Diagnostic utility of a second minor salivary gland biopsy in patients with suspected Sjögren's syndrome: A retrospective cohort study.

OBJECTIVE: To determine whether repeated minor salivary gland biopsy (MSGB) has a clinical diagnostic utility in patients with suspicion of Sjögren's syndrome (SS). METHODS: Clinical, biological, pathological data and physician's diagnosis after each MSGB from patients with suspected primary or secondary SS who had benefited from 2 MSGB at Brest University Hospital between January 1st, 1990 and January 14th, 2015, were retrospectively collected. We compared the characteristics of patients with and without first positive MSGB, concordance between the MSGB, and analyzed the modifications of diagnosis after the second MSGB. RESULTS: Ninety-three patients were included, first MSGB was positive for 23 and negative for 70. Patients with first positive MSGB had more often renal involvement (P<0.05) and hypergammaglobulinemia (P=0.01), anti-SSA antibodies (P<0.05) and positive second biopsy with focus score ≥ 1 or Chisholm>2 (P<0.01). The mean time between the 2 MSGB was 5.7±4.3 years. The concordance between the results of the 2 biopsies was low (κ = 0.34). MSGB influenced diagnostic's change in 10 cases where the second MSGB was always guided by new specific clinical manifestations. CONCLUSION: We observed a low concordance between 2 MSGB in patients with suspected pSS in our study. Despite this variability, performing a second MSGB changed the initial diagnosis in only a minority of the patients and was particularly useful when clinical manifestations had deeply evolved.

Sicca syndrome in systemic sclerosis: a narrative review on a neglected issue.

SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren's disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc.

Comparison of 18- and 22-MHz probes for the ultrasonographic diagnosis of giant cell arteritis.

PURPOSE: Little is known about the diagnostic concordance of images provided by ultrasound probes with emitting frequencies below or above 20 MHz for the diagnosis of giant cell arteritis (GCA). METHODS: We compared, using Cohen's kappa statistic, data obtained with an 18-MHz and a 22-MHz probe for the ultrasonographic evaluation of temporal arteries in 80 patients referred for suspected GCA. RESULTS: The halo sign was found in 25% of cases with the 18-MHz probe and in 35% with the 22-MHz probe. The compression sign was positive in 42% of cases with the 18-MHz probe and 48% with the 22-MHz probe. GCA was finally diagnosed in 20 patients (25%). The kappa coefficient of agreement was 0.76 (P < .001) for the halo sign, and 0.75 (P < .001) for the compression sign. CONCLUSIONS: Images obtained by 18 MHz and 22-MHz frequency probes showed a good level of agreement for the diagnosis of GCA, but the 22-MHz probe yielded a correct diagnosis of GCA in 3 of the 7 patients in whom examination with the 18-MHz probe was negative.

Normal salivary gland ultrasonography could rule out the diagnosis of Sjögren's syndrome in anti-SSA-negative patients with sicca syndrome.

OBJECTIVE: To evaluate the relevance of salivary gland ultrasound (SGUS) and its place in the diagnostic algorithm in patients referred with dry syndrome (DS) for a suspicion of Sjögren's syndrome (SS). METHODS: We included all patients assessed at our dedicated DS clinic from June 2015 to September 2019 for which a SGUS has been carried out. Images were read blindly and the worst salivary gland was scored according to OMERACT classification. Clinical features, disease activity and treatments were collected. RESULTS: 337 patients were seen from June 2015 to September 2019. 269 patients underwent SGUS. 77 patients were diagnosed with SS and 192 did not meet the ACR/EULAR criteria for SS: non-Sjögren's DS (NSDS). Of these 192 patients, 60 had another possible cause of DS, and 132 patients were diagnosed with SAPS (sicca, asthenia, polyalgia syndrome).SGUS abnormalities were significantly higher in patients with SS versus NSDS: 51% vs 8% for a score ≥2 (p<0.0001), and 43% vs 3% for a score ≥3 (p<0.0001). SGUS score ≥2 had a specificity (Sp) of 91%, sensitivity (Se) of 57%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 82% for SS diagnosis. SGUS's characteristics in SSA-negative patients were similar to the whole population (Se=42%, Sp=91%, PPV=42%, NPV=92%). The high specificity and NPV in this population could avoid labial salivary gland biopsy (LSGB) in SSA-negative patients with normal SGUS (186 patients, 69%). CONCLUSION: SGUS is useful for SS diagnosis. If anti-SSA antibodies are negative and SGUS score <2, the diagnosis of SS is very improbable and LSGB could be avoided.

