Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease: A Pulmonary Perspective on Recent Guidelines

Abstract

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) represents a heterogeneous group of pulmonary disorders with substantial effects on morbidity and mortality. The clinical course varies according to the underlying rheumatic disease, radiological phenotype, extent of lung involvement and risk of progression. Although interstitial lung disease is particularly frequent in systemic sclerosis and idiopathic inflammatory myopathies, it also significantly contributes to outcomes in rheumatoid arthritis, Sjögren’s disease and mixed connective tissue disease. Early recognition is essential, as clinically silent disease may progress to irreversible fibrosis, whereas some patients may present with rapidly progressive or progressive fibrosing phenotypes requiring urgent or intensified treatment. Recent American College of Rheumatology/American College of Chest Physicians (ACR/CHEST) and European Respiratory Society/European Alliance of Associations for Rheumatology (ERS/EULAR) guidelines provide an important framework for screening, monitoring and management of SARD-ILD, but differ in several clinically relevant aspects. ACR/CHEST adopts a largely risk-based and pragmatic approach, whereas ERS/EULAR places greater emphasis on disease-specific assessment, the central role of high-resolution computed tomography in screening and structured monitoring according to progression risk. In treatment, both guidelines support immunosuppression as the main therapeutic strategy, while recognizing the growing role of antifibrotic therapy in selected patients with fibrotic or progressive disease. The available evidence remains strongest for systemic sclerosis-associated interstitial lung disease, with important uncertainties persisting across other SARD subtypes. This narrative review summarizes the epidemiology, clinical and radiological phenotypes, and pathobiological basis of SARD-ILD, and critically discusses recent guideline recommendations from a pulmonary perspective. Particular emphasis is placed on translating the differences between the current guidelines into practical multidisciplinary decisions regarding screening, longitudinal assessment, treatment selection and future research priorities.

Key Summary Points

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) is heterogeneous, and decisions regarding screening, monitoring and treatment should be guided by the underlying rheumatic disease and risk of progression.

The American College of Rheumatology/American College of Chest Physicians (ACR/CHEST) guideline recommends a risk-based screening approach using high-resolution computed tomography (HRCT) and pulmonary function tests, whereas the European Respiratory Society/European Alliance of Associations for Rheumatology (ERS/EULAR) guideline places greater emphasis on disease-specific HRCT-based screening, recommending universal screening in selected high-risk diseases.

ERS/EULAR explicitly recommends that pulmonary function tests should not replace HRCT for interstitial lung disease (ILD) screening, while both guidelines retain pulmonary function tests as a central component of follow-up once ILD has been identified.

ACR/CHEST recommends repeat HRCT when clinically indicated, whereas ERS/EULAR provides suggested intervals for HRCT monitoring according to the underlying disease and risk of progression.

Treatment should be guided by both the underlying rheumatic disease and ILD behaviour: immunosuppressive therapy remains central across SARD-ILD, while antifibrotic treatment is considered mainly in SSc-ILD and in patients who develop progressive pulmonary fibrosis.

Introduction

Systemic autoimmune rheumatic diseases (SARD) are chronic, immune-mediated disorders characterized by persistent systemic inflammation and multi-organ involvement. Lung involvement is a common manifestation of SARD, particularly significant because of its substantial impact on morbidity and mortality [1]. Systemic autoimmune rheumatic disease-associated interstitial lung diseases (SARD-ILD) include a wide range of autoimmune conditions, such as systemic sclerosis (SSc), rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIMs), Sjögren’s syndrome (SjD), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Although these disorders share common immunological features, the prevalence, clinical course, radiological patterns and pulmonary manifestations of ILD vary substantially between disease entities. For instance, interstitial lung involvement is particularly common in SSc and inflammatory myopathies, whereas it occurs less frequently in SLE [2].

High-resolution computed tomography (HRCT) commonly reveals patterns similar to those observed in idiopathic interstitial pneumonias, including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organising pneumonia (OP), and lymphocytic interstitial pneumonia (LIP) [3]. This heterogeneity poses substantial challenges for clinicians, particularly in distinguishing inflammatory from fibrotic phenotypes, predicting disease progression, and determining the optimal timing of therapeutic intervention. In recent years, the introduction of targeted immunomodulatory agents and antifibrotic therapies has expanded treatment options and shifted the clinical focus towards early identification of high-risk patients and timely intervention [4]. The complexity of these disorders has highlighted the need for multidisciplinary collaboration between pulmonologists, rheumatologists, radiologists and pathologists to optimise diagnosis and management [5].

In this context, a clinically oriented synthesis of the current evidence is essential. This narrative review aims to provide a comprehensive overview of SARD-ILD. Here, current knowledge regarding epidemiology, pathobiology, clinical and radiological phenotypes is summarised, and key diagnostic and prognostic considerations are discussed. In addition, screening, monitoring and treatment strategies—including immunosuppressive, biologic, and antifibrotic therapies—are addressed within a framework that integrates similarities and differences across current evidence and guideline recommendations, with emphasis on disease behaviour, progression assessment and multidisciplinary care.

This manuscript focuses on the recent 2023 ACR/CHEST and 2025/2026 ERS/EULAR guidelines, supported by pivotal clinical trials, major observational studies and recent reviews relevant to SARD-ILD, highlighting key similarities and differences in screening, monitoring and treatment and translating these recommendations into practical clinical considerations.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Representative high-resolution computed tomography images included in this article were obtained from the authors’ archive, were fully anonymised prior to inclusion, and contain no identifiable patient information. Written informed consent was obtained from the patients for publication of the anonymised radiological images. The signed consent forms can be provided upon request.

Epidemiology and Clinical Spectrum of SARD- ILD

Epidemiology of SARD-ILD

ILD is a common extra-articular manifestation of SARD, and population-based data indicate that patients with SARD have a significantly increased risk of developing ILD compared to the general population [6, 7]. The reported prevalence of ILD varies widely depending on the underlying disease, study population and diagnostic approach. In a nationwide cohort study, the risk of ILD was markedly elevated across multiple rheumatic diseases, with the highest incidence observed in SSc and IIMs [8]. SSc is the disease most strongly associated with ILD. Lung involvement frequently occurs early in the disease course and is a leading cause of mortality in patients with SSc. In SSc, ILD is detected in approximately 40–60% of patients, particularly with systematic HRCT screening [9]. Several clinical and serological factors influence the risk of ILD in SSc, including male sex, early disease, diffuse cutaneous disease subtype and the presence of anti-topoisomerase I (anti-Scl-70) antibodies [10, 11].

IIMs are frequently associated with pulmonary involvement, with ILD reported in approximately 20–65% of cases [12]. This association is particularly prominent in antisynthetase syndrome, in which antisynthetase antibodies, such as anti-Jo-1 (anti-histidyl-tRNA synthetase) antibodies, are more commonly associated with chronic fibrosing patterns [13]. In RA, ILD is a well-recognised extra-articular manifestation, with prevalence estimates typically ranging from 10% to 30% depending on the population studied and the diagnostic approach used [14]. Despite its relatively lower prevalence than SSc, RA remains the most common autoimmune rheumatic disease worldwide and therefore contributes substantially to the overall burden of SARD-ILD. RA-ILD usually develops later in the disease course and is more frequently observed in older patients, particularly male patients with a history of smoking [15]. In addition, serologic markers such as high titres of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies have been associated with an increased risk of pulmonary involvement [16].

MCTD also demonstrates relatively frequent pulmonary involvement, often resembling the ILD patterns observed in SSc [17]. SjD and MCTD demonstrate intermediate prevalence rates, generally reported between 10% and 30%, whereas ILD occurs less frequently in SLE, typically affecting fewer than 10% of patients [18, 19]. Variation in prevalence estimates reflects methodological differences, including variations in screening approaches, the use of HRCT and changes in classification criteria. The increasing use of HRCT and pulmonary function tests has improved the detection rates of subclinical diseases, contributing to the higher prevalence reported in recent studies [1].

