OBJECTIVE:Sjögren disease (SjD) is a systemic autoimmune disease characterized by increased risk of B-cell non-Hodgkin lymphoma. Although cryoglobulinemia and serum monoclonal component (MC) are well-recognized paraproteinemias in SjD, no large-scale study has directly compared their isolated and combined impact on phenotype and lymphoproliferative risk. METHODS:A retrospective, multicenter, cross-sectional study was conducted within the Italian GRISS registry. Patients with SjD were stratified into four groups: isolated monoclonal gammopathy (MC-alone), isolated cryoglobulinemia (CRYO-alone), both (MC+CRYO), or neither (controls). Demographics, lymphoma history, ever-documented ClinESSDAI domains, and laboratory lymphoproliferative risk-related markers were analyzed. Primary and secondary outcomes assessed lymphoma diagnosis and the distribution of laboratory lymphoproliferative risk-related markers and ClinESSDAI domains across groups, with associations tested using logistic regression adjusted for confounders. RESULTS:1202 SjD patients were enrolled: 58 (4.83%) in the MC-alone, 32 (2.66%) in the CRYO-alone, 35 (2.91%) in the MC+CRYO, and 1077 (89.60%) controls. Compared with controls, only the MC+CRYO group showed significant association with lymphoma (OR 6.30, 95%CI 2.66-14.92; p < 0.001), while MC-alone and CRYO-alone were not associated. Cryoglobulinemia, alone or combined with MC, correlated with laboratory lymphoproliferative risk-related markers such as rheumatoid factor (p < 0.001) and low C4 (p < 0.001), and with ClinESSDAI vasculitic features (cutaneous [p < 0.001], renal [p < 0.05], PNS [p < 0.001]). The MC+CRYO group additionally displayed a lymphoproliferative phenotype correlating with constitutional (p < 0.05), glandular (p < 0.05), hematological (p < 0.001), and lymphadenopathy (p < 0.001) domains. CONCLUSION:Cryoglobulinemia in SjD associates with vasculitic disease activity, whereas the coexistence of serum MC and cryoglobulins identifies a distinct, high-risk subset characterized by advanced B-cell expansion and increased lymphoma susceptibility.

OBJECTIVES:Lymphoid interstitial pneumonia (LIP) is a rare form of Interstitial Lung Disease (ILD), often associated with Sjögren Disease (SjD). However, the clinical-serologic characteristics of SjD-LIP remain poorly characterized. Our objective was to describe the clinical course and outcome of SjD-associated LIP and to compare this subgroup with other SjD-ILD patterns. METHODS:SjD patients with High-resolution Computed Tomography (HRCT)-confirmed ILD followed in Pisa Rheumatology Unit (January 2019-November 2024) were retrospectively enrolled. ILD patterns were classified through multidisciplinary discussion. Clinical and laboratory data were collected according to ESSDAI definitions, along with pulmonary symptoms and function tests (PFTs). RESULTS:Fifty-five SjD-ILD patients were included (M: F = 9:46), of whom 11 were diagnosed with LIP (F: M = 11:0). LIP patients showed thin-walled parenchymal cysts as the predominant HRCT finding, and largely preserved pulmonary function (median forced vital capacity [FVC] 101% [IQR 98-105]; DLCO 76% [IQR 75-81]). After a median 5-years follow-up (IQR 2-7) all LIP patients were alive with stable PFTs. Compared with the remaining 44 non-LIP, LIP patients were younger at SjD diagnosis (P < 0.001) and more frequently presented purpura (P = 0.012), constitutional symptoms (P = 0.001), lymphadenopathy (P = 0.023), hypergammaglobulinemia (P < 0.001), triple anti-Ro60/52/La positivity (P = 0.035) and C3 hypocomplementemia (P = 0.009). ILD preceded SjD diagnosis in 30/44 non-LIP vs. 1/11 LIP patients (P < 0.001), with lower FVC% (P = 0.049) and DLCO% (P = 0.036) in non-LIP. CONCLUSION:LIP defines a distinct, immunologically active phenotype within the spectrum of SjD-ILD, characterized by greater extrapulmonary systemic involvement and serologic markers of B cell hyperactivity, but limited pulmonary functional impact. These findings support long-term lymphoma surveillance and a potential role for B cell targeted therapies in selected patients.