[Contribution of Doppler ultrasound for the diagnosis of giant cell arteritis]. / Apport de l'écho-doppler pour le diagnostic d'artérite à cellules géantes.

Ultrasound is a useful imaging modality for the diagnosis of giant cell arteritis. Ultrasound of temporal arteries is recommended as the first imaging modality in patients with suspected predominantly cranial giant cell arteritis. The thickening of the arterial wall (halo sign) is the ultrasound finding most suggestive of giant cell arteritis. In patients in whom there is a high clinical suspicion of giant cell arteritis and a halo sign, the diagnosis of giant cell arteritis may be made without temporal artery biopsy.

Minimally invasive ultrasound-guided parotid gland biopsy in cadavers performed by rheumatologists.

Introduction: Surgical biopsy of minor salivary glands is routinely performed for the diagnosis of Sjögren syndrome. However, surgical biopsies of the minor labial glands may result in various complications in up to 6% of patients. On the other hand, adverse events following core needle biopsies of the parotid gland in non-rheumatological settings have been reported as very rare. Aim: The objective of this study was to assess the feasibility and determine the presence of parotid gland tissue in ultrasound-guided parotid gland biopsies performed by rheumatologists in cadavers. Material and method: Two senior rheumatologists obtained, under direct ultrasound visualization in in-plane technique, biopsies of 8 parotid glands from 4 different cadavers using a core biopsy needle. One biopsy per gland was taken. Results: All histological exams showed typical parotid gland tissue without any neuronal or vascular tissue. Conclusion: In conclusion, we demonstrated that minimally invasive, ultrasound-guided core needle biopsy of the parotid gland is a highly precise and easy method to obtain salivary gland tissue.Introduction: Surgical biopsy of minor salivary glands is routinely performed for the diagnosis of Sjögren syndrome. However, surgical biopsies of the minor labial glands may result in various complications in up to 6% of patients. On the other hand, adverse events following core needle biopsies of the parotid gland in non-rheumatological settings have been reported as very rare. Aim: The objective of this study was to assess the feasibility and determine the presence of parotid gland tissue in ultrasound-guided parotid gland biopsies performed by rheumatologists in cadavers. Material and method: Two senior rheumatologists obtained, under direct ultrasound visualization in in-plane technique, biopsies of 8 parotid glands from 4 different cadavers using a core biopsy needle. One biopsy per gland was taken. Results: All histological exams showed typical parotid gland tissue without any neuronal or vascular tissue. Conclusion: In conclusion, we demonstrated that minimally invasive, ultrasound-guided core needle biopsy of the parotid gland is a highly precise and easy method to obtain salivary gland tissue.

Peripheral-blood b-cell subset disturbances in inflammatory joint diseases induced by Tropheryma whipplei.

OBJECTIVE: To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple's disease (WD). METHOD: Consecutive patients seen between 2010 and 2016 for suspected inflammatory joint disease were identified retrospectively. Results of standardized immunological and serological tests and of peripheral-blood B-cell and T-cell subset analysis by flow cytometry were collected. Patients with criteria suggesting WD underwent PCR testing for Tropheryma whipplei, and those with diagnosis of WD (cases) were compared to those without diagnosis (controls). We used ROC curve analysis to evaluate the diagnostic value of flow cytometry findings for WD. RESULTS: Among 2917 patients seen for suspected inflammatory joint disease, 121 had suspected WD, including 9 (9/121, 7.4%) confirmed WD. Proportions of T cells and NK cells were similar between suspected and confirmed WD, whereas cases had a lower proportion of circulating memory B cells (IgD-CD38low, 18.0%±9.7% vs. 26.0%±14.2%, P = 0.041) and higher ratio of activated B cells over memory B cells (4.4±2.0 vs. 2.9±2.2, P = 0.023). Among peripheral-blood B-cells, the proportion of IgD+CD27- naive B cells was higher (66.2%±18.2% vs. 54.6%±18.4%, P = 0.047) and that of IgD-CD27+ switched memory B cells lower (13.3%±5.7% vs. 21.4%±11.9%, P = 0.023), in cases vs. controls. The criterion with the best diagnostic performance was a proportion of IgD+CD27- naive B cells above 70.5%, which had 73% sensitivity and 80% specificity. CONCLUSION: Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.

Diagnostic performance of temporal artery ultrasound for the diagnosis of giant cell arteritis: a systematic review and meta-analysis of the literature.

