Performance of a diagnostic score for gouty arthritis: results from a cohort of acute arthritis suspected of being septic.

Septic arthritis (SA) and gout are the main suspected etiologies of acute monoarthritis. Differentiating them is essential because SA is an emergency. The performance of a gout diagnostic score developed by Janssens et al. was investigated in a cohort of patients with acute arthritis suspected of being septic. This was an ancillary study of a single-center cohort of patients with suspected SA. Patients were classified into three groups according to the final diagnosis (gout, SA or other diagnosis). We assessed the performance of the score (sensitivity [Se], specificity [Sp], positive and negative predictive value [PPV, NPV], area under the receiver operating characteristic [ROC] curve) for the diagnosis of gouty arthritis. In total, 138 patients were included: 28 (20.3%) had gout, 42 (30.4%) SA, and 68 (49.3%) another diagnosis. The median diagnostic score was 7.0 [4.5; 8.8] for patients with gout, 3.5 [2.5; 6.0] for those with SA and 3.0 [2.0-5.0] for those with another diagnosis. With a score threshold of ≥ 8, the Se for a diagnosis of gout was 28.6%, Sp 96.4%, PPV 66.7%, and NPV 84.1%. With a threshold of ≤ 4, the Se was 82.1%, Sp 64.5%, PPV 37.1%, and NPV 93.4%. The area under the ROC for the diagnostic score was 0.79. The performance of the clinico-biological score of Janssens et al. for a diagnosis of gout applied to a cohort of patients with acute arthritis and suspected of being septic was poor. Joint aspiration remains necessary to differentiate SA from another etiology.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

OBJECTIVES: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). METHODS: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. RESULTS: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. CONCLUSIONS: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Concomitant fibromyalgia in primary Sjögren's syndrome in the French ASSESS cohort: comparison of the ACR 1990 and ACR 2016 criteria, FiRST questionnaire and physician's opinion.

OBJECTIVES: Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS. METHODS: Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. RESUKLTS: FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39). CONCLUSIONS: The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

Therapeutic education improves rheumatoid arthritis patients' knowledge about methotrexate: a single center retrospective study.

To assess, by means of a questionnaire, the effectiveness of a therapeutic education session on rheumatoid arthritis patients' knowledge about methotrexate. Retrospective study of data collected in routine care. STROBE guidelines were used. Rheumatoid arthritis patients treated with methotrexate had a therapeutic education session conducted by a rheumatology nurse at time 0 and 6 months after. They completed a questionnaire to assess their knowledge about methotrexate before the first therapeutic education session and 6 and 12 months after. A score from 0 to 100 was calculated based on 20 questions. A total of 66 patients were enrolled (50 women), with a mean age of 57 years, median disease duration of 4 years, and methotrexate treatment duration of 2 years. The knowledge score improved 6 months after the first therapeutic education session and was unchanged at 12 months. Significant improvement was observed in knowledge about the need for contraception, the contraindication of trimethoprim, the maximum dose not to be exceeded, reduction in alcohol consumption, and the value of combining folic acid with methotrexate. Knowledge about the risk of hypersensitivity pneumonitis did not improve. Skills related to the need for and timing of laboratory testing and contraception were evaluated using two role-playing situations. None of the skills improved. A therapeutic education session improves patients' knowledge about methotrexate at 6 months.

Management of inflammatory rheumatic conditions in the elderly.

The number of elderly people with chronic inflammatory rheumatic diseases is increasing. This heterogeneous and comorbid population is at particular risk of cardiovascular, neoplastic, infectious and iatrogenic complications. The development of biotherapies has paved the way for innovative therapeutic strategies, which are associated with toxicities. In this review, we have focused on the scientific and therapeutic changes impacting the management of elderly patients affected by RA, SpA or PsA. A multidimensional health assessment resulting in an integrated therapeutic strategy was identified as a major research direction for improving the management of elderly patients.

Is early-onset primary Sjögren's syndrome a worse prognosis form of the disease?

OBJECTIVES: Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome. METHODS: Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis. RESULTS: Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001). CONCLUSION: Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.

Role of the IL-12/IL-35 balance in patients with Sjögren syndrome.

BACKGROUND: An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of TH1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35. OBJECTIVE: We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies. METHODS: The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively. RESULTS: We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS. CONCLUSION: Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease.

