Häufigkeit und Einteilung kutaner Manifestationen bei rheumatoider Arthritis.

HINTERGRUND UND FRAGESTELLUNG: Hautveränderungen bei rheumatoider Arthritis (RA) sind nur in wenigen Studien an größeren Patientenkollektiven untersucht. Deshalb sollen hier die aktuelle Prävalenz und das Spektrum an Hautveränderungen bei RA unter Berücksichtigung von Krankheitsaktivitäts-Scores, Anti-CCP-Antikörpern sowie neueren medikamentösen Therapien erfasst werden. PATIENTEN UND METHODIK: Zwischen November 2006 und Juli 2007 wurden prospektiv 214 Patienten, die im Funktionsbereich Rheumatologie mit RA behandelt wurden, erfasst. ERGEBNISSE: Bei 27,5 % der Untersuchten wurden RA-assoziierte Hautveränderungen beobachtet, wobei es sich fast ausschließlich um Rheumaknoten handelte. Signifikant gehäuft traten Rheumaknoten bei längerer Erkrankungsdauer, Nachweis von Rheumafaktoren und Anti-CCP-Antikörpern, aber auch unter Gabe von Leflunomid und TNFα-Blockern auf. Vergleichsweise niedrige Prävalenzen wurden hingegen für die "palisadenförmige neutrophile und granulomatöse Dermatitis" und die "rheumatoide Vaskulitis" ermittelt. SCHLUSSFOLGERUNGEN: Trotz zunehmend frühzeitiger Therapie der RA und dem Einsatz neuerer Medikamente ist die Prävalenz von Rheumaknoten als wichtigste Manifestation der RA am Hautorgan hoch. Deren verstärkte Ausbildung unter Leflunomid und TNFα-Blockern könnte ein Hinweis dafür sein, dass bei der Entstehung von Rheumaknoten eine pathogenetische Wegstrecke eine Rolle spielt, die von den Therapeutika nur unzureichend beeinflusst wird. Hingegen scheinen die palisadenförmige neutrophile und granulomatöse Dermatitis und die "rheumatoide Vaskulitis" durch neuere Medikamente besser beeinflussbar zu sein.

Incidence and classification of cutaneous manifestations in rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: There have only been few studies examining rheumatoid arthritis (RA)-related skin manifestations in larger patient populations. Herein, we present current data on the prevalence and spectrum of cutaneous lesions in RA, addressing disease activity scores, anti-CCP antibodies as well as novel pharmacological approaches. PATIENTS AND METHODS: Between November 2006 and July 2007, 214 patients with RA treated at the Division of Rheumatology, University Hospital Jena, Germany, were prospectively examined. RESULTS: 27.5 % of patients exhibited RA-related skin manifestations, almost all of which were rheumatoid nodules. These lesions occurred significantly more frequently in patients with longstanding disease, those testing positive for rheumatoid factor and anti-CCP-antibodies, as well as individuals on leflunomide and TNF-alpha antagonists. Comparatively lower prevalence rates were observed for palisading neutrophilic and granulomatous dermatitis and rheumatoid vasculitis. CONCLUSIONS: Despite increasingly early treatment of RA and use of novel pharmacological agents, there is a high prevalence of rheumatoid nodules, which represent the most common cutaneous manifestation in RA. The higher prevalence of rheumatoid nodules in patients on leflunomide and TNF-alpha antagonists might be an indication that pharmacological treatment has only limited effects on their formation, possibly due to pathogenetic pathways that are only inadequately affected by drug therapies. By contrast, palisading neutrophilic and granulomatous dermatitis and rheumatoid vasculitis appear to respond better to novel pharmacological agents.

The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis.

The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.

Influence of Rituximab on markers of bone remodeling in patients with rheumatoid arthritis: a prospective open-label pilot study.

Immune system and bone are interacting in a complex way. Rheumatoid arthritis is characterized not only by joint destruction, but also by development of systemic osteopenia and osteoporosis. The CD20-depleting antibody Rituximab (Rtx) is a novel therapeutic option able significantly to slow the destructive joint process of rheumatoid arthritis. However, there are little data whether Rtx influences systemic bone remodeling. In the present prospective study, we evaluated the influence of Rtx on markers of bone metabolism with a follow-up of 3-15 months after Rtx therapy (2 dose of each 1,000 mg) in 13 patients with rheumatoid arthritis. There was no significant change of the bone formation markers bone alkaline phosphatase and c-terminal propeptide of collagen I. However, a non-significant tendency of decrease of RANKL (with no chance of osteoprotegerin) and a significant decrease of the bone degradation marker desoxypyridinolin crosslinked collagen I was observed 15 months after Rtx application. These initial results provide no evidence of a negative systemic influence of Rtx on bone remodeling. In contrast, it appears that Rtx lowered osteoclast activity often found increased in active rheumatoid arthritis contributing to osteoporosis in this disease.

