Raynaud phenomenon and vasculitis of the limbs

• Raynaud phenomenon is an exaggerated, reversible narrowing of the small arteries that feed the fingers and toes, triggered by cold or strong emotion, producing a characteristic colour change and sometimes pain or numbness.
• About 3 to 5 percent of people are affected worldwide; roughly 80 to 90 percent of cases are primary Raynaud phenomenon with no underlying disease, while 10 to 20 percent are secondary to a connective tissue or vascular disorder.^[2][4]
• Secondary Raynaud phenomenon is the form that matters most for internal medicine and cardiology, because more than 90 percent of people with systemic sclerosis have it, and roughly 10 to 20 percent of cases of Raynaud phenomenon are in fact the first clue to an underlying connective tissue disease.^[2]
• Thromboangiitis obliterans, also called Buerger disease, is a separate, non-atherosclerotic inflammatory disease of small and medium limb arteries and veins, seen almost only in smokers, that begins in young adults and can ulcerate or lead to gangrene of digits.
• Treatment is stepped: keep warm and stop smoking first; if attacks persist, calcium channel blockers, especially dihydropyridines such as nifedipine, are the first drug class; second-line agents come next, and Buerger disease is managed by absolute smoking cessation with revascularisation when possible. ^[3]

By the end of this page you should be able to:

1. Tell primary from secondary Raynaud phenomenon and explain what the colour change means mechanically.
2. Explain why cold and emotion trigger attacks, and why systemic sclerosis changes the disease from a nuisance into a threat.
3. Recognise the clinical clues, capillaroscopic and serological, that push a case toward secondary Raynaud phenomenon and systemic sclerosis.
4. Describe thromboangiitis obliterans, apply the modern diagnostic clues, and explain why smoking cessation is the treatment.
5. Plan stepped management of Raynaud phenomenon, including drug, dose, route and cautions, and know when to refer.
6. Outline low-resource and special-group practice (children, occupational vibration, pregnancy).

Raynaud phenomenon was first described by Maurice Raynaud in 1862, who thought it was an exaggerated neurological reflex. Sir Thomas Lewis studied it in 1930.^[8] The term is spelled with no apostrophe in most current English-language sources; older texts still write "Raynaud's". The historical terms "Raynaud disease" (primary) and "Raynaud syndrome" (secondary) still appear. The patient may also report attacks at the toes, ears, nose or nipples, but the fingers are the classic site.

Raynaud phenomenon is common. Most reviews place the prevalence at 3 to 5 percent of the general population, although wider estimates of 1.6 to 7.2 percent and even up to 10 percent appear, depending on climate, definition and ascertainment method.^[2][4][3] Because vasospasm is provoked by cold, prevalence rises toward colder latitudes and falls in the tropics.

• Sex. Women are affected several times more often than men. Review figures range from 2 to 20 percent of women versus 1 to 12 percent of men, and from 2.1 to 15.8 percent of women versus 0.8 to 6.5 percent of men. Premenopausal women carry the highest risk.^{[2][4] [3]}
• Type. Primary Raynaud phenomenon accounts for 80 to 90 percent of cases and runs a benign course. Secondary Raynaud phenomenon accounts for 10 to 20 percent and carries the complications.
• Scleroderma. In systemic sclerosis, Raynaud phenomenon is almost universal, reported in more than 90 percent of patients, and it is often the first manifestation, sometimes by years. Population studies have found 91 to 96 percent of people with systemic sclerosis reporting Raynaud phenomenon.^{[7] [2]}
• Age. Primary Raynaud phenomenon starts young, with a median age of onset around 14 years. Secondary Raynaud phenomenon tends to begin after 40 years, often with more severe symptoms and, in systemic sclerosis, sometimes contemporaneous with or even after the other manifestations.^{[2] [3]}
• Connective tissue context. In 10 to 20 percent of cases Raynaud phenomenon is the first manifestation of an underlying connective tissue disease, and 14 to 37 percent of primary cases eventually progress to secondary Raynaud phenomenon.^[1][2]
• Climate. Regions with cold winters show higher prevalence and more severe vasospasm.