A randomised, double-blind, placebo-controlled study assessing the efficacy of high doses of vitamin D on functional disability in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the short-term efficacy of vitamin D (cholecalciferol) supplementation on functional disability in RA patients. METHODS: 1) Patients: RA (ACR 1987 revised criteria) in non-remission (DAS28 >2.6) whose treatment was not expected to be changed over a 3-month period following inclusion and presenting with vitD deficits (serum 25OHD <30ng/mL). 2) Study design: prospective randomised placebo-controlled trial (NCT02243800). 3) Study arms: either vitD ampoules (cholecalciferol 100,000IU) or placebo. 4) Outcome measures: primary: improvement in patients' functional disability using the Health Assessment questionnaire (HAQ); secondary: improvement in DAS28ESR, DAS28CRP, ESR, CRP, RAID score, fatigue (EVA and FACIT), and SF36. RESULTS: Overall, 59 patients were included, 83.1% females, aged 59.8±10.9 years on average, with RA for 17.0±9.7 years. Thirty patients received placebo and 29 vitD. At 6 months, HAQ scores tended to be increased in the placebo group (+0.08±0.25), while slightly numerically decreased in the vitD group (-0.03±0.23) (p=0.11). After adjusting for age, gender, season, and initial vitD status, the between-group difference achieved statistically significance (p=0.046). After adjusting for age, gender, season, and initial vitD status, there was no significant difference in the secondary criteria between the 2 groups except for ESR and CRP (p=0.002 and 0.04, respectively). CONCLUSIONS: In this randomised, double-blind, placebo-controlled clinical trial in patients with RA and VitD deficiency, high doses of cholecalciferol resulted in a statistically significant improvement in functional disability at month 6, which, however, was clinically not relevant.

Management of dyslipidaemia in high-risk patients with recent-onset rheumatoid arthritis: targets still not met despite specific recommendations. Results from the ESPOIR cohort during the first five years of follow-up.

OBJECTIVES: Reduction of LDL-cholesterol (LDLc) is essential to decrease the cardiovascular mortality in rheumatoid arthritis (RA). Between 2005 and 2010, French recommendations for dyslipidaemia defined the LDLc target based on the number of cardiovascular risk factors. In 2006, it was recommended to consider LDLc objectives with RA being counted as an additional cardiovascular risk factor. Our objective was to assess lipid target achievement between 2006 and 2010 in a cohort of patients with recent-onset RA. METHODS: 814 patients were included between 2002 and 2005 in a French cohort of patients with early arthritis and a high probability of RA (ESPOIR). Repeated cross-sectional analyses for cardiovascular risk factors, cholesterol levels were performed every year from 2006 to 2010 to determine lipid profile and achievement of the LDLc goal according to the French guidelines. RESULTS: On the 620 patients analysed at the first point, 77% were female, 89.8% fulfilled the ACR criteria for RA and 2.7% received a statin. The proportion of patients failing to achieve the LDLc target did not improve following the publication of specific RA guidelines in 2006 (15.3 to 22.5% between 2006 and 2010). In patients with the highest cardiovascular risk, more than 58% did not reach the LDLc target. CONCLUSIONS: Specific recommendations for RA published in 2006 decreased LDLc target but did not improve management of dyslipidaemia in daily life which remained suboptimal particularly in patients at highest risk.

Characteristics of spontaneous coagulase-negative staphylococcal spondylodiscitis: a retrospective comparative study versus Staphylococcus aureus spondylodiscitis.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are increasingly implicated in recent patient series of spondylodiscitis, but there are no series of CoNS-spondylodiscitis available. The objective of this study was to compare the characteristics of patients with spontaneous CoNS-spondylodiscitis with those patients with Staphylococcus aureus (SA) spondylodiscitis. METHODS: This was a retrospective single center study involving 147 spontaneous infectious spondylodiscitis cases observed between 2000 and 2015. The 26 cases of CoNS-spondylodiscitis (15 confirmed) were compared with 30 cases of SA-spondylodiscitis. CoNS infection was considered confirmed if the same CoNS was isolated in at least two samples at two different times. RESULT: Patients with CoNS-spondylodiscitis were older (70 vs. 61 years of age; p = 0.01), had associated cancer more often (15% vs. 0%; p = 0.04) and had a longer diagnostic delay (>15 days in 88% vs. 60%; p = 0.01); experienced fever less often (19% vs. 50%; p = 0.01), and had lower white blood cell (7.6 vs. 9.9G/L; p = 0.01) and polymorphonuclear leucocyte counts (5.6 vs. 7.5G/L; p = 0.04). Patients with CoNS spondylodiscitis had less pronounced inflammatory syndrome (erythrocyte sedimentation rate [ESR]: 62 vs. 81 mm at 1 h; p = 0.03; CRP: 60 vs. 147 mg/L; p = 0.0003) and less common (ESR < 30 mm: 23% vs. 0%; p = 0.01; CRP < 10 mg/L: 23% vs. 0%; p = 0.005) in comparison with patients with SA infection. The infection entry site was most often an intravascular catheter (20% vs. 3%; p = 0.008). The level of positive percutaneous needle biopsies was comparable between CoNS and SA. Two patients who died both had SA infections. CONCLUSION: CoNS-spondylodiscitis involved at least 10% of spontaneous spondylodiscitis cases and was more common in elderly patients, afflicted by comorbidities, and its presentation was less virulent than that of those with SA-spondylodiscitis.

