To assess Chlamydophila psittaci (Cp) subclinical infection in patients with Sjögren's syndrome (SS).Seventy-four SS patients (55.4 ±13.4 yrs; 94.6% females) were studied. Among them, 18 had salivary gland mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, 20 myoepithelial sialoadenitis (MESA), and 36 no lymphoproliferative disorders (LPD). The presence of Cp DNA was assessed in peripheral blood of all patients by specific PCR protocols. Paired salivary gland samples were also investigated whenever available (34 cases), including lymphomatous and non-lymphomatous samples, as well as major and minor salivary gland tissues. As controls, 225 blood donors were analysed in the peripheral blood.Overall, Cp DNA was detected in 11/74 (14.9%) SS patients vs. 1/225 (0.4%) controls (p<0.0001). Cp was detected at higher frequency in MALT lymphoma patients (6/18, 33.3%), as compared with MESA (3/20, 15%) or patients without LPD (2/36, 5.6%), (MALT lymphomas vs. others: p=0.02). A similar Cp prevalence was observed in blood vs. salivary gland tissues, however with a higher frequency in the major than in the minor salivary glands (5/18, 27.8%, vs. 1/17, 5.9%, p=0.18). Cp-positive patients were all rheumatoid factor positive (11/11, 100% vs. 40/63, 63.5% Cp-negative; p=0.014), while no difference was noticed for anti-SSA/SSB positivity.In the light of accepted models of MALT B-cell lymphomagenesis and considering previous data implicating Cp infection in ocular adnexa MALT lymphoma, our results suggest that Cp infection could be involved also in a fraction of patients with SS developing lymphoma. The potential therapeutic implications of these findings appear worthwhile.
To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV.From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma.1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy.pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.
CrCryoglobulinemia is a known risk factor lymphoma in primary Sjögren9s syndrome (pSS) and it is an hallmark of a more aggressive systemic disease. Whether this is related to the sole presence of serum cryoglobulins (SC) or also to an associated cryoglobulinemic vasculitis (CV) is unknown, since criteria for the classification of the latter were developed and validated only very recently (1,2).
Objectives
The aim of this study is to describe the characteristics of cryoglobulinemia in the course of pSS and to evaluate the association with CV, classified according to the validated criteria (1,2), and with B-cell lymphoma.
Methods
144 consecutive patients with pSS were repeatedly evaluated for SC according to the standard methods (3). The 2011 classification criteria for CV and the presence of lymphoma were investigated in positive cases.
Results
SC were repeatedly present in 28/144 patients (19.4%), with a median of three determinations (range 2-33) per patient. In 14/28 cases (50%), the presence of SC was fluctuating, while in 14/28 cases (50%) SC were persistently positive in all the tests performed. SC were type II in 11/28 (39.3%) patients (8/11 persistently positive, 3/11 fluctuating), and type III in 7/28 patients (2/7 persistently positive, 5/7 fluctuating); in 10/28 cases, SC typing was not performed for the insufficient cryocrit (4/10 persistent, 6/10 fluctuating). Patients with positive SC fulfilled the CV classification criteria in 16/28 cases (57.1%). CV was more frequent in pSS with persistent SC (11/14, 78,6%) than pSS with fluctuating SC (5/14, 35,7%) (p=0,02, Pearson). Lymphoma was observed in 4/12 (33.3%) pSS patients with SC without CV, and in 6/16 (54.5%) pSS patients with CV.
Conclusions
Persistently detectable, rather than fluctuating SC, are more associated with CV and with malignant lymphoma in pSS. The repetition of SC testing is then recommended in pSS.
References
De Vita S, et al. Preliminary classification criteria for the cryoglobulinaemic vasculitis. Ann Rheum Dis. 2011;70(7):1183-90. Quartuccio L, et al. Validation of the classification criteria for cryoglobulinaemic vasculitis. Rheumatology (Oxford). 2014;53(12):2209-13. Brouet JC, et al. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med 1974;57:775-88.
Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the vascular wall. The pathogenesis of AAV is strongly associated with B cell-derived ANCAs; thus, Rituximab (RTX) has become a promising drug in the induction and maintenance treatment of AAV. The purpose of this review is to describe the efficacy and safety of RTX in the induction of remission and maintenance therapy of AAV. Herein, we summarize the randomized controlled trials that have contributed to the refinement of the use of RTX in AAV in the past decades. RTX has been proven to be effective both in new-onset disease and in relapsing disease. Although the optimal duration of AAV maintenance therapy remains unknown, the ANCAs and the B-cell repopulation may offer support for the administration of further RTX cycles (or not). The safety of RTX is comparable with cyclophosphamide, with the advantage of a low risk of malignancy and no concern for fertility. In conclusion, RTX now plays an important role in the induction and maintenance therapy of AAV. Optimizing RTX-based treatment strategies in AAV is one of the main goals of the current research in AAV.
Although evidence of precocious cardiovascular (CV) involvement in primary Sjögren's syndrome (SS) is lacking, young SS women display signs of subclinical atherosclerosis. Among disease-related immunologic features, leukopenia and anti-SSA appear to correlate with subclinical atherosclerotic damage (1,2). However, long-term occurrence of CV events and traditional risk factors role for CV disease in these patients have not been clarified (3).
Objectives
Evaluate prevalence and clinical significance of traditional CV risk factors in a cohort of primary SS patients.
Methods
Data from 1,170 SS patients were retrospectively analyzed. Following CV risk factors were considered: smoking (current/previous), hypercholesterolemia (total cholesterol serum level >240 mg/dl), hypertriglyceridemia (serum triglyceride level >150 mg/dl), high-density lipoprotein cholesterol (HDL-c) level (reduced <40 mg/dl, normal: 40-60 mg/dl, increased >60 mg/dl), low- density lipoprotein cholesterol (LDL-c) level (reduced <130 mg/dl; normal: 130-160 mg/dl; increased >160 mg/dl), hypertension (physician diagnosis and/or active anti-hypertensive therapy), diabetes mellitus (active diabetes therapy and/or ≥2 fasting glycemia >126 mg/dl), obesity (according to body mass index). CV events included: fatal/non fatal ischemic myocardial infarction (IMA), stroke, transient ischemic attack (TIA), angina, heart failure (HF), peripheral arterial disease (PAD). Multivariate analysis was performed to compare clinical and immunologic SS features according to CV risk factors number (≤2 or >2).
Results
Complete data from 711 (693 female, 18 men) patients were available. A total of 605 (589 female and 16 men, mean age at diagnosis 51.3±13.8 years) and 106 (104 female and 2 men, mean age at diagnosis 53.9±11 years) patients displayed ≤2 and >2 CV risk factors, respectively. Hypercholesterolemia was the most prevalent CV risk factor (33%), followed by hypertension (30%), increased LDL-c (18%), obesity (11%), hypertriglyceridemia (9%), reduced HDL-c (8%), past smoking (7%), diabetes mellitus (3%) and current smoking (2%). Angina and HF were reported in 1% and IMA, stroke and TIA in <1% of patients. No patient reported PAD. At multivariate analysis, presence >2 CV risk factors was significantly associated with older age, lung involvement, leukopenia and circulating anti-SSA/Ro. Patients >2 CV risk factors received immunosuppressive therapy more frequently than the other group.
Conclusions
Hypercholesterolemia is the most prevalent traditional CV risk factors in a SS cohort. Patients with more CV risk factors may be at increased risk of extra-glandular involvement and to require more often immunosuppressive therapy, suggesting that high disease activity may be associated with an unfavorable CV profile. Interestingly, persistent leukopenia and circulating anti-SSA, as already shown in previously reported studies (1,2), may play a role in the pathogenesis of atherosclerotic damage and consequent CV events in SS.
