Search

Die Gicht ist eine Stoffwechselerkrankung. Sie beruht auf einem erhohten Harnsaurespiegel im menschlichen Organismus. Fast eine Million Menschen sind von ihr in Deutschland betroffen. Meist beginnend am Groszeh, ist die Arthritis urica die haufigste Arthritis-Form in den Industrielandern. Zu viel Harnsaure in der Gelenkflussigkeit fuhrt zur Kristallbildung des Salzes der Harnsaure. Weise Blutkorperchen fressen diese Kristalle auf, dabei werden sie selbst geschadigt, zerfallen und setzen Entzundungsstoffe frei. Letztere fuhren zum heftig schmerzenden Gichtanfall mit Rotung, Schwellung, Uberwarmung und Bewegungsunfahigkeit des betroffenen Gelenkes. Sind es zuerst nur einzelne Gichtanfalle, kommt es ohne Behandlung bald zur chronischen Gicht mit Gelenkzerstorung, Gichtknoten – auch in den Weichteilen – und eingeschrankter Nierenfunktion. Lebensstilanderungen und medikamentose Therapie zur Senkung der Harnsaure sind notwendig und machen die Gicht gut behandelbar.

Die Spondyloarthritiden sind eine Erkrankungsgruppe, die sowohl die Wirbelsaule als auch die Gelenke an Armen und Beinen befallen kann. Die Gelenkentzundungen betreffen meist asymmetrisch die groseren Gelenke (Huft-, Knie- oder Sprunggelenke). Sehnenentzundungen und Entzundungen der Sehnenansatze am Knochen kommen hinzu (Fersenschmerzen, Schmerzen an den Sitzbeinhockern). Zusatzlich bestehen auch Wurstfinger oder Wurstzehen. Die Entzundung an der Wirbelsaule beginnt in den Kreuz-Darmbein-Gelenken (Sakroiliitis). Der entzundliche Ruckenschmerz ist dann das wichtigste klinische Symptom. Zu den Spondyloarthritiden werden die ankylosierende Spondylitis (Morbus Bechterew), die Arthritis psoriatica (Schuppenflechte-Arthritis), die reaktiven Arthritiden (nach Infektionen) und die Gelenk- und Wirbelsaulenbeschwerden bei den entzundlichen Darmerkrankungen wie Morbus Crohn und Colitis ulcerosa gezahlt.

Das Fibromyalgie-Syndrom (FMS) ist eine Schmerzerkrankung, die andere rheumatische Krankheiten begleiten oder allein auftreten kann. Neben einem Ganzkorperschmerz sind Leistungsminderung und Schlafstorungen wichtige Symptome. Weitere korperliche Beschwerden konnen hinzukommen. Die Diagnose wird dadurch gestellt, dass ahnliche Erkrankungen ausgeschlossen werden. Es gibt keinen einzigen Test, der das FMS beweist. Die Erkrankung ist zurzeit nicht heilbar. Der Kranke muss lernen, mit seinen Beschwerden zurecht zu kommen. Dabei helfen ihm eine vom Spezialisten vermittelte Verhaltenstherapie und viel korperliche Bewegung. Medikamente haben nur einen begrenzten Einfluss.

Der Begriff Rheuma umfasst ca. 200 verschiedene Erkrankungen, die sich durch Schmerzen und Funktionsstorungen im Bewegungsapparat bemerkbar machen. Die Einteilung erfolgt in drei Hauptgruppen: entzundlich-rheumatische Erkrankungen, sog. Verschleiserkrankungen an Gelenken und Wirbelsaule sowie Stoffwechselerkrankungen, die zu deutlichen Gelenk- und Knochenveranderungen fuhren. Wichtige entzundlich-rheumatische Erkrankungen sind die rheumatoide Arthritis, Morbus Bechterew, Arthritis bei Schuppenflechte (Arthritis psoriatica) und die Erkrankungen, die nicht nur den Bewegungsapparat betreffen, sondern sich vor allem an inneren Organen und Haut bemerkbar machen, wie die Kollagenosen (z. B. systemischer Lupus erythematodes) und Vaskulitiden (z. B. Riesenzellarteriitis und granulomatose Polyangiitis oder Morbus Wegener). Die haufigsten Gelenkerkrankungen sind die Arthrosen. Stoffwechselerkrankungen mit Krankheitszeichen am Bewegungsapparat sind Gicht und Osteoporose.

Osteoporose bedeutet verminderte Knochenmasse und verminderte Anzahl von Knochenbalkchen, die dem Knochen Stabilitat verleihen. Ein osteoporotischer Knochen kann bereits bei geringer Krafteinwirkung brechen. Wahrend die Osteoporose selbst ganz unbemerkt verlauft, bereitet der eingetretene Knochenbruch oft an der Wirbelsaule oder am Schenkelhals meist erhebliche Beschwerden. Wichtigste Risikofaktoren einer Osteoporose sind steigendes Lebensalter und weibliches Geschlecht, weitere Risikofaktoren kommen hinzu. In der Rheumatologie sind die entzundlichen Erkrankungen und der Gebrauch von Glukokortikoiden wichtige weitere Ausloser fur eine Osteoporose mit Knochenbruchen. Immobilitat und zu geringe Sonnenlichtexposition erhohen das Risiko weiterhin.

