High-Resolution CT Findings in Interstitial Lung Disease Associated with Connective Tissue Diseases: Differentiating Patterns for Clinical Practice-A Systematic Review with Meta-Analysis

Abstract

Objectives: Connective tissue diseases (CTDs) include a diverse group of systemic autoimmune conditions, among which interstitial lung disease (ILD) is acknowledged as a major determinant of prognosis. High-resolution computed tomography (HRCT) is the gold standard for ILD assessment. The distribution of HRCT patterns across CTDs remain incompletely defined. The objective of this systematic review is to synthesize available evidence regarding the prevalence of specific radiological patterns within CTD-ILDs and to assess whether specific patterns occur at different frequencies among individual CTDs. Methods: The inclusion criteria encompassed original human studies published in English between 2015 and 2024, involving adult participants (≥18 years) with CTD-ILDs assessed primarily by HRCT and designed as retrospective, prospective, or cross-sectional trials with extractable data. We systematically searched PubMed, Scopus, and Web of Science (January 2025). Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies, and the JBI Critical Appraisal Checklist for cross-sectional studies. Data were extracted and categorized by HRCT pattern for each CTD, and then summarized descriptively and statistically. Results: We analyzed 23 studies published between 2015 and 2024, which included 2020 patients with CTD-ILDs. The analysis revealed non-specific interstitial pneumonia (NSIP) as the most prevalent pattern overall (36.5%), followed by definite usual interstitial pneumonia (UIP) (24.8%), organizing pneumonia (OP) (9.8%) and lymphoid interstitial pneumonia (LIP) (1.25%). HRCT distribution varied by CTD: NSIP predominated in systemic sclerosis, idiopathic inflammatory myopathies, and mixed connective tissue disease; UIP was most frequent in rheumatoid arthritis; LIP was more common in Sjögren's syndrome. While global differences were statistically significant, pairwise comparisons often lacked significance, likely due to sample size constraints. Discussion: Limitations include varying risk of bias across study designs, heterogeneity in HRCT reporting, small sample sizes, and inconsistent follow-up, which may reduce precision and generalizability. In addition to the quantitative synthesis, this review offers a detailed description of each radiologic pattern mentioned above, illustrated by representative examples to support the recognition in clinical settings. Furthermore, it includes a brief overview of the major CTDs associated with ILD, summarizing their epidemiological data, risk factors for ILD and clinical presentation and diagnostic recommendations. Conclusions: NSIP emerged as the most common HRCT pattern across CTD-ILDs, with UIP predominating in RA. Although inter-disease differences were observed, statistical significance was limited, likely reflecting sample size constraints. These findings emphasize the diagnostic and prognostic relevance of HRCT pattern recognition and highlight the need for larger, standardized studies.

Keywords: autoimmune lung involvement; connective tissue diseases; diffuse parenchymal lung disease; high-resolution computed tomography; imaging patterns; interstitial lung disease; radiologic features; rheumatologic lung disease.

Figure 1

PRISMA 2020 flow diagram—literature review of studies published between 2015 and 2024 [7].

Figure 2

Proportion of HRCT patterns among CTD-ILD patients.

Figure 3

Distribution of ILD patterns across CTDs.

Figure 4

Comparative distribution of ILD patterns (UIP, NSIP, OP, and Other) across CTDs: box-and-whisker analysis. Orange circle: outlier (value beyond 1.5 × the interquartile range), red square: extreme outlier (value beyond 3 × the interquartile range).

Figure 5

Impact of HRCT Acquisition Parameters on the Assessment of ILD: Comparison of Slice Thickness and Respiratory Phase. We present the case of a 71-year-old man who was evaluated in our clinic for a three-month history of dry cough and exertional dyspnea on moderate effort. He had previously undergone two imaging assessments in different centers, performed eight days apart. The first scan (A) was acquired in expiration, with a slice thickness of 2 mm. The second scan had a slice thickness of 0.6 mm and included images captured in both expiration (B) and inspiration (C). Findings include diffuse interstitial lung abnormalities with reticulation, ground-glass opacities, and traction bronchiectasis. When comparing the first two images (both acquired in expiration), the second image appears to have more defined lung structures. The 2 mm scan has a slightly more blurred appearance, reducing the visibility of small airway or parenchymal abnormalities. Furthermore, on the third image (acquired in inspiration), the lungs are more inflated, allowing better differentiation of true ground-glass opacities versus normal lung attenuation. In addition, airway structures appear less crowded, making it easier to assess traction bronchiectasis and the reticular pattern.

