Prevalenza e correlazioni clinico-sierologiche della Fatigue in corso di sindrome di Sjogren primitiva.

La sindrome di Sjogren è una connettivite sistemica a prevalente coinvolgimento del sistema ghiandolare esocrino, la cui manifestazione clinica principale è rappresentata da una sindrome sicca sia orale che oculare. Ai sintomi ghiandolari si possono associare manifestazioni sistemiche, organo specifiche ed alterazioni del profilo sierologico-laboratoristico. Tendenzialmente la malattia ha un decorso benigno, tuttavia la complicanza più grave è rappresentata dalla comparsa di un linfoma non Hodgkin a cellule B di tipo marginale (MALToma). La Fatigue nella sindrome di Sjogren è un elemento clinico di importanza rilevante. Lo studio monocentrico osservazionale cross-sectional, condotto su una coorte di 49 pazienti della U.O. di Reumatologia dell'Università di Pisa, ha messo in luce la notevole prevalenza della Fatigue nella sindrome di Sjogren e il suo impatto sulla percezione della qualità di vita dei pazienti. Si è dimostrata l'associazione della Fatigue con la fibromialgia, la tiroidite cronica autoimmune e con i disturbi del sonno secondari a malattia. Si è inoltre delineata la correlazione tra disturbi del sonno secondari a malattia (espressi come punteggio al PSQI) e la secchezza orale, oculare, la nicturia e il dolore notturno (espressi come punteggi alla relativa scala VAS). Pertanto si conclude che è necessario dare maggiore importanza alla Fatigue dal punto di vista clinico e terapeutico, impostando trattamenti adeguati e mirati soprattutto nei confronti della fibromialgia e dei disturbi del sonno secondari a malattia

Ruolo della Risonanza Magnetica delle Ghiandole Salivari Maggiori per lo Studio delle Lesioni Sospette per Natura Linfoproliferativa nei Pazienti con Sindrome di Sjögren

Background: la sindrome di Sjögren (SS) è una patologia autoimmune che coinvolge tipicamente le ghiandole salivari maggiori caratterizzata da un rischio incrementato rispetto alla popolazione generale di sviluppare linfomi MALT (MALT-L) delle ghiandole salivari maggiori. La risonanza magnetica delle ghiandole salivari maggiori (SG-MRI) è una metodica, che grazie all’utilizzo di sequenze specifiche (es: DWI), si presenta come una metodica di primo piano per lo studio delle neoplasie delle ghiandole salivari. Lo scopo dello studio è la tipizzazione morfologica e DWI delle lesioni sospette per linfoma nei pazienti con SS e tumefazione persistente delle ghiandole salivari maggiori, valutando eventuali associazioni tra le caratteristiche morfologiche presenti in risonanza e ecografia (SGUS). Materiali e metodi: si tratta di uno studio osservazionale monocentrico condotto su 28 pazienti seguiti presso la UO di Reumatologia di Pisa, 19 con diagnosi di SS e 9 con scialoadenite non-SS, che sono stati sottoposti a SG-MRI per lo studio di tumefazione delle ghiandole salivari maggiori. Sono stati raccolti ed analizzati dati clinici, laboratoristici, ecografici e ottenute sequenze standard e specifiche in SG-MRI. Le immagini sono state valutate indipendentemente da 2 radiologi esperti di SG-MRI e patologia di testa-collo. Risultati: è stata riscontrata associazione statisticamente significativa fra la presenza di aree sospette per linfoma e aspetto solido-cisto delle lesioni, presenza di cisti polisettate e sostituzione adiposa ghiandolare. Alle sequenze DWI l’ADC medio delle lesioni sospette per NHL (0,75 ± 0,13 x 10^-3 mm²/s) è risultato significativamente inferiore all’ADC ghiandolare medio dei pazienti con SS senza aree sospette (1,08 ± 0,19 x 10^-3 mm²/s) e dei pazienti non-SS (1,28 ± 0,22 x 10^-3 mm²/s). l’ADC ghiandolare medio dei pazienti con SS è risultato significativamente inferiore all’ADC medio dei pazienti non-SS. Alla SGUS un valore pari a 3 allo score OMERACT è associato a ADC value ghiandolare medio significativamente inferiore rispetto all’ADC medio associato a punteggi pari a 0, 1 e 2. Conclusioni: La SGMR appare come una metodica di importanza rilevante per la caratterizzazione morfologica e in diffusione delle lesioni sospette per MALT-L in SS e per definire correttamente l’area in cui attuare accertamento bioptico mirato. I pazienti che all’ecografia presentano score OMERACT 3 sono i pazienti meritevoli di follow up stretto volto a riscontrare precocemente lesioni ecografiche sospette per NHL

Total area of inflammatory infiltrate and percentage of inflammatory infiltrate identify different clinical-serological subsets of primary Sjögren's syndrome better than traditional histopathological parameters

Recently, the total area of the inflammatory infiltrate and the percentage of inflammatory infiltrate have been proposed as novel histopathological parameters to improve the stratification of patients with Sjögren's syndrome (SS) in clinical trials. Both these parameters provide a more accurate assessment of the extent of the infiltrate in minor salivary gland biopsies (MSGBs) and may overcome the bias related to the Focus score (FS). To date, however, only few studies have investigated their clinical value and feasibility. In this study we revised consecutive MSGBs obtained routinely in a real-life clinical setting and correlated the total area of the inflammatory infiltrate and the percentage of inflammatory infiltrate both with the other MSGB histopathological parameters and with patients' clinical features in order to explore their usefulness in SS diagnostic work-up

One year in review 2020: pathogenesis of primary Sjögren's syndrome

The pathogenesis of primary Sjögren's syndrome (pSS) remains poorly understood. However, important efforts have been made during the last few months. In this review, following the others of this series we will summarise the most recent literature on pSS pathogenesis focusing in particular on new insights into pSS animal models, genetics and epigenetics, innate and adaptive immune system abnormalities and tertiary lymphoid structures. Hopefully, novel insights into pSS pathogenesis will pave the way to new therapeutic approaches to the disease improving patients' management and prognosis

CLINICAL AND BIOLOGICAL FEATURES DISTINGUISH MYELOID DISEASES FROM MYELOID DISORDERS ASSOCIATED WITH AUTOIMMUNE DISEASES.

