Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation.

OBJECTIVE: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status. METHODS: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients. RESULTS: In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher ß2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations. CONCLUSION: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies.

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.

Diagnostic accuracy of blood B-cell subset profiling and autoimmunity markers in Sjögren's syndrome.

INTRODUCTION: The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria. METHODS: In a single-center cohort of patients with suspected pSS, we tested the diagnostic performance of anti-SSA, antinuclear antibody (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio defined as (Bm2 + Bm2')/(eBm5 + Bm5), determined using flow cytometry. The reference standard was a clinical diagnosis of pSS established by a panel of experts. RESULTS: Of 181 patients included in the study, 77 had pSS. By logistic regression analysis, only ANA ≥1:640 (sensitivity, 70.4%; specificity 83.2%) and B-cell ratio ≥5 (sensitivity, 52.1%; specificity, 83.2%) showed independent associations with pSS of similar strength. In anti-SSA-negative patients, presence of either of these two criteria had 71.0% sensitivity but only 67.3% specificity for pSS; whereas combining both criteria had 96.2% specificity but only 12.9% sensitivity. Adding either of these two criteria to the AECG criteria set increased sensitivity from 83.1% to 90.9% but decreased specificity from 97.1% to 85.6%, whereas adding both criteria in combination did not substantially modify the diagnostic performance of the criteria set. The adjunction of RF + ANA ≥1:320, as proposed in the new American College of Rheumatology (ACR) criteria, did not improve the diagnostic value of anti-SSA. CONCLUSIONS: Blood B-cell subset profiling is a simple test that has good diagnostic properties for pSS. However, adding this test, with or without ANA positivity, does not improve current classification criteria.

Skin infection by Staphylococcus aureus in a fisherman: difficulty in continuing work on board.

BACKGROUND AND AIM: The aim of this study was to understand why an infectious skin disease due to colonisation by Staphylococcus aureus methi-S led to disembarkation of a fisherman for treatment and follow-up. MATERIALS AND METHODS: While discussing this case we have analysed different reasons why the studied fisherman could not be successfully treated on board. RESULTS: A 42-year-old fisherman was first presented with skin lesions while fishing for hake. When the fisherman had developed a fever and exfoliative skin lesions on both hands, the ship's captain called the radio-medical centre for the maritime consultation in Toulouse and for the advice on treatment. After 3 days on penicillin, the fever decreased, but the dermatitis became incapacitating. On his return to shore, the fisherman was hospitalised. Bacteriological swabs of the skin lesion showed colonisation with Staphylococcus aureus methi-S with presence of Panton Valentine leukocidin. Seven-day treatment witha follow-up of antibioticotherapy was necessary to resolve the skin eruption and obtain definitive apyrexia. Treatment ashore was advised because of difficulty in continuing manual work on board whilst suffering from significant skin lesions and also due to fear of contagion. CONCLUSIONS: Skin infection with Staphylococcus aureus methi-S with presence of Panton Valentine leukocidinis difficult to treat on board because of difficulty in carrying out manual work when hands are affected, and also due to slow improvement of dermatitis even when appropriate treatment is undergone. The maritime environment is also a risk factor for skin abrasion, which can lead to secondary colonisation of pathogenic bacteria.

Occupational dermatitis in workers exposed to detergents, disinfectants, and antiseptics.

Anti-infective prevention has led to a significant use of disinfectants, detergents, and antiseptics in various areas of activities. Most of these products are skin irritants and allergens, which can cause skin disorders in exposed workers. The authors conducted a descriptive and retrospective study on occupational dermatitis diagnosed at an occupational dermatology hospital consultation service, targeting exposed workers in the health, food, and cleaning industries. These included 20.9% (61 of 291) of the patients seen at this consultation. An occupational origin was proven for 50 of these 61 patients. The most frequent dermatoses were irritant contact dermatitis (42%) and allergic contact dermatitis (26.3%). The main allergens were disinfectants and antiseptics (26.3%), especially quaternary ammoniums, aldehydes, and nickel. Patients exposed to disinfectants, detergents, and antiseptics in the workplace represent an important part (about 1 of 5) of occupational dermatology consultations, although factors may be contributory. Prevention and knowledge are necessary for this increasing issue.

What is intrinsic atopic dermatitis?

Many authors favor a distinction between the extrinsic and intrinsic forms of atopic dermatitis. In this review, the controversy is discussed and several definitions are presented. After reviewing many papers on this topic, it is our opinion that it is useful to separate the intrinsic and extrinsic forms of atopic dermatitis or atopic eczema and atopiform dermatitis because the pathophysiology appears to be different between them. However, these terms require concrete definition and clarification of the distinction between these two concepts. This debate is a new step in the history of atopic dermatitis. It is possible that a single patient could suffer from one form and then from another but genetic differences suggest that two types could really exist.