The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope

Abstract Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.


Why the guideline is needed
Systemic autoimmune rheumatic diseases (SARDs) is a term that covers a broad spectrum of clinical conditions of autoimmune aetiology [1].Interstitial lung disease (ILD) is a common manifestation of several SARDs and is associated with excess morbidity and mortality.
SARDs associated with ILD include RA, SSc, SS, idiopathic inflammatory myopathy (IIM), MCTD, SLE, ANCAassociated vasculitis (AAV) and axial SpA (axSpA).The terms CTD and collagen vascular disease have been historically used to describe this group of conditions and particularly SSc, SS, IIM, MCTD and SLE.However, CTD and collagen vascular disease are not reflective of our current understanding of the pathophysiology or organ involvement of these conditions and the term SARD is therefore preferred for the purposes of this guideline.
There are currently no UK guidelines related to the management of SARD-ILD and there is a concern that the condition may be underdiagnosed and consequently undertreated.It is important to understand that within the broad spectrum of SARD-ILD, distinct clinical phenotypes such as rapidly progressive ILD and progressive pulmonary fibrosis (PPF) (also termed progressive fibrosing ILD) have specific diagnostic and management considerations.
Strategies for screening people with existing SARDs for ILD are not clearly defined.In RA, many people have subclinical ILD and it is unclear if abnormalities on imaging in the absence of clinical symptoms should influence treatment and the frequency of monitoring.Screening for ILD also has the potential to overdiagnose minor interstitial lung abnormalities as ILD, the prognostic significance of which is unclear.
The data supporting the use of commonly used immunomodulatory strategies and newer therapies (e.g.antifibrotic drugs) in the treatment of SARD-ILD is steadily growing [2][3][4].Antifibrotic drugs are now recommended in the National Institute for Health and Care Excellence (NICE) guideline for pulmonary fibrosis-ILD [5] and it is vital that all healthcare professionals caring for people with SARD-ILD are aware of the appropriate use of such treatment.
A EULAR task force is expected to publish its guideline for SARD-ILD in 2024 and the ACR published their summary guidance in August 2023 [6].However, there is a need for UK-specific guidance that takes into account the resources of the UK health service, including local licencing and funding policies.The guideline will therefore be a useful document to support local and national policy-making in the UK.This guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol [7].

Current practice
Current practice is variable across the UK [19].Most people with SARD-ILD are managed in secondary or tertiary care settings, with dual-specialty rheumatology-respiratory clinics and multidisciplinary teams (MDTs) operating in some, but not all, centres.Previous disease-specific British Society for Rheumatology (BSR) guidelines have advocated screening for ILD in all people with SSc [20] and those with high-risk IIM subtypes [21], but no such recommendations have been made in RA or other SARDs.
The NICE idiopathic pulmonary fibrosis (IPF) guideline states that people with suspected ILD should be referred to a specialist centre for confirmation of the diagnosis and development of a treatment plan by an MDT with relevant clinical expertise and training [22].The approach to SARD-ILD diagnosis can vary depending on the availability of resources and expertise.Some medical therapies are used off-licence and reimbursement is often dependent on validation from the treating tertiary centre, but varies by region.
In RA, methotrexate (MTX) is a recommended first-line treatment for active joint disease.However, it is still sometimes avoided in those with RA-ILD due to concerns regarding MTX pneumonitis, which carries a higher mortality in people with reduced pulmonary reserve [26].This remains an area of controversy and will be examined in detail in the guideline.

Who the guideline is for?
This guideline is for any health professional in the UK who cares directly for people with SARD-ILD, including rheumatologists, pulmonologists, rheumatology and respiratory specialist nurses, radiologists, primary care clinicians, allied health professionals, specialty trainees, pharmacists and other stakeholders such as patient organizations and charities.

Equality considerations
People of all ethnicities are affected by SARD-ILD, meaning language and cultural barriers will have to be addressed to ensure all receive equitable access to care and high-quality education and treatment.

What will the guideline cover?
This guideline is being developed to provide recommendations on the screening, diagnosis, monitoring, pharmacological and non-pharmacological management of adults with SARD-ILD in the UK.

Groups that will be covered
Overarching principles will cover people with ILD associated with RA, SSc, SS, IIM, MCTD, SLE, AAV and axSpA.Another group included at the scoping stage are those people with ILD in whom clinical and serological profiles raise suspicion of SARD but do not meet classification criteria of a specific diagnosis.This will include patients in which ILD is the first, the predominant or the sole manifestation of SARD.This group remains poorly defined and previous labels include interstitial pneumonia with autoimmune features (IPAF), undifferentiated CTD-associated ILD, lung-dominant CTD and autoimmune-featured ILD.Each term has different but overlapping criteria.For the purposes of this guideline, this group will be referred to as 'ILD with suspected SARD' in order to ensure that our literature search includes relevant evidence for all the aforementioned terms.
For the purposes of the literature review, we elected to divide SARDs into the following four groups (Fig. 1): RA-ILD, CTD-ILD (SSc, IIM, MCTD, SS and SLE-related ILD), other (AAV and axSpA-related ILD) and ILD with suspected SARD.We acknowledge that these categories have limitation, and do not reflect clinical manifestations or the underlying pathophysiology of these conditions.