Primary Raynaud phenomenon is idiopathic. There is no known structural vessel disease. The cause is thought to be a heightened sensitivity of the digital circulation to cold and emotion, with alpha-2C-adrenergic receptor overactivity and reduced release of vasodilator neuropeptides such as calcitonin gene-related peptide. Primary Raynaud phenomenon often runs in families, indicating a genetic component. Female sex and low body mass index add risk, and Raynaud phenomenon is commoner in young women aged 15 to 30 years.^[4]

Secondary Raynaud phenomenon arises from an underlying disorder or exposure. The list a medical student must know is short and organised by mechanism.

• Connective tissue disease. Systemic sclerosis (limited and diffuse), systemic lupus erythematosus, mixed connective tissue disease, Sjogren syndrome, dermatomyositis and, less often, rheumatoid arthritis. Systemic sclerosis is the important one: it is the classical secondary cause and the one that turns Raynaud phenomenon into digital ulcers.
• Occupation. Hand-arm vibration syndrome from pneumatic tools and other vibratory machinery; heavy manual work in the cold.
• Structural arterial disease. Thoracic outlet syndrome, large-vessel brachiocephalic disease, advanced atherosclerosis.
• Haematological. Cryoglobulinaemia, cryofibrinogenaemia, paraproteinaemia, hyperviscosity, cold agglutinins.
• Endocrine. Thyroid disease.
• Drugs and chemicals. Beta-blockers, clonidine, ergot alkaloids, sympathomimetics, interferon, tyrosine kinase inhibitors, gemcitabine and other chemotherapeutic agents, vinyl chloride monomer, arsenic.
• Local injury. Frostbite, repeated cold damage.

Smoking is a consistent aggravating and causative factor rather than a mere association. Nicotine is a vasoconstrictor; tobacco use increases the incidence and severity of attacks and is the central cause of thromboangiitis obliterans (below). Blood viscosity and sympathetic hyperactivity are plausible mechanisms.

Digital ulcers develop when prolonged vasospasm and structural microvascular damage outstrip perfusion. In systemic sclerosis the digital artery lumen narrows progressively, capillaries drop out, and tissue becomes critically ischaemic, so ulceration, or even dry gangrene of a fingertip, becomes a marker of advanced secondary disease.

Everything that happens in an attack follows from an imbalance between constriction and dilation in the digital circulation, most marked in the arteriovenous anastomoses of the fingers and toes.

1. Cold is sensed. Cooling of the skin is detected by mitochondria in vascular smooth muscle cells; these organelles act as thermosensors and release reactive oxygen species.
2. Intracellular signalling. Reactive oxygen species activate Rho and Rho-kinase, which reorganise the cytoskeleton and move alpha-2C-adrenergic receptors from an intracellular store in the Golgi/endoplasmic reticulum to the cell surface.
3. Vasoconstriction. Alpha-2C receptors now bind catecholamines, and cold-induced constriction results. In a normal person this is a modest, useful thermoregulatory reflex; in Raynaud phenomenon it is amplified.
4. Loss of the counterbalance. Vasodilator neuropeptides such as calcitonin gene-related peptide are reduced in Raynaud phenomenon, so the normal braking signal is weakened. Secondary disease adds structural damage: endothelial injury, intimal proliferation, capillary loss, and increased sensitivity to endothelin-1.
5. The colour phases. Intense vasospasm first empties blood from the digital arterial bed, producing pallor. Slow, hypoxic, deoxygenated blood then sits in the digits, producing cyanosis. When vasospasm relaxes, reactive hyperaemia returns and the digits flush red. Pallor and cyanosis are the two colours required for diagnosis; a third phase is common but not required.
6. Pain and numbness. Ischaemia and reperfusion irritate digital nerves and produce the aching, tingling and numbness patients describe, usually symmetrical and identical in corresponding fingers of both hands.

Oestrogen explains the female predominance. Epidemiological studies show more primary Raynaud phenomenon in women, especially before the menopause, and in post-menopausal women taking unopposed oestrogen replacement. Oestrogen upregulates alpha-2C-adrenergic receptor expression through membrane G-protein-coupled oestrogen receptor signalling, via cAMP, Rap, JNK and the AP-1 transcription factor. In plain terms, oestrogen increases the number of the very receptors that trigger cold-induced constriction, which is why women in their reproductive years are most vulnerable. This is a research frontier, not a treatment target yet, but it explains the sex bias well.