Vaskulitiden sind Entzundungen der Blutgefase, die durch Autoimmunprozesse hervorgerufen werden. Abhangig davon, welche Blutgefase betroffen sind, zeigen sich ganz unterschiedliche klinische Krankheitsbilder. Bei der Entzundung der grosen Blutgefase, wie der Schlafenarterie und ihrer Aste bei Menschen uber 50 Jahren, treten ganz plotzlich heftige Kopfschmerzen auf. Hohe Entzundungszeichen bei den Laboruntersuchungen begleiten die Kopfschmerzen. Bei der Ultraschalluntersuchung der Schlafenarterie zeigt sich ein charakteristischer Befund, der die Diagnose sichert. Bei einem Teil der Kranken ist die Arteriitis temporalis mit den Symptomen der Polymyalgia rheumatica vergesellschaftet. Bei dieser Erkrankung bestehen heftige Schmerzen in der Muskulatur des Schulter- und/oder des Beckengurtels. Die Granulomatose mit Polyangiitis (GPA), der fruhere Morbus Wegener, ist eine entzundliche Erkrankung der kleinen Blutgefase mit typischen Autoantikorpern: Anti-Neutrophile Cytoplasmatische Antikorper (ANCA).

Rheuma ist heute gut behandelbar. In den letzten Jahrzehnten hat sich bei der medikamentosen Therapie des entzundlichen Rheumas sehr viel verandert. Das Behandlungsziel ist die Remission, das bedeutet: ein entzundungsfreier Zustand. Wird dieses Ziel, zum Beispiel bei einer rheumatoiden Arthritis, mit der herkommlichen Basistherapie nicht erreicht, konnen Biologika oder sogenannte JAK-Hemmer, meist in Kombination mit Methotrexat, zum Einsatz kommen. Glukokortikoide („Kortison“) sind weiterhin, besonders bei den entzundlichen Systemerkrankungen, unverzichtbar. Ihr Einsatz sollte jedoch zeitlich begrenzt sein, um ihre Nebenwirkungen zu reduzieren. Kortisonfreie Rheumamittel, die nichtsteroidalen Antirheumatika, sollten bei Bedarf so niedrig wie moglich und so kurz wie notig verabreicht werden. Opioide sollten wegen der Sturzgefahr nur sehr zuruckhaltend verwandt werden. Zur Rheuma-Therapie gehoren immer auch ein gesunder Lebensstil, einschlieslich einer gesunden Ernahrung, Bewegungstherapie und weitere physikalische Therapieverfahren.

Die rheumatoide Arthritis ist die haufigste entzundlich-rheumatische Erkrankung und betrifft in Deutschland ca. eine halbe Million Menschen. Es ist eine Autoimmunerkrankung, bei der wucherndes Rheumagewebe Knorpel und Knochen der Gelenke zerstort. Dadurch kommt es zu Schmerzen und nicht mehr richtig funktionierenden geschwollenen Gelenken. Am haufigsten beginnt die Erkrankung in den kleinen Gelenken der Hande und Fuse. Auch Sehnen, Schleimbeutel und sogar innere Organe, wie die Lunge, konnen geschadigt werden. Die Krankheit verlauft schubformig. Der Nachweis von Rheumafaktoren und Antikorpern gegen citrulliniertes Peptid/Protein-Antigen (ACPA) im Labor ist fur die Diagnose hilfreich, aber nicht beweisend. Wichtigstes bildgebendes Verfahren ist der Gelenkultraschall. Der rechtzeitige Einsatz der sogenannten Basistherapie, bevor Gelenkschaden entstanden sind, ist dringend notwendig. Die Einfuhrung der Biologika hat dazu gefuhrt, dass heute bei vielen Kranken ein entzundungsfreier Zustand erreicht werden kann. Auserhalb von Schubsituationen ist Bewegung als aktive Trainingstherapie angesagt.

In der Rheumatologie fuhren Anamnese und korperliche Untersuchung bereits zu einer Verdachtsdiagnose der rheumatischen Erkrankung. Laboruntersuchungen und bildgebende Verfahren, wie Rontgen und Ultraschall, bestatigen diese dann. Bei der Anamnese spielen die vier W-Fragen eine grose Rolle: Wo tut es weh? Wann tut es weh? Wie schnell sind die Schmerzen entstanden? Womit stehen die Schmerzen im Zusammenhang? Bei der korperlichen Untersuchung reicht es nicht aus, nur die Gelenke zu untersuchen, sondern der gesamte Korper muss vom Arzt in Augenschein genommen werden. Vor allem die rheumatischen Systemerkrankungen wie Kollagenosen und Vaskulitiden zeigen sich vor allem an der Haut und an inneren Organen. Durch rheumatologische Bewertungsverfahren, wie beispielsweise DAS28, BASDAI oder Funktionsfragebogen Hannover, ist die Verlaufsbeurteilung der Erkrankungen exakter geworden. Die rheumatologischen Scores charakterisieren den betroffenen Patienten sehr genau und machen Vergleiche mit anderen moglich.

Viele rheumatische Erkrankungen sind durch den Rheumatologen leicht zu erkennen. Sie haben eine ganz spezifische Vorgeschichte und sehr typische Krankheitszeichen. 11 verschiedene Krankengeschichten werden mit ihren Symptomen zum Zeitpunkt des Beginns der Erkrankung vorgestellt. Sie betreffen rheumatoide Arthritis, axiale Spondyloarthritis (Morbus Bechterew), Arthritis bei Schuppenflechte (Arthritis psoriatica), reaktive Arthritis, Sjogren-Syndrom, systemischen Lupus erythematodes, Arteriitis temporalis, Fibromyalgie-Syndrom, Heberden-Arthrose, Gicht und Osteoporose. Hier findet der betroffene Leser seine eigene Krankheitsgeschichte wieder.

