Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Anifrolumab in Refractory Systemic Lupus Erythematosus: A Real-World, Multicenter Study.

OBJECTIVE: To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE). METHODS: The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score (P = 0.01), and physician global assessment (P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P < 0.001) and in tender (P = 0.03) and swollen (P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders. CONCLUSION: This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

Factors associated to long-term retention rate of Janus kinase inhibitors in a multi-failure rheumatoid arthritis population.

OBJECTIVES: We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in rheumatoid arthritis (RA) patients with particular regards to difficult-to-treat subgroups. METHODS: The diffusion of Janus kinase inhibitors (JAKi) for the treatment of RA has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities. RESULTS: Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients. CONCLUSIONS: In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.

The impact of two different rituximab-based strategies in cryoglobulinaemic vasculitis secondary to Sjögren's disease: a monocentric cohort study.

OBJECTIVES: To compare two different rituximab (RTX)-based therapeutic approaches on vasculitic and lymphoproliferative-related disease activity and on non-Hodgkin lymphoma (NHL) development in a cohort of patients affected by cryoglobulinaemic vasculitis secondary to Sjögren's disease (Sjögren-CryoVasc). METHODS: Three Sjögren-CryoVasc treatment groups were identified: 1) early RTX induction followed by maintenance; 2) late RTX induction with possible on-demand retreatment; 3) no RTX treatment. The following outcomes were evaluated: a) changes in cumulative ESSDAI, considering vasculitic-related and lymphoproliferative-related domains and changes in ESSDAI specific to each single vasculitic-related and lymphoproliferative-related domain; b) development of NHL; c) occurrence of persistent hypogammaglobulinemia associated with serious infections. RESULTS: 13 Sjögren-CryoVasc patients were identified: 1) 5/13 treated earlier with RTX with subsequent maintenance; 2) 5/13 treated late with RTX with possible on-demand retreatment; 3) 3/13 not treated with RTX. The two RTX groups showed a decrease in the ESSDAI score with group 1 showing the most substantial reduction (p=0.028). Patients receiving RTX exhibited significant improvement in cutaneous, PNS, and articular vasculitic-related ESSDAI domains (p=0.007; p=0.006; p=0.03, respectively). By contrast RTX did not greatly affect the lymphoproliferative-related ESSDAI domains, even if an improvement was noted in the glandular and nodal domains for group 1 (p=0.03; p=0.03, respectively). No differences in NHL occurrence or safety concerns were observed among the groups. CONCLUSIONS: RTX is an effective and safe treatment to control Sjögren-CryoVasc disease activity with a greater impact when administered earlier with a maintenance regimen. RTX alone cannot, however, affect the possible evolution of Sjögren-CryoVasc into an overt NHL.

Diagnostic pathway and treatment preferences for systemic lupus erythematosus: a physician-based discrete choice experiment.

OBJECTIVES: To assess physicians' preferences on diagnostic pathways and treatment priorities for systemic lupus erythematosus (SLE) using a discrete choice experiment (DCE). METHODS: A board of 11 SLE experts and a DCE expert statistician defined informative profiles of diagnostic pathways, pharmacological therapies, and two distinct profiles of mild-moderate and severe SLE. An independent panel of 115 clinicians involved in SLE management was invited to participate. Parameter estimates from the model were interpreted as relative preference weights (PWs). The mean PWs were used to calculate each attribute's relative importance (RI). RESULTS: 95 clinicians (57% females, 71% rheumatologists) completed the DCEs. The DCEs could not identify a hierarchy of importance among diagnostic pathway attributes. Nevertheless, "referral time to a rheumatologist" was considered more important for mild-moderate (RI=25%) and severe (RI=20%) SLE. Among the therapeutic attributes, the effect on organ damage progression after 12 months showed the highest preference for mild-moderate (RI=35%) and severe (RI=41%) SLE patients, followed by reduction in disease activity levels (max RI=19%) and glucocorticoid dose (max RI=13%) after six months. Reducing prednisone dose below 5 mg/day scored higher utility levels for mild-moderate (PW=66.1) than severe (PW=14.2) SLE. Administration route, action rapidity, patient-global assessment, and serious infection risk showed lesser relevance (RI 7-8%). No distinctions were found among subgroups categorised by the clinicians' areas of expertise. CONCLUSIONS: These DCEs highlight a high degree of awareness among lupus-treating physicians, with no differences across medical specialties, of the unmet need for early diagnosis and prevention of damage accrual in SLE management.

Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Preferences for diagnostic pathways and treatment choice in systemic lupus erythematosus: a patient-based discrete choice experiment.