Clinical Presentation and Disease Heterogeneity

The clinical spectrum of SARD-ILD is highly heterogeneous, ranging from asymptomatic or subclinical disease to severe, rapidly progressive respiratory failure. The onset of ILD can precede, coincide with or follow the diagnosis of the underlying SARD, complicating early recognition and management [20]. In many patients with SARD, ILD may be detected incidentally during routine screening or imaging performed for other indications. Subclinical disease is particularly common in SSc, where HRCT abnormalities may precede respiratory symptoms by several years [21]. In contrast, a subset of patients develops rapidly progressive ILD (RP-ILD) characterised by acute and diffuse lung injury. This phenotype is most often observed in IIMs, especially in anti-MDA5 (anti-melanoma differentiation-associated gene 5)-positive disease, and is associated with high mortality [22]. A subset of patients with SARD-ILD may develop a progressive fibrotic phenotype resembling idiopathic pulmonary fibrosis (IPF). These patients experience progressive decline in lung function, worsening respiratory symptoms and increased fibrosis on imaging despite standard immunosuppressive therapy [23]. Recognition of this phenotype has important therapeutic implications, as antifibrotic agents such as nintedanib have been shown to slow the rate of lung function decline in progressive fibrosing ILD associated with autoimmune diseases [24].

Radiological Phenotypes

HRCT plays a central role in the evaluation of SARD-ILD, providing essential information for diagnosis, phenotyping and prognostic assessment. SARD-ILD shows a range of radiological patterns, most commonly NSIP, while UIP, OP and LIP are less frequent [25] (Fig. 1). In SSc-ILD, HRCT most commonly demonstrates a NSIP pattern, characterised by predominantly basal ground-glass opacities and varying degrees of fibrosis with reticulation and traction bronchiectasis, with a higher ground-glass-to-fibrosis ratio compared with RA-ILD (Fig. 1A). In contrast, RA-ILD more frequently exhibits a UIP pattern, characterised by a basal predominant honeycombing and traction bronchiectasis, and a lower ground-glass-to-fibrosis ratio [26] (Fig. 1B).

Fig. 1.

Representative high-resolution computed tomography (HRCT) patterns in SARD-associated interstitial lung disease; images are from the authors’ own archive: A early NSIP pattern in systemic sclerosis showing ground-glass opacities and reticulation; B UIP pattern in rheumatoid arthritis with honeycombing and traction bronchiectasis; C OP pattern in idiopathic inflammatory myopathies; D NSIP/OP overlap pattern with bronchiolocentric features in systemic lupus erythematosus; E LIP pattern in Sjögren’s disease characterised by ground-glass opacities and cysts

Radiological patterns may provide important diagnostic clues in specific disease contexts. OP is characterised by patchy consolidations and ground-glass opacities and is more commonly observed in IIMs, sometimes overlapping with NSIP [27] (Fig. 1C, D). LIP, which may present with ground-glass opacities, nodules and thin-walled cysts, is typically associated with SjD [28] (Fig. 1E). Importantly, radiological patterns are not merely descriptive but have significant clinical implications. NSIP is generally associated with a more favourable prognosis and a greater degree of reversibility with immunosuppressive therapy, whereas UIP is linked to a more progressive fibrotic course and worse outcomes [29]. Mixed or overlapping patterns are also common, reflecting the complex interplay between inflammation and fibrosis in SARD-ILD [30]. In addition to pattern recognition, HRCT is essential for assessing disease extent, monitoring progression and identifying complications such as infection, acute exacerbation or drug-related lung injury. Given the complexity and variability of imaging findings, interpretation within a multidisciplinary framework remains critical for accurate diagnosis and optimal management [31].

Pathobiological Mechanisms

Pulmonary involvement in SARD results from a complex interplay between immune-mediated inflammation and fibrotic remodelling pathways. Although the underlying autoimmune disorders differ in their immunologic drivers, several shared pathogenic mechanisms contribute to lung injury and fibrogenesis in SARD-ILD. These processes involve dysregulated immune responses, aberrant fibroblast activation, endothelial dysfunction and altered epithelial repair mechanisms.

Immune-Mediated Inflammation and Lung Injury

The initial phase of lung involvement in many autoimmune rheumatic diseases is characterised by immune-mediated injury to the alveolar epithelium and pulmonary interstitium. Activated macrophages, dendritic cells, and neutrophils release inflammatory mediators that promote tissue injury and amplify immune signalling. Simultaneously, autoreactive T and B lymphocytes contribute to chronic inflammation through cytokine secretion and auto-antibody production [32]. Several cytokines and growth factors have been implicated in SARD-ILD pathogenesis, including transforming growth factor-β (TGF-β), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and platelet-derived growth factor (PDGF). These mediators promote fibroblast recruitment and activation while impairing normal epithelial repair processes. Persistent immune activation ultimately leads to excessive extracellular matrix deposition and progressive pulmonary fibrosis [33]. Auto-antibodies also appear to play important roles in disease pathogenesis and phenotypic heterogeneity. For example, antitopoisomerase I antibodies in SSc are strongly associated with the development of interstitial lung disease, whereas antisynthetase antibodies such as anti-Jo-1 are linked to ILD in IIMs [34, 35]. In dermatomyositis, anti-MDA5 antibodies have been associated with RP-ILD, suggesting that specific immune pathways may drive distinct clinical phenotypes [36].

Fibrotic Pathways and Aberrant Tissue Repair

Fibrosis in SARD-ILD results from irregular wound healing following repeated epithelial damage. Activated fibroblasts and myofibroblasts produce excessive extracellular matrix components such as collagen and fibronectin, leading to progressive architectural distortion of the lung parenchyma. TGF-β is a central regulator of fibrogenesis and promotes fibroblast proliferation, differentiation into myofibroblasts and extracellular matrix deposition [37]. In addition to fibroblast activation, endothelial dysfunction and microvascular injury contribute to disease progression, particularly in SSc where vasculopathy is a hallmark feature [38].

In clinical practice, the difference between inflammatory and fibrotic phenotypes of SARD-ILD is not always clear. Many patients exhibit overlapping features of inflammation and fibrosis, and disease behaviour may change. For example, an initially inflammatory interstitial pneumonia may gradually transition to a predominantly fibrotic phenotype characterised by progressive lung function decline [39]. This evolving disease course has contributed to the recognition of progressive fibrosing phenotypes. The concept of progressive pulmonary fibrosis (PPF) has emerged to describe a subgroup of patients who demonstrate ongoing fibrotic progression despite conventional immunosuppressive therapy. These patients share clinical and radiological features with idiopathic pulmonary fibrosis and may benefit from antifibrotic therapies [23].

In conclusion, understanding the interaction between immune-mediated inflammation and fibrotic remodelling remains critical for the development of targeted therapies and tailoring treatment strategies according to the disease phenotype.

Screening Strategies and Early Detection

Early identification of interstitial lung disease in patients with SARD is essential because pulmonary involvement may remain asymptomatic in its initial stages but can progress to irreversible fibrosis if left untreated. Importantly, ILD is a major determinant of morbidity and mortality in SARD, with significant impact on long-term outcomes and survival. Consequently, timely screening and early detection are critical components of clinical management.