Leflunomide in the treatment of patients with early rheumatoid arthritis--results of a prospective non-interventional study.

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (< or =1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of < or =5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 < or = 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies.

[Carpal tunnel syndrome in diabetes mellitus]. / Das Karpaltunnelsyndrom bei Diabetes mellitus.

The carpal tunnel syndrome (CTS) occurs frequently in patients with diabetes mellitus. The prevalence of CTS is higher in diabetic patients with peripheral polyneuropathy compared to patients with diabetes, who do not have diabetes-related late complications (30% vs. 14%). Moreover, CTS seems to be a risk factor for later manifestation of diabetes mellitus, as patients with newly diagnosed diabetes showed CTS manifestation 1.4-fold more often than the age-matched reference population. This paper describes the diagnostics, differential diagnostics and particularities in the therapy of patients with both CTS and diabetes. In case of oral or local application of corticoids, the persistent elevation of blood glucose levels has to be taken into account with potential need for intensification of diabetes therapy. In case of progression of the CTS, surgery is indicated.

Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells.

INTRODUCTION: Advanced glycation end products (AGEs) have been introduced to be involved in the pathogenesis of osteoarthritis (OA). The influence of AGEs on osteoarthritic fibroblast-like synovial cells (FLS) has been incompletely understood as yet. The present study investigates a potential influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth, and on the expression of proinflammatory and osteoclastogenic markers in cultured FLS. METHODS: FLS were established from OA joints and stimulated with AGE-BSA. The mRNA expression of p27Kip1, RAGE (receptor for AGEs), nuclear factor kappa B subunit p65 (NFkappaB p65), tumor necrosis factor alpha (TNF-alpha, interleukin-6 (IL-6), receptor activator of NFkappaB ligand (RANKL) and osteoprotegerin was measured by real-time PCR. The respective protein expression was evaluated by western blot analysis or ELISA. NFkappaB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and early apoptosis were assessed. The specificity of the response was tested in the presence of an anti-RAGE antibody. RESULTS: AGE-BSA was actively taken up into the cells as determined by immunohistochemistry and western blots. AGE-induced p27Kip1 mRNA and protein expression was associated with cell cycle arrest and an increase in necrotic, but not apoptotic cells. NFkappaB activation was confirmed by EMSAs including supershift experiments. Anti-RAGE antibodies attenuated all AGE-BSA induced responses. The increased expression of RAGE, IL-6 and TNF-alpha together with NFkappaB activation indicates AGE-mediated inflammation. The decreased expression of RANKL and osteoprotegerin may reflect a diminished osteoclastogenic potential. CONCLUSIONS: The present study demonstrates that AGEs modulate growth and expression of genes involved in the pathophysiological process of OA. This may lead to functional and structural impairment of the joints.

Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis.

Cardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study to determine the prevalence and clinical impact of cardiac involvement in CSS patients. We performed a multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac workup included electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy.We analyzed 49 patients with CSS: 22 patients had clinical evidence of cardiac involvement. A negative antineutrophil cytoplasmic antibodies (ANCA) test and much higher eosinophil counts (9947 vs. 3657/microL, respectively, p < 0.001) distinguished patients with cardiac involvement from those without. Impaired left ventricular function (50%), mild to severe valvular insufficiencies (73%), and pericardial effusions (41%) were common findings in these patients. Endomyocarditis was found in 13 patients (59%) as detected by cardiac MRI, cardiac thrombus formation, and endomyocardial biopsy, and was associated with impaired cardiac function. After a mean follow-up of 47 months, most patients had regained or maintained good cardiac function. However, patients with endomyocarditis had a more severe outcome. Two patients died (61 and 99 mo after diagnosis, respectively), both due to severe cardiomyopathy and heart failure.Cardiac involvement is common in patients with CSS and is associated with the absence of ANCA and high eosinophil counts. Endomyocarditis may represent the most severe manifestation eventually causing fatal outcome. A structured clinical assessment incorporating cardiac imaging with echocardiography and MRI can identify impaired cardiac function and endomyocardial abnormalities.

Implementation of Z-scores as an age- and sex-independent parameter for estimating joint space widths in rheumatoid arthritis.