OBJECTIVES: Starting from the unmet need of early diagnosis and treatment in systemic lupus erythematosus (SLE), the study aims to explore patient preferences in diagnostic pathways and treatment modalities. It seeks to integrate clinical priorities with patient perspectives, providing an optimal approach to SLE treatment that remains uncertain. METHODS: A discrete choice experiment (DCE) has been conducted to investigate whether patient preferences align while maintaining consistent attributes and levels, providing a direct assessment of relative preferences and hypothetical treatment approaches in SLE. RESULTS: DCE results demonstrated that obtaining an early diagnosis is the most crucial attribute for patients. Additionally, a multidisciplinary care team, capable of enhancing clinical outcomes and patient satisfaction, is essential, along with a clinical centre conveniently located within 30 minutes of the patient's home. Lastly, patients prefer the opportunity to reduce glucocorticoid to a dosage ≤5 mg/day, and eventually discontinue, aligning with the new EULAR recommendations, and favour oral and subcutaneous routes of administration for new course of treatment. CONCLUSIONS: Patient preferences contribute to enhancing the care pathway for SLE by optimising disease management, with a focus on multidisciplinarity and psychological support.

Ultrasound-guided core needle biopsy of deep fascia: A cadaveric study evaluating feasibility, accuracy and reliability.

Over the past few decades, researchers and clinicians have dedicated significant attention to fascial tissues. Current interest focuses on their anatomical and pathophysiological features. Breakthroughs in ultrasound (US) and magnetic resonance imaging (MRI) have enhanced our ability to study the dynamics and alterations of the tissue structures. However, a microscopic perspective is also essential for a comprehensive understanding of some pathologies of the fasciae. The aim of this study was to investigate, using a cadaveric study: (1) the ease of visualization of the landmarks used for the US-guided fascial core needle biopsy (CNB); (2) the consistency and accuracy of needle placement inside fascial layers using US guidance and confirmed by histological examination; (3) inter-rater reliability. We assessed the feasibility of US-guided CNB in different topographical regions of human cadavers: the thoracolumbar fascia (TLF), fascia lata (FL), and crural fascia (CF). The results, confirmed by histological examination, revealed no significant difference in needle placements between the in-plane approaches in the long and short axes for all locations and fasciae studied (long axis: 91.88%; short axis: 96.22%); p > 0.05. US-guided core needle biopsy with the in-plane approach is feasible, consistent and reliable. It could provide most or all of high-quality fascial tissue samples required for pathological examination. It could also reveal changes in fascial pathologies, capturing the exact site of pathology thanks to US guidance, in particular in patchy diseases such as eosinophilic fasciitis.

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity.

PURPOSE: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series. METHODS: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies. RESULTS: A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients' older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029). CONCLUSIONS: The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Physical activity assessment with wearable devices in rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVES: In the management of rheumatic musculoskeletal disorders (RMDs), regular physical activity (PA) is an important recognized non-pharmacological intervention. This systematic review and meta-analysis aims to evaluate how the use of wearable devices (WDs) impacts physical activity in patients with noninflammatory and inflammatory rheumatic diseases. METHODS: A comprehensive search of articles was performed in PubMed, Embase, CINAHL and Scopus. A random-effect meta-analysis was carried out on the number of steps and moderate-vigorous physical activity (MVPA). Univariable meta-regression models were computed to assess the possibility that the study characteristics may act as modifiers on the final meta-analysis estimate. RESULTS: In the analysis, 51 articles were included, with a total of 7488 participants. Twenty-two studies considered MVPA outcome alone, 16 studies considered the number of steps alone, and 13 studies reported information on both outcomes. The recommended PA threshold was reached for MVPA (36.35, 95% CI 29.39, 43.31) but not for daily steps (-1092.60, -1640.42 to -544.77). Studies on patients with fibromyalgia report a higher number (6290, 5198.65-7381.62) of daily steps compared with other RMDs. Patients affected by chronic inflammatory arthropathies seemed to fare better in terms of daily steps than the other categories. Patients of younger age reported a higher overall level of PA than elderly individuals for both the number of steps and MVPA. CONCLUSION: Physical activity can be lower than the recommended threshold in patients with RMDs when objectively measured using WD. WDs could be a useful and affordable instrument for daily monitoring physical activity in RMDs and may support an increase in activity levels. PROSPERO TRIAL REGISTRATION: CRD42021227681, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227681.

Predicting lymphoma in Sjögren's syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording.

OBJECTIVE: Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. METHODS: A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. RESULTS: PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. CONCLUSION: A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis.