Zwolf Sozialgesetzbucher regeln in Deutschland soziale Fragen. „Niemand darf wegen seiner Behinderung benachteiligt werden“, ist sogar im Grundgesetz festgeschrieben. Wenn durch chronische Krankheiten eine Beeintrachtigung der Leistungsfahigkeit vorliegt, kann eine medizinische Rehabilitation die Erwerbstatigkeit wieder herstellen. Eine Umgestaltung des Arbeitsplatzes als Leistung zur Teilhabe fuhrt evtl. dazu, dass Sie sogar im bisherigen Arbeitsumfeld verbleiben konnen. Ist Ihre Leistungsfahigkeit jedoch sehr deutlich eingeschrankt, wird eine Erwerbsminderungsrente gezahlt. Bei dauerhafter Behinderung wird ein Grad der Behinderung gewahrt. Er beinhaltet Nachteilsausgleiche. Bei starker Behinderung kann ein Pflegegrad festgelegt werden. Er ermoglicht vor allem finanzielle Hilfen. Fur alle Leistungen mussen Sie Antrage stellen. Lassen Sie sich dabei beraten.

Zu den Kollagenosen wird eine Gruppe systemischer Autoimmunerkrankungen gerechnet, wie Sjogren-Syndrom, systemischer Lupus erythematodes, systemische Sklerose, autoimmune Myositiden und die Mischkollagenosen. Ihr gemeinsames Merkmal ist der Nachweis von Autoantikorpern gegen Zellkerne und ihre Bestandteile, die Anti-Nuklearen Antikorper (ANA). Wahrend das Sjogren-Syndrom noch eine haufigere Erkrankung ist, gehoren die weiteren Kollagenosen zu den seltenen Krankheiten.

Background and Objectives Knee osteoarthritis (OA) is a significant public health burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between geographical regions, most likely due to the lack of standardised indication criteria. We set out to define indication criteria for the German healthcare system for TKA in patients with knee OA, on the basis of best evidence and transparent multi-stakeholder consensus. Methods We undertook a complex mixed methods study, including an iterative process of systematic appraisal of existing evidence, Delphi consensus methods and stakeholder conferences. We established a consensus panel representing key German national societies of healthcare providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists, physiotherapists), payers, and patient representatives. A priori defined consensus criteria were at least 70% agreement and less than 20% disagreement among the consensus panel. Agreement was sought for (1) core indication criteria defined as criteria that must be met to consider TKA in a normal patient with knee OA, (2) additional (not obligatory) indication criteria, (3) absolute contraindication criteria that generally prohibit TKA, and (4) risk factors that do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results The following 5 core indication criteria were agreed within the panel: 1. intermittent (several times per week) or constant knee pain for at least 3 – 6 months; 2. radiological confirmation of structural knee damage (osteoarthritis, osteonecrosis); 3. inadequate response to conservative treatment, including pharmacological and non-pharmacological treatment for at least 3 – 6 months; 4. adverse impact of knee disease on patientʼs quality of life for at least 3 – 6 months; 5. patient-reported suffering/impairment due to knee disease. Additional indication criteria, contraindication criteria, and risk factors for adverse outcome were also agreed by a large majority within the multi-perspective stakeholder panel. Conclusion The defined indication criteria constitute a prerequisite for appropriate provision of TKA in patients with knee OA in Germany. In eligible patients, shared-decision making should eventually determine if TKA is performed or not. The next important steps are the implementation of the defined indication criteria, and the prospective investigation of predictors of success or failure of TKA in the context of routine care provision in Germany.

Objective. To describe characteristic ultrasound findings and clinical features of patients with newly diagnosed cranial and large-vessel (LV) GCA in a specialized ultrasound clinic. Methods. This case–control study includes all consecutive patients between 1997 and 2006 with newly diagnosed GCA. Duplex ultrasound of the temporal, subclavian, axillary and proximal brachial arteries was performed in all patients with suspected temporal arteritis, PMR, arm claudication, unclear inflammation or pyrexia of unknown origin (PUO). Results. In 53 of 176 patients, ultrasound depicted characteristic vasculitic homogeneous wall swelling of the axillary, subclavian and/or proximal brachial arteries. These were affected in 98, 61 and 21%, respectively, in the 53 patients. The findings were bilateral in 79%. Axillary arteries were stenotic or occluded in 51 and 2% and temporal artery ultrasound and histology were positive in 62 and 67% of LV-GCA cases, respectively. A significantly greater number of LV-GCA patients were female (83 vs 65%) and younger (mean 66 vs 72 yrs) as compared with those without proximal arm involvement. Headaches (38 vs 75%), jaw claudication (24 vs 48%) and anterior ischaemic optic neuropathy (4 vs 19%) occurred significantly less frequently. The median time until diagnosis was significantly longer (31 vs 8 weeks). ESR and presence of PMR were similar in both groups. Conclusions. Performing axillary artery ultrasound in all patients with suspected temporal arteritis, PMR, arm claudication, unclear inflammation or PUO increases the diagnostic yield for LV-GCA. Patients with LV-GCA differ from those without arm involvement.

