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

renal crisis

1st line – ACE inhibitor + hydration

Back
ACUTE
|
renal crisis
1st line – 

ACE inhibitor + hydration

Scleroderma renal crisis (SRC) is a medical emergency of new-onset hypertension with elevated creatinine and intravascular hemolysis.

SRC is rare in limited cutaneous systemic sclerosis and occurs more commonly in early diffuse cutaneous systemic sclerosis.

Treatment includes rapid control of blood pressure with intensive use of ACE inhibitors titrated to blood pressure response and hydration (as many of the blood vessels are in complete spasm).[32][40] The use of ACE inhibitors is not prophylactic of SRC.[42][43] Use of ACE inhibitors has reduced the mortality of SRC from 80% to 20%, likely due to increasing bradykinin.[40][41] 

For patients who appear volume-depleted, consider intravenous hydration with normal saline. Rate and volume will depend on the clinical condition and response of the individual patient, but a rate of 200 mL per hour with reassessment after 1 liter would be typical.

Consult specialist for guidance on dose escalation in these patients.

Primary options

captopril: 12.5 to 25 mg orally two to three times daily initially, increase according to response, maximum 450 mg/day

OR

enalapril: 2.5 to 5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

enalaprilat: 0.625 to 1.25 mg intravenously every 6 hours initially, increase according to response, maximum 20 mg/day

OR

lisinopril: 5-10 mg orally once daily initially, increase according to response, maximum 40 mg/day

Consider – additional antihypertensive

Back
ACUTE
|
renal crisis
Consider – 

additional antihypertensive

Treatment recommended for SOME patients in selected patient group

The longer it takes to normalize blood pressure, and the higher the presenting creatinine, the more likely that dialysis or death may result. The ACE inhibitor should not be stopped even if the creatinine is rising. Additional antihypertensive agents may be added to an ACE inhibitor to achieve rapid blood pressure control.

Diuretic should not be given unless there is congestive heart failure, as the depletion of intravascular volume may cause more vasospasm and hemolysis.

Primary options

nifedipine: 10 mg orally (immediate-release) three times daily initially, increase according to response, maximum 180 mg/day

OR

nicardipine: 20 mg orally (immediate-release) three times daily initially, increase according to response, maximum 120 mg/day

Secondary options

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

OR

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

Tertiary options

diltiazem: 30 mg orally (immediate-release) four times daily initially, increase according to response, maximum 360 mg/day

OR

hydralazine: 10 mg orally four times daily initially, increase according to response, maximum 300 mg/day

OR

nitroprusside: 0.3 to 0.5 micrograms/kg/min intravenous infusion initially, increase according to response, maximum 4 micrograms/kg/minute

OR

minoxidil: 5-10 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

labetalol: 200 mg orally twice daily initially, increase according to response, maximum 800 mg/day

OR

prazosin: 1 mg orally two to three times daily initially, increase according to response, maximum 20 mg/day

2nd line – renal dialysis or transplantation

Back
ACUTE
|
renal crisis
2nd line – 

renal dialysis or transplantation

Dialysis may be required. Renal transplant can be considered in renal failure after scleroderma renal crisis.[40]

Plus – ACE inhibitor + hydration

Back
ACUTE
|
renal crisis
Plus – 

ACE inhibitor + hydration

Treatment recommended for ALL patients in selected patient group

Dialysis may be required. If dialysis is needed, the ACE inhibitor should not be stopped, as even 1 year after dialysis there could be renal function recovery. For patients who appear volume-depleted, consider intravenous hydration with normal saline. Rate and volume will depend on the clinical condition and response of the individual patient, but a rate of 200 mL per hour with reassessment after one liter would be typical.

Consult specialist for guidance on dose escalation in these patients.

Primary options

captopril: 12.5 to 25 mg orally two to three times daily initially, increase according to response, maximum 450 mg/day

OR

enalapril: 2.5 to 5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

enalaprilat: 0.625 to 1.25 mg intravenously every 6 hours initially, increase according to response, maximum 20 mg/day

OR

lisinopril: 5-10 mg orally once daily initially, increase according to response, maximum 40 mg/day

ONGOING

no renal crisis

1st line – smoking cessation, exercise, and physical therapy

Back
ONGOING
|
no renal crisis
1st line – 

smoking cessation, exercise, and physical therapy

Smoking cessation is recommended (especially for patients with Raynaud phenomenon and digital ulcers). Regular exercise and improving range of motion (ROM) of areas where skin and tendons are involved may improve or maintain ROM and function. Appropriate for patients with contractures and diminished ROM.

