Enhancing student understanding of rheumatic disease pathologies through augmented reality: findings from a multicentre trial.

OBJECTIVE: The possibility of combining real and virtual environments is driving the increased use of augmented reality (AR) in education, including medical training. The aim of this multicentre study was to evaluate the students' perspective on the AR-based Rheumality GO!® app as a new teaching concept, presenting six real anonymised patient cases with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). METHODS: The study encompassed 347 undergraduate medical students (232 women and 115 men) from four medical universities in Germany (Jena, Bad Nauheim/Gießen, Nuremberg, Erlangen). The course was divided into a theoretical refresher lecture followed by six AR-based cases in each of the three indications presented in the Rheumality GO!® app. All participants evaluated the course after completion, assessing the benefit of the app from a student´s perspective using a questionnaire with 16 questions covering six subject areas. RESULTS: The use of the AR-based app Rheumality GO!® improved the understanding of pathologies in RA, PsA, and axSpA for 99% of the participants. For 98% of respondents, the concept of AR with real patient data has made a positive impact on the teaching environment. On the other hand, 82% were in favour of the use of virtual tools (e.g. AR) in addition to this conventional approach. CONCLUSION: The results of our survey showed that from medical students' perspective, an AR-based concept like the Rheumality GO!® app can complement rheumatology teaching in medical school as an effective and attractive tool though not replace bedside teaching.

The relationship between structural analysis of the hand and clinical characteristics in psoriatic arthritis.

Up to now, there is only limited information available on a possible relationship between clinical characteristics and the mineralization of metacarpal bones and finger joint space distance (JSD) in patients with psoriatic arthritis (PsA). Computerized digital imaging techniques like digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) have significantly improved the structural analysis of hand radiographs and facilitate the recognition of radiographic damage. The objective of this study was to evaluate clinical features which potentially influence periarticular mineralization of the metacarpal bones and finger JSD in PsA-patients. 201 patients with PsA underwent computerized measurements of the metacarpal bone mineral density (BMD) with DXR and JSD of all finger joints by CAJSA. DXR-BMD and JSD were compared with clinical features such as age and sex, disease duration, C-reactive protein (CRP) as well as treatment with prednisone and disease-modifying antirheumatic drugs (DMARDs). A longer disease duration and an elevated CRP value were associated with a significant reduction of DXR-BMD, whereas JSD-parameters were not affected by both parameters. DXR-BMD was significantly reduced in the prednisone group (-0.0383 g/cm²), but prednisone showed no impact on finger JSD. Patients under the treatment with bDMARDs presented significant lower DXR-BMD (-0.380 g/cm²), JSDMCP (-0.0179 cm), and JSDPIP (-0.0121 cm) values. Metacarpal BMD was influenced by inflammatory activity, prednisone use, and DMARDs. In contrast, finger JSD showed only a change compared to baseline therapy. Therefore, metacarpal BMD as well as finger JSD represent radiographic destruction under different aspects.

Diagnosing lung involvement in inflammatory rheumatic diseases-Where do we currently stand?

Lung involvement is the most common and serious organ manifestation in patients with inflammatory rheumatic disease (IRD). The type of pulmonary involvement can differ, but the most frequent is interstitial lung disease (ILD). The clinical manifestations of IRD-ILD and severity can vary from subclinical abnormality to dyspnea, respiratory failure, and death. Consequently, early detection is of significant importance. Pulmonary function test (PFT) including diffusing capacity of the lungs for carbon monoxide (DLCO), and forced vital capacity (FVC) as well as high-resolution computed tomography (HRCT) are the standard tools for screening and monitoring of ILD in IRD-patients. Especially, the diagnostic accuracy of HRCT is considered to be high. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) allow both morphological and functional assessment of the lungs. In addition, biomarkers (e.g., KL-6, CCL2, or MUC5B) are being currently evaluated for the detection and prognostic assessment of ILD. Despite the accuracy of HRCT, invasive diagnostic methods such as bronchoalveolar lavage (BAL) and lung biopsy are still important in clinical practice. However, their therapeutic and prognostic relevance remains unclear. The aim of this review is to give an overview of the individual methods and to present their respective advantages and disadvantages in detecting and monitoring ILD in IRD-patients in the clinical routine.