Secondary Raynaud phenomenon in systemic sclerosis is a different problem in the same vessel. Early disease shows functional vasospasm; later disease shows structural fibrosis, capillary dropout and intimal thickening that convert a reversible spasm into fixed or semi-fixed narrowing. That is why a patient with scleroderma can have normal colour between attacks but still develop fingertip ulcers, and why responses to vasodilator drugs become incomplete.

Most patients describe attacks rather than continuous pain. Useful questions are: "Do your fingers change colour in the cold? Do they go white, blue or both? Are both hands affected? Does heat or warming at the body core stop it? Is there numbness or pain?"

• Attacks begin suddenly, often minutes after handling something cold, moving from a warm room into cold air, or holding a cold drink; emotional stress and vibrating tools can trigger them too.
• The fingers go white, then blue, then red; the patient often brings a photograph.
• Numbness, tingling, aching or throbbing during the attack and in recovery.
• Symmetrical involvement of corresponding fingers of both hands in primary disease. The thumb is often spared.
• Attacks last minutes to an hour.
• Frequency varies; some patients have only a few per winter, others daily in cold weather.
• Primary disease is a nuisance: it interferes with ADLs, typing, shopping and winter sports, but does not damage tissue.
• Secondary disease is different: pain between attacks, slow-healing fingertip cracks, ulcers at the nail folds or digital tips, blackening of the tip, and symptoms of the underlying connective tissue disease such as puffy fingers, reflux, breathlessness or dry eyes.

Between attacks the examination can be entirely normal in primary disease. During or soon after an attack you may see pallor or cyanosis with sharp demarcation at the distal interphalangeal joints or proximal phalanges, and a line along which colour change stops.

• Skin. In secondary disease look for puffy fingers, sclerodactyly, telangiectasia at the nail folds, calcinosis and digital pits or scars. These five findings are the hand clues to systemic sclerosis.
• Nailfold capillaroscopy. Dilated, giant or dropout capillaries at the nailfold indicate microvascular disease and point toward secondary Raynaud phenomenon and systemic sclerosis. Normal capillaries support primary disease.
• Pulses and bruits. Peripheral pulses are normal in primary Raynaud phenomenon and in systemic sclerosis; a unilaterally absent pulse, a bruit or an asymmetrical attack pushes the diagnosis toward large-vessel occlusion or thoracic outlet syndrome.
• Complications. Digital ulcers, pitting scars, fissures and, rarely, dry digital gangrene.

The three questions are whether this is Raynaud phenomenon at all, whether it is primary or secondary, and whether the alternative is a connective tissue disease mimic.

Investigations are chosen to answer two questions: is this Raynaud phenomenon at all, and is it primary or secondary. In primary disease no test is positive. In secondary disease the work-up is for systemic sclerosis and related disorders.

• History and a standard patient interview. The diagnosis rests on history. The consensus diagnostic questions are reproduced under diagnostic criteria. A standardised interview is a recognised criterion; photographs of the colour change are helpful.
• Clinical assessment and pulses. Warm hands, good pulses and no bruits favour a functional vasospasm.
• Nailfold capillaroscopy. In secondary care. Giant or avascular capillary patterns support secondary disease; a normal pattern supports primary disease. Capillaroscopy should be performed by an experienced operator with good optical quality.
• Antinuclear antibody. By indirect immunofluorescence. A negative or low-titre ANA is compatible with primary disease; a moderate or high titre, or systemic-sclerosis-specific antibodies, indicates secondary disease. Anti-centromere pattern, anti-topoisomerase (anti-Scl-70) and anti-RNA polymerase III are the systemic sclerosis-associated antibodies.
• Erythrocyte sedimentation rate. A raised ESR is not required for diagnosis and is non-specific; it supports an inflammatory secondary cause when raised.
• Cold challenge test. Objective but not part of the diagnostic criteria, because a colour change on cold water exposure can be painful and uninformative.
• Autoantibody panel and systemic sclerosis screen. When secondary disease is suspected: ANA, extractable nuclear antigen profile, complement, immunoglobulins, rheumatoid factor, cryoglobulins.
• Systemic sclerosis organ screening (when systemic sclerosis is diagnosed or likely): full blood count, renal function, urinalysis (protein, casts), high-resolution computed tomography of the chest and pulmonary function tests for interstitial lung disease, echocardiography for pulmonary arterial hypertension, screening for malignancy in late-onset diffuse disease.
• Vibration assessment and occupational history when vibration is possible.
• Arterial duplex and imaging when a unilateral or postural pattern, absent pulse, or digital ischaemia out of keeping with Raynaud phenomenon suggests large-vessel disease.

