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ID PMID Title PublicationDate abstract
24392761 Pain in primary Sjögren's syndrome: the role of catastrophizing and negative illness perc 2014 OBJECTIVES: Pain is a major factor in health quality in Sjögren's syndrome (SS), but little is known about the factors that contribute to pain severity. Because pain perception has been linked to catastrophizing in other diseases, we assessed subjects with primary SS (pSS) to explore a possible link between pain, illness appraisal, and catastrophizing. METHOD: A total of 92 subjects who met American-European consensus criteria for the diagnosis of pSS completed a questionnaire that included health history, medication use, illness perceptions, pain severity, mood, fatigue, pain anxiety, and pain catastrophizing. Linear regression was used to test the effect of each variable on pain severity. Multivariate models were constructed using backwards elimination to assess the significant predictors of pain severity. RESULTS: From linear regression analysis, catastrophizing was more strongly predictive of pain severity than age, fatigue, depression, or anxiety in both seropositive and seronegative pSS patients. In the multivariate model identified using backwards selection, four variables (pain catastrophizing, fibromyalgia status, serological status, and the conviction that illness would have severe consequences) predicted 55% of the variance in pain severity. CONCLUSIONS: Pain catastrophizing was a significant predictor of pain severity in both seropositive and seronegative pSS patients. This study suggests that behavioural interventions designed to reduce pain catastrophizing and negative appraisal of illness could be of benefit in pSS patients. Research is needed to test the effect of psycho-educational therapies on key patient-reported outcomes, particularly pain, depression, and fatigue, in pSS.
23968282 The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease, septic sh 2013 Aug 22 BACKGROUND: Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. DISCUSSION: There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still's disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. SUMMARY: Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed "Hyperferritinemic Syndrome".
23644453 Long-term Ro60 humoral autoimmunity in primary Sjögren's syndrome is maintained by rapid 2013 Jul Long-term humoral autoimmunity to RNA-protein autoantigens is considered a hallmark of systemic autoimmune diseases. We use high resolution Orbitrap mass spectrometric autoantibody sequencing to track the evolution of a Ro60-specific public clonotypic autoantibody in 4 patients with primary Sjögren's syndrome. This clonotype is specified by a VH3-23/VK3-20 heavy and light chain pairing. Despite apparent stability by conventional immunoassay, analysis of V-region molecular signatures of clonotypes purified from serum samples collected retrospectively over 7years revealed sequential clonal replacement. Prospective longitudinal studies confirmed clonotype loss and replacement at approximately three-monthly intervals. Levels of secreted anti-Ro60 clonotypes fluctuated markedly over time, despite minimal changes in clonal affinity. Our novel findings indicate a relentless turnover of short-lived clonotypic variants, masquerading as long-lived Ro60 humoral autoimmunity.
23052840 A potential role of the GRO-α/CXCR2 system in Sjögren's syndrome: regulatory effects of 2013 Feb Chemokines, small pro-inflammatory cytokines, are involved in migration of inflammatory cells in inflamed tissues and recent studies established their role in angiogenesis, hematopoiesis, cancer and autoimmune conditions. Growth related oncogene-alpha (GRO-α), a member of the CXC chemokine family, and its receptor CXCR2 are involved in the inflammatory processes. Since there is no previous report that supports a possible role of GRO-α/CXCR2 receptor complex during inflammation and neovascularization existing in the autoimmune disease Sjögren's syndrome (SS), in this study, we examined CXCR2 and its ligand GRO-α expression in SS tissues. Immunohistochemistry revealed that GRO-α and its receptor CXCR2 were expressed at high levels in diseased tissues compared to healthy controls. In addition, human salivary gland epithelial cells (SGEC) cultures were submitted to a pro-inflammatory microenvironment using cytokines IL-6 and TNF-α in order to demonstrate that CXCR2 may change its initial expression pattern to another under inflammatory condition. The data show an increased expression of CXCR2 depending on the inflammatory cytokine used in culture in a time-dependent manner. Furthermore, silencing of the pro-angiogenic chemokine GRO-α is proportionally correlated with decreased expression of CXCR2 in pro-inflammatory cytokine-stimulated SGEC indicating the GRO-α/CXCR2 complex as a novel therapeutic target for the chronic inflammatory disease Sjögren's syndrome.
