High-Protein Nutritional Supplements Improve Nutritional Status in Malnourished Patients with Systemic Sclerosis.

(1) Background: Impaired nutritional status in systemic sclerosis (SSc) is prevalent. (2) Objective: This study aimed to identify pre-cachexia and malnutrition in SSc patients and to estimate the effectiveness of a high-protein oral nutritional supplement (ONS) in improving their nutritional status. (3) Materials and methods: The SSc population comprised 56 patients and a control group of 49 healthy persons. After a baseline clinical evaluation, bioelectrical impedance analysis (BIA), and laboratory tests, SSc patients were divided into well-nourished, pre-cachectic, and malnourished categories. SSc patients with a nutritional disbalance received a high-protein ONS once daily for 3 months. Patients were reassessed at 3 and 12 months after inclusion in the study. (4) Results: SSc patients, in comparison to the control group, had a significantly lower seven-point SGA value [6(0) vs. 7(1), p < 0.001)], lean tissue mass [LTM, 35.1 (10.5) vs. 40.1 (10.10), p = 0.008], and lean tissue index [LTI, 13.5 (3) vs. 14.9 (4), p = 0.009]. Of the 56 SSc patients, 40 (71.4%) were well nourished, 5 (8.9%) had pre-cachexia, and 11 (19.7%) were malnourished. A high-protein ONS in the pre-cachexia group stabilized the SGA value, anthropometric measurements, and BIA after 3 and 12 months. In malnourished patients, it significantly improved the SGA value [5(0) vs. 6(0), p = 0.002], LTI [12.1 (2.1) vs. 12.7 (3.2), p = 0.021] and LTM [31.1 (7.7) vs. 35.1 (9.1), p = 0.021], and that effect remained stable at 12 months. (5) Conclusion: Malnutrition is a common complication of SSc that can be improved with nutritional intervention.

Metabolomics in systemic sclerosis.

Systemic sclerosis is a rare autoimmune condition leading to incurable complications. Therefore fast and precise diagnosis is crucial to prevent patient death and to maintain quality of life. Unfortunately, currently known biomarkers do not meet this need. To address this problem researchers use diverse approaches to elucidate the underlying aberrations. One of the methods applied is metabolomics. This modern technique enables a comprehensive assessment of multiple compound concentrations simultaneously. As it has been gaining popularity, we found it necessary to summarize metabolomic studies presented so far in a narrative review. We found 11 appropriate articles. All of the researchers found significant differences between patients and control groups, whereas the reported findings were highly inconsistent. Additionally, we have found the investigated groups in most studies were scarcely described, and the inclusion/exclusion approach was diverse. Therefore, further study with meticulous patient assessment is necessary.

Celiac trunk thrombosis in a patient with antiphospholipid syndrome induced by median arcuate ligament compression: a case presentation and literature review.

Median arcuate ligament syndrome (MALS) is a rare disorder caused by the compression of the celiac axis by the fibrous structure of the diaphragm called the median arcuate ligament. Patients with MALS are usually undiagnosed unless characteristic symptoms such as nausea and vomiting, postprandial pain, and weight loss are presented. We report a case of a 29-year-old patient diagnosed with MALS and secondary antiphospholipid syndrome (APS) that developed celiac trunk, common hepatic artery and splenic artery thrombosis. There is not enough information on MALS as a trigger of thrombosis in predisposed patients such as those with APS. However, the case gives rise to suspicion and highlights the diagnostic processes, especially for patients with APS presenting postprandial abdominal pain and weight loss. This review likewise aims at the importance of Doppler ultrasonography as a screening tool and computer tomography (CT) or magnetic resonance (MR) both in the angiography variant, especially to diagnose confirmation and underlying treatment options.

Lipid Alterations in Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease with an elusive etiology and poor prognosis. Due to its diverse clinical presentation, a personalized approach is obligatory and needs to be based on a comprehensive biomarker panel. Therefore, particular metabolomic studies are necessary. Lipidomics addressed these issues and found disturbances in several crucial metabolic pathways. Aim of Review: The review aims to briefly summarize current knowledge related to lipid alterations in systemic sclerosis, highlight its importance, and encourage further research in this field. Key Scientific Concepts of Review: In this review, we summarized the studies on the lipidomic pattern, fatty acids, lipoproteins, cholesterol, eicosanoids, prostaglandins, leukotrienes, lysophospholipids, and sphingolipids in systemic sclerosis. Researchers demonstrated several alternate aspects of lipid metabolism. As we aimed to present our findings in a comprehensive view, we decided to divide our findings into three major groups: "serum lipoproteins," "fatty acids and derivatives," and "cellular membrane components," as we do believe they play a prominent role in SSc pathology.

