Connective tissue disease-associated interstitial lung disease: a rheumatologist's perspective

Abstract

Pulmonary involvement is common in patients with underlying autoimmune and connective tissue diseases (CTDs) and can encompass a broad spectrum of disorders involving the airways, pleura, parenchyma, vascular system, bronchiectasis and nodules with significant overlap in these pathologies. Interstitial lung disease (ILD) is the most common pulmonary manifestation of systemic autoimmune rheumatic diseases and CTDs. Particular diseases, such as systemic sclerosis, rheumatoid arthritis and inflammatory myopathies, frequently associate with ILD and high-risk patients should be screened. Antibody profiling and imaging characteristics should be used to prognosticate where possible, along with regular surveillance to ensure therapies are optimised. Immunosuppressive therapies can be effective for patients with CTD-associated ILD, but difficulties arise in distinguishing between treatment failures and complications of immunosuppression.

Shareable abstract

Pulmonary manifestations are common and are amongst the leading causes of death for patients with rheumatic diseases. Immunosuppressive therapies can be effective for CTD-ILD. Screening patients at high risk for ILD allows earlier intervention. https://bit.ly/4lu8Y6t

Educational aims

• Pulmonary manifestations are common and are amongst the leading causes of death for patients with rheumatic diseases. Particular diseases, such as systemic sclerosis, rheumatoid arthritis (RA) and inflammatory myopathies, frequently associate with interstitial lung disease (ILD) and high-risk patients should be screened. Antibody profiling and imaging characteristics should be used to prognosticate where possible, along with regular surveillance to ensure therapies are optimised.

• Immunosuppressive therapies can be effective for patients with connective tissue disease-associated ILD but difficulties arise in distinguishing between treatment failures and complications of immunosuppression. Methotrexate, for instance, should not be stopped in RA-ILD. This is where the multidisciplinary team becomes crucial in fine tuning immunosuppressive and antifibrotic therapies. Monitoring for common toxicities is an important component of management. Rheumatologists are committed to targeted therapies for patients with inflammatory diseases and would like to see the development of damage and disease activity tools as clinical decision aids.

Introduction

Pulmonary involvement is common in patients with underlying autoimmune and connective tissue diseases (CTDs) and can encompass a broad spectrum of disorders involving airways, pleura, parenchyma, vascular system, bronchiectasis and nodules with significant overlap in these pathologies. Systemic autoimmune rheumatic diseases (SARDs) include inflammatory myopathies (IIM), systemic sclerosis (SSc), inflammatory arthritis, Sjögren disease (SjD), mixed CTD (MCTD) or undifferentiated CTD and systemic lupus erythematosus (SLE). Interstitial lung disease (ILD) is the most common pulmonary manifestation of SARDs and CTDs. The reported prevalence of ILD in patients with rheumatic disease varies widely according to the diagnostic modalities used and underlying disorder. Management and diagnosis of CTD-associated ILD (CTD-ILD) requires thoughtful evaluation of clinical, radiological, physiological and immunological findings as part of an evolving, patient-centred, multidisciplinary approach.

In rheumatoid arthritis (RA), the most common inflammatory arthropathy, ILD is reported in 7–10% of patients with a higher prevalence in patients screened with high-resolution computed tomography (HRCT). In patients with SSc and IIM we see a very high proportion of patients with ILD, with lower reported prevalence in those with SLE. In a Norwegian cohort of patients with SSc, ILD was demonstrated in 50% on HRCT [1]. In MCTD, ILD was diagnosed in 27–53% after a decade of follow-up [2], and in IIM the frequency of ILD was 11–20% [3]. Age-adjusted survival is markedly diminished for all patients with CTD-ILD. In SSc the 10-year survival rates are low, at 66%, with lung manifestations the most frequent cause of death [4, 5]. There is a marked decline in survival demonstrated in those with ILD compared with those with rheumatic diseases without pulmonary involvement [6].

Strategies for improving outcomes for these patients are of crucial importance. Targeted and steroid-sparing regimens have been integrated into routine care for patients with rheumatic diseases for decades and many of the principles developed as we progressed through the biologic era can be applied to other diseases and specialties. With the assessment of single organ disease in mind, the principles of “Treat to Target” were developed and applied to inflammatory arthritis (e.g. RA) based on the recognition that early detection of disease and timely initiation of immunosuppressive therapies improves outcomes [7]. This radically changed the approach taken to early inflammatory arthritis with clear definitions for diagnosis, quantification of disease activity and indications for therapeutic switches. This protocoled approach to the management of these patients with early disease has revolutionised outcomes. The application of these principles to CTD-ILD remains challenging as we often fail to identify early disease, there are a limited number of therapeutic options and targets, and it can be difficult to define success.

