Primer Sjögren hastalığında sicca şiddeti sistemik inflamasyonu değil, semptom amplifikasyonunu yansıtır

Öz

Amaç: Primer Sjögren hastalığında (pSD) sicca semptom şiddetinin sistemik inflamatuvar aktiviteyi mi yoksa semptom amplifikasyonunu mu yansıttığını netleştirmek; ayrıca kuruluk şiddetinin fonksiyonel bozukluk ve duygu durum bozukluğu ile ilişkisini ağırlıklı olarak tedavi gören bir kohortta incelemektir. Gereç ve Yöntemler: Bu kesitsel, tek merkezli çalışmada, 2016 ACR/EULAR sınıflandırma kriterlerini karşılayan yetişkin pSD hastaları değerlendirilmiştir. Sistemik hastalık aktivitesi "EULAR Sjögren’s Syndrome Disease Activity Index" (ESSDAI) kullanılarak belirlenmiştir. Oral ve oküler kuruluk şiddeti görsel analog skalalar (VAS) ile ölçülmüştür. Sağlıkla ilişkili yaşam kalitesi EQ-5D-5L indeksi ve Kısa Form-36 (SF-36) fiziksel ve zihinsel bileşen skorları ile; depresif semptomlar ise Beck Depresyon Envanteri ile değerlendirilmiştir. Sistemik hastalık aktivitesi ile ilişkiler lojistik regresyon modelleriyle incelenmiştir. Kuruluğun sistemik aktiviteyi ve fibromiyaljiyi belirlemedeki performansı "Receiver Operating Characteristic" (ROC) analizleri ile değerlendirilmiştir. Semptom heterojenliği gözetimsiz kümeleme (unsupervised cluster) analizi ile araştırılmıştır. Bulgular: İncelenen 107 hastanın %86,9'unda düşük sistemik hastalık aktivitesi mevcuttur. Sicca şiddeti sistemik hastalık aktivitesi ile ilişki göstermemiş ve orta-yüksek hastalık aktivitesini öngörmemiştir. Akciğer tutulumu, fibromiyalji ve eritrosit sedimentasyon hızı (ESH), yüksek sistemik hastalık aktivitesi ile bağımsız olarak ilişkili bulunmuştur. Kuruluk şiddeti inflamatuvar aktivite için zayıf bir ayırt edicilik gösterse de; fibromiyalji, depresif semptomlar ve bozulmuş yaşam kalitesi ile güçlü bir ilişki sergilemiştir. Kümeleme analizi; orta dereceli kuruluk şiddetine rağmen belirgin fonksiyonel ve psikolojik bozulma ile karakterize bir "semptom amplifikasyon" fenotipi tanımlamıştır. Sonuç: pSD'de sicca semptom şiddeti sistemik inflamasyondan ziyade fonksiyonel ve psikolojik yükü yansıtmaktadır. Bu bulgular, fenotip odaklı ve hasta merkezli değerlendirme stratejilerini desteklemektedir.

Anahtar Kelimeler

• primer Sjögren hastalığı
• sicca semptomları
• fonksiyonel bozukluk
• duygu durum bozukluğu
• essdai
• yaşam kalitesi
• fibromiyalji
• semptom amplifikasyonu

Sicca severity in primary Sjögren’s disease reflects symptom amplification rather than systemic inflammatory activity

