Vascular cell adhesion molecule 1 in patients with severe osteoarthritis of the hip : A prospective cross-sectional study.

BACKGROUND: Osteoarthritis (OA) of the hip is a frequent and debilitating joint disease. Only few clinical risk factors for hip OA are established and clinically applicable biomarkers to identify patients at risk are still lacking. The glycoprotein vascular cell adhesion molecule 1 (VCAM-1) is expressed by chondrocytes and synovial tissue and was a predictive marker for development of severe large joint OA in a previous study. OBJECTIVE: It was tested whether increased serum levels of VCAM-1 are prevalent in patients with severe OA of the hips. METHODS: In this prospective, multicenter, cross-sectional study, risk factors of severe hip OA were investigated in patients scheduled for hip joint arthroplasty and 100 patients were randomly selected for validation of VCAM-1 as a potential biomarker for hip OA. Serum samples were analyzed by an enzyme-linked immunosorbent assay and compared with a sex and age-matched control cohort. RESULTS: The groups were similar in age, gender ratio and prevalence of diabetes. Serum concentrations of VCAM-1 were 8% higher in OA patients compared to controls, without reaching statistical significance (818 ng ml-1, 95% confidence interval, CI 746-891 ng ml-1 versus 759 ng m-1, 95% CI 711-807 ng ml-1; P = 0.4839). CONCLUSION: The results of this study show that serum concentrations of VCAM-1 cannot distinguish patients with severe hip OA from age and sex-matched controls.

HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.

OBJECTIVE: Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis. METHODS: In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls. RESULTS: No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population. CONCLUSION: Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip.

Bone Involvement in Rosai-Dorfman Disease (RDD): a Case Report and Systematic Literature Review.

PURPOSE OF REVIEW: Rosai-Dorfman disease (RDD) is a rare histiocytic disorder typically presenting as painless cervical lymphadenopathy. Extranodal involvement is common and may also affect bones. Here, we present a patient with typical nodal disease and multifocal bone manifestations. Further, a systematic literature review was performed to better understand the phenotype, clinical course and treatment options of such patients. RECENT FINDINGS: RDD is a nonmalignant, classically sporadic histiocytosis. Nevertheless, increasing evidence also suggests familial forms of the disease. According to our literature review, bone involvement is exceedingly rare and heterogeneous. Clinical outcome in terms of mortality seems to be favorable in most cases. Currently, therapy strategies include surgical and immunosuppressive treatments, but the optimal treatment of osseous RDD remains to be defined. Patients with osseous RDD may present to rheumatologists with arthralgia or arthritis. Due to the rarity of the disease, diagnosis and treatment remain challenging.

Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

INTRODUCTION: Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) with highly active disease. The role of these biomarkers in relapsing disease is unclear. METHODS: Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients). Epidemiological, clinical and laboratory data were available for all visits. RESULTS: At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels. CONCLUSIONS: Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.

Efficacy and safety of rituximab in rheumatic diseases.

B-cell depleting therapy is now in clinical use for more than 10 years in rheumatology. In 2001, a first report was published on five rheumatoid arthritis patients responding to the chimeric anti-CD20 antibody rituximab. Since then, numerous clinical trials, prospective and retrospective studies, registry data as well as case reports on the use of rituximab in autoimmune rheumatic diseases have been published. This review gives a short overview on clinical data of rituximab in rheumatic diseases currently available.

Pachydermodactyly: a review.

Synovitis is the characteristic feature of inflammatory joint disease. If synovitis is localized to interphalangeal joints, rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis are among the most common differential diagnoses. The absence of pain, tenderness, and limitation of function despite progressive swelling of proximal interphalangeal joints suggests an alternative diagnosis, for example pachydermodactyly (PDD). This is a benign disease, associated with asymptomatic, progressive swelling of periarticular soft tissue, which usually occurs in young males. PDD is probably the result of repetitive mechanical stimulation. One hundred and twenty-one cases have been reported in the literature. Some of these were initially misdiagnosed and treated for inflammatory arthritis. We provide a comprehensive review of the literature on pachydermodactyly to promote awareness of this rare but important differential diagnosis of arthritis.

IgG4- related disease: an orphan disease with many faces.

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD.

Low bone mineral density and fragility fractures in permanent vegetative state patients.

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (ß-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. .

Establishing a sensitive and specific assay for determination of glucocorticoid bioactivity.

Glucocorticoids are hormones that play a major role in energy homeostasis and stress response of the body. As drugs they are most frequently used for immunosuppressive and anti-inflammatory purposes. Glucocorticoids are exploited successfully in the treatment of a wide variety of diseases; however, some patients develop side-effects, while others fail to respond to this form of therapy. Alterations in pharmacodynamic and pharmacokinetic actions might contribute to individual differences in glucocorticoid sensitivity. Antibody-based methods such as RIA (Radioimmunoassay) and ELISA (Enzyme-linked immunosorbent assay) are routinely used to determine glucocorticoid serum levels. However, as these techniques measure the total amount of a specific glucocorticoid and do not discriminate between protein-bound and freely available (i.e. biologically active) glucocorticoids, the results do not necessarily reflect the active levels of glucocorticoid, i.e. the "glucocorticoid milieu" in a patient. Being able to determine glucocorticoid bioactivity in serum or other body fluids could help identifying glucocorticoid-sensitive or -resistant patients and help finding explanations for different responses in individual patients. For this reason, we established a glucocorticoid bioactivity assay that is based on the measurement of glucocorticoid-dependent reporter gene activity. Making use of a human T-cell leukemia line, equipped with the glucocorticoid receptor and the fluorescence protein Venus as the assay's reporter (Jurkat(GR)-MMTV-VNP), glucocorticoid bioactivity can be determined from small amounts of serum or other biologic fluids. The developed glucocorticoid bioassay is both sensitive and reproducible, without any relevant cross-reactivity with steroid hormones other than glucocorticoids and can be practically applied in daily laboratory routine.