PATHOGENESIS, DIAGNOSIS, AND TREATMENT OF SYSTEMIC SCLEROSIS – AN INTEGRATIVE REVIEW OF THE CURRENT APPROACHES
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6270Keywords:
Systemic Sclerosis, Fibrosis, Vasculopathy, Autoantibodies, ImmunosuppressantsAbstract
Systemic sclerosis is a rare autoimmune connective tissue disorder marked by immunological dysregulation, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting in considerable morbidity and mortality. The disease results from a complex interaction between genetic susceptibility, epigenetic modifications, environmental triggers, endothelial dysfunction, and aberrant immune responses. These mechanisms promote persistent inflammation, stimulation of fibroblasts and abundant extracellular matrix deposition, eventually causing irreversible tissue fibrosis and organ dysfunction. The diagnosis is based on clinical manifestations, supported by specific antibodies detection, capillaroscopy, and appropriate functional and imaging tests. To facilitate diagnosis, the American College of Rheumatology/European League Against Rheumatism issued guidelines in 2013, enabling earlier diagnosis and more accurate prognostic assessment. Although no curative therapy is currently available, treatment has advanced considerably and focuses on suppressing disease activity, slowing fibrosis, and preventing organ complications. Current therapeutic strategies include immunosuppressive agents, biologic therapies, antifibrotic drugs, and targeted vasodilator treatments tailored to individual organ involvement. Emerging approaches, such as JAK-STAT pathway inhibitors, CAR-T cell therapy, and stem cell transplantation, may further improve long-term outcomes in selected patients. Despite substantial progress in understanding disease mechanisms and expanding therapeutic options, systemic sclerosis remains a clinically heterogeneous disorder requiring early diagnosis, multidisciplinary management, and individualized treatment to optimize survival and quality of life.
References
Good, S. D., Lee, J. Y., Johnson, R. E., & Volkmann, E. R. (2025). A scoping review of the epidemiology of systemic sclerosis and its organ manifestations: 2018–2024. Current Opinion in Rheumatology, 37(2), 103–112. https://doi.org/10.1097/BOR.0000000000001063
Bairkdar, M., Rossides, M., Westerlind, H., Hesselstrand, R., Arkema, E. V., & Holmqvist, M. (2021). Incidence and prevalence of systemic sclerosis globally: A comprehensive systematic review and meta-analysis. Rheumatology, 60(7), 3121–3133. https://doi.org/10.1093/rheumatology/keab190
Alba, M. A., Velasco, C., Simeón, C. P., Fonollosa, V., Trapiella, L., Egurbide, M. V., Sáez, L., Castillo, M. J., Callejas, J. L., Camps, M. T., Tolosa, C., Ríos, J. J., Freire, M., Vargas, J. A., Espinosa, G., & RESCLE Registry. (2014). Early- versus late-onset systemic sclerosis: Differences in clinical presentation and outcome in 1,037 patients. Medicine, 93(2), 73–81. https://doi.org/10.1097/MD.0000000000000018
Elhai, M., Meune, C., Boubaya, M., et al. (2017). Mapping and predicting mortality from systemic sclerosis. Annals of the Rheumatic Diseases, 76(11), 1897–1905. https://doi.org/10.1136/annrheumdis-2017-211448
Rubio-Rivas, M., Royo, C., Simeón, C. P., Corbella, X., & Fonollosa, V. (2014). Mortality and survival in systemic sclerosis: Systematic review and meta-analysis. Seminars in Arthritis and Rheumatism, 44(2), 208–219. https://doi.org/10.1016/j.semarthrit.2014.05.010
Volkmann, E. R., Andréasson, K., & Smith, V. (2023). Systemic sclerosis. The Lancet, 401(10373), 304–318. https://doi.org/10.1016/S0140-6736(22)01692-0
Stern, E. P., & Denton, C. P. (2015). The pathogenesis of systemic sclerosis. Rheumatic Disease Clinics of North America, 41(3), 367–382. https://doi.org/10.1016/j.rdc.2015.04.002
Desbois, A. C., & Cacoub, P. (2016). Systemic sclerosis: An update in 2016. Autoimmunity Reviews, 15(5), 417–426. https://doi.org/10.1016/j.autrev.2016.01.007
Agarwal, S. K., Tan, F. K., & Arnett, F. C. (2008). Genetics and genomic studies in scleroderma (systemic sclerosis). Rheumatic Disease Clinics of North America, 34(1), 17–40. https://doi.org/10.1016/j.rdc.2007.10.001
Medhasi, S., & Chantratita, N. (2022). Human leukocyte antigen (HLA) system: Genetics and association with bacterial and viral infections. Journal of Immunology Research, 2022, Article 9710376. https://doi.org/10.1155/2022/9710376
Tan, F. K. (2003). Systemic sclerosis: The susceptible host (genetics and environment). Rheumatic Disease Clinics of North America, 29(2), 11–37. https://doi.org/10.1016/S0889-857X(03)00015-2
Gladman, D. D., Kung, T. N., Siannis, F., Pellett, F., Farewell, V. T., & Lee, P. (2005). HLA markers for susceptibility and expression in scleroderma. The Journal of Rheumatology, 32(8), 1481–1487.