Managing multi-organ involvement can also be a challenge. In CTD-ILD we are often presented with extrapulmonary disease in addition to lung manifestations. In multi-organ disease we seek to provide multidisciplinary, individualised, targeted management for the multiple manifestations, with patient education and shared decision making. For example, in SLE, composite disease activity is assessed at each clinic visit with regular evaluation of organ damage using validated scoring systems [8]. The most used are the SLE Disease Activity Index (SELENA-SLEDAI or SLEDAI-2K) [9] and the British Isles Lupus Assessment Group (BILAG) [9, 10]. Therapies are then adapted according to disease activity and damage index. These tools trigger us to distinguish between active inflammatory disease and irreversible damage which will not respond to intensification of immunosuppression. We can assess disease activity and damage across multiple organ systems in a standardised manner and adjust therapies accordingly. In the setting of ILD with rheumatic diseases, it can be very challenging for rheumatologists to assess disease activity in the lungs, to establish what changes represent damage and to define therapeutic targets with the patients.

In this review we outline the rheumatic diseases commonly associated with ILD, the management and monitoring of our most used immunosuppressive agents, the challenges in defining disease activity and recommended screening protocols for ILD in patients at risk.

Rheumatic diseases and antibodies associated with ILD

Antibody testing is of crucial importance in rheumatic diseases. The identification of antibody targets is useful in disease sub-setting and can help predict future outcomes early in the disease course. However, there are also many patients who test positive for certain antibodies, upon finding an abnormality on pulmonary computed tomography (CT), who do not reach the criteria for the diagnosis of a rheumatic disease. Interstitial pneumonia with autoimmune features (IPAF) is the term used for patients with ILD who have features of autoimmunity, but are not classifiable as a specific rheumatic disease. The classification criteria for IPAF requires two out of three of the following: a clinical domain (extrathoracic feature), a serological domain, and a morphological domain (imaging, histopathological or pulmonary function tests (PFTs)) [11]. Other patients test positive for an antibody of unclear clinical significance, keeping an open mind in these cases and re-evaluating for features of autoimmune disease, taking the radiological features into account, is of paramount importance in interpreting these results.

SSc is characterised by immune dysfunction, vascular abnormalities and diffuse fibrosis. The estimated prevalence is 25 cases per 100 000 with a female predominance (4:1). ILD is one of the leading causes of morbidity and death. Raynaud's phenomenon (triphasic skin colour changes associated with temperature changes or emotional triggers) is the most common presenting manifestation in SSc. ILD can be identified by screening or in rare cases shortness of breath can be the primary presenting complaint. Patients with SSc are classified into two categories according to the anticipated pattern of cutaneous involvement (limited or diffuse) as per the American College of Rheumatology classification criteria [12]. The classification system includes the extent of skin thickening (Rodnan skin score), fingertip lesions, telangiectasia, Raynaud's, abnormal nail fold capillaries (which can be evaluated using capillaroscopy), antibody type and the presence of pulmonary arterial hypertension or ILD.

In SSc, 75–95% of patients demonstrate a positive antinuclear antibody (ANA). The most common ANA patterns in SSc are anti-centromere antibodies, antibodies to topoisomerase I, also known as anti-Scl-70 and anti-RNA polymerase antibodies. Scl-70 associates with diffuse cutaneous disease and a high risk for pulmonary fibrosis with further associations demonstrated with digital ulcers and skeletal and cardiac myositis [13]. Anti-centromere antibodies are associated with limited cutaneous disease with a relative protection from ILD but a higher risk of pulmonary hypertension. The presence of anti-RNA polymerase antibodies has been associated with diffuse cutaneous disease, renal crisis and myositis, but not specifically with ILD.

RA is the most common chronic autoimmune inflammatory arthropathy. It affects ∼1% of European and North American adults with a peak age of incidence at 50–60 years. In 2019, Ireland had the highest incidence of RA in Europe at 38.6 per 100 000 population [14]. Patients at higher risk for the development of RA-ILD are males, seropositive (positive for either rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibodies or both), >60 years of age, smokers and patients with higher disease activity. The most common type of ILD in RA is usual interstitial pneumonia, less common types are organising pneumonia and nonspecific interstitial pneumonia (NSIP). Other presentations of rheumatoid lung disease are pulmonary nodules, bronchiectasis, bronchiolitis obliterans and pleural disease [15].