Summary Background Circadian rhythms are changed in patients with rheumatoid arthritis. A new modified-release delivery system has been developed which adapts the release of the administered glucocorticoid to the circadian rhythms of endogenous cortisol and disease symptoms to improve the benefit–risk ratio of glucocorticoid therapy in rheumatoid arthritis. We aimed to assess the efficacy and safety of a new modified-release prednisone tablet compared with immediate-release prednisone in patients with this disease. Methods In a 12-week, multicentre, randomised, double-blind trial, 288 patients with active rheumatoid arthritis were randomly assigned to either a modified-release prednisone tablet (n=144) or to an immediate-release prednisone tablet (n=144). The modified-release tablet was taken at bedtime and prednisone was released with a delay of 4 h after ingestion. This treatment was compared with morning administration of immediate-release prednisone as an active comparator. The primary outcome measure was duration of morning stiffness of the joints. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00146640. Findings The mean relative change in duration of morning stiffness of the joints from baseline to end of treatment was significantly higher with modified-release prednisone than with immediate-release prednisone (−22·7% vs −0·4%; difference=22·4% [95% CI 0·49–44·30]; p=0·045). Patients in the prednisone modified-release group achieved a mean reduction of 44·0 (SD 136·6) min compared with baseline. The absolute difference between the treatment groups was 29·2 min (95% CI −2·59 to 61·9) in favour of modified-release prednisone (p=0·072). The safety profile did not differ between treatments. Interpretation Modified-release prednisone is well tolerated, convenient to administer, and produces a clinically relevant reduction of morning stiffness of the joints in addition to all known therapeutic effects of immediate-release prednisone.

The histopathologic analysis of the synovial tissue is important to distinguish rheumatoid arthritis (RA) from other forms of synovitis and to provide information about prognosis and therapeutic strategies at early stages of the disease. In this context, the present study was performed to investigate the correlation between immunohistopathological and morphological features of synovitis and the expression of collagenase 3 (MMP-13) known to contribute significantly to cartilage degradation in RA. In the histopathologic scoring system used in this study, type I synovitis is characterized by B lymphocyte infiltration and an intact lining, and is only mild destructive to cartilage and bone. Type II shows marked diffuse infiltrations of macrophages and T lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%) were positive for the expression of collagenase 3 mRNA in the synovial tissue. Among these patients, 19 showed a histopathologic type II synovitis and only 2 patients had undifferentiated synovitis. In contrast, synovial tissue samples from patients without collagenase 3 mRNA expression were characterized in 6 cases by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis. The analysis of the clinical data revealed that RA patients with a histopathologic type II synovitis and synovial tissue collagenase 3 mRNA expression had elevated levels of systemic markers of inflammation and received stronger therapies. The data suggest, that collagenase 3 expression and the histopathologic type II synovitis are associated with a severe and destructive course of RA.

Objective: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. Design and setting: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998–2001 values (€1 ≈ $US0.91, average of the period from the year 2000 through 2001). Main outcome measures and results: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of €271 777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of €5004 per ACR20RYG, €9535 per ACR50RYG, €7996 per ACR70RYG, and an incremental cost utility of €8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. Conclusions: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.

Objective. Infliximab, a monoclonal antibody against tumour necrosis factor a (TNF-a), is approved in Europe for the treatment of patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. This report provides analyses from a 3-yr extension study, as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month randomized controlled trial of infliximab in patients with AS. Methods. Of the 49 patients with AS who completed the second year of the study, 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index, the Bath AS Metrology Index, patient’s and physician’s global assessments, quality of life (Short Form-36), C-reactive protein (CRP) and erythrocyte sedimentation rate were assessed throughout the study period. Results. The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study. Forty-three patients (62% of the 69 patients enrolled at baseline and 93% of the patients who started the third year) completed week 156. In the intention-to-treat analysis, an ASAS ‘5 out of 6’ and ASAS 40% response was seen by 46% and 50% of the patients, respectively. The scores for other efficacy assessments were similar to the values observed at weeks 54 and 102. Median CRP levels remained low (1.5 mg/l at week 156). There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study. Conclusions. Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy. Long-term infliximab treatment was well tolerated by patients in this study.

To quantify direct costs of medication and cost of illness (according to functional capacity) for patients with rheumatoid arthritis (RA) in Germany, allowing further use in a health economic evaluation of sequential therapy with disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e. rheumatological, care in Germany.The analysis was conducted from the societal perspective in Germany using a modelling approach, which was based on secondary analysis of existing data and on data from a sample of 583 patients from the German rheumatological database of 1998. Functional capacity was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs were calculated from resources utilised and patients' work capacity. Direct costs consisted of outpatient medical services, inpatient treatment, long-term care and rehabilitation treatment. Indirect costs incurred by sick leave and premature retirement were quantified according to the human-capital approach.Average total direct costs (year 1998-2001 values) per patient per year for continuous treatment with the selected DMARDs comprising costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1 approximately equal to $US 0.91; average of the period from 2000 through 2001)] followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for RA-related non-DMARD medication of euro 554 per patient, including management of ADRs. Mean cost of illness (year 1998 values) excluding medication cost amounted to euro 17,868 per RA patient per year. Annual costs increased with increasing disability, i.e. decreasing functional capacity, of RA patients from euro 6029 per patient with more than 94% of functional capacity to euro 28,509 per patient with20% of functional capacity. In general, there was a predominance of indirect costs in each of the categories of functional capacity, ranging between 74% and 87% of total (direct and indirect) annual costs per RA patient. Annual direct costs increased from euro 811 to euro 7438 per patient with increasing disability. Inpatient treatment was the predominant component of direct costs. Patients in the worst category (20%) of function experienced hospital costs that were 6.5 times higher than those of patients in the best category (94%).On the basis of the data presented it can be concluded that the results of this investigation are typical for patients in rheumatological care in Germany and can therefore be used in a health economic analysis of different DMARD sequences aimed at changing disease progression over time.