Arnett, F. C., Gourh, P., Shete, S., et al. (2010). Major histocompatibility complex (MHC) class II alleles, haplotypes, and epitopes which confer susceptibility or protection in the fibrosing autoimmune disease systemic sclerosis: Analyses in 1,300 Caucasian, African American, and Hispanic cases and 1,000 controls. Annals of the Rheumatic Diseases, 69(5), 822–827. https://doi.org/10.1136/ard.2009.111906
Truchetet, M. E., Brembilla, N. C., & Chizzolini, C. (2023). Current concepts on the pathogenesis of systemic sclerosis. Clinical Reviews in Allergy & Immunology, 64(3), 262–283. https://doi.org/10.1007/s12016-021-08889-8
Radstake, T. R., Gorlova, O., Rueda, B., et al. (2010). Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nature Genetics, 42(5), 426–429. https://doi.org/10.1038/ng.565
Allanore, Y., Saad, M., Dieudé, P., et al. (2011). Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLOS Genetics, 7(7), e1002091. https://doi.org/10.1371/journal.pgen.1002091
Dieude, P., Wipff, J., Guedj, M., et al. (2009). BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis & Rheumatism, 60(11), 3447–3454. https://doi.org/10.1002/art.24885
Martin, J.-E., Broen, J. C., Carmona, F. D., et al. (2012). Identification of CSK as a systemic sclerosis genetic risk factor through genome-wide association study follow-up. Human Molecular Genetics, 21(12), 2825–2835. https://doi.org/10.1093/hmg/dds099
Wang, Y., Fan, P. S., & Kahaleh, B. (2006). Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis & Rheumatism, 54(7), 2271–2279. https://doi.org/10.1002/art.21948
Dees, C., Schlottmann, I., Funke, R., Distler, A., Palumbo-Zerr, K., Zerr, P., Lin, N. Y., Beyer, C., Distler, O., Schett, G., & Distler, J. H. (2014). The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Annals of the Rheumatic Diseases, 73(6), 1232–1239. https://doi.org/10.1136/annrheumdis-2012-203194
Suliman, B. A. (2024). Potential clinical implications of molecular mimicry-induced autoimmunity. Immunity, Inflammation and Disease, 12(2), e1178. https://doi.org/10.1002/iid3.1178
Randone, S. B., Guiducci, S., & Cerinic, M. M. (2008). Systemic sclerosis and infections. Autoimmunity Reviews, 8(1), 36–40. https://doi.org/10.1016/j.autrev.2008.07.022
Moroncini, G., Mori, S., Tonnini, C., & Gabrielli, A. (2013). Role of viral infections in the etiopathogenesis of systemic sclerosis. Clinical and Experimental Rheumatology, 31(2, Suppl. 76), 3–7.