Consider – immunosuppressant therapy

Back
ONGOING
|
no renal crisis
Consider – 

immunosuppressant therapy

Treatment recommended for SOME patients in selected patient group

Immunosuppressant therapy may be considered in some patients, such as those with lung involvement, myositis, or inflammatory arthritis.

Methotrexate may be used for inflammatory arthritis and myositis.[29][30]

Patients with interstitial lung disease may be given mycophenolate, cyclophosphamide, azathioprine, or rituximab.[31][32][33]

Immunosuppressants may be used for skin involvement in early active disease.

Primary options

methotrexate: consult specialist for guidance on dose

OR

mycophenolate mofetil: consult specialist for guidance on dose

OR

cyclophosphamide: consult specialist for guidance on dose

OR

azathioprine: consult specialist for guidance on dose

OR

rituximab: consult specialist for guidance on dose

Plus – vasodilator

Back
ONGOING
|
no renal crisis
|
with digital ischemia or digital ulcers
Plus – 

vasodilator

Treatment recommended for ALL patients in selected patient group

Digital ulcers can be a serious complication and may be treated with prostacyclins (e.g., iloprost) or phosphodiesterase-5 inhibitors (e.g., sildenafil).[32] Endothelin receptor antagonists (e.g., bosentan) have also been used; although they do not heal ulcers, they prevent the occurrence of new ulcers.[32]

Intravenous iloprost is generally considered to be the first-line prostacyclin; however, the intravenous formulation is not available in the US. Intravenous epoprostenol can be used as an alternative to intravenous iloprost.

Primary options

epoprostenol: consult specialist for guidance on dose

OR

sildenafil: consult specialist for guidance on dose

OR

bosentan: consult specialist for guidance on dose

Consider – analgesia

Back
ONGOING
|
no renal crisis
|
with digital ischemia or digital ulcers
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

Pain relief is an important component of symptom management.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications.

Nonsteroidal anti-inflammatory drugs or acetaminophen should be considered.

Primary options

celecoxib: 200 mg orally once daily when required

OR

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

Secondary options

acetaminophen: 650-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Plus – supportive care + analgesia

Back
ONGOING
|
no renal crisis
|
with Raynaud phenomenon
Plus – 

supportive care + analgesia

Treatment recommended for ALL patients in selected patient group

Avoiding the cold, wearing warm mittens and a hat, and using hand or foot warmers can help prevent attacks of Raynaud phenomenon (RP). Pharmacologic treatment of RP may proceed in tandem with treatment of other manifestations.

Local pain management algorithms should be followed, and treatment should be tailored to medical history and any relative/absolute contraindications.

Nonsteroidal anti-inflammatory drugs or acetaminophen should be considered.

Primary options

celecoxib: 200 mg orally once daily when required

OR

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

Secondary options

acetaminophen: 650-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Consider – calcium-channel blocker

Back
ONGOING
|
no renal crisis
|
with Raynaud phenomenon
Consider – 

calcium-channel blocker

Treatment recommended for SOME patients in selected patient group

Recommended first-line agents include nifedipine and nicardipine.[21][32][33] These agents reduce the frequency and severity of Raynaud phenomenon (RP) attacks in people with systemic sclerosis.[34]

There is no consensus on what drugs to combine for RP treatment. If RP is severe, medications are often switched or added, although hypotension can limit options due to the additive effects of multiple treatments each of which can lower blood pressure.

Primary options

nifedipine: 10 mg orally (immediate-release) three times daily initially, increase according to response, maximum 180 mg/day

OR

nicardipine: 20 mg orally (immediate-release) three times daily initially, increase according to response, maximum 120 mg/day

Consider – oral phosphodiesterase (PDE)-5 inhibitor

Back
ONGOING
|
no renal crisis
|
with Raynaud phenomenon
Consider – 

oral phosphodiesterase (PDE)-5 inhibitor

Treatment recommended for SOME patients in selected patient group

When dihydropyridine calcium-channel blockers have failed or are not tolerated, oral PDE-5 inhibitors may be used.[21][32][33] Oral PDE-5 inhibitors have been shown to decrease the frequency, severity, and duration of Raynaud phenomenon (RP) attacks in people with secondary RP.[35]

There is no consensus on what drugs to combine for RP treatment. If RP is severe, medications are often switched or added, although hypotension can limit options due to the additive effects of multiple treatments each of which can lower blood pressure.