Nuts and bolts of salivary gland pathology in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the diagnosis of pSS and therefore broadly applied in clinical practice. Tissue can be obtained from labial salivary glands (LSG) biopsy or from major salivary glands (MSG) biopsy, namely the parotid; in this latter scenario, the procedure can be either an open surgical biopsy or a US guided core needle biopsy.In this review we will: i) present the histopathological findings that may be encountered by pathologists on biopsies from pSS patients; ii) discuss the advantages and disadvantages of the surgical and/or imaging guided procedures to obtain tissues from LSG or MSG; iii) describe the histopathological features of lymphoma of MSG in pSS patients.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

Sjögren's syndrome: one year in review 2023.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Secretagogue effect of PDE4 inhibitor apremilast on human salivary gland organoids obtained from primary Sjögren's syndrome patients.

OBJECTIVES: The aim of the study was to culture vital salivary gland organoids obtained through labial or parotid biopsy of primary Sjögren's syndrome (pSS) patients in order to evaluate their morphological and functional features in basal condition and after stimulation with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activator forskolin and phosphodiesterase 4 (PDE4) inhibitor apremilast, their in vitro regenerative capacity and the immune-histological resemblance with original tissue. METHODS: Salivary gland tissues from five pSS patients were processed to obtain vital organoids; swelling assay and cell proliferation tests were performed after forskolin and apremilast application. Immunochemistry evaluation on original salivary gland tissue and corresponding organoids was performed, and secretomics analysis was conducted to assess their functional status. REULTS: After application of forskolin and apremilast, we observed organoid swelling after 30 minutes, compatible with a positive functional status and enhancement of saliva production. In 3 cases, apremilast induced organoid proliferation. All cases were positive for cytokeratin 14 (CK14) and most for cytokeratin 5 (CK5). All the cases were positive for amylase; its secretion, and thus functional status of organoids, was confirmed by its high concentration in the culture medium. A focal ductal differentiation was found in some cases, highlighted by epithelial membrane antigen (EMA) positivity. The more differentiated EMA positive areas were negative for the staminal marker CK14, showing a sort of "complementary staining". CONCLUSIONS: Our data highlighted that differentiated cells and vital functional organoids that recapitulate the development of original salivary glands can be obtained from pSS epithelium. For the first time, the direct stimulating effect of PDE4 inhibitor apremilast on pSS human salivary gland organoids is reported, opening new perspectives on targeting oral dryness with drugs that combine secretagogue and immunomodulatory effects.

COVID-19 vaccination rate and safety profile in a multicentre Italian population affected by mixed cryoglobulinaemic vasculitis.

OBJECTIVES: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. The aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile. METHODS: All MCV patients referring to participating centres were assessed with an interview-based survey about vaccination, reasons for not getting vaccinated, adverse events (AE), and disease flares within a month after vaccination. RESULTS: A total of 416 patients were included in the study. Among participants, 7.7% did not get vaccinated, mainly for fear related to vaccine side-effects (50%) or medical decision (18.8%). They were more frequently treated with chronic glucocorticoids or rituximab (p=0.049 and p=0.043, respectively). Mild and self-limiting AE were recorded in 31.7% of cases, while post-vaccination vasculitis flares were observed in 5.3% of subjects. Disease relapses were mainly observed in patients with peripheral neuropathy or skin vasculitis (40% and 25%, respectively). CONCLUSIONS: Vaccination against SARS-CoV-2 has been performed in a high percentage of MCV patients with encouraging safety profile. Vasculitis flares rate was in line with that observed for other autoimmune diseases, despite patients with purpura or peripheral neuropathy seem to be at risk for symptoms' exacerbation. Patients' hesitancy, rituximab and glucocorticoids treatment were the main reasons for delaying vaccination.

Clinical and histological features of patients with primary Sjögren's syndrome and autoimmune thyroiditis: a national multicentre cross-sectional study.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of patients with pSS and associated AT. METHODS: In this multicentre cross-sectional study, data from 2546 pSS were collected and the presence of AT was reported. In a subgroup, the histology of minor salivary glands was evaluated. Differences between pSS with and without AT were evaluated. RESULTS: A concomitant pSS and AT was detected in 19.6% of cases. Patients with pSS and AT displayed a lower prevalence of lymphoma, male sex and disease-modifying anti-rheumatic drugs (DMARDs) use and a higher prevalence of fibromyalgia, coeliac disease and hypergammaglobulinaemia. Multivariable analysis confirmed a higher prevalence of fibromyalgia and coeliac disease and lower use of DMARDs. In a subgroup of patients (n=232), a significantly higher focus score and number of foci was detected in pSS without AT (n=169) as compared to pSS with AT (n=54). CONCLUSIONS: This is the largest study evaluating the coexistence of pSS and AT. We confirm a high association between pSS and AT and describe the presence of a different phenotype characterized by a higher rate of celiac disease and fibromyalgia. Although not significant, the lower prevalence of both lymphoma and intake of DMARDs, along with a significantly lower focus score and number of foci, possibly suggest a more favourable outcome in concomitant pSS and AT which further deserve future investigations.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.