Objectives: To determine standard reference values for musculoskeletal ultrasonography in healthy adults. Methods: Ultrasonography was performed on 204 shoulders, elbows, hands, hips, knees, and feet of 102 healthy volunteers (mean age 38.4 years; range 20–60; 54 women) with a linear probe (10–5 MHz; Esaote Technos MP). Diameters of tendons, bursae, cartilage, erosions, hypoechoic rims around tendons and at joints were measured with regard to established standard scans. Mean, minimum, and maximum values, as well as two standard deviations (2 SD) were determined. Mean values ±2 SD were defined as standard reference values. Results: Hypoechoic rims were normally present in joints and tendon sheaths owing to physiological synovial fluid and/or cartilage. Similarly, fluid was found in the subdeltoid bursa in 173/204 (85%), at the long biceps tendon in 56 (27%), in the suprapatellar recess in 158 (77%), in the popliteal bursae in 32 (16%), and in the retrocalcaneal bursa in 49 (24%). Erosions of >1 mm were seen at the humeral head in 47 (23%). Values for important intervals were determined. The correlation between two investigators was 0.96 (0.78–0.99). The reliability of follow up investigations was 0.83 (0.52–0.99). Conclusions: Fluid in bursae as well as hypoechoic rims within joints and around tendons are common findings in healthy people. This study defines standard reference values for musculoskeletal ultrasonography to prevent misinterpretation of normal fluid as an anatomical abnormality.

Objective Treatment of ankylosing spondylitis (AS) with infliximab, an anti–tumor necrosis factor α monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. Methods This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31–63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36–67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in ∼70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. Conclusion Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.

Objective. Takayasu arteritis is a large-vessel vasculitis that occurs predominantly in young females. The diagnosis is not usually established before arterial stenoses or occlusions are present. The aim of the study was to find out if sonography can aid in the diagnosis of the disease in earlier stages. Methods. We describe three patients with early disease who had no haemodynamically relevant stenoses. They are compared with nine patients who were diagnosed in the stenoticuocclusive stage of the disease. All patients were German Caucasian females. Colour Doppler sonography and angiography were performed in all cases. Results. Patients with early disease had general symptoms of fatigue and arthralgia and laboratory signs of inflammation, but neither bruits nor decrease of pulse rate. Sonography of the carotid and subclavian arteries demonstrated a characteristic, homogeneous, midechoic, circumferential thickening of the wall. At this stage of the disease it was difficult to get unequivocal results with angiography. In all nine remaining patients, sonography also demonstrated inflammation of the subclavian or carotid arteries, as did angiography in eight of these patients. Conclusion. Sonography of the carotid and subclavian arteries aids in the detection of early Takayasu arteritis. In young females with unclear symptoms and laboratory findings of generalized inflammation, the primary extracranial branches of the aortic arch should be investigated by sonography to detect early Takayasu arteritis.

Objective Recent studies suggest that giant cell arteritis (GCA) may be an antigen-driven disease. Since Chlamydia pneumoniae has been identified in arterial vessel walls, it was hypothesized that this organism might be associated with GCA. Methods Fourteen paraffin-embedded temporal artery biopsy specimens from 9 patients with GCA were examined by immunohistochemistry and by polymerase chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens were available from both the left and right arteries. Four temporal artery specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery specimens from 5 patients without GCA or PMR served as controls. Results C pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient samples. One GCA patient sample was immunopositive only; another was PCR positive only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control samples from the PMR patients was immunopositive, but PCR negative, for C pneumoniae. The C pneumoniae–positive PMR patient also had respiratory symptoms. The remaining 9 control samples were negative for C pneumoniae by both immunohistochemistry and PCR. Immunohistochemistry showed that bacteria predominate in the adventitial layer of temporal arteries, in granulomatous infiltrates. Dendritic cells were examined by immunohistochemistry for their presence and localization in consecutive temporal artery specimens, and showed a strong topographic relationship with C pneumoniae. Like the bacterium, dendritic cells predominate in the adventitial layer of the arteries. Conclusion C pneumoniae was found in temporal artery specimens from most GCA patients, in 1 specimen from a PMR patient, and in no other control specimens; thus, it may play a role in the pathogenesis of the disease. Dendritic cells may represent the antigen-presenting cells in this situation.

