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Objective: Serum prealbumin is a recognized marker of malnutrition, but its role in the prognosis of patients with SSc has not yet been investigated. The aim of the present multicentre prospective study was to investigate the association between prealbumin and mortality, independent of clinical features, in a cohort of SSc outpatients., Methods: Patients were followed up according to standard clinical guidelines with visits at least every 6 months. Data collected included records of skin and internal organ involvement, survival and causes of death., Results: During a median follow-up of 48 months [interquartile range (IQR) 25-58], 34/299 patients (11%) died. In univariable survival analysis, age; male sex; lung, gastrointestinal or multiple visceral organ involvement (two or more); co-morbidities (two or more) and low serum prealbumin were significant predictors of mortality. In bivariable Cox models, alternatively adjusted for significant predictors, prealbumin was independently and significantly associated with the outcome. Mortality rates were particularly influenced by low prealbumin in patients without significant co-morbidities or multiple organ involvement., Conclusion: In SSc patients, low serum prealbumin is an independent predictor of mortality, particularly in those without significant internal organ involvement. Further research on this nutritional marker is warranted., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim of this study was to describe a single-center experience in the treatment and follow-up of cystoid macular edema patients. Clinical records of all patients with cystoid macular edema followed up in the Rheumatologic and Ophthalmological Unit of our center between 1993 and 2013 were retrospectively evaluated. The outcome was assessed by visual acuity and optical coherence tomography status during follow-up. Comparisons were made by Fisher's exact test (p < 0.05 significant). In this study 16 eyes in 9 patients were analyzed. Our study includes mainly post-uveitic (78 %) cases with a high prevalence of human leukocyte antigen B51 (67 %). Systemic immunosuppressive therapy was prescribed in 87 % of cases. The most frequently used drugs were cyclosporine, interferon-α, and infliximab. The first two molecules appeared respectively the most used as the first option and the one with the longest survival on treatment. Interferon-α was the most effective drug in contrasting visual acuity loss compared to the majority of drugs, but significantly more effective than mycophenolate (p = 0.01) in reducing macular edema. At the end of follow-up, 50 % of patients showed a significant visual loss, while 88 % did not present macular edema. In our small cohort, interferon-α is the most promising drug in contrasting visual acuity loss in cystoid macular edema. Visual prognosis remains severe in these patients.

Objectives: Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterised by skin and muscle inflammation, internal organ involvement and serum disease-specific autoantibodies. The recently identified anti-MDA5 (melanoma differentiation-associated gene 5) antibodies are associated with clinically amyopathic DM (CADM), rapidly progressive interstitial lung disease, severe skin manifestations, and poor prognosis. Our objective was to examine the clinical significance of anti-MDA5 antibodies in a cohort of European Caucasian patients with PM/DM, considering that data on anti-MDA5 serology are limited to Asian and US cohorts., Methods: Sera from 76 consecutive adult Italian patients with PM/DM were analysed by immunoprecipitation (IP) of 35S-methionine radiolabelled HeLa and K562 cell extracts, ELISA using recombinant MDA5 protein and IP-Western Blot using rabbit anti-MDA5 antibodies. Clinical associations of anti-MDA5 antibody positive patients were analysed., Results: Anti-MDA5 antibodies were identified in 5/76 (7%) PM/DM cases and all 5 cases were CADM; anti-MDA5 was the second most common autoantibody in DM after anti-MJ/NXP-2, found in 24% of cases. Compared to 29 anti-MDA5 (-) DM, anti-MDA5 (+) patients have more typical DM skin disease (digit pulp/periungual lesions, Gottron's papules, heliotrope rash) (p=ns). Interstitial lung disease was observed in 3/5 anti-MDA5 (+) patients but only 14% of anti-MDA5 (-) cases (p=0.048)., Conclusions: Our study on European patients with PM/DM confirms that anti-MDA5 antibodies are not uncommon. All anti-MDA5 (+) cases are affected by CADM with typical skin disease, while rapidly progressive pulmonary involvement was diagnosed only in one case. Further studies in larger cohorts are necessary to define the clinical significance of anti-MDA5 antibodies in European PM/DM.

Objectives: Aseptic meningitis is a rare and aggressive complication of rheumatoid arthritis (RA), usually histologically characterised by rheumatoid nodules and lymphocytic aggregates in leptomeninges. The aim of this study was to describe the clinical onset and evolution of aseptic meningitis occurring during anti-TNF-alpha (TNF-α) therapy., Methods: we retrospectively analysed the clinical records of patients with RA or ankylosing apondylitis (AS) treated by TNF-α drugs in the last 10 years., Results: Four out of 718 patients, treated with TNF-α, developed meningitis after a mean of 5 years (SD: 3.7) of TNF-α exposure (0.55%). Three subjects were affected by long-standing RA (median: 11 years, IQR:8.5-25), one patient by active AS of 8 years' duration. RA patients were treated with etanercept (2 cases) and infliximab (1 case), in association with methotrexate and prednisone. The AS patient was treated with adalimumab. Neurological onset was focal epilepsy (3 cases) and dysarthria (1 case). RM showed leptomeningeal enhancement of basal nuclei (1 case) or fronto-parietal zone (3 cases), associated in one patient with cerebritis. Bacterial, viral or parasitic infections were excluded. One patient underwent cerebral biopsy showing T and B lymphocytes' aggregates. All patients discontinued TNF-α drugs and were treated with high dose of steroids, added to methotrexate in two cases. Neurological symptoms resolved without residuals, and meningeal enhancement showed resolution with high latency., Conclusions: Meningeal inflammation is a rare manifestation occurring in long-standing RA and AS in clinical remission. TNF-α therapy did not prevent this extra-articular complication.