Reference ranges vary by laboratory; always compare with the local reference interval.

An international Delphi consensus (Maverakis 2014) developed a 3-step approach and 5 additional criteria for primary Raynaud phenomenon.^[1]

Step 1. Ask the patient about colour history. An attack must include pallor (white) and either cyanosis (blue) or reperfusion erythema (red), and must be triggered by cold or emotion.

Step 2. Apply the criteria a physician uses to make or exclude secondary causes: features such as sclerodactyly, digital ulcers, calcinosis, skin fibrosis and an abnormal nailfold capillaroscopy point to secondary Raynaud phenomenon; their absence supports primary.

Step 3. Classify as primary or secondary. Primary Raynaud phenomenon requires: (1) the three-step criteria for Raynaud phenomenon; (2) normal nailfold capillaroscopy (normal or perfect-normal patterns); (3) physical examination negative for findings suggestive of secondary causes (ulcerations, necrosis or gangrene, sclerodactyly, calcinosis, skin fibrosis); (4) no history of an existing connective tissue disease; and (5) a negative or low-titre ANA, for example 1:40 by indirect immunofluorescence. Notably, a normal ESR and a normal ANA are not required for diagnosis; a low but abnormal ANA is allowed. No minimum number of attacks and no minimum duration of symptoms are required. ^[1]

Raynaud phenomenon is one item of the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria for systemic sclerosis.^[7] A patient with skin thickening of the fingers proximal to the metacarpophalangeal joints is classified as having systemic sclerosis on that finding alone. Otherwise a weighted score is used, and a total score of 9 or more classifies systemic sclerosis. Raynaud phenomenon contributes 3 points; scleroderma-related antibodies contribute 3; skin thickening of the fingers contributes 2 or 4; finger-tip ulcers 2 and pitting scars 3; telangiectasia and abnormal nailfold capillaries 2 each; pulmonary arterial hypertension or interstitial lung disease 2. The criteria are for classification and research, not a bedside diagnosis, but the list is a good memory aid for what matters.

The message for a student is that Raynaud phenomenon plus systemic-sclerosis-specific autoantibody or abnormal capillaries, taken together, already carries most of the score. In practice, when you see Raynaud phenomenon in an adult with positive autoantibodies or an abnormal nailfold, you are looking at early systemic sclerosis until proven otherwise: refer to rheumatology, because an early diagnosis changes follow-up and treatment of organ disease.

Thromboangiitis obliterans is a progressive, non-atherosclerotic, segmental, inflammatory disease affecting small and medium arteries, and sometimes veins and nerves, of the limbs. Leo Buerger gave it its eponym in 1908 after extensive pathological studies of amputated limbs; von Winiwarter had described it in 1879.^[5][6]

Key features from the opened literature:

• Age and sex. Onset is between 20 and 50 years; it is found more often in men who smoke.^[6]
• Aetiology unknown, but it does not occur without tobacco. It is rarely seen in patients who do not smoke. Cigarette smoking is essential to the diagnosis and to the disease course.
• Pathology. Segmental inflammatory thrombosis of the distal-most vessels, with relative sparing of the larger proximal arteries. Gross appearance is of a thrombosed, inflamed small vessel, and the process can migrate along a limb.
• Clinical picture. Initial coldness, paraesthesia and exertional pain in the foot, leg, arm or hand, often mistaken for joint or neuromuscular pain. With progression there is calf claudication, ischaemic rest pain and ulcers or gangrene of the toes, feet or fingers. Migratory superficial phlebitis occurs in up to about 16 percent of patients and signals a systemic inflammatory process. Upper-limb involvement is common.^[6]
• Diagnosis. It is a diagnosis of exclusion made after atherosclerosis, embolism, hypercoagulability, autoimmune vasculitis, diabetes and thoracic outlet compression have been reasonably excluded. Several diagnostic schemes exist. The classical Shionoya criteria are a historical gold standard; in practice only a minority of patients satisfy them. Modern Japanese guidance in particular uses a minimum set: onset before 50 years of age, no atherosclerotic risk factors, and either occlusion of the popliteal artery or an upper-extremity artery or a history of migratory phlebitis. Newer Japanese vascular guidelines emphasise symptoms and characteristic imaging at onset, and the imaging hallmark is distal, segmental occlusive disease with corkscrew collaterals.^[5]
• Course. The disease waxes and wanes; amputation of digits is common in continuing smokers, while long-term survival is good and major amputation is uncommon. Remission follows sustained abstinence from tobacco.

The older literature blurs the line between Raynaud phenomenon and thromboangiitis obliterans, and some StatPearls formulations describe digital colour change as "Raynaud phenomenon" in Buerger disease. In practice, Buerger disease presents with distal, often asymmetric ischaemia and ulceration in a smoker, not the symmetric cold-induced phases of Raynaud phenomenon; the two can coexist but should not be confused.

• Prevalence. 3 to 5 percent of the general population have Raynaud phenomenon, with figures up to 7.2 or 10 percent in some series depending on climate and definition. Women 2 to 20 percent, men 1 to 12 percent, depending on the study. ^[4]
• Proportion primary. 80 to 90 percent of cases. Secondary cases 10 to 20 percent, but these are the ones that matter. ^[2]
• Systemic sclerosis. More than 90 percent of people with systemic sclerosis have Raynaud phenomenon.
• Nailfold capillaroscopy deserves to be learned as a skill rather than a number: giant capillaries and dropout are the microvascular signature of systemic sclerosis.
• Diagnosis of primary Raynaud phenomenon formally tolerates a low-titre ANA; a moderate or high titre is secondary until proven otherwise.
• Thromboangiitis obliterans. Onset 20 to 50 years; migratory superficial phlebitis in up to 16 percent. In modern Japanese surveillance only about 12 percent of newly registered patients meet the classic Shionoya criteria, which is why diagnostic criteria are evolving.^[5][6]

Step 1, before any drug: conservative measures.

• Keep the whole body warm, not just the hands: warm core, warm boots, layered clothing, gloves and heated steering wheels. A cold core reflexively clamps the digit vessels.
• Avoid triggers: cold exposure, sudden temperature change, vibration, emotional stress where possible.
• Stop smoking completely; nicotine is a potent vasoconstrictor and smoking worsens secondary disease.
• Review the drug chart and stop any vasospastic drug if it can be changed, such as beta-blockers and ergot. Treat any underlying connective tissue disease with the rheumatology team.
• For severe cold-induced attacks in occupational settings, modify exposure and rotate tasks.

Step 2, pharmacological therapy, for symptoms that persist despite adequate conservative measures.

• Calcium channel blockers are first-line pharmacological therapy for Raynaud phenomenon, both primary and secondary. Dihydropyridines such as nifedipine and amlodipine are the subtype used; they are fast acting and highly selective for vascular smooth muscle, whereas verapamil is not routinely used and diltiazem is not the first-line subtype. Oral nifedipine is the usual recommendation. Doses used in practice are oral nifedipine 30 to 60 milligrams per day and amlodipine 5 to 10 milligrams per day, with titration from the lowest dose because side effects are dose-limiting: headache, flushing, dizziness, palpitations and ankle oedema. Increase the dose only if the lower dose is tolerated and still ineffective.^[2][4]
• Phosphodiesterase type 5 inhibitors (sildenafil 25 to 100 milligrams, vardenafil 5 to 20 milligrams by mouth) improve digital perfusion and reduce attack severity and are used, especially in secondary Raynaud phenomenon, when calcium channel blockers fail or are not tolerated. They are vasodilators acting via nitric oxide and cyclic guanosine monophosphate; side effects include headache, flushing and hypotension.^[4]
• Prostacyclin analogues, especially intravenous iloprost at 0.5 to 2 nanograms per kilogram per minute, are recommended for severe or refractory disease with digital ischaemia or ulcers, usually in secondary Raynaud phenomenon. Epoprostenol (intravenous 2 to 25 nanograms per kilogram per minute) and treprostinil (1 to 2 nanograms per kilogram per minute subcutaneously or intravenously) are alternatives, and more recent prostanoid-receptor agonists have been studied for digital vasculopathy. Iloprost is given as a supervised intravenous infusion; it causes flushing and jaw pain and requires monitoring.^[4]
• Third-line and adjunctive agents. Angiotensin receptor blockers such as losartan 25 to 100 milligrams daily can help in primary Raynaud phenomenon but are less convincing in systemic sclerosis; ACE inhibitors such as quinapril showed no benefit in long-term study. Fluoxetine 20 to 60 milligrams daily has mixed evidence. Topical nitrates are plausible vasodilators but cause headache and skin irritation and have inconsistent evidence. Bosentan 62.5 to 125 milligrams twice daily, an endothelin receptor antagonist, is used for systemic-sclerosis digital ulcer disease rather than pure vasospasm. Botulinum toxin type A, 50 to 100 units injected locally into the digits, has growing evidence for refractory attacks and ulcers and is well tolerated but short lived at 3 to 6 months.^[4]
• Surgical and interventional options. Digital sympathectomy and fat grafting are reserved for severe, drug-refractory secondary disease with critical ischaemia. Upper thoracic sympathectomy is rarely used now because results wane. Stem cell and tissue-based approaches remain experimental.

Step 3, prevention of tissue loss. Once an ulcer is present, the plan shifts to protected wound care, infection control and avoidance of trauma, with prolonged prostacyclin infusion and consideration of endothelin blockade.

The single treatment that changes the course is absolute smoking cessation, by any route including nicotine replacement and pharmacotherapy for tobacco dependence. With sustained abstinence the disease remits and major amputation is avoided; with continued smoking the disease progresses to digit loss.

• All patients should be identified and supported with smoking cessation services, and patients should understand that even low-level or occasional smoking can sustain the disease.
• Symptomatic and medical treatment includes analgesia, wound care, infection treatment, and vasodilator and antiplatelet therapy as needed. Trials of specific drugs such as iloprost have been studied, but the evidence base is small and heterogenous.
• Revascularisation. Surgery is often impractical because target vessels are too distal and autologous vein is often unavailable because of migratory thrombophlebitis. Endovascular angioplasty has growing short-term evidence: in one meta-analysis of 69 patients treated by catheter-directed thrombolysis, angioplasty or both, one-year limb loss was uncommon and combined catheter-directed thrombolysis with angioplasty performed best. Bypass surgery and therapeutic angiogenesis (including autologous bone marrow mononuclear cell implantation) have shown reasonable results in selected cases.
• Sympathectomy, lumbar or thoracic, may be used for ischaemic rest pain and ulcer healing.
• Amputation of necrotic digits is required when tissue cannot be saved, with the aim of preserving as much limb function as possible. Major amputation is uncommon and should be a late resort.

Raynaud phenomenon is often diagnosed in adolescence and may improve or fluctuate through pregnancy; the mechanism is not fully understood. Dietary and conservative measures come first. Drug choices in pregnancy and in children should be made with a paediatric rheumatologist and obstetric team, because safety and dosing data are limited for many agents. Systemic sclerosis onset during pregnancy requires specialist multidisciplinary care. Cold exposure should be minimised throughout.

Refer to rheumatology or vascular medicine promptly when any of the following are present: onset of Raynaud phenomenon after 40 years; asymmetric or unilateral attacks; attacks not clearly triggered by cold or emotion; abnormal nailfold capillaries; a raised ESR or positive ANA without explanation; any digital ulcer, pitting scar, calcinosis or sclerodactyly; systemic symptoms suggesting connective tissue disease; failure of first-line management; occupational vibration exposure needing certification; or a young heavy smoker with distal digital ischaemia and migratory phlebitis suggesting thromboangiitis obliterans. Refer the same day for critical digital ischaemia, necrosis, or acute limb-threatening ischaemia.

• Digital ulcers in secondary Raynaud phenomenon, often slow to heal and prone to infection, sometimes requiring admission.
• Gangrene and amputation in severe secondary disease or in thromboangiitis obliterans.
• Stroke or embolism is not a typical complication of Raynaud phenomenon itself, but in thromboangiitis obliterans smoking drives vascular events generally.
• Psychological and functional burden: pain, disfigurement, loss of hand use, and chronic cold sensitivity.
• Progression to secondary disease in 14 to 37 percent of primary cases over time, so review and re-examine periodically, especially if features change. ^[2]

Primary Raynaud phenomenon has an excellent prognosis: it does not cause tissue loss and can often be controlled by avoiding triggers and using calcium channel blockers when needed. Secondary Raynaud phenomenon follows the prognosis of its underlying disease: in systemic sclerosis it is lifelong and contributes to morbidity, especially through digital ulcers and hand function loss. Thromboangiitis obliterans has a good long-term survival but remission depends on smoking cessation; continued smoking leads to repeated digital loss. Newer revascularisation and cell-based therapies improve outcomes in selected patients but have not replaced smoking cessation.

• Children. Raynaud phenomenon is uncommon before adolescence. In very young children an underlying connective tissue disease should be considered, and international paediatric consensus uses similar management to adults with attention to paediatric dosing and safety data.
• Older adults. New-onset Raynaud phenomenon after 40 should be worked up for secondary causes, and secondary rather than idiopathic disease becomes likely.
• Occupational vibration. Workers with hand-arm vibration syndrome need recognition, workplace modification and documentation. Attacks may be severe and vascular change can become fixed.
• Immunocompromised and acral cyanosis. In any vulnerable patient, suspect alternative causes of acral ischaemia, including infection, embolism and drug effects, and do not attribute digital cyanosis to Raynaud phenomenon without evidence.
• Low body mass index and outdoor workers. Low body mass worsens cold-induced attacks; practical cold protection, core warming and meal timing help.

• The diagnosis is clinical. A standardised history, pulse and blood pressure examination, and careful inspection of hands and nailfolds give most of the answer without expensive tests.
• Nailfold capillaroscopy can be performed with an ophthalmoscope or dermatoscope; a simple magnifying glass and good light are better than nothing, and photographs shared with a rheumatology centre can avoid travel.
• When laboratory testing is limited, prioritise an ANA and erythrocyte sedimentation rate and a review of the drug history; target further testing to clinical suspicion.
• Keep patients off the cold floor: socks, footwear, gloves, a hat and core warming cost little and work.
• Nifedipine and amlodipine are inexpensive and widely available; use the lowest effective dose by mouth and titrate carefully.
• Sildenafil is increasingly available and affordable in many markets; ensure blood pressure monitoring.
• For thromboangiitis obliterans, smoking cessation support, wound care and infection control are cheap and high-impact; surgical revascularisation is often not available, so refer early to a vascular centre when possible.
• Digital ulcers can be managed in primary care with debridement, dressings and infection control so long as the patient is not critically ischaemic.

• Raynaud phenomenon is a reversible, cold- or emotion-triggered digital vasospasm producing biphasic or triphasic colour change; two phases are enough to diagnose.
• Primary Raynaud phenomenon is common, benign, symmetric, starts young, attacks corresponding fingers and leaves no ulcers or pits.
• Secondary Raynaud phenomenon, especially in systemic sclerosis, is the dangerous form: later onset, asymmetric or severe, raised inflammatory markers, positive autoantibodies and abnormal nailfold capillaries, with ulcers and pitting scars.
• More than 90 percent of people with systemic sclerosis have Raynaud phenomenon, which is often the first clue years before scleroderma declares itself.
• Diagnosis rests on history using a standardised interview; the international consensus relaxed the criteria to allow a low-titre ANA and does not require a normal ESR, and no minimum number of attacks.
• ACR-EULAR systemic sclerosis criteria assign 3 points to Raynaud phenomenon and classify systemic sclerosis at 9 or more. ^[7]
• Calcium channel blockers, especially dihydropyridines such as nifedipine, are first-line pharmacological therapy at nifedipine 30 to 60 milligrams per day or amlodipine 5 to 10 milligrams per day.
• Second-line options include PDE-5 inhibitors such as sildenafil 25 to 100 milligrams; intravenous iloprost 0.5 to 2 nanograms per kilogram per minute for severe disease; and reserved use of bosentan or botulinum toxin. ^[4]
• Thromboangiitis obliterans is a smoking-driven disease of young men with distal segmental ischaemia; absolute smoking cessation is the treatment, with surgery and angiogenesis as adjuncts.
• Conserve heat, avoid smoking, adjust drugs, titrate calcium channel blockers carefully, and refer promptly when secondary features appear.

Systemic sclerosis and scleroderma, cardiovascular physical examination, peripheral arterial disease, pulmonary arterial hypertension, interstitial lung disease, digital ulcer disease, vasculitis, stroke and transient ischaemic attack, atrial fibrillation