rarely an emergency except when it causes critical digital ischaemia — severe resting pain, tissue loss, absent capillary refill or incipient gangrene, almost always in secondary Raynaud (especially systemic sclerosis). This is a rheumatological and vascular emergency; admit, warm, and start urgent vasodilation. (No jokes here — this is where patients lose digits.)[1][2]

For the acute severe attack that is not yet critical, the immediate measures are whole-body warming (a warm bath or shower, heated clothing), simple analgesia and a prompt dose of a short-acting calcium-channel blocker (nifedipine 10 mg), while the patient is worked up for secondary causes.[1]

The treatment ladder — five steps

Management is stratified by primary versus secondary disease and by severity, climbing from lifestyle through oral vasodilators to intravenous and surgical options.[1]

[3] [1] [1]

Step 1 — lifestyle (everyone, often enough for primary)

The foundation is non-pharmacological and is frequently sufficient for primary Raynaud. Dress warmly before going out (layers, hat, gloves, thick socks), use heated gloves, hand warmers and battery-heated clothing, and keep the whole body warm, not just the hands. Stop smoking — nicotine is a vasoconstrictor and blunts drug therapy. Reduce caffeine and manage stress. Critically, withdraw drugs that provoke Raynaud: beta-blockers (switch to an ACE inhibitor or losartan), sympathomimetic decongestants (pseudoephedrine), ergotamine, clonidine and triptans where possible, and the offending chemotherapy combination where feasible. Vibration avoidance and job modification are central for HAVS.[1]

Step 2 — first-line: the dihydropyridine calcium-channel blockers

The dihydropyridine CCBs are first-line in both primary and secondary Raynaud, relaxing vascular smooth muscle and cutting attack frequency and severity by roughly two to three attacks per week.[1][2][6]

• Nifedipine modified-release 10 mg OD, titrated to 30 to 40 mg OD (maximum 120 mg per day in divided doses) — start low to minimise headache, flushing, ankle oedema and reflex tachycardia; the modified-release form improves tolerability.[1]
• Amlodipine 5 mg OD, titrated to 10 mg OD — a well-tolerated alternative with a longer half-life and fewer side effects.

[6]

The Cochrane 2021 review of vasodilators for primary Raynaud is the evidence examiners cite: dihydropyridine CCBs are the only drug class with consistent benefit in primary disease. The other vasodilator classes — ACE inhibitors, alpha-blockers, PDE-5 inhibitors, nitrates and SSRIs — are low to very low certainty in primary, and notably PDE-5 inhibitors showed no clear benefit in primary Raynaud (their benefit is confined to secondary disease).[6]

Step 3 — add-on oral agents

When a CCB is insufficient or not tolerated, add or substitute by comorbidity and tolerability:[1]

• Losartan 50 mg OD (up to 100 mg OD) — modestly effective, well tolerated, useful when CCBs cause oedema.[1]
• Prazosin 1 mg TDS, titrated to 2 to 5 mg TDS — directly opposes alpha-adrenergic vasoconstriction; first-dose hypotension is the main caution.
• Fluoxetine 20 mg OD — an SSRI that lowers platelet serotonin; recommended by EULAR 2017 for systemic-sclerosis-related Raynaud.
• Statins (atorvastatin 40 mg OD) — improve endothelial function; an adjunct, not primary therapy.
• Topical nitrates — glyceryl trinitrate 0.4 per cent (MQX-503 metered-dose) applied to the fingers; headache and tachyphylaxis limit use — best as a spot treatment for one intractable digit.

[3]

Step 4 — severe and refractory secondary Raynaud

For digital ulcers, recurrent severe attacks or critical ischaemia in secondary Raynaud, escalate:[1]

• PDE-5 inhibitors — sildenafil 25 to 50 mg TDS, or tadalafil 20 mg alternate days or three times weekly. They raise cyclic GMP and potentiate nitric-oxide-mediated vasodilation; EULAR 2017 specifically recommends them for systemic-sclerosis-related Raynaud and digital ulcers, and they are among the most effective oral agents for secondary disease.[1]
• Intravenous prostacyclin (iloprost) — 0.5 to 2 ng per kg per minute by continuous IV infusion, titrated to tolerance (headache, nausea, hypotension, flushing), over 6 hours daily for 3 to 5 days, repeated every few weeks to months for severe disease. The most potent acute vasodilator; it also inhibits platelet aggregation and promotes ulcer healing.
• Endothelin-receptor antagonist — bosentan 62.5 mg BD for 4 weeks, then 125 mg BD — reserved for the prevention of new digital ulcers in systemic sclerosis with multiple ulcers despite CCB and PDE-5 inhibitor therapy.

