[Long-term complications, monitoring and interventional treatment of large vessel vasculitis]. / Langzeitkomplikationen, Monitoring und interventionelle Therapien bei Großgefäßvaskulitiden.

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) both belong to the group of large vessel vasculitides and require long-term drug treatment. Glucocorticoids (GC) are the first choice for the treatment of both diseases. For GCA immunosuppressants, such as tocilizumab or methotrexate should be considered in cases of treatment refractory and relapses or if there is a high risk for GC-related adverse events. In TAK patients the use of immunosuppressive agents should be considered for all patients. In the course of the disease, severe disease-associated and treatment-associated complications can occur. The most frequent disease-associated complications include visual impairment up to blindness in GCA, as well as vascular stenoses with ischemia and aortic aneurysms with possible dissection in GCA and TAK. Percutaneous transluminal angioplasty (PTA) and stenting are minimally invasive, low-risk interventional procedures for GCA and TAK patients with clinically significant vascular stenoses, despite a tendency to restenosis. Interventional procedures should be weighed up against vascular surgical approaches depending on the localization and the total clinical situation. All interventions should be conducted in a phase of stable remission when possible. For monitoring of disease activity in patients with GCA and TAK, assessment of clinical manifestations as well as C­reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are useful; however, both are unreliable under interleukin­6 block with tocilizumab. The value of new biomarkers independent from interleukin­6 and the importance of imaging (sonography, magnetic resonance angiography, computed tomography and positron emission tomography-CT) for monitoring GCA and TAK still have to be investigated in future studies.

[S3 guidelines on treatment of polymyalgia rheumatica : Evidence-based guidelines of the German Society of Rheumatology (DGRh), the Austrian Society of Rheumatology and Rehabilitation (ÖGR) and the Swiss Society of Rheumatology (SGT) and participating medical scientific specialist societies and other organizations]. / S3-Leitlinie zur Behandlung der Polymyalgia rheumatica : Evidenzbasierte Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh), der Österreichischen Gesellschaft für Rheumatologie und Rehabilitation (ÖGR) und der Schweizerischen Gesellschaft für Rheumatologie (SGR) und der beteiligten medizinisch-wissenschaftlichen Fachgesellschaften und weiterer Organisationen.

Polymyalgia rheumatica (PMR) occurs almost exclusively in persons aged 50 years or older and it is the second most common inflammatory rheumatic disease in older people after rheumatoid arthritis. Since there are no specific tests for PMR, the exclusion of clinically similar differential diagnoses is essential to ascertain the diagnosis. These recommendations for the management of PMR assume an already established diagnosis of PMR. It is recommended to initiate treatment with glucocorticoids immediately after diagnosis and to provide appropriate patient information and education about the impact of the disease and its treatment. Methotrexate should be considered in patients at high risk for relapse and/or glucocorticoid-related adverse events. These guidelines have been elaborated because there is significant heterogeneity in the management of PMR in clinical practice in Germany (but also Europe and worldwide), despite the large number of patients with this disease. These guidelines are primarily based on the 2015 EULAR-ACR recommendations for the management of PMR, which were updated by the guideline committee and adapted to the German speaking countries.

Update on treatment of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease in the elderly after rheumatoid arthritis. It is clinically characterised by pain and stiffness in the neck, proximal shoulder and hip girdle. Glucocorticoids (GCs) are the cornerstone of PMR treatment, but they are associated with potentially severe side effects. Among GC-sparing agents, methotrexate revealed a modest benefit in clinical trials, and recently, there have been promising reports from tocilizumab. In this review, we summarize the available evidence on the treatment of PMR and the possible role in the future of other agents under investigation.

[Diagnostics and treatment of polymyalgia rheumatica]. / Diagnostik und Therapie der Polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is the most common autoimmune inflammatory disease in older persons with an average age of onset of 73 years. Typical symptoms include acute or subacute bilateral shoulder pain with severe stiffness and often neck and bilateral hip pain. Giant cell arteritis (GCA) occurs in approximately 20 % of cases and up to two thirds of patients with GCA have symptoms of PMR. There are many disease which mimic PMR, elderly onset rheumatoid arthritis is frequently misdiagnosed as PMR. Although there are no specific laboratory tests, C­reactive protein and erythrocyte sedimentation rates are elevated in over 90 % of patients. The diagnosis may be aided by imaging, especially ultrasonography and magnetic resonance imaging (MRI). Treatment currently consists of glucocorticoids at an initial dose of 12.5-25 mg prednisone equivalent daily. Treatment duration is typically 2­3 years but may be longer. Under certain conditions low-dose methotrexate can be used as adjuvant therapy.

Fast track pathway reduces sight loss in giant cell arteritis: results of a longitudinal observational cohort study.