25193912 Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome. 2014 Sep Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.
24461537 CD4(-)CD8(-) T-cells in primary Sjögren's syndrome: association with the extent of glandu 2014 Jun OBJECTIVES: Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters. METHODS: Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed. RESULTS: In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells. CONCLUSIONS: Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease.
24461387 The diagnosis and classification of mixed connective tissue disease. 2014 Feb The term "mixed connective tissue disease" (MCTD) concerns a systemic autoimmune disease typified by overlapping features between two or more systemic autoimmune diseases and the presence of antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP). Since the first description of this condition in 1972, the understanding of clinical manifestations and long-term outcome of MCTD have significantly advanced. Polyarthritis, Raynaud's phenomenon, puffy fingers, lung involvement and esophageal dysmotility are the most frequently reported symptoms among the different cohorts during the course of the disease. Moreover, in recent years a growing interest has been focused on severe organ involvement such as pulmonary arterial hypertension and interstitial lung disease which can accrue during the long-term follow-up and can still significantly influence disease prognosis. Over the last years, significant advances have been made also in disease pathogenesis understanding and a central pathogenetic role of anti-U1RNP autoantibodies has clearly emerged. Although controversies on disease definition and classification still persist, MCTD identifies a group of patients in whom increased surveillance for specific manifestations and prognostic stratification became mandatory to improve patient's outcomes.
24672948 [Effect of Tetramethyl pyrazine on serum levels of IL-1beta, IL-6, and IL-2, and NO and PG 2014 Feb OBJECTIVE: To observe the effect of Tetramethyl pyrazine (TMP) on the cytokines and inflammatory mediators in the serum and the synovial fluid of collagen-induced arthritis (CIA)rats, and further to investigate its possible mechanisms for treating rheumatoid arthritis (RA). METHODS: Type II CIA rat model was established. Rats in the TMP group were administered with TMP at 50 mg/kg and 100 mg/kg, once daily. Dexamethasone at 2.0 mg/kg was intramuscularly injected to those in the Dexamethasone treated group, once daily. Normal saline at 2 mL/kg was given to those in the normal control group and the model group, once daily. All medication was started from the 7th day, lasting to the 35th day. CIA rats' foot swelling degree was observed. Contents of serum IL-1, IL-6, IL-2, NO and PGE2in the synovial fluid were detected by radioimmunoassay and nitrate reduction method. RESULTS: Compared with the normal group, the foot swelling obviously increased, contents of NO and PGE2 in the synovial fluid were obviously elevated in the model group (P < 0.01). Compared with the model group, the foot swelling could be obviously inhibited by 100 mg/kg TMP and Dexamethasone; serum levels of IL-1 and IL-6 obviously decreased, serum IL-2 level obviously increased, contents of NO and PGE, decreased (P < 0.01). TMP 50 mg/kg could obviously inhibit the foot swelling of CIA rats (P < 0.01). There was no statistical difference in other indices (P > 0.05). CONCLUSIONS: TMP at 100 mg/kg showed obvious inhibition on CIA rats. Its inhibitory effect might be correlated to inhibiting activities of endogenous cytokines and the generation of inflammatory mediators in inflammation local regions, improving contents of anti-inflammation cytokines, and inducing the balance of the inflammatory cytokine network.
23929822 Genetic inactivation of the allograft inflammatory factor-1 locus. 2013 Oct Allograft inflammatory factor-1 (Aif-1) is a 17 kDa EF hand motif-bearing protein expressed primarily in developing spermatids and cells of monocyte/macrophage lineage. Increased Aif-1 expression has been identified in clinically important conditions, including rheumatoid arthritis, systemic sclerosis, endometriosis, and transplant-associated arteriosclerosis. Largely similar gene products arising from the same locus are known as ionized Ca(2+) binding adapter-1 (Iba1), microglial response factor-1 (MRF1), and daintain; Iba1 in particular has emerged as a histologic marker of microglia and their activation in pathologic CNS conditions, including the response to facial nerve axotomy and stroke, uveitis, and experimental autoimmune neuritis and encephalomyelitis. Nevertheless, how aif-1 gene products affect cellular function is only partly understood, and the physiologic significance of these products for male fertility, immune system development, and inflammation has not been described. To permit such investigations, we generated a mouse line with targeted deletion of the coding regions of the aif-1 gene. Here we report that mice lacking Aif-1 breed well and show normal post-natal growth, but show resistance to disease in a model of collagen-induced arthritis. We anticipate that these mice will be useful for studies of Aif-1 function in a variety of immune and inflammatory disease models.
