Band 5, Heft 3

Interstitial lung disease (ILD) is a frequent important complication of systemic sclerosis (SSc). Factors relevant to aetiopathogenesis of SSc are also central to SSc-ILD. Severity of SSc-ILD is variable but it has a major impact on morbidity and mortality. Factors determining SSc-ILD susceptibility reflect the genetic architecture of SSc and are increasingly being defined. There are aspects linked to immunogenomics and non-immunological genetic factors that may be less conserved and underlie some of the geographical and racial diversity of SSc. These associations may also underlie important links between autoantibody subgroups and patient level risk of SSc-ILD. Examination of blood and tissue samples and observational clinical research together with integrated analysis of in vitro and in vivo preclinical models have elucidated pathogenic mechanisms of SSc-ILD. These have confirmed the potential importance of immune mechanisms in the innate and adaptive immune systemic as well as a significant role for profibrotic pathways especially transforming growth factor beta (TGFbeta) and its regulators and downstream mediators. Recent analysis of clinical trial cohorts as well as integrated and multilevel high dimensional analysis of bio-samples has shed further light on SSc-ILD. This is likely to underpin future advances in stratified and precision medicine for treatment of SSc.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI [fibroblast activation protein inhibitor]) are novel radionuclides used in the selective positron emission tomography/computed tomography (PET/CT) detection of profibrotic fibroblasts, a key player in fibrotic tissue remodeling. Application of 68Ga-FAPI in different target organs undergoing fibrosis, such as lung and heart, highlights its efficacy in detecting ongoing fibrotic processes, since FAPI tracer uptake has been correlated with clinical disease progression markers in SSc-ILD. This feature could enable physicians to detect subclinical fibrotic activity and tailor an individualised therapy plan on a case by case basis. The use of 68Ga-FAPI in ILD and other fibrotic conditions may emerge as a novel tool in future clinical practice for both activity monitoring and treatment optimisation. Other tracers tested in ILD of different etiologies have shown promising results and may in future also be considered for potential application in SSc-ILD.

Systemic sclerosis (SSc) or scleroderma is an autoimmune disease characterized by immune dysregulation which leads to progressive fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is present in approximately 65% of patients with SSc and it accounts for approximately 40% of all SSc deaths. Risk factors associated with the development of systemic sclerosis related interstitial lung disease (SSc-ILD) include male sex, African heritage, high modified Rodnan skin score (mRSS), presence of anti-Scl-70/Topoisomerase I antibodies, and nucleolar pattern on antinuclear antibody (ANA). The primary tool to diagnose ILD in patients with SSc is high-resolution computed tomography (HRCT). Full pulmonary function tests (PFTs) with diffusing capacity of the lungs for carbon monoxide (DLco) and ambulatory desaturation testing should be obtained following the diagnosis of SSc-ILD for disease monitoring. The purpose of this review is to provide an updated guide for the management of SSc-ILD. Our proposed first line treatment for SSc-ILD is immunosuppressive therapy such as mycophenolate mofetil, tocilizumab, and rituximab which are discussed in depth, and we present the evidence-based data that has justified the use of these pharmacotherapies. Other immunosuppressive treatments are also reviewed, and we discuss the role of antifibrotic therapy. Finally, we dive into other avenues of treatments such as chimeric antigen receptor (CAR)-T cell therapy and hematopoietic stem cell transplant.

Early diagnosis of interstitial lung disease (ILD) and pulmonary hypertension (PH) is crucial in systemic sclerosis (SSc) for both management and treatment. However, diagnosing SSc-ILD can be challenging because symptoms of lung involvement are often non-specific at the early stages of disease. High-resolution computed tomography (HRCT) of the chest is recognized as the most accurate imaging modality for baseline and follow-up evaluation of SSc-ILD. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern, with peripheral ground-glass opacities and extensive traction bronchiectasis. Less common HRCT manifestations include usual interstitial pneumonia (UIP) pattern, followed by diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH) and organizing pneumonia (OP). The extent of disease on HRCT is known to relate with prognosis and serial assessments can be helpful in monitoring disease progression or treatment response. We discuss the main chest computed tomography (CT) manifestations of SSc, highlighting the role of imaging at both baseline and follow-up evaluations.