OBJECTIVES:In a cross-sectional study, we aimed at characterizing possible impairments in sleep health and rest-activity parameters between patients with Sjögren's Disease (SjD) and healthy controls (HCs). Furthermore, we explored possible predictors of such disturbances in the SjD group. METHODS:Participants' sleep and rest-activity rhythms were assessed via 7-day continuous accelerometry, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the reduced Morningness-Eveningness Questionnaire, allowing the creation of a multidimensional sleep health index. Parametric tests explored between-group differences in sleep and rest-activity parameters, while functional linear modelling characterized between-group, time-related differences in accelerometric activity. Within the SjD cohort, regression analysis was employed to explore disease activity, patient-reported disease burden, and the Hospital Anxiety and Depression Scale (HADS) as possible predictors of sleep and rest-activity parameters. RESULTS:Forty-six SjD patients and forty age-, sex- and BMI-matched HCs were included. Compared with HCs, SjD patients reported lower sleep health (P = 0.005) and delayed mid-sleep point (P = 0.009) and acrophase (P = 0.033). Functional linear modelling confirmed the objective shift towards eveningness in SjD patients. In SjD patients, patient-reported disease burden predicted sleep quality (β = 0.41; P = 0.044) and sleepiness (β = 0.83; P = 0.010), while disease activity predicted daily steps (β=-526; P = 0.013), total sleep time (β = 0.15; P = 0.0496) and sleep regularity (β=-1.3; P = 0.030). Finally, HADS predicted daily steps (β = -238; P = 0.041), total sleep time (β = -0.08; P = 0.035) and sleep efficiency (β = -0.65; P = 0.012). CONCLUSIONS:SjD is associated with impaired sleep health and rest-activity rhythms. In SjD patients, such alterations differentially associate with disease activity and patient-reported outcomes, supporting a multifactorial model of sleep and circadian rhythms disruption.

BackgroundWhile Sjögren disease (SjD) overlap is known to modulate the clinical-serologic manifestations of other connective tissue diseases, the association with anti-synthetase syndrome (ASyS) has been seldom described in Caucasian cohorts. Anti-Ro52 autoantibodies, shared by both conditions, may blur early diagnostic attribution, particularly when glandular symptoms precede myositis-spectrum features.ObjectivesTo characterize the clinical phenotype, serological profile, and disease trajectory of patients fulfilling classification criteria for both SjD and ASyS.MethodsWe conducted a multicentre retrospective study (2018-2025) across three Italian referral centres, including patients meeting both the 2016 ACR/EULAR SjD criteria and the Connor’s/provisional CLASS classification criteria for ASyS. Clinical features, serology, interstitial lung disease (ILD) characteristics, treatments, and outcomes were systematically collected. SjD activity was assessed using the ESSDAI and an adapted ESSDAI excluding the classic ASyS triad (pulmonary, articular and muscular domains).ResultsSeventeen female patients of Caucasian ethnicity were identified. At the time of connective tissue disease diagnosis, 7 were classified as SjD and 10 received concomitant diagnoses; all reported early sicca symptoms. Regarding serology, anti-Ro52 antibodies were detected in all patients, most often (88%) in the absence of anti-Ro60 antibodies. Anti-synthetase antibodies were present in all cases, mainly non-Jo-1 specificities (77%), while anti-Jo-1 was observed in a minority of patients (23%). ILD was the leading organ involvement (14/17, 82%), typically with acute/subacute onset and NSIP or NSIP/OP patterns. ILD drove treatment decisions and accounted for four deaths, whereas most survivors showed stabilization or mild improvement under immunosuppressive treatment. Systemic assessment indicated a predominantly ASyS-driven phenotype: although ESSDAI was moderately elevated (median 15, IQR 7.5-21), the adapted ESSDAI markedly decreased (median 5, IQR 0-6.5), reflecting limited SjD-specific systemic activity.ConclusionsThe SjD-ASyS overlap seem characterized by a coherent clinical-serological phenotype, defined by anti-Ro52-positive sicca presentation, non-Jo1 anti-ARS autoantibodies and early interstitial lung disease. Pulmonary involvement represents the main driver of disease course and outcomes in this subset. Recognition of this pattern may improve early identification of ASyS in Ro52-positive SjD presentations. Further prospective studies are warranted to clarify whether this subset reflects a distinct phenotype within the ASyS spectrum rather than a coincidental overlap of two independent diseases.

