Current Perspectives on Periodontitis in Systemic Sclerosis: Associative Relationships, Pathogenic Links, and Best Practices.

Systemic sclerosis is a chronic, autoimmune, multisystemic disease characterized by aberrant extracellular matrix protein deposition and extreme progressive microvasculopathy. These processes lead to damage within the skin, lungs, or gastrointestinal tract, but also to facial changes with physiognomic and functional alterations, and dental and periodontal lesions. Orofacial manifestations are common in SSc but are frequently overshadowed by systemic complications. In clinical practice, oral manifestations of SSc are suboptimally addressed, while their management is not included in the general treatment recommendations. Periodontitis is associated with autoimmune-mediated systemic diseases, including systemic sclerosis. In periodontitis, the microbial subgingival biofilm induces host-mediated inflammation with subsequent tissue damage, periodontal attachment, and bone loss. When these diseases coexist, patients experience additive damage, increasing malnutrition, and morbidity. The present review discusses the links between SSc and periodontitis, and provides a clinical guide for preventive and therapeutical approaches in the management of these patients.

An ultrasonographic insight into musculoskeletal manifestation in 100 systemic lupus erythematosus patients.

OBJECTIVES: We aimed to investigate the prevalence of US findings in the hand joints and related tendons and explore clinical and laboratory associations in SLE patients of the typical lupus clinic. METHODS: One hundred consecutive SLE patients were enrolled in the study. Using B-mode and Doppler US, bilateral wrist, metacarpophalangeal and proximal interphalangeal joints were examined for synovitis and erosions, as well as for signs of hand tenosynovitis. RESULTS: US detected synovitis (grade 1-3) in 75% and erosive changes in 25% of the cohort. We found that clinical examination underestimated grade ≥2 synovitis by 13%, while US detected SH grade ≥2 in 10% of asymptomatic patients. The overall inflammatory burden, reflected by the US score, was associated with disease activity (respectively with CPR, SELENA-2K, MS-BILAG, and hypocomplementemia), as well as the presence of bone erosions. Rhupus patients had higher inflammatory markers, significantly more synovial hypertrophy, more erosions, more grade 3 tenosynovitis, and were more likely to receive methotrexate (p<0.001) than patients with SLE arthritis, while patients with Jaccoud's arthropathy were more likely to accumulate damage. The dominant hand exhibited more inflammatory changes (respectively synovial hypertrophy grade ≥2) at both the wrist and MCP joints; however, handedness was not associated with structural damage. CONCLUSIONS: In conclusion: 1. joint involvement in SLE is frequent and underacknowledged; 2. the overall inflammatory burden is associated with systemic disease activity and joint damage; (3) destructive arthritis is more likely to occur in the context of concomitant RA or within an "RA-like" subtype of SLE arthropathy; 4. hand dominance is associated with synovitis, but not structural changes; 5. US assessment may help tailor the management of joint involvement, thus preventing joint damage and disability in SLE patients.

Upper gastrointestinal involvement in systemic sclerosis: Findings in a real-life setting.

Gastrointestinal tract involvement is the most common visceral affectation in systemic sclerosis (SSc), but the manifestations may vary in extension and severity. Endoscopic and histopathological gastroesophageal findings were investigated in patients with SSc. A total of 79 consecutive patients with definite SSc were enrolled in a cross sectional study. Clinical data were collected, upper gastrointestinal endoscopy and biopsies from gastric mucosa were performed in all cases. Fifty-seven (72.1%) out of 79 SSc patients had gastroesophageal symptoms. The most frequent were dysphagia, present in 33 (41.7%) and gastroesophageal reflux symptoms in 23 (29.1%) patients. Out of the 79 patients, 22 were asymptomatic, but in 16 esophageal and gastric mucosa changes were endoscopically detected. Reflux esophagitis was found in 39 (49.3%) patients. The presence of esophageal manifestations was not related to the disease duration or with its other variables. Signs of gastritis were endoscopically described in 47 (59.4%) and confirmed on histopathologic examinations in 45 patients. In 31 patients without any endoscopic changes, 18 (22.7%) showed signs of gastritis on histopathologic examination. No significant statistical differences were found between symptomatic and asymptomatic patients or between those with limited cutaneous SSc and those with diffuse cutaneous SSc in terms of clinical, endoscopic or histopathological findings, except the higher proportion of hiatal hernia in symptomatic patients. The results of this study might suggest that upper gastrointestinal endoscopy should be performed during the early stage of the disease and then periodically in patients diagnosed with SSc, even in the absence of typical symptoms.

Renal Cell Carcinoma With Extensive Tumor Thrombus Into the Inferior Vena Cava and Right Atrium in a 70-Year-Old Man.

