The Treatment of Lung Involvement in Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) patients are often affected by interstitial lung disease (ILD) and, although there have been recent treatment advances, it remains the leading cause of death among SSc, with a 10-year mortality up to 40%. African Americans and subjects with diffuse cutaneous SSc or anti-topoisomerase 1 antibodies are most commonly affected. Currently, early ILD diagnosis can be made, and it is pivotal to improve the prognosis. The diagnostic mainstay test for SSc-ILD is high-resolution computed tomography for the morphology and pulmonary function tests for the functional aspects. Treatment planning and intensity are guided by the disease severity and risk of progression. Traditionally, therapy has depended on combinations of immunosuppressants, particularly cyclophosphamide and mycophenolate mofetil, which can be supplemented by targeted biological and antifibrotic therapies. Benefits have been observed in trials on hematopoietic autologous stem cell transplantation for patients with progressive SSc, whilst lung transplantation is reserved for refractory SSc-ILD cases. Herein, recent advances in SSc-ILD treatment will be explored.

Evaluation of Correlations between Genetic Variants and High-Resolution Computed Tomography Patterns in Idiopathic Pulmonary Fibrosis

“…Prompt diagnosis of IPF is a must so as to allow for appropriate care and support with the administration of anti-fibrotic therapy and evaluation for lung transplantation [ 1 , 2 , 3 ]. Accurate diagnosis of IPF is of vital importance, as other forms of ILD have similar clinical presentations to IPF but necessitate different treatment strategies [ 4 , 5 , 6 , 7 , 8 ].…”

The Relationship between Pulmonary Damage and Peripheral Vascular Manifestations in Systemic Sclerosis Patients

“…This is due to the paucity of high-quality, randomized, controlled trials that specifically target SSc-ILD. Moreover, historically, studies have favored cyclophosphamide (CYC) for SSc-ILD treatment, as also suggested in the most recent European League against Rheumatism (EULAR) recommendations [ 2 , 49 ]. Supportive data have shown that nintedanib, a multi-tyrosine kinase inhibitor, and tocilizumab (TCZ) significantly inhibit the progressive functional decline [ 2 , 49 ].…”

“…Moreover, historically, studies have favored cyclophosphamide (CYC) for SSc-ILD treatment, as also suggested in the most recent European League against Rheumatism (EULAR) recommendations [ 2 , 49 ]. Supportive data have shown that nintedanib, a multi-tyrosine kinase inhibitor, and tocilizumab (TCZ) significantly inhibit the progressive functional decline [ 2 , 49 ]. Current innovative proposals have also recently been made on the basis of clinical and preclinical evidence for rituximab (RTX) and pirfenidone (PIRF), as well as hematopoietic stem cell and lung transplantation [ 2 , 49 ].…”

“…Supportive data have shown that nintedanib, a multi-tyrosine kinase inhibitor, and tocilizumab (TCZ) significantly inhibit the progressive functional decline [ 2 , 49 ]. Current innovative proposals have also recently been made on the basis of clinical and preclinical evidence for rituximab (RTX) and pirfenidone (PIRF), as well as hematopoietic stem cell and lung transplantation [ 2 , 49 ]. However, the safety and efficacy of emerging experimental therapies for SSc-ILD do require further investigation.…”

“…Other findings were that high-resolution computed tomography (HRCT) evidenced interstitial abnormalities in as many as 90% of patients, and 40–75% had changes in pulmonary function tests (PFT) [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ].…”