Background To evaluate the classification accuracy of ultra-high frequency ultrasound (UHFUS) of labial salivary glands (LSGs) using both Grey Scale (GS) and colour Doppler (CD). We also investigated its role as an alternative to the highest-weighted classification criteria, its classification performance in combination with SSA status, its contribution to patient stratification and age-related classification variability. Methods A total of 270 patients with suspected Sjögren’s disease (SjD) (136 SjD, 134 Sicca) underwent UHFUS. In addition to OMERACT GS (modified to LSG), CD and composite GS+CD Scores, distinct GS morphological lesions were assessed. Diagnostic accuracy parameters were calculated, and additional analyses included correlation, logistic regression and cluster analysis. Results The optimal classification cut-off was GS ≥2, yielding 66.2% sensitivity and 84.3% specificity. GS Score 3 was highly specific (98.5%), while very hypoechoic areas were exclusively observed in SjD. CD ≥2 showed accuracy comparable to GS, and GS+CD ≥3 enhanced accuracy. Incorporating GS into the American College of Rheumatology/European League Against Rheumatism criteria in place of biopsy achieved excellent accuracy (area under the curve 0.945). Using GS, GS+CD and SSA status, more than 75% of patients could be classified with an accuracy of 94%. Cluster analysis suggests different phenotypes: in Sicca, GS positivity indicated non-immune inflammatory alterations or sialoadenosis; in SjD, GS negativity defined low-grade inflammation. Classification accuracy of GS varied with age, whereas CD remained stable. Conclusions UHFUS of LSGs is a promising diagnostic tool in SjD when biopsy is not feasible. This study provides novel insights into GS lesions, Doppler assessment, phenotypes and age-related changes of ultrasound.

Abstract Sjögren disease (SjD) is a chronic systemic autoimmune disorder characterized by immune-mediated destruction of moisture-producing glands (e.g. tears/saliva), leading to dryness. It also affects organs outside the glands, reflecting its systemic nature. Neurologic involvement is a common complication of SjD that can occur in up to 20% of SjD patients. Neurological manifestations in SjD span the central, peripheral, and autonomic systems, with the highest incidence of involvement occurring within the peripheral nervous system (PNS). The heterogeneity of neurologic manifestations in SjD complicates the diagnosis and treatment, which should be directed toward the underlying neuropathologic mechanism which is often unclear. Optimizing the diagnosis, evaluation, and management of these manifestations is essential to prevent severe disability and to design more effective clinical trials. In this review, we summarize the current understanding of SjD-related peripheral neuropathies. By detailing their specific pathogenetic mechanisms, we advocate for a targeted diagnostic and therapeutic framework designed to improve long-term patient outcomes.

Systemic vasculitides encompass a spectrum of inflammatory disorders affecting several organs and districts, with significant implications for morbidity and mortality. This annual review provides an updated overview of key advancements in vasculitis research, including emerging biomarkers, novel insights into pathogenesis, and therapeutic innovations in both large and small vessel vasculitis. Particular attention is given to emerging concepts, including the role of cellular senescence and stromal cells in vascular inflammation, the expanding spectrum of single-organ vasculitis, and the growing recognition of VEXAS syndrome as a vasculitis-related entity.

