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We investigated the effects of photopheresis in systemic sclerosis by analysing its influence on lymphocytes with regard to apoptosis and expression of bcl-2 and fas. Peripheral blood lymphocytes isolated immediately before and 24 h after photopheresis were investigated for apoptosis, bcl-2 and fas expression by fluorocytometry, and compared to controls. In addition, leucocytes from systemic sclerosis patients taken directly from the photopheresis system were tested for apoptosis after 24 h in culture. fas expression was similar in controls and patients with systemic sclerosis just before photopheresis, but increased 24 h after photopheresis, mainly due to an increase of CD4+CD95+ cells. bcl-2 was overexpressed in scleroderma peripheral lymphocytes, but not influenced by photopheresis. As compared to healthy controls, the percentage of apoptotic cells 24 h after photopheresis was high in cultured lymphocytes, but not ex vivo. The significant increase in fas on peripheral lymphocytes observed in this study may be a major operative mechanism of photopheresis in addition to (and possibly related to) the induction of apoptosis. [ABSTRACT FROM PUBLISHER]

The article presents a case study of an 83-year-old female with severe kyphoscoliosis who developed esophageal ulceration mimicking malignancy. The patient was presented with a three-week history of odynophagia, dysphagia and nocturnal food regurgitation. The most probable cause of mechanical ulceration was alimentary bolus obstruction. The case shows that kyphoscoliosis may cause ulceration independent of drug history.

Objectives: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc., Methods: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed., Results: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years., Conclusion: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Large data bases and the projects arising from them have led to a much improved understanding of systemic sclerosis over the last decade. Serology has developed further so that more autoantibodies are available for routine testing. Capillary microscopy has become standard and relevant progress has also been made in therapy. Many diagnostic terms found in medical documentation do not adequately reflect this progress. The nomenclature is inconsistent and, therefore, confusing. The international classification of diseases (ICD) nomenclature is, from our point of view, also in need of improvement. This article aims to reestablish a common German language standard for systemic sclerosis, which reflects current knowledge and is suitable for implementation in the clinical routine.

Objectives: As interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients is associated with increased mortality due to loss of diffusion capacity and pulmonary hypertension, regular screening for structural abnormalities of the lung is advised. In addition to standard radiological examination with computed x-ray tomography, ultrasound of the lung could allow non-invasive and radiation-free structural monitoring of the lung. The objective of this study was to test the frequency of abnormalities in lung sonography in patients with RA who did not have clinical signs or symptoms of lung disease., Methods: In a prospective study of 64 consecutive patients with rheumatoid arthritis and 40 healthy volunteers, we screened the pleura and the pulmonary parenchyma for sonographic abnormalities. All RA patients underwent high resolution computer tomography of the lung., Results: 28% of RA patients showed pleural nodules or B-line phenomena. In these patients, CT scans showed signs of incipient interstitial lung disease. Lung sonography showed sporadic abnormalities in 7% of the healthy controls., Conclusions: Transthoracic ultrasound of the lung is an inexpensive and safe tool to screen patients with RA for incipient pulmonary structural changes.

Objectives: Sera from patients with lymphoid neoplasias contain rheumatoid factors (RF) so often that RF are of limited use for diagnosing arthritis in lymphoma patients. Antibodies against citrullinated peptides (ACPA) might be helpful in distinguishing between true RA and rheumatoid factor-positive conditions with arthritis. We compared the specificity of RF and of ACPA for the diagnosis of RA in patients with B-cell chronic lymphocytic leukemia (CLL)., Methods: One hundred and seven patients with CLL without any clinical signs of arthritis and five patients with RA and concomitant CLL were included in the investigation. Serum samples were tested for RF-isotypes IgM, IgG and IgA. ACPA were determined with an ELISA that detects anti-cyclic citrullinated peptide (aCCP) antibodies., Results: RF well beyond the cut-off levels were detected in 50% of the CLL patients without RA. The isotype distribution was 41% IgM-RF, 20% IgG-RF and 3% IgA-RF. None of the 107 CLL patients without arthritis had Accp antibodies. Within the whole cohort of CLL patients the specificity for the diagnosis of RA was 100% for aCCP antibodies and 59% for IgM-RF., Conclusions: Only aCCP antibodies but not IgM-, IgG- or IgA-RF are useful for the diagnosis of RA in patients with CLL.