The 2023 American College of Rheumatology/American College of Chest Physicians (ACR/CHEST) guidelines adopt a risk-based screening strategy, recommending evaluation for ILD primarily in patients considered at increased risk rather than universal screening. The 2023 ACR/CHEST guidelines conditionally recommend risk-based screening with both HRCT and pulmonary function tests (PFTs) in patients with SARD at increased risk of ILD, including those without respiratory symptoms. These conditional recommendations reflect low certainty of evidence and support individualised decision-making [40]. Risk factors guiding screening in the ACR/CHEST framework vary across SARD subtypes and include demographic, clinical and serological features [40]. In contrast, the 2025 ERS/EULAR guidelines place HRCT at the centre of screening. ERS/EULAR strongly recommends against replacing HRCT with PFTs, including FVC and DLCO, because lung function tests have low sensitivity and may miss early or mild ILD. The ERS/EULAR recommendations are also more disease-specific: HRCT screening is recommended for all patients with SSc and MCTD, whereas a risk-based HRCT approach is suggested for RA and Sjögren’s disease. In IIM, HRCT screening is recommended in patients with risk factors and may be considered more broadly in selected patients (Table 1). This difference in approach between the two guidelines reflects ILD prevalence in different disease subtypes, disease courses and evidence. Among SARD, SSc has the strongest recommendation for systematic screening, reflecting the high prevalence of ILD, which may affect 40–60% of patients and is often present early in the disease course, as well as its association with progressive fibrosis and increased mortality [10]. Both guidelines recognise SSc as a particularly high-risk disease, but frame screening differently. The ACR/CHEST guideline follows a risk-based approach, and highlights features such as diffuse cutaneous disease, anti-topoisomerase I antibody positivity, early disease and elevated inflammatory markers as factors that increase the likelihood of ILD. In contrast, the ERS/EULAR guideline recommends HRCT screening for all patients with SSc, reflecting the high prevalence of ILD at or near diagnosis and the limited ability of PFTs to exclude early disease. In RA, the ACR/CHEST and ERS/EULAR guidelines are broadly aligned in supporting a risk-based rather than universal HRCT screening strategy. Routine HRCT screening of all patients with RA is not generally recommended because subclinical abnormalities may be common and the clinical significance of mild imaging findings in asymptomatic patients remains uncertain. Therefore, screening is guided by clinical context and risk factors, including older age, male sex, smoking history, high disease activity, and serological markers such as high-titre rheumatoid factor and anti-CCP antibodies. However, ERS/EULAR places greater emphasis on HRCT as the preferred screening modality, noting that PFTs may miss early or mild ILD and should not replace HRCT [41, 42]. In IIM, MCTD and SjD, the two guidelines overlap in recognising disease-specific risk factors, but ERS/EULAR is more HRCT-centred. It recommends HRCT screening for all patients with MCTD and for IIM patients with risk factors, and suggests that most IIM patients without risk factors could also be screened, except those with inclusion body myositis. SjD remains risk-based in both frameworks. This broader HRCT-based approach reflects the risk of rapidly progressive ILD in selected IIM phenotypes and the limited sensitivity of PFTs for early disease detection. Therefore, PFTs should not be used as standalone screening tools but remain important for functional assessment and longitudinal monitoring [43, 44].

Table 1.

Screening Strategies for SARD-ILD: Comparison of ACR/CHEST (2023) and ERS/EULAR (2025)

Disease	ACR/CHEST (2023)	ERS/EULAR (2025)
SSc	Risk-baseda screening (HRCT + PFT)	Screen all patients (HRCT)
RA	Risk-baseda screening (HRCT + PFT)	Risk-basedb screening (HRCT)
IIM	Risk-baseda screening (HRCT + PFT)	Risk-basedc screening (HRCT); PFT alone insufficient (HRCT recommended in most patients, even without risk factors, except inclusion body myositis
MCTD	Risk-baseda screening (HRCT + PFT)	Screen all patients (HRCT)
SjD	Risk-baseda screening (HRCT + PFT)	Risk-basedd screening (HRCT)
SLE	Not addressed; outside the scope of the guideline	No specific recommendation

ACR American College of Rheumatology, CHEST American College of Chest Physicians, CTD-ILD connective tissue disease-associated interstitial lung disease, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, HRCT high-resolution computed tomography, IIM idiopathic inflammatory myopathies, MCTD mixed connective tissue disease, PFT pulmonary function test, RA rheumatoid arthritis, SjD Sjögren’s disease, SLE systemic lupus erythematosus, SSc systemic sclerosis

^a In the ACR/CHEST guidelines, risk-based screening refers to evaluation of patients at increased risk of ILD based on disease-specific clinical features, demographic characteristics, and serological markers

^b Older age, male sex, smoking history, high disease activity, RF/anti-CCP positivity, elevated inflammatory markers

^c Antisynthetase syndrome, clinically amyopathic dermatomyositis, mechanic’s hands, arthritis, anti-MDA5, antisynthetase, anti-Ro52 antibodies

^d Older age, male sex, extrapulmonary involvement, elevated inflammatory markers

Consistent with its selective, risk-based approach, the ACR/CHEST guidelines recommend against the use of chest radiography, 6-min walk testing (6MWT), bronchoscopy, and surgical lung biopsy as screening tools for ILD. In a similar effort to avoid low-yield or inappropriate screening modalities, the ERS/EULAR guidelines suggest that lung ultrasound, whether performed using short or extended protocols, should not replace HRCT for ILD screening. Together, these recommendations reinforce the central role of HRCT in screening, while recognising that the supporting evidence is generally of low or very low certainty [40, 45]. Unlike some guideline-based approaches that suggest a stepwise strategy, current evidence does not support a uniform screening algorithm for all SARD. The optimal use and timing of pulmonary function tests and HRCT remain uncertain, reflecting the balance between early detection and the risk of overdiagnosis [46].

Disease Assessment, Risk Stratification and Monitoring of SARD-ILD

Disease assessment and monitoring are essential components of SARD-ILD management. Monitoring aims to assess disease trajectory, treatment response, and emerging complications using a combination of symptoms, pulmonary function tests, HRCT findings, exercise assessment, oxygen desaturation, and patient-reported outcome measures (PROMs). Prognostic risk factors guide baseline risk stratification, monitoring intensity and treatment decisions. The risk factors depicting poorer outcomes are broadly similar between the two guidelines. They vary according to ILD subtype and span clinical, immunological, physiological and radiological factors (Table 2).

Table 2.

Risk factors informing SARD-ILD screening according to recent guidelines

Disease	ACR/CHEST (2023)	ERS/EULAR (2025)
SSc	Anti-Scl-70 positivity	Not specified as risk-based screening; all patients with SSc are recommended for HRCT screening
	Nucleolar ANA pattern
	Diffuse cutaneous disease
	Male sex
	African American race
	Early disease
	Elevated acute-phase reactants
RA	High-titre RF or anti-CCP	Older age
	Smoking	Smoking history
	Older age at RA onset	Elevated RF/anti-CCP
	High disease activity	Increased inflammatory markers
	Male sex	Male sex
	Higher BMI	High articular disease activity
IIM	Antisynthetase antibodies	Antisynthetase syndrome
	Anti-MDA5	Clinically amyopathic dermatomyositis
	Anti-Ku	Mechanic’s hands
	Anti-Pm/Scl	Arthritis
	Anti-Ro52	Antisynthetase antibodies
	Mechanic’s hands	Anti-MDA5
	Arthritis/arthralgia	Anti-Ro52
	Ulcerating lesions
MCTD	Dysphagia	Not specified as risk-based screening; all patients with MCTD are recommended for HRCT screening
	Raynaud phenomenon
	SSc-like clinical or laboratory features
SjD	Anti-Ro52	Older age
	ANA positivity	Male sex
	Raynaud phenomenon	Active extrapulmonary organ involvement
	Older age	Increased inflammatory markers
	Lymphopenia
	Severe dental caries
SLE	Not included in the guideline scope	No recommendation because of insufficient evidence

