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Our objective was to determine the prevalence of antinuclear antibodies (ANAs) in patients with malignancies and to investigate if their presence might be related with development of musculoskeletal symptoms or paraneoplastic rheumatic syndromes. Antinuclear antibodies were determined by indirect immunofluorescence on Hep-2 cells in 274 neoplastic patients and in a control group of 140 age-adjusted healthy subjects. Antinuclear antibody specificities (anti-DNA and antiENA) were investigated in patients with rheumatological symptoms and positive ANA. Antinuclear antibodies were detected in 76 of 274 (27.7%) patients with malignancies and in nine of 140 (6.4%) healthy subjects. Twenty patients reported paraneoplastic rheumatic symptoms or syndromes. Two of them developed clinical symptoms mimicking rheumatoid arthritis (rheumatoid-like arthropathy), one systemic lupus erythematosus (lupus-like syndrome), one dermatomyositis and four cutaneous vasculitides. Musculoskeletal symptoms and paraneoplastic rheumatic symptoms and syndromes were both more frequently observed in patients with positive ANA. Antinuclear antibody specificities were found in only two cases. We can conclude that there is an increased incidence of antinuclear antibodies in malignant conditions. Musculoskeletal symptoms and rheumatic paraneoplastic symptoms and syndromes seem to be more frequent in patients with cancer-related positive ANAs. The failure to find ANA specificities (anti-ENA, anti-DNA) in patients with malignancies and positive ANAs in our study may simply reflect molecular differences between the autoantigens involved in cancer and those characteristically involved in the systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objectives: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation., Methods: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed., Results: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories., Conclusions: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.

Background: Pulmonary arterial hypertension (PAH) is one of the most relevant causes of death in systemic sclerosis. The aims of this study were to analyse the recently published DETECT algorithm comparing it with European Society of Cardiology/European Respiratory Society (ESC/ERS) 2009 guidelines: as screening of PAH; (2) identifying median pulmonary arterial pressure (mPAP) ≥21 mmHg; and (3) determining any group of pulmonary hypertension (PH)., Methods: Eighty-three patients fulfilling LeRoy's systemic sclerosis diagnostic criteria with at least right heart catheterization were studied retrospectively. Clinical data, serological biomarkers, echocardiographic and hemodynamic features were collected. SPSS 20.0 was used for statistical analysis., Results: According to right heart catheterization findings, 35 patients with PAH and 28 with no PH met the standards for DETECT algorithm analysis: 27.0% of patients presented with functional class III/IV. Applying DETECT, the sensitivity was 100%, specificity 42.9%, the positive predictive value 68.6% and the negative predictive value 100%, whereas employing the ESC/ERS guidelines these were 91.4%, 85.7%, 88.9% and 89.3%, respectively. There were no missed diagnoses of PAH using DETECT compared with three patients missed (8.5%) using ESC/ERS guidelines. The DETECT algorithm also showed greater sensitivity and negative predictive value to identify patients with mPAP ≥21 mmHg or with any type of PH., Conclusions: The DETECT algorithm is confirmed as an excellent screening method due to its high sensitivity and negative predictive value, minimizing missed diagnosis of PAH. DETECT would be accurate either for early diagnosis of borderline mPAP or any group of PH.

Objectives: To compare a cohort of patients with systemic sclerosis sine scleroderma (ssSSc) vs. patients with limited cutaneous systemic sclerosis (lcSSc)., Methods: Forty-five patients with ssSSc and 186 patients with lcSSc were investigated. Demographic, clinical and immunologic features and survival were compared., Results: There were no significant differences between ssSSc and lcSSc in gender, age at onset and interval between onset and diagnosis. ssSSc patients fulfilled the ACR criteria for SSc less than lcSSc patients (13%/77%, p<0.0001). There were no significant differences in articular involvement, myopathy, tendon friction rubs and gastrointestinal, pulmonary, cardiac and renal involvements. There was a trend to higher prevalence of pulmonary arterial hypertension (PAH) in ssSSc patients (29%/19%) but not reach significant difference. The prevalence of antinuclear and anticentromere antibodies and slow capilaroscopic pattern was similar. Sicca syndrome (13%/30%; p=0.024), digital ulcers (16%/50%; p<0.0001), calcinosis (11%/26%; p=0.047) and acroosteolysis (0% /10%; p=0.028) were more frequently in lcSSc. Survival at 5, 10, and 15 yr was not different in ssSSc and lcSSc patients (100%/98%, 100%/98%, and 92%/89%, respectively)., Conclusions: ssSSc and lcSSc patients share demographic, clinical and immunologic features. Survival is also similar in both groups. Differences are mainly due to peripheral vascular manifestations. However, despite great similarities, we believe that ssSSc patients should be considered as a different subset in order to avoid misdiagnosis. ssSSc patients should be truly differentiated from early SSc using sensitive and specific studies looking for any asymptomatic organ involvement.