New lung mass in a patient with granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a potentially lethal ANCA-associated small-vessel vasculitis characterized by a typical triad of upper respiratory tract, lung, and kidney involvement. Lung involvement in GPA occurs in 25-80% of cases. The most common radiographic and computed tomography (CT) abnormalities of pulmonary GPA are lung nodules and masses, very often multiple and with cavitation. As there are various clinical presentations, the diagnosis of GPA can be challenging, and the illness is difficult to distinguish from other diseases such as infection or malignancy. Following the improved survival rates in patients with GPA, there is accumulating evidence to suggest an increased occurrence of different types of cancer. Exposure to cyclophosphamide seems to be one of its main causes. We present the case of a patient with chronic GPA who was hospitalized owing to a new infiltrate in the lung, suggesting relapse of the disease, and finally diagnosed with small cell lung cancer. Data regarding lung cancer in GPA patients are limited. While there are some case reports and short case series in the literature, there are no detailed data regarding an association between CYC exposure and lung cancer development in vasculitis. It is necessary to consider the causes of pulmonary masses other than a GPA relapse. Bronchoscopy with biopsy and histopathological examination are crucial in proper differential diagnosis. GPA patients require long-term follow-up to monitor for the development of complications during treatment.

Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds With Disease Presentation.

OBJECTIVE: Amino acids (AA) and their derivatives play an integral role in the synthesis of structural and regulatory elements in human organisms and therefore pathologies such as systemic sclerosis that may alter the blood pattern of these compounds. This study aimed to evaluate changes in plasma concentrations of amino acid-related metabolites in systemic sclerosis in a search for potential biomarkers and mechanisms of the disease. METHODS: Plasma samples from 42 patients diagnosed with systemic sclerosis (SSc) according to the 2013 American College of Rheumatology and European League Against Rheumatism ACR/EULAR classification criteria were compared to 27 matched healthy controls. Liquid chromatography/mass spectrometry was applied for the analysis of 36 amino acid-related metabolites. RESULTS: The analysis of plasma AA metabolite patterns revealed the number of changes including an increase (20%) in concentrations of NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in SSc vs. healthy subjects. Furthermore, SSc patients had higher glutamine, proline, betaine, 1-methylhistidine, and methylnicotinamide levels, while the concentration of tryptophan was lower. The specific metabolic pattern was identified for several aspects of disease presentation. Most interestingly NOS inhibitor L-NAME was elevated in patients with diffuse systemic sclerosis or telangiectasia. CONCLUSIONS: These results provide further evidence for the involvement of endothelium-dependent pathways in the mechanisms and presentation of SSc. Endothelial dysfunction biomarkers may be useful in the assessment of presentation and prognosis in SSc.

Dendritic cells' characteristics in patients with treated systemic lupus erythematosus.

The systemic lupus erythematosus (SLE) is a chronic autoimmune disease related to a loss of immune tolerance against autoantigens that leads to tissue inflammation and organ dysfunction. Constant stimulation of dendritic cells (DC) with autoantigens is hypothesized to increase the B cells' activity which are involved in production of autoantibodies that play an essential role in the SLE development. We focused our study on detecting alterations in DCs at the cellular and molecular levels in patients with treated SLE, depending on the disease activity and treatment. In order to phenotype subpopulations of DCs, multicolor flow cytometry was used. Transcriptional changes were identified with quantitative PCR, while soluble cytokine receptors were assessed with the Luminex technology. We show that SLE patients display a higher percentage of activated myeloid DCs (mDCs) when compared to healthy people. Both, the mDCs and plasmacytoid DCs (pDCs) of SLE patients were characterized by changes in expression of genes associated with their maturation, functioning and signalling, which was especially reflected by low expression of regulatory factor ID2 and increased expression of IRF5. pDCs of SLE patients also showed increased expression of IRF1. There were also significant changes in the expression of APRIL, MBD2, and E2-2 in mDCs that significantly correlated with some serum components, i.e. anti-dsDNA antibodies or complement components. However, we did not find any significant differences depending on the disease activity. While the majority of available studies focuses mainly on the role of pDCs in the disease development, our results show significant disturbances in the functioning of mDCs in SLE patients, thus confirming mDCs' importance in SLE pathogenesis.