ACR American College of Rheumatology, ANA antinuclear antibody, anti-CCP anti-cyclic citrullinated peptide, Anti-MDA5 anti-melanoma differentiation-associated gene 5 antibody, Anti-Pm/Scl anti-polymyositis/scleroderma antibody, Anti-Scl-70 anti-Scleroderma-70 antibody, BMI body mass index, CHEST American College of Chest Physicians, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, HRCT high-resolution computed tomography, IIM idiopathic inflammatory myopathy, ILD interstitial lung disease, MCTD mixed connective tissue disease, PFT pulmonary function test, RA rheumatoid arthritis, RF rheumatoid factor, SARD-ILD systemic autoimmune rheumatic disease–associated interstitial lung disease, SjD Sjögren’s disease, SLE systemic lupus erythematosus, SSc systemic sclerosis

Monitoring strategies for SARD-ILD differ between the 2023 ACR/CHEST and 2025 ERS/EULAR guidelines, largely reflecting how each framework conceptualises risk of disease progression. Both recognise that progression is heterogeneous and influenced by underlying SARD subtype, baseline severity, and clinical risk factors; however, they operationalise this differently. The 2023 ACR/CHEST recommendations adopt a broader, more pragmatic approach in which monitoring frequency is primarily guided by disease duration and overall clinical course, with more intensive follow-up in early or recently diagnosed disease and less frequent assessment once stability is established. This approach emphasises flexibility and clinician judgement, typically relying on serial PFTs as the main monitoring tool, with HRCT reserved for suspected progression. In contrast, the 2025 ERS/EULAR guideline incorporate a more explicit risk-based model, where monitoring intensity is determined not only by disease duration but also by the estimated risk of progression, integrating factors such as HRCT pattern and extent, pulmonary function impairment, SARD subtype, and other clinical predictors. Consequently, patients at higher risk of progressive fibrosing disease undergo closer and more structured follow-up, often with predefined intervals for both PFTs and repeat imaging, even in the absence of overt clinical deterioration. Serial PFTs remain central to monitoring because they are widely available, acceptable for repeated assessment, and avoid radiation exposure, while providing objective information on functional decline. HRCT is used as a complementary tool when progression is suspected or when symptoms and PFT trends are discordant. The suggested follow-up schedule is summarised in Table 3.

Table 3.

Comparison of PFT monitoring intervals in SARD-ILD between ERS/EULAR (2025) and ACR/CHEST (2023)

	SARD-ILD subtype	PFT parameters	Initial follow-up interval	Subsequent follow-up interval	Notes
ERS/EULAR (2025)	SSc-ILD	FVC, DLCO	Every 3–6 months during the first 3–5 years	At least every 6–12 months thereafter; earlier if progression is suspected	—
	RA-ILD	FVC, DLCO, FEV₁	Every 3–6 months during the first 1–2 years	At least every 6–12 months thereafter; earlier if progression is suspected	FEV₁ included because of possible concomitant airway involvement
	IIM-ILD	FVC, DLCO	Every 3–6 months during the first year	At least every 6–12 months thereafter; earlier if progression is suspected	—
	SjD-ILD	FVC, DLCO, FEV₁	Every 3–6 months during the first year	At least every 6–12 months thereafter; earlier if progression is suspected	Airway involvement may be present
	MCTD-ILD	—	No specific recommendation	—	No disease-specific PFT monitoring recommendation
	SLE-ILD	—	No specific recommendation	—	No disease-specific PFT monitoring recommendation
ACR/CHEST (2023)	SSc-ILD	PFTs	Every 3–6 months during the first year	Less frequently once stable	More frequent monitoring may be appropriate in higher-risk or progressive disease
	RA-ILD	PFTs	Every 3–12 months during the first year	Less frequently once stable	—
	IIM-ILD	PFTs	Every 3–6 months during the first year	Less frequently once stable	More frequent monitoring may be appropriate in active or rapidly progressive disease
	SjD-ILD	PFTs	Every 3–12 months during the first year	Less frequently once stable	More frequent monitoring may be considered with symptom worsening, UIP pattern, anti-Ro52 positivity, or worsening PFTs
	MCTD-ILD	PFTs	Every 3–12 months during the first year	Less frequently once stable	More frequent monitoring may be considered with prominent SSc/IIM features
	SLE-ILD	Not included in the guideline scope	—	—	—

ACR American College of Rheumatology, CHEST American College of Chest Physicians, DLCO diffusing capacity of the lung for carbon monoxide, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, FEV₁ forced expiratory volume in 1 s, FVC Forced vital capacity, IIM idiopathic inflammatory myopathy, ILD interstitial lung disease, MCTD mixed connective tissue disease, PFT pulmonary function test, RA rheumatoid arthritis, SARD-ILD systemic autoimmune rheumatic disease–associated interstitial lung disease, SjD Sjögren’s disease, SLE systemic lupus erythematosus, SSc systemic sclerosis

The 2025 ERS/EULAR guidelines also provide recommendations on HRCT monitoring frequency tailored to underlying disease and progression risk. The suggested intervals are summarised in Table 4. In contrast, the 2023 ACR/CHEST guidelines do not specify HRCT intervals but emphasise that HRCT is a valuable adjunct to PFTs, especially when symptoms change, unreliable PFTs or clinical uncertainty raises concerns regarding ILD progression, infection, malignancy, or when assessing treatment response.

Table 4.

Comparison of HRCT monitoring strategies in SARD-ILD between ERS/EULAR (2025) and ACR/CHEST (2023)

SARD-ILD subtype	ACR/CHEST (2023)	ERS/EULAR (2025)
SSc-ILD	No specific intervala	Every 1–2 years (earlier if progression/high-risk)
RA-ILD	No specific intervala	Every 1–2 years (earlier if progression/high-risk)
IIM-ILD	No specific intervala	3–6 months (high-risk)
		Annual HRCT (first 2 years)
		± Additional HRCT if clinical suspicion of progression
Other SARD-ILD (SjD, MCTD, SLE)	No specific intervala	Every 1–2 years (earlier if progression/high-risk)

^*ACR/CHEST does not specify fixed intervals and recommends imaging based on clinical indication.

ACR American College of Rheumatology, CHEST American College of Chest Physicians, CTD-ILD connective tissue disease-associated interstitial lung disease, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, IIM idiopathic inflammatory myopathies, HRCT high-resolution computed tomography, MCTD mixed connective tissue disease, RA rheumatoid arthritis, SjD Sjögren’s disease, SLE systemic lupus erythematosus, SSc systemic sclerosis

The 6MWT is suggested as a tool for assessing ILD severity and prognosis across SARD-ILD [45]. Shorter walk distances and greater oxygen desaturation have been shown to predict disease progression in SSc-ILD [47–52], while, in RA-ILD, they correlate with mortality and acute respiratory deterioration [53, 54]. In IIM-ILD, walk distance aligns with lung function parameters [55, 56], and, in other SARD-ILD, a reduced walk distance is associated with more severe ILD and poorer outcomes [57–59]. The test is appropriate when lower-limb involvement does not significantly limit performance, such as in RA-ILD without major joint damage or IIM-ILD without marked muscle weakness [45]. The 2025 ERS/EULAR guidelines recommend 6MWT monitoring every 6–12 months for high-risk patients and annually in low-risk patients [45]. The 2023 ACR/CHEST guidelines suggest assessing ambulatory desaturation every 3–12 months [40]. However, this assessment is not routinely performed by many rheumatologists, and logistical challenges may limit its feasibility in some settings. PROMs can be used to evaluate symptoms, disease impact and patient needs in SARD-ILD [45]. They correlate with other markers of disease severity and provide a non-invasive method that capture patient-centred perspectives that complement clinical assessment. However, they have not been incorporated in clinical practice or guideline recommendations due to lack of easy-to-use standardised assessment tools.