The case of a male patient is reported, who presented with renal carcinoma and tumor thrombus in the inferior vena cava (IVC) extending from the right atrium (RA) to the bifurcation of IVC, common and external right iliac vein thrombosis, common and deep right femoral vein thrombosis, right popliteal vein thrombosis, with pulmonary and hepatic metastasis, treated with sorafenib. Renal cell carcinoma (RCC), the most common form of kidney cancer, occurs in 90% of cases and is nearly twice as common in men as in women. The diagnosis of RCC is accompanied by intravascular tumor thrombus in 10% of cases, and further extension of the tumor reaching RA is detected in approximately 1% of all patients. Therapy for advanced renal cell cancer has evolved considerably in the past decade, with new agents greeted like "buried treasure." Before 2005, the widely used systemic agents were cytokine interferon alfa and interleukin-2, which yielded modest efficacy and substantial toxicity. Tyrosine kinase inhibitors (TKIs) increase progression-free survival and/or overall survival as both first-line and second-line treatments for metastatic RCC. Sorafenib is an oral multikinase inhibitor with activity against Raf-1 serine/threonine kinase, B-Raf, vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor (PDGFR), FMS-like tyrosine kinase 3 (FLT-3), and c-KIT.

The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia.

AIM: The purpose of this study is to compare and correlate US evaluation with clinical scores of the disease activity in patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM). MATERIAL AND METHODS: Ten patients diagnosed with RA according to the 2010 ACR/EULAR classification criteria and associated FM based on the ACR 1990 classification criteria and two control groups, one with RA (10 patients) and one with FM (10 patients), were included. Clinical assessment was performed and the disease activity scores were calculated. Synovial/tenosynovial hypertrophy, fluid collections in grey scale (GS), and Power Doppler (PD) US assessed by US in the 28 joints included in the disease activity score 28 (DAS28). RESULTS: GS US score and PD US scores were correlated with DAS28 only in patients with RA (Pearson r coefficients 0.3 and 0.5). Mean DAS28 score was significantly higher in the RA/FM group, compared to RA and FM (5.6 versus 4.6 versus 4.5, respectively). Patients with RA/FM had similar median US scores to RA patients, while in FM group significantly lower median US scores were detected (16 versus 9.5 versus 0 for GS US and 3.5 versus 1.5 versus 0 for PD US, respectively). CONCLUSIONS: Disease activity scores should be interpreted with caution in patients with RA and FM. When available, US should be used to guide treatment decisions in patients with RA and FM.

The evolution of time-intensity curves of contrast enhanced ultrasonography in early arthritis patients with wrist involvement.

AIMS: The aim of the study was to assess the evolution of time-intensity curves parameters of contrast-enhanced ultrasonography (CEUS) after 6 months of conventional treatment in early arthritis patients with wrist involvement. MATERIAL AND METHODS: Patients diagnosed with early rheumatoid arthritis or undifferentiated arthritis on the basis of 2010 ACR/EULAR classification criteria, with bilateral wrist arthritis and both radiocarpal (RC) and intercarpal (IC) synovial hypertrophy identified by grey-scale ultrasonography, were enrolled. Synovial hypertrophy was semi-quantitatively scored (grade 0-3) by grey-scale and by Power Doppler at wrist level. CEUS was performed using Sonovue. The region of interest was selected as the area corresponding to the synovial hypertrophy of the RC and IC joints. Time-intensity curves parameters were calculated with Contrast Dynamic Software. The minimum and the maximum values of Peak, area under the curve (AUC), and slope were selected for each patient at baseline and after 6 months of conventional treatment. The difference between the visits was noted as "Δ". RESULTS: Eleven patients fulfilled the inclusion criteria. Maximum time-intensity curves parameters' difference significantly decreased at 6 months: Peak (30.00+/-5.90% vs 23.22+/-5.22%, p=0.008), AUC (1206.08+/-216.91%s vs 949.13+/-280.12%s, p=0.04) and slope (1.6 (1.4;2.3) %/s vs 1(0.7;1.2) %/s, p=0.03). Moderate correlations were found between maximum ΔPeak, maximum ΔAUC and maximum ΔPower Doppler grade (r=0.44, p=0.17; r=0.46, p=0.16, respectively). CONCLUSIONS: Peak and AUC for joints that had high baseline values significantly decreased following treatment with conventional synthetic drugs in EA patients with wrist arthritis. This decrease in Peak and AUC was moderately correlated with a decrease in US parameters. The joint with the highest values of these parameters may be used for evaluation of EA patients at follow-up.

The role of intraoperative ultrasound for the assessment of the focal liver lesions in patients with colorectal cancer.

