Approach
Treatment can be divided into modifying the disease overall and treating specific organ involvement or symptoms. Smoking cessation is recommended (especially for patients with Raynaud phenomenon [RP] 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. Combinations of treatment may be used: for example, the treatment of RP with two medications.
General principles of treatment
Immunosuppressant therapy may be considered in some patients, such as those with lung involvement, myositis, or inflammatory arthritis:
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.
Digital ulcers
Digital ulcers can be a serious complication and may be treated with prostacyclins (e.g., iloprost) or phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil).[32] Endothelin receptor antagonists (e.g., bosentan) have also been used; although they do not promote healing of existing ulcers, they prevent the occurrence of new ulcers.[32]
Pain relief
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 (NSAIDs) or acetaminophen should be considered.
Raynaud phenomenon
In systemic sclerosis, including limited cutaneous systemic sclerosis (lcSSc), RP is more severe than in idiopathic RP. Avoiding the cold, wearing warm mittens and a hat, and using hand or foot warmers can help prevent attacks of RP.
Recommended first-line agents include nifedipine and nicardipine.[21][32][33] These agents reduce the frequency and severity of RP attacks in people with systemic sclerosis.[34]
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 RP attacks in people with secondary RP.[35]
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]
Intravenous prostacyclins (particularly iloprost), sometimes in combination with oral sildenafil, are used to treat complications of severe 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.
Pharmacologic treatment of RP may proceed in tandem with treatment of other manifestations. 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.
Dysphagia
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. But if there is a stricture, dilations can be helpful and then often need to be repeated over time. If the patient is at high risk of aspiration, a jejunal feeding tube may be needed.
Calcinosis
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. No drug therapy is effective for calcinosis. It is probably important to treat RP, as underlying ischemia worsens the calcinosis, and to avoid local trauma, as that is where more calcinosis tends to form. Surgical resection can achieve good results, but the calcinosis may recur.[21]
With contractures and diminished ROM
Contractures and decreased 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. Splinting may be helpful to reduce contractures.[39]
With scleroderma renal crisis (SRC)
SRC is a medical emergency of new-onset hypertension with elevated creatinine and intravascular hemolysis. SRC is rare in lcSSc and occurs more commonly in early diffuse cutaneous systemic sclerosis (dcSSc). Treatment includes rapid control of blood pressure (BP) with ACE inhibitors and hydration (as many of the blood vessels are in complete spasm).[40][32] ACE inhibitors have reduced the mortality of SRC from 80% to 20%; this effect is likely to be due to increasing bradykinin.[40][41] The use of ACE inhibitors is not prophylactic of SRC.[42][43]
The longer it takes to normalize BP and the higher the presenting creatinine, the more likely that dialysis or death may result. High BP needs to be treated quickly and intensively using ACE inhibitors and adding any other antihypertensive treatment (e.g., calcium-channel blocker, hydralazine, nitroprusside, minoxidil, labetalol, alpha-blocker) as needed.
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. Renal transplant can be considered in renal failure after SRC.[40]
With GERD
GERD occurs where there is a patent lower esophageal sphincter allowing for reflux of stomach contents into the esophagus. Supportive measures include avoiding eating after the evening meal 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. Proton-pump inhibitors may be used to treat GERD in SSc, although evidence from large randomized controlled trials is lacking.[32] Proton-pump inhibitors, often at double the normal dose, work best if taken before a meal. The addition of H2 antagonists or prokinetic agents may be indicated if reflux is severe.[32]
With carpal tunnel syndrome
Resting hand splints, injecting the carpal tunnel with corticosteroids, or surgery for median nerve release may be appropriate treatment options. For patients who have significant inflammation or arthritis, the addition of NSAIDs may help relieve symptoms together with wrist splints. For patients who have significant edema, and swelling of skin and or tendons/wrists, a low dose of a corticosteroid may help relieve symptoms, together with mainstay therapy, until other treatment starts to work: for example, treatment of inflammatory arthritis if wrist swelling/tenosynovitis is the cause of the compression of the median nerve.
With inflammatory arthritis
Arthralgia is often treated with disease-modifying antirheumatic drugs (DMARDs). Corticosteroids are commonly used in combination with a first-line DMARD. They can be used as a chronic treatment option and also as management for acute flares of disease activity.
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