Ophthalmic complications are common in acute GCA. Do temporal artery ultrasound and clinical parameters correlate with the occurrence and severity of ophthalmic complications?The results of temporal artery ultrasound examinations are compared with the occurrence of anterior ischaemic optic neuropathy (AION), central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), diplopia and amaurosis fugax in 222 consecutive patients with newly diagnosed, active GCA.Temporal artery ultrasound displayed vasculitic wall swelling (halo), stenoses and/or acute occlusions in 84% (58% in 67 large-vessel GCA patients and 95% in 155 patients without proximal arm vasculitis). Ophthalmic complications occurred in 64 (29%), AION in 30 (14%), CRAO in 7 (3%), BRAO in 2 (1%), amaurosis fugax in 16 (7%) and diplopia in 9 patients (4%). Ophthalmic complications were insignificantly more common if temporal artery ultrasound was positive (31 vs 17%; P = 0.11) as a greater number of patients without arm vasculitis showed eye involvement (34 vs 18%; P = 0.02). The number of pathological temporal artery segments, presence of stenoses or bilateral findings did not correlate with ophthalmic complications. Ageor= 72 yrs at diagnosis correlated with a higher incidence of ophthalmic complications.Ophthalmic complications occurred less frequently if proximal arm vasculitis was present. Findings of temporal artery ultrasound did not correlate with eye complications.

Objective To study the localization and cell type–specific expression of collagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA). Methods The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase–polymerase chain reaction, and in situ hybridization. Immunohistochemical detection of cell type–specific antigens was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. Results Collagenase 3 mRNA was detected in synovial membrane specimens of 21 of 36 RA patients (58%) and correlated with an increase in erythrocyte sedimentation rate (P < 0.05) and C-reactive protein levels (P < 0.005). Collagenase 3 mRNA was localized in fibroblast-like cells of the lining and sublining layers, and at the synovial membrane–cartilage interface. Four of 10 primary synovial fibroblast cell cultures showed basal expression of collagenase 3 mRNA, which was stimulated 2–4-fold upon interleukin-1β or tumor necrosis factor α treatment and, in contrast to interstitial collagenase mRNA, 5–10-fold by increasing the intracellular level of cAMP. The stimulation by cAMP analogs was completely abolished by protein kinase A inhibitors. Conclusion Some RA patients show collagenase 3 mRNA expression in the synovial membrane, which correlates with elevated levels of systemic markers of inflammation in these patients. In synovial fibroblasts, the expression of collagenase 3 and interstitial collagenase mRNA is differentially regulated by distinct protein kinase signal transduction pathways.

Objective. In patients with Sjogren's syndrome (SS), B lymphocytes have been found to infiltrate salivary glands, resulting in sialadenitis and keratoconjunctivitis. The disease is frequently associated with benign and neoplastic lymphoproliferation. The present study was undertaken to investigate whether clonal B cell expansion takes place in lymphocytic infiltrations of salivary glands under (auto- [?]) antigen stimulation, by analyzing in more detail the variable part (V H -D-J H ) of the immunoglobulin heavy chain genes expressed in these B cells. Methods. Biopsies of the labial salivary glands and lymph nodes were performed on 2 female patients with SS. The Ig gene rearrangements in these tissues were amplified by reverse transcriptase-polymerase chain reaction using specific primers. Results. A total of 94 V H -D-J H transcripts were cloned and sequenced. Our data suggest a polyclonal origin of the B cell infiltrates. In 92 of the transcripts, V H genes were modified by somatic mutation. Further analysis showed counterselection for replacement mutations within the framework regions, suggesting that those B cells were stimulated and selected for functional expression of a surface Ig. In labial salivary glands from both patients, clonally related B cells became evident. Members of 1 particular clone were found in both the lip and lymph node material. Conclusion. These data provide evidence, on the nucleotide sequence level, that an antigen-triggered clonal B cell expansion takes place in the salivary glands of patients with SS who do not have histologic evidence of developing lymphoma. It may be speculated that those B cell clones expand during disease progression, resulting in lymphomagenesis.

The aim of this study is to compare clinical features and treatment of young onset rheumatoid arthritis with late-onset rheumatoid arthritis.Nine thousand five hundred forty-one patients with rheumatoid arthritis (RA) enrolled in the national database of the German Collaborative Arthritis Centres in 2007-2009 were stratified by age at disease onset: up to 65 years (YORA),65 years (LORA). To enable unbiased comparisons between the two groups despite their systematic differences in age and disease duration, we performed two separate matched-pairs analyses: the impact of current age was assessed by matching YORA and LORA patients for disease duration and sex (n=1,550 pairs). To identify the influence of disease duration, a second sample matched for age and sex (n=1,158 pairs) was drawn.At identical age, YORA patients had higher disease activity (DAS28), worse functional capacity and were less frequently in remission when compared with LORA patients. YORA patients also suffered more frequently from RA-related co-morbidities such as cardiovascular disease, chronic renal disease and osteoporosis. Matched for disease duration, there were no differences between the two groups concerning disease severity and remission rates, global health or pain intensity. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received significantly fewer synthetic or biologic DMARDs than YORA patients.Duration of RA, rather than age, explains differences in disease burden between YORA and LORA patients. The lower prescription rates of synthetic and in particular biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients.

