The clinical phenotype of primary Sjögren's syndrome patients with lymphadenopathy.

OBJECTIVES: Previous cohort studies have shown that around 10% of patients with primary Sjögren's syndrome (pSS) develop lymphadenopathy during their disease course. However, no studies have described their clinical phenotype. The present study aims to describe the clinical manifestations and laboratory findings of pSS patients presenting long-standing lymphadenopathy. METHODS: From a total of 1234 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those with stable lymphadenopathy unrelated to lymphoma were identified (lymphadenopathy group). Their clinical data were collected and compared with 2 control groups: a) the remaining unmatched pSS patients without lymphadenopathy (unmatched non-lymphadenopathy group) and b) pSS patients without lymphadenopathy matched for age, sex, and disease duration, in an approximately 1:1 ratio (matched non-lymphadenopathy group). RESULTS: One hundred and sixty-five (13.37%) patients presented persistent, stable lymphadenopathy. They were characterised by younger age at both pSS onset and diagnosis, and by shorter disease duration. Compared to the unmatched nonlymphadenopathy group, patients with lymphadenopathy had more frequently salivary gland enlargement (p<0.001), higher focus score at first salivary gland biopsy (p=0.017), palpable purpura (p<0.001), peripheral nervous system involvement (p=0.012), glomerulonephritis (p<0.001), and leukopenia (p<0.001), while the results of the matched comparison were similar. Regarding the serological profile, the comparison with the unmatched group demonstrated higher frequency of ANA (p=0.013), anti-Ro/SSA (p=0.001), and anti-La/SSB (p<0.001) positivity for the lymphadenopathy group, while in the matched comparison only higher rates of anti-Ro/SSA positivity (p=0.002) remained statistically significant. CONCLUSIONS: pSS patients presenting non-lymphoma related stable lymphadenopathy constitute a subgroup of younger individuals with B-cell hyperactivation.

Sjögren's syndrome towards precision medicine: the challenge of harmonisation and integration of cohorts.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease with diverse clinical picture and outcome. The disease affects primarily middle-aged females and involves the exocrine glands leading to dry mouth and eyes. When the disease extends beyond the exocrine glands (systemic form), certain extraglandular manifestations involving liver, kidney, lungs, peripheral nervous system and the skin may occur. Primary SS is considered the crossroad between autoimmunity and lymphoproliferation, since approximately 5% of patients develop NHL associated lymphomas. As with every chronic disease with complex aetiopathogenesis and clinical heterogeneity, pSS has certain unmet needs that have to be addressed: a) classification and stratification of patients; b) understanding the distinct pathogenetic mechanisms and clinical phenotypes; c) defining and interpreting the real needs of patients regarding the contemporary diagnostic and therapeutic approaches; d) physician and patients' training regarding the wide spectrum of the disease; e) creating common policies across European countries to evaluate and manage SS patients. To achieve these goals, an intense effort is being currently undertaken by the HarmonicSS consortium in order to harmonise and integrate the largest European cohorts of pSS patients. In this review, we present an overview of our perception and vision, as well as new issues arising from this project such as harmonisation protocols and procedures, data sharing principles and various ethical and legal issues originating from these approaches.