New Insights in Lung Involvement Secondary to Autoimmune Diseases

Dear Colleagues,

Respiratory failure is among the main causes of mortality in many Systemic Autoimmune Diseases (SAD), including Rheumatoid Arthritis (RA), Vasculitides and Connective Tissue Diseases.

Lung involvement in the context of SAD typically results in Interstitial Lung Disease (ILD), however obstructive conditions due to small airways involvement are not uncommon.

ILD may represent the first manifestation of SAD, dominating the clinical picture compared to more nuanced non-respiratory signs and symptoms. In these cases, proper classification of the underlying SAD becomes a true challenge and may be subjected to variations during follow-up (e.g., Interstitial Pneumonia with autoimmune features progressing to a specific SAD).

Diagnosis and management of SAD-related lung involvement often requires a multidisciplinary approach involving pulmonologists and rheumatologists, which is not always feasible in routine clinical practice.

This Special Issue aims to collect the most recent findings regarding diagnosis and management of patients affected by SAD with lung involvement. We believe that this focused approach will significantly contribute to current knowledge on this topic. Another purpose of this Special Issue is to stimulate the scientific debate and a closer collaboration between pulmonologists and rheumatologists aimed at a mutual sharing of competences.

In this Special Issue, original research articles, brief reports of original data and reviews are welcome. Research areas may include (but should not be limited to) the following:

• Diagnostic approach to SAD patients with lung involvement;
• Imaging techniques for assessment of SAD-related lung involvement, including application of artificial intelligence to HRCT analysis;
• Risk factors for lung involvement in SAD patients;
• Prognosis of SAD with lung involvement;
• Pathogenic mechanisms underlying lung involvement in SAD;
• Multidisciplinary evaluation of SAD patients with lung involvement;
• Therapeutic strategies for SAD-related lung involvement.

We look forward to receiving your contributions.

Dr. Gianluca Sambataro
Dr. Giovanni Zanframundo
Dr. Domenico Sambataro
Guest Editors

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• interstitial lung disease
• interstitial pneumonia with autoimmune features
• antisynthetase syndrome
• rheumatoid arthritis
• Sjogren’s syndrome
• systemic sclerosis
• idiopathic inflammatory myopathy

Title: Interstitial Lung Disease phenotypes and predictive risk factors in primary Sjögren’s syndrome
Authors: Gaetano La Rocca1*, Francesco Ferro1, Gianluca Sambataro2,3, Elena Elefante1, Inmaculada Concepción Navarro1, Chiara Romei4, Marta Mosca1, and Chiara Baldini 1
Affiliation: 1 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy; [email protected] (F.F.); [email protected] (E.E.); [email protected] (G.F.); [email protected] (I.C.N.); [email protected] (M.M.); [email protected] (C.B.) 2 Rheumatology Unit, Department of Clinical and Experimental Medicine, AOE Cannizzaro, University of Ca-tania, Via Messina 829, 95126, Catania, Italy; [email protected] 3 Artroreuma S.R.L., Rheumatology Outpatient Clinic Associated with the National Health System, Corso S. Vito 53, 95030, Catania, Italy 4 Radiodiagnostic Unit 2, Department of Diagnostic Imaging, University of Pisa, Via Paradisa 2, 56124 Pisa, It-aly; [email protected]
Abstract: Background/Objectives: Interstitial Lung Disease (ILD) prevalence and risk factors for its devel-opment in patients with primary Sjögren’s syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-ILD phenotypes. Aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To char-acterize different pSS-ILD phenotypes. Methods: clinical, laboratory and imaging data of pSS pa-tients attending our center from January 2016 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT for all patients. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F=6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients presented more often pSS-related hematologic abnormalities (p=.012), cutaneous involvement (p=.027), inflammatory arthralgias (p=.026), C4-hypocomplementemia (p=.012) and positive RF (p=.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p=.008) and presented more severe fibrosis on HRCT (p=.008). On the univariate analysis higher ESSDAI (p=.011), Raynaud’s phenomenon (p=.009), anti-Ro52 (p=.031), hypergammaglobulinemia (p=.011), RF (p=.038) and C4-hypocomplementemia (p=.044) at baseline were associated to ILD development during fol-low-up. On the multivariate analysis higher ESSDAI (p=.05) and Raynaud’s phenomenon (p=.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a rela-tively common and clinically heterogenous manifestation of pSS. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD in these cases.