The term interstitial lung disease (ILD) refers to a group of more than 200 lung disorders characterised by inflammation and/or fibrosis (scarring) in the lung tissues. Autoimmune connective tissue diseases such as scleroderma (SSc) account for approximately 20% of cases of ILD.

Among the connective tissue diseases, SSc is one of the more common causes of ILD. One of the ways of determining who has ILD is a high resolution CT (HRCT) scan of the chest. HRCT scans of the chest show changes in the lungs consistent with ILD in up to 75% of people with SSc but not everyone has “clinically significant ILD” meaning it causes symptoms of breathlessness on exertion and cough and needs treatment. 

SSc-ILD usually develops in the first five years of the disease course, with the majority of cases developing within two years of the first non-Raynaud’s symptom of SSc. It is more common in people with the diffuse SSc subtype of SSc and people with certain SSc-specific autoantibodies, namely, anti-Scl70, anti-Th/To, anti-U3RNP and anti-PM-Scl antibodies, while the anti-centromere antibody typically associated with the limited subtype of SSc reduces the risk of ILD. 

SSc-ILD varies from limited extent, non-progressive lung involvement to progressive pulmonary fibrosis which can significantly impact social function, well-being, productivity and sleep. Indeed, SSc-ILD is the leading cause of SSc-related death but a number of advances in the treatments for ILD in recent years have the potential to improve the outcomes of people with SSc-ILD. 

These include the first randomised clinical trials in SSc-ILD to show a benefit in this condition, namely improvement in lung function, quality of life and skin disease. These were studies of immunomodulatory drugs that target the inflammatory component of ILD, cyclophosphamide and mycophenolate. Since then, mycophenolate has become the drug of choice for clinically significant SSc-ILD and also for skin disease in people with the diffuse SSc subtype. 

Nintedanib is a newer drug which was developed to target fibrosis and can be used in conjunction with mycophenolate. It has been shown to reduce decline in lung function in a clinical trial of patients with SSc-ILD and is now available in Australia on the Pharmaceutical Benefit Scheme for use in fibrotic lung diseases such as SSc-ILD if shown to be progressive. Progressive pulmonary fibrosis is defined as having at least two of the following criteria:

1. 1. Increase in respiratory symptoms, usually breathlessness on exertion
   2. Decline in lung function
   3. Evidence of progression on HRCT scan of the chest

The availability of new treatments for SSc-ILD has led to changes in the approach to screening for SSc-ILD with the aims of identifying early ILD before symptoms begin and identifying those with clinically significant ILD who may be at risk of progressive pulmonary fibrosis. It is now recommended that people with SSc have a HRCT scan of the chest and lung function tests when the diagnosis of SSc is first made. People at higher risk of developing ILD should be screened with lung function tests every 3-6 months for at least the first 3 – 5 years after the diagnosis of SSc. This applies to people with the diffuse SSc subtype, the anti-Scl-70 antibody, more widespread skin thickening and elevation of the inflammatory marker, C-reactive protein. Thereafter and in people without risk factors eg the limited SSc subtype and the anti-centromere antibody, should have lung function tests every year. If the lung function declines or new respiratory symptoms develop or increase, the HRCT scan of the chest should be repeated to assess whether ILD has developed or existing ILD has become progressive. 

In addition to mycophenolate and cyclophosphamide, other pharmacological treatments that are used occasionally include rituximab and intravenous immunoglobulin. Unlike other forms of ILD, glucocorticoids such as prednisolone tend not to be used in SSc-ILD due to the risk of scleroderma renal crisis in some people with the diffuse SSc subtype. Non-pharmacological measures for SSc-ILD include pulmonary rehabilitation, smoking cessation, ensuring immunisations are up to date, optimising control of gastro-oesophageal reflux, psychological support, oxygen therapy and rarely, lung transplantation.

These advances in the treatment and understanding of the risk of progressive pulmonary fibrosis have been possible due to research studies by investigators such as the Australian Scleroderma Interest Group that have enabled changes in lung function and the extent of fibrosis on HRCT scans that predict progression to be defined. Current research is directed towards identifying biomarkers such as levels of molecules in the blood that predict progression and there are a number of pharmaceutical company-sponsored randomised clinical trials of new anti-fibrotic drugs currently recruiting people with SSc-ILD. 

H2RA- Histamine 2 receptor antagonist (raniditine, zantac)

Prof Susanna Proudman, MBBS (Hons), FRACP