24646084 Immunization with vaccines and Sjögren's syndrome. 2014 Apr Sjögren's syndrome (SjS) is a systemic autoimmune disease with complex pathogenesis and still unknown etiology. Infections are listed among the main environmental factors triggering the disease in genetically predisposed individuals. Among other environmental factors, the role of immunization with vaccines in the etiopathogenesis of SjS has not yet been elucidated. Although immunization with vaccines is safe for the majority of subjects, in rare cases it can trigger or exacerbate autoimmune and rheumatic inflammatory conditions. In this paper we investigate the possible links between immunization with vaccines and the pathogenesis of SjS. The current scientific evidence about safety and efficacy of vaccines in the course of SjS are also reviewed.
24435354 Life-threatening complications of adult-onset Still's disease. 2014 Mar Adult-onset Still's Disease (AOSD) since its description in 1971 has proven to be a very complex and challenging disease entity. This rare auto-inflammatory disease is classically described by the "Still's triad" of fever, rash, and arthritis, although the atypical cases frequently outnumber the typical ones. The exact pathogenesis and etiologic factors responsible for the clinical features remain largely obscure, despite recent suggestive cytokine biology findings. Diagnosis is made on clinical grounds, following the exclusion of mimickers of infectious, autoimmune or neoplastic etiology, with the additional consideration of non-specific laboratory abnormalities such as peripheral leukocytosis and elevation of serum ferritin and other acute phase reactants. The disease manifestations are protean and can include diverse complications, affecting multiple organ systems. Moreover, the severity of the organ involvement can vary considerably, representing a wide spectrum from the self-limited to severe. The mainstay of therapy has evolved from the traditional use of corticosteroids and oral immunosupressants to the newer targeted treatments with biologic agents. The scope of this review is to alert the clinician to the existence of life-threatening AOSD complications, namely the macrophage activation syndrome, disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, diffuse alveolar hemorrhage, and pulmonary arterial hypertension. Such knowledge may lead in earlier recognition, prompt treatment, and, ideally, improved patient outcomes.
24429168 Tocilizumab in adult-onset Still's disease: the Israeli experience. 2014 Feb OBJECTIVE: To describe the Israeli experience of treating adult-onset Still's disease (AOSD) with tocilizumab (TCZ). METHODS: Israeli rheumatologists who treated AOSD with TCZ filled in questionnaires on symptoms, number of tender and swollen joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and dosage of prednisone at initial TCZ administration, after 6 months, and at the end of followup. RESULTS: Nine male and 6 female patients, aged 33 ± 12 years, mean disease duration 9 years (range: 1-25) were identified. They had used a mean of 3.6 disease-modifying drugs, including 10 patients with tumor necrosis factor blockers. Intravenous TCZ 8 mg/kg was administered every 4 weeks (12 patients) or every 2 weeks (3 patients). All patients completed at least 6 months of treatment. The mean followup period was 15.7 ± 9 months. At the onset of therapy, despite the use of prednisone (27.6 ± 26.3 mg/d), all patients reported joint pain. Fever was reported in 9 patients, rash in 7, pleuritis in 3, and hepatitis in 2 before TCZ use, with mean ESR and CRP levels of 60 ± 28 mm/h and 11.6 ± 15 mg/dl, respectively. After 6 months of treatment and at the end of followup, the number of tender and swollen joints, the ESR and CRP levels, and the prednisone dosage decreased significantly. Only 2 patients still complained of mild arthralgias, and none reported systemic symptoms at the end of followup. CONCLUSION: TCZ 8 mg/kg was extremely efficacious in treating adult patients with refractory Still's disease. Both TCZ and interleukin 1 blockade should be considered in the treatment algorithm of AOSD. Randomized controlled studies are needed to validate these findings.