Background: Videocapillaroscopy of the nail fold is the current gold standard to assess progressive changes of the capillary network in patients with systemic sclerosis (SSc). Reflectance confocal microscopy (RCM) is a non-invasive optical imaging tool that allows in vivo visualization of the skin structures and cutaneous microcirculation., Objective: To investigate qualitative and quantitative changes of the cutaneous microcirculation and dermal-epidermal alterations of SSc patients by RCM and to correlate the images with findings of videocapillaroscopy and histology., Methods: Ten patients affected by diffuse-type SSc with skin involvement and 10 healthy controls were enrolled. All subjects underwent RCM of the dorsal and ventral surfaces of the middle third of the left forearm and nailfold videocapillaroscopy. Skin biopsies for histological and immunohistochemical investigations were taken from 5 patients and 2 healthy controls., Results: At RCM observation, the diameter, perimeter and area of cutaneous capillaries were significantly increased in comparison to healthy controls, as histologically confirmed, whereas blood flow speed was significantly slower. Videocapillaroscopy showed a pathologic pattern of disease activity in 8 SSc patients and was non-specific in the remaining 2. In addition, RCM showed epidermal atrophy, flattening of rete ridges and dermal fibrosis in 7 SSc patients with long-standing disease but not in 3 patients with a recent onset., Conclusion: RCM provides measurable morphological and functional findings of microcirculation in patients suffering from diffuse-type SSc. These findings can integrate with, but not substitute, those provided by standard videocapillaroscopy. In addition, unlike videocapillaroscopy, RCM allows the investigation of epidermal and dermal changes.

Objectives: We aimed to analyse the annual incidence of anti-Ku antibodies and to study their clinical associations in patients mainly affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) overlap diseases., Methods: Anti-Ku were detected by counterimmunoelectrophoresis in a total of 203 sera during 14 years of anti-ENA detection. Anti-Ku+ sera belong to 46 patients, mostly affected by UCTD (12 cases), SSc spectrum diseases (13 cases), including SSc/PM, SSc/DM and SSc; and SLE spectrum diseases (9 cases), including SLE, SLE/APS, SLE/SS, SLE/PM., Results: Anti-Ku antibodies represent 2% of all anti-ENA positive sera, and are found in 1.3-3% of anti-ENA positive sera per year. Anti-Ku+ SSc represents 2% of all SSc patients. All anti-Ku+ SSc spectrum diseases showed a limited cutaneous disease; myositis, dysphagia and isolated anti-Ku in more than 70% of cases. Interstitial lung disease (ILD) was found in 54% of SSc patients, frequently with mild functional impairment. When compared with other limited SSc cases, anti-Ku+ SSc showed a higher rate of male patients, arthritis, myositis and ILD. A lower rate of digital ulcers was found, although both groups showed the same rate of SSc pattern at nailfold capillaroscopy. Anti-Ku+ SLE patients (representing 1.5% of all SLE) showed cutaneous features, Raynaud's phenomenon, multiple autoantibodies, without major organ manifestations. Isolated anti-Ku+ patients significantly show a diagnosis within SSc spectrum diseases, with arthralgias, Raynaud's phenomenon, dysphagia, ILD, myositis and sclerodactyly., Conclusions: In SLE spectrum diseases, anti-Ku are found associated with other autoantibodies, without a peculiar clinical profile, except for Raynaud's phenomenon and severe alterations of capillary bed. In SSc anti-Ku are frequently associated with myositis and ILD, mostly found as isolated autoantibodies.

Background: Rheumatoid arthritis (RA) is associated with increased mortality and morbidity because of accelerated atherosclerosis. The study assessed the prevalence of left and right ventricle diastolic and systolic dysfunction in outpatients with RA., Methods: The study included 93 outpatients with RA. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted., Results: In the group of RA patients, we found high prevalence of left ventricular systolic and diastolic dysfunction and right diastolic dysfunction compared with controls (13.5% vs 5.5 %, 76.3% vs 48.8% and 41.9% vs 6.6%, respectively; P < 0.001). Rheumatoid arthritis patients and controls showed significant differences about mitral, tricuspid, and pulmonary flow velocity curves; tissue Doppler curves of the lateral and the septal myocardial walls of the left ventricle; and basal myocardial free wall of the right ventricle. There were not any correlations between inflammatory and functional disease parameters and variables of systolic and diastolic function., Conclusions: Our study shows a high prevalence of left ventricular systolic and diastolic dysfunction in a population of outpatients affected by rheumatoid arthritis.

