Pulmonary hypertension, characterized by rapidly progressive dyspnea, occurs in 7% to 12% of patients typically 10 to 15 years after onset of Raynaud phenomenon. The diffusing capacity is disproportionally reduced relative to vital capacity, and the electrocardiogram shows evidence of right-sided heart dysfunction. The prognosis is poor, and the mortality is significantly higher than in patients with idiopathic pulmonary arterial hypertension. The newer classes of novel vasoactive agents may have improved the prognosis of these patients. These agents include parenteral prostacyclin or its analogs, phosphodiesterase-5 inhibitors (sildenafil or tadalafil), or the endothelin receptor antagonists (bosentan or ambrisentan). Many patients require a combination of these therapies.

Cardiac Manifestations. Clinically symptomatic pericardial disease is infrequent (5% to 16%). A large pericardial effusion (>200 mL) can lead to cardiac tamponade and is a marker for poor outcome with an increased risk for impending renal crisis. Symptomatic scleroderma cardiomyopathy, resulting from myocardial microvasculopathy and fibrosis, is rare. Systolic or diastolic dysfunction may develop in this setting. Supraventricular and ventricular arrhythmias are found more frequently in patients with diffuse disease and are strongly associated with mortality.

Renal Manifestations. Twenty-five percent of patients with dcSSc may develop scleroderma renal crisis, which is defined as new onset of accelerated hypertension and rapidly progressive oliguric renal failure. Plasma renin activity is elevated, and mild proteinuria and microscopic hematuria can develop. Microangiopathic hemolytic anemia and thrombocytopenia are prominent hematologic features. Some patients present with congestive heart failure, ventricular arrhythmias, or large pericardial effusions. Specific factors associated with a higher risk of developing scleroderma renal crisis include early diffuse disease (<4 years), rapid progression of skin thickening, new cardiac events (e.g., pericardial effusion and/or congestive heart failure), presence of anti-RNA polymerase III antibody, and antecedent high-dose glucocorticoid use (e.g., >20 mg prednisone daily).

DIFFERENTIAL DIAGNOSES

The differential diagnosis of systemic sclerosis requires consideration of several scleroderma-like disorders. Diffuse fasciitis with eosinophilia is associated with swelling, stiffness, and restricted range of motion but usually spares the hands and face. There is sometimes an association with preceding trauma. Sclerodactyly and fibrosis of the palmar fascia occurs in insulin-dependent diabetes mellitus, particularly juvenile-onset type—a condition called diabetic cheiroarthropathy. Nephrogenic systemic fibrosis may develop in patients with renal insufficiency after exposure to gadolinium-containing contrast agents administered for MRI procedures. Chronic graft-versus-host disease, particularly after allogeneic bone marrow or stem cell transplantation, may produce many common clinical and histologic features that mimic scleroderma. Environmental exposures (e.g., inhalation of epoxy resins, vinyl chloride, silica dust, organic solvents, and pesticides; ingestion of toxic rapeseed oil; or injection of paraffin or bleomycin) may produce features of scleroderma.

DIAGNOSTIC APPROACH

The diagnosis of systemic sclerosis is based on a thorough clinical evaluation and supported by the detection of specific autoantibodies and by the detection of major target organ involvement.

Autoantibodies associated with dcSSc are anti-topoisomerase I (Scl 70) or anti-RNA polymerase III antibodies. Anti-centromere antibody is found in 70% to 80% of patients with lcSSc and 5% of those with dcSSc. Additional helpful evaluation includes radiographs of the hands, showing acro-osteolysis and calcinosis cutis (see Plate 5-57). Pulmonary function testing demonstrating a restrictive pattern with decreased forced vital capacity and reduced diffusion capacity (DLCO) and high-resolution chest CT showing ground-glass opacification are sensitive indicators of interstitial lung disease. A skin biopsy from an affected area that demonstrates the typical changes (progressive increase in dermal collagen with loss of appendages) can sometimes establish the diagnosis when the diagnosis is otherwise uncertain.