Gaetano La Rocca

Background and Objectives: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with heterogeneous extraglandular involvement, including the kidney. Tubulointerstitial nephritis (TIN) is the hallmark kidney lesion of pSS, but its clinical and histological features, compared with other causes of TIN, remain incompletely characterized. This study aimed to describe the clinical, laboratory, and histological features of biopsy-proven pSS-associated TIN (pSS-TIN) and to compare them with TIN of other etiologies. Materials and Methods: We retrospectively analyzed native-kidney biopsies (2015–2025) with histological diagnosis of TIN, from adult and pediatric patients, excluding cases with neoplasms or concomitant acute glomerular injury. Clinical, laboratory, and histological data of pSS-TIN patients were compared with other TIN etiologies using the Mann–Whitney U test, Fisher’s exact test, and Spearman’s correlation; p < 0.05 was significant. Results: Among 690 native-kidney biopsies, 35 showed TIN; after excluding cases with glomerular involvement, 14 patients with pSS-TIN and 16 patients with no-pSS-TIN patients were analyzed. All pSS-TIN patients were female, and biopsy occurred after a significantly longer interval from disease diagnosis than patients with no-pSS-TIN (p = 0.018). Acute kidney injury was less frequent (p = 0.021) and kidney function was better preserved in pSS-TIN, while the urea-to-creatinine ratio was similar between groups. Standard urinalysis was abnormal in only about half of patients in both groups. Longer disease duration correlated with lower eGFR in pSS-TIN (p = 0.033). Predominantly chronic histological damage was associated with higher proteinuria (p = 0.037) across the entire cohort, and germinal-center-like lymphoid structures were observed in two pSS-TIN patients with extensive acute damage. In our cohort, no statistically significant association was detected between kidney function indices and the severity of chronic damage. Conclusions: In this biopsy-based cohort, pSS-TIN showed a predominantly chronic presentation, less acute kidney injury, and a longer diagnostic interval than other TIN forms. Routine urinary and functional parameters may not reliably reflect chronic tubulointerstitial damage, highlighting the importance of careful renal screening and timely nephrological assessment, with kidney biopsy when clinically indicated.

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.

Background: While 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. Objectives: To characterize the clinical phenotype, serological profile, and disease trajectory of patients fulfilling classification criteria for both SjD and ASyS. Methods: We 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). Results: Seventeen 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. Conclusions: The 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.

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. 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. 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). 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.

Background: Interstitial lung disease (ILD) is the most frequent extra-muscular manifestation in patients with idiopathic inflammatory myopathies (IIMs). Although high-resolution chest tomography (HRCT) represents the gold standard for the evaluation of ILD, lung ultrasound (LUS) might be a useful tool for its assessment. The aim of our study was to evaluate the number and distribution of pleural irregularities (PIs) identified by lung US in a cohort of patients with IIMs and to find possible correlations with clinical, serological and HRCT data to verify the potential usefulness of lung US for the study of ILD in patients with IIM. Patients and methods: Fifty-three patients with IIM according to EULAR/ACR classification criteria were enrolled. All patients underwent a clinical evaluation with measurement of disease activity and myositis-specific autoantibodies, pulmonary function tests, HRCT evaluated with the Warrick score, and lung US for the measurement of PIs. Results: The number of PIs was higher in patients with myositis-specific autoantibodies, particularly those with anti-synthetase autoantibodies (p < 0.001) and in patients with high-grade dyspnea (p < 0.03). A negative correlation was identified between PIs and pulmonary function tests, particularly TLC (r = −0.74; p < 0.001) and DLCO (r = −0.56; p < 0.001). Interestingly, PI score was higher in patients with ILD identified with HRCT (p = 0.015) and a positive correlation between PIs and Warrick score (r = 0.542; p < 0.001) was also found. Conclusions: The study of PIs with lung US represents a promising diagnostic tool for the bedside evaluation of patients with IIMs. This can possibly allow for a reduction in unnecessary HRCTs, reducing the exposition of patients to ionizing radiations, optimizing resources and reducing the costs of patients’ management.

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.

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.

Review; Authors: C. Baldini, L.G. Chatzis, G. Fulvio, G. La Rocca, E. Pontarini, M. Bombardieri