Factors associated of 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 RA patients with particular regards to difficult-to-treat subgroups. METHODS: The diffusion of Janus kinase inhibitors (JAKi) for the treatment of rheumatoid arthritis (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.

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.

Bosentan Does Not Affect Renal Resistive Index in Scleroderma/Systemic Sclerosis Patients.

INTRODUCTION: If properly evaluated, chronic kidney disease can be found in up to 50% of patients with systemic sclerosis (SSc). The renal resistive index (RRI) is a marker of intrarenal vascular resistance and can predict SSc-associated vasculopathy. This study aimed to determine the impact of bosentan, a nonselective endothelin-1 receptor antagonist, on RRI and kidney function in SSc patients with recurrent digital ulcers. METHODS: Twenty-one patients (age 57 ± 9 years, 19 females) were recruited in a 16-week prospective open-label uncontrolled study. Standardized procedures were used to measure general clinical and laboratory characteristics, systolic, diastolic, and mean arterial pressure (MAP), pulse pressure (PP), diastolic to systolic blood pressure (D/S) ratio, and urinary endothelin-1 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate kidney function as an estimated glomerular filtration rate (eGFR). RRI was measured by Doppler ultrasound as the average of three samplings of intrarenal blood flow in different kidney regions of both kidneys. Patients with secondary causes of kidney disease or kidney diseases associated with albuminuria were excluded. RESULTS: Bosentan treatment for 16 weeks did not change RRI (0.731 ± 0.049-0.730 ± 0.054, p = 0.925), but increased urine endothelin-1 to creatinine ratio (0.27 ± 0.15-0.49 ± 0.57 pg/mg, p = 0.032) and reduced MAP (123 ± 10-101 ± 11 mm Hg, p < 0.001), PP (76 ± 11-68 ± 10 mm Hg, p = 0.003), D/S ratio (0.563 ± 0.044-0.538 ± 0.031, p = 0.006), and eGFR (92 ± 20-84 ± 24 mL/min/1.73 m2, p = 0.003). DISCUSSION/CONCLUSION: In conclusion, in patients with SSc complicated by digital ulcers and normal to mildly diminished kidney function, bosentan had no effect on intrarenal hemodynamics, but reduced blood pressure levels and kidney function.

Chest high-resolution computed tomography in primary Sjögren's syndrome: an up-to-date primer for rheumatologists.

Pulmonary manifestations, including airway involvement and interstitial lung disease, are the most frequent extra-glandular complications of primary Sjögren's syndrome (pSS). Chest high-resolution computed tomography (HRCT) is a cornerstone of pulmonary diagnostic imaging, aiming to detect, characterise, and quantify such conditions. In patients with pSS-related lung abnormalities, HRCT proved helpful in various clinical scenarios, including baseline and follow-up evaluation, assessment of superimposed infections, suspected progressive interstitial lung diseases, and acute exacerbation. This review aims to provide a primer for rheumatologists on chest HRCT, illustrating the up-to-date technique, imaging findings, and clinical indications in pSS and highlighting the importance of rheumatologist-radiologist constructive collaboration in the clinical management of such patients.

Usefulness of ultrasound guided core needle biopsy of the parotid gland for the diagnosis of primary Sjögren's syndrome.

OBJECTIVES: The diagnosis and classification of primary Sjögren's syndrome (pSS) relies on labial biopsy, whereas the role of open parotid biopsy is mainly reserved to evaluate the lymphoproliferative complications. Recently ultrasound-guided core needle biopsy (US-guided CNB) appeared as a novel and safe technique useful in lymphoma assessment, however, its potential role in the diagnosis of pSS has never been assessed.The main aim of this study was to evaluate the diagnostic value of US-guided CNB of the parotid glands in patients affected by pSS. METHODS: Patients affected by pSS who underwent US-guided CNB for a suspected glandular lymphoma were included. Adequacy of the samples and histopathological features related to pSS were analysed. RESULTS: US-guided CNB was performed on 29 parotid glands. The biopsied samples were adequate for diagnosis in 28/29 (96.5%) cases. Fifteen patients showed pathologic features of parotid lymphoma. Among the remaining patients, 9/13 presented focus score≥1; LELs were present in 8/13 patients, and GCs in 11/13. In 8 cases the histological features were coherent with MESA/LESA. Acinar atrophy, fibrosis and duct dilatation were also evaluated. CONCLUSIONS: This preliminary study suggests the possible usefulness of US-guided CNB for the diagnosis of pSS by enabling the collection of adequate salivary gland tissue to assess the FS, GCs, LELs, and other histopathologic features also useful in the management of pSS patients.

Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren's syndrome?

OBJECTIVE: Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. METHODS: Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). RESULTS: Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. CONCLUSION: US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.

New developments in ultrasound in rheumatology: innovative tools and promising applications.

In the setting of rheumatology, the assessment of the involvement of joints and peri-articular structures was the first application of ultrasonography in the management of rheumatic diseases. In this field, the main novelties are related to the development of new technical tools to help overcome some of the limitations of conventional ultrasonographic assessment. In the meantime, there has been a growing interest in the application of ultrasound to extra-articular sites, relying on the definition of new indications. The present review aims to provide a critical analysis of the technical developments and new fields of application of ultrasonography in rheumatology.

Magnetic resonance imaging assessment of ASAS-defined active sacroiliitis in patients with inflammatory back pain and suspected axial spondyloarthritis: a study of reliability.

OBJECTIVES: The main purpose was to investigate the intra- and inter-rater reliability of the Assessment of SpondyloArthritis international Society (ASAS) definition of positive MRI for active sacroiliitis (ASAS-positive MRI), in a sample of patients with inflammatory back pain (IBP) and suspected axial spondyloarthritis (axSpA), who underwent sacroiliac joints (SIJ) MRI. We also evaluated the intra- and inter-rater reliability for the detection of the recently ASAS-refined findings indicating inflammatory activity. METHODS: We retrospectively identified 105 consecutive patients with IBP and suspected axSpA who underwent SIJ MRI. Two radiologists in two distinct reading sessions assessed the prevalence of ASAS-positive MRI and of ASAS-defined signs of inflammatory activity. We determined the intra-rater and inter-rater reliability of the above-mentioned variables by means of prevalence-adjusted bias-adjusted kappa (PABAK) statistic, and verified whether there was any significant difference in providing the diagnosis of ASAS-positive MRI on an inter-rater basis (McNemar test). RESULTS: We observed substantial reliability in assessing a SIJ MRI as ASAS-positive both on intra-rater basis (PABAK ranging 0.70-0.77) and inter-rater basis (PABAK 0.71 for the first reading, and 0.64 for the second reading). No significant difference in the rate of diagnosis between raters was found (p>0.99 for both reading sets). Intra-rater and inter-rater reliability for inflammatory activity signs ranged from moderate to almost perfect. CONCLUSIONS: The substantial intra- and inter-rater reliability in assessing the ASAS-positive MRI supports its use for classification purposes. The variable reliability of inflammatory activity signs suggests they are suboptimal as a complement to the current definition of ASAS-positive MRI.

Sonographic features of lymphoma of the major salivary glands diagnosed with ultrasound-guided core needle biopsy in Sjögren's syndrome.

OBJECTIVES: To identify ultrasound (US) features of lymphomas (L) of major salivary glands (SGs) in primary Sjögren's syndrome (pSS) patients and to differentiate US pattern of L and non-L. METHODS: Prospectively, from September 2019 to March 2021, 27 pSS-patients with clinical findings suspicious for L of the SGs underwent US evaluation followed by US-guided core-needle biopsy (CNB). For each patient, we assessed the OMERACT score, dichotomised (0/1 "lower", 2/3 "higher"), and we compared it between L-pSS and nonL-pSS groups. For focal lesions, echogenicity, inner appearance, shape, margins, presence of septa, vascularisation and posterior acoustic features were also assessed and compared between the two groups; we planned to consider as "suspicious" features more frequently associated with L. We expected to compare frequencies at which two or more "suspicious" features were simultaneously present between L-pSS and nonL-pSS. P<0.05 were considered statistically significant. RESULTS: L-pSS showed more inhomogeneous glandular pattern (100% vs. 69.2% higher OMERACT; p=0.0407). For focal lesions, the "suspicious" features identified were: OMERACT grade 3, very hypoechoic, homogenous, oval shape, well-defined margins, presence of septa, colour-Doppler vascularization, posterior acoustic enhancement. 6/8 and 7/8 simultaneous suspicious features were significantly higher among L-pSS patients, compared to nonL-pSS (88.9% vs. 28.6%, p=0.034 for 6/8 features; 77.8% vs. 14.3%, p=0.040 for 7/8 features). CONCLUSIONS: L of the major SGs in pSS was always associated with OMERACT scores 2 or 3 and presented with diffuse or focal patterns. For focal lesions, the association of more "suspicious" features made the diagnosis of L increasingly more likely. This information can help to improve planning of US-guided CNB.