OBJECTIVE: To evaluate the concordance between intraoperative ultrasound (IOUS) and abdominal ultrasound (US) for the characterization of focal liver lesions in patients with colorectal cancer, and to evaluate the way in which IOUS influences the initially established hepatic surgical protocol based on abdominal US only. METHOD: In this prospective study 73 patients with colorectal cancer and focal liver lesions found during IOUS were included. Abdominal US and IOUS findings were compared. The initially established hepatic surgical protocol based on abdominal US only was recorded. All patients in whom IOUS influenced this protocol and the way in which this was influenced were recorded. RESULTS: Of the 73 patients, 41 (56.2%) had focal liver lesions classified as malignant by IOUS. In 26 of the 73 patients (35.6%), there were discordances between abdominal US and IOUS. IOUS influenced the operative protocol in 9 of the 73 patients included in the study (12.3%), and in 8 of the 41 patients with malignant lesions (19.5%). IOUS influenced the operative protocol by cancelling the preoperative hepatic surgery decision by evidencing the additional multiple malignant focal liver lesions, following the classification of some lesions as benign or by demonstrating the non-resectable character of other lesions. IOUS also determined unplanned hepatic resections by detecting resectable malignant lesions undiagnosed by abdominal US, and extended or limited the scheduled hepatic surgery based on abdominal US only. CONCLUSIONS: There were inconsistencies between IOUS and abdominal US, therefore in patients with colorectal cancer IOUS provided additional information about focal liver lesions. IOUS influenced the operative protocol and consequently, unnecessary liver surgery was avoided. Also, IOUS identified malignant resectable liver lesions which were undetected by abdominal US.

A real life boceprevir use in treatment-experienced HCV genotype 1 patients with advanced fibrosis.

BACKGROUND: A number of high quality randomized clinical trials examining the efficacy and safety of triple therapy in genotype-1 HCV-infected patients have been published. However, these trials included a small number of patients with advanced fibrosis, and selected a population different from that in real-world settings. AIM: To determine the efficacy of boceprevir, pegInterferon and ribavirin regimen in genotype-1 treatment-experienced HCV-infected patients with cirrhosis and bridging fibrosis in real-life setting. METHOD: 167 treatment-experienced patients (85.6% relapsers) out of which 33.5% had cirrhosis, with a mean age of 52.6 years, registered in the Romanian Name Patient Program Database were included into the study. RESULTS: 16.7% of patients had a viral load >100 IU/mL. Undetectable HCV RNA was encountered in 77.3% of patients at week 12. Multiple logistic regression analysis revealed the following independent predictors, measured at week 8, for an HCV RNA ≥100 IU/mL at week 12 of triple therapy: alanine aminotransferase values (p=0.01), hemoglobin level (p=0.04) and <2 log drop of viral load (p<0.0001). A stopping score at 8 weeks was created as the sum of these 3 parameters, with a total of 4 possible points. AUROC of this score was 0.84, with a sensitivity of 75% and a specificity of 86.2%. CONCLUSION: Triple therapy in this cohort of real-life genotype-1 HCV-infected patients with advanced fibrosis showed robust early virological response (EVR) rates. A week 8 model predicting lack of EVR was created, with good clinical utility that can be validated in prospective larger cohorts.

Ultrasound assessment for the rapid classification of early arthritis patients.

OBJECTIVE: The present study aimed to assess the role of ultrasound (US) in the rapid classification of early rheumatoid arthritis (RA) by investigating whether the US features of inflammation and bone damage in early arthritis overlap with the actual clinical concept of classifying and identifying an aggressive disease. METHODS: Patients with recent-onset arthritis of at least 1 peripheral joint of the hands and/or the feet were consecutively included in this study. Clinical examination, laboratory tests, the Disease Activity Score 28 (DAS28), and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA were assessed for all patients. Medication with disease-modifying antirheumatic drugs was recorded. Ultrasound assessment was performed at the following anatomical sites: wrists, metacarpophalangeal joints 2 to 5, and metatarsophalangeal joints 2 to 5 for assessing the presence/absence of synovial hypertrophy, the presence/absence of power Doppler signal, and the presence/absence of bone erosions.The US features of inflammation and bone damage were analyzed in comparison with the DAS28, with the presence/absence of rheumatoid factor and anti-cyclic citrullinated peptide, with the fulfillment of the new 2010 ACR/EULAR classification criteria, and with the initiated disease-modifying antirheumatic drug. The prescription of methotrexate was considered a marker of an aggressive disease. RESULTS: The US features of inflammation and bone damage correlated with the activity scores measured by the DAS28. The presence of US bone erosions overlapped with the presence of rheumatoid factor and anti-cyclic citrullinated antibodies. Synovial hypertrophy, intra-articular power Doppler signal, and bone erosions detected in at least 1 anatomical site were seen in patients fulfilling (77.7%) and in patients not fulfilling (72.7%) the 2010 ACR/EULAR classification criteria for RA. Synovial hypertrophy was found in at least 1 site in 83.3% and 58.8% of patients in whom methotrexate was prescribed and in whom methotrexate was not prescribed, respectively (P = 0.01). The US features were not correlated with the initiation of sulfasalazine or hydroxychloroquine. The patients presenting bone erosions received in significantly higher percentages the indication for methotrexate (50%) compared with sulfasalazine (20%), P = 0.03, or hydroxychloroquine (26%), P = 0.05. CONCLUSIONS: The US features of inflammation might be of help in classifying early arthritis patients despite the presence of the immune markers for RA. Together with the US features of bone damage, these might be used as an indicator of a more aggressive disease. The absence of correlation between the US findings of RA and the 2010 ACR/EULAR classification criteria indicates a possible independent contribution of US in the understanding of the future evolution of these patients.