[3]

The bosentan trap: expecting bosentan to heal an existing ulcer. RAPIDS-2 (188 patients) showed a 30 per cent reduction in the number of NEW digital ulcers with bosentan but no difference in healing of the cardinal ulcer — it prevents, it does not heal. Bosentan needs monthly liver function monitoring (transaminase elevation) and is teratogenic, so reliable contraception is mandatory.[4]

Step 5 — surgical and local interventions

• Botulinum toxin A — 25 to 100 units per hand, injected around the digital arteries or into palmar skin; reduces sympathetic tone, helps refractory pain and ulcer healing, but repeats are needed.[1]
• Digital (peri-arterial) sympathectomy — surgical stripping of sympathetic fibres around the digital artery; reserved for a single critically ischaemic digit unresponsive to medical therapy.
• Cervical or lumbar sympathectomy — largely abandoned for the upper limb (benefit is transient); still occasionally used for lower-limb disease.
• Amputation — only for irreversible necrosis or auto-amputation.
• Fat grafting (lipofilling) — an emerging adjunct to promote ulcer healing and soften sclerotic tissue.

[2] [1]

Specific subtypes — the scenarios that recur

Primary Raynaud (Raynaud disease). Idiopathic, benign, young women, symmetric, normal nailfold, negative ANA, no tissue loss. Diagnostic criteria: symptoms for over 2 years with no progression and no features of secondary disease. Management is reassurance and lifestyle, with a short course of a CCB if attacks are troublesome. Reassess periodically for evolution.[1]

Systemic-sclerosis-associated Raynaud. The archetype of secondary Raynaud — structural obliterative vasculopathy drives recurrent ulcers and critical ischaemia. Treat the underlying disease (immunosuppression for skin and lung, ACE inhibitors for renal crisis, PAH-specific therapy) plus aggressive vasodilation: titrated CCB, add a PDE-5 inhibitor, escalate to IV iloprost for severe disease, and bosentan to prevent new ulcers. The EULAR 2017 recommendations formalise this ladder.[3]

Hand-arm vibration syndrome (HAVS, vibration white finger). A compensable occupational disease in miners, forestry workers, fitters and grinders; the cumulative vibration exposure is diagnostic. Vibration avoidance and job modification are central — vasodilators help symptoms but cannot reverse the structural damage. Coexistent sensorineural hearing loss and carpal tunnel syndrome are common.[1]

Drug-induced Raynaud. Withdraw the offending agent (beta-blocker, ergotamine, clonidine, stimulant, triptan) and substitute as needed; chemotherapy-related Raynaud (bleomycin, cisplatin, vinblastine) may partially resolve after the regimen ends.[1]

Buerger disease (thromboangiitis obliterans). Young male heavy smokers with distal ischaemia, Raynaud, superficial thrombophlebitis migrans and instep claudication. Complete smoking cessation is the only effective treatment — vasodilators and sympathectomy disappoint, and amputation is common if he keeps smoking.[1]

Paediatric Raynaud. Almost always primary and benign — but any feature of secondary disease (asymmetry, ulcers, abnormal nailfold, positive ANA) mandates the full adult work-up, as systemic sclerosis and SLE can present in adolescence.[1]

Complications and the pitfalls that bite

Digital ulcers are the commonest complication of secondary Raynaud — painful, slow to heal, prone to infection, and a major source of disability in systemic sclerosis. Pitting ice-pick scars of the digital pulp are markers of prior microinfarction and are themselves a diagnostic clue to systemic sclerosis. In severe disease, critical ischaemia, gangrene and auto-amputation or surgical amputation occur; sclerodactyly, flexion contractures and loss of hand function compound the disability, and calcinosis cutis produces painful hard deposits that can ulcerate through the skin. Treatment-related adverse effects — headache, peripheral oedema, flushing and hypotension with CCBs and PDE-5 inhibitors; tachyphylaxis and headache with nitrates — round out the morbidity.[1]

