Sistemik Skleroz Hastalarında Sağ Kalım: Tek Merkez Kohortu

Abstract

Sistemik sklerozis (SSk), oto-antikor pozitifliği, vaskülopati, deride ve iç organlarda progresif fibrozis ile karakterize olan kronik bir hastalıktır. Hastalığın tutulumuna bağlı olan veya hastalıkla ilişkili olmayan sebeplerle SSk’de yaşam beklentisi azalmıştır. SSk’a bağlı ölüm oranları yıllar içerisinde azalma göstermiş olsa da, genel popülasyona oranla hala yüksek seyretmektedir. Çalışmamızda, merkezimizde takip ettiğimiz SSk hastalarının başlıca ölüm sebeplerini ve ilişkili klinik, laboratuvar ve demografik özelliklerini bildirmeyi amaçladık. Kocaeli Üniversitesi Tıp Fakültesi Romatoloji Polikliniği’nde 2007-2022 arasında SSk tanısı ile takip edilen 168 hasta arasından 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) sınıflama kriterlerini dolduran 157 hasta dahil edildi. Hastaların çoğu (%66,4) sınırlı cilt tutulumlu, hastalık süresi 10,3 (±6,3) yıl olan kadınlardan (%88) oluşmaktaydı. 15 yıllık takip sırasında 23’ü (%14,6) hayatını kaybedildi. Ölen hastaların tanı sırasındaki yaşları daha ileri, dijital ülserleri (aktif ve inaktif) ve malignite sıklığı daha fazla saptandı. İki hasta grubu arasında oto-antikor ve major organ tutulumu açısından fark görülmedi. Kohortumuzdaki en sık ölüm sebebi enfeksiyon (n=5, %21,7) olup bu hastaların 3’ü (%13) COVID19 ve 2’si (%8,7) başka enfeksiyöz etkenlere bağlı pnömoni sebebiyle kaybedildi. Enfeksiyondan sonra en sık ikinci ölüm sebebi malignite (n=4, %17,4) olarak saptandı. Cox regresyon analizi sonucunda tanı sırasındaki yaşta yaklaşık 1 yıl artış ölüm riskinde 10 kat artış (hazard oranı (HR)= 10,93; %95 GA=10,51-11,37) ile ilişkili bulundu. Sonuç olarak, çalışmamız ülkemizde dikkatli takip edilen SSk kohortlarından bildirilmiş az sayıdaki sağ kalım verilerine katkı sağlamaktadır. Sonuçlarımız yorumlanırken SSk hastalarının klinik özelliklerinin coğrafi ve etnik farklılıklar gösterebileceği göz önünde bulundurulmalıdır.

Keywords

• Sistemik skleroz
• sağ kalım
• enfeksiyon
• malignite

Survival in Patients with Systemic Sclerosis: A Single Center Cohort

Abstract

Systemic sclerosis (SSc) is a chronic disease characterized by auto-antibody positivity, vasculopathy, and progressive fibrosis in the skin and internal organs. Life expectancy in SSc is decreased due to reasons both related to the involvement of the disease or not related to the disease. Although mortality rate due to SSc have decreased over the years, it still remains increased compared to the general population. In our study, we aimed to report the main causes of death and associated clinical, laboratory and demographic characteristics of SSc patients followed in our center. Among 168 patients followed up with the diagnosis of SSc in Kocaeli University Faculty of Medicine Rheumatology Polyclinic between 2007 and 2022, 157 patients who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria were included. Most of the patients (66.4%) were women (88%) with limited skin involvement and the disease duration was 10.3 (±6.3) years. During the 15-year follow-up, 23 (14.6%) patients died. The patients who died were older at the time of diagnosis with more digital ulcers (active and inactive) and malignancy. There was no difference between the two patient groups in terms of auto-antibody and major organ involvements. The most common cause of death in our cohort was infection (n=5, 21.7%), and 3 (13%) of these patients died due to COVID19 and 2 (8.7%) due to pneumonia due to other infectious agents. The second most common cause of death after infection was found to be malignancy (n=4, 17.4%). As a result of Cox regression analysis, an increase of approximately 1 year in age at diagnosis was associated with a 10-fold increase in the risk of death (hazard ratio (HR) = 10.93; 95% CI = 10.51-11.37). In conclusion, our study contributes to the few survival data reported to date from SSc cohorts in our country that are carefully followed. While interpreting our results, it should be considered that the clinical features of SSc patients may show geographical and ethnic differences.

Keywords

• Systemic sclerosis
• survival
• infection
• malignancy

References

1. 1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685–99. https://doi.org/10.1016/S0140-6736(17)30933-9.
2. 2. Elhai M, Meune C, Avouac J, et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology 2012;51:1017–26.
3. 3. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007 Jul;66(7):940-4. doi: 10.1136/ard.2006.066068. Epub 2007 Feb 28. PMID: 17329309; PMCID: PMC1955114.
4. 4. Coffey CM, Radwan YA, Sandhu AS, Crowson CS, Bauer PR, Matteson EL, Makol A. Epidemiology and Trends in Survival of Systemic Sclerosis in Olmsted County (1980-2018): A Population-based Study. J Scleroderma Relat Disord. 2021 Oct;6(3):264-270
5. 5. Rubio-Rivas M, Royo C, Simeón CP, et al. Mortality and survival in systemic sclerosis: systematic review and metaanalysis. Semin Arthritis Rheum 2014; 44(2): 208–219.
6. 6. Elhai M, Meune C, Boubaya M, Avouac J, Hachulla E, Balbir-Gurman A, et al. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis. 2017;76:1897–905. https:// doi. org/ 10. 1136/ annrheumdis- 2017- 211448.
7. 7. 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 2013;72:1747-55.
8. 8. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:202-5.

9. 9. Bennett R, Bluestone R, Holt PJ, et al. Survival in scleroderma. Ann Rheum Dis 1971; 30: 581–588.
10. 10. Medsger TA Jr and Masi AT. Survival with scleroderma. II. A life-table analysis of clinical and demographic factors in 358 male U.S. veteran patients. J Chronic Dis 1973; 26(10):647–660.
11. 11. Altman RD, Medsger TA Jr, Bloch DA, et al. Predictors of survival in systemic sclerosis (scleroderma). Arthritis Rheum 1991; 34: 403–413.
12. 12. Xiong A, Cao Y, Xiang Q, Song Z, Zhang Y, Zhou S, Qiang Y, Chen H, Hu Z, Cui H, Luo J, Wang Y, Yang Y, Yang M, Shuai S. Angiotensin-converting enzyme inhibitors prior to scleroderma renal crisis in systemic sclerosis: A systematic review and meta-analysis. J Clin Pharm Ther. 2022 Mar 1. doi: 10.1111/jcpt.13621. Epub ahead of print. PMID: 35233779.
13. 13. Meier FM, Frommer KW, Dinser R, Walker UA, Czirjak L, Denton CP, Allanore Y, Distler O, Riemekasten G, Valentini G, Müller-Ladner U; EUSTAR Co-authors. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis. 2012 Aug;71(8):1355-60. doi: 10.1136/annrheumdis-2011-200742. Epub 2012 May 21. PMID: 22615460.
14. 14. Özden Yılmaz, E. , Üsküdar Cansu, D. , Korkmaz, C. Clinical and Laboratory Results and Prognosis Patients with Scleroderma: A Single Center Experience. Osmangazi Tıp Dergisi 40 (2018): 70-78
15. 15. Zengin O, Balci MA, Pamuk ON, Kisacik B, Donmez S, Onder ME, Aksoy S, Onat AM. The Survival and Prognostic Factors of Patients with Systemic Sclerosis Turkish Experience [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).
16. 16. Steen VD and Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. ArthritisRheum 2000; 43(11): 2437–2444