SjD is a systemic autoimmune disease characterised by underactive lacrimal and salivary gland function that associates with a wide spectrum of multi-organ manifestations. It can be found as a primary diagnosis or can be comorbid in the setting of other rheumatic diseases. The most frequently detected antibodies in SjD are anti-Ro/SSA and anti-La/SSB and the most common symptoms are ocular and oral dryness. There is a wide variation in reported prevalences (1–23 per 10 000 persons), with female preponderance [16]. Most therapies are directed at symptomatically treating sicca. Lung involvement occurs in ∼9–20% of patients [17]. Respiratory manifestations occur on a spectrum of severity and include small airways disease, tracheobronchial disease, ILD, cystic lung disease and lymphoma. The most common clinical presentation is upper respiratory tract involvement and the most unfavourable form of respiratory involvement after lymphoma is ILD. The first association between ILD and SjD was lymphocytic interstitial pneumonitis [18]; however, NSIP is the most common subtype of ILD seen. Lymphoproliferative disease appears more commonly in smokers and those with lymphopenia, Ro-52 antibodies and elevated C-reactive protein [19].

IIMs are a group of systemic autoimmune diseases characterised by muscle weakness and inflammation [20], which include dermatomyositis, anti-synthetase syndrome, polymyositis and inclusion body myositis. Amyopathic myositis describes the clinical syndrome and culpable antibody in the absence of overt muscle involvement. Myositis autoantibodies are present in up to 40% of patients with myositis (either polymyositis or dermatomyositis) and are associated with an increased risk of ILD. IIMs are frequently comorbid with other autoimmune diseases such as SSc and MCTD [21]. Unlike other ILDs, IIM-ILD usually occurs acutely with systemic disease and typically in younger patients. The most common radiological finding in IIM-ILD was NSIP or organising pneumonia, while usual interstitial pneumonia was less common [22]. Antibody profiling is of particular importance in IIM-related lung disease (outlined in table 1) [23].

TABLE 1.

Antibody profiling in inflammatory myopathy (IIM)-related interstitial lung disease (ILD)

Antibody name	Clinical manifestation	Incidence of ILD
Ro (SSA) (includes Ro60 and Ro52)	Myositis often with SSc or SLE; SjD; may be associated with ILD (especially Ro52)	∼22% [24]
Rheumatoid factor	RA, SSc	7–10% [25]
Anti-CCP	RA	7–10% [25]
Jo-1	Polymyositis, dermatomyositis and ILD, anti-synthetase syndrome	∼82% [26]
PL-7	Polymyositis, dermatomyositis and ILD	∼77% [26]
PL-12	ILD is more common than myositis (either polymyositis or dermatomyositis)	∼83% [26]
EJ	Dermatomyositis is more common than polymyositis and ILD, anti-synthetase syndrome	∼90% [26]
MDA-5	Myositis (either polymyositis or dermatomyositis) with rapidly progressive ILD	∼94% [27]
Anti-SAE	Dermatomyositis	18% in Europe, ∼64% in Asian populations [28]
PM/Scl	Polymyositis or dermatomyositis/SSc overlap	∼86% [29]
U1RNP	MCTD (overlap syndrome)	Unknown
Ku	Myositis (either polymyositis or dermatomyositis)/SSc/SLE overlap	∼76% [30]

SSc: systemic sclerosis or scleroderma; SLE: systemic lupus erythematosus; SjD: Sjögren disease; RA: rheumatoid arthritis; MCTD: mixed connective tissue disease. Information from [23].

Screening

Strategies for screening people with existing rheumatic diseases for ILD are incompletely defined, and in some cases identifying mild disease (particularly RA) which may never progress or lead to any symptoms is currently of unclear benefit. The identification of early disease does, however, allow us to use immunosuppressive approaches for disease elsewhere that are also helpful for pulmonary manifestations. In time, the hope is that we can demonstrate that early identification and treatment can improve outcomes. The American College of Rheumatology “conditionally” recommends screening for ILD in patients at increased risk using PFTs and HRCT with recommendations “against” the use of chest radiography, 6-min walk test, surgical lung biopsy and bronchoscopy as screening tools.