Groups that will not be covered
This guideline is not intended to cover people with idiopathic pulmonary fibrosis or other causes of ILD such as asbestosis, silicosis, hypersensitivity pneumonitis, radiation or non-antirheumatic drug-induced ILD.
A statement on the management of pulmonary sarcoidosis has recently been published by the British Thoracic Society (BTS) [27], and while sarcoidosis is an important cause of ILD, management of its multisystem manifestations is beyond the scope of this guideline.This guideline will not cover the diagnosis and management of SARD-ILD in paediatric populations (<16 years of age).ILD is a rare complication of SARD-ILD in children and there is insufficient literature available upon which to make any evidence-based recommendations.Also, the management of pulmonary hypertension and other complications will not be covered.

Settings
The guideline is being developed primarily for use in rheumatology and respiratory secondary and tertiary care settings but will also be of interest to other specialities involved in shared care, including primary care.

Related guidance
2023-ACR guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic disease (publication pending).
2008-Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society [28].
2021-Interstitial lung disease associated with autoimmune rheumatic diseases: checklists for clinical practice (Italian guideline-Delphi process) [30].2020-Japanese 2020 guide for the diagnosis and treatment of interstitial lung disease associated with connective tissue disease [31].

RA-ILD:
2022-Spanish Societies of Rheumatology and Pneumology and Thoracic Surgery recommendations for the management of rheumatoid arthritis-related interstitial lung disease.Part 2: treatment [32].
2023-Treatment of systemic sclerosis-associated interstitial lung disease: evidence-based recommendations.an official American Thoracic Society clinical practice guideline [34].

2016-BSR and British Health Professionals in
Rheumatology guideline for the treatment of systemic sclerosis [20].
Sarcoidosis: 2021-European Respiratory Society clinical practice guidelines on treatment of sarcoidosis [36].
2020-Diagnosis and detection of sarcoidosis.An official American Thoracic Society clinical practice guideline [37].

Key issues and draft questions
The following key issues and draft questions have been identified by the working group and will be used to develop more detailed questions to be addressed following a systematic search of the literature.
� Which people with known SARD should be screened for ILD?
� How often should screening take place?� What modalities should be used for screening?� How should subclinical ILD be managed when identified in people with SARD?
� What pharmacological management should be considered in SARD-ILD?� What non-pharmacological therapies are of clinical benefit?� Should any anti-rheumatic drugs be avoided or used with caution in those at risk of SARD-ILD?� How should people newly diagnosed with ILD, with positive SARD-associated autoantibodies but no other clinical manifestations of a SARD be managed?

Overarching principles
Screening: � Who should be screened?Does this differ according to underlying SARD or by antibody profile?� What tests should be performed to screen for ILD?
� Clinical examination In order to produce evidence-based recommendations for specific treatments, a systematic literature search will be undertaken using the Population, Intervention, Comparison and Outcomes (PICO) framework.

Comparison
Comparison will be against either placebo or standard-ofcare therapy.

Outcomes
The primary outcome to be examined will be progression as measured by the decline in pulmonary function tests.Secondary outcomes will include mortality, acute exacerbation rate, radiological progression, quality of life and potential serious adverse effects of the intervention.
Narrative/consensus recommendations will also be produced to cover the following aspects of management:

Approaches to audit of the guideline
Audit tools will be created to enable guideline users to easily assess local service delivery.

Figure 1 .
Figure1.Chart demonstrating the types of SARD-ILD that will be included in the guideline.These have been grouped into four sections to aid the organization of the systematic review How should management of the underlying SARD be balanced with the management of ILD? � Are any anti-rheumatic drugs associated with the development or worsening existing SARD-ILD?� How should those with ILD found to have positive autoantibodies without underlying SARD be managed?� Specific interventions to be examined are: � Chest X-ray � High-resolution computed tomography (HRCT) of the chest � Lung function tests � Six-minute walk test � Lung ultrasound � How do we determine prognosis?� Autoantibody profile � Lung function test parameters � Imaging features on HRCT chest � Quantitative HRCT chest analyses � Functional exercise capacity tests � Progressive pulmonary fibrosis � At what frequency and by which modes should people with SARD-ILD be monitored?� Frequency of lung function tests � Frequency of HRCT chest imaging � How should we define deterioration and improvement?� When to escalate or de-escalate therapy Management: � � IVIG � Anti-fibrotic therapies � Proton pump inhibitors � Plasma exchange � Extra-corporeal membrane oxygenation � Lung transplant � Haematopoietic stem cell transplant � Physiotherapy and pulmonary rehabilitation � Antimicrobial prophylaxis