Radiographic remission in rheumatoid arthritis quantified by computer-aided joint space analysis (CASJA): a post hoc analysis of the RAPID 1 trial.

BACKGROUND: The reduction of finger joint space width (JSW) in patients with rheumatoid arthritis (RA) is strongly associated with joint destruction. Treatment with certolizumab pegol (CZP), a PEGylated anti-TNF, has been proven to be effective in RA patients. The computer-aided joint space analysis (CAJSA) provides the semiautomated measurement of joint space width at the metacarpal-phalangeal joints (MCP) based on hand radiographs. The aim of this post hoc analysis of the RAPID 1 trial was to quantify MCP joint space distance (JSD-MCP) measured by CAJSA between baseline and week 52 in RA patients treated with certolizumab pegol (CZP) plus methotrexate (MTX) compared with MTX/placebo. METHODS: Three hundred twenty-eight patients were included in the post hoc analysis and received placebo plus MTX, CZP 200 mg plus MTX and CZP 400 mg plus MTX. All patients underwent X-rays of the hand at baseline and week 52 as well as assessment of finger joint space narrowing of the MCP using CAJSA (Version 1.3.6; Sectra; Sweden). The joint space width (JSW) was expressed as mean joint space distance of the MCP joints I to V (JSD-MCPtotal). RESULTS: The MTX group showed a significant reduction of joint space of - 4.8% (JSD-MCPtotal), whereas in patients treated with CZP 200 mg/MTX and CZP 400 mg/MTX a non-significant change (JSD-MCPtotal + 0.6%) was observed. Over 52 weeks, participants with DAS28 remission (DAS28 ≤ 2.6) exhibited a significant joint space increase of + 3.3% (CZP 200 mg plus MTX) and + 3.9% (CZP pegol 400 mg plus MTX). CONCLUSION: CZP plus MTX did not reduce JSD-MCPtotal estimated by CAJSA compared with MTX/placebo. Furthermore, clinical remission (DAS28 ≤ 2.6) in patients treated with CZP plus MTX was associated with an increasing JSD, indicating radiographic remission in RA.

Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Response in rheumatoid arthritis.

The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: - 3.53, minimum: - 6.77; maximum: + 0.48) and CZP 200 mg (median: - 3.13, minimum: - 6.37; maximum: - 0.52) compared to the methotrexate group (median - 2.41, minimum: - 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: - 0.009 g/cm2, minimum: - 0.059 g/cm2; maximum: + 0.095 g/cm2) and CZP 400 mg (median: - 0.008 g/cm2, minimum: - 0.064 g/cm2; maximum: + 0.080 g/cm2). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: - 0.024 g/cm2, minimum: - 0.102 g/cm2; maximum: + 0.057 g/cm2). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.

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.

Psoriatic arthritis is associated with bone loss of the metacarpals.

BACKGROUND: BoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring methods. METHODS: The study includes 104 patients with verified PsA. The BX method was used to measure the Metacarpal Index (MCI) at the metacarpal bones (II-IV). Additionally, the T-score of the MCI (T-scoreMCI) was calculated. Radiographic severity was determined by the Psoriatic Arthritis Ratingen Score (Proliferation Score and Destruction Score) as published by Wassenberg et al. and the Psoriatic Arthritis modified van der Heijde Sharp Score (Joint Space Narrowing Score and Erosion Score). RESULTS: For the total PsA study cohort, the T-scoreMCI was significantly reduced by -1.289 ± 1.313 SD. The MCI negatively correlated with the Proliferation Score (r = -0.732; p < 0.001) and the Destruction Score (r = -0.771; p < 0.001) of the Psoriatic Arthritis Ratingen Score. Lower coefficients of correlations were observed for the Psoriatic Arthritis modified van der Heijde Sharp Score. In this context, a severity-dependent and PsA-related periarticular demineralisation as measured by the MCI was quantified. The strongest reduction of -30.8 % (p < 0.01) was observed for the MCI in the Destruction Score. CONCLUSIONS: The BX MCI score showed periarticular demineralisation and severity-dependent bone loss in patients with PsA. The measurements of the BX technique were able to sensitively differentiate between the different stages of disease manifestation affecting bone integrity and thereby seem to achieve the potential to be a surrogate marker of radiographic progression in PsA.