Therapeutic Approaches in SARD-ILD

First-Line Treatment

The current management of SARD-ILD is centred on immunosuppression as a first-line approach. However, the evidence base is limited and mostly derived from studies on SSc populations. For other SARD-ILD, treatment recommendations rely mainly on low-quality retrospective observational data or small uncontrolled studies, thus leading to only conditional recommendations in the guidelines based on pragmatic and/or usual care decisions. Although both the ACR/CHEST 2023 and ERS/EULAR 2025 guidelines agree on this principle, they differ mainly in how they prioritise agents according to disease subtype and risk of progression. The differences between the guidelines, therefore, arise more from divergent interpretations of a limited and low-certainty evidence base than from genuine disagreement, as both sets of recommendations arrive at broadly similar therapeutic conclusions through different methodological approaches. Glucocorticoids should be framed as adjunctive rather than foundational long-term therapy. In non-SSc SARD-ILD, they are often used as short-term bridging treatment, particularly in inflammatory myositis-associated ILD or when disease activity is high and are conditionally recommended as first-line treatment in almost all SARD-ILD, except SSc. In SSc-ILD, glucocorticoids should be avoided or minimised because of the risk of scleroderma renal crisis, which is why ACR/CHEST strongly recommends against them as first-line treatment in this setting, while ERS/EULAR just emphasizes the need for rapid withdrawal in all diseases [4, 45].

Both guidelines position MMF as a central treatment option, not only because it has the most consistent supportive evidence but also a more favourable tolerability profile. In the Scleroderma Lung Study I (SLS I), 12 months of oral cyclophosphamide produced a modest but statistically significant benefit in lung function, with a mean placebo-adjusted improvement of 2.53% in predicted FVC at 12 months. This was accompanied by significant improvements in dyspnoea, functional ability, selected health-related quality-of-life domains, and skin thickening, although toxicity remained a concern [60]. Subsequently, SLS II compared 24 months of MMF with 12 months of oral cyclophosphamide followed by placebo and did not show superiority of one drug over the other. Both MMF and cyclophosphamide improved predicted FVC over 24 months, with adjusted increases of 2.19% and 2.88%, respectively, and no significant between-group difference. However, MMF was significantly better tolerated than cyclophosphamide, with less leukopenia and thrombocytopenia. These studies provide the rationale for the conditional recommendations in both guidelines for SSc-ILD, with extrapolation to other SARD-ILD subtypes where direct evidence is limited [61].

The main divergence between the guidelines is related to the strength of recommendations for tocilizumab, an interleukin 6 (IL-6) receptor antagonist. This is based on interpretation of the significance of the findings from the faSScinate and focuSSced randomised controlled trials (RCT). These RCTs were phase 2 and 3 trials of tocilizumab in SSc. The presence of ILD was not a pre-requisite for inclusion in the trials, and in both studies the primary endpoint of a change in modified Rodnan skin score (mRSS) was not met. The basis of the guideline recommendations stems from the positive findings in the secondary endpoint of FVC and hence the contrasting opinions on the strength and significance of these results. In an earlier phase 2 RCT, fewer patients in the tocilizumab arm had an FVC decline of 10% (10% vs. 23%) at 48 weeks compared to placebo. Similarly, in the subsequent phase 3 RCT the change from baseline of percent predicted FVC was − 4.6 in the placebo arm and − 0.4 in the tocilizumab group (nominal P = 0.0002). Based on these results, ERS/EULAR strongly recommends tocilizumab in a distinct subgroup of patients with SSc-ILD based on the inclusion criteria of the trials. This includes patients with early diffuse cutaneous SSc, increased inflammatory markers, or recent skin progression. Conversely, ACR/CHEST guideline provide a conditional recommendation for tocilizumab in SSc-ILD and MCTD-ILD [4, 45].

RCT evidence outside SSc is much more limited and the majority of guideline recommendations for other immunosuppressants are conditional due to low-quality evidence, principally observational studies. Rituximab, azathioprine and MMF feature as conditional recommendations in the treatment of RA-ILD and other SARD-ILD, whereas calcineurin inhibitors and Janus-kinase (JAK) inhibitors for IIM-ILD only.

Rituximab features prominently as a therapy for all SARD-ILD based on more robust evidence from a number of RCTs, although the supporting evidence comes from heterogeneous trial populations. The RECITAL RCT compared rituximab with intravenous cyclophosphamide in patients with severe or progressive connective tissue disease related ILD (CTD-ILD) related to SSc, IIM, or MCTD. Rituximab was not superior to cyclophosphamide for the primary endpoint of FVC change at 24 weeks; however, both groups showed improvement in FVC, with unadjusted mean increases of 97 mL in the rituximab group and 99 mL in the cyclophosphamide group. Improvements in respiratory-related quality of life were also observed in both groups, while rituximab was associated with fewer adverse events and lower corticosteroid exposure over 48 weeks [62]. In SSc, the DESIRES trial evaluated rituximab against placebo in patients with systemic sclerosis and skin involvement, with concomitant ILD present in most patients. Rituximab significantly improved the primary endpoint of modified Rodnan skin score at 24 weeks compared with placebo and also showed a modest but significant benefit in FVC among patients with ILD, with a between-group difference of 2.96% predicted FVC in favour of rituximab [63]. The EVER-ILD trial evaluated the efficacy of rituximab in addition to MMF compared with MMF alone in patients with CTD-ILD, idiopathic pneumonia with autoimmune features (IPAF), or idiopathic interstitial pneumonia with an NSIP pattern or NSIP-like HRCT pattern. Rituximab plus MMF was superior to MMF alone for the primary endpoint, with a between-group difference of 3.60% predicted FVC at 6 months, and also improved progression-free survival, although infections were more frequent in the combination group [64]. Together, these studies support rituximab as a potential alternative to cyclophosphamide in severe or progressive CTD-ILD requiring intravenous therapy, and as a possible add-on strategy to MMF in selected patients with inflammatory or progressive NSIP-pattern disease.

Antifibrotics

The antifibrotic therapies pirfenidone and nintedanib are the cornerstone treatments for idiopathic pulmonary fibrosis. The shared fibrotic mechanisms have rationale for their utility in SARD-ILD. Nintedanib has been included as an “additional” option for first-line treatment in patients with SSc-ILD in the ACR/CHEST guideline, whilst ERS/EULAR recommended nintedanib either alone or in combination with MMF, based on the findings of the SENSCIS trial. The SENSCIS RCT evaluated nintedanib in patients with SSc-ILD with at least 10% fibrosis. Patients were treated with concomitant MMF (48.5%) and 51.9% had diffuse cutaneous SSc. Patients randomised to nintedanib declined by − 52.4 mL per year compared to − 93.3 mL per year decline in placebo with a statistically significant difference of 41.0 mL. There was no difference in the secondary endpoints of change in Rodnan skin scores and quality of life between the two groups [65]. Furthermore, the INBUILD RCT explored the efficacy of nintedanib in a heterogenous group of ILD with a progressive phenotype defined as PPF. SARD-ILD was a pre-specified heterogenous group comprised of RA-ILD (52.4%), SSc-ILD (22.9%), MCTD-ILD (11.2%), and other SARD-ILD (13.5%) and comprised approximately 25.6% (170 SARD-ILD/663 total cohort) of patients in the INBUILD RCT. The study demonstrated a − 178.6 mL/year decline in placebo compared to − 75.9 mL/year in nintedanib in the SARD-ILD cohort, a reduction in FVC decline of 104 mL (P = 0.012) [66]. Based on these trials, the two guidelines differ mainly in how broadly they position antifibrotic therapy across SARD-ILD subtypes and disease stages. In the ACR/CHEST guideline, nintedanib is conditionally recommended as a first-line ILD treatment option only for SSc-ILD, whereas it is conditionally recommended against as a first-line therapy for SjD-ILD, IIM-ILD and MCTD-ILD; for RA-ILD, the panel did not reach consensus. The same guideline also conditionally recommends against adding nintedanib or pirfenidone to mycophenolate in patients without evidence of ILD progression, and against upfront combination antifibrotic therapy with mycophenolate. However, when ILD progresses despite first-line therapy, nintedanib is conditionally recommended as a treatment option across SARD-ILD, while pirfenidone is reserved as an add-on option for progressive RA-ILD, particularly with a UIP pattern [40]. In contrast, ERS/EULAR suggests nintedanib for SSc-ILD and any CTD-ILD with progressive pulmonary fibrosis, and also suggests nintedanib in combination with MMF in SSc-ILD, reflecting SENSCIS data [4, 67].

