Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca ...(systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted and supported an international collaborative study group (EULAR-SS Task Force) aimed at developing consensual recommendations to provide a homogeneous approach to the patient with primary SjS presenting with systemic involvement. This review summarizes the key factors that should be taken into account in the diagnostic approach in a patient with suspected SjS according to the main clinical patterns of presentation, and is especially focused on organ-specific systemic disease presentations, including a consensus set of recommendations in order to reach an early diagnosis. Close collaboration with the different specialties involved through a comprehensive multidisciplinary approach is essential in SjS patients presenting with systemic involvements.
Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy. Methods: A population-based cohort study was conducted based on ...data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM). Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon–rectum–anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21). Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended.
This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF ...inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2
allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA- = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2
haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2
SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2
allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.
Abstract Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying ...features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no > 2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15 months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19 months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings ( p = 0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p = 0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.
Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to ...assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels ("fish school-like" pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA.
Common variable immunodeficiency disorders (CVID) are a group of rare diseases of the immune system and the most common symptomatic primary antibody deficiency in adults. The "variable" aspect of ...CVID refers to the approximately half of the patients who develop non-infective complications, mainly autoimmune features, in particular organ specific autoimmune diseases including thyroiditis, and cytopenias. Among these associated conditions, the incidence of lymphoma, including mucosal associated lymphoid tissue (MALT) type, is increased. Although these associated autoimmune disorders in CVID are generally attributed to Systemic Lupus Erythematosus (SLE), we propose that Sjogren's syndrome (SS) is perhaps a better candidate for the associated disease. SS is an autoimmune disorder characterized by the lymphocytic infiltrates of lacrimal and salivary glands, leading to dryness of the eyes and mouth. Thus, it is a lymphocyte aggressive disorder, in contrast to SLE where pathology is generally attributed to auto-antibody and complement activation. Although systemic lupus erythematosus (SLE) shares these features with SS, a much higher frequency of MALT lymphoma distinguishes SS from SLE. Also, the higher frequency of germ line encoded paraproteins such as the monoclonal rheumatoid factor found in SS patients would be more consistent with the failure of B-cell VDJ switching found in CVID; and in contrast to the hypermutation that characterizes SLE autoantibodies. Thus, we suggest that SS may fit as a better "autoimmune" association with CVID. Examining the common underlying biologic mechanisms that promote lymphoid infiltration by dysregulated lymphocytes and lymphoma in CVID may provide new avenues for treatment in both the diseases. Since the diagnosis of SLE or rheumatoid arthritis is usually based on specific autoantibodies, the associated autoimmune features of CVID patients may not be recognized in the absence of autoantibodies.
The aim of the present study was to define subsets of patients suffering from polymyalgia rheumatica, where methotrexate (MTX) up to 20 mg/week might be more effective.
A total of 100 patients with ...polymyalgia rheumatica treated with MTX were studied. The criteria for MTX introduction were: (i) relapse during the first month of therapy, when tapering glucocorticoids (GC); (ii) requiring long-term GC (i.e. >24 consecutive months); (iii) requiring ≥5 mg/day of prednisone equivalents after 4 months of GC therapy; (iv) GC-related side-effects; and (v) a high risk of GC-related side-effects. All the patients were followed for at least 12 months. A group of patients treated with GC alone in the same center was also compared with the whole MTX group.
Follow up varied from 12 to 185 months (median 46.5 months). Remission with current prednisone dose ≤2.5 mg/day at month +12 was observed in 59 out of 100 patients; remission with GC suspension at month +12 was observed in 38 out of 100, without significant difference among groups. Approximately half of the patients showed at least one relapse (54/100) during the follow-up period. The cumulative dose of GC was 1.5 g (range 0.1-15.2 g) . New GC-related side-effects were recorded in 16 out of 100 patients at last follow up. Compared with the GC alone group, the MTX group showed younger age, higher prevalence of female sex and higher level of inflammation.
MTX up to 20 mg/day was useful in defined subsets of polymyalgia rheumatica, also in the long term. No significant differences were noticed among the five subgroups. Geriatr Gerontol Int 2018; 18: 1410-1414.
Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year ...retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan–Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7 years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1 years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03–0.73;
p
= 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29–0.69;
p
< 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.
The disease course in primary Sjögren's Syndrome (pSS) differs in different subsets of patients. The aim of this study was to clarify whether the pattern of organ involvement may improve the ...prediction of the very long-term disease outcome.
We collected the data of 255 patients. The total European League Against Rheumatism (EULAR), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score was compared with the pattern of organ involvement, as differentiated by the single ESSDAI domains: (i) at disease diagnosis, and (ii) in the follow-up, by verifying the appearance of new ESSDAI domains and/or the worsening of already active ESSDAI domains.
The mean follow-up duration was 9.1 ± 6.9 years. At disease diagnosis, only the articular activity at baseline could predict the long-term outcome of pSS detected at last follow-up visit, being protective in terms of stable or improved disease activity, as measured by ESSDAI OR 2.9 (1.6-5.4),
= 0.01. In the follow-up, the onset, and/or worsening of either the peripheral nervous system (PNS) domain (by multivariate and univariate analysis), or the biological domain (only by univariate analysis) correlated with a higher disease activity at the last visit PNS domain: OR 5.9 (2.4-14.5),
< 0.0001; biological domain: OR 1.9 (1.0-3.8),
= 0.043. A significantly higher number of patients with articular involvement were taking hydroxychloroquine at the last follow-up visits, if compared with patients without (41/130, 31.5 vs. 13/125, 10.4%,
< 0.0001).
Single organ disease manifestations of SS, herein identified as the articular, PNS and biologic involvement, are relevant to predict the very long-term outcome in pSS.
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