1,25-Dihydroxyvitamin D3 prevents bone loss of the secondary spongiosa in arthritic rats by an increase of bone formation and mineralization and inhibition of bone resorption.

BACKGROUND: Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. However, because the direct effects of 1,25-dihydroxyvitamin D3 (1,25(OH) 2D3) on bone formation and resorption are very complex, the net effect of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation should be investigated. Therefore, we examined the influence of 1,25(OH)2D3 therapy on arthritis-induced alterations of periarticular and axial bone as well as disease activity, inflammation and joint destruction in antigen-induced arthritis (AIA) of the rat. METHODS: AIA was induced in 20 eight-week-old female Wistar rats. 10 rats without arthritis were used as healthy controls. AIA rats received 1,25(OH)2D3 (0.2 µg/kg/day, i.p., n = 10) or vehicle (n = 10) at regular intervals for 28 consecutive days beginning 3 days before arthritis induction. Bone structure of the secondary spongiosa of the periarticular and axial bone was analyzed using histomorphometry. Parameters of mineralization were investigated using tetracycline labelling. Clinical disease activity, inflammation and joint destruction were measured by joint swelling and histological investigation, respectively. RESULTS: AIA led to significant periarticular bone loss. 1,25(OH)2D3 treatment resulted in a highly significant increase in trabecular bone volume and bone formation rate in comparison to both vehicle-treated AIA and healthy controls at periarticular (p < 0.01 and p < 0.001, respectively) and axial bone (p < 0.001 and p < 0.001, respectively). In addition, bone resorption was reduced by 1,25(OH)2D3 at the axial bone (p < 0.05 vs. vehicle-treated AIA). Joint swelling as well as histological signs of inflammation and joint destruction were not influenced by 1,25(OH)2D3. CONCLUSIONS: The results of the study indicate a marked osteoanabolic effect of 1,25(OH)2D3 presumably due to a substantial increase in mineralization. Thus, 1,25(OH)2D3 may be an effective osteoanabolic treatment principle to antagonize the inflammation-associated suppression of bone formation in rheumatoid arthritis.

Bilateral pulmonary embolism in twins with PAI-1 4G/5G gene polymorphism: a case report.

The aetiology of venous thromboembolism in adolescents is frequently associated with hereditary abnormalities of the coagulation system, autoimmune disorders or malignancies. The advent of specific laboratory tests has refined the identification of genetic traits. In this case report, we describe the occurrence of pulmonary embolism in young twins. Intensive tumour screening remained unremarkable. Evaluation of established risk factors for a clotting disorder remained negative, with the exception of a plasminogen activator inhibitor-1 4G/5G polymorphism. Despite the mild association accompanied by the presence of the 4G allele, this polymorphism might predispose to venous thromboembolism in some cases in general and in our case in particular.

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.

Churg-strauss syndrome presenting with cardiac mass and right ventricular obstruction.

A 57-year-old woman presenting with asthma, hypereosinophilia, and generalized unspecific symptoms was diagnosed with Churg-Strauss syndrome. Echocardiography revealed a cardiac mass obliterating the right ventricle and severely impaired left ventricular function, which were caused by endomyocardial fibrosis. Cortisone and cyclophosphamide therapy resulted in amelioration of left ventricular function and significant size reduction of the right ventricular mass.

Dercum's disease (Lipomatosis dolorosa): successful therapy with pregabalin and manual lymphatic drainage and a current overview.

Dercum's disease which is also termed lipomatosis dolorosa is a rare and relatively unknown disease. In this entity the upper arms, elbows, stomach wall, buttocks, thighs and knees are predominantly affected showing painful subcutaneous adipose tissue deposits. In addition severe hyperalgesia can be triggered by light pressure and touch. Analgesic and/or nonsteroidal antirheumatic drugs have usually only a minor or no effect. Here, we report a patient with Dercum's disease who was successfully treated with pregabalin and manual lymphatic drainage, and present a current overview of the literature.

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.

[Fulminate liver failure in a 39-year-old female patient with leukocytosis, unclear fever, and arthralgic pain]. / Fulminantes Leberversagen bei einer 39-jährigen Patientin mit Leukozytose, unklaren Fieberschüben und Arthralgien.