OBJECTIVES: To investigate the effectiveness of a fast track pathway (FTP) on sight loss in patients with suspected giant cell arteritis (GCA). METHODS: A longitudinal observational cohort study was conducted in the secondary care rheumatology department. One hundred and thirty-five newly referred suspected GCA patients seen via the FTP (Jan. 2012-Dec. 2013) were compared to 81 patients seen through the conventional referral and review system (Jan. 2009-Dec. 2011). RESULTS: The FTP resulted in significant reduction in irreversible sight loss from 37.0% (as seen in the historical cohort 2009-2011) to 9.0 % (2012-2013, OR 0.17, p=0.001). Adjustment for clinical and demographic parameters including known risk factors for GCA associated blindness did not significantly change the primary result (OR 0.08, p=0.001). FTP resulted in a reduction of time from symptom onset to diagnosis, particularly by reduction of time from general practitioner's (GP) referral to the rheumatology review (79% of FTP patients were seen within one working day compared to 64.6 % in the conventional pathway, p=0.023). The FTP has seen a reduction in number of GP appointments. CONCLUSIONS: There was a significant reduction of permanent sight loss with a fast track GCA pathway. The effect may be due to multiple factors including better GP education and reduction in delayed diagnosis. These results need verification at other sites.

Ultrasound screening for interstitial lung disease in rheumatoid arthritis.

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

[Adalimumab for the treatment of ulcerative colitis--a consensus report by the working group inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung der Colitis ulcerosa--ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.

Feasibility of 3D ultrasound to evaluate upper extremity nerves.

PURPOSE: This study investigates the performance of a 3 D Ultrasound (US) system in imaging elbow and wrist nerves. MATERIALS AND METHODS: Twenty healthy volunteers with asymptomatic median, ulnar and radial nerves were prospectively investigated. Bilateral 3DUS scans of the elbows and wrists were acquired by using a commercially available US scanner (18 MHz, AplioXG, Toshiba) and stored as a 3 D volume by a dedicated software (CURE, Robarts Research Institute). Retrospectively, qualitative (image quality, atypical nerve location, findings potentially associated with compression neuropathy) and quantitative (cross-sectional area measurements) evaluations were performed. RESULTS: In all 200 nerves 3DUS was feasible (100%). Image quality was insufficient in 13.5% (25 ulnar nerve elbow, 2 radial nerve) and sonomorphology was not assessable in those nerves. Measurement of cross sectional areas was feasible in all nerves (100%). Median cross-sectional area (range) were: median nerve elbow 7 mm2 (6-9), radial nerve 3 mm2 (1-4), ulnar nerve elbow 8 mm2 (5-11), median nerve wrist 8 mm2 (5-10), and ulnar nerve wrist 4 mm2 (2-6). No significant changes in nerve cross-sectional area along each nerve was found. Ulnar nerve subluxation was found in 2 nerves (6.7%). No anconeus epitrochlearis muscle or osteophytes were found. CONCLUSION: 3DUS is a feasible method for assessing nerves of the upper extremity and has been shown to provide a good overview of the median, ulnar and radial nerve at the elbow and wrist, but is limited for evaluation of the ulnar nerve in the cubital tunnel. This technique enables reliable measurements at different locations along the nerve.

Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

INTRODUCTION: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics. RESULTS: From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis. CONCLUSION: This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.

[Expectations of rheumatologists on imaging results]. / Erwartungen des Rheumatologen an die Bildgebung.

CLINICAL/METHODICAL ISSUE: Clinical examination and laboratory results are often insufficient to support therapeutic decisions. STANDARD RADIOLOGICAL METHODS: Diagnosis and organ-related imaging may provide important additional information for initial diagnosis (differential diagnoses), follow-up and prognosis. Especially functional imaging techniques, such as ultrasound and magnetic resonance imaging are becoming more and more important for early diagnosis. METHODICAL INNOVATIONS: Imaging is already recognized in the classification criteria of several rheumatic diseases and new criteria for spondyloarthritis and polymyalgia rheumatica aim more and more at early diagnosis using functional imaging techniques, such as ultrasound and magnetic resonance imaging. PERFORMANCE: Specific imaging findings are helpful for eliminating differential diagnoses. During follow-up disease control the status as well as progression of structural damage can be documented. In selected diseases imaging allows prognostic statements on both disease progression and therapeutic response to specific medication. ACHIEVEMENTS: The evidential value of imaging results varies with the rheumatological expectations. PRACTICAL RECOMMENDATIONS: Overall rheumatological expectations on imaging differ widely and therefore support a differentiated use of imaging techniques.

[Giant-cell arteritis: update: diagnosis and therapy]. / Riesenzellarteritis : Update: Diagnose und Therapie.