Primary options

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

Consider – topical nitrate or vasodilator therapy or fluoxetine or ACE inhibitor/angiotensin-II receptor antagonist

Back
ONGOING
|
no renal crisis
|
with Raynaud phenomenon
Consider – 

topical nitrate or vasodilator therapy or fluoxetine or ACE inhibitor/angiotensin-II receptor antagonist

Treatment recommended for SOME patients in selected patient group

If calcium-channel blockers and oral PDE-5 inhibitors are not effective, alternative agents include ACE inhibitors (e.g., captopril) or angiotensin-II receptor antagonists (e.g., losartan), fluoxetine, topical nitrates, or topical vasodilators (i.e., topical PDE-5 inhibitors may be used; however, they are not widely available and may need to be specially compounded).[21][33] 

There is no consensus on what drugs to combine for Raynaud phenomenon (RP) treatment. If RP is severe, medications are often switched or added, although hypotension can limit options due to the additive effects of multiple treatments each of which can lower blood pressure.

Primary options

nitroglycerin topical: (0.2%) apply to the affected area(s) twice daily

OR

fluoxetine: 20-60 mg orally once daily

OR

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

captopril: 12.5 to 25 mg orally two to three times daily initially, increase according to response, maximum 450 mg/day

Consider – prostacyclin

Back
ONGOING
|
no renal crisis
|
with Raynaud phenomenon
Consider – 

prostacyclin

Treatment recommended for SOME patients in selected patient group

Intravenous prostacyclins (particularly iloprost), sometimes in combination with oral sildenafil, are used to treat complications of severe Raynaud phenomenon (RP), such as threatened digital loss due to ischemia and digital ulcers.[21][32][33][36] Treatment with prostacyclins alone has been shown to decrease the frequency/severity of attacks and heals/prevents digital ulcers.[37][38] Intravenous iloprost is generally considered to be the first-line prostacyclin; however, the intravenous formulation is not available in the US, and the inhaled formulation is generally not recommended for this indication. Intravenous epoprostenol can be used as an alternative to intravenous iloprost.

A prostanoid would not normally be combined with a PDE-5 inhibitor due to the potential for drug interactions, and combining a prostacyclin and PDE-5 inhibitor can cause significant hypotension. However, if a patient has severe enough RP 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

Plus – supportive care

Back
ONGOING
|
no renal crisis
|
with dysphagia
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Dysphagia may be managed conservatively by eating slowly, chewing food well, and avoiding difficult-to-swallow foods. Patients should avoid lying down after eating; this may reduce dysphagia by using gravity to help propel food through the esophagus. If abnormal peristalsis is the sole cause of dysphagia, esophageal dilations are unlikely to be of benefit.

Consider – esophageal dilation

Back
ONGOING
|
no renal crisis
|
with dysphagia
Consider – 

esophageal dilation

Treatment recommended for SOME patients in selected patient group

If there is a stricture, dilations can be helpful and then often need to be repeated over time.

Consider – jejunal feeding tube

Back
ONGOING
|
no renal crisis
|
with dysphagia
Consider – 

jejunal feeding tube

Treatment recommended for SOME patients in selected patient group

If the patient is at high risk of aspiration, a jejunal feeding tube may be needed.

Plus – analgesia

Back
ONGOING
|
no renal crisis
|
with calcinosis
Plus – 

analgesia

Treatment recommended for ALL patients in selected patient group

Calcinosis can be adherent to bone or tendons. There is no means of prevention, and treatment is symptomatic.

Pain should be treated conventionally with nonopioid agents to the greatest extent possible (e.g., nonsteroidal anti-inflammatory drugs or acetaminophen).

Primary options

celecoxib: 200 mg orally once daily when required

Secondary options

acetaminophen: 650-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Consider – surgical excision

Back
ONGOING
|
no renal crisis
|
with calcinosis
Consider – 

surgical excision

Treatment recommended for SOME patients in selected patient group

Surgical resection can achieve good results, but the calcinosis may recur.[21]

Plus – intensive physical therapy

Back
ONGOING
|
no renal crisis
|
with diminished joint range of motion
Plus – 

intensive physical therapy

Treatment recommended for ALL patients in selected patient group

Contractures and decreased range of motion (ROM) of the fingers, wrists, and other areas (elbows, shoulders, and even lower extremities) are important complications bearing on overall wellbeing.

As it is difficult to reverse contractures, prevention assumes paramount importance in management.

It is important to initiate ROM exercises early with a physical therapist or occupational therapist.