The five classic pitfalls:[1]

1. Labelling secondary as primary and discharging the patient — defend with nailfold capillaroscopy and ANA at baseline and re-review.
2. Prescribing a beta-blocker for comorbid hypertension or migraine in a Raynaud patient — switch to an ACE inhibitor, losartan or a rate-limiting agent.
3. Treating the vasospasm while ignoring a proximal large-vessel lesion — image any asymmetric, pulseless or unilateral case.
4. Expecting bosentan to heal an existing ulcer — it prevents new ulcers only.
5. Forgetting contraception and liver monitoring on bosentan.

[4]

Prognosis and disposition

Primary Raynaud is benign — attacks lessen with age and warming, life expectancy is normal, and no organ disease develops. But about 5 to 20 per cent of patients first labelled 'primary' later evolve into a connective tissue disease, most often systemic sclerosis within 2 to 5 years. The combination of abnormal nailfold capillaroscopy and a positive ANA identifies this at-risk subgroup, who need periodic reassessment (nailfold, autoantibodies, PFTs, echocardiogram) so organ disease is caught before it declares itself.[1][5][7]

Secondary Raynaud's prognosis is driven by the underlying disease. In systemic sclerosis, interstitial lung disease and pulmonary arterial hypertension are the leading causes of death, while recurrent digital ulcers and critical ischaemia threaten the digits. Early detection (baseline and serial nailfold capillaroscopy, PFTs with DLCO, echocardiogram, renal monitoring) and aggressive vasodilation improve digital outcomes and quality of life even though they do not change the underlying disease trajectory.[7]

Disposition. Primary Raynaud is managed in primary care with lifestyle and, if needed, a CCB. Suspected secondary Raynaud is referred to rheumatology for nailfold capillaroscopy, autoantibody profiling and organ surveillance. Critical digital ischaemia is admitted under rheumatology and vascular surgery for IV iloprost and wound care.[3]

Special populations

Pregnancy. Primary Raynaud often improves in pregnancy (a vasodilated state). Review the drugs: losartan is teratogenic (FDA category D) and must be stopped pre-conception; nifedipine is relatively safe. Bosentan is absolutely contraindicated in pregnancy — enforce reliable contraception in any woman of childbearing potential.[4]

Elderly. New-onset Raynaud after 60 is almost always secondary — to atherosclerosis, a drug effect, or a paraneoplastic or connective tissue disease process — and warrants aggressive investigation, not reassurance.[1]

Systemic sclerosis with renal crisis. Avoid high-dose steroids (above 15 mg per day prednisolone) in systemic sclerosis — they precipitate scleroderma renal crisis; manage Raynaud with CCBs (which also protect the kidney) and PDE-5 inhibitors.[3]

Anticoagulated or prothrombotic patients. In antiphospholipid syndrome with digital ischaemia, combine vasodilators with anticoagulation; aspirin 75 mg OD is standard antiplatelet prophylaxis in secondary Raynaud with ulcers.[1]

Evidence, guidelines and regional differences

The management of Raynaud — especially systemic-sclerosis-associated disease — rests on a small set of landmark trials and one international guideline ladder.[1]

[3] [1] [4] [6] [5]

Regional deltas. EULAR (Europe) sets the international reference ladder for systemic-sclerosis-related Raynaud, endorsing CCB, PDE-5 inhibitor, IV iloprost, fluoxetine and bosentan.[3] NICE (UK) recommends nifedipine first-line, with referral for specialist assessment when secondary Raynaud is suspected and admission for critical ischaemia. ACR (US) practice is concordant with EULAR; the FDA-approved topical for Raynaud is nitrates (glyceryl trinitrate or nitroglycerin, MQX-503), while bosentan is licensed in Europe for SSc with multiple digital ulcers, with availability and reimbursement varying by country. In low-resource settings (including much of India and South Asia), where nifedipine and amlodipine are cheap and widely available while iloprost, bosentan and PDE-5 inhibitors are expensive or scarce, the dihydropyridine CCB remains the practical backbone, with PDE-5 inhibitors and specialist referral reserved for severe secondary disease.[1]

[1]