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in some cases, disease progression and prognosis. Following the results of the PANTHER study, immunosuppressive drugs are now not recommended for the treatment of IPF; however, their use for the treatment of UIP secondary to ARDs is still under debate. The aim of this review is to summarize existing knowledge on the clinical presentation of autoimmune UIP and its treatment with immunosuppressive drugs. We searched PubMed for English language clinical trials and studies on treatment of ARDs-ILD, looking for specific treatments of UIP-ARDs. The available clinical trials rarely stratify patients by ILD pattern, and clinical studies generally lack a comparison with a placebo group. In Systemic Sclerosis, UIP patients showed a non-significant trend of worsening under immunosuppression. On the contrary, in Interstitial Pneumonia with Autoimmune Features and, above all, Rheumatoid Arthritis, immunosuppressive treatment produced promising results in the management of UIP patients. In conclusion, the current evidence about the immunosuppressive treatment of UIP-ARDs is limited and conflicting. There is an urgent need to adequately assess this topic with specific clinical trials, as has already been performed for IPF. The possibility should be considered that different ARDs can respond differently to immunosuppression. Finally, a wider use of histological samples could produce valuable information from a diagnostic, therapeutic, and research point of view.

Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived ‘syndrome’ as indicative of a vague collection of symptoms, prompting the Sjögren’s Foundation to abandon the term. Furthermore, the traditional distinction between ‘primary’ and ‘secondary’ forms fails to account for the complex interplay between overlapping autoimmune diseases. Following a bibliometric analysis, systematic literature review and a Delphi consensus process with equal involvement of professional and patient representatives, five recommendations are now issued. First, the term ‘Sjögren disease’ should replace ‘Sjögren syndrome’. Second, the acronym ‘SjD’ should be used as an abbreviation for ‘Sjögren disease’. Third, the descriptor ‘associated’ should be used in lieu of ‘secondary’ for Sjögren disease occurring in association with a second systemic autoimmune disease for which classification criteria are fulfilled. Fourth, Sjögren disease is the preferred terminology in common parlance and in clinical diagnosis, without differentiation as to primary and associated forms. Fifth, the differentiation between primary and associated Sjögren is recommended for scientific studies to define a homogeneous population. In conclusion, the consensus endorses ‘Sjögren disease’ as the official nomenclature to acknowledge the distinct pathogenesis of this disorder and to improve clarity in both clinical practice and research. In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.

Background: Sjögren’s disease (SD) is an autoimmune condition causing progressive salivary and lacrimal glands dysfunction following lymphocytic infiltration in the glandular tissue. SD patients are more prone to oral health impairment due to a reduction in salivary flow. This study evaluated the relationship between oral health, functional tests, and patient reported outcomes in a cohort of SD patients. Methods: Patients diagnosed with SD underwent complete dental examination, with the recording of the decayed–missing–filled teeth index (DMFT), probing pocket depth (PPD), full mouth bleeding score (FMBS), and full mouth plaque score (FMPS). Hyposalivation was assessed using the unstimulated whole saliva flow rate (UWS). Patients were administered the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index, EULAR Sjögren’s syndrome disease activity index, Oral Health Impact Profile-14 (OHIP-14), Patient Acceptable Symptom State questionnaires, and a visual analog scale for xerostomia (VASx). Results: Fifty patients in total were enrolled. Reduced UWS was associated with higher DMFT, FMBS, and FMPS. Significant correlation was observed for UWS with VASx and OHIP-14 (p < 0.05). Conclusions: Quality of life and oral health appear mildly impaired in SD patients as an effect of reduced salivary flow, with higher DMFT and tendency towards gingival inflammation and plaque accumulation.