ERS/EULAR further suggests pirfenidone only in RA-ILD with a UIP pattern, while no recommendation is made for pirfenidone in other SARD-ILD because of insufficient evidence. Pirfenidone currently has its strongest disease-specific rationale in RA-ILD. In TRAIL1, pirfenidone did not significantly reduce the composite endpoint of a 10% or greater decline in percent predicted FVC or death, but it slowed the decline in both absolute FVC and percent predicted FVC, with the clearest signal in patients with a UIP pattern [68]. As the trial was stopped early and underpowered, pirfenidone should be viewed as a selective option in fibrotic RA-ILD rather than as established standard therapy, but the study led to the specific ERS/EULAR conditional recommendation of pirfenidone in this population.

Nerandomilast is a phosphodiesterase 4B inhibitor with both immunosuppressive and anti-fibrotic properties. Although it does not feature in the SARD-ILD guidelines, as they were published before the finalised FIBRONEER RCT, it warrants mention as a recently approved therapy in PPF. The FIBRONEER-ILD study had similar inclusion to INBUILD. In a subgroup analysis of 325 patients with SARD-ILD comprising 36.3% with RA, 23.1% with SSc and 14.5% MCTD, nerandomilast reduced the annual rate of decline of FVC in patients with SARD-ILD with a −61.2 mL decline in the 9 mg nerandomilast group, − 64.9 mL in the 18 mg nerandomilast group and – 107.1 mL in the placebo group [69].

Escalation, Surveillance and Rapidly Progressive ILD

In patients who progress despite first-line treatment, escalation should be guided by prior therapy, the likely dominant mechanism of progression, and the balance between efficacy and toxicity. Overall, for patients showing signs of progression despite optimal first-line immunosuppressive therapy, the ACR/CHEST recommends switching to MMF over other treatment options if not already in use [4]. Depending on the disease subtype, escalation may involve switching to or adding rituximab, cyclophosphamide, tocilizumab, calcineurin inhibitors, JAK inhibitors, IVIG, or nintedanib. In both guideline frameworks, long-term glucocorticoids should generally be avoided, and escalation is usually driven by persistent progression rather than by routine sequential intensification. Notably, comparative head-to-head treatment data are scarce, limiting definitive sequencing recommendations.

In systemic sclerosis, rituximab is supported by indirect but clinically meaningful evidence: although the DESIRES trial was originally designed around skin outcomes, subsequent analyses suggested benefit on pulmonary function as well, supporting its use in progressive SSc-ILD [63, 70]. The drug appears as a second-line option conditional recommendation in all SARD-ILD in the ACR/CHEST guidelines. By contrast, in selected patients with limited ILD, preserved lung function, minimal symptoms, and no evidence of progression, immediate pharmacological treatment may not be necessary. However, this should be understood as structured surveillance rather than therapeutic inactivity, with serial pulmonary function testing, symptom review, and interval HRCT when clinically indicated. This approach is consistent with the ERS/EULAR guideline emphasis on risk stratification, particularly in patients with early SSc, anti-MDA5-associated IIM, extensive HRCT involvement, or objective physiologic decline [45].

Rapidly progressive ILD (RP-ILD) should be approached as a clinical emergency rather than as a routine chronic ILD phenotype. The ACR/CHEST guideline is particularly useful in this setting because it provides a pragmatic treatment framework recommending pulse intravenous methylprednisolone together with upfront double or triple therapy using agents such as rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, or JAK inhibitors, especially in suspected or confirmed anti-MDA5-associated disease. In this context, rapid disease control becomes the overriding therapeutic priority, and management is driven less by conventional outpatient sequencing and more by the need to prevent respiratory failure and death [4]. ERS/EULAR does not provide the same algorithmic detail for RP-ILD, but it does address rapidly progressive and severe disease particularly within IIM, where the risk is highest and close follow-up is most relevant [45].

Special Considerations

Treatment selection in SARD-ILD should be individualised according to the underlying rheumatic phenotype, risk of progression, extrapulmonary disease, and the low certainty of the supporting evidence. In practice, this means that the “best” ILD-directed drug is not always the best overall treatment for the patient, particularly when joint disease, skin disease, myositis, or other systemic features also require control [4, 45]. In RA-ILD, treatment selection should be guided by the need to control both lung disease and articular disease activity. This is not a minor practical issue. The ERS/EULAR guideline notes that uncontrolled articular disease and impaired FVC are associated with increased mortality, and that several therapies, including abatacept and JAK inhibitors, improved both respiratory outcomes and measures of rheumatoid activity [45]. Accordingly, in a patient with active RA-ILD and ongoing synovitis, a purely lung-directed strategy with MMF alone may be insufficient, and biologic therapy such as rituximab or abatacept may be preferable when joint control is also required. Similarly, methotrexate should not be viewed as an ILD treatment, but rather as a conventional RA disease-modifying agent whose role in patients with coexisting ILD should be judged in the context of overall rheumatoid disease control, rather than automatically excluded on the basis of lung involvement alone.

Morphological pattern should also be interpreted as a prognostic modifier rather than a disease-specific treatment algorithm, since UIP, NSIP, and organising pneumonia may each occur within RA-ILD, SSc-ILD, and IIM-ILD, and the same pattern does not necessarily imply the same therapeutic response across diseases. A UIP pattern has been associated with the worst prognosis, but, at the same time, a fibrotic or UIP pattern does not preclude benefit from immunosuppression in certain SARD subtypes [71]. The ERS/EULAR guideline, for instance, explicitly suggests pirfenidone in RA-ILD with UIP pattern, whereas the ACR/CHEST guideline more broadly cautions against routine upfront combination antifibrotic therapy in the absence of progression [45]. Disease-specific phenotype also matters in other SARD. Organising pneumonia, which is common in idiopathic inflammatory myopathies, often responds well to glucocorticoids and other immunosuppressive therapies, but is also found in other diseases, including RA, whereas LIP in Sjögren’s disease may be mild enough in selected patients to justify surveillance rather than immediate pharmacological treatment [72]. This helps explain why ERS/EULAR opted to treat some phenotypes separately even without robust evidence, rather than applying a single uniform treatment pathway across all SARD [45]. The role of non-pharmacological management has also not been fully addressed in the guidelines, but is acknowledged as of great importance and a future research priority by ERS/EULAR and as “additional integrative” interventions by ACR/CHEST, since every patient with SARD-ILD should be considered for lung transplant, oxygen therapy, rehabilitation, and palliative measures when appropriately indicated [4, 45].

Overall, the two guidelines are more similar than different in their therapeutic philosophy. Both place immunosuppression at the centre of treatment, both acknowledge that evidence quality is low outside SSc-ILD, and both reserve antifibrotic therapy mainly for selected strictly fibrotic or progressive fibrotic phenotypes rather than for routine upfront use. The main distinction is structural: ACR/CHEST is more prescriptive, with explicit recommendations for first-line treatment, progression, and rapidly progressive ILD, whereas ERS/EULAR is somewhat less hierarchical and more explicitly anchored to specific diseases and populations studied in clinical trials [4, 45]. For practical considerations, they should be interpreted as two complementary, rather than contradictory, approaches. A more detailed comparison of treatment approaches is presented in Table 5. The main differences in screening, monitoring, and treatment recommendations are summarised in Table 6.