In a series of 11000 patients withmyeloproliferative neoplasms (MPN) and 43,000 matched controls, a Swedish group reported that a prior history of autoimmune diseases (ADs) was significantly associated with a higher risk of MPN. More recently, our group showed that in chronic myeloid leukemia (CML) some genes correlated with AD (GLYPR1, PCARD, S100) were highly expressed at diagnosis and that the treatment with Imatinib impacted on the “inflammatory” profile of CML patients. Aims To investigate the frequency of myeloid malignancies (i.e myelodysplastic syndrome (MDS) and chronic, either Philadelphia-positive or Philadelphia-negative, myeloproliferative disorders (MPNs)) in patients with ADs, their influence on the ADs clinical course and vice-versa, and to identify several distinctive clinical and biological features. Methods A retrospective systematic search through the electronic health records of the patients admitted at Rheumatology from 2009 and 2019 was performed to select those presenting with ADs and MDS or MPNs. Categorical variables were compared using chi square test and Fisher’s test; continuous variables were compared using Student’s t-test. A 2-tailed value of p <0.05 was taken to indicate statistical significance. Results Out of the medical records of 5040 patients, we identified 55 patients (33 F: 22 M, mean age: 61 years) with ADs and myeloid malignancies (1%): 20/55 with AD and MDS and 35/55 with AD and MPNs. No demographic differences were observed in the two subgroups. Regarding MDS, anemia was the most common hematologic presenting finding (16/20, 80%), with diagnosis of refractory anemia with excess of blasts (RAEB I/II) done in 25% of cases, followed by syderoblastic anemia in 12%. In the MPNs, 12/35 patients (34%) had a diagnosis of chronic myeloid leukemia (CML), 9/35 (26%) had MF 8/35 (23%) had an ET and 6/35 (17%) a PV. The JAK2 V617F mutation was detected in 100%, 57%, and 66% of PV, ET, and MF patients respectively. Regarding the temporal appearance of myeloid malignancy, MDS occurred concurrently (10/20) or followed (10/20) the diagnosis of Ads, whereas MPNs generally preceded the diagnosis of ADs (19/35). In MDS, the most commonly diagnosed ADs were seronegative arthritis (5/20, 25%), large and small vessel vasculitis (4/20, 20%), Systemic Lupus Erythematosus (3/20, 15%) and other ones in the remaining 8 cases. In patients with MPNs, the diagnosis of rheumatoid arthritis (2/9, 22%), and anti-phospholipid syndrome (3/9, 33%) were often associated with MF, whereas anti-Ro52 (TRIM21) positive systemic connective tissue disorders (4/8, 50%) were more frequently detected in ET. Cardiovascular events were observed in 14/55 (26%): 4/20 (20%) in MDS, 3/12 (25%) in CML and 7/23 (30%) in Philadelphia-negative MPNs. In this cohort, as expected, cardiovascular events were all observed in patients presenting JAK2V617F mutation. Conclusion Our study shows that the frequency of MDS and MPNs in ADs is not negligible and might be considered in the assessment of cardiovascular risk in systemic autoimmunity. It has been reported that, under viral infection, TRIM21 is up-regulated by activation of the IFN/JAK/STAT pathway; interestingly, anti-Ro52 (TRIM21) were over-represented in MPN, where the JAK/STAT signal is hyper activated. This could explain also our observation that frequently the onset of ADs follows the diagnosis of MPN. Ackowledges: this study received support from university of Pisa PRA 2018 PI Prof. Petrin

Impact of first wave of SARS-CoV-2 infection in patients with Systemic Lupus Erythematosus: Weighting the risk of infection and flare.

IntroductionThe aim of this study was to investigate the incidence and clinical presentation of SARS-CoV-2 infections in a Systemic Lupus Erythematosus (SLE) cohort; to assess correlations with disease characteristics and rheumatic therapy; and to evaluate the occurrence of treatment discontinuation and its impact on disease activity.Materials and methodsSLE patients monitored by a single Italian centre were interviewed between February and July 2020. Patients were considered to be positive for SARS-CoV-2 infections in case of 1) positive nasopharyngeal swab; 2) positive serology associated with COVID19 suggesting symptoms. The following data were also recorded: clinical symptoms, adoption of social distancing measures, disease activity and treatment discontinuation.Results332 patients were enrolled in the study. Six patients (1.8%) tested positive for SARS-CoV-2 infection, with the incidence being significantly higher in the subgroup of patients treated with biological Disease-Modifying Anti-Rheumatic Drugs (p = 0.005), while no difference was observed for other therapies, age at enrollment, disease duration, type of cumulative organ involvement or adoption of social isolation. The course of the disease was mild. Thirty-six patients (11.1%) discontinued at least part of their therapy during this time period, and 27 (8.1%) cases of disease flare were recorded. Correlation between flare and discontinuation of therapy was statistically significant (pConclusionTreatment discontinuation seems to be an important cause of disease flare. Our findings suggest that abrupt drug withdrawal should be avoided or evaluated with caution on the basis of individual infection risk and comorbidities