Figure 6

Longitudinal HRCT Changes of a UIP Pattern in a Patient With IPF (2018–2021). 2018: The baseline HRCT shows subpleural and basal predominant reticulation with early honeycombing and traction bronchiectasis, consistent with UIP. Ground-glass opacities are minimal (red arrows). 2019: There is a slight increase in reticular opacities and honeycombing, with more pronounced architectural distortion, suggesting disease progression (red arrows). 2020: Further fibrotic progression is evident, with an increase in honeycombing and traction bronchiectasis. The lung volume appears slightly reduced (red arrows). 2021: The final HRCT shows extensive fibrosis with coalescent honeycombing, more severe traction bronchiectasis and significant volume loss, indicative of advanced disease. Ground-glass opacities remain minimal, supporting a fibrotic rather than an inflammatory process (red arrows).

Figure 7

Evolution From Probable UIP to Definite UIP on HRCT in a Patient with IPF over Seven Years (2018–2025). Serial HRCT scans from 2018, 2022, and 2025 show progressive fibrotic changes consistent with idiopathic pulmonary fibrosis. The 2018 scan demonstrates a probable UIP pattern with subpleural, basal reticulations and traction bronchiectasis, but no definitive honeycombing (red arrow). By 2022, early honeycombing appears alongside increased fibrosis (red arrow). In 2025, there is extensive subpleural honeycombing, architectural distortion, and traction bronchiectasis, meeting criteria for a typical UIP pattern (red arrow). This evolution illustrates radiologic progression from a probable to a typical UIP pattern over time.

Figure 8

Multiplanar HRCT Evaluation in a 43-Year-Old Patient with Systemic Sclerosis. The axial slice (A) demonstrates bilateral, predominantly peripheral and basal-predominant reticular opacities with associated traction bronchiectasis (red arrow). There is no evident honeycombing or significant ground-glass opacity. These features are consistent with a fibrotic NSIP pattern, which is the most common form of ILD in systemic sclerosis. In the coronal view (B), the upper lobes appear relatively spared, supporting the diagnosis of an NSIP pattern (first red arrow). Traction bronchiectasis is also evident (second red arrow). The sagittal section (C) illustrates vertical extent and subpleural fibrosis with traction bronchiectasis, most prominent in the posterior basal segments. Also, there appears to be relative sparing of the immediate subpleural region (red arrows).

Figure 9

Radiologic Evolution of OP Under Corticosteroid Therapy. This case illustrates the radiological evolution of a 60-year-old woman over a six-month period, from April 2019 (top row) to October 2019 (bottom row). Initial scans reveal bilateral, asymmetric consolidations in peripheral and peribronchovascular regions. There are several focal areas where rounded regions of ground-glass opacities are surrounded by a rim of consolidation, creating the characteristic atoll appearance (red arrow), suggesting the OP diagnosis. In contrast, the follow-up images from October 2019 demonstrate a marked radiologic improvement, with near-complete resolution of the previously noted consolidations and ground-glass opacities, indicating a favorable response to corticosteroid therapy, additionally supporting the diagnosis of OP.

Figure 10

HRCT Features Suggestive of Lymphocytic Interstitial Pneumonia in a Patient with Suspected Autoimmune Disease. Axial (A,B) and coronal (C) views show multiple thin-walled cysts with peribronchovascular and subpleural distribution, predominantly in the lower lobes (red arrows). Patchy areas of ground-glass opacity are seen throughout both lungs, along with ill-defined centrilobular and subpleural nodules. Subtle peribronchovascular interstitial thickening is also noted. This constellation of findings—diffuse ground-glass opacities, cystic change, nodularity, and perilymphatic distribution—is highly suggestive of LIP, particularly in the clinical context of autoimmune disease such as Sjögren’s syndrome.

