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Multicenter Study
. 2020 Oct 19:11:594096.
doi: 10.3389/fimmu.2020.594096. eCollection 2020.

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

Andreas V Goules  1   2 , Ourania D Argyropoulou  1   2 , Vasileios C Pezoulas  3 , Loukas Chatzis  1   2 , Elena Critselis  4   5 , Saviana Gandolfo  6 , Francesco Ferro  7 , Marco Binutti  6 , Valentina Donati  7 , Sara Zandonella Callegher  6 , Aliki Venetsanopoulou  1   2 , Evangelia Zampeli  8 , Maria Mavrommati  5 , Paraskevi V Voulgari  9 , Themis Exarchos  10 , Clio P Mavragani  11 , Chiara Baldini  7 , Fotini N Skopouli  5 , Dimitrios I Fotiadis  3   12 , Salvatore De Vita  6 , Haralampos M Moutsopoulos  8   13 , Athanasios G Tzioufas  1   2
Affiliations
Multicenter Study

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

Andreas V Goules et al. Front Immunol. .

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: age group; clinical phenotype characteristics; data driven analysis; lymphoma; primary Sjögren’s syndrome.

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Figures

Figure 1
Figure 1
Distribution pattern of lymphoma occurrence across pSS course in: (A) matched early onset compared to middle-aged onset pSS lymphoma patients (n = 24) and (B) matched late onset compared to middle-aged onset pSS lymphoma patients (n = 12).
Figure 2
Figure 2
Prevalence and classical predictors for lymphoma using simple statistics and data driven approaches. Comparison of prevalence and classical predictors for lymphoma between (A) pSS patients with early disease onset and their matched middle-aged controls and (B) pSS patients with late disease onset and their matched middle-aged controls. Independent predictors for lymphoma after data driven analysis with FCBF based multivariable logistic regression analysis are shown with asterisk. The second asterisk connotes a negative association. SGE, salivary gland enlargement.
See this image and copyright information in PMC

References

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