24131909 Neurological involvement in Primary Sjögren Syndrome. 2013 Jan OBJECTIVES: To perform an observational retrospective cross-sectional case-control study to evaluate prevalence, clinical patterns and outcomes of neurological involvement in a cohort of Primary Sjögren Syndrome (pSS) patients followed up in a single center. MATERIAL AND METHODS: From a total of 93 pSS patients, diagnosed according to the 2002 criteria proposed by the American-European Consensus Group, we reviewed the clinical data of those with neurological complaints that were referred to observation by Neuroimmunology doctors. Demographic, clinical, seroimmunological data were compared between patients with and without neurological involvement. RESULTS: Neurological involvement was detected in 26 (28%) of the 93 patients. Neurological symptoms preceded the diagnosis of pSS in 12 (46%) patients. They were all females. The mean age at disease onset and neurological onset were 41,2 and 47,9 years, respectively. Twelve patients (46%) had peripheral system involvement (PNS), 13 (50%) patients had central nervous involvement (CNS) disorders and one (4%) patient had both PNS and CNS involvement. In patients with PNS, pure sensory neuropathy (small fiber neuropathy confirmed by quantitative sensory testing and sural neuropathy) occurred most frequently (n =5), followed by cranial nerve involvement affecting trigeminal, facial, or trochlear nerves (n = 4). Multiple mononeuropathy (n = 1), sensorimotor polyneuropathy (n=1), autonomic neuropathy (n=1) and myasthenia gravis (n = 1), were also observed. In patients with CNS disorders, headache (n=3) occurred most frequently, in two patients with MRI abnormalities compatible with inflammatory disease. Spinal cord involvement (n=2), seizures (n = 2), motor and sensory deficit (n=2), movement disorders (n=2), neuromyelitis optica (n=2), aseptic meningitis (n=1) were others manifestations observed. Cognitive dysfunction was observed in 3 of these patients. The frequency of constitutional symptoms (such as fever and fatigue) and lung involvement was significantly higher (p< 0,05) and the articular symptoms were significantly less frequent (p< 0,05) in pSS with neurological involvement. The neurologic outcome was good in 77% of the patients. CONCLUSION: The current study underlines the diversity of neurologic complications of pSS. The frequency of neurologic manifestations as first manifestation of pSS, especially in the event of CNS involvement, could explain why SS is frequently under diagnosed or late diagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement.
23128336 Hematological complications of neonatal lupus: case report and review of the literature. 2013 Nov Neonatal thrombocytopenia is a common clinical problem and may be a result of maternal and/or fetal conditions. We present a young patient with thrombocytopenia as a result of neonatal lupus, a passively acquired autoimmune disease. The diagnosis was suspected on the basis of the presence of a facial rash. This case highlights the characteristic eruption of neonatal lupus and an underappreciated cause of neonatal thrombocytopenia for the pediatric hematologist. We also review the hematological complications of neonatal lupus.
24646086 Macrophages: important players in primary Sjögren's syndrome? 2014 Apr Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by immune-mediated destruction of the salivary and lacrimal glands with unknown etiology. Due to recent research utilizing human subjects as well as laboratory animal models, our understanding of the pathophysiological and immunological mechanisms of pSS has made great strides. As a consequence, targeted, immune-based therapies are gaining increased attention as the ideal way to conquer autoimmune diseases like pSS. Currently, however, there is no effective treatment to target specific immunological events or effector immune cells in the pathogenesis of pSS (discussed in other reviews of the current issue). Here, we summarize our current understanding and knowledge of the roles of monocytes/macrophages in the pathogenesis of pSS. Human studies, especially utilizing salivary gland biopsies, demonstrate the infiltration of macrophages and its correlation with disease severity. Moreover, animal model studies have shown the functional involvement of macrophages in promoting the ocular component of pSS.