Exam pearls

The mantra: white-blue-red, reversible; young and symmetric is primary, old or scarred is secondary — nailfold and ANA decide.[1]

Ward-round test — four stems, thirty seconds each

Stem 1 — the freezer-aisle student (answer)

A 22-year-old woman has bilateral symmetric white-blue-red attacks in the cold for two years, normal nailfolds, negative ANA, no ulcers. What is this, and what do you do? Model: Classic primary Raynaud (Raynaud disease) — young, symmetric, normal nailfold, negative ANA, no tissue loss, symptoms over 2 years with no progression. Reassure; give lifestyle advice (cold avoidance, heated clothing, smoking cessation, avoid beta-blockers) and a dihydropyridine CCB (nifedipine MR 10 to 40 mg OD) only if attacks are troublesome. Document baseline nailfold capillaroscopy and ANA, and re-review periodically — because about 5 to 20 per cent of 'primary' later evolve into systemic sclerosis, and you want to catch the converters.[1][6]

Stem 2 — the fingertip ulcer you must not reassure (answer)

A 52-year-old presents with asymmetric attacks, one non-healing digital pulp ulcer, pitting scars, and nailfold megacapillaries with dropout. ANA is positive. What is the diagnosis, and which two tests best predict this? Model: Secondary Raynaud due to systemic sclerosis — older, asymmetric, tissue loss, abnormal nailfold, positive ANA. The two results that best predict progression from isolated Raynaud to systemic sclerosis are abnormal nailfold capillaroscopy (giant capillaries, dropout) plus a positive ANA, and this pair is embedded in the ACR or EULAR 2013 criteria. Request the scleroderma-specific antibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III), stage the organs (PFTs with DLCO, high-resolution CT chest, echocardiogram, renal function), and start aggressive vasodilation.[5][7]

Stem 3 — the pulseless hand (answer)

A 48-year-old smoker has unilateral Raynaud of the left hand, an absent left radial pulse, arm claudication on that side, and a 20 mmHg blood-pressure difference between arms. What is this, and what is the trap? Model: This is large-vessel occlusive disease, not vasospastic Raynaud — think atherosclerosis, Takayasu, Buerger, subclavian stenosis or thoracic outlet. The vascular trap is to treat it only with a CCB: image the vessels (arterial Doppler, CT or MR angiography) first, because nailfold capillaroscopy will miss the proximal lesion and vasodilators waste the window for revascularisation.[1]

Stem 4 — the bosentan prescription (answer)

A 44-year-old with systemic sclerosis has had four new digital ulcers this year despite a maximally titrated CCB and a PDE-5 inhibitor. The registrar starts bosentan 125 mg BD and expects the current ulcer to heal. Correct them. Model: Bosentan prevents new ulcers; it does not heal existing ones. RAPIDS-2 showed a 30 per cent reduction in the number of NEW digital ulcers but no difference in healing of the cardinal ulcer. Add the two safety duties the registrar forgot: monthly liver function tests (transaminase elevation) and reliable contraception (bosentan is teratogenic). For an existing ulcer, keep the CCB plus PDE-5 inhibitor, consider IV iloprost, and give meticulous wound care.[4]

References

1. [1]Herrick AL, Wigley FM. Raynaud's phenomenon Best Pract Res Clin Rheumatol, 2020.PMID 32007400
2. [2]Ture HY, Lee NY, Kim NR, Nam EJ. Raynaud's Phenomenon: A Current Update on Pathogenesis, Diagnostic Workup, and Treatment Vasc Specialist Int, 2024.PMID 39040029
3. [3]Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis Ann Rheum Dis, 2017.PMID 27941129
4. [4]Matucci-Cerinic M, Denton CP, Furst DE, et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial Ann Rheum Dis, 2011.PMID 20805294
5. [5]van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative Arthritis Rheum, 2013.PMID 24122180
6. [6]Su KY, Sharma M, Kim HJ, Kaganov E, Hughes I, Abdeen MH, Ng JHK. Vasodilators for primary Raynaud's phenomenon Cochrane Database Syst Rev, 2021.PMID 33998674
7. [7]Ruaro B, Pizzorni C, Paolino S, et al. Correlations between nailfold microvascular damage and skin involvement in systemic sclerosis patients Microvasc Res, 2019.PMID 30974112