Germline variation of TNFAIP3 in primary Sjögren's syndrome-associated lymphoma.

BACKGROUND AND OBJECTIVE: A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association. PATIENTS AND METHODS: The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts. RESULTS: The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively). CONCLUSIONS: This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.

Performance of Fibromyalgia Rapid Screening Tool (FiRST) to detect fibromyalgia syndrome in rheumatic diseases.

OBJECTIVE: To evaluate the performance of the Fibromyalgia Rapid Screening Tool (FiRST) self-questionnaire for the detection of FM associated with inflammatory rheumatic diseases. METHODS: This cross-sectional, French single-centre study was carried out between September 2014 and April 2015 in all patients who consulted for RA, SpA or CTD. Diagnosis of FM was based on ACR 90 criteria and rheumatologist opinion. RESULTS: The self-questionnaire was completed by 605 patients (279 RA, 271 SpA, 57 CTD). It detected 143 concomitant FMs (24.4%). When assessed against ACR 90 criteria, FiRST had a sensitivity of 74.5%, a specificity of 80.4%, a positive predictive value of 26.6% and a negative predictive value (NPV) of 97.1%. Specificity was lower in the CTD group (RA: 84.4%, SpA: 80.2%, CTD: 59.6%) (P = 0.001). When assessed against the rheumatologist's opinion, FiRST had a sensitivity of 75.8%, a specificity of 85.1%, a positive predictive value of 48.3% and an NPV of 95%. Sensitivity was lower in the SpA group than in the CTD group (66% vs 94.4%) (P = 0.004). Performance varied according to self-questionnaire items. CONCLUSION: Although it performs less well in inflammatory rheumatic disease, FiRST's opinion is close to that of the rheumatologist. It can be used by the rheumatologist in clinical practice for patients facing an apparent treatment failure and to rule out a potential FM diagnosis which could interfere with the treatment response.

Psoriatic arthritis treated by anti-TNFs: a monocentric trial of 102 cases in Auvergne, France.

OBJECTIVES: While several registries have already evaluated the retention of anti-TNF therapy in psoriatic arthritis (PsA), they sometimes reach divergent conclusions. Our study therefore sought to assess therapeutic retention rates and predictive factors of response in a patient cohort from Auvergne, France, followed up in routine clinical practice. METHODS: Medical records of all PsA patients treated from 2002 to May 2015 were analysed. PsA diagnosis was established based on the CASPAR criteria. RESULTS: In total, 102 patients were analysed, comprising 62 men (44.6±12.6 years) and 40 women (37.8±13.4). Mean PsA evolution was 2.7 years (0.8-11.2). The most common forms were peripheral (47/102, 45.1%) and mixed (46/102, 46.1%) PsA. The anti-TNF treatment initiated was etanercept in 47 cases (45.2%), adalimumab in 29 (27.9%), infliximab in 20 (19.2%), and golimumab in six [5.8%]. In 28 cases (27.4%), anti-TNF was associated with methotrexate (MTX). Overall, the median duration of anti-TNF retention was 76.5 months. The hazard ratios (HR) for treatment cessation did not significantly differ between the etanercept and monoclonal antibody groups (HR=1.35[0.96-1.93], p=0.08). After 5 years, approximately 30.8% of etanercept patients and 68.8% of monoclonal antibody patients (adalimumab 71.2%; infliximab 67.2%) were still being treated. Combining with MTX did not prolong the overall retention rate (HR=0.85[0.37-1.96], p=0.71). Tobacco use was predictive of discontinuation (p=0.03). CONCLUSIONS: Our study demonstrates good anti-TNF treatment retention in PsA patients, as well as confirming the deleterious effect of smoking while providing no argument in favour of combined treatment with MTX to improve maintenance.

The development of a questionnaire to evaluate rheumatoid arthritis patient's knowledge about methotrexate.