The American College of Rheumatology/American College of Chest Physicians guidelines highlight antibody and disease features placing patients at high risk for ILD in whom screening ought to be undertaken [31]. In SSc, those with anti-Scl-70 or ANAs with nucleolar pattern, African ethnicity, diffuse skin disease, elevated acute phase reactants and recent onset disease should be considered for screening [31]. In patients with RA, risk factors for ILD include high titre rheumatoid factor and CCP antibodies, smokers, older age at onset, male gender and high body mass index [32, 33]. The IIMs are particularly associated with ILD when they associate with anti-synthetase antibodies (Jo-1, PL-7, PL-12, EJ, OJ, KS, Ha and Zo), anti-MDA-5, anti-KU, anti-PM/Scl, Ro52 and clinically with the presence of mechanics hands, arthritis and ulcerating cutaneous lesions [26]. In SjD, the presence of Ro52 antibodies, ANAs, Raynaud's phenomenon, older age and lymphopenia highlight patients at risk for ILD.

Management

Patients with ILD require multi-specialty combined care. For some, the disease can be mild and non-progressive, while for others, distinct clinical phenotypes such as rapidly progressive ILD and progressive pulmonary fibrosis (PPF) (also termed progressive fibrosing ILD) have a poor prognosis. IIM- and SSc-associated ILD frequently have a progressive phenotype and, thus, PFTs every 3–6 months are recommended. While in RA, SjD and MCTD, PFTs every 3–12 months in the first year are recommended and then less frequently once clinically stable. In all patients the American College of Rheumatology recommend CT testing as needed [31].

The data supporting the use of commonly used immunomodulatory strategies and newer therapies (e.g. antifibrotic drugs) in combination in the treatment of CTD-ILD is steadily growing. First-line therapies in patients with CTD-ILD vary somewhat according to the underlying autoimmune disease. Except for SSc, all patients are recommended to receive short-term corticosteroids. This offers both patient and clinician insights as to the reversibility of the disease process. Mycophenolate can be considered for all patients with SARD-ILD and is usually considered as first-line therapy except for in patients with RA in whom rituximab often offers the additional benefit of control of articular manifestations. Tocilizumab can be considered in SSc; therapeutic guidelines are laid out in the 2024 American Thoracic Society publication [34].

In those with progression of ILD on their first therapy, a switch in immunosuppressive agent, or the addition of a second agent should be considered with consideration for an antifibrotic agent, and ultimately, referral for lung transplantation at an appropriate time for those with progressive disease. Patients with rapidly progressive disease, and those with antibodies associated with poor pulmonary outcomes (e.g. MDA-5), should be considered for a multi-targeted approach with early consideration for lung transplantation referral.

Good data exist supporting the role of immunosuppression and antifibrotics in SSc-ILD. The Scleroderma Lung Study II showed that mycophenolate mofetil was safer and as effective as cyclophosphamide over a 2-year period [35]. The SENSCIS trial compared patients with SSc-ILD on mycophenolate and nintedanib with patients on mycophenolate monotherapy [36]. The results demonstrated an improvement in forced vital capacity (FVC) with mycophenolate and nintedanib together. This opened the door to combining immunosuppressive therapy and antifibrotics. The faSScinate trial showed benefits of tocilizumab in ILD in diffuse SSc, by slowing down FVC decline. This trial also showed improved skin thickening in the tocilizumab arm, which did not meet statistical significance [37]. The focuSSced trial showed stability in lung function by using FVC as the primary outcome, although this failed to meet statistical significance [38]. Oesophageal dysmotility and aspiration are also significant contributors to pulmonary pathology in SSc and should be addressed with routine use of proton pump inhibitors and management of oesophageal disease and gastrointestinal dysmotility where possible [39].

Immunosuppressive medications used in ILD and how to prescribe them

Medication monitoring is a critical part of chronic care for these patients with notable toxicities associated with immunosuppressive therapy. Antifibrotic monitoring often mirrors the safety monitoring bloods needed for immunosuppressive therapies. Where possible these should be consolidated to avoid duplication of tasks and minimise unnecessary blood draws. Please note that the management of immunosuppression in pregnancy and in those planning pregnancy is not dealt with in this review.