Neuro-Sjögren: Uncommon or underestimated problem?

OBJECTIVES: Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune background with possible complications from peripheral (PNS) and central nervous system (CNS). The aim of this study was to assess the prevalence and to describe the phenotype of peripheral neuropathies in patients with SS. MATERIALS & METHODS: We studied fifty patients with primary Sjögren's syndrome for peripheral nervous system involvement. All patients underwent neurological and rheumatological examination followed by nerve conduction studies (NCS) of nine peripheral nerves. RESULTS: Thirty-six patients (72%) fulfilled the criteria for the diagnosis of neuropathy. Carpal tunnel syndrome (54%) and axonal sensorimotor neuropathy (22%) were the most common. Neurological symptoms preceded the diagnosis of SS in eight patients. CONCLUSIONS: Peripheral neuropathies are frequent in SS patients. Neurologists should be aware of possible autoimmune causes of neuropathies because clinical manifestations of neuropathy may precede the development of other symptoms of the autoimmune disease.

Cardiac Involvement in Systemic Sclerosis: Diagnostic Tools and Evaluation Methods.

The heart is one of the major organs commonly involved in systemic sclerosis (SSc). Myocardial fibrosis has been identified in a high percentage of these patients. Most SSc patients with cardiac involvement (CI) are subclinical, especially early on in the course of their disease. To accurately identify CI and improve diagnosis and treatment, imaging techniques should be implemented on a regular basis following diagnosis. In this review, we discuss the up-to-date pathophysiologic basis of CI, the cardiac manifestations, and the diagnostic methods that have been published in the literature. Recent studies have shown that tissue Doppler imaging is a promising evaluation technique in the bedside detection of CI. Cardiovascular magnetic resonance is an operator-independent method used for detecting SSc CI. It is an especially useful tool in the early stages of the disease when patients may be asymptomatic. At present, it is the most promising imaging technique for the diagnosis, follow-up, and response to therapy in clinical practice.

Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review.

Pulmonary embolism is the most common pulmonary manifestation of primary antiphospholipid syndrome (PAPS). However, PAPS may manifest in the respiratory system also due to non-thrombotic processes. In the following paper we present a case of PAPS-related diffuse alveolar hemorrhage (DAH). Because of sparse literature and a lack of randomized controlled trials, there are currently no recommendations regarding the optimal choice of steroid-sparing agent in treating PAPS-related DAH. In our patient, treatment with cyclophosphamide or mycophenolate mofetil along with low dose prednisone was ineffective, partially because of infectious complications, whereas addition of monthly intravenous immunoglobulin to mycophenolate mofetil and prednisone, appears to control the disease.

Hypertrophic pachymeningitis as an important neurological complication of granulomatosis with polyangiitis.

Headache is a common symptom in patients with granulomatosis with polyangiitis (GPA) mainly due to chronic sinusitis or orbital disease. Meningeal involvement may thus remain unrecognized for a long time. This can lead to a significant delay in accurate diagnosis, serious local damage of the central nervous system and high relapse rates. New diagnostic techniques such as contrast MRI allow one to identify inflammation of the dura mater in the course of GPA more frequently. The objective of this article is to characterize hypertrophic pachymeningitis (HP) in patients with GPA and report diagnostic difficulties associated with this complication.

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease. MATERIAL AND METHODS: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009. RESULTS: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%). CONCLUSIONS: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.

Serial Lung Ultrasonography to Monitor Patient With Diffuse Alveolar Hemorhage.

Diffuse alveolar haemorrhage (DAH) leads to acute respiratory failure. This is why it requires rapid diagnosis and implementation of appropriate treatment. The standard diagnosis of a patient with DAH includes laboratory tests, diagnostic imagining (X-ray of the chest, high-resolution computed tomography), and bronchoscopy with bronchoalveolar lavage. We present a description of 2 patients diagnosed with systemic connective tissue disease and DAH, monitored with the help of lung ultrasound. To our knowledge, this is the first description of the use of lung ultrasound in DAH in adult patients.

How do patients and doctors-to-be perceive systemic lupus erythematosus?