AIMS AND OBJECTIVES: Assess knowledge concerning methotrexate in rheumatoid arthritis patients by means of a questionnaire. BACKGROUND: Methotrexate is the standard drug for rheumatoid arthritis treatment. It has potentially serious side effects that can be largely prevented by making sure that patients are well informed and comply with prescription guidelines. DESIGN: Cross-sectional survey. METHODS: A questionnaire on methotrexate (mode of action, administration, drug interactions), side effects, monitoring and lifestyle implications was offered to all the rheumatoid arthritis patients treated with the drug seen between March and September 2013 in a large hospital in France. RESULTS: One hundred and eighty-three patients (143 women), mean age 60 (13·5) years, with a median disease duration of 12 years [7-20] and treated with methotrexate for eight years [5-13] took part. Methotrexate was identified as a disease-modifying antirheumatic drug by 78% of the patients. The weekly administration method was well assimilated (97%); 67% indicated that the rationale for folic acid was to reduce treatment toxicity. Only 21% knew that trimethoprim was contraindicated. Half were aware of the haematologic risk and 36% were aware of the risk of hypersensitivity pneumonitis. There was knowledge concerning laboratory testing (80%), but 54% thought they were only being monitored for rheumatoid arthritis activity. Only 13% of the men, but 90% of the women, of childbearing age knew that contraception was essential, and 75% indicated that alcohol consumption should be limited. A low knowledge score correlated significantly with age and low educational level. It was independent of sex, duration of treatment for rheumatoid arthritis. CONCLUSIONS: Rheumatoid arthritis patient's knowledge concerning methotrexate is poor, particularly for the most serious side effects (haematologic and hypersensitivity pneumonitis), interactions with trimethoprim, and in men, the need for contraception. RELEVANCE TO CLINICAL PRACTICE: Patient knowledge concerning methotrexate should be regularly checked and supported using the different therapeutic education tools available, especially when patients are older people and have had limited schooling.

Development of the Sjögren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy.

OBJECTIVES: To determine which outcome measures detected rituximab efficacy in the Tolerance and Efficacy of Rituximab in Sjögren's Disease (TEARS) trial and to create a composite endpoint for future trials in primary SS (pSS). METHODS: Post hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS trial. The results were validated using data from two other randomized controlled trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and infliximab, respectively. RESULTS: Five outcome measures were improved by rituximab in the TEARS trial: patient-assessed visual analogue scale scores for fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and ESR. We combined these measures into a composite endpoint, the SS Responder Index (SSRI), and we defined an SSRI-30 response as a ≥30% improvement in at least two of five outcome measures. In TEARS, the proportions of patients with an SSRI-30 response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs 21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI-30 response rates after 12 and 24 weeks in the single-centre rituximab trial were 68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No significant differences in SSRI-30 response rates were found between infliximab and placebo at any of the time points in the infliximab trial. CONCLUSION: A core set of outcome measures used in combination suggests that rituximab could be effective and infliximab ineffective in pSS. The SSRI might prove useful as the primary outcome measure for future therapeutic trials in pSS.

Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome.

Several autoimmune diseases, including primary Sjögren's syndrome (pSS), are associated with an increased risk for lymphoma. Polymorphisms of TNFAIP3, which encodes the A20 protein that plays a key role in controlling nuclear factor κB activation, have been associated with several autoimmune diseases. Somatic mutations of TNFAIP3 have been observed in the mucosa-associated lymphoid tissue lymphoma subtype frequently associated with pSS. We studied germline and somatic abnormalities of TNFAIP3 in 574 patients with pSS, including 25 with lymphoma. Nineteen additional patients with pSS and lymphoma were available for exome sequence analysis. Functional abnormalities of A20 were assessed by gene reporter assays. The rs2230926 exonic variant was associated with an increased risk for pSS complicated by lymphoma (odds ratio, 3.36 [95% confidence interval, 1.34-8.42], and odds ratio, 3.26 [95% confidence interval, 1.31-8.12], vs controls and pSS patients without lymphoma, respectively; P = .011). Twelve (60%) of the 20 patients with paired germline and lymphoma TNFAIP3 sequence data had functional abnormalities of A20: 6 in germline DNA, 5 in lymphoma DNA, and 1 in both. The frequency was even higher (77%) among pSS patients with mucosa-associated lymphoid tissue lymphoma. Some of these variants showed impaired control of nuclear factor κB activation. These results support a key role for germline and somatic variations of A20 in the transformation between autoimmunity and lymphoma.