OBJECTIVE: To compare normative data of joint space distances (JSD) with the JSD of patients with rheumatoid arthritis (RA) as measured by computer-aided joint space analysis (CAJSA) at the metacarpophalangeal (MCP) articulations, and to differentiate age- and sex-related alterations from the disease-related joint space narrowing. METHODS: In total, 256 healthy subjects and 248 patients with verified RA (following revised ACR criteria) underwent computerized semiautomated measurements of JSD (CAJSA, version 1.3.6) at the MCP articulation (JSD-MCP) based on digital radiographs. The Z-score, a comparative parameter that differentiates joint space alterations caused by RA-related cartilage destruction from age- and sex-related changes, was calculated. RESULTS: Our data showed a relationship between measured joint space widths (MCP total and MCP thumb to little finger) and age for healthy subjects and also the RA group. The RA group revealed an age-related joint space narrowing that was surpassed by the RA-related narrowing of joint space widths classified by Sharp joint space narrowing score and resulting in smaller Z-scores for RA patients. CONCLUSION: The CAJSA technique seems to distinguish age-related JSD changes in healthy volunteers from RA-induced alterations. In addition the Z-score was also able to differentiate RA-dependent narrowing of JSD. Calculation of the Z-scores based on sex- and age-specific reference data may facilitate earlier identification of patients with RA, allowing initiation of a more optimal, individually adapted therapeutic strategy.

Long-term moderate intervention with n-3 long-chain PUFA-supplemented dairy products: effects on pathophysiological biomarkers in patients with rheumatoid arthritis.

n-3 long-chain PUFA (n-3 LC-PUFA) may improve cardiovascular and inflammatory diseases. The effects of n-3 LC-PUFA-supplemented dairy products on inflammation and immunological parameters, biomarkers of oxidative stress, serum lipids, and on disease activity were determined in patients with rheumatoid arthritis (RA). Forty-five subjects (forty-three females and two males) were randomly divided into two groups in a double-blind, placebo-controlled cross-over study. Both groups received placebo or verum products consecutively for 3 months with a 2-month washout phase between the two periods. Blood samples were taken at the beginning and at the end of each period. The dairy products generally improved serum lipids by increasing HDL and lowering lipoprotein a. The n-3 LC-PUFA supplements act to lower TAG. Additionally, a decreased lipopolysaccharide-stimulated cylo-oxygenase-2 expression was found in patients who had consumed the enriched dairy products. The majority of the CD analysed were not influenced, although n-3 LC-PUFA did suppress the immune response as lymphocytes and monocytes were found to be significantly decreased. The n-3 LC-PUFA did not increase the biomarkers of oxidative stress such as 8-iso-PGF(2alpha) and 15-keto-dihydro PGF(2alpha), and DNA damage like 7,8-dihydro-8-oxo-2'-deoxyguanosine. The long-term consumption of dairy products (2 x 12 weeks) diminished the excretion of hydroxypyridinium crosslinks, and favoured the diastolic blood pressure. The consumption of moderate doses of n-3 LC-PUFA in combination with dairy products did not improve the disease activity. However, there is evidence of cardioprotective effects. Furthermore, the long-term consumption of dairy products acts against the cartilage and bone destruction in RA.

Impact of sex, age, body mass index and handedness on finger joint space width in patients with prolonged rheumatoid arthritis using computer-aided joint space analysis.

To evaluate the associations between sex, age, body mass index (BMI) and handedness regarding the radiogeometric detectable joint space distances of the finger articulations in patients suffering from a prolonged course of rheumatoid arthritis (RA). The joint space widths were measured by a new available Computer-aided joint space analysis (CAJSA); 128 patients with RA underwent computerized semi-automated joint space analysis of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP II-V), proximal-interphalangeal joint (JSD-PIP II-V) and distal-interphalangeal joint (JSD-DIP II-V) based on digitally performed radiographs of the hand (Radiogrammetry Kit, Version 1.3.6; Sectra; Sweden). The joint space distance (JSD) of each articulation was expressed as JSD total in millimeter. The patient cohort was differentiated for gender, age, handedness and BMI (BMI < 20; BMI 20-25, BMI > 25). JSD revealed a significant age-related narrowing of 24.8% (JSD-MCP), 22.6% (JSD-PIP) and 28.7% (JSD-DIP) between the ages of 20 and 79. Additionally, males showed a significantly wider JSD compared to the female cohort for all age groups. All JSD-distances were varied between the right and left hand. The JSD-MCP demonstrated significant differences regarding the BMI groups. In contrast to JSD-MCP an effect of the BMI on measurements of JSD-PIP and JSD-DIP could not be observed. These influences must be differentiated from disease-related alterations caused by RA.