Objectives: To describe the clinical-biological characteristics of patients with scleroderma (SSc) and pulmonary artery hypertension (PAH). To establish the relationship between pulmonary functional tests (PFT), Doppler echocardiography (ECHO) and the severity of the PAH., Material and Methods: Retrospective study of patients with scleroderma treated at a tertiary center. All participants received a protocol study, which included a complete analysis and additional tests: Doppler Echocardiography and pulmonary functional tests (PFT) with carbon monoxide diffusing capacity (DLCO)., Results: Overall, 331 patients were treated, including 68 (20.5%) with PAH. The limited subtype of Scleroderma was the most prevalent. The Person's correlation coefficient was used for the following variables: FVC-sPAP, FVC/DLCO-sPAP, DLCO-sPAP and TRV-sPAP, showed a significant moderate linear association in the relationship DLCO-sPAP and TRV-sPAP. 29 deaths occurred, with 12 of them related to PAH. The median time between the PAH diagnosis and death was 1.8 years., Conclusions: The decrease in DLCO and the increase in TRV are negative predictor factor of PAH which, at the same time, means a worsening prognosis for patients with Scleroderma., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Objective: To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis., Methods: We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P < 0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P < 0.05), and sicca syndrome (37.5% vs 14.5%, P < 0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor., Conclusions: The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study aims to determine the effectiveness of mycophenolate sodium (MS) in patients with scleroderma (SSc)-related interstitial lung disease (ILD). In a prospective observational study, we evaluated 14 consecutive SSc-ILD patients who were treated with MS for 12 months. The effect of MS on lung function was examined by using longitudinal data analytic methods. Wilcoxon rank-sum tests were used to examine the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) by pulmonary function testing. As a group, the median values for FVC, FEV1 and DLCO did not change significantly after 12 months of MS therapy and fulfilled the definition of stable disease by the American Thoracic Society. Individually, after 12 months of treatment, 6 out of 14 patients showed a pulmonary improvement defined as an increase of more than 10% in FVC, and 5 out of 14 patients remained stable. By contrast, the median FVC had declined a non-significant 7.2% from the previous 12 months before MS initiation. No significant drug adverse effects were registered. These prospective data suggest that MS is a safe and well-tolerated therapy for SSc-ILD patients, and it is capable of preventing functional pulmonary deterioration.

Objective: Interstitial lung disease (ILD) frequently complicates systemic sclerosis (SSc). Cyclophosphamide (CYC) is a promising immunosuppressive therapy for SSc-related ILD. Our objective was to investigate the effectiveness of an intravenous CYC (iv CYC) pulse regime in SSc-related ILD during treatment and thereafter., Methods: In a prospective observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months. Clinical status, pulmonary functional testing (PFT) and high resolution computed tomography (HRCT) of the chest were evaluated at enrolment and 6, 12 and 24 months thereafter. After treatment withdrawal, patients were followed up every 6 months with PFT and chest HRCT to monitor lung disease., Results: Clinical improvement was apparent in 8 out of 10 patients. The median values of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) as well as ground-glass pattern on HRCT did not change significantly after 6, 12 and 24 months of therapy. The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months (range: 12-48 months). The final median FVC was 54.5% of predicted value (interquartile range, IQR= 31.6%-94%). Only one patient suffered a FVC deterioration greater than 10%, even though less than 160 ml. The final median DLCO was 68% of predicted value (IQR=38.3-83.6%). Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15%., Conclusions: An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter.

The presence, composition and significance of cryoglobulins was studied in a group of 80 patients suffering from different chronic liver diseases. 43 patients (53.75%) had detectable levels of cryoglobulins and there was a significant correlation (p less than 0.02) between the presence of these and the group of chronic active hepatitis. The immunochemical analysis of the cryoglobulins showed a clear predominance of type III (mixed polyclonal). There was a statistically significant correlation (p less than 0.001) between the appearance of cryoglobulins in chronic liver disease (in general) and extrahepatic clinical manifestations. When the subgroups were analyzed, this correlation was significant in the group of patients with chronic active hepatitis (p less than 0.002) and in those with liver disease of unknown origin (p less than 0.001). The type of cryoglobulins most frequently found in the group of patients with extrahepatic manifestations was also type III (mixed polyclonal).