Ultrasound assessment of lacrimal glands: a cross-sectional study in healthy subjects and a preliminary study in primary Sjögren's syndrome patients.

OBJECTIVES: This study aimed to: i) perform an ultrasonographic (US) evaluation of the lacrimal glands (LGs) in healthy subjects in order to define the sonographic elementary lesions which could be identified in the LGs and describe their frequencies in healthy subjects; ii) test the intra and inter-rater agreement between four rheumatologists; iii) preliminary assess whether the elementary lesions of the LGs let us differentiate healthy subjects from primary Sjögren's syndrome (pSS) patients. METHODS: A consensus meeting was held to define the sonographic lesions to be evaluated. Healthy subjects and pSS patients underwent lacrimal glands ultrasound (LGUS) examinations in two Italian Rheumatology Clinics. A web-based reliability exercise was performed on healthy subjects' images by four rheumatologists. Afterward, images of pSS patients were evaluated for the presence of the sonographic lesions previously defined and compared to the US findings in healthy subjects. RESULTS: Fifty-seven healthy subjects and 17 pSS patients were evaluated. The intra and inter-rater reliability score was good-excellent for almost all the agreed US features assessed (glandular parenchyma visibility, size, homogeneity, hypoechoic areas, hyperechoic spots, fibrous gland appearance, fatty deposition). Among the LGUS elementary lesions in pSS patients compared with healthy subjects, we detected a significantly difference in glandular inhomogeneity [13/33 (39.4%) vs. 9/63 (14.3%), p=0.01], and in fibrous gland appearance [3/33 (9.1%) vs. 0/63 (0%), p=0.04]. CONCLUSIONS: In this preliminary study, LGUS proved to have a good-excellent intra and inter-rater reliability. The glandular parenchyma inhomogeneity and the fibrous gland appearance could help differentiate pSS patients from healthy subjects.

Hyperechoic bands detected by salivary gland ultrasonography are related to salivary impairment in established Sjögren's syndrome.

OBJECTIVES: In primary Sjögren's syndrome (pSS) dryness of eye and mouth is the cardinal referred symptom. Assessing the rate of activity and damage in the salivary glands of pSS patients is essential to improve disease management. Up to now, a differentiation of activity and damage ultrasonographic (US) lesions is an open issue. The aim of this preliminary study was to identify US lesions which better correlate with loss of function of salivary glands in pSS. METHODS: Salivary glands ultrasonography of consecutive patients with established pSS, fulfilling AECG and ACR/EULAR criteria was performed. The association between sialometry and Visual Analogue Scale (VAS) oral dryness and SGUS lesions was assessed trough univariate and multivariate analysis. RESULTS: In 75 established pSS patients, mean disease duration 12.4±7.2 years, the hyperechoic bands of parotid gland (PG) and submandibular gland (SMG) were significantly associated with sialometry (p<0.001) and VAS oral dryness (PG p=0.002, SMG p<0.001). The global glandular involvement (scored according to De Vita et al., 1992) was associated with sialometry (PG p=0.025, SMG p<0.001) and with VAS oral sicca (PG p=0.015, SMG p<0.001). The multivariate analysis selected the hyperechoic bands of PG and SMG as the variables independently associated with sialometry and the hyperechoic bands and the homogeneity in the SMG as associated with VAS oral dryness. CONCLUSIONS: These results indicate that salivary impairment in pSS, as objectively evaluated by sialometry, could be mainly associated with damage (i.e., hyperechoic bands) in established pSS. Additional follow-up studies and improved scoring tools are needed.

Ultrasonographic detection of subclinical enthesitis and synovitis: a possible stratification of psoriatic patients without clinical musculoskeletal involvement.