23884987 Multiple autoimmune syndrome revealed by nephrogenic diabetes insipidus and hypokalaemic p 2013 Oct A presentation of postpartum polydipsia and polyuria followed by periodic weakness led to the diagnosis of nephrogenic diabetes insipidus and hypokalaemic paralysis, both of which are complications of primary Sjögren's syndrome (pSS). The clinically dominant pSS was taken to coexist with long-latent systemic lupus erythematosus and asymptomatic autoimmune thyroid disease. This case of multiple autoimmune syndrome is a distinctive subgroup of autoimmune disorders that is increasingly recognized. Female hormone levels appeared to play a role in disease pathogenesis in this case. The patient was predicted to have a favourable prognosis due to the absence of major organ involvement. This case revealed an uncommon form of complex polyautoimmune phenomena and should prompt physicians to extend immunological screening, particularly for females with multiple illnesses.
24527077 Diagnosis of Felty's syndrome, distinguished from hematological neoplasm: A case report. 2014 Mar Felty's syndrome (FS) is characterized by the three conditions of rheumatoid arthritis (RA), neutropenia and splenomegaly, and occurs in few cases of longstanding erosive RA. Discriminating between rare occurrences of autoimmune diseases and malignancies is crucial. The present study describes the case of a 17-year-old female with a two-year history of RA, presenting with an irregular fever, hepatosplenomegaly and enlarged lymph nodes. The antinuclear antibody titer was 1:320, while antibody results for anti-dsDNA, anti-Sm and rheumatoid factor were negative. The clinical presentation was similar to that of lymphoma. However, the fluorodeoxyglucose-positron emission tomography and biopsy examinations of the liver and cervical lymph node did not support the diagnosis of lymphoma. According to the laboratory results and clinical symptoms, the differential diagnosis indicated FS, and immunosuppressive agents were administered. Two weeks later, the patient no longer had a fever, and the transaminase levels were normal, associated with shrinkage of the liver and spleen.
24233383 Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collage 2013 Dec The PK/PD of abatacept, a selective T cell co-stimulation modulator, was examined in rats with collagen-induced arthritis (CIA) using a nonlinear mixed effect modeling approach. Male Lewis rats underwent collagen induction to produce rheumatoid arthritis. Two single-dose groups received either 10 mg/kg intravenous (IV) or 20 mg/kg subcutaneous (SC) abatacept, and one multiple-dose group received one 20 mg/kg SC abatacept dose and four additional 10 mg/kg SC doses. Effects on disease progression (DIS) were measured by paw swelling. Plasma concentrations of abatacept were assayed by enzyme-linked immunosorbent assay. The PK/PD data were sequentially fitted using NONMEM VI. Goodness-of-fit was assessed by objective functions and visual inspection of diagnostic plots. The PK of abatacept followed a two-compartment model with linear elimination. For SC doses, short-term zero-order absorption was assumed with F = 59.2 %. The disease progression component was an indirect response model with a time-dependent change in paw edema production rate constant (k in ) that was inhibited by abatacept. Variation in the PK data could be explained by inter-individual variability in clearance and central compartment volume (V 1 ), while the large variability of the PD data may be the result of paw edema production (k in 0 ) and loss rate constant (k out ). Abatacept has modest effects on paw swelling in CIA rats. The PK/PD profiles were well described by the proposed model and allowed evaluation of inter-individual variability on drug- and DIS-related parameters.
24744271 Metabolomics approach in allergic and rheumatic diseases. 2014 Jun Metabolomics is the analysis of the concentration profiles of low molecular weight compounds present in biological fluids. Metabolites are nonpeptide molecules representing the end products of cellular activity. Therefore, changes in metabolite concentrations reveal the range of biochemical effects induced by a disease or its therapeutic intervention. Metabolomics has recently become feasible with the accessibility of new technologies, including mass spectrometry and high-resolution proton nuclear magnetic resonance, and has already been applied to several disorders. Indeed, it has the advantage of being a nontargeted approach for identifying potential biomarkers, which means that it does not require a preliminary knowledge of the substances to be studied. In this review, we summarize the main studies in which metabolomic approach was used in some allergic (asthma, atopic dermatitis) and rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) to explore the feasibility of this technique as a novel diagnostic tool in these complex disorders.
24899571 Identification of lymphoma predictors in patients with primary Sjögren's syndrome: a syst 2015 Jan 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.