A 37-year old male with newly diagnosed, untreated Wegener's granulomatosis including glomerulonephritis, sinusitis, conjunctivitis, arthralgias, and positive cANCA, developed a pulsating tumor in the left submandibular region and a reversible ischemic neurologic deficit. Ultrasonography revealed both a hyperechoic wall thickening of the left proximal internal carotid artery as is known in Takayasu's arteritis and a surrounding hypoechoic region typical for perivasculitis. The wall thickening and the perivascular infiltrate could be less clearly seen by MRI. Ultrasonography, angiography, and MRI demonstrated a 3 cm long, 30%, stenosis. Angiography and MRI additionally found a more distally located kinking of the internal carotid artery that was missed by ultrasonography. Carotid artery vasculitis is a rare complication of Wegener's granulomatosis. In this case ultrasonography was superior to angiography and MRI to visualize the artery wall and the surrounding tissue, but it failed to evaluate the whole distance of the vessel.

NKG2D, involved in T-cell activation and viral defense, shows a single-nucleotide polymorphism (SNP) in the transmembrane region, characterized by a substitution of alanine with threonine. We examined the association of systemic lupus erythematosus (SLE) with one of the NKG2D gene variants. We also studied the functional impact of that allele in SLE. Restriction fragment length polymorphism/polymerase chain reaction specific for the SNP rs2255336 G--> A was performed with 247 German SLE patients and 447 controls and with 284 Spanish SLE patients and 180 controls. NKG2D expression on peripheral blood lymphocytes of SLE patients was analyzed via fluorescence activated cell sorter. In addition, proliferation assays were performed. We found that the NKG2D alanine/alanine (G/G) gene variant was significantly associated with SLE in the German cohort (70.4% vs 60.8% controls; p = 0.0027) and almost significantly in the Spanish cohort (66.2% vs 62.2% controls; p = 0.054). In a pooled analysis, the prevalence of G/G was 68.2% in SLE versus 61.2% in the controls (p = 0.0024). There were no significant differences in the expression levels of NKG2D on peripheral blood lymphocytes of the different genotypes. A comparison of the coreceptor activity of the genotypes in response to CD3 and NKG2D antibodies revealed a trend toward higher proliferation in the A/A genotype. In conclusion, based on our study results, SLE is associated with the SNP rs2255336 of NKG2D.

Objectives:To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance.Methods:The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed.Results:200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected.Conclusion:Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

Objective. The prognosis of large-vessel GCA (LV-GCA) has not yet been investigated. How does it compare to GCA without arm vasculitis (GCA controls)? Methods. Charts of 53 LV-GCA patients and 53 GCA controls were reviewed following a predetermined protocol. Telephone interviews of patients or their primary care physicians were conducted. Forty LV-GCA patients underwent follow-up duplex ultrasound examinations of proximal arm arteries. Results. The mean observation time was 50 (S.D. � 31) months. None of the LV-GCA patients developed ischaemic arm complications. In 30%, proximal arm artery wall swelling disappeared completely. It decreased in 53%. In 8% it remained unchanged, in 5% it increased and in 5% arteries occluded with collateral flow. After the start of treatment, anterior ischaemic optic neuropathy developed neither in LV-GCA patients nor in GCA controls, amaurosis fugax occurred in 4 and 6%, arterial hypertension in 53 and 66%, strokes in 9 and 9%, myocardial infarction in 2 and 2%, diabetes mellitus in 30 and 25%, osteoporosis in 38 and 23%, and osteoporotic fractures in 15 and 4%, respectively. Mean corticosteroid dose was 3.7mg/day. Mean duration of therapy was 42 months. All differences were insignificant. Four LV-GCA patients developed vasculitic popliteal artery stenoses. Conclusions. The prognosis of LV-GCA is benign with regard to ischaemic complications. Proximal artery wall swelling decreases in most cases. Its course is similar to GCA without proximal arm arteritis.

To verify ultrasonographic criteria for examination of the major salivary glands in diagnosis of primary and secondary Sjögren's syndrome (SS).Three hundred sixteen consecutive patients with rheumatic diseases were selected according to the European Consensus Study Group diagnostic criteria for SS. Fifty-seven had primary SS, 33 had secondary SS, 78 had Sicca symptoms, and 148 patients served as asymptomatic controls. This cohort was analyzed for size and parenchymal echogenicity of the major salivary glands by ultrasonography.Evident parenchymal inhomogenicity in 2 or more major salivary glands was detected by ultrasonography in patients with primary and secondary SS with a sensitivity of 63.1% and 63.6%, respectively. The specificity of this imaging approach in our cohort was 98.7%. The volume of submandibular glands was reduced in patients with primary and secondary SS by about 30% compared to patients with sicca symptoms and asymptomatic controls. In receiver-operating characteristic (ROC) curve analysis, the detection of reduced volumes of both submandibular glands in patients with primary and secondary SS had a specificity of 93% and a sensitivity of 48% at the cutoff point of 3.0 ml. Of note, the volume of the parotid glands did not differ between the groups of patients. In patients with primary SS, parenchymal inhomogenicity of the salivary glands was strongly associated with positivity for anti-Ro and/or anti-La antibodies.Ultrasonographic detection of parenchymal inhomogenicity of the major salivary glands and observation of reduced volume of the submandibular glands resulted in high specificities for diagnosis of primary and secondary SS. The data indicate that ultrasonography of major salivary glands is a noninvasive imaging procedure with high diagnostic value for the diagnosis of primary and secondary SS.

