Identification of lymphoma predictors in patients with primary Sjögren’s syndrome: a systematic literature review and meta-analysis

Abstract

To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome

“…Cryoglobulinemia, which involves a cold‐precipitable immunoglobulin with RF activity, is a well‐established predictive factor for lymphoma development in primary SS and has been demonstrated to be associated with more severe phenotype . Despite the clear link between cryoglobulinemia and RF, RF had never been shown to be independently associated with occurrence of lymphoma in primary SS before the current study . Of course, confirmation of this finding in independent cohorts is needed.…”

Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis

“…Lymphoma is a leading cause of mortality in patients with pSS . Reported predictors of lymphoma include lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins . Although no study specifically evaluated the correlation between IL‐17 and the development of lymphoma in pSS, a relationship between IL‐17 and lymphoproliferative disease has been posited.…”

Long-term follow-up in primary Sjögren’s syndrome reveals differences in clinical presentation between female and male patients

“…It is well known that pSS patients have an increased risk for developing non-Hodgkin lymphoma [35–38]. Sex-specific risk for lymphoma development in patients with rheumatic disease has been seldom studied, mainly due to the inclusion of mostly female patients.…”