Sjögren's disease (SjD) and systemic lupus erythematosus (SLE) are distinct autoimmune disorders and their clinical overlap presents a unique immunological entity with specific challenges. While the clinical manifestations of the SjD-SLE overlap have been extensively characterised, its underlying pathogenetic mechanisms remain less understood. This review underscores the immunological features of the overlap, highlighting the roles of genetic predisposition, interferon pathway activation and B-cell dysregulation. Key genetic factors, particularly those associated with HLA and cytokine signaling, underpin disease susceptibility by promoting aberrant immune responses. The consequent and persistent interferon pathway activation drives chronic inflammation and establishes a feedback loop with autoantibody production. Furthermore, Extrafollicular B-cell responses are central to generating hallmark autoantibodies, such as anti-dsDNA and rheumatoid factor, which are frequent in the overlap. Finally, the continuous activation of interferons and B-cells not only increase disease activity but also contributes to lymphoproliferative complications. Despite progress in elucidating these mechanisms, patients with SjD-SLE overlap remain underrepresented in clinical trials, limiting therapeutic advancements. Emerging strategies, including interferon receptor inhibitors, BAFF-blocking antibodies, and advanced B-cell depletion therapies, may offer promising options to hit the distinct immunological abnormalities of these patients.

Primary Sjögren's disease (pSjD) is an autoimmune rheumatic disease involving exocrine glands and associated with high symptom burden (dryness, fatigue, pain), systemic features and salivary gland dysfunction. B-cell hyperactivity is common, with an increased risk of mucosa-associated lymphoid tissue lymphoma. This review describes the unmet need, scientific validity of outcome measures, optimisation of clinical trial design, therapeutic advances and how clinical improvement relates to health-related quality of life, additional quality-adjusted life years and economic benefit in pSjD. It derives from the EU-funded Necessity IHI Academic-Industry collaborative Consortium project while also drawing on work by the European Alliance of Associations for Rheumatology Sjögren's task force and others. The NECESSITY Consortium, formed within the framework of the Innovative Health Initiative (IHI), comprises 20 academic partners, 1 patient group partner and 4 industry partners (NECESSITY; https://necessity-h2020.eu). Patient leaders have been closely involved, with expert advice obtained from the European Medicines Agency and the United States Food and Drug Administration during the development phase of a new outcome measure, the Sjögren's Tool for Assessing Response composite response criteria. This tool is now undergoing validation through the NECESSITY IHI clinical trial and industry-sponsored trials.

Objectives:Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist. We aimed to inventory transitional care programs for rare CTDs across Europe. Methods:In April 2023, the ERN ReCONNET Transition of Care Task Force, consisting of expert clinicians, patient advocates and coordination team members, created a survey to assess transitional care practices. The survey was distributed to ERN ReCONNET and ERN RITA centres and responses received by 15 March 2024 were analysed. Results:A total of 67 responses from 59 centres across 20 European countries were collected. Paediatric rheumatologists typically initiated the transition process (49% of centres). Twenty centres had joint clinics. Despite positive self-assessments of transitional programs, significant limitations were noted. Transition policies varied, with only 40% of centres having a formal standardized policy and less than half of the centres adhering to available transition of care guidelines. Transfer readiness was evaluated using validated questionnaires in 13% of centres, while 29% transitioned patients based solely on age without any readiness assessments. The main challenges included finding adult-oriented centres and the lack of guidelines or engagement from adult centres. Adult healthcare providers also noted a lack of training in adolescent medicine. Conclusion:The survey highlighted diverse transition practices and resources across centres, with challenges in readiness evaluation and the use of guidelines. Despite these obstacles, respondents rated ongoing transition processes positively. Enhancing patient perspectives in the transition process is crucial to meet their needs during this critical phase.

Interstitial Lung Disease (ILD) is one of the most common causes of mortality in idiopathic Inflammatory Myopathies (IIM). Despite these conditions being commonly associated with proximal weakness, skin rashes and arthritis, ILD can be the first or the sole clinical feature in up to 60% of patients, potentially leading to incorrect diagnosis. The early recognition of an underlying IIM in ILD patients can allow for prompt treatment, which could potentially stabilize or even improve the lung disease, also avoiding the development of other clinical features associated with the condition. The objective of this review is to describe the clinical, serological and radiological features associated with IIM-ILD, mainly focusing on dermatomyositis and antisynthetase syndrome.