Rubio-Rivas, M., Moreno, R., & Corbella, X. (2017). Occupational and environmental scleroderma: Systematic review and meta-analysis. Clinical Rheumatology, 36(3), 569–582. https://doi.org/10.1007/s10067-016-3533-1
Shah, A. A., Rosen, A., Hummers, L., Wigley, F., & Casciola-Rosen, L. (2010). Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis & Rheumatism, 62(9), 2787–2795. https://doi.org/10.1002/art.27549
Ko, J., Noviani, M., Chellamuthu, V. R., Albani, S., & Low, A. H. L. (2023). The pathogenesis of systemic sclerosis: The origin of fibrosis and interlink with vasculopathy and autoimmunity. International Journal of Molecular Sciences, 24(18), 14287. https://doi.org/10.3390/ijms241814287
Vona, R., Giovannetti, A., Gambardella, L., Malorni, W., Pietraforte, D., & Straface, E. (2018). Oxidative stress in the pathogenesis of systemic scleroderma: An overview. Journal of Cellular and Molecular Medicine, 22(7), 3308–3314. https://doi.org/10.1111/jcmm.13630
Ntelis, K., Solomou, E. E., Sakkas, L., Liossis, S. N., & Daoussis, D. (2017). The role of platelets in autoimmunity, vasculopathy, and fibrosis: Implications for systemic sclerosis. Seminars in Arthritis and Rheumatism, 47(3), 409–417. https://doi.org/10.1016/j.semarthrit.2017.05.004
Cutolo, M., Soldano, S., & Smith, V. (2019). Pathophysiology of systemic sclerosis: Current understanding and new insights. Expert Review of Clinical Immunology, 15(7), 753–764. https://doi.org/10.1080/1744666X.2019.1614915
Bruni, C., Frech, T., Manetti, M., Rossi, F. W., Furst, D. E., De Paulis, A., et al. (2018). Vascular leaking, a pivotal and early pathogenetic event in systemic sclerosis: Should the door be closed? Frontiers in Immunology, 9, 2045. https://doi.org/10.3389/fimmu.2018.02045
Matucci-Cerinic, M., Kahaleh, B., & Wigley, F. M. (2013). Review: Evidence that systemic sclerosis is a vascular disease. Arthritis & Rheumatism, 65(8), 1953–1962. https://doi.org/10.1002/art.37988
Denton, C. P. (2016). Advances in pathogenesis and treatment of systemic sclerosis. Clinical Medicine, 16(1), 55–60. https://doi.org/10.7861/clinmedicine.16-1-55
O’Reilly, S. (2013). Role of interleukin-13 in fibrosis, particularly systemic sclerosis. BioFactors, 39(6), 593–596. https://doi.org/10.1002/biof.1117
Guillevin, L., Bérezné, A., Seror, R., Teixeira, L., Pourrat, J., Mahr, A., et al. (2012). Scleroderma renal crisis: A retrospective multicentre study on 91 patients and 427 controls. Rheumatology, 51(3), 460–467. https://doi.org/10.1093/rheumatology/ker271
Günther, J., Rademacher, J., van Laar, J. M., Siegert, E., & Riemekasten, G. (2015). Functional autoantibodies in systemic sclerosis. Seminars in Immunopathology, 37(5), 529–542. https://doi.org/10.1007/s00281-015-0513-5
Berger, M., & Steen, V. D. (2017). Role of anti-receptor autoantibodies in pathophysiology of scleroderma. Autoimmunity Reviews, 16(10), 1029–1035. https://doi.org/10.1016/j.autrev.2017.07.019
Hasegawa, M. (2016). Biomarkers in systemic sclerosis: Their potential to predict clinical courses. The Journal of Dermatology, 43(1), 29–38. https://doi.org/10.1111/1346-8138.13156
Heijnen, I. A. F. M., Foocharoen, C., Bannert, B., et al. (2013). Clinical significance of coexisting antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis: A EUSTAR group-based study. Clinical and Experimental Rheumatology, 31(2, Suppl. 76), 96–102.
Stochmal, A., Czuwara, J., Trojanowska, M., & Rudnicka, L. (2020). Antinuclear antibodies in systemic sclerosis: An update. Clinical Reviews in Allergy & Immunology, 58(1), 40–51. https://doi.org/10.1007/s12016-018-8718-8
Villalta, D., Imbastaro, T., Di Giovanni, S., et al. (2012). Diagnostic accuracy and predictive value of extended autoantibody profile in systemic sclerosis. Autoimmunity Reviews, 12(2), 114–120. https://doi.org/10.1016/j.autrev.2012.07.005
Caetano, J., Nihtyanova, S. I., Harvey, J., Denton, C. P., & Ong, V. H. (2018). Distinctive clinical phenotype of anti-centromere antibody-positive diffuse systemic sclerosis. Rheumatology Advances in Practice, 2(1), rky002. https://doi.org/10.1093/rap/rky002
Valenzuela, A., & Chung, L. (2015). Calcinosis: Pathophysiology and management. Current Opinion in Rheumatology, 27(6), 542–548. https://doi.org/10.1097/BOR.0000000000000220
Harvey, G. R., & McHugh, N. J. (1999). Serologic abnormalities in systemic sclerosis. Current Opinion in Rheumatology, 11(6), 495–502.
Affandi, A. J., Radstake, T. R., & Marut, W. (2015). Update on biomarkers in systemic sclerosis: Tools for diagnosis and treatment. Seminars in Immunopathology, 37(5), 475–487. https://doi.org/10.1007/s00281-015-0506-4
Nihtyanova, S. I., Sari, A., Harvey, J. C., Leslie, A., Derrett-Smith, E. C., Fonseca, C., et al. (2020). Using autoantibodies and cutaneous subset to develop outcome-based disease classification in systemic sclerosis. Arthritis & Rheumatology, 72(3), 465–476. https://doi.org/10.1002/art.41153
Kuwana, M. (2017). To-do list at diagnosis of systemic sclerosis with positive anti-RNA polymerase III antibodies. The Journal of Rheumatology, 44(5), 550–552. https://doi.org/10.3899/jrheum.170037
Wirz, E. G., Jaeger, V. K., Allanore, Y., et al. (2016). Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: A 10-year longitudinal study from the EUSTAR database. Annals of the Rheumatic Diseases, 75(7), 1285–1292. https://doi.org/10.1136/annrheumdis-2015-207271
Cavazzana, I., Vojinovic, T., Airo’, P., Fredi, M., Ceribelli, A., Pedretti, E., Lazzaroni, M. G., Garrafa, E., & Franceschini, F. (2022). Systemic sclerosis-specific antibodies: Novel and classical biomarkers. Clinical Reviews in Allergy & Immunology, 64(3), 412–430. https://doi.org/10.1007/s12016-022-08946-w
Shah, A. A., Rosen, A., Hummers, L., Wigley, F., & Casciola-Rosen, L. (2010). Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis & Rheumatism, 62(9), 2787–2795. https://doi.org/10.1002/art.27549
Koenig, M., Joyal, F., Fritzler, M. J., Roussin, A., Abrahamowicz, M., Boire, G., et al. (2008). Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: A twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis & Rheumatism, 58(12), 3902–3912. https://doi.org/10.1002/art.24038
Radić, M., Martinović Kaliterna, D., & Ljutić, D. (2006). The level of anti-topoisomerase I antibodies highly correlates with metacarpophalangeal and proximal interphalangeal joint flexion contractures in patients with systemic sclerosis. Clinical and Experimental Rheumatology, 24(4), 407–412.
Herrick, A. L., Assassi, S., & Denton, C. P. (2022). Skin involvement in early diffuse cutaneous systemic sclerosis: An unmet clinical need. Nature Reviews Rheumatology, 18(5), 276–285. https://doi.org/10.1038/s41584-022-00765-9
Gelber, A. C., Manno, R. L., Shah, A. A., Woods, A., Le, E. N., Boin, F., et al. (2013). Race and association with disease manifestations and mortality in scleroderma: A 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature. Medicine, 92(4), 191–205. https://doi.org/10.1097/MD.0b013e31829be125
Graf, S. W., Hakendorf, P., Lester, S., et al. (2012). South Australian Scleroderma Register: Autoantibodies as predictive biomarkers of phenotype and outcome. International Journal of Rheumatic Diseases, 15(1), 102–109. https://doi.org/10.1111/j.1756-185X.2011.01688.x
van den Hoogen, F., Khanna, D., Fransen, J., et al. (2013). 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases, 72(11), 1747–1755. https://doi.org/10.1136/annrheumdis-2013-204424
Nawaz, I., Nawaz, Y., Nawaz, E., Manan, M. R., & Mahmood, A. (2022). Raynaud’s phenomenon: Reviewing the pathophysiology and management strategies. Cureus, 14(1), e21681. https://doi.org/10.7759/cureus.21681
Wiąk-Walerowicz, K., Wielosz, E., & Majdan, M. (2024). The usefulness of nailfold capillaroscopy in scleroderma-spectrum disorders: A single-centre observational study. Postępy Dermatologii i Alergologii, 41(3), 296–300. https://doi.org/10.5114/ada.2024.141158
Chasov, V., Mukhametshin, S., Gilyazova, E., Davletshin, D., Tikhomirova, M., Topchu, I., Valiullina, A., Prete, M., & Bulatov, E. (2026). Emerging cell-based therapies for systemic sclerosis: From stem cells to CAR-T cells. Current Issues in Molecular Biology, 48(1), 76. https://doi.org/10.3390/cimb48010076
Del Galdo, F., Lescoat, A., Conaghan, P. G., et al. (2024). EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Annals of the Rheumatic Diseases, 84(1), 29–40. https://doi.org/10.1136/ard-2024-226430
Hughes, M., Ong, V. H., Anderson, M. E., et al. (2015). Consensus best practice pathway of the UK Scleroderma Study Group: Digital vasculopathy in systemic sclerosis. Rheumatology, 54(11), 2015–2024. https://doi.org/10.1093/rheumatology/kev201
Roustit, M., Blaise, S., Allanore, Y., et al. (2013). Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: Systematic review and meta-analysis of randomised trials. Annals of the Rheumatic Diseases, 72(10), 1696–1699. https://doi.org/10.1136/annrheumdis-2012-202836
Hughes, M., Allanore, Y., El Aoufy, K., et al. (2021). A practical approach to the management of digital ulcers in patients with systemic sclerosis: A narrative review. JAMA Dermatology, 157(7), 851–858. https://doi.org/10.1001/jamadermatol.2021.1463
Korn, J. H., Mayes, M., Matucci Cerinic, M., et al. (2004). Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis & Rheumatism, 50(12), 3985–3993. https://doi.org/10.1002/art.20676
Omair, M. A., Alahmadi, A., Johnson, S. R., et al. (2015). Safety and effectiveness of mycophenolate in systemic sclerosis: A systematic review. PLOS ONE, 10(5), e0124205. https://doi.org/10.1371/journal.pone.0124205
Namas, R., Tashkin, D. P., Furst, D. E., et al. (2018). Efficacy of mycophenolate mofetil and oral cyclophosphamide on skin thickness: Post hoc analyses from two randomized placebo-controlled trials. Arthritis Care & Research, 70(3), 439–444. https://doi.org/10.1002/acr.23282
Campochiaro, C., De Luca, G., Lazzaroni, M. G., et al. (2020). Safety and efficacy of rituximab biosimilar (CT-P10) in systemic sclerosis: An Italian multicentre study. Rheumatology, 59(12), 3731–3736. https://doi.org/10.1093/rheumatology/keaa136
Pope, J. E., Bellamy, N., Seibold, J. R., et al. (2001). A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis & Rheumatism, 44(6), 1351–1358. https://doi.org/10.1002/1529-0131(200106)44:6%3C1351::AID-ART227%3E3.0.CO;2-I
Van Laar, J. M., Farge, D., Sont, J. K., et al. (2014). Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: A randomized clinical trial. JAMA, 311(24), 2490–2498. https://doi.org/10.1001/jama.2014.6368
Trang, G., Steele, R., Baron, M., et al. (2012). Corticosteroids and the risk of scleroderma renal crisis: A systematic review. Rheumatology International, 32(3), 645–653. https://doi.org/10.1007/s00296-010-1697-6
Xiong, A., Cao, Y., Xiang, Q., et al. (2022). Angiotensin-converting enzyme inhibitors prior to scleroderma renal crisis in systemic sclerosis: A systematic review and meta-analysis. Journal of Clinical Pharmacy and Therapeutics, 47(6), 722–731. https://doi.org/10.1111/jcpt.13621
Volkmann, E. R., Tashkin, D. P., Li, N., et al. (2017). Mycophenolate mofetil versus placebo for systemic sclerosis-related interstitial lung disease: An analysis of Scleroderma Lung Studies I and II. Arthritis & Rheumatology, 69(7), 1451–1460. https://doi.org/10.1002/art.40114
Maher, T. M., Tudor, V. A., Saunders, P., et al. (2023). Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomised, controlled, phase 2b trial. The Lancet Respiratory Medicine, 11(1), 45–54. https://doi.org/10.1016/S2213-2600(22)00359-9
Tashkin, D. P., Elashoff, R., Clements, P. J., et al. (2006). Cyclophosphamide versus placebo in scleroderma lung disease. The New England Journal of Medicine, 354(25), 2655–2666. https://doi.org/10.1056/NEJMoa055120
Highland, K. B., Distler, O., Kuwana, M., et al. (2021). Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: A subgroup analysis of the SENSCIS trial. The Lancet Respiratory Medicine, 9(1), 96–106. https://doi.org/10.1016/S2213-2600(20)30330-1
Roofeh, D., Lin, C. J. F., Goldin, J., et al. (2021). Tocilizumab prevents progression of early systemic sclerosis-associated interstitial lung disease. Arthritis & Rheumatology, 73(7), 1301–1310. https://doi.org/10.1002/art.41668
Junfei, Z., Meihua, G., Shuai, Z., et al. (2023). Retrospective comparative study of the efficacy of JAK inhibitor (tofacitinib) in the treatment of systemic sclerosis-associated interstitial lung disease. Clinical Rheumatology, 42(10), 2823–2832. https://doi.org/10.1007/s10067-023-06660-2
Wang, X., Wu, X., Tan, B., et al. (2024). Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell, 187(18), 4890–4904.e9. https://doi.org/10.1016/j.cell.2024.06.027
Bes, C., & Çetinkaya, E. (2022). Current treatment of systemic sclerosis-associated interstitial lung disease. Tuberkuloz ve Toraks, 70(1), 85–92. https://doi.org/10.5578/tt.20229910
Galiè, N., Barberà, J. A., Frost, A. E., et al. (2015). Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. The New England Journal of Medicine, 373(9), 834–844. https://doi.org/10.1056/NEJMoa1413687
Badesch, D. B., Tapson, V. F., McGoon, M. D., et al. (2000). Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease: A randomized, controlled trial. Annals of Internal Medicine, 132(6), 425–434. https://doi.org/10.7326/0003-4819-132-6-200003210-00002
Gaine, S., Chin, K., Coghlan, G., et al. (2017). Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. European Respiratory Journal, 50(2), 1602493. https://doi.org/10.1183/13993003.02493-2016
Rubin, L. J., Galiè, N., Grimminger, F., et al. (2015). Riociguat for the treatment of pulmonary arterial hypertension: A long-term extension study (PATENT-2). European Respiratory Journal, 45(5), 1303–1313. https://doi.org/10.1183/09031936.00090614
Morrisroe, K., Stevens, W., Huq, M., et al. (2017). Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension. Arthritis Research & Therapy, 19(1), 122. https://doi.org/10.1186/s13075-017-1341-x
Vigone, B., Caronni, M., Severino, A., et al. (2017). Preliminary safety and efficacy profile of prucalopride in the treatment of systemic sclerosis (SSc)-related intestinal involvement: Results from the open-label cross-over PROGASS study. Arthritis Research & Therapy, 19(1), 145. https://doi.org/10.1186/s13075-017-1340-y
Hughes, M., Allanore, Y., Baron, M., et al. (2022). Proton pump inhibitors in systemic sclerosis: A reappraisal to optimise treatment of gastro-oesophageal reflux disease. The Lancet Rheumatology, 4(11), e795–e803. https://doi.org/10.1016/S2665-9913(22)00183-7
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Olaf Krawczyk, Wojciech Kopyciński, Norbert Krawczyk, Piotr Wilczkowski, Natalia Krzysztofek, Monika Kamela, Katarzyna Boszczyk, Małgorzata Grzybowska, Adrianna Baran, Aleksandra Palka
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