Objective: Autoantibodies in the systemic rheumatic diseases are clinically useful biomarkers of the diagnosis or of certain clinical characteristics. An unusual pattern of immunoprecipitation, in which the D, E, F, and G proteins of small nuclear RNPs (snRNP) but without other components of the snRNP, was noticed at the autoantibody screening. The purpose of this study was to examine the target antigens and clinical manifestations associated with this specificity., Methods: Autoantibodies in sera from 1,966 American patients (including 434 with systemic lupus erythematosus, 121 with scleroderma, 86 with polymyositis/dermatomyositis [PM/DM]) and 248 Italian patients with autoimmune diseases were screened by immunoprecipitation of (35) S-methionine-labeled cell extracts. Sera with which D, E, F, and G proteins of snRNP was immunoprecipitated, but without the other snRNP proteins, were further examined by analysis of RNA components by immunoprecipitation (silver staining), Western blotting using survival of motor neuron (SMN) complex, and immunofluorescence., Results: Three sera that immunoprecipitated D, E, F, and G proteins without other components (U1-70K, A, B'/B, C) of the snRNP were found. Four additional proteins (130 kd, 120 kd, 38 kd, and 33 kd) were also commonly immunoprecipitated. The target antigen was identified as SMN complex (Gemin 3, Gemin 4, SMN, and Gemin 2, respectively), which plays a critical role in the assembly of snRNP. In immunofluorescence analyses, all 3 sera showed nuclear dots (Cajal bodies) and cytoplasmic staining. Only 1 serum was weakly positive on Western blotting of SMN, suggesting that these sera mainly recognize native molecule or quaternary structure. All 3 patients were white women with PM, an interesting finding, since deletion or mutation of SMN is known to cause spinal muscular atrophy., Conclusion: SMN complex was identified as a new Cajal body autoantigen recognized by sera from white patients with PM. The biologic and clinical significance of anti-SMN autoantibodies will need to be clarified., (Copyright © 2011 by the American College of Rheumatology.)

Pregnancy represents a physiologic condition where maternal immune system tolerates the semi-allogenic fetus. The fetal tissues are directly exposed to the maternal blood with potential attacks from maternal immune system, including the activation of complement cascade. Small amounts, of both early and late components, of complement are physiologically found in the placenta, maybe in relation to the vascular remodeling process. A significant increase of complement activation was associated with different pathologic pregnancy outcomes, namely pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth retardation, and anti-phospholipid syndrome (APS). In some, but not in all, mice models of APS, complement activation plays a major role in pregnancy loss, with a massive accumulation of C3 in the placenta, while C3 deficient mice didn't show fetal resorption. Basing on these findings, anti-phospholipid antibodies and complement activation (via C3a, C5a, and MAC) may cooperate in triggering a local inflammatory process, eventually leading to placental thrombosis, hypoxia, and neutrophil infiltration. However, histological analysis of human placenta tissues from APS women shows small rather than widespread inflammation. In a similar manner, complement activation can be detected in human APS placentas but without any relationship with pregnancy outcome and therapy. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are really taking place in APS.

The complement (C') cascade is an important part of the innate immunity. It acts through three major pathways: classical (CP), alternative (AP) and mannose-binding-lectin (MP). C' reduction is a key feature in systemic lupus erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of our study are to correlate C' variations with disease activity and verify the presence of C' deficiencies. We tested for three C' pathways 52 sera from 20 patients affected by SLE. A significant correlation between the ECLAM score and the degree of activation of the CP (Mann-Whitney; P = 0.001) was recorded, while the correlation with anti-dsDNA antibodies did not reach statistical significance (Mann-Whitney; P > 0.05). In conclusion, the ELISA assay can be considered well suited for testing SLE samples. We detected a significant link between the phases of lupus activity and the reduction of the CP.

The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with systemic sclerosis (SSc), to compare it with that of patients with rheumatoid arthritis (RA), and to correlate it with other parameters. HR-QOL was evaluated by the Short Form 36 (SF-36), SSc disease activity and severity by preliminary indexes recently proposed, disability by the Health Assessment Questionnaire (HAQ), and depressive symptoms by the Beck Depression Inventory. HR-QOL perception was not statistically different in patients with SSc and RA, except that patients with diffuse cutaneous involvement had worse scores in the general health and mental health dimensions than patients with RA (p=0.03). Compared with RA, patients with SSc tended to perceive less bodily pain (p=0.06) and have less disability (p=0.04) but to report higher depressive symptom scores (p=0.05). SSc patients' HR-QOL was associated with some disease severity scales (general, kidney and, less significantly, heart), but it was poorly correlated with the other evaluated disease activity and severity indexes. A strong correlation with disability and with depressive symptoms was observed. In conclusion, patients with SSc perceived a reduced HR-QOL similar to that of patients with RA. SF-36 may provide useful information in their evaluation.