Despite major recent advances in the therapeutic management of Giant cell arteritis (GCA), the diagnosis accuracy of temporal artery ultrasound remains controversial in this disease. We performed a systematic review to determine the sensitivity, specificity, and summary positive (LR+) and negative (LR-) likelihood ratios of temporal artery ultrasound for the diagnosis of GCA. For this, we searched EMBASE, MEDLINE and the Cochrane Database of Systematic Reviews without language restriction. Original articles reporting on diagnostic accuracy of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA, were selected. Sensitivity and specificity from each study were used to fit a bivariate diagnosis accuracy model. Of 1280 articles identified, 48 underwent full-text review, and 25 were included. Based on a total of 20 studies, the sensitivity and specificity of hypoechoic halo compared to positive temporal artery biopsy were respectively of 68% (95% CI: 57-78) and 81% (95%CI: 75-86). The summary mean positive and negative likelihood ratios were respectively of 3.64 (95%CI: 2.76-4.73) and 0.40 (0.28-0.52). Taking into account 11 studies reporting on the presence of any abnormal sign on temporal artery ultrasound yielded similar results with largely overlapping 95% confidence interval regions. This study provides the summary estimates of the diagnostic properties of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA. Those parameters allow the calculation of the post-test probability of GCA in a given patient, based on the results of temporal artery ultrasound and will help improving the diagnosis strategy for this common disease.

Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative.

OBJECTIVES: To evaluate the reliability of consensus-based ultrasound (US) definitions of elementary components of enthesitis in spondyloarthritis (SpA) and psoriatic arthritis (PsA) and to evaluate which of them had the highest contribution to defining and scoring enthesitis. METHODS: Eleven sonographers evaluated 40 entheses from five patients with SpA/PsA at four bilateral sites. Nine US elementary lesions were binary-scored: hypoechogenicity, thickened insertion, enthesophytes, calcifications, erosions, bone irregularities, bursitis and Doppler signal inside and around enthesis. Kappa statistics were used to evaluate reliability. Sonographers were also asked to state which lesions can be considered as inflammatory or structural and should be included in the final definition of enthesitis. Only the lesions, scored as present in at least 75% of the entheses considered as having an enthesitis, were included in the final definition. RESULTS: The prevalence of detected lesions was quite low except for enthesophytes (55%) and bone irregularities (54%). Reliability ranged from poor to good (the lowest for thickened enthesis (kappa 0.1 (95% CI 0 to 0.7)) and the highest for enthesophytes (kappa 0.6 (95% CI 0.5 to 0.7)). When adjusted for low prevalence, kappa values increased for all lesions, with the best result observed for detecting Doppler signal at insertion (0.9) and for bursitis (0.8). The US components included in the final definition were hypoechogenicity, increased thickness at enthesis, erosions and calcifications/enthesophytes and Doppler signal at insertion. CONCLUSION: By using a consensus-based stepwise approach, a final reliable US score and definition of enthesitis in SpA/PsA were produced. Further studies are sought for implementing this score in clinical trials and practice.

Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable or uninterpretable.

Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP. Methods: We used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI cohort, we evaluated correlations between PMR-AS items to select the best item for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin-PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin-PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during tocilizumab therapy. Results: In the CRI cohort, agreement between PMR-AS and clin-PMR-AS was excellent (κ = 0.90). Linear regression between PMR-AS and clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP-imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24 (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion: Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR activity in everyday practice in patients without available CRP values and in those receiving IL-6 antagonist therapy.

Comparison of 2002 AECG and 2016 ACR/EULAR classification criteria and added value of salivary gland ultrasonography in a patient cohort with suspected primary Sjögren's syndrome.

BACKGROUND: The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients. METHODS: Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen's κ coefficient. Characteristics of discordantly categorised patients were detailed. RESULTS: We prospectively included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria set. Concordance was excellent (κ = 0.92). Compared to patients fulfilling both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had similar age and symptom duration but lower frequencies of xerophthalmia and xerostomia (p < 0.01 for each) and salivary gland dysfunction (p < 0.01); most had systemic involvement (91%), including three (27%) with no sicca symptoms; 91% had abnormal salivary gland biopsy and 46% anti-Sjögren's-syndrome-related antigen A (anti-SSA); 64% were diagnosed with pSS by the physician. SGUS was abnormal in 12% of the 165 patients fulfilling no criteria set. Including SGUS among the ACR/EULAR criteria increased sensitivity from 87.4% to 91.1% when physician diagnosis was the reference standard. CONCLUSIONS: Agreement between AECG and ACR/EULAR criteria sets is excellent. ACR/EULAR criteria are slightly more sensitive and classified some patients without sicca symptoms as having pSS. Including SGUS in the ACR/EULAR criteria may further improve their sensitivity.