BACKGROUND: Fulminate liver insufficiency can have many causes and is a challenge for differential diagnosis. CASE REPORT: A 39-year-old woman was admitted because of a nonitching macular-papular exanthema on both thighs with spreading to the trunk. In addition, the patient complained of dysphagia, symmetrical arthralgias, myalgias, fever of 38 degrees C, and night sweats. An outpatient treatment with nonsteroidal antirheumatics, antihistamines and penicillin was started for 3 days before admission. On admission, a neutrophilic leukocytosis (23.6 Gpt/l), an increase in C-reactive protein (185 mg/l), and a ferritin level of 1,740 microg/l were found. Liver enzymes were increased (alanine aminotransferase 1.03 micromol/l.s, aspartate aminotransferase 1.06 micromol/l.s, gamma-glutamyltransferase 2.73 micromol/l.s, and lactate dehydrogenase 12.48 micromol/l.s). Sonographic examination showed a mild hepatosplenomegaly, but otherwise normal findings. X-rays of the lungs, hands, and ankles were normal. An echocardiography was within normal limits. Extensive serologic investigations including assays for hepatitides A, B and C as well as repeated blood cultures were negative. Antibiotic therapy was continued without any improvement. In addition, acetaminophen (4 x 1,000 mg/day) and ibuprofen (3 x 600 mg/day) were given. Liver function worsened and an icterus developed. The patient was transferred to the authors' university hospital. Because of the clinical findings of fever episodes, a typical macular exanthema, lymphadenopathy, hepatosplenomegaly, arthralgias, myalgias, dysphagia, and the presence of neutrophilic leukocytosis, fever, an increase in ferritin, but negative serologic titers and no bacteremia, a working diagnosis of Still's disease was made. The patient was treated with high-dose methylprednisone (250 mg/day for 3 days, then 100 mg/day). Liver biopsy revealed subacute hepatitis with necrosis and accompanying cholangitis. The prednisone therapy induced a fast remission and improvement of liver function, liver transplantation was not necessary. The patient is, 16 months after the incident, without symptoms under prednisone 3 mg/day, and the liver function is normal. CONCLUSION: The etiology of Still's disease is unknown and the disease is characterized by fever episodes, a typical macular-papular exanthema, lymphadenopathy, hepatosplenomegaly, and arthralgias. A mild to moderate increase in liver enzymes is often found as part of this disease. Rarely, a fulminate liver failure has been described, particularly in the presence of co-administration of nonsteroidal antirheumatics or acetaminophen. Still's disease must be considered as part of the differential diagnosis of acute liver failure, because an early diagnosis and consequent therapy with prednisone may prevent the need for liver transplantation.

Hypercalcemia in rheumatoid arthritis: relationship with disease activity and bone metabolism.

To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.

The advanced glycation end product pentosidine correlates to IL-6 and other relevant inflammatory markers in rheumatoid arthritis.

OBJECTIVE: Oxidative stress and inflammatory processes accelerate the formation of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this study was to investigate the relationships between levels of pentosidine in serum and synovial fluid, proinflammatory cytokines, other markers of inflammatory activity, and the state of radiologically visible bone destruction in patients with rheumatoid arthritis (RA). OBJECTIVES: One hundred thirty-three nondiabetic RA patients and 56 age-matched, healthy subjects were included. Serum and synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured. RESULTS: Serum levels of pentosidine were on average significantly higher in RA patients than in healthy subjects and correlated significantly to ESR, CRP, and serum levels of IL-6. Serum and synovial fluid pentosidine did not show any differences. Rheumatoid factor-positive RA patients had higher pentosidine levels in the synovial fluid than rheumatoid factor-negative patients. Correlations could not be found between pentosidine and the other cytokines or cytokine receptors measured. CONCLUSION: The binding of AGE on cell receptors induces activation of nuclear factor kappa B, resulting in enhanced synthesis of proinflammatory cytokines. Moreover, AGE generation may also lead to the formation of new, immunologically relevant epitopes at synovial proteins. Both mechanisms could contribute to initiation and perpetuation of the inflammatory and destructive processes in RA.