Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

severe secondary RP: critical ischemia with digital ulcers or threatened digital loss

1st line – prostacyclin and/or phosphodiesterase-5 inhibitor

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
1st line – 

prostacyclin and/or phosphodiesterase-5 inhibitor

Prostacyclins (particularly iloprost) are used to treat complications of severe secondary RP, such as threatened digital loss due to ischemia 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.

Phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) 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]​​​​ Trials have shown a positive benefit with sildenafil in RP.[57][58]​​​​ Longer-acting PDE-5 inhibitors such as tadalafil are also used. Although dosing for tadalafil is more convenient, it has shown positive findings in RP only in a small crossover study, but not in combination with prostacyclins.[59]​ A trial of vardenafil versus placebo in RP has shown that vardenafil is associated with a reduction in frequency and duration of RP attacks and Raynaud's Condition Score (RCS).[60]​​ A 2023 Cochrane systematic review reported that PDE-5 inhibitors may reduce the frequency and duration of RP attacks.[62]

A prostacyclin would not normally be combined with a PDE-5 inhibitor due to the potential for drug interactions. Also, combining a prostacyclin and PDE-5 inhibitor can cause significant hypotension. However, if RP is sufficently severe to warrant prostanoid treatment, the patient would likely be referred to an expert center where a combination treatment may be considered.

Primary options

epoprostenol: 2 nanograms/kg/min intravenous infusion initially, increase by 2 nanograms/kg/min every 15 mins or longer according to response

More

OR

sildenafil: 12.5 mg orally twice daily initially, increase according to response, maximum 100 mg/day (given in 2-3 divided doses)

OR

tadalafil: 5-40 mg orally once daily

OR

vardenafil: consult specialist for guidance on dose

Plus – lifestyle measures

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with secondary RP who have progressed to digital ulceration. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Patients should be advised to quit smoking and avoid drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]​ Patients should also be advised to moisturize the skin around ulcers, avoid contact with cleaning agents, avoid manipulation of ulcers, wear protective gloves, and promote circulation through exercise.[32]​ If dexterity limitations are reported, patients should undergo occupational therapy assessment for aids (e.g., key holders).

Plus – treatment of underlying condition

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Plus – 

treatment of underlying condition

Treatment recommended for ALL patients in selected patient group

Treatment for the underlying condition that has resulted in secondary RP should be instigated after appropriate specialist consultation.

Consider – atorvastatin

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

atorvastatin

Treatment recommended for SOME patients in selected patient group

Atorvastatin has 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]​​

Primary options

atorvastatin: 40 mg orally once daily

Consider – analgesia

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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 ischemia 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 acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – aspirin

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

aspirin

Treatment recommended for SOME patients in selected patient group

Aspirin may be beneficial in helping prevent microthrombi formation.

Primary options

aspirin: 81 mg orally once daily

Consider – surgical debridement

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

surgical debridement

Treatment recommended for SOME patients in selected patient group

If there is a large fingertip ulcer, debridement by a surgeon may be necessary to remove necrotic tissue and/or infection and to promote healing.[4]​ If gangrene has progressed in spite of treatment, amputation of the digit may be required.

Consider – systemic antibiotics

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

systemic antibiotics

Treatment recommended for SOME patients in selected patient group

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, cephalexin, or erythromycin. However, you should consult your local protocols for guidance.

If infection is not resolved after 7 days of treatment (e.g., continued discolored purulence), treat for another 3 to 7 days.

If osteomyelitis is suspected, seek specialist advice from a microbiologist. See Osteomyelitis.

Primary options

cephalexin: 500 mg orally four times daily

Secondary options

erythromycin base: 250-500 mg orally four times daily

Consider – topical antibacterial ointment

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

topical antibacterial ointment

Treatment recommended for SOME patients in selected patient group

Topical antibacterials can be used if there is no evidence of a serious infection, but these may be working as a barrier and lubricant more than an antibacterial.

Primary options

mupirocin topical: apply ointment thinly to ulcer twice daily

OR

bacitracin/polymyxin B topical: apply ointment thinly to ulcer twice daily

Consider – bosentan

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

bosentan

Treatment recommended for SOME patients in selected patient group

Can be used to help prevent formation 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.