Systemic sclerosis-polymyositis overlap syndrome associated with autoimmune hepatitis and cerebral vasculitis.

Autoimmune hepatitis (AIH) is a chronic disorder characterized by persistent hepatocellular inflammation and necrosis. AIH overlap syndromes with other autoimmune diseases have been reported, including connective tissue diseases (CTD). Reports of AIH in systemic sclerosis (SSc), however, are scarce and have been particularly described in the limited SSc subtype. We report a case of systemic sclerosis-polymyositis overlap syndrome that developed AIH and subsequently, cerebral vasculitis. To our knowledge, this is the first report of such a complex mosaic of autoimmunity. We also review the literature regarding scleroderma-related AIH.

Contrast-enhanced ultrasonography in inflammatory arthritis.

The degree of inflammation is the keystone of therapy management in rheumatoid arthritis and other arthritides. The assessment of synovial perfusion using power Doppler ultrasound is an important point in the quantification of the joint inflammation but it is limited by the subjectivity of the vascularization grading and incapacity to detect flows in very small vessels. Contrast agent improves the ultrasound ability to depict and quantify blood flows in synovitis. Contrast-enhanced ultrasonography (CEUS) better differentiates synovitis from collection and distinguishes the active synovitis from inactive fibrotic or necrotic pannus. Quantitative assessment of inflammation is possible analyzing the time-intesity curves and by the correct measurement of the synovial thickness. The additional informations and the diagnostic value of CEUS in arthritides are still controversial but its excellent imaging of synovial vessels open the way for further clinical applications. This review aims to discuss the actual knowledges of CEUS in inflammatory arthritis.

Musculoskeletal ultrasonography in Romania - results from a specific questionnaire.

UNLABELLED: Musculoskeletal ultrasonography (MSUS) is currently used in daily medical practice, as an extension of the clinical examination. The development of training programmes for MSUS has increased the interest of physicians from different specialties in performing this exploration. We realized a survey in order to describe the current practice of MSUS in Romania, as well as determining physicians' preferences for MSUS training implementation. METHODS: In 2010, 196 questionnaires were completed and returned at two congresses in Romania. RESULTS: Most of the participants were rheumatologists and radiologists, followed by physical medicine and rehabilitation doctors, internal medicine doctors, general practitioners and other specialists. 41% of respondents practice MSUS themselves. Doctors use MSUS as a diagnostic tool (95%) and for monitoring diseases (75%). Lack of training and lack of MSUS competence were the main reasons for not performing MSUS. The respondents expressed their preference for future training to be via a programme of regular, intensive courses and active participation in clinics where MSUS is performed. Most of the participants consider mentoring the assessement method of choice. CONCLUSION: The majority of participants in this survey use MSUS in the management of their patients. The results indicate participants' preferences on how training should be delivered in the future.

Subpleural lung tumors ultrasonography.

The assessment of patients with pulmonary focal abnormalities continues to represent an important problem in pulmonary diagnosis. A large number of lung nodules remains undetermined after bronchoscopy, radiological and CT imaging analysis. Ultrasound can contribute to the determination of the nature of peripheral lung tumors, serving as an important aid in decision-making. It helps the investigator to decide the appropriate subsequent step in order to establish the etiologic diagnosis: another imagistic investigation, ultrasonographic guided transthoracic needle biopsy or surgery. This pictorial essay summarizes the main sonographic signs of subpleural lung tumors and the differentiation of benign and malignant lesions.

Treatment with infliximab in a patient with ankylosing spondylitis and Crohn's disease.

The association of Crohn's disease and ankylosing spondylitis is described in up to 30% of cases. Treatment of both conditions is not an easy task. We present the case of a 53 year old woman, diagnosed with colonic Crohn's disease and ankylosing spondilitis, treated initially with increasing doses of sulphasalazine and moderate dose of corticosteroids, with the persistence of severe gastrointestinal and articular symptoms. She underwent therapy with tumor necrosis factor alpha (TNFalpha) inhibitor infliximab, with a spectacular improvement of symptoms, signs and quality of life.