Effects of leflunomide and methotrexate in rheumatoid arthritis detected by digital X-ray radiogrammetry and computer-aided joint space analysis.

The aim of the present study was to evaluate the effect of long-term leflunomide and methotrexate (MTX) therapy during the course of rheumatoid arthritis (RA) estimated by digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) as diagnostic tools for the quantification of disease-related periarticular osteoporosis and joint space narrowing. Fourty matchable patients with verified RA were treated with leflunomide or MTX during an observation period of 2.5 years. All patients underwent complete computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR as well as semi-automated measurements of joint space widths (JSW) at the metacarpophalangeal articulations (MCP, thumb to small finger) and proximal interphalangeal joints (PIP, index finger to small finger) using digitized hand radiographs. DXR-BMD revealed an increase of 0.4% (leflunomide-group) versus a reduction of -9.1% (MTX-group). Regarding DXR-MCI, a reduction of -1.1% (leflunomide-group) and -5.3% (MTX-group) was observed. The CAJSA parameters showed a decline of -2.7% (JSW-MCP) versus -2.1% (JSW-PIP) in patients treated with leflunomide. An accentuated joint space narrowing was revealed (JSW-MCP: -5.7%; JSW-PIP: -6.2%) in the MTX group. Digital X-ray radiogrammetry and CAJSA could discriminate the influence of different therapeutic regimes on periarticular osteoporosis and joint space narrowing showing a less accentuated radiographic progression in patients treated with leflunomide.

Benefit of a 17-year long-term bisphosphonate therapy in a patient with Gorham-Stout syndrome.

This case report of a 61-year-old woman suffering from Gorham-Stout syndrome shows osteolyses of the left pelvis, proximal femur and lumbar spine. The therapeutic regime has included two courses of percutaneous radiotherapy and also continuous application of bisphosphonates over 17 years. Despite this antiresorptive therapy, elevated urinary excretion of desoxypyridinoline has indicated the persistence of increased bone destruction. The radiological progression following bisphosphonate treatment was only moderate. However, physical disability is reduced, but without soaring handicaps suggesting that long-term bisphophonate therapy is a therapeutical option for this rare syndrome.

Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis.

EBV is a candidate trigger of rheumatoid arthritis (RA). We determined both EBV-specific T cell and B cell responses and cell-associated EBV DNA copies in patients with RA and demographically matched healthy virus carriers. Patients with RA showed increased and broadened IgG responses to lytic and latent EBV-encoded Ags and 7-fold higher levels of EBV copy numbers in circulating blood cells. Additionally, patients with RA exhibited substantial expansions of CD8(+) T cells specific for pooled EBV Ags expressed during both B cell transformation and productive viral replication and the frequency of CD8(+) T cells specific for these Ags correlated with cellular EBV copy numbers. In contrast, CD4(+) T cell responses to EBV and T cell responses to human CMV Ags were unchanged, altogether arguing against a defective control of latent EBV infection in RA. Our data show that the regulation of EBV infection is perturbed in RA and suggest that increased EBV-specific effector T cell and Ab responses are driven by an elevated EBV load in RA.

Patients with rheumatoid arthritis have an altered circulatory aggrecan profile.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-immune disease with extensive articular cartilage destruction. Aggrecan depletion, mediated by aggrecanases is one of the first signs of early cartilage erosion. We investigated, whether measurement of aggrecan and fragments thereof in serum, could be used as biomarkers for joint-disease in RA patients and furthermore characterized the fragments found in the circulation. METHODS: The study consisted of 38 patients, 12 males (62.2 +/- 16.0 years) and 26 females (59.8 +/- 20.7 years) diagnosed with RA: 41.5 +/- 27.5 mm/h erythrocyte sedimentation rate (ESR), 38.4 +/- 34.7 mg/ml C-reactive protein (CRP) and 4.8 +/- 1.7 disease activity score (DAS) and 108 healthy age-matched controls. Aggrecan levels were measured using two immunoassays, i.e. the (374)ARGSVI-G2 sandwich ELISA measuring aggrecanase-mediated aggrecan degradation and the G1/G2 sandwich assay, detecting aggrecan molecules containing G1 and/or G2 (total aggrecan) We further characterized serum samples by western blots, by using monoclonal antibodies F-78, binding to G1 and G2, or by BC-3, detecting the aggrecanase-generated N-terminal 374ARGSVI neo-epitope. RESULTS: Total aggrecan levels in RA patients were significantly decreased from 824.8 +/- 31 ng/ml in healthy controls to 570.5 +/- 30 ng/ml (31% decrease, P < 0.0001), as measured by the G1/G2 ELISA. Western blot analysis with F-78 showed one strong band at 10 kDa, and weaker bands at 25 and 45 kDa in both healthy controls and RA patients. In contrast, staining for aggrecanase-activity revealed only one strong band in RA patients of 45 kDa. CONCLUSION: This is the first study, which characterizes different aggrecan fragments in human serum. The data strongly suggests that total aggrecan levels, i.e. aggrecan molecules containing G1 and/or G2 are lower in RA patients, and that RA patients have at least one specific subpopulation of aggrecan fragments, namely aggrecanse generated 374ARGSVI fragments. Further clinical studies are needed to investigate the potential of G1/G2 as a structure-related biochemical marker in destructive joint-diseases.

Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis.

The aim of our study was to compare the significance of risk factors for osteoporosis according to gender and menopausal state in patients with rheumatoid arthritis (RA). Bone mineral density (dual X-ray absorptiometry), cumulative glucocorticoid dose, age, disease duration, body mass index (BMI) and parameters of disease activity and bone turnover were registered in 343 postmenopausal women, 100 premenopausal women and 108 men with RA. Osteoporosis was found in a significantly higher percentage in postmenopausal women (55.7%) and in men (50.5%) in comparison with premenopausal women (18%; P < 0.001). The following risk factors for osteoporosis were found: older age, low BMI and high cumulative glucocorticoid dose in postmenopausal women, low BMI and high cumulative glucocorticoid dose in men and low BMI in premenopausal women. There is a very high prevalence of osteoporosis not only in postmenopausal women but also in men with RA. Osteoporosis risk factors are strongly dependent from gender and menopausal state.

sRANKL and OPG in serum and synovial fluid of patients with rheumatoid arthritis in comparison to non-destructive chronic arthritis.

The aim of this study was to investigate sRANKL and OPG levels in serum and synovial fluid (SF) and to evaluate their relations in patients with RA in comparison to those with non-erosive arthritis (NEA). The study included 45 unselected RA patients with knee joint effusions and 27 patients with knee joint effusions because of NEA. Serum and SF samples were investigated isochronously. OPG and sRANKL were measured by ELISA assays. In RA, sRANKL levels were higher in serum than in SF (P = 0.007). In contrast, the NEA revealed higher sRANKL in SF compared to the serum (P = 0.001). Though in RA the average levels of sRANKL(ser) were 5.6 times and of sRANKL(syn) 1.5 times higher than in NEA, the differences were not significant. The free (unbound) OPG in SF was not significantly different in RA compared to NEA. Also in serum, the measured free OPG was only slightly higher in RA. There were no significant differences between RA and NEA concerning ESR and CRP. Significant correlations could be found between sRANKL(syn )and CRP (r = 0.453; P = 0.005) as well as ESR (r = 0.362; P = 0.033) in RA. Nearly a positive correlation was evident also between sRANKL(syn) and CRP in NEA (r = 0.520; P = 0.08). RA and NEA differ in particular concerning their power and intensity to destruct the juxtaarticular bone. This is the most remarkable finding of this study, that in RA a high part of sRANKL seems to be OPG bound and cleared by the blood stream, but the sRANKL neutralizing capacity of produced OPG in opposite to NEA is not sufficient to prevent osteoclast activation and bone destruction in the RA joint.

Cryoglobulinaemia type III with severe neuropathy and immune complex glomerulonephritis: remission after plasmapheresis and rituximab.

We describe the case of a 78-year-old woman with peripheral neuropathy, neurogenic muscular atrophy, skin ulcers, arthritis and immune complex glomerulonephritis. Detection of mixed cryoglobulins in combination with typical clinical symptoms, and the exclusion of hepatitis C and other underlying diseases, led to the rare diagnosis of essential cryoglobulinaemic vasculitis type III. Because initial interventions with prednisolone, plasmapheresis and cyclophosphamide pulse therapy failed to induce remission, therapy with rituximab, a chimeric monoclonal antibody that reacts specifically with the CD20 antigen, was initiated. Rituximab was administered intravenously at a dose of 375 mg/m(2) body surface. After five applications, the patient showed remission of clinical symptoms and complete normalisation of laboratory values. These results suggest that rituximab is an alternative therapeutical approach with strikingly good clinical outcome in patients with cryoglobulinaemic vasculitis type III.