Table 5.

Comparison of recommended treatment approaches in SARD-ILD between ERS/EULAR (2025) and ACR/CHEST (2023)

Diseases	2023 ACR/CHEST guidelines	2025 ERS/EULAR guidelines
Treatment hierarchy	Predominantly conditional recommendations, reflecting low/very-low certainty evidence (the only strong recommendation is against corticosteroids in SSc), grouped into practical first-line and progression pathways across SARD-ILD	Mix of strong and conditional recommendations, using disease-specific algorithms and Evidence-to-Decision framework. Greater emphasis on SARD subtype and progression risk
SSc-ILD	Conditionally recommends MMF, azathioprine, rituximab, cyclophosphamide, and nintedanib as first-line treatment options. Conditionally recommends tocilizumab in SSc-ILD (and MCTD-ILD with SSc phenotype). Strongly recommends against glucocorticoids as first-line therapy	Suggests MMF, rituximab, and cyclophosphamide. Recommends tocilizumab in early diffuse cutaneous SSc with inflammatory activity. Suggests nintedanib, alone or with MMF
RA-ILD	Conditionally recommends MMF, azathioprine, rituximab, and cyclophosphamide as treatment options. No consensus on first-line nintedanib. Conditionally recommends pirfenidone after progression despite first-line therapy	Suggests immunosuppressive treatment. Suggests pirfenidone in RA-ILD with UIP pattern
IIM-ILD	Conditionally recommends MMF, rituximab, cyclophosphamide, calcineurin inhibitors, and JAK inhibitors in relevant settings. For RP-ILD, recommends combination strategies	Recommends immunosuppressive treatment. Suggests combination therapy including glucocorticoids and immunosuppressants, particularly in severe disease
Other SARD-ILDs	Includes SjD-ILD and MCTD-ILD; most recommendations are conditional and extrapolated from limited evidence. Does not include SLE-ILD	Includes SjD-ILD, MCTD-ILD, and SLE-ILD. Suggests immunosuppressive treatment in other SARD-ILDs
Glucocorticoids	Conditionally recommends as first-line therapy in all non-SSc SARD-ILD. Strongly recommends against first-line use in SSc-ILD. Long-term use discouraged after progression	Used mainly as part of combination therapy in inflammatory phenotypes (especially IIM-ILD). Emphasizes tapering/minimization when possible
Nintedanib	Conditionally recommends nintedanib in SSc-ILD and after progression despite first-line therapy for all SARD-ILD. Conditionally recommends against upfront antifibrotic + MMF combination without progression	Suggests nintedanib in SSc-ILD and in SARD-ILD with progressive pulmonary fibrosis (PPF), including with background immunosuppression
Pirfenidone	Conditionally recommends against first-line use. Conditionally recommends in RA-ILD progression; against routine use in non-RA SARD-ILD progression	Suggests pirfenidone in RA-ILD with UIP pattern. No recommendation for non-RA SARD-ILD
Severe/rapidly worsening disease	Provides specific RP-ILD pathway, including pulse methylprednisolone and combination immunomodulatory therapy	Emphasizes early aggressive treatment in high-risk progressive phenotypes within disease-specific pathways

Key differences between 2023 ACR/CHEST and 2025 ERS/EULAR guidance on therapeutic strategies

ACR American College of Rheumatology, CHEST American College of Chest Physicians, CNI calcineurin inhibitor, CTD-ILD connective tissue disease-associated interstitial lung disease, CYC cyclophosphamide, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, IIM-ILD idiopathic inflammatory myopathy-associated interstitial lung disease, IV intravenous, IVIG intravenous immunoglobulin, JAKi Janus kinase inhibitor, MDA-5 melanoma differentiation-associated gene 5, MMF mycophenolate mofetil, PPF progressive pulmonary fibrosis, RA-ILD rheumatoid arthritis-associated interstitial lung disease, RCT randomised controlled trial, RP-ILD rapidly progressive interstitial lung disease, RTX rituximab, SARD systemic autoimmune rheumatic diseases, SSc-ILD systemic sclerosis-associated interstitial lung disease, UIP usual interstitial pneumonia

Table 6.

Comparison of SARD-ILD management strategies: ACR/CHEST (2023) and ERS/EULAR (2025)

	Disease	Screening	PFT monitoring	HRCT monitoring	Treatment
ACR/CHEST	SSc-ILD	Risk-based (HRCT + PFT)	Every 3–6 months, 6–12 months (if stable)	Based on clinical need	First-line: MMF, AZA, RTX, CYC, TCZ, nintedanib; GC strongly againsta Progression: MMF, RTX, CYC, nintedanib ± TCZ
	RA-ILD	Risk-based (HRCT + PFT)	Every 3–12 months less frequent if stable	Based on clinical need	First-line: GC, MMF, AZA, RTX, CYC; nintedanib: no consensus Progression: MMF, RTX, CYC, nintedanib ± TCZ; add pirfenidone
	IIM-ILD	Risk-based (HRCT + PFT)	Every 3–6 months, 6–12 months	Based on clinical need	First-line: GC, MMF, AZA, RTX, CYC, CNI, JAKi. Progression: MMF, RTX, CYC, nintedanib, CNI/JAKi.b
	SjD-ILD	Risk-based (HRCT + PFT)	Every 3–12 months, less frequent if stable	Based on clinical need	General SARD-ILD recommendationsc
	MCTD-ILD	Risk-based (HRCT + PFT)	Every 3–12 months, less frequent if stable	Based on clinical need	General SARD-ILD recommendationsc
	SLE-ILD	Not addressed	Not addressed	Not addressed	Not addressed
ERS/EULAR	SSc-ILD	Screen all (HRCT; do not replace with PFT)	Every 3–6 (early), 6–12 months (long-term)	Every 1–2 years (earlier if high risk)	First-line: TCZ d in selected early diffuse SSc; MMF, RTX, CYC, nintedanib. Progression/PPF: nintedanib ± MMF or combination immunosuppression
	RA-ILD	Risk-based (HRCT)	Every 3–6 months(early), 6–12 months (long term), (earlier if progression)	Every 1–2 years	First-line: conditionally suggests immunosuppressive treatment. Progression/PPF: nintedanib; pirfenidone if UIP patterne
	IIM-ILD	Risk-based (high-risk; HRCT recommended in most patients)	Every 3–6 → 6–12 months	3–6 months in high-risk → then annually(first 2 years)	First-line: immunosuppressive treatment. Progression/PPF: combination immunosuppression including GC; nintedanib if PPFf
	SjD-ILD	Risk-based screening	Every 3–6 → at least 6–12 months	Every 1–2 years	First-line: immunosuppressive treatment. Progression/PPF: nintedanib ± immunosuppression
	MCTD-ILD	Screen all patients	No specific recommendation	Every 1–2 years	First-line: immunosuppressive treatment. Progression/PPF: nintedanib ± immunosuppression
	SLE-ILD	No specific recommendation	No specific recommendation	No specific recommendation	First-line: immunosuppressive treatment. Progression/PPF: nintedanib ± immunosuppression

First-line refers to initial pharmacological treatment; progression/PPF refers to treatment after disease progression or in progressive pulmonary fibrosis

ACR American College of Rheumatology, AZA azathioprine, CHEST American College of Chest Physicians, CNI calcineurin inhibitor, CTD-ILD connective tissue disease-associated interstitial lung disease, CYC cyclophosphamide, ERS European Respiratory Society, EULAR European Alliance of Associations for Rheumatology, GC glucocorticoids, HRCT high-resolution computed tomography, IIM idiopathic inflammatory myopathy, ILD interstitial lung disease, JAKi Janus kinase inhibitor, MCTD mixed connective tissue disease, MMF mycophenolate mofetil, PFT pulmonary function test, PPF progressive pulmonary fibrosis, RA rheumatoid arthritis, RTX rituximab, SARD-ILD systemic autoimmune rheumatic diseases-associated interstitial lung disease, SjD Sjögren’s disease, SLE systemic lupus erythematosus, SSc systemic sclerosis, TCZ tocilizumab, UIP usual interstitial pneumonia