In a patient with active extracranial giant cell arteritis, duplex ultrasonography demonstrated hypoechoic mural thickening of the brachial, axillary, subclavian, and carotid arteries with bilateral subtotal occlusions of the brachial and axillary arteries. The ultrasound image of the artery walls became midechoic within 8 weeks, and hyperechoic within one year after start of treatment with corticosteroids. A similar hypoechoic mural thickening of the temporal arteries has been recently described in active giant cell arteritis. The dark ultrasound image is due to an edema of the vessel wall in the acute stage. The brighter ultrasound image might be due to fibrosis in the chronic stage of the disease.

To analyze the safety and efficacy of the anti-tumor necrosis factor agent infliximab in patients with ankylosing spondylitis (AS) after discontinuation of longterm therapy over 1 year and readministration, using clinical and laboratory assessments including serum levels of antibodies to infliximab (ATI).Altogether 42/43 patients with AS in a 3-year multicenter trial discontinued therapy after continuous treatment with infliximab (5 mg/kg/6 wks). Infliximab was only readministered in case of a clinical relapse [judged by Bath AS Disease Activity Index (BASDAI) and physician global assessment4]. ATI were measured at different timepoints. The primary outcome was safety, and efficacy outcomes were secondary.One patient dropped out after the eighth infusion after retreatment due to repeated local infections. ATI were detected in this patient only. No other relevant adverse events were observed. One patient remained in clinical remission without therapy for more than 1 year. The other 40 patients (97.6%) were reinfused because of clinical relapse. There was no correlation between ATI and clinical measures. BASDAI 50% responses were seen in 25 (63%) and partial remission in 12 (30%) patients. The mean (+/- SD) BASDAI score dropped from 6.0 +/- 1.4 at the time of relapse to 2.6 +/- 2.0, and the median C-reactive protein from 11.2 to 1.8 mg/l after 1 year (all p0.05).Readministration of infliximab after discontinuation of longterm treatment was generally safe and efficacious. Ongoing remission after discontinuation was rare. There was only one patient with relevant adverse events. ATI were detected only in this patient, but there was no correlation to clinical data. Formation of ATI seems to be rare after longterm infliximab therapy in AS.

Case reports: Three patients—two with Wegener’s granulomatosis and one with an overlap syndrome of rheumatoid vasculitis, systemic lupus erythematosus, and antiphospholipid syndrome—are described. All patients experienced a sudden onset of Raynaud’s phenomenon or acrocyanosis when they had a flare of their disease. Discussion: Ultrasonography (US) showed dark (hypoechoic) arteries without colour signals, resembling the US pattern of embolism. In contrast, US in patients with systemic sclerosis is entirely different, delineating a smaller artery lumen, reduced pulsation, and thickened, slightly hyperechoic artery walls.

To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists.Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished.We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose7.5 mg.Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis--Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2-3.2)); ARA remission, OR 2.05 (95% CI 1.2-3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS286. Sustained remission at 6 and 12 months was achieved in10% of the patients. Severely disabled patients (or = 50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (or = 67% of full function) than controls (OR 3.88 (95% CI 1.7-8.8)). 'Functional remission' (or = 83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04-4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.

Objective To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment. Methods Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. Results Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7–27.2) among patients receiving etanercept, 28.3 (95% CI 23.1–34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0–9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5–9.1), 6.2 (95% CI 4.0–9.5), and 2.3 (95% CI 1.3–3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9–5.4) for patients receiving etanercept and 2.1 (95% CI 0.8–5.5) for patients receiving infliximab, compared with controls. Conclusion Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.

Articular symptoms are frequent manifestations of hereditary haemochromatosis. The clinical signs of the arthropathy of haemochromatosis are not specific and difficult to identify in case of co-incidence of haemochromatosis with Heberden’s and Bouchard’s osteoarthritis or rheumatoid arthritis (RA). Here the manifestation of RA in a patient is reported who was successfully treated for haemochromatosis. Six months after terminating phlebotomy, the patient presented again suffering from impressive swelling of all MCP joints, showing strong synovitis in ultrasound, and from morning stiffness longer than 1 h. ESR, CRP, IgM rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were markedly elevated. Based on these findings the diagnosis of RA was made. Therefore, the high prevalence of RA and haemochromatosis in the general population underlines the usefulness of a screening for HFE gene mutations in RA patients with an atypical course of the disease as well as in patients with undifferentiated arthritis.

Temporal arteritis, including large-vessel giant cell arteritis, and Takayasu's arteritis are the two primary large-vessel vasculitides. Patients with temporal arteritis often present with headache, swollen temporal arteries, impairment of vision or symptoms of polymyalgia rheumatica. Clinical examination includes palpation of the temporal arteries and radial pulses, auscultation of the subclavian and axillary region, and fundoscopy. The presence of jaw claudication, diplopia and temporal artery abnormalities correlates with a high probability of positive histology. Duplex ultrasonography of the temporal arteries delineates a characteristic hypoechoic, oedematous wall swelling, stenoses and occlusions. It detects the same pathologies in the axillary arteries and other arteries in large-vessel giant cell arteritis. Angiography, magnetic resonance imaging, magnetic resonance angiography, electron beam computed tomography, computed tomography angiography and positron emission tomography show characteristic changes in the aorta and its primary branches in large-vessel giant cell arteritis and Takayasu's arteritis. Takayasu's arteritis often begins with diffuse symptoms such as low-grade fever, arthralgia, fatigue and weight loss. Clinical examination is important to detect bruits, pulse reduction and blood pressure differences. Profound experience exists with angiography. Other imaging methods are interesting alternatives as they are less invasive and may depict the inflammatory wall swelling.