OBJECTIVES: To evaluate the prevalence of articular/extra-articular inflammatory lesions and structural damage on ultrasonography in patients suffering from psoriasis as well as to assess possible correlations between ultrasonographic elementary lesions and clinical features. METHODS: Psoriatic patients without musculoskeletal symptoms and healthy controls (HCs) were recruited. All patients received a blinded extended ultrasonographic examination of 42 joints, 12 entheses and 32 tendons. Active synovitis was defined by the presence of a grade ≥2 for grey scale (GS) and ≥1 for power Doppler (PD), while active enthesitis corresponded to entheseal hypoecogenicity in GS and entheseal PD signal (<2 mm from bone insertion). RESULTS: Forty psoriatic patients and 20 HCs were included. A total of 2516 joints and 712 entheses were scanned. Active synovitis was found in 11/40 (27.5%) psoriatic patients and 0/20 HCs (p=0.01). Articular synovitis (GS≥2) was more frequent in psoriasis than in HCs [34/40 (85.0%) and 11/20 (55.0%) respectively; p=0.024). Active enthesitis was found only in psoriatic patients, with a prevalence of 20.0% (8/40) (p=0.04). No significant difference in the prevalence of tenosynovitis or paratenonitis was observed between psoriatic patients and HCs. In psoriasis cohort, age was correlated with the presence of active synovitis (p=0.03), while male sex and a higher PASI score were independently correlated with the presence of active enthesitis (p=0.05 and p=0.034, respectively). CONCLUSIONS: Active enthesitis and synovitis could be useful to identify subclinical psoriatic arthritis. This might represent a relevant clinical step to better stratify patients with psoriasis.

Risk of developing psoriatic arthritis in psoriasis cohorts with arthralgia: exploring the subclinical psoriatic arthritis stage.

OBJECTIVE: Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis. METHODS: Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs). RESULTS: 384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%). CONCLUSIONS: The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.

Sonographic Appearance of Lacrimal Glands in Sjögren's Syndrome at High Risk for Lymphoma Development.

Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease characterized by the destruction of exocrine glands, mainly salivary and lacrimal glands. The diagnosis is generally made upon objective tests aimed at assessing salivary and lacrimal glandular function, autoantibody assays, and the results of labial salivary gland biopsies. A major salivary gland biopsy is usually reserved to assess lymphoproliferative complications. Recently, the sonographic evaluation of the major salivary glands has gained a crucial role in assessing the glandular parenchyma and early detecting abnormalities, while the role of ultrasonography in the assessment of lacrimal glands is still secondary. Our case report is about a male patient who presented parotid gland swelling and purpuric lesions, with preserved salivary and lacrimal glandular function. Considering the presence of risk factors associated with lymphoproliferative development and the peculiar characteristics detected by salivary and lacrimal gland ultrasonography, we performed a parotid gland biopsy, confirming Sjögren's syndrome. Our case demonstrates that lacrimal gland ultrasonography could be implemented, along with major salivary gland ultrasonography, as a routine procedure in evaluating patients with suspected or definite diagnoses of pSS.

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study.

BACKGROUND: Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. METHODS: One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. RESULTS: At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.  At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24. CONCLUSIONS: This is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.

Salivary Gland Ultrasound in Primary Sjögren's Syndrome: Current and Future Perspectives.

Salivary gland ultrasound (SGUS) is the imaging modality of choice for the assessment of parotid and submandibular gland parenchyma. Being highly effective, non-invasive and easy to perform, SGUS has become increasingly popular among specialists in assessing salivary gland (SG) abnormalities, including those commonly found in primary Sjögren's syndrome (pSS). SGUS may be useful in the assessment of pSS and its complications, the most serious being the development of non-Hodgkin's lymphoma (NHL). SGUS may also be useful in the characterization and differential diagnosis of diffuse and focal abnormalities commonly associated with pSS, and may act as a guide for core-needle biopsy (CNB), an established, safe, and feasible technique, which provides enough viable tissue for the diagnosis and assessment of lymphoproliferative diseases of the SG. The combination of SGUS with other tools, such as sonoelastography and artificial intelligence (AI), could further improve the usefulness of SGUS in the management of pSS. In this perspective, we summarize current and future applications of SGUS in pSS.

Sjögren syndrome: looking forward to the future.

Primary Sjögren's syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.