Primary Sjögren’s Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development

Συγγραφείς : Andreas V. Goules, (…) S. Gandolfo, H.M.Moutsopoulos, A.G.Tzioufas

Abstract :

Objectives: To study the clinical, serological and histologic features of primary Sjögren’s
syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to
explore the differential effect on lymphoma development.
Methods: From a multicentre study population of 1997 consecutive pSS patients, those
with early or late disease onset, were matched and compared with pSS control patients of
middle age onset. Data driven analysis was applied to identify the independent variables
associated with lymphoma in both age groups.

Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland
enlargement (SGE, lymphadenopathy, Raynaud’s phenomenon, autoantibodies, C4
hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3%
vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11–3.27), while old pSS patients (15%, n =
293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs.
2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34–8.17) compared to their middle-aged pSS
controls, respectively. In young pSS patients, cryoglobulinemia, C4
hypocomplementemia, lymphadenopathy, and SGE were identified as independent
lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4

hypocomplementemia and male gender were the independent lymphoma associated
factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3
years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred
within the first 6 years.
Conclusion: Patients with early and late disease onset constitute a significant proportion
of pSS population with distinct clinical phenotypes. They possess a higher prevalence of
lymphoma, with different predisposing factors and lymphoma distribution across time.
Keywords: primary Sjögren’s syndrome, data driven analysis, age group, lymphoma, clinical phenotype characteristics

Early and late onset SS