High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjögren's Syndrome: Data from the TEARS Randomized Trial.

PURPOSE: To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren's syndrome [pSS]. MATERIALS AND METHODS: Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14), half met the Sjögren's Syndrome Responder Index [SSRI]-30 definition of a response at week 24. RESULTS: The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade ≤3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0-1.3] in the responders versus 4.0 [2.7-5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate. CONCLUSION: In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS.

Predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis.

OBJECTIVE: To evaluate the predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis (RA). METHODS: A post hoc analysis was performed on a prospective 2-year study of 59 patients with active RA starting on antitumour necrosis factor (TNF). Tenderness and synovitis was assessed clinically at baseline, followed by blinded ultrasound assessment (B-mode and power Doppler ultrasound (PDUS)) on the hands and feet (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal and 10 metatarsophalangeal (MTP) joints). Radiographs of these joints were performed at baseline and at 2 years. The risk of radiographic progression with respect to the presence of baseline tenderness or synovitis, as well as its persistence (after 4 months of anti-TNF), was estimated by OR (95% CI). RESULTS: Baseline tender joints were the least predictive for radiographic progression (OR=1.53 (95% CI 1.02 to 2.29) p<0.04), when compared to synovitis (clinical OR=2.08 (95% CI 1.39 to 3.11) p<0.001 or PDUS OR=1.80 (95% CI 1.20 to 2.71) p=0.005, respectively). Tender joints with the presence of synovitis were predictive of radiographic progression (OR=1.89 (95% CI 1.25 to 2.85) p=0.002), especially seen in the MTP joints. Non-tender joints with no synovitis were negatively predictive (OR=0.57 (95% CI 0.39 to 0.82) p=0.003). Persistence of tender joints was negatively predictive (OR=0.38 (95% CI 0.18 to 0.78) p=0.009) while persistence of synovitis was predictive (OR=2.41 (95% CI 1.24 to 4.67) p=0.01) of radiographic progression. CONCLUSIONS: Synovitis is better than tenderness to predict for subsequent structural progression. However, coexistence of tenderness and synovitis at the level of an individual joint is predictive of structural damage, particularly in the MTP joints. TRIAL REGISTRATION NUMBER: NCT00444691.

Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren's syndrome.

OBJECTIVES: To determine whether B-cell markers (blood and minor salivary gland [SG] B-cell depletion [BCD], autoantibodies, B-cell-activating factor [BAFF]) are associated with clinical response to rituximab in patients with primary Sjögren's syndrome (pSS). METHODS: 45 patients with pSS were included: in group I, 14 received low-dose rituximab (two 375-mg/m(2) infusions) in an open-labelled study; in group II, 17 received full-dose rituximab (two 1000-mg infusions) and 14 received a placebo in a randomized, controlled study. The proportion of SG B cells was assessed using pixel-based software analyses of digitized double-immunostained (CD3/CD20) whole SGs. Response was defined at week-24 according to the Sjögren's Syndrome Responder Index (SSRI)-30. RESULTS: Response rate was 50% in both groups of rituximab-treated patients. Duration of blood BCD was similar in both groups despite the difference in rituximab dosage, and was highly correlated with residual serum-rituximab levels at week-16. SG B-cell dynamics mirrored blood B-cell levels, with a drastic decrease in SG B-cells at week-12 (group I), but an increase in ∼ 50% of patients in group II by week-24, in whom blood B cells had already returned. Duration of BCD was not associated with the clinical response, but responders had lower baseline proportions of SG B cells. Baseline serum BAFF level was correlated with the proportion of SG B-cells and other B-cell-activation markers, and was associated with the clinical response with higher levels in non-responders. CONCLUSIONS: In pSS, half of the patients display an intense BAFF-driven B-cell activation and do not respond to a single course of rituximab.

Lymphopenia in early arthritis: Impact on diagnosis and 3-year outcomes (ESPOIR cohort).