Objective: IL-10 is a pleiotropic cytokine involved in the regulation of innate and cell-mediated immunity and a key mediator within the disturbed SLE immune system. IL-10 binds to IL10R1, which is expressed on a variety of immune cells and activates the JAK-STAT pathway. Two (out of several known) genetic IL10R1 variants may alter IL-10 binding or signal transduction. Here we investigate the differential activity of these IL10R1 variants and their possible association with RA or SLE susceptibility., Methods: IL10R1-wt, IL10R1-S138G, IL10R1-G330R, or IL10R1- S138G +G330R were cloned into pIRESpuro3 and transfected into HeLa cells. Single cell clones were tested for IL-10-induced SOCS3- and SLAM gene expression by real-time PCR. DNA from 182 RA patients, 222 SLE patients, and 250 healthy controls was genotyped by allele-specific PCR., Results: A biphasic increase of SOCS3 mRNA was observed that peaked at 15 minutes and 4 hours after IL-10 stimulation. The presence of IL10R1 S138G and G330R showed a weaker induction of both SOCS3 and SLAM upon stimulation with IL-10. In RA a homozygous G330R genotype was more commonly present than in controls (15.4% vs. 7.6%; p<0.05). In SLE the G330R allele frequency was also increased (36.3% vs. 30.0%; p<0.05) without showing a gene-dose relationship at the genotype level., Conclusions: Based on these results, both variants of the IL10R1 gene are loss-of-function alleles. IL10R1 G330R may possibly contribute to RA or SLE disease susceptibility in Caucasian populations.

Objective: Sphingosine-1-phosphate (S1P) is a messenger molecule, with important functions in inflammation and wound healing. The present study was performed to elucidate a possible role of S1P signaling in articular chondrocytes., Methods: Human and bovine primary chondrocytes were cultured in monolayer. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect S1P receptor mRNA. Proliferation of S1P stimulated chondrocytes was measured by 3H-thymidine uptake. Supernatants of cultured bovine chondrocytes stimulated with S1P alone or in combination with interleukin-1beta (IL-1beta) were tested for nitric oxide (NO) formation and expression of inducible nitric oxide synthase (iNOS). Matrixmetalloprotease-13 (MMP-13) and aggrecanase-1 (ADAMTS-4) were evaluated using real-time PCR. Glycosaminoglycan (GAG) loss from bovine cartilage explants was evaluated using the dimethylene blue method., Results: S1P1, S1P2 and S1P3 but not S1P4 and S1P5 receptor mRNA were detected in human and bovine chondrocytes. S1P dose dependently induced proliferation in bovine and human chondrocytes. S1P significantly reduced NO formation and iNOS mRNA and protein expression, both in un-stimulated and IL-1beta stimulated bovine chondrocytes. Furthermore, S1P dose dependently inhibited IL-1beta induced expression of ADAMTS-4 and MMP-13 and diminished IL-1beta mediated GAG depletion from cartilage explants., Conclusion: These results suggest that S1P provides an anti-catabolic signal in articular chondrocytes.

Objective: To determine the effect on the humoral immune system of long term treatment of patients with RA with etanercept., Methods: 12 consecutive patients with seropositive RA treated with etanercept were studied and followed up for 9 months. Clinical efficacy of treatment was evaluated using the 28 joint count Disease Activity Score (DAS28). Serum samples were collected at baseline and after 9 months and serum immunoglobulin, RF isotypes, and anti-cyclic citrullinated peptide (aCCP), antinuclear, nucleosome, and dsDNA antibodies determined. For comparison 7 patients with seropositive RA treated with adalimumab were studied., Results: DAS28 decreased significantly after the first month and then was constant for the whole study (5.7 (0.3) v 3.8 (0.2), p< or=0.000). Serum IgA-RF and IgG-RF increased significantly after 9 months' etanercept treatment (mean (SEM) IgA-RF rose from 19.5 (4.8) to 30.5 (5.9) IU/ml, p< or=0.01; IgG-RF from 20.6 (8.1) to 33.8 (11.5) IU/ml, p< or=0.04). Serum levels of total immunoglobulin and specific autoantibodies remained unchanged during the study. In patients treated with adalimumab, no significant changes in serum levels of RF isotypes and aCCP antibodies were seen., Conclusion: Etanercept, although effective in treating the clinical symptoms of RA, seems to have a pivotal effect on RF-producing B cells either directly or indirectly.

Objective: Since the development of posttraumatic osteoarthritis (OA) is a relatively slow process, estimation of OA risk would be of value with regard to chondroprotective measures and medication. In this study we investigated the significance of pro-matrixmetalloproteinase-3 (proMMP-3) for this purpose., Design: Synovial fluid (SF) and serum samples were collected from 259 patients of our trauma clinic at the time of arthroscopy. The extent of cartilage damage was assessed according to the Outerbridge-score. ProMMP-3 levels in SF and serum were determined by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody. Additionally we determined SF and serum levels of total MMP-3 and COMP levels as well as TIMP-1 and -2 concentrations in 40 randomly selected patients by ELISA., Results: Serum proMMP-3 levels of the total cohort were markedly increased compared to healthy controls (P<0.007). The comparison of serum and SF lavage proMMP-3 concentrations showed a significant correlation (r(s)=0.41, P<0.0001), however, only 26% of the investigated samples were increased above normal ranges. The grade of cartilage damage did not correlate with enzyme concentration neither in patients' serum nor in SF samples. ProMMP-3 SF concentration was increased early after trauma. Furthermore, proMMP-3 correlated significantly with total MMP-3 serum and SF levels as well as COMP SF levels., Conclusions: The measurement of proMMP-3 in serum or SF did not reflect the present cartilage damage and thus appears to have only minor potential for clinical use, but it should be considered for longitudinal studies, since it may reflect a risk for cartilage degradation in a subset of patients.

