roadmap to vasculitis a rheumatological treasure hunt part iv management of vasculitis

Abstract At the stop sign we read the "red flags" and made up our mind and followed one of the road signs pointing to secondary, primary or fake vasculitis. Since then we have steadily followed the road map and passed the first (patient history and physical exam), second and third milestones (laboratory, imaging and pathology studies in the primary care and specialized centres) and have finally reached our destination at the fourth milestone (Part IV) on the road map review to vasculitis. In the management of these syndromes, Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI) are not widely used in the routine clinical work, but they are introduced as the idea behind them is really valid. The backbone of the medical therapy is the use of immunosuppressive doses of prednisone (1 mg/kg/day). In some life-threatening and non-responsive vasculitides this is combined with cyclophosphamide 2–4 mg/kg/day or 0.5–1.0 g/m 2 i.v. every 2–4 weeks (European Vasculitis group uses 15 mg/kg every 2–3 weeks), often at 3–6 months substituted either with methotrexate or azathioprine. In contrast, i.v. immunoglobulins are to be used in Kawasaki's syndrome; cyclosporine, dapsone or colchicine in Behcet's disease; calcium channel blockers in BACNS; and NSAID in small vessel disease; whereas plasmapheresis or immunoadsorption are added to the therapy in Goodpasture's syndrome. Particular attention is drawn to the treatment of the triggers, use of biologicals and new cytostatic drugs and anti-metabolites, prevention of thromboembolic complications with anti-platelet drugs as well as to odd and orphan entities. A short travelogue ends our odyssey as the last sign on our roadmap

roadmap to vasculitis a rheumatological treasure hunt

Abstract Vasculitis is characterized by inflammation of the wall of blood vessels. It involves immunologically mediated responses to usually unknown antigens, which result in vessel wall damage. Weakening of the vessel wall can lead to aneurysms, dissections or bleeding and narrowing of the lumen (caused by vasculitis per se and complicating thrombosis and embolization) resulting in ischemic damage and necrosis of the affected end organs and tissues. The first part of this four-part review describes the red flags and stop signs, which could help the busy doctor to stop and to start to think of the possibility of vasculitis. This is particularly important as many of these syndromes are life-threatening and hence their diagnostics can be compared to "a rheumatologic treasure hunt" as the treasured life of the patient is often at stake. Everything starts with simple measures, namely taking the patient history and conducting a complete physical examination. This is often enough for the identification of triggering factors as causes as well as targets of therapy in secondary vasculitides. They are often also enough for the right diagnosis, which only needs to be confirmed, perhaps by specialists, with more elaborate and expensive methodology

roadmap to vasculitis a rheumatological treasure hunt part ii classification features of individual vasculitides and differential diagnosis against pseudovasculitis

Abstract Since the triggering factors causing primary vasculitides are by definition not (yet) known, we have to classify them to clinical syndromes based on the size, site, type and effect of the blood vessel involvement. ACR classification criteria and Chapel Hill nomenclature are useful tools to familiarize with the primary vasculitides, although a lot of criticism has been voiced in the literature indicating that they only represent the best available consensus. The present text takes advantage of the recent developments such as introduction of the anti-neutrophilic cytoplasmic auto (ANCA) antibodies, and divides the vasculitides to those affecting typically the large, medium and small arteries or only small blood vessels. In addition, some vasculitides, which are still difficult to place to the vasculitis map, like Burger's disease, Goodpasture's syndrome, primary angiitin of the central nervous system (PACNS) and panniculitis, are dealt with. As it is a long and winding road, attention has to be paid to the clinical details to follow the road sign to "pseudovasculitis", when that is the right way to go. They represent a bunch of non-vasculitic conditions, which lead to structural or vasospastic impairment of the blood flow, bleeding or thromboembolism and hyperviscosity. These imitators have to some extent, similar clinical symptoms and signs as well as laboratory and radiological findings to those found in true systemic vasculitides. This also emphasizes the importance of internal medicine as the intellectual (albeit not necessarily organizational) home of rheumatology and rheumatologists as we deal with conditions like atherosclerosis, antiphospholipid antibody syndrome, infectious endocarditic, myxoma of the heart and cholesterol embolism

Changes in articular cartilage after meniscectomy and meniscus replacement using a biodegradable porous polymer implant

Purpose: To evaluate the long-term effects of implantation of a biodegradable polymer meniscus implant on articular cartilage degeneration and compare this to articular cartilage degeneration after meniscectomy. Methods: Porous polymer polycaprolacton-based polyurethane meniscus implants were implanted for 6 or 24 months in the lateral compartment of Beagle dog knees. Contralateral knees were meniