Approach

There is minimal evidence on the comparative efficacy of treatment options for Raynaud's phenomenon (RP), and management varies depending on disease severity and symptoms.[4]

Treatment for primary or mild secondary RP usually consists of lifestyle changes and pharmacological therapies. Treatment for moderate to severe secondary RP may warrant additional pharmacological therapies or surgery if patients have progressed to digital ulceration or gangrene.

In all patients, if treatment is ineffective, if there is suspicion of connective tissue disease or another underlying condition (secondary RP), or if treatment for severe secondary RP is needed (e.g., digital ulceration or critical ischaemia), referral to a rheumatologist is recommended.[4]

Lifestyle measures

Many cases of RP do not require pharmacological treatment unless symptoms become severe. Non-pharmacological interventions should be considered first in primary or mild secondary RP and mainly include preventative measures and avoidance of triggers, for instance:[4][31]

  • Keeping warm and avoiding damp (e.g., wear gloves, use hand warmers)

  • Moisturising dry skin

  • Quitting smoking

  • Avoiding injury to digits and vibration exposure

  • Avoiding stress

  • Withdrawal from vasoconstrictor drugs when possible

  • Avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, ciclosporin, caffeine, cocaine, amphetamines).

If dexterity limitations are reported, patients should undergo occupational therapy assessment for aids (e.g., key holders).

Pharmacological treatment can be considered in people with mild disease who do not respond to lifestyle measures. Lifestyle measures should also be considered alongside pharmacological treatment in people with secondary RP who have progressed to digital ulceration. Additional recommendations include moisturising the skin around ulcers, avoiding contact with cleaning agents, avoiding injury to digits, avoiding manipulation of ulcers, wearing protective gloves, and promoting circulation through exercise.[32]​​

Pharmacological treatments

Calcium-channel blockers

The goals of pharmacological treatment are to decrease frequency, severity, and duration of attacks. The recommended first-line pharmacological treatment is calcium-channel blockers, which have been shown to decrease the frequency/severity of attacks, often by 30%.[4][33]​​​​​​​[34][35] [ Cochrane Clinical Answers logo ] ​​​​​​ [ Cochrane Clinical Answers logo ] ​​​​ Meta-analyses have demonstrated that dihydropyridine calcium-channel blockers are effective in primary and secondary RP. Recommended agents include nifedipine, nicardipine, and less well-studied agents, including amlodipine or felodipine.[4][35]​​[36][37]​​​​​​[38]​​​​

Non-dihydropyridine calcium-channel blockers (e.g., diltiazem) can be offered if dihydropyridine calcium-channel blockers cannot be used or are ineffective.[4][36]​​[39]​​​

Calcium-channel blockers may not be effective in all patients and may have adverse effects such as hypotension, lightheadedness, flushing, and ankle puffiness. Short-acting calcium-channel blockers may cause orthostatic hypotension, and many people with RP are young and have normal-to-low blood pressure. If the short-acting calcium-channel blocker is tolerated but not effective, then the dose can be increased.[4]

Alternative vasodilators

There is a lack of evidence for the use of vasodilators other than calcium-channel blockers in RP.[40]​ However, when calcium-channel blockers have failed or are not tolerated, other vasodilators may be trialled.[4][35][41]

Two studies have shown a reduction in RP attacks in patients treated with the angiotensin-II receptor antagonist losartan, with one study showing improvement in RP symptoms compared with nifedipine.[42][43][44]

The association between selective serotonin-reuptake inhibitors (SSRIs) and RP is controversial. Treatment with fluoxetine showed a decrease in frequency and severity of attacks in one randomised trial.[45]​ However, other studies report that SSRIs may exacerbate RP symptoms.[7][46]

Topical nitrates have been shown to be effective in reducing the frequency and severity of attacks, reducing ulcer size, lowering Raynaud’s Condition Score (RCS), and improving blood flow in several randomised controlled trials; however, adverse effects such as headaches may limit their use.[47][48][49][50]

Treatment with the alpha-blocker prazosin has shown modest improvement in RP in three randomised controlled trials; however, adverse effects may be common and no further trials have been conducted since 1986.[51][52][53]

ACE inhibitors have also been used as alternatives to calcium-channel blockers but have shown conflicting results.[44]​ A 2021 systematic review found that captopril and enalapril may increase the frequency of attacks in primary RP.[40]​ A randomised controlled trial found that treatment with quinapril showed no improvement in secondary RP attacks.[54]

Severe disease

Phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil, and udenafil) can be used for patients with moderate to severe secondary RP when calcium-channel blockers have failed or are not tolerated.​[4][41][55]​​[56]​​ Two trials have shown positive benefit with sildenafil in RP. One was a multi-centre trial that studied limited cutaneous systemic sclerosis patients with significant RP who were non-smokers, while the other was a single-site crossover trial in patients with RP.[57][58]​​ Tadalafil has also shown positive results in an RP trial in scleroderma and mixed connective tissue disease patients with at least 4 attacks per week. The medication was effective and also seemed to help digital ulcers, which was a secondary end point.[59] Similarly, when examining the results of vardenafil compared with placebo in a randomised crossover trial, there was a reduction in the number of attacks per week, the cumulative duration of attacks, and RCS in 53 patients with either primary or secondary RP.[60]​​ One PDE-5 inhibitor trial has shown negative data for RP.[61] Long-acting PDE-5 inhibitors (e.g., tadalafil) may be better tolerated than short-acting PDE-5 inhibitors, causing less hypotension and perhaps better adherence. A 2023 Cochrane systematic review reported that PDE-5 inhibitors may reduce the frequency and duration of RP attacks; however, the evidence was of low certainty and little to no difference in pain was reported.[62]

Prostacyclins (particularly iloprost), sometimes in combination with sildenafil, are used to treat complications of severe secondary RP, such as threatened digital loss due to ischaemia and digital ulcers.[4][33]​​​​ These drugs can be effective for several months after treatment. Treatment with prostacyclins alone has been shown to decrease the frequency/severity of attacks and heals/prevents digital ulcers.[41][63]​​ Intravenous iloprost is generally considered to be the first-line prostacyclin; however, the intravenous formulation may not be available in some countries, and the inhaled formulation is generally not recommended for this indication. Therefore, intravenous epoprostenol can be used as an alternative to intravenous iloprost. Inhaled prostacyclins are not commonly used for RP; however, they have a role in treating pulmonary arterial hypertension in connective tissue diseases and can improve RP symptoms. Oral prostacyclins are usually not stable and/or well absorbed and tend to be less effective than intravenous iloprost.[64][65]

Atorvastatin has also been found to decrease new ulcer formation in patients with secondary RP and may be used in patients with past or present ulcers, but is not indicated for the prevention of digital ulcers.​[35][66]

Bosentan, an endothelial receptor antagonist, has also been used for the prevention of systemic sclerosis-related digital ulcers.[67][68][69]​​​​ It has been found to reduce the incidence of new ulcers by 30% to 50%.[68]​ However, it is not superior to usual care in healing current ulcers. It had no effect on uncomplicated RP in the systemic sclerosis digital ulcer trials.[67][70]​​[71]​​​

Aspirin may be beneficial in helping prevent micro-thrombi formation, but there are no trials with aspirin in RP.[72]​​

Wound care of digital ulcers should also be considered.[35]​ Topical antibacterials can be used if there is no evidence of a significant infection, but they may be working as a barrier and lubricant more than an antibacterial.

Antibiotics should be given when ulcers are infected. Infections are often due to Staphylococcus aureus or Pseudomonas aeruginosa, but can also be caused by Escherichia coli, Enterococcus faecalis, Streptococcus epidermidis, or Bacillus morganii.[73] If there is frank purulence, it is advisable to take a swab for culture and sensitivities prior to starting antibiotics, and to tailor treatment based on swab sensitivities and severity of infection. Examples of antibiotic options may include cloxacillin, cefalexin, or erythromycin. However, you should consult your local protocols for guidance. If infection is not resolved after 7 days of treatment (e.g., continued discoloured purulence), treat for another 3 to 7 days. If osteomyelitis is suspected, seek consultant advice from a microbiologist. See Osteomyelitis.

Pain relief is an important component of symptom management. Vasodilators treat the pain of RP if they are effective in reducing the frequency, severity, or duration of attacks. However, analgesics may be required to treat pain from severe or prolonged ischaemia or complications such as gangrene or digital ulcers. Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Opioids may be required. Digital ulcers may be very painful, and opioids such as codeine or oxycodone may be indicated. Rarely, transdermal fentanyl is used if other opioids are not effective or not tolerated, typically for patients with gangrene or osteomyelitis.

Surgery

There is limited evidence in support of surgical management of RP. For patients with secondary RP who have progressed to digital ulceration or gangrene, however, surgery may be indicated.[4]​ For some digital ulcers, debridement by a surgeon may be necessary to remove necrotic tissue and/or infection and promote healing. If gangrene has progressed in spite of treatment, amputation of the digit may be required.

Surgical sympathectomy may be effective in the treatment of severe RP that has failed pharmacological treatment.[6][35]​ Techniques available include stellate ganglion or lumbar sympathetic blocks, proximal cervical sympathectomies via endoscopic surgery, and selective palmar and/or digital sympathectomies.[74] Such techniques may not be available in all centres. A 2022 study reported pain relief with prevention of major amputation in 68 children with rheumatological disorders presenting with RP after sympathetic blocks (including stellate ganglion blocks).[75]​ In one retrospective study of 17 patients with systemic sclerosis, localised palmar or digital sympathectomy improved pain and ulcer healing.[76]

Complementary and alternative therapies

Several alternative therapies or supplements have been claimed to help improve RP; however, these lack sufficient evidence and rely on patient testimonials. Complementary and alternative therapies that have been investigated in randomised controlled trials include evening primrose oil,​ omega-3 fatty acids,​ Ginkgo biloba,​​ biofeedback, acupuncture,​ and low-level laser therapy.[77][78]​​​​[79][80][81]​​​​​[82]​ A review and meta-analysis of complementary and alternative medicines in the treatment of RP found most trials were negative, of poor quality, and done prior to 1990.[83] However, given the limited risks associated with these treatments, using them as an adjunctive therapy may be considered for patients at any stage of RP severity, but patients should be informed on their lack of shown efficacy.

One study involving patients with RP who were deficient in vitamin D showed improvements on the visual analogue scale with use of oral vitamin D3 supplementation compared with placebo supplementation.[84]

The effects of ceramic or silver-lined gloves in RP have also been investigated. One study reported improvement in pain and dexterity in patients using ceramic-lined gloves for 3 months compared with cotton gloves, whereas a 2022 study investigating silver-lined gloves found no improvement compared with normal gloves.[85][86]

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