Scleroderma is an autoimmune disorder characterized by thickening of the skin and scar formation in affected organs. Interstitial lung disease (ILD) is a common comorbidity associated with scleroderma, and is a frequent source of symptoms in patients. In the vast majority of patients, ILD manifests as a non-specific interstitial pneumonitis (NSIP) pattern on high-resolution chest CT (HRCT) or lung biopsy, which is estimated to occur in 50 to 60% of patients with diffuse cutaneous scleroderma. In a multi-ethnic cohort study of patients with scleroderma, early development of ILD was associated with African-American ethnicity, hypothyroidism, cardiac involvement, and laboratory abnormalities (1). Although most patients will have clinical manifestations of scleroderma prior to being diagnosed with ILD, a percentage of patients will have ILD as the primary manifestation of scleroderma. In these cases, physical exam findings (e.g. sclerodactyly, Raynaud’s phenomena), serologic testing showing the presence of specific auto-antibodies, and/or abnormal nailfold capillaroscopy may point the clinician to the presence of scleroderma. In other cases, laboratory and/or clinical manifestations of scleroderma may not appear for some time after the ILD diagnosis; in such cases, it is incumbent on the physician to keep a high index of suspicion for an underlying connective tissue disease diagnosis.
Management of patients with scleroderma-associated ILD includes immunosuppressant medications such as mycophenolate or cyclophosphamide (2, 3) which may serve to decrease lung inflammation and fibrosis. More recently, the anti-fibrotic drug nintedanib was recently FDA approved, capable of slowing the rate of decline of lung function in patients with scleroderma-associated ILD (4). A separate ongoing study evaluating the effect of another anti-fibrotic drug, pirfenidone, on decline of lung function in scleroderma-associated lung disease is based on promising phase II data (5).
In addition to ILD, 10-15% of patients with scleroderma will develop pulmonary hypertension (PH) during the course of their disease. Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than 20 mmHg supine and at rest, a pulmonary capillary wedge pressure ≤ 15 mmHg, and a peripheral pulmonary vascular resistance ≥ 3 Wood units without co-existing ILD. The World Health Organization (WHO) classifies pulmonary hypertension into 5 groups (6); generally speaking, scleroderma patients most often are diagnosed with Group 1 (pulmonary arterial hypertension (PAH)) and Group 3 (PH due to chronic lung disease) disease. Group 1 PAH is the most common cause of death in scleroderma, and patients with long-standing limited cutaneous scleroderma, decreased diffusion capacity for carbon monoxide, and high FVC/DLCO ration (>1.6) are at highest risk for developing PAH in scleroderma. Both 2-dimension echocardiogram and right heart catheterization are used to diagnose PAH in scleroderma, with right heart catheterization remaining the gold-standard. Management of PAH in scleroderma usually requires PH-specific therapy, such as prostacyclins, endothelin receptor antagonists, nitric oxide, or other therapies. Non-PH directed therapy, such as oxygen, diuretics, and exercise therapy (pulmonary or cardiac rehabilitation) are also of benefit in these patients.
The ATS and the Scleroderma Foundation are dedicated to supporting research designed to improve our understanding of the causes of ILD in patients with scleroderma, and to identify new therapies in pursuit of improving the health of scleroderma patients.
Four Facts About Scleroderma
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