Consider – splinting

Back
ONGOING
|
no renal crisis
|
with diminished joint range of motion
Consider – 

splinting

Treatment recommended for SOME patients in selected patient group

Splinting may be helpful to reduce contractures.[39]

Plus – supportive care

Back
ONGOING
|
no renal crisis
|
with GERD
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

GERD occurs where there is a patent lower esophageal sphincter allowing for reflux of stomach contents into the esophagus.

The treatment is to avoid eating after evening meals and raising the head of the bed (e.g., using blocks to elevate the head of the bed).

Alcohol, chocolate, caffeine, and peppermint (food triggers) should be avoided.

Plus – proton-pump inhibitors

Back
ONGOING
|
no renal crisis
|
with GERD
Plus – 

proton-pump inhibitors

Treatment recommended for ALL patients in selected patient group

First-line treatment for GERD.[32]

Primary options

omeprazole: 20 mg orally once daily

OR

esomeprazole: 20-40 mg orally once daily

OR

rabeprazole: 20 mg orally once daily

OR

pantoprazole: 40 mg orally once daily

OR

lansoprazole: 15-30 mg orally once daily

Consider – H2 antagonist or prokinetic agent

Back
ONGOING
|
no renal crisis
|
with GERD
Consider – 

H2 antagonist or prokinetic agent

Treatment recommended for SOME patients in selected patient group

If reflux is severe, addition of an H2 antagonist or a prokinetic agent (e.g., domperidone or metoclopramide) may be indicated.[32] However, domperidone is not currently available in the US.

Primary options

cimetidine: 800 mg orally twice daily

OR

famotidine: 20 mg orally twice daily

OR

metoclopramide: 10-15 mg orally four times daily

Plus – wrist splint + nonsteroidal anti-inflammatory drug (NSAID)

Back
ONGOING
|
no renal crisis
|
with carpal tunnel syndrome
Plus – 

wrist splint + nonsteroidal anti-inflammatory drug (NSAID)

Treatment recommended for ALL patients in selected patient group

For patients who have significant inflammation or arthritis, addition of an NSAID may help relieve symptoms, together with wrist splints.

Primary options

ibuprofen: 400-800 mg orally every 6-8 hours when required, maximum 3200 mg/day

OR

celecoxib: 200 mg orally once daily when required

Consider – corticosteroid injection

Back
ONGOING
|
no renal crisis
|
with carpal tunnel syndrome
Consider – 

corticosteroid injection

Treatment recommended for SOME patients in selected patient group

Injecting the carpal tunnel with a corticosteroid may be required.

Primary options

methylprednisolone acetate: single doses of 20-40 mg intracarpally with or without a local anesthetic have been reported; however, consult a specialist for further guidance on dose

OR

dexamethasone sodium phosphate: single doses of 4 mg intracarpally with or without a local anesthetic have been reported; however, consult a specialist for further guidance on dose

OR

hydrocortisone sodium succinate: single doses of 25-100 mg intracarpally have been reported; however consult a specialist for further guidance on dose

Consider – surgical release

Back
ONGOING
|
no renal crisis
|
with carpal tunnel syndrome
Consider – 

surgical release

Treatment recommended for SOME patients in selected patient group

Surgery for median nerve release may be required.

Plus – disease-modifying antirheumatic drug (DMARD)

Back
ONGOING
|
no renal crisis
|
with inflammatory arthritis
Plus – 

disease-modifying antirheumatic drug (DMARD)

Treatment recommended for ALL patients in selected patient group

Arthralgia is often treated with DMARDs.

If already started, methotrexate can be continued. Other options include sulfasalazine, leflunomide, or hydroxychloroquine.

Primary options

methotrexate: 7.5 to 25 mg orally/intramuscularly once weekly given on the same day of each week

OR

sulfasalazine: 500-1000 mg/day orally given in 2 divided doses initially, increase according to response, maximum 3000 mg/day

OR

leflunomide: 100 mg orally once daily for 3 days, followed by 10-20 mg once daily

OR

hydroxychloroquine sulfate: 200-400 mg/day orally

Plus – oral corticosteroid

Back
ONGOING
|
no renal crisis
|
with inflammatory arthritis
Plus – 

oral corticosteroid

Treatment recommended for ALL patients in selected patient group

Corticosteroids are used commonly in combination with a DMARD in these patients. They can be used as a chronic treatment option and also as management for acute flares of disease activity.

Primary options

prednisone: 1-10 mg orally once daily

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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

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