Liver function tests need to be checked monthly during treatment, and the duration of treatment required for prevention of digital ulcers is unknown but may be indefinitely.[67][70]​​[71]​ This use is off-label in the US.

Primary options

bosentan: 62.5 mg orally twice daily for 1 month, followed by 125 mg orally twice daily thereafter

More

2nd line – surgical sympathectomy

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
2nd line – 

surgical sympathectomy

Surgical sympathectomy may be effective in the treatment of severe RP that has failed pharmacologic 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 centers. A 2022 study reported pain relief with prevention of major amputation in 68 children with rheumatologic disorders presenting with RP after sympathetic blocks (including stellate ganglion blocks).[75]​ In one retrospective study of 17 patients with systemic sclerosis, localized palmar or digital sympathectomy improved pain and ulcer healing.[76]

Plus – lifestyle measures

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with secondary RP who have progressed to digital ulceration. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Patients should be advised to quit smoking and avoid drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]​ Patients should also be advised to moisturize the skin around ulcers, avoid contact with cleaning agents, avoid manipulation of ulcers, wear protective gloves, and promote circulation through exercise.[32]​ If dexterity limitations are reported, patients should undergo occupational therapy assessment for aids (e.g., key holders).

Plus – treatment of underlying condition

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Plus – 

treatment of underlying condition

Treatment recommended for ALL patients in selected patient group

Treatment for the underlying condition that has resulted in secondary RP should be instigated after appropriate specialist consultation.

Consider – atorvastatin

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

atorvastatin

Treatment recommended for SOME patients in selected patient group

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

Primary options

atorvastatin: 40 mg orally once daily

Consider – analgesia

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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 ischemia 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 acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – aspirin

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

aspirin

Treatment recommended for SOME patients in selected patient group

Aspirin may be beneficial in helping prevent microthrombi formation.

Primary options

aspirin: 81 mg orally once daily

Consider – surgical debridement

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

surgical debridement

Treatment recommended for SOME patients in selected patient group

If there is a large fingertip ulcer, debridement by a surgeon may be necessary to remove necrotic tissue and/or infection and to promote healing.[4]​ If gangrene has progressed in spite of treatment, amputation of the digit may be required.

Consider – systemic antibiotics

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

systemic antibiotics

Treatment recommended for SOME patients in selected patient group

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, cephalexin, or erythromycin. However, you should consult your local protocols for guidance. 

If infection is not resolved after 7 days of treatment (e.g., continued discolored purulence), treat for another 3 to 7 days.

If osteomyelitis is suspected, seek specialist advice from a microbiologist. See Osteomyelitis.

Primary options

cephalexin: 500 mg orally four times daily

Secondary options

erythromycin base: 250-500 mg orally four times daily

Consider – topical antibacterial ointment

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

topical antibacterial ointment

Treatment recommended for SOME patients in selected patient group

Topical antibacterials can be used if there is no evidence of a serious infection, but these may be working as a barrier and lubricant more than an antibacterial.

Primary options

mupirocin topical: apply ointment thinly to ulcer twice daily

OR

bacitracin/polymyxin B topical: apply ointment thinly to ulcer twice daily

Consider – bosentan

Back
ACUTE
|
severe secondary RP: critical ischemia with digital ulcers or threatened digital loss
Consider – 

bosentan

Treatment recommended for SOME patients in selected patient group

Can be used to help prevent formation 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.

Liver function tests need to be checked monthly during treatment, and the duration of treatment required for prevention of digital ulcers is unknown but may be indefinitely.[67][70]​​[71] ​This use is off-label in the US.

Primary options

bosentan: 62.5 mg orally twice daily for 1 month, followed by 125 mg orally twice daily thereafter

More
ONGOING

primary or mild secondary RP

1st line – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
1st line – 

lifestyle measures

Many patients with RP do not require treatment unless symptoms become severe.

Nonpharmacologic interventions should be considered first in primary or mild secondary RP and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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]

2nd line – calcium-channel blocker

Back
ONGOING
|
primary or mild secondary RP
2nd line – 

calcium-channel blocker

Calcium-channel blockers have been shown to decrease the frequency/severity of RP 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]​​

Nondihydropyridine classes of 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]

Calcium-channel blockers can be prescribed on an "as required" basis, such as in cold weather.

Primary options

nifedipine: 10 mg orally (immediate-release) three times daily, titrate according to response, maximum 180 mg/day; 30-60 mg orally (extended-release) once daily

OR

nicardipine: 20 mg orally three times daily, maximum 120 mg/day

Secondary options

felodipine: 2.5 mg orally once daily, titrate according to response, maximum 10 mg/day

OR

amlodipine: 2.5 mg orally once daily, titrate according to response, maximum 10 mg/day

Tertiary options

diltiazem: 30 mg orally (immediate-release) four times daily, maximum 360 mg/day

Plus – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with primary or mild secondary RP, and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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]

3rd line – ACE inhibitor or angiotensin-II receptor antagonist

Back
ONGOING
|
primary or mild secondary RP
3rd line – 

ACE inhibitor or angiotensin-II receptor antagonist

ACE inhibitors (e.g., captopril) 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 randomized controlled trial found that treatment with quinapril showed no improvement in secondary RP attacks.[54]

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]

Primary options

losartan: 25-100 mg orally once daily

OR

captopril: 25-150 mg orally three times daily

Plus – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with primary or mild secondary RP, and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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]

3rd line – selective serotonin-reuptake inhibitor

Back
ONGOING
|
primary or mild secondary RP
3rd line – 

selective serotonin-reuptake inhibitor

Selective serotonin-reuptake inhibitors (SSRIs) may be used as a third-line option when other drugs have failed or are not tolerated.

The association between SSRIs and RP is controversial. Treatment with the SSRI fluoxetine also showed a decrease in frequency and severity of attacks in one randomized trial.[45]​ However, other studies report that SSRIs may exacerbate RP symptoms.[7][46]

Primary options

fluoxetine: 20-60 mg orally once daily

Plus – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with primary or mild secondary RP, and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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]

3rd line – topical nitrate

Back
ONGOING
|
primary or mild secondary RP
3rd line – 

topical nitrate

Topical nitroglycerin may be used as a third-line option when other drugs have failed or are not tolerated.

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

Primary options

nitroglycerin topical: (2%) apply to the affected area(s) twice daily

Plus – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with primary or mild secondary RP, and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain from severe or prolonged ischemia 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 acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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]

4th line – alpha-blocker

Back
ONGOING
|
primary or mild secondary RP
4th line – 

alpha-blocker

Alpha-blockers may be used as a fourth-line option when all other drugs have failed or are not tolerated.

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

Primary options

prazosin: 1 mg orally twice daily

Plus – lifestyle measures

Back
ONGOING
|
primary or mild secondary RP
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle measures should also be considered alongside treatment in people with primary or mild secondary RP, and mainly include preventative measures and avoidance of triggers. These include keeping warm and avoiding damp: for instance, by wearing gloves or using hand warmers. Advice should be given about quitting smoking, moisturizing dry skin, and avoiding drugs known to exacerbate RP (e.g., beta-blockers, ergotamine, clonidine, cyclosporine, caffeine, cocaine, amphetamines). Avoiding injury to digits and exposure to vibration, as well as minimizing stress, are also recommended. Vasoconstrictor drugs should be discontinued where possible.[4][31]

Consider – analgesia

Back
ONGOING
|
primary or mild secondary RP
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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, additional analgesics may be required to treat pain.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications. Simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be sufficient. Short- or long-acting opioids may be required. Digital ulcers may be very painful, and 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. Local palmar and/or digital sympathectomy is a last-line option.

Primary options

acetaminophen: 325-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 300-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) twice or three times daily when required

OR

diclofenac sodium: 100 mg orally (extended-release) once daily when required

Secondary options

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

OR

oxycodone: 5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (extended-release) every 12 hours when required

Tertiary options

fentanyl transdermal: 12.5 micrograms/hour patch applied every 72 hours, increase to 25 micrograms/hour patch applied every 72 hours if required

Consider – complementary and alternative therapies

Back
ONGOING
|
primary or mild secondary RP
Consider – 

complementary and alternative therapies

Treatment recommended for SOME patients in selected patient group

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 randomized 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 analog 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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