Figure 11

Serial HRCT Scans in a 53-Year-Old Patient with Systemic Sclerosis and ILD with a NSIP Pattern (2016–2025). Axial HRCT images acquired in 2016 (top row) and 2025 (bottom row) demonstrate radiological progression of fibrotic NSIP in a patient with systemic sclerosis. In 2016, the scans reveal bilateral, symmetric reticular opacities with peripheral and basal predominance, mild traction bronchiectasis, and relative subpleural sparing—features consistent with fibrotic NSIP. Nine years later, the 2025 images show a marked increase in reticulation and traction bronchiectasis (red arrows). There is visible lower lobe volume loss and architectural distortion, indicating progression of fibrotic remodeling. These findings reflect a worsening fibrotic phenotype over time, emphasizing the chronic and progressive nature of SSc-associated ILD. Mild to moderate dilatation of the esophagus is visible, more prominently in the 2025 images, consistent with progressive esophageal involvement typical of systemic sclerosis. The presence of intraluminal gas and increased luminal diameter suggests dysmotility, which may contribute to chronic aspiration and exacerbate pulmonary disease progression in SSc.

Figure 12

HRCT Scans in a 35-Year-Old Patient with Rheumatoid Arthritis and ILD with an UIP Pattern. Image (A) demonstrates the “upper lobe sign,” characterized by predominant fibrotic involvement of the anterior segments of the upper lobes (red arrows). Image (B) shows “exuberant honeycombing,” with extensive, clustered cystic airspaces comprising more than 70% of the fibrotic regions (red arrows). Coronal reconstructions (Images C,D) reveal the “straight edge sign,” particularly evident in Image D with the red demarcation line, indicating an abrupt interface between normal and fibrotic lung tissue, forming a well-defined linear boundary.

Figure 13

HRCT (2019) Demonstrating a Fibrotic NSIP Pattern in a Patient with Primary Sjögren’s Syndrome. A 49-year-old female with a 30 pack-year smoking history presented in February 2019 with progressive exertional dyspnea (mMRC grade 3) and significant resting hypoxemia (SpO₂ 80% on room air). Serologic evaluation revealed positive anti-SSA (Ro) and anti-SSB (La) antibodies, accompanied by clinical manifestations of xerophthalmia and xerostomia, establishing the diagnosis of primary Sjögren’s syndrome. The axial HRCT images from 2019 demonstrate the characteristic radiological pattern of fibrotic NSIP. The images show bilateral, symmetric reticular opacities and ground-glass changes predominantly in the lower lung zones. There is clear subpleural sparing (B), visible as a thin rim of relatively preserved lung immediately beneath the pleura, which is a distinguishing feature of NSIP (red arrow). Architectural distortion and lower lobe volume loss are present, but there is no evidence of honeycombing. In addition to these findings, there is clear evidence of traction bronchiolectasis. This is seen as irregular, dilated bronchioles within areas of fibrotic lung parenchyma, reflecting traction on the small airways (A,C,D–red arrows).

Figure 14

Radiological Evolution and Clinical Correlation in a Case of Dermatomyositis and Antisynthetase Syndrome-Associated ILD. A 67-year-old male underwent serial chest CT scans between November 2022 and June 2023, demonstrating progressive ILD later linked to DM with antisynthetase syndrome. In November 2022, the patient was diagnosed with SARS-CoV-2 infection. At that time, he exhibited no signs of myositis and was not further evaluated. HRCT from November 2022 revealed an OP pattern, characterized by multifocal consolidations and the presence of the “atoll sign” (reversed halo sign) (red arrow), consistent with post-viral or inflammatory changes. A follow-up scan in December 2022 (non-HRCT, 5 mm slices) showed partial resolution post-steroid therapy, though detailed interstitial evaluation was limited due to suboptimal image resolution. By June 2023, the patient developed progressive dyspnea, proximal muscle weakness and myalgia. He was subsequently diagnosed with dermatomyositis and antisynthetase syndrome, confirmed by positive anti-Jo-1 and anti-Ro-52 antibodies. HRCT at this stage revealed a NSIP pattern with bilateral, symmetric ground-glass opacities and reticulations, indicating a chronic fibrosing ILD process. These images demonstrate a radiological transition from an OP pattern to fibrotic NSIP over approximately seven months, correlating with the clinical onset of inflammatory myopathy, highlighting the importance of longitudinal imaging and consideration of autoimmune etiologies.