OBJECTIVES: In patients with early arthritis naive to disease-modifying antirheumatic drugs, we evaluated the prevalence of initial and persistent lymphopenia, underlying diagnoses, and risk of infection or malignancy. METHODS: Eight hundred and thirteen patients with early arthritis included in the ESPOIR cohort had a clinical examination, laboratory tests (viral serology, immunological tests, and cytokine profile), and radiographs. We determined the prevalence of lymphopenia at baseline and after 3 years, associated factors, diagnoses, and risk of infection or malignancy. RESULTS: At baseline, 50/813 (6.2%) patients had lymphopenia. Lymphopenia was associated with positive rheumatoid factor (P=0.02), cytopenia (P≤0.05), hepatitis C (P=0.05), higher C-reactive protein and DAS28 (P≤0.05 for both). Cytokine profile and radiological progression were not significantly different between patients with and without lymphopenia. Suspected diagnoses at inclusion were rheumatoid arthritis (RA, n=27), unclassified arthritis (n=15), systemic lupus erythematosus (SLE, n=3), spondyloarthritis (n=2), Sjögren's syndrome (n=1), hematologic disease (n=1), and fibromyalgia (n=1). Fifteen patients out of 42 (35.7%) with initial lymphopenia had persistent lymphopenia after 3 years, including 5 with documented causes (lupus, hepatitis C, undernutrition, azathioprine, and tamoxifen); none had PVB19, HIV, or HBV infection and none experienced infections, solid or hematologic malignancies during follow-up. Final diagnoses in these 15 patients were RA (n=6), unclassified arthritis (n=6), SLE (n=1), spondyloarthritis (n=1), and fibromyalgia (n=1). CONCLUSIONS: Lymphopenia is rare in early arthritis. The most common rheumatic cause is RA, in which marked inflammation and other cytopenias are common. Lymphopenia in early arthritis is often short-lived, even when methotrexate is prescribed.

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis.

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.

Reliability of histopathological salivary gland biopsy assessment in Sjögren's syndrome: a multicentre cohort study.

OBJECTIVE: The aim of this study was to assess intraobserver and interobserver reliability of minor salivary gland biopsy (MSGB) in SS. METHODS: All MSGBs available from the Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) study were subjected to a standardized blinded assessment by a single specifically trained pathologist twice at a 2 month interval; both the Chisholm-Mason (CM) grade and the focus score (FS) were determined. Baseline histopathological reports by local pathologists at each study centre were compared with the first standardized blinded assessment. Agreement was assessed for the dichotomized FS (dFS) and dichotomized CM (dCM) grade, as well as for nine other histopathological features. RESULTS: Eighty-nine MSGBs were studied. Intraobserver κ values were 1 for dFS, 0.80 for dCM, 0.67 for germinal centre-like structures, 0.44 for fibrosis and 0.29 for confluent foci. Most of the local histopathological reports based their diagnosis on the CM grade, although the FS was often reported or the data needed to determine it were provided. Interobserver agreement κ values were 0.71 for dFS, 0.64 for dCM, 0.46 for focal lymphocytic sialadenitis, 0.42 for non-specific chronic inflammation and 0.16 for fibrosis. CONCLUSION: Although FS reliability was good, disparities were noted in the assessment methods used by local pathologists. The protocol for FS determination was not followed routinely, with the result that the FS was often overestimated. Germinal centre-like structures, which predict lymphoma, showed good reliability but were inconsistently reported.

The Differential Diagnosis of Dry Eyes, Dry Mouth, and Parotidomegaly: A Comprehensive Review.

Primary Sjögren's syndrome (pSS) is a frequent autoimmune systemic disease, clinically characterized by eyes and mouth dryness in all patients, salivary gland swelling or extraglandular systemic manifestations in half of the patients, and development of lymphoma in 5 to 10 % of the patients. However, patients presenting with sicca symptoms or salivary gland swelling may have a variety of conditions that may require very different investigations, treatments, or follow-up. Eye and/or mouth dryness is a frequent complaint in clinical setting, and its frequency increases with age. When evaluating a patient with suspected pSS, the first step is to rule out its differential diagnoses, before looking for positive arguments for the disease. Knowledge of normal and abnormal lachrymal and salivary gland physiology allows the clinician to prescribe the most adapted procedures for evaluating their function and structure. New tests have been developed in recent years for evaluating these patients, notably new ocular surface staining scores or salivary gland ultrasonography. We describe the different diagnoses performed in our monocentric cohort of 240 patients with suspected pSS. The most frequent diagnoses are pSS, other systemic autoimmune diseases, idiopathic sicca syndrome and drug-induced sicca syndrome. However, other diseases are important to rule out due to their specific management, such as sarcoidosis, granulomatosis with polyangeitis, IgG4-related disease, chronic hepatitis C virus or human immunodeficiency virus infections, graft-versus-host disease, and head and neck radiation therapy. At the light of these data, we propose a core of minimal investigations to be performed when evaluating a patient with suspected pSS.