Mycophenolate mofetil

Mycophenolate mofetil is a pro-drug of mycophenolic acid, an inhibitor of inosine-5-monophosphate dehydrogenase. This medicine depletes guanosine nucleotides in B and T lymphocytes inhibiting their proliferation and leading to suppression of cell-mediated immune responses and antibody formation [40]. Mycophenolate should be started at a dose of 500 mg twice daily with a titration upwards to a therapeutic dose of 1–1.5 g twice daily. In the case that mycophenolic acid is chosen (often for reasons of gastrointestinal tolerance), the starting dose is 360 mg twice daily increasing to a target therapeutic dose of 720–1080 mg twice daily. Both agents can be associated with marrow suppression and hepatotoxicity with a black box warning regarding pregnancy and teratogenicity. Patients on these agents require a full blood count with differential and liver and renal panels at baseline and every 2–3 weeks following every dose increase. Once on stable therapy patients should have these bloods performed quarterly [41].

Rituximab

Rituximab is a chimeric murine/human monoclonal antibody targeting the B cell marker CD20, which leads to the removal of B cells from the circulation via antibody-dependent, cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis [42]. Rituximab is infused as a 1 g dose on day 1 and day 15. This can be repeated at 24 weeks as needed. Rituximab can associate with cytopenias, hypogammaglobulinaemia, infection and hepatitis B reactivation, and has a black box warning for progressive multifocal leukoencephalopathy. Patients should have screening for latent tuberculosis (TB) before starting therapy, hepatitis B and C serologies, and a full blood count with a repeat every 2–4 months. The decision to dose reflexively every 6 months rather than as needed or according to B cell re-population will vary on a case-by-case basis and can depend upon whether rituximab is being used as an add-on therapy in severe disease or as the primary treatment.

Tocilizumab

Tocilizumab is an anti-interleukin-6 receptor alpha antibody which is licensed for the management of SSc fibrotic lung and skin disease. Tocilizumab can be administered intravenously or subcutaneously. The s.c. dose is 162 mg weekly, and this was the preparation used in SSc clinical trials [43]. This therapy can associate with transaminitis, hyperlipidaemia and bowel perforation in the setting of diverticular disease. Prior to starting tocilizumab patients should be screened for latent TB, hepatitis B and C and baseline lipids. A full blood count, renal and liver panel should be checked every 4–8 weeks for the first 6 months and every 3 months thereafter. Lipids should be repeated 8 weeks after starting therapy, 6 months after starting therapy and then annually.

Azathioprine

Azathioprine is a purine analogue that causes a reduction in nucleotide synthesis leading to decreased B and T cell proliferation. Azathioprine should be started at 50 mg daily p.o. with a gradual increase to a therapeutic level of 2–3 mg·kg⁻¹ per day with thiopurine methyltransferase levels checked prior to starting therapy. This agent can associate with hepatotoxicity, leukopenia and rarely pancreatitis. Monitoring should include baseline full blood count with liver function and renal testing 2–3 weeks after starting, after any dose increase and every 3 months once on a stable dose [44].

Cyclophosphamide

Cyclophosphamide i.v. can be dosed according to several protocols. The American College of Rheumatology guidelines recommend a dose of 500–750 mg·m⁻² every 4 weeks for 6 months. Notable toxicities include marrow suppression, infertility, haemorrhagic cystitis, hair loss and long-term malignancy including bladder cancer. Patients on this treatment should have full blood count with differential, viral screening and testing for latent TB. At day 10–14 post-infusion a repeat full blood count should be taken and again before the next dose. Patients should have urinalysis every 4–6 weeks on stable dosing [45].

Methotrexate

Methotrexate is commonly prescribed for rheumatic diseases. It is a dihydrofolate reductase inhibitor and is considered first-line therapy in many rheumatic diseases. Folic acid is co-prescribed with methotrexate. A common dose for methotrexate in inflammatory disease is 15–20 mg taken once weekly. Toxicity monitoring is quarterly once on stable dosing, but more frequent at the start of therapy. Liver abnormalities and cytopenias can occur and it is recommended that patients limit or abstain from alcohol. Historically, methotrexate was suspected as a causative agent for ILD but there is little evidence to support this. The development of ILD secondary to methotrexate is rare and drug-related pulmonary disease presents early with an acute pneumonitis (0.5%). Historically, the treatment of inflammatory pneumonitis involved stopping methotrexate, however, more recent evidence suggests that this not the case [46].

