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

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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.

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Acknowledgments

The authors are grateful to Maria Piedad Gonzalez for her assistance in designing the reference search strategy performance and primary reference selection. Members of the Systemic Autoimmune Disease working group SER provided the main questions for this review, and the research and paper preparation were performed by members of the Evidence Based working group SER. All authors contributed to the interpretation of results and provided final approval for publication. This study was funded by the Spanish Rheumatology Foundation (FER, for its Spanish acronym) through an unrestricted grant from ROCHE pharmaceuticals. The sponsor had a role neither in the design or conduct of the study; the collection, analysis or interpretation of data; the preparation, review or approval of the report, nor in the decision to submit the article for publication. Researchers were independent from funders. Dr. Pego-Reigosa was supported by the Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012-2013.1). The rest of authors declare no conflict of interest. Dr. Pereda, the corresponding author, and Dr. Nishishinya had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The information reported here has not been presented in any forum.

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Authors and Affiliations

  1. Instituto Traumatológico Quirón, Barcelona, Spain

    Maria B. Nishishinya

  2. Rheumatology Department, Clínica Mediterráneo, Avenida Mediterraneo 353 bloque 2 4 °C, 04009, Almería, Spain

    Claudia A. Pereda

  3. Reumatology Department, Hospital Universitario Infanta Sofía, Madrid, Spain

    Santiago Muñoz-Fernández

  4. Rheumatology Department, Complejo Hospitalario Universitario de Vigo, Pontevedra, Spain

    José M. Pego-Reigosa

  5. Instituto de Investigación Biomédica de Vigo (IBIV), Pontevedra, Spain

    José M. Pego-Reigosa

  6. Rheumatology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

    Iñigo Rúa-Figueroa

  7. Rheumatology Department, Hospital Universitario de Puerta de Hierro-Majadahonda, Madrid, Spain

    José-Luis Andreu & Mónica Fernández-Castro

  8. Rheumatology Department, Hospital Marina Baixa, Villajoyosa, Alicante, Spain

    José Rosas

  9. Institute for Musculoskeletal Health, Madrid, Spain

    Estibaliz Loza Santamaría

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  1. Maria B. Nishishinya
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Correspondence to Claudia A. Pereda.

Additional information

Maria B. Nishishinya, Claudia A. Pereda, Santiago Muñoz-Fernández and Estibaliz Loza Santamaría belong to “Evidence based working group of the Spanish Society of Rheumatology—SER”. Santiago Muñoz-Fernández, José M. Pego-Reigosa, Iñigo Rúa-Figueroa, José-Luis Andreu, Mónica Fernández-Castro and José Rosas belong to “Systemic Autoimmune Disease working group—SER”.

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Nishishinya, M.B., Pereda, C.A., Muñoz-Fernández, S. et al. Identification of lymphoma predictors in patients with primary Sjögren’s syndrome: a systematic literature review and meta-analysis. Rheumatol Int 35, 17–26 (2015). https://doi.org/10.1007/s00296-014-3051-x

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