Sjogren's syndrome
Risk, Predictors, and Clinical Characteristics of Lymphoma Development in Primary Sjögren's Syndrome

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Objective

To assess the risk and predictors of lymphoma development in a large cohort of patients with primary Sjögren's syndrome (pSS).

Methods

Cox-regression analyses were used to study the predictive value of clinical and laboratory findings at pSS diagnosis, and Kaplan-Meier survival curves to compare survival probability between patients who developed lymphoma and the total cohort. Expected risk for lymphoma was calculated by comparison with the background population.

Results

Eleven (4.5%) from 244 patients developed a non-Hodgkin lymphoma (NHL). Diffuse large B-cell and mucosa-associated lymphoid tissue lymphomas occurred at a similar frequency. Three (27.3%) patients died: 2 due to transformation from mucosa-associated lymphoid tissue to diffuse large B-cell. Purpura (HR 8.04, 95% confidence interval [CI] 2.33-27.67), parotidomegaly (HR 6.75, 95%CI 1.89-23.99), anemia (HR 3.43, 95%CI 1.04-11.35), leukopenia (HR 8.70, 95%CI 2.38-31.82), lymphocytopenia (HR 16.47, 95%CI 3.45-78.67), hypergammaglobulinemia (HR 4.06, 95%CI 1.06-15.58), low C3 (HR 36.65, 95%CI 10.65-126.18), and low C4 (HR 39.70, 95%CI 8.85-126.18) levels at pSS diagnosis were significant predictors of NHL development, but only hypocomplementemia and lymphocytopenia were independent risk factors. Hypocomplementemia was related to earlier development of NHL and higher mortality. The cumulative risk of developing lymphoma ranged from 3.4% in the first 5 years to 9.8% at 15 years. Standardized incidence ratio (95%CI) for NHL development was 15.6 (95%CI 8.7-28.2).

Conclusions

Patients with pSS have a 16-fold increased risk of developing lymphoma. This risk increases with time. Hypocomplementemia and lymphocytopenia at pSS diagnosis are the strongest predictors. Survival is clearly reduced in patients with hypocomplementemia. Indolent lymphomas tend to evolve over time toward a more aggressive histologic type.

Section snippets

Patients and Methods

All patients consecutively diagnosed with pSS and followed up consecutively at our department between January 1988 and December 2008 were eligible for the study. Patients were followed at regular intervals of 6 to 12 months or more frequently if required. All patients fulfilled 4 or more of the preliminary diagnostic criteria for pSS proposed in 1993 by the European Community Study Group (13). A complete history and physical examination was obtained in all cases. Diagnostic tests for

Results

The study cohort consisted of 244 patients (235 females and 9 males), with a mean age of 57.8 ± 13.6 years (median 59 year; range 17-88 years) at pSS diagnosis. All patients fulfilled the diagnostic criteria for pSS proposed by the European Community Study Group (13), and 201 (82.38%) fulfilled the American-European Consensus criteria (18). The median follow-up was 8.6 years (1 to 20 year).

Eleven patients developed a NHL: 4 of MALT type, 3 DLBCL, 3 follicular lymphoma, and 1 both MALT and

Discussion

The present series is 1 of the largest single-center experiences on patients with pSS-associated lymphoproliferative disease. In accordance with previous reports (5, 7, 8, 9) we confirmed the preponderance of B-cell malignancies in pSS patients. Eleven of 244 (4.5%) patients developed a NHL in our series, similar to others that estimated this probability about 5 to 8% (5, 7, 8, 9, 11). The relative risk of developing lymphoma was estimated to be 16 times higher than the general population,

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    The authors have no conflicts of interest to disclose.

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