Giant-cell arteritis (GCA) is the most common form of vasculitis in patients over 50 years old. Loss of vision is the most common severe complication but involvement of extracranial arteries including the aorta is more frequent than previously assumed. The role of dendritic and T-cells indicates the presence of an antibody but a clear association with underlying infections has not yet been demonstrated. Even if the inflammation parameters in blood are mostly increased in the diagnosis of GCA, specific laboratory tests for the diagnosis of GCA are not available. Of the imaging procedures ultrasonography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography can be useful to localize and estimate the extent of vascular involvement. Glucocorticoids are still the standard therapy of GCA, whereby the cumulative dose can possibly be reduced by additional methotrexate. In addition acetylsalicylic acid is recommended as prophylaxis against cardiovascular and cerebrovascular events as well as prophylaxis and therapy of accompanying osteoporosis.

Association of ultrasound-confirmed axillary artery vasculitis and clinical outcomes in giant cell arteritis.

OBJECTIVES: The aim of this observational study was to compare clinical outcomes including glucocorticoid treatment and relapses between giant cell arteritis (GCA) patients with (axGCA) and without axillary artery involvement (non-axGCA). METHODS: Axillary artery ultrasound was performed in 101 GCA patients at multiple time points. Patients with signs of vasculitis of the axillary arteries at baseline were compared to patients without signs of axillary artery involvement. Cumulative GC doses and relapse rates were calculated as well as survival curves to compare the time until GC discontinuation and occurrence of the first clinical relapse. A linear mixed model was used to assess the effect of a clinical relapse on the intima media thickness (IMT) in axGCA patients. RESULTS: Sixty-seven patients were classified as axGCA, 34 as non-axGCA patients. Compared with non-axGCA, axGCA patients yielded a higher (albeit not significant) median time until GC discontinuation (42 months (95% CI: 33-84) vs 30 months (95% CI: 21-42), p=0.060) and median cumulative GC dose (6801mg (range 1748-34169) vs 5633mg (range: 2553-19967), p=0.051). Time until the first relapse (axGCA: 12 months (95% CI: 8-42) vs non-axGCA: 13.5 months (95% CI: 6-27), p=0522) and relapse rates (2 (range: 0-16) vs 1 (range: 0-13), p=0.67) were similar in both groups. Relapses resulted in an increase of the IMT by 0.18mm (95% CI: 0.07-0.30, p=0.003). CONCLUSION: Patients with axGCA have a trend towards longer treatment duration and higher GC requirements as compared to non-axGCA patients. A relapse leads to an increase of the IMT by 0.18mm.

[Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology]. / Infliximab in der Therapie des Morbus Crohn - ein praktischer Leitfaden: aktualisierter ÖGGH-Konsensus der Arbeitsgruppe Chronisch-entzündliche Darmerkrankungen der ÖGGH.

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD), fistulating Crohn's disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually.

Urate oxidase (rasburicase) for treatment of severe acute gout: a case report.

A 73-year-old female patient was referred to our department because of gouty arthritis in the right first toe. The patient suffered from progressive renal failure because of pauci-immune necrotising glomerulonephritis. As severe hyperuricaemia would further worsen progredient renal insufficiency and therapy with allopurinol was contraindicated because of renal insufficiency and previous pancytopenia, the patient was treated twice with intravenous rasburicase. This therapy was well tolerated by the patient and led to the decrease of serum uric acid below the detection limit within 24 hours.

[Current therapeutic options for giant cell arteritis]. / Aktuelle Therapieansätze bei Riesenzellarteriitis.

Giant cell arteritis is the most common systemic vasculitis and affects large and medium-sized vessels. Glucocorticoids are the current standard in the therapy of giant cell arteritis. To reduce the glucocorticoid dose the European League Against Rheumatism (EULAR) suggests the addition of disease-modifying antirheumatic drugs. Of these, methotrexate represents the best investigated drug; possible alternatives include azathioprine, tumor necrosis factor-alpha inhibitors and cyclophosphamide.

[Polymyalgia rheumatica]. / Polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common chronic inflammatory rheumatic disease with unknown aetiology, affecting predominately people of middle age and older. Besides clinical symptoms and diagnostics, imaging techniques including sonography and magnetic resonance imaging may provide evidence of typical inflammatory lesions with bilateral bursitis subdeltoidea or subacromialis, tenosynovitis of the biceps tendon sheath and/or synovitis of the shoulder joints and thus may support the diagnosis of this disease in difficult cases. Corticosteroids are the cornerstone of treatment of PMR, but adverse events because of chronic corticosteroid use are observed in more than 50% of treated patients. Whether immunosuppressants, such as methotrexate and tumour necrosis factor-alpha inhibitors are effective in the therapy of PMR has still not yet been clarified.

Clinical and functional characterisation of a novel TNFRSF1A c.605T>A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

OBJECTIVES: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. METHODS: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFalpha in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. RESULTS: TNFRSF1A sequencing disclosed a novel V173D/p.Val202Asp substitution encoded by exon 6 in one family, the c.194-14G>A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFalpha-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. CONCLUSIONS: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients.