MALİGNİTE VE PRİMER SJÖGREN SENDROMU ARASINDAKİ İLİŞKİ; TEK MERKEZ SONUÇLARI

Öz

Amaç: Bu çalışmada, polikliniğimizde primer Sjögren sendromu (pSS) tanısı ile takip edilen hastalarda malignite verilerini sunmayı amaçladık.
Yöntem: 2004-2019 yılları arasında pSS tanısı alan 151 hastanın verileri retrospektif olarak incelendi ve malignite tanısı alan 14 hastanın klinik, demografik özellikleri değerlendirildi. Standardize insidans oranları (SIR'ler) hesaplandı.
Bulgular: Malignite saptanan 14 hastanın tamamı kadın, yaş ortalaması 55.9±12 yıl ve hastalık süresi 10.5±5.3 yıl idi. pSS tanısı ile takip edilen hastaların %9'unda malignite saptandı. Bir hastaya serviks kanseri, dört hastaya meme kanseri, üç hastaya tiroid papiller karsinom, bir hastaya MALT (mukoza ile ilişkili lenfoid doku) lenfoma, bir hastaya diffüz büyük B hücreli lenfoma (DBBHL), bir hastaya mikozis fungoides, bir hastaya vulvar epitelyal karsinom ve iki hastaya akciğer kanseri tanısı konulmuştu. Malignitesi olan ve olmayan hastalar klinik ve laboratuvar bulguları açısından karşılaştırıldı. İki grupta lenfadenopati ve interstisyel akciğer hastalığı varlığı ile EULAR primer Sjögren sendromu hastalık aktivite indeksi (ESSDAI) aktivite skorları arasında anlamlı fark vardı.
Sonuç: Çalışmamızda Sjögren Sendromunda hem hematolojik [SIR27.27 (%95 CI 5.6-79.7)] hem de solid maligniteler [SIR 7.75 (%95 CI 3.9-13.9)] için risk artışı gözlendi.

Anahtar Kelimeler

• Sjögren sendromu
• Malignite
• Lenfoma
• Solid Kanser

THE RELATIONSHIP BETWEEN MALIGNANCY AND PRIMARY SJOGREN'S SYNDROME; SINGLE CENTER RESULTS

Öz

Objective: In this study, we aimed to present malignancy data in patients who were followed up in our outpatient clinic with a diagnosis of primary Sjogren’s syndrome (pSS).
Methods: Data of 151 patients diagnosed with pSS between 2004-2019 were retrospectively reviewed and clinical, demographic characteristics of 14 patients diagnosed with malignancy were examined. Standardized incidence ratios (SIRs) were calculated.
Results: All 14 patients with malignancy were female, their mean age was 55.9±12 years, and the disease duration was 10.5±5.3 years. Malignancy was detected in 9% of the patients who were followed up with the diagnosis of pSS. One patient was diagnosed with cervix cancer (CA), four patients with breast CA, three patients with thyroid papillary CA, one patient with MALT (mucosa-associated lymphoid tissue) lymphoma, one patient with diffuse large B-cell lymphoma (DLBCL), one patient with mycosis fungoides, one patient with vulvar epithelial carcinoma, and two patients with lung CA. Patients with malignancy and those without were compared in terms of clinical and laboratory findings. There was a significant difference between the presence of LAP and ILD and EULAR primary Sjogren's syndrome disease activity ındex (ESSDAI) activity scores of two groups.
Conclusion: In our study, an increased risk was observed for both hematological [SIR27.27 (95% CI 5.6-79.7)] and solid malignancies [SIR 7.75 (95% CI 3.9-13.9)] in Sjogren's Syndrom.

Anahtar Kelimeler

• Sjogren’s syndrome
• Malignancy
• Lymphoma
• Solid Cancer

Kaynakça

1. 1-Moutsopoulos HM. Sjogren’s syndrome: autoimmune epithelitis. Clin Immunol Immunopathol. 1995;72(2):162-165.
2. 2- Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med. 1978:89(6):888-892.
3. 3- Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005:165(20):2337-2344.
4. 4- Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren’s syndrome. Arthritis Rheum. 2002:46(3):741-747
5. 5- Lazarus MN, Robinson D, Mak V, Møller H, Isenberg D A. Incidence of cancer in a cohort of patients with primary Sjogren’s syndrome. Rheumatology. 2006:45(8)1012-1015.
6. 6-Zhang W, Feng S, Yan S, Zhao Y, Li M, Sun J et al. Incidence of malignancy in primary Sjogren's syndrome in a Chinese cohort. Rheumatology (Oxford). 2010:49(3):571-577.
7. 7- Shiboski CH, Shiboski SC, Seror R, Criswell AL, Labetoulle M, Lietman TM et al. American College of Rheumatology/European League Against Rheumatism Classification Criteria for primary Sjogren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheum. 2017:69(1):35-45
8. 8- Liang Y, Yang Z, Qin B, Zhong R. Primary Sjogren’s syndrome and malignancy risk: a systematic review and meta-analysis. Ann Rheum Dis. 2014:73(6):1151-1156

9. 9- Brito-Zerón P, Kostov B, Fraile G, Caravia-Durán D, Maure B, Rascón FJ et al. Characterization and risk estimate of cancer in patients with primary Sjögren syndrome. J Hematol Oncol. 2017:10(1):90
10. 10- Kauppi M, Pukkala E, Isomäki H. Elevated incidence of hematologic malignancies in patients with Sjögren’s syndrome compared with patients with rheumatoid arthritis (Finland). Cancer Causes Control. 1997;8:201–4
11. 11-Weng MY, Huang YT, Liu MF, Lu TH. Incidence of cancer in a nationwide population cohort of 7852 patients with primary Sjogren's syndrome in Taiwan. Ann Rheum Dis. 2012:71(4):524-7. doi: 10.1136/annrheumdis-2011-200402. Epub 2011 Nov 9.
12. 12 -Brom M, Moyano S,Gandino IJ, Soriano ER, Scolnik M. Incidence of cancer in a cohort of patients with primary Sjögren syndrome in Argentina. Rheumatol Int. 2019:39(10):1697-1702.
13. 13-Kang J, Kim H, Kim J, Choi S, Jung SY, Jang EJ et al (2020) Risk of malignancy in Korean patients with primary Sjögren’s syndrome. Int J Rheum Dis. 2020:23(9):1240-1247.
14. 14-Ed. Şencan İ, Keskinkılıç B (2017) Türkiye Kanser İstatistikleri. T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu https://hsgm.saglik.gov.tr/depo/birimler/kanserdb/istatistik/2014
15. 15-Masaki Y, Sugai S. Lymphoproliferative disorders in Sjogren’s syndrome. Autoimmun Rev. 2004:3(3):175-82.
16. 16-Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome. The J Clin Invest. 2002:109(1):59-68.
17. 17-Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjogren’s syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006:65(6):796-803.
18. 18-Pillemer SR. Lymphoma and other malignancies in primary Sjogren’s syndrome. Ann Rheum Dis. 2006:65(6):704-706.
19. 19-Jonsson R, Nginamau E, Szyszko E, Brokstad KA. Role of B cells in Sjogren’s syndrome from benign lymphoproliferation to overt malignancy. Front Biosci. 2007:12:2159-2170.
20. 20-Nocturne G, Mariette X. Sjogren syndrome associated lypmhomas: an update on pathogenesis and management. Br J Haematol. 2015: 168(3):317-327
21. 21-Voulgarelis M and Moutsopoulos HM. Malignant lymphoma in primary Sjogren’s syndrome. Isr Med Assoc J. 2001:3(10): 761-766
22. 22-Solans-Laque R, Lopez-Hernandez A, Bosch-Gil JA, Palacios A, Campillo M, Vilardell-Tarres M. Risk, predictors, and clinical characteristics of lymphoma development in primary Sjogren’s syndrome. Semin Arthritis Rheum. 2011:41(3): 415-423
23. 23-Suvajdzic N, Djurdjevic P, Todorovic M, Perunicic M, Stojanović R, Novkovic A et al. Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of systemic autoimmune diseases. Med Oncol. 2012:29(3):2207-2211
24. 24-Risselada AP, Kruize AA, Bijlsma JWJ. Clinical features distinguishing lymphoma development in primary Sjogren’s syndrome—a retrospective cohort study. Semin Arthritis Rheum. 2013:43(2):171-177.
25. 25-Quartuccio L, Isola M, Baldini C, Priori R, Bocci EB, Carubbi F et al. Biomarkers of lymphoma in Sjogren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. J Autoimmun. 2014:51:75-80.
26. 26-Retamozo S, Gheitasi H, Quartuccio L, Kostov B, Corazza L, Bové A et al. Cryoglobulinaemic vasculitis at diagnosis predicts mortality in primary Sjogren syndrome: analysis of 515 patients. Rheumatology (Oxford). 2016:55:1443-1451.
27. 27-Brodsky RA. High dose cyclophosphamide treatment for autoimmune disorders. Scientific World Journal.2002:2:1808-1815.
28. 28-Matteson EL, Hickey AR, Maguire L, Tilson HH, Urowitz MB. Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. J Rheumatol. 1991:18(6):809-814.
29. 29-Jones M, Symmons D, Finn J, Wolfe F. Does exposure to immunosuppressive therapy increase the 10 year malignancy and mortality risks in rheumatoid arthritis? A matched cohort study. Br J Rheumatol. 1996:35(8): 738-745.
30. 30-Asten P, Barrett J, Symmons D. Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases. J Rheumatol. 1999:26(8)1705-1714.
31. 31-Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006:54(3):692-701.
32. 32-Salliot C and van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009:68(7): 1100-1104.
33. 33-Kotlyar DS, Lewis JD, Beaugerie L, Tierney A, Brensinger CM, Gisbert JP et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathiophrine and 6-mercaptopurine. A meta-analysis. Clin. Gastroenterol Hepatol. 2015:13(5):847-858.e4
34. 34-Slimani S, Lukas C, Combe B, Morel J. Rituximab in rheumatoid arthritis and the risk of malignancies: report from a French cohort. Joint Bone Spine. 2011:78(8):484-487
35. 35-Van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm safety of Rituksimab: Final report of rheumatoid arthritis global cilinical trial program over 11 years. J Rheumatol. 2015:42(10)1761-1766