^aACR/CHEST recommendations are conditional unless otherwise stated. In SSc-ILD, glucocorticoids are strongly recommended against as first-line therapy and after progression

^b CNI and JAKi are specifically recommended as options for IIM-ILD

^cIn the ACR/CHEST treatment guideline, MMF, AZA, RTX and CYC are conditionally recommended as first-line treatment options for SARD-ILD overall. Glucocorticoids are conditionally recommended as first-line treatment for SARD-ILD other than SSc-ILD. Tocilizumab is additionally conditionally recommended as a first-line option for SSc-ILD and MCTD-ILD

^d TCZ is recommended for selected patients with SSc-ILD, particularly those with early diffuse cutaneous disease and inflammatory features

^e In RA-ILD, pirfenidone is suggested for patients with a UIP pattern, whereas nintedanib is suggested in the setting of progressive pulmonary fibrosis

^fIn IIM-ILD, combination immunosuppressive therapy including glucocorticoids is suggested, particularly in severe or progressive disease; nintedanib is considered when progressive pulmonary fibrosis is present

Multidisciplinary Care

Multidisciplinary care is fundamental to managing SARD-ILD. A multidisciplinary team (MDT) typically includes pulmonologists, rheumatologists, and thoracic radiologists, with expansion to pathologists when clinically indicated. Collaborative evaluation improves diagnostic precision, supports earlier recognition of progression and individualised treatment decisions.

Guideline recommendations differ in MDT expectations. The ERS/EULAR 2025 guidelines [45] advocate for routine structured MDT discussions at diagnosis and major decision points, defining pulmonologists, rheumatologists, and radiologists as the minimum core. In contrast, the 2023 ACR/CHEST guidelines [40] recommend rheumatology–pulmonology collaboration but acknowledge variability in multidisciplinary integration across clinical settings, thus, they appear more pragmatic and acknowledge global differences in MDT provision. This multidisciplinary input is particularly important when treatment priorities differ between organ systems. Patients with active arthritis, myositis, or systemic inflammation may require escalation of immunosuppression, whereas those with predominantly fibrotic or progressive pulmonary disease may require antifibrotic therapy or combination strategies. In such scenarios, MDT discussions are essential to determine whether immunosuppression, antifibrotic therapy, or a combination approach is most appropriate based on the relative contributions of inflammation and fibrosis. This includes careful consideration of the timing and sequencing of therapies, as well as balancing pulmonary benefits against extrapulmonary disease control, infection risk, drug toxicity, and patient preferences. MDT deliberation is particularly valuable when considering agents such as rituximab, cyclophosphamide, MMF, nintedanib, or combination regimens, where therapeutic goals may differ across organ domains and require nuanced, individualised decision-making.

Clinical Implications and Future Directions

Current guidelines provide a structured framework for the detection, monitoring, and treatment of SARD-ILD. They support earlier recognition of ILD, closer multidisciplinary collaboration, and more consistent follow-up of patients at risk of progression. However, important gaps remain in screening, monitoring, and treatment, particularly outside SSc-ILD.

For screening, the main challenge is to define which patients should undergo systematic evaluation. The ACR/CHEST guidelines support risk-based screening with HRCT and PFTs in patients at increased risk of ILD, whereas ERS/EULAR places greater emphasis on HRCT-based, disease-specific screening. However, validated risk prediction tools are still lacking, especially for RA, Sjögren’s disease, and less common SARD. Serum biomarkers may help refine risk-based screening strategies in the future. KL-6 is the most widely studied biomarker in SARD-ILD, and CA15-3 has shown promising diagnostic performance for HRCT-detected ILD in newly diagnosed patients with SARD. Recent RA-ILD data also suggest that peripheral biomarker signatures may improve ILD discrimination beyond clinical risk factors alone [73, 74]. However, biomarkers, genetic markers, quantitative HRCT, lung ultrasound, and artificial intelligence-based tools require prospective validation and standardised clinical pathways before routine use [75, 76].

For monitoring, better evidence is needed to define optimal follow-up intervals and clear thresholds for progression across SARD-ILD subtypes. This is particularly important in RA-ILD and IIM-ILD, where disease behaviour can be variable and sometimes rapidly progressive [77]. Serial FVC and DLCO remain central to follow-up, while HRCT, 6MWT and patient-reported outcomes provide complementary information. Newer tools such as quantitative HRCT, home spirometry, and wearable oximetry may improve early detection of progression, but their role in routine care remains uncertain [78].

Immunosuppressive therapy remains the main treatment approach for many SARD-ILD, while antifibrotic therapy is increasingly considered in patients with PPF. However, high-quality randomised trials are still limited, especially in SjD-ILD, MCTD-ILD, SLE-ILD and non-SSc progressive SARD-ILD. Further studies are needed to define the best timing, duration, sequencing, and combination of immunosuppressive and antifibrotic therapies. Until stronger evidence is available, treatment decisions should remain individualised and based on multidisciplinary assessment, disease behaviour, comorbidities, and patient preferences.

In clinical practice, the ACR/CHEST and ERS/EULAR guidelines may be most useful for different but overlapping decisions. The ERS/EULAR guideline provides a more disease-specific framework for screening and monitoring, particularly in SSc and IIM, where ILD may be present early in the disease course and early HRCT-based detection is clinically important. In contrast, the ACR/CHEST guideline offers a more pragmatic treatment framework across the broader SARD-ILD spectrum, including first-line treatment, progression despite initial therapy and rapidly progressive ILD. Thus, clinicians may preferentially refer to ERS/EULAR when deciding whom to screen and how to monitor patients within specific SARD subtypes, whereas ACR/CHEST may be especially helpful when considering therapeutic sequencing and escalation. However, these recommendations should not be viewed as competing algorithms, as both require careful individualisation according to disease subtype, ILD severity, progression risk, extrapulmonary involvement, and multidisciplinary assessment.

Author Contributions

Conceptualization: Gulfem Ozduygu and Nazia Chaudhuri. Literature search and interpretation: Gulfem Ozduygu, Punchalee Kaenmuang, Alexandra B. F. Guedes, Alexandre F. Amaral, and Nazia Chaudhuri. Visualization: Gulfem Ozduygu, Punchalee Kaenmuang, Alexandra B. F. Guedes, and Alexandre F. Amaral. Writing – original draft preparation: Gulfem Ozduygu, Punchalee Kaenmuang, Alexandra B. F. Guedes, and Alexandre F. Amaral. Writing – review and editing: Gulfem Ozduygu, Punchalee Kaenmuang, Alexandra B. F. Guedes, Alexandre F. Amaral, and Nazia Chaudhuri. Supervision: Nazia Chaudhuri. All authors meet the ICMJE authorship criteria, have reviewed and approved the final manuscript, and agree to be accountable for all aspects of the work.

Funding

No funding or sponsorship was received for the preparation or publication of this article.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

Conflict of Interest

Nazia Chaudhuri is an Editorial Board member of Advances in Therapy. Nazia Chaudhuri was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Gulfem Ozduygu, Punchalee Kaenmuang, Alexandra B. F. Guedes, and Alexandre F. Amaral have nothing to disclose.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Representative high-resolution computed tomography images included in this article were obtained from the authors’ archive, were fully anonymised prior to inclusion, and contain no identifiable patient information. Written informed consent was obtained from the patients for publication of the anonymised radiological images. The signed consent forms can be provided upon request.