Connective tissue disease-related interstitial lung disease (CTD-ILD)

Connective tissue disease-interstitial lung disease (CTD-ILD) has various manifestations however the most frequent patterns seen on CT are NSIP or UIP. CTD-ILD should be suspected in younger patients especially women and never-smokers and particulary if there is involvement of pleura, airways or vessels. ILD is sometimes the presenting feature of CTD ¹.

Etiology

The proportion of patients with a diagnosis of a particular CTD who develop ILD varies according to the diagnosis. The following figures are approximate ¹:

• systemic sclerosis 90%

• myositis 80%

• mixed connective tissue disease 70%

• rheumatoid disease 60%

• Sjögren’s syndrome 30%

• systemic lupus erythematosus 15%

• ankylosing spondylitis

Pathology

Pathologic features show typical patterns of lung injury or fibrosis but frequently do not suggest a diagnosis of CTD. Lymphoid hyperplasia and multicompartment disease are pointers to underlying CTD, necrobiotic nodules are indicative of RA and hematoxylin bodies are a feature of SLE ¹.

Presentation

Patients may present with systemic disease as well as dyspnea, cough and inspiratory crepitations. Lung function tests demonstrate restriction and decreased diffusion capacity.

Radiology

Various patterns occur:

• symmetric lower lobe fibrosing NSIP (most frequent)

• UIP (straight edge sign, exuberant honeycombing, four corner sign)

• OP and infection may be presenting feature of RA and systemic sclerosis

• fibrosing OP (polymyositis or antisynthetase syndrome)

• diffuse alveolar damage

• pleural or pericardial effusions (SLE)

• bronchial wall thickening

• diffuse alveolar hemorrhage (SLE)

• dilated esophagus (systemic sclerosis)

• Anterior upper lobe honeycombing is a specific feature of RA-ILD (UIP or mixed UIP/NSIP pattern).

Acute exacerbation more commonly complicates RA-ILD and has a poor outcome.

Treatment

Asymptomatic lung disease is monitored. Symptomatic lung disease is treated with antifibrotics or immunosupression.

Key points

CTD-ILD is under-diagnosed. Apart from systemic sclerosis, lung disease is absent from the diagnostic criteria for CTD, and yet lung disease may be the only (or the first) manifestation. The baseline lung function, prognosis and treatment of CTD-ILD differs from that of idiopathic ILD, so the distinction is clinically important. CTD-ILD is frequently symmetrical and lower lobe predominant with volume loss.

Antisynthetase syndromes are a sub-group of idiopathic inflammatory myopathies that have a 90% incidence of ILD. Diffuse alveolar damage is common either as the presenting complaint or more commonly as an exacerbation and the mortality is > 50%. Anti-Jo-1 is the most frequent subtype.

Potential pitfalls

NSIP is the most frequent pattern of CTD-ILD and the presence of NSIP pattern should prompt a search for esophageal dilatation, pleural and pericardial thickening or effusions, vasculitis, myocarditis and soft-tissue calcification as well as appropriate investigation and multidisciplinary evaluation.

Mixed NSIP pattern and OP is a common presentation of idiopathic inflammatory myopathies.

Many cases of NSIP pattern are misdiagnosed as UIP pattern.

Consider CTD-ILD if the pattern is ‘unclassifiable’.

UIP pattern is more frequent than NSIP pattern in rheumatoid disease and other features may be present e.g. bronchial wall thickening, constrictive bronchiolitis, erosive arthropathy.

Blood tests have limited sensitivity and specificity; ESR and CRP may be normal, and definitive categorization may be impossible due to overlapping autoantibody results. The tests are most useful when there is high pre-test probability ².