Overlap of ACA-positive systemic sclerosis and Sjögren's syndrome: a distinct clinical entity with mild organ involvement but at high risk of lymphoma

Objectives: We aimed to assess the prevalence of patients with either primary Sjögren's syndrome (pSS) and positive anticentromere antibodies (ACA) and secondary Sjögren's syndrome (sSS) and limited cutaneous ACA positive-systemic sclerosis (SSc) in two large cohorts of patients with pSS and SSc¸ and also to compare the clinical features of these two subsets with those of patients affected by 'ACA-positive SSc without sicca symptoms' and 'pSS'. Methods: In this retrospective monocentric study, the case records of 'overlap' patients fulfilling both the classification criteria for SS and the LeRoy criteria for early SSc were identified from two datasets of patients with limited cutaneous ACA positive SSc (209 subjects) and with pSS (402 subjects) who attended our Rheumatology Unit in the years between 1989 and 2011. Control groups were represented by SSc subjects without sicca symptoms ('SSc group') and ACA negative Pss patients ('pSS group'). SSc patients with sicca symptoms ('Sicca-SSc group') who did not complete the diagnostic algorithm for SS were excluded from the analysis. Demographic, clinical and immunological data of the patients enrolled were collected cumulatively over the entire follow up period. Statistical analysis was performed using SPSS 13 (SPSS Inc., Chicago IL, USA). Results: Out of the two datasets 41 'overlap' patients were selected. The control groups were represented by 102/209 SSc subjects without sicca symptoms ('SSc group') and 387/402 pSS patients ('pSS group'). Eighty-one 'sicca-SSc' with an incomplete work-up for SS were excluded from the analysis. The prevalence of ACA positive pSS patients among pSS was 3.7% (15/402), while the frequency of patients with definite sSS in the SSc cohort was 20% (26/128). No differences were detected between 'overlap' patients and control groups, relatively to demographic characteristics. 'Overlap patients' were characterised by a milder SSc disease (i.e. lower frequency of sclerodactily, negative evolution of the capillaroscopy pattern or absence of severe systemic involvement) whereas, as far as the SS-related manifestations were concerned, although often lacking in specific autoantibodies (i.e. rheumatoid factor, anti-Ro/SSA, anti-La/SSB), the 'overlap patients' displayed a full blown SS phenotype with recurrent salivary gland enlargement, purpura, fatigue, arthralgias, and leukocytopenia. It is noteworthy that the prevalence of non-Hodgkin's lymphoma in the 'overlap patients' was higher than in pSS. Conclusions: Taken together, the results of our work emphasise the existence of a novel distinct clinical entity which might tentatively be called 'ACA-positive limited scleroderma/SS overlap syndrome' characterised by a benign SSc clinical course but at a high risk of non-Hodgkin's lymphoma.