Antifibrotics

Nintedanib

Nintedanib is an oral, intracellular tyrosine kinase inhibitor that binds to growth factor receptors inhibiting the proliferation of fibroblasts. It is typically commenced at doses of 150 mg twice daily. Nintedanib is well tolerated, the most reported side-effect is diarrhoea which can be managed through dietary changes and medication. Monitoring of liver function tests is also required as up to 5% of patients may develop liver abnormalities. Nintedanib was initially established as an antifibrotic treatment for idiopathic pulmonary fibrosis after the TOMORROW and INPULSIS trials showed a significant improvement in FVC when compared with a placebo group. It has since been approved for use in PPF, such as CTD-ILD, in combination with immunosuppressive agents but not as a monotherapy. The INBUILD trial and SENSCIS trial showed a lower rate of FVC decline when compared with placebo in a CTD-ILD cohort [47].

Pirfenidone

Pirfenidone is an antifibrotic that downregulates pro-inflammatory cytokines, inhibiting collagen synthesis which reduces the level of fibrosis. The dosage is increased over a 2-week period before reaching a maintenance dose of 801 mg three times daily. Like nintedanib, gastrointestinal side-effects are one of the most reported symptoms, in particular diarrhoea and reflux. There is a higher incidence of liver abnormalities so blood monitoring monthly for the first 6 months is advised and every 3 months thereafter. The TRAIL1 trial showed slower annual decline in FVC compared with that in the placebo group in patients with RA-ILD [48]. The use of pirfenidone is limited in SSc-ILD given the high frequency of side-effects but trials so far show a significantly lower decline in FVC % [49–51]. Current trials of pirfenidone in PPF have been hampered by methodological issues, and it is therefore not currently licensed for this indication.

Disease progression

Progressive ILD, for the American College of Rheumatology/American College of Chest Physicians guidelines, has been defined as per the criteria used in the INBUILD trial [52]. These were a decline in FVC of >10% predicted or 5–10% predicted with worsening symptoms or increased fibrosis on HRCT thorax or worsening respiratory symptoms and increased fibrosis within 24 months. Rapid progressors are those with rapid progression from breathing room air, or from baseline oxygen requirement, to high oxygen requirement or intubation within days to weeks (without an alternative cause). In rapidly progressive ILD management strategies involve combined immunosuppressive treatment, in addition to antifibrotics. There can be a role for immunoglobulins in specific cases.

For those on immunosuppressive therapies who are deemed “progressive”, the question is whether this relates to a failure of therapy (be it antifibrotic, immunosuppressive or both), a need to change mechanism, to intensify dosing or on the contrary a need to dial-back immunosuppressive therapies due to the damage attributable to superimposed infection or aspiration. In patients with ILD these are complex decisions which require multidisciplinary input. This is often the point at which we discuss criteria for transplantation referral and palliative care.

Conclusion

Pulmonary manifestations are common and are amongst the leading causes of death for patients with rheumatic diseases. Particular diseases, such as SSc, RA and IIMs, frequently associate with ILD and high-risk patients should be screened. Antibody profiling and imaging characteristics should be used to prognosticate where possible, along with regular surveillance to ensure therapies are optimised.

Immunosuppressive therapies can be effective for patients with CTD-ILD but difficulties arise in distinguishing between treatment failures and complications of immunosuppression. This is where the multidisciplinary team becomes crucial in fine tuning immunosuppressive and antifibrotic therapies. Monitoring for common toxicities is an important component of management.

Rheumatologists are committed to targeted therapies for patients with inflammatory diseases and would like to see the development of damage and disease activity tools as clinical decision aids. Referral for transplantation assessment, discussions regarding suitability for transplantation and potential barriers such as obesity, and involvement of palliative care where needed is often the remit of the respiratory service and combined care helps to ensure that these issues are dealt with in a timely manner.

As we screen patients at high risk for ILD, it is probable that we will encounter early and milder disease. This will enable us to intervene in a timely fashion and to be more aggressive in our management of patients with poor prognostic features. The literature from rheumatoid diseases tells us that early intervention improves outcomes; this is yet to be proven in our patients with ILD, but we hope that this will be the case. Early detection will further inform us on imaging and serological features that are a low risk for progression, allowing us to reassure patients. As we screen for earlier disease it is likely that we will identify more cases, making it crucial that multidisciplinary pathways are established to optimise care for these complex patients.

Key points

• Pulmonary manifestations are common and are amongst the leading causes of death for patients with rheumatic diseases.

• Particular diseases, such as SSc, RA and IIMs, frequently associate with ILD and high-risk patients should be screened.

• Antibody profiling and imaging characteristics should be used to prognosticate where possible, along with regular surveillance to ensure therapies are optimised.

• Immunosuppressive therapies can be effective for patients with CTD-ILD and methotrexate for instance should not be stopped in RA-ILD.