Objective: We investigated whether chondrocytes derived from osteoarthritic cartilage may lose their responsiveness to cartilage-derived morphogenetic protein-1, -2 (CDMP-1, -2) and osteogenic protein-1 (OP-1) compared with healthy cells, thus leading to an impaired maintenance of matrix integrity., Design: Chondrocytes were isolated from articular cartilage from patients with and without osteoarthritic lesions. Cells were grown as monolayer cultures for 7 days in a chemically defined serum-free basal medium (BM) in the presence of recombinant CDMP-1, -2, and OP-1. Glycosaminoglycan synthesis was measured by [35S]Sulfate incorporation into newly synthesized macromolecules. Cell proliferation was investigated by [3H]Thymidine incorporation. The endogenous gene expression of CDMPs/OP-1 and their respective type I and type II receptors was examined using RT-PCR. The presence of CDMP proteins in tissue and cultured cells was detected by Western immunoblots., Results: mRNAs coding for CDMPs and their respective receptors are endogenously expressed not only in healthy, but also in osteoarthritic cartilage. CDMP proteins are present in both normal and osteoarthritic articular cartilage and cultured chondrocytes. CDMP-1, CDMP-2 and OP-1 markedly increased glycosaminoglycan synthesis in both healthy (P< 0.01) and osteoarthritic (P< 0.05) human articular chondrocytes. A comparison of the glycosaminoglycan biosynthetic activity between healthy and osteoarthritic samples revealed no detectable difference, neither in stimulated nor in unstimulated cultures. [(3)H]Thymidine incorporation showed that CDMPs/OP-1 did not affect cell proliferation in vitro., Conclusion: CDMPs and OP-1 exert their anabolic effects on both healthy and osteoarthritic chondrocytes indicating no loss in responsiveness to these growth factors in OA. The endogenous expression of CDMPs/OP-1 and their receptors suggest an important role in cartilage homeostasis., (Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.)

Malignancy-associated musculoskeletal syndromes can present in a variety of ways which are not distinguishable from idiopathic rheumatic diseases. Furthermore, there are some rare, but typical syndromes with a high association with neoplasms. To perform a quick and exact diagnosis while avoiding useless invasive and expensive diagnostic procedures is a major challenge for the clinician. This article focuses on the clinical features of paraneoplastic musculoskeletal syndromes and theories about the underlying pathogenesis. We try to highlight those clinical and laboratory aspects which could be a clue to hidden malignancies. Paraneoplastic rheumatic syndromes are rare conditions, but timely recognition can save lives.

Background: Sodiumchondroitinsulfate, Condrosulf, is used in osteoarthritis therapy and belongs to the group of symptomatic slow-acting drugs for osteoarthritis. The aim of this study was to investigate the effects of Condrosulf on total proteoglycan synthesis and cell proliferation in human osteoarthritis and healthy juvenile bovine chondrocytes in vitro., Methods: Chondrocytes were grown as monolayers and stimulated for 7 (human cartilage), or 4, 8 and 12 days (bovine cartilage) with different concentrations of Condrosulf (100 micrograms/ml, 500 micrograms/ml, 1000 micrograms/ml, 2500 micrograms/ml and 5000 micrograms/ml). Proteoglycan synthesis was measured by [35S]Sulfate incorporation. The cell proliferation rate was determined using a [3H]Thymidin assay. The expression of the cartilage markers aggrecan and collagen type II was assessed by Northern blot analysis., Results: We show that the incubation with Condrosulf did not affect proteoglycan synthesis neither in osteoarthritis, nor in healthy chondrocytes under the present culture conditions. Cell proliferation rate was also not increased by Condrosulf stimulation. The results of the Northern blot assays demonstrated a dose-dependent down regulation of aggrecan expression on mRNA level., Conclusions: These data indicate a lack of direct anabolic effects of Condrosulf on the biosynthetic activity of cultured articular chondrocytes. The well known ease of clinical symptoms, such as pain or swelling under Condrosulf medication may be interpreted by an interaction with pro-inflammatory cytokines.

Objective: To assess the risk of infection in patients with systemic lupus erythematosus (SLE) treated with plasmapheresis in addition to intravenous (I.V.) pulse cyclophosphamide (CYC)., Methods: We searched the records of all our SLE patients for those who had undergone plasmapheresis plus I.V. CYC treatment (n = 9). Consecutive patients with similarly high SLE activity who underwent I.V. CYC therapy but not plasmapheresis were included as controls (n = 12). We evaluated both groups for severe infections, outcome, and confounding clinical variables., Results: Seven of 9 plasmapheresis-treated patients had serious bacterial or viral infections, including 3 cases of cytomegalovirus infections. Among the 12 patients treated with I.V. CYC alone, only 2 had severe infections (P < 0.01). Three patients in the plasmapheresis group and none in the control group died of infections. Treatment efficacy, however, was similar for both groups., Conclusion: Among SLE patients treated with plasmapheresis and I.V. CYC, life-threatening bacterial and viral infections and mortality occur more frequently than among patients with similarly active SLE treated with I.V. CYC alone.