20th February 2025

Connective tissue disease-associated interstitial lung disease

Overview of connective tissue disease-associated ILD

Several connective tissue diseases (CTD) have respiratory complications, including systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), Sjögren’s syndrome, systemic lupus erythematosus (SLE), ankylosing spondylitis and mixed connective tissue disease. This chapter will briefly describe pulmonary involvement in some of the major rheumatological conditions, particularly focusing on interstitial lung disease.

The majority of these diseases cause lower zone fibrosis with the notable exception being ankylosing spondylitis, which causes upper zone fibrosis.

Symptoms and signs are often those associated with the underlying CTD such as rashes, joint pain, constitutional symptoms, ulcers, synovitis, joint deformity, dysphagia, sclerodactyly (particularly in SSc), dry mucosa (present in Sjögren’s), Gottron’s papules (seen in dermatomyositis), and proximal muscle weakness (for example in inflammatory myopathies).

In addition, respiratory features such as dyspnoea, cough and crackles may be noted.

Bloods should be sent to screen for CTD, including ANA, anti-dsDNA, anti-ribonucleoprotein antibody, anti-smith antibody, anti-Scl-70, anti-Ro, anti-La, rheumatoid factor, anticyclic citrullinated peptide, anti-Jo-1 antibody, creatine kinase, aldolase, ESR, CRP.

Lung function tests in most of these conditions show a restrictive pattern with a low KCO.

HRCT usually shows a non-specific interstitial pneumonia pattern although variation between conditions will apply.

Management is driven by a multidisciplinary team approach. There is a low threshold for starting treatment in the hope of preventing pulmonary fibrosis. In most CTD-associated ILD, the mainstay of treatment is steroids and adjuvant immunosuppressive agents.

See note on nintedanib – this has now been approved as a treatment option for chronic progressive fibrosing interstitial lung diseases.

Rheumatoid arthritis

RA can affect the lung in a multitude of ways, including pleuritis, pleural effusion, pulmonary fibrosis, Caplan syndrome and vasculitis. We will focus on pulmonary fibrosis in this section.

Pulmonary fibrosis in RA is often asymptomatic. It is most common in seropositive patients, those with high ANA titres, nodules and multisystem disease. If present, symptoms include dyspnoea and cough. Crackles are mostly bibasal.

Management options are steroids and immunosuppressive therapy, however prognosis is poor and these therapies are often not effective.

Systemic lupus erythematosus

As in RA, SLE may affect the lung in multiple ways. We will focus on interstitial involvement: diffuse ILD and acute lupus pneumonitis.

Diffuse ILD occurs in the majority of patients but is often asymptomatic.

Acute lupus pneumonitis can result in very severe disease with features such as cough, dyspnoea, fever, pain and hypoxia. Examination reveals widespread crepitations. Widespread infiltrates may be seen on CXR.

Management is with steroids and cytotoxic drugs. It can later develop into chronic pneumonitis.

Idiopathic inflammatory myopathies

This group of diseases includes polymyositis (PM) and dermatomyositis (DM).

ILD features often in patients with these conditions, more commonly in those with anti-synthetase antibodies (including anti-Jo) or anti-MDA5 antibodies.

Clinical features include dyspnoea, cough, joint pain and fevers, with fine bibasal crackles on examination.

Early treatment is recommended in ILD associated with PM/DM to prevent disease progression. Steroids are often used. Other options include rituximab, however this should be discussed with a rheumatology specialist.

Systemic sclerosis

Most patients with SSc will have some evidence of ILD and the presence of anti-topoisomerase antibodies (Scl-70) appears to be strongly associated with development of significant lung disease.

Features of systemic sclerosis associated with dyspnoea should prompt suspicion of associated ILD. On examination, bibasal crackles might be noted.

Low-dose steroids should be used if required as high doses carry the risk of renal crisis. Other options for management include cyclophosphamide or mycophenolate mofetil.

Ankylosing spondylitis

Notably, ankylosing spondylitis causes bilateral apical fibrosis, as opposed to the bibasal pattern seen in most other CTD-associated ILD. Cysts or cavities may also develop.

Lung function tests typically show a restrictive pattern, however, it should be noted that this may be partly related to spinal deformity.

References

• Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013;143(3):814-24
• Oliveira RP, Ribeiro R, Melo L, Grima B, Oliveira S, Alves JD. Connective tissue disease-associated interstitial lung disease. Pulmonology. 2020
• Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008;63 Suppl 5:v1-58
• Chapman SJR, G. V.; Shrimanker, R. S.; Turnbull, C. D.; Wrightson, J. M. Oxford Handbook of Respiratory Medicine. Fourth Edition ed. Oxford, United Kingdom: Oxford University Press; 2021
• NICE. Nintedanib for treating progressive fibrosing interstitial lung diseases. National Institute for Health and Care Excellence, 2021 [accessed 18/03/2024]