Öz

Aim: To clarify whether sicca symptom severity reflects systemic inflammatory activity or symptom amplification in primary Sjögren’s disease (pSD), and to examine its relationship with functional impairment and mood disturbance in a predominantly treated cohort. Material and Methods: In this cross-sectional, single-center study, adult patients fulfilling the 2016 ACR/EULAR classification criteria for pSD were evaluated. Systemic disease activity was assessed using the EULAR Sjögren’s Syndrome Disease Activity Index. Oral and ocular dryness severity were measured using visual analog scales. Health-related quality of life was assessed with the EQ-5D-5L index and Short Form 36 physical and mental component scores, and depressive symptoms with the Beck Depression Inventory. Logistic regression models examined associations with systemic disease activity. Receiver operating characteristic analyses assessed the performance of dryness severity for identifying systemic activity and fibromyalgia. Symptom heterogeneity was explored using unsupervised cluster analysis. Results: Among 107 patients, 86.9 percent had low systemic disease activity. Sicca severity showed no association with systemic disease activity and did not predict moderate to high disease activity. Pulmonary involvement, fibromyalgia, and erythrocyte sedimentation rate were independently associated with higher systemic disease activity. Although dryness severity showed poor discrimination for inflammatory activity, it was strongly associated with fibromyalgia, depressive symptoms, and impaired quality of life. Cluster analysis identified a symptom amplification phenotype characterized by marked functional and psychological impairment despite moderate dryness severity. Conclusion: In pSD, sicca symptom severity primarily reflects functional and psychological burden rather than systemic inflammation, supporting phenotype-oriented, patient-centered assessment strategies.

Anahtar Kelimeler

• Primary Sjögren’s disease
• sicca symptoms
• functional impairment
• mood disturbance
• ESSDAI
• quality of life
• fibromyalgia
• symptom amplification

Kaynakça

1. Ramos-Casals M, Brito-Zeron P, Bombardieri S, Bootsma H, De Vita S et al. EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies. Ann Rheum Dis 2020; 79: 3-18.
2. Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A et al. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome. Ann Rheum Dis 2010; 69: 1103-09.
3. Meijer JM, Meiners PM, Huddleston Slater JJ, Spijkervet FK, Kallenberg CG et al. Health-related quality of life, employment and disability in patients with Sjogren's syndrome. Rheumatology 2009; 48: 1077-82.
4. Tarn JR, Howard-Tripp N, Lendrem DW, Mariette X, Saraux A et al. Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol 2019; 1: e85-e94.
5. Bowman SJ, Fox R, Dorner T, Mariette X. Patient-reported outcomes in primary Sjögren’s syndrome: the evolution of measuring disease impact. Arthritis Res Ther 2020; 22: 68.
6. Vivino FB, Bunya VY, Massaro-Giordano G, Johr CR, Giattino SL et al. Sjogren's syndrome: An update on disease pathogenesis, clinical manifestations and treatment. Clin Immunol 2019; 203: 81-121.
7. Verstappen GM, Pringle S, Bootsma H, Kroese FGM. Epithelial-immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis. Nat Rev Rheumatol 2021; 17: 333-48.
8. Flament T, Bigot A, Chaigne B, Henique H, Diot E et al. Pulmonary manifestations of Sjögren's syndrome. Eur Respir Rev 2016; 25: 110-23.

9. Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E et al. Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology 2014; 53: 839-44.
10. Hauser W, Ablin J, Fitzcharles MA, Littlejohn G, Luciano JV et al. Fibromyalgia. Nat Rev Dis Primers 2015; 1: 15022.
11. Segal BM, Pogatchnik B, Henn L, Rudser K, Sivils KM. Pain severity and neuropathic pain symptoms in primary Sjögren's syndrome: a comparison study of seropositive and seronegative Sjögren's syndrome patients. Arthritis Care Res 2013; 65: 1291-98.
12. Alunno A, Leone MC, Giacomelli R, Gerli R, Carubbi F. Lymphoma and Lymphomagenesis in Primary Sjögren's Syndrome. Front Med (Lausanne) 2018; 5: 102.
13. Cui Y, Zhao Y, Zeng X. Depression in primary Sjögren’s syndrome: a systematic review and meta-analysis. Clin Rheumatol 2018; 37: 2377-87.
14. Lendrem D, Mitchell S, McMeekin P, Bowman S, Price E et al. Health-related utility values of patients with primary Sjögren's syndrome and its predictors. Ann Rheum Dis 2014; 73: 1362-68.