Scleroderma or systemic sclerosis (SSc) is a rare systemic autoimmune disease that is characterized by vasculopathy, immune dysregulation, and fibroblast dysfunction, which can result in fibrosis in various organ systems.1 SSc is broadly categorized into two main subsets: diffuse cutaneous SSc and limited cutaneous SSc. Diffuse cutaneous SSc is characterized by extensive fibrotic disease, with skin thickening proximal to the elbows, knees, and neck, as well as a high prevalence of interstitial lung disease (ILD). Limited cutaneous SSc manifests largely as vascular disease, resulting in Raynaud phenomenon, pulmonary arterial hypertension, and skin sclerosis confined to the distal extremities.
American Thoracic Society clinical practice guidelines define scleroderma-related ILD (SSc-ILD) as the presence of both SSc and ILD.2 SSc diagnosis should follow 2013 American College of Rheumatology and European Alliance of Associations for Rheumatology guidelines. ILD diagnosis is defined as the radiologic presence of reticulation, traction bronchiectasis, traction bronchiolectasis, honeycomb cysts, ground-glass opacities or air space consolidation, other interstitial lung abnormalities, or any of the recognized patterns of interstitial pneumonias reported in the context of SSc. Disease progression is marked by worsening dyspnea or cough, decline in forced vital capacity (FVC) or diffusing capacity of carbon monoxide (DLCO), and worsening in the extent or severity of ILD features on radiologic testing.
Lung fibrosis is common among those with SSc, although exact prevalence is difficult to determine due to the rarity of the disease and regional differences in diagnostic criteria for both SSc and ILD. A population-based study in Norway taking place from 2000-2012 found that of the 815 residents with diagnosed SSc, 50% had ILD and 46% had declining pulmonary function consistent with developing ILD.3
Disease Progression and Prognosis
A 2022 study of 89 patients with SSc-ILD explored the effect of their condition on quality of life using the King’s Brief Interstitial Lung Disease (KBILD, scores from 0-100, where higher scores indicate better health status) quality of life assessment questionnaire.13 The average score was 58.4, with only 9.4% of patients scoring ≥75. When broken out into the three parts of the KBILD questionnaire, average scores were 63.8 for psychology, 48.5 for breathlessness and activities, and 75.2 for chest symptoms. When ranking symptoms on a five-point scale, patients reported that fatigue was their most severe symptom with a mean score of 4.4.
SSc-ILD has a variable course; some patients have stable lung involvement whereas others have highly progressive lung involvement. A 2021 study using the European Alliance of Associations for Rheumatology Scleroderma Trial Research (EUSTAR) database showed that among patients with SSc-ILD (n=826), 33% of patients had stable lung function during 5 years of follow-up, 58% had a pattern of slow lung function decline with more periods of stability or improvement than decline, and 8% had a rapid continuous decline.14 There was no significant differences in mortality between patients with significant ILD progression (12%), moderate progression (15%), or stable ILD (9%).
References
- Varga J. Systemic Sclerosis (Scleroderma) and Related Disorders. In: Jameson J, Fauci A, Kasper D, Hauser S, Longo D, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 20 ed. McGraw-Hill Education; 2018.
- Raghu G, Montesi SB, Silver RM, et al. Treatment of Systemic Sclerosis-associated Interstitial Lung Disease: Evidence-based Recommendations. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. Sep 29 2023;doi:10.1164/rccm.202306-1113ST
- Hoffmann-Vold AM, Fretheim H, Halse AK, et al. Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort. Am J Respir Crit Care Med. Nov 15 2019;200(10):1258-1266. doi:10.1164/rccm.201903-0486OC
- Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. Jul 2007;66(7):940-4. doi:10.1136/ard.2006.066068
- Khanna D, Nagaraja V, Tseng CH, et al. Predictors of lung function decline in scleroderma-related interstitial lung disease based on high-resolution computed tomography: implications for cohort enrichment in systemic sclerosis-associated interstitial lung disease trials. Arthritis Res Ther. Dec 23 2015;17:372. doi:10.1186/s13075-015-0872-2
- Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. Oct 2010;69(10):1809-15. doi:10.1136/ard.2009.114264
- Walker UA, Tyndall A, Czirják L, et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis. Jun 2007;66(6):754-63. doi:10.1136/ard.2006.062901
- Gilson M, Zerkak D, Wipff J, et al. Prognostic factors for lung function in systemic sclerosis: prospective study of 105 cases. European Respiratory Journal. 2010;35(1):112-117. doi:10.1183/09031936.00060209
- Wangkaew S, Euathrongchit J, Wattanawittawas P, Kasitanon N, Louthrenoo W. Incidence and predictors of interstitial lung disease (ILD) in Thai patients with early systemic sclerosis: Inception cohort study. Mod Rheumatol. Jul 2016;26(4):588-93. doi:10.3109/14397595.2015.1115455
- McNearney TA, Reveille JD, Fischbach M, et al. Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors. Arthritis Rheum. Mar 15 2007;57(2):318-26. doi:10.1002/art.22532
- Rahaghi FF, Hsu VM, Kaner RJ, et al. Expert consensus on the management of systemic sclerosis-associated interstitial lung disease. Respir Res. Jan 9 2023;24(1):6. doi:10.1186/s12931-022-02292-3
- van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. Nov 2013;72(11):1747-55. doi:10.1136/annrheumdis-2013-204424
- Allanore Y, Constans J, Godard D, et al. Quality of life in SSc-ILD patients: Understanding the impact of the ILD and the needs of the SSc-ILD patients and their need for caregivers in France. J Scleroderma Relat Disord. Feb 2022;7(1):49-56. doi:10.1177/23971983211013979
- Hoffmann-Vold AM, Allanore Y, Alves M, et al. Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis. Feb 2021;80(2):219-227. doi:10.1136/annrheumdis-2020-217455
- Ioannidis JP, Vlachoyiannopoulos PG, Haidich AB, et al. Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med. Jan 2005;118(1):2-10. doi:10.1016/j.amjmed.2004.04.031