The aim of the present study was to assess and compare illness perception of systemic lupus erythematosus (SLE) held by 6th-year medical students and patients suffering from SLE. The study group consisted of 104 students (66 women; 63.5 %), mean age 24.7 (±1), and 64 outpatients with SLE (60 women; 93.7 %). All patients were treated at a university rheumatology outpatient clinic. Mean patients' age was 44.3 years (±12.5). Mean duration of the disease was 11 years (±6.8). The Polish version of Brief Illness Perception Questionnaire (B-IPQ) was used to assess five dimensions of illness perception. The students were asked to complete a modified version of B-IPQ designed to measure health professionals' illness perception. Significant differences were found in all but one B-IPQ scores. The students obtained significantly higher scores than the SLE patients in consequences, identity, concern and emotional response, whereas significantly lower scores in personal control, treatment control and understanding were noted among students. No differences were found in timeline scores. Medical students' perception of SLE is more threatening and more negative than that of patients'. Doctors-to-be perceive SLE as being less controllable, more burdensome and having more consequences than patients do. Additionally, they believe the disease causes more emotional concern. The article discusses possible explanations together with positive and negative aspects of the discrepancies.

Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis--potential biomarkers of disease activity and drug treatment.

This study aimed to evaluate changes in plasma amino acid and nicotinamide metabolites concentrations in rheumatoid arthritis (RA) in a search for potential biomarkers of the disease activity and the effect treatment. Analysis of plasma metabolite patterns with liquid chromatography/mass spectrometry revealed specific changes in RA as well as correlations with clinical parameters. Combined concentration parameter calculated as [aspartic acid] + [threonine] + [tryptophan] - [histidine] - [phenylalanine] offered the strongest correlation (p < 0.001) with pain joint count, swollen joint count and DAS 28. Such analysis of amino acid and related metabolite pattern offers potential for diagnosis as well as for monitoring disease progression and therapy in RA.

Metabolomics and its potential in diagnosis, prognosis and treatment of rheumatic diseases.

The main aim of metabolomics is to make a comprehensive study of metabolites, the intermediates of biochemical processes in living organisms. Any pathophysiological mechanism caused by disease will inevitably lead to related changes in the concentrations of specific metabolites. In line with this, metabolomics offers a promising laboratory tool for the analysis of potential diagnostic biomarkers that may be used to assess susceptibility to a disease and to evaluate the prognosis and therapeutic response to treatment. Recent data have shown that metabolomics analysis in rheumatoid arthritis has made possible more efficient diagnosis, discrimination between patients with regard to disease activity, prediction of the response to a particular treatment approach, differentiation between rheumatic disease subtypes and greater understanding of the pathophysiology of this disease. Here we characterize metabolomics as a comprehensive laboratory tool and review its potential in the diagnosis, prognosis and treatment of rheumatic diseases such as rheumatoid arthritis.

Different pattern of T-cell subpopulations in peripheral blood of patients with rheumatoid arthritis at various stages of disease development.

INTRODUCTION:  The comparison of changes in peripheral T-cell subpopulations at different stages of rheumatoid arthritis (RA) development may be important to understand the pathomechanism and to elucidate the course of RA. So far, there have been no comprehensive studies regarding the proportions of T cells in early and long­lasting RA. OBJECTIVES:  The aim of this study was to assess the proportion of the main peripheral T-cell subpopulations in patients at various stages of RA development. PATIENTS AND METHODS:  We enrolled 75 patients who were divided into 4 subgroups depending on the diagnosis: undifferentiated arthritis (UA), which later developed into RA (UA­RA) and other diseases (UA­non­RA); clinically confirmed untreated RA; long-term treated RA; and the control group. Flow cytometry was used to assess T-cell subpopulations. RESULTS:  Patients with clinically confirmed untreated RA differed (P <0.05) in the proportion of CD4+ T-cell subpopulations expressing activation markers compared with controls (CD69, CD25, HLA­DR, CD95) and UA patients (CD95). Untreated RA patients had the highest proportion of regulatory CD4+ T cells compared with control and other groups. The percentage of CD28- T cells was higher only in the group with clinically confirmed RA but not in those with early RA (at the UA stage). CONCLUSIONS:  The peripheral T lymphocyte phenotype in very early RA is not similar to that observed in clinically­confirmed RA. Patients with a confirmed diagnosis of RA can be easily differentiated based on the absolute numbers of the main T-cell subpopulations; however, the percentage of the main T-cell subpopulations do not discriminate those patients in the UA cohort who will develop RA.