Clinical Review

Systemic Scleroderma: The Truth Beneath a "Skin Disease"

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References

A musculoskeletal exam may also prove helpful. Range of motion and joint mobility should be assessed, especially if sclerotic skin causes flexion contractures, producing shortened fingers or articular deformities.16

Diagnostic Work-up
If suspicion of SSc persists, the disease can be further assessed through laboratory values and imaging. No one test ensures a definitive diagnosis, but serologic testing for autoantibodies is helpful.5,33

The provider may order an antinuclear antibody (ANA) test or rheumatoid factor testing to confirm connective tissue disease (CTD). However, it is important to remember that a positive ANA result is found in patients with other CTDs, including 30% of those with rheumatoid arthritis and 95% of those with systemic lupus erythematosus.33 Since anticentromere antibodies are present in 70% to 80% of patients, and antibodies against topoisomerase I DNA (anti-Scl-70) exist in about 40% of patients, confirmed presence of either has a specificity of 95% to 99% for the diagnosis of SSc.34

Imaging and other tests help to assess the involvement of SSc and the extent of associated fibrosis in internal organs. X-ray of the hands can reveal intra-articular calcifications and osteopenia, as well as soft-tissue calcinosis.11,17

Chest x-ray and CT can detect interstitial lung disease.33 Imaging will also help differentiate active alveolitis (ground-glass appearance) from pulmonary fibrosis (honeycombing).6 Clinicians may order pulmonary function testing to confirm restrictive lung disease. Doppler echocardiography will show cardiac and pulmonary vascular involvement and can confirm the presence of pulmonary hypertension. ECG, Holter monitoring, and ultrasonography can be used to further assess suspected myocardial disease and arrhythmias.35

GI changes, including esophageal stricture and Barrett’s esophagus, can be investigated through esophageal manometry and endoscopy.3,18 In addition to renal function testing, urinalysis and peripheral blood smear are necessary to confirm renal crisis, especially in patients with worsening hypertension or with new anemia not associated with blood loss.6

Classification
Diagnosis of SSc is made based on the patient’s clinical presentation, but the degree of organ involvement must also be determined by symptoms, history, physical examination, laboratory work-up, and imaging studies, as detailed above. The 1980 Preliminary Criteria for the Classification of Systemic Sclerosis36 is 97% sensitive and 98% specific for SSc,37,38 although additional criteria (eg, certain autoantibodies, nail-fold capillary changes) have been proposed to improve sensitivity for limited SSc.9,38 (For the major and minor criteria from the 1980 document, see Table 26,10,36).

Accurate, early classification of SSc is critical. Patients are most likely to respond to therapeutic efforts in the disease’s early stages, and prognosis depends on the degree of disease severity and organ involvement.37,38

Treatment
No treatment modality has yet been found to reverse the fibrotic damage of SSc, but several therapies can slow disease progression.39 Because of the heterogeneous nature of the disease, management is individualized according to patient symptoms and organ involvement.40 Treatment is directed at preventing vascular damage, immune cell activation, and fibrosis.10,41 Table 32,12,41,42 shows treatment strategies to address all three disease processes.

In early SSc, vascular intervention and immunosuppressive treatment are most important because they can prevent later stages that involve fibrosis.2 Vasodilators (calcium channel blockers, such as amlodipine and nifedipine; ACE inhibitors, including enalapril and captopril; and angiotensin receptor blockers, such as losartan) have been found effective, particularly for treatment of Raynaud’s phenomenon and to prevent further renal damage.12,41 An abundance of recent evidence suggests that bosentan, an endothelium receptor antagonist, is helpful in treating pulmonary hypertension and preventing digital ulcers by regulating the inflammatory response.2,12,13,30,39,43

Cyclophosphamide is used for patients with interstitial lung disease and any associated alveolitis.5,41 In one randomized double-blind trial, methotrexate improved skin scores (ie, softened fibrosis), creatinine clearance, and overall well-being in 68% of patients who received it over a 24-week period.42

In later stages of SSc, suppressing fibrosis is the goal. d-Penicillamine is considered a first-line agent, because it interferes with collagen cross-linking.41 No conclusive data exist to support its dosing and efficacy, although findings vary from no effect to 70% benefit in improving skin scores and decreasing five-year mortality rates.2,6,41

Patient Education
Patient compliance will require education, as several months’ treatment may be required before results are evident. Supportive and symptomatic therapy will greatly improve quality of life as well.

Patients should be told that GI reflux and motility disorders can be controlled with proton pump inhibitors.41 They should also be advised to elevate the head when in bed and to eat small, frequent meals.

Arthralgias, arthritis, and deep tissue fibrosis that cause joint contractures and tendon friction rubs may be controlled by NSAIDs.41 The manifestations of Raynaud’s phenomenon can be minimized by avoiding exposure to cold temperatures and wearing warm clothes; smoking cessation is also advised.5

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