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.

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.

Salivary gland ultrasonography improves the diagnostic performance of the 2012 American College of Rheumatology classification criteria for Sjögren's syndrome.

OBJECTIVE: The aim of this study was to evaluate whether salivary gland ultrasonography (SGUS) improves the diagnostic performance of the 2012 ACR classification criteria for SS. METHODS: We studied a cohort of 101 patients with suspected SS seen at a single centre in Brittany, France. An SGUS echostructure score ≥2 was considered abnormal. The reference standard was a clinical diagnosis of SS made by a group of experts blinded to SGUS findings. RESULTS: SS was diagnosed in 45 patients. Similar proportions of patients with and without SS had an ocular staining score ≥3. Adding RF positivity and ANA titre ≥1:320 as an alternative to anti-SSA/SSB positivity increased the sensitivity of the serological item without modifying specificity compared with using anti-SSA/SSB alone. SGUS was 60.0% sensitive and 87.5% specific for SS. Adding the SGUS score to the ACR criteria increased sensitivity from 64.4% to 84.4% and only slightly decreased specificity, from 91.1% to 89.3%. CONCLUSION: The diagnostic performance of the ACR classification criteria for SS is notably improved by adding the SGUS score. SGUS should be included in future classification criteria for SS.

Proposal of a quantitative PCR-based protocol for an optimal Pseudomonas aeruginosa detection in patients with cystic fibrosis.

BACKGROUND: The lung of patients with cystic fibrosis (CF) is particularly sensitive to Pseudomonas aeruginosa. This bacterium plays an important role in the poor outcome of CF patients. During the disease progress, first acquisition of P. aeruginosa is the key-step in the management of CF patients. Quantitative PCR (qPCR) offers an opportunity to detect earlier the first acquisition of P. aeruginosa by CF patients. Given the lack of a validated protocol, our goal was to find an optimal molecular protocol for detection of P. aeruginosa in CF patients. METHODS: We compared two formerly described qPCR formats in early detection of P. aeruginosa in CF sputum samples: a qPCR targeting oprL gene, and a multiplex PCR targeting gyrB and ecfX genes. RESULTS: Tested in vitro on a large panel of P. aeruginosa isolates and others gram-negative bacilli, oprL qPCR exhibited a better sensitivity (threshold of 10 CFU/mL versus 730 CFU/mL), whereas the gyrB/ecfX qPCR exhibited a better specificity (90% versus 73%). These results were validated ex vivo on 46 CF sputum samples positive for P. aeruginosa in culture. Ex vivo assays revealed that qPCR detected 100 times more bacterial cells than culture-based method did. CONCLUSION: Based on these results, we proposed a reference molecular protocol combining the two qPCRs, which offers a sensitivity of 100% with a threshold of 10 CFU/mL and a specificity of 100%. This combined qPCR-based protocol can be adapted and used for other future prospective studies.

Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria?

OBJECTIVE: To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjögren's syndrome (SS) and to suggest modifications of the American-European Consensus Group (AECG) classification criteria. METHODS: We conducted a cross-sectional study in a prospective cohort of patients with suspected primary SS that was established between 2006 and 2011. The echostructure of the bilateral parotid and submandibular glands was graded from 0 to 4, and the gland size was measured; blood flow to the parotid gland was assessed using Doppler waveform analysis. The reference standard was a clinical diagnosis of primary SS as determined by a group of experts blinded to the results of SGUS. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic value of the 0-4-point echostructure grade for each of the 4 major salivary glands, the sum of the grades for the 4 glands, and the highest grade among the 4 glands. RESULTS: Of the 158 patients in the study, 78 had a diagnosis of primary SS according to the experts, including 61 patients (78.2%) who met the AECG criteria. Doppler waveform analysis and gland size measurement showed poor diagnostic performance. The results of ROC curve analysis showed that the highest grade among the 4 glands provided the best diagnostic value. The optimal grade cutoff was 2 (62.8% sensitivity and 95.0% specificity). A weighted score was constructed using scores for the 5 variables selected by logistic regression analysis, as follows: (salivary flow×1.5)+(Schirmer's test×1.5)+(salivary gland biopsy×3)+(SSA/SSB×4.5)+(SGUS×2). According to ROC curve analysis, a score of ≥5 of 12.5 had 85.7% sensitivity and 94.9% specificity, compared with 77.9% sensitivity and 98.7% specificity for the AECG criteria. The addition of SGUS to the AECG criteria increased sensitivity to 87.0% but did not change specificity. CONCLUSION: Modifications of the AECG criteria, including the addition of a SGUS score, notably improved diagnostic performance.

Salmonella carriage in adopted children from Mali: 2001-08.

OBJECTIVES: Salmonella spp. are among the most frequently encountered bacterial pathogens in children adopted abroad, especially from developing countries. The aim of this study was to investigate the carriage of Salmonella in international adoptees over an 84 month period. This screening programme was initiated after serious infections occurred in adopted children. MATERIAL AND METHODS: Stool samples taken at the first visit to the outpatient adoption practice and subsequently every month from children adopted from an orphanage in Bamako (Mali) and from all members of their adoptive families were screened for Salmonella. Bacteria were characterized by standard biochemical methods, serotyping, disc diffusion antibiograms and PFGE. ß-Lactamase genes were sought by PCR. RESULTS: Over the study period, 55 families that adopted 61 children from the state orphanage of Bamako were surveyed. Ninety-two Salmonella spp. were isolated from faecal samples from 30 families that had adopted a child. The isolates were all identified as Salmonella enterica of different serovars, Babelsberg and Enteritidis being the most prevalent. PFGE classified the Salmonella isolates into nine genotypic profiles matching with their serovar. Of the 41 non-duplicate isolates, 8 were susceptible to all tested antibiotics and 26 Salmonella isolates produced an extended-spectrum ß-lactamase (ESBL). PCR and DNA sequencing revealed that all the ESBL-producing isolates harboured the bla(TEM-1) gene, 21 isolates harboured in addition the bla(SHV-12) gene and the 5 remaining isolates harboured the bla(CTX-M-15) gene. CONCLUSIONS: International adoption may contribute to the global emergence and spread of multidrug-resistant Salmonella.