References
Gerli R; Arthritis Care Res 2010;62:712 Vaudo G; Arthritis Rheum 2005;52:3890 Gerli R; Rheumatology 2006;45:1580
Objective: Salivary gland ultrasound (SGUS) is emerging as a valid tool in the management of primary Sjögren's syndrome (pSS). This study aimed to investigate whether pSS patients with normal-appearing or pathological SGUS findings showed different clinical, laboratory, and pathologic pSS-related features, and to compare the results by using two different SGUS scores. Methods: Consecutive pSS patients, according to the ACR-EULAR classification criteria, were evaluated. Salivary glands were scored using the early 1992 score by De Vita et al. and the latest 2019 OMERACT score, both being semiquantitative 0–3 scoring systems focused on ultrasonographic parenchymal inhomogeneity (grades 0 and 1, normal-appearing; grades 2 and 3, pathological). The patients were then divided into two groups: “SGUS normal-appearing” if all the salivary glands had normal-appearing parenchyma (grade 0 or 1), or “SGUS pathological” if the grade was 2 or 3 in at least one salivary gland. The associations between SGUS and pSS-related clinical, laboratory, and pathological features were then investigated in the two groups. Results: One hundred pSS patients were evaluated, the mean age (±SD) was 60.9 ± 12.0 years, and mean disease duration was 11.7 ± 7.2 years. Twenty-nine out of 100 (29%) patients were in the “SGUS normal-appearing” group and 71/100 (71%) were in the “SGUS pathological” group. A normal-appearing SGUS was significantly associated with the absence of anti-La/SSB antibodies ( p < 0.001) and normal unstimulated salivary flow rate ( p = 0.02) by both univariate and multivariate analyses. By univariate analysis, a normal-appearing SGUS was significantly associated also with the absence of rheumatoid factor ( p = 0.002) and of serum monoclonal component ( p = 0.003), ESSDAI < 5 ( p = 0.03), and with a negative lip biopsy ( p = 0.029). No associations were found with other items, including anti-Ro/SSA ( p = 0.145), Schirmer's test ( p = 0.793), ESSPRI ( p = 0.47), and demographic data. No differences in these results were observed by using the two SGUS scoring systems. Conclusion: The SGUS allowed the identification of different phenotypes of pSS, and different SGUS scores focused on salivary gland inhomogeneity may be effective to this end.
Eosinophilic granulomatosis with polyangiitis is associated with a high risk of acute arterial and venous thromboembolic events (AVTE), particularly around the time of diagnosis and in patients with high disease activity or history of previous AVTEhttp://bit.ly/3sKnvzQ
Belimumab, a monoclonal anti-B lymphocyte Stimulator (BLyS) antibody, appeared effective in Sjögren's syndrome (SS) in the phase II open-label 52-week BELISS study. Herein, the follow-up after the end of the BELISS study and suspension of the drug was reported in order to further verify the efficacy of belimumab in SS.13 SS patients were followed after the end of the belimumab treatment. The patients were all female, aged 54±15 years; all the patients presented anti-SSA and/or anti-SSB positivity. Composite scores for SS disease activity were collected at month 6 and month 12 after the end of the trial. The changes of IgG, IgA, IgM immunoglobulin serum levels, and rheumatoid factor (RF) level were reported. BLyS serum levels were also analysed. Statistics for paired comparisons were used.ESSDAI score increased from 3.5±3.7 at week 52 (end of the trial) to 7.0±5.7 at month 12 after the end of the trial (p=0.003). RF level increased from 31.0 (8.0-224.6) IU/ml at week 52 to 69 (11-666) IU/ml at month 12 after the end of the trial (p=0.008). IgM level increased from 131.9±73.6 mg/dl at week 52 to 165±84.6 mg/dl at month 12 after the end of the trial (p=0.04). A significant increase of serum BLyS levels also increased from 1304 (667-3835) pg/ml at week 52 to 2882 (1353-6178) pg/ml twelve months after belimumab suspension (p=0,04).Targeting BLyS by belimumab appears effective in SS, with the inhibition of RF-positive B cell proliferation.
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