Scleroderma - Interstitial Lung Disease

Systemic sclerosis (SSc) is a fibrotic autoimmune disorder, which impacts the lungs with high frequency. Pulmonary involvement due to interstitial lung disease (ILD) is present in 55 to 90% of patients on high-resolution chest CT and leads to increased mortality when present. The Interstitial and Diffuse Lung Disease NetWork has provided resources and new findings on scleroderma.


  1. Presentation and Diagnosis:
  2. Scleroderma is an autoimmune disease characterized by vasculopathy and fibrosis with multiorgan involvement. Scleroderma-related interstitial lung disease (SSc-ILD) contributes significantly to mortality and morbidity in these patients. Early diagnosis requires vigilance in monitoring for progressive cough, dyspnea on exertion, and/or crackles on exam, with a low threshold to pursue high-resolution chest computed tomography (HRCT). Abnormal HRCT and exam findings are often present prior to the patient’s perception of symptoms. Pulmonary function tests demonstrate restriction and a gas exchange abnormality as disease progresses. Biopsy is rarely required for the diagnosis of scleroderma-ILD as the HRCT pattern typically predicts the underlying histology.
  3. Prognosis and Treatment:
  4. Histopathologic patterns do not predict disease course as well as the severity of physiologic and radiographic disease at initial presentation.
  5. Early treatment is recommended based on large randomized clinical trials demonstrating improvement in physiologic indices and symptoms in these patients. However, the marginal improvements noted in clinical trials must be weighed against the potential for drug toxicity when considering initiation of treatment and while choosing the appropriate agent.
  6. Scleroderma Lung Study:
  7. I (SLS-I) was a landmark double-blind, randomized, placebo-controlled trial of oral cyclophosphamide (≤2 mg/kg/day) vs placebo administered to symptomatic patients with SSc-ILD for 1 year. The patients were followed for an additional year after completion of therapy. This study demonstrated that one year of oral cyclophosphamide had a significant beneficial effect on physiologic parameters and dyspnea in these patients. However, there was a higher frequency of adverse events related to cyclophosphamide, and treatment efficacy was not sustained without continued treatment.
  8. A more recent retrospective study reported a significant improvement in the extent of quantitative ILD on HRCT in a subgroup of patients treated with oral cyclophosphamide in the SLS-1 study, compared with patients receiving placebo.
  9. Given drug toxicity concerns from the SLS-I study, the Scleroderma Lung Study – II (SLS-II) study was conducted to evaluate the efficacy of a 2-year course of mycophenolate mofetil (MMF) compared with cyclophosphamide. This randomized, double-blind, parallel group trial reported significant improvements in physiological parameters in patients treated with MMF and cyclophosphamide with similar efficacy. However mycophenolate motetil was better tolerated and associated with less toxicity, making it a more viable initial treatment choice in patients with SSc-ILD.
  10. A retrospective study also reported improvements in frequent cough and cough-related quality of life in the MMF and cyclophosphamide treatment arms of the SLS-II study.
  11. A recent retrospective study demonstrated significant improvement in pulmonary function and dyspnea in patients treated with MMF in the treatment arm of SLS-II in comparison to those enrolled in the placebo arm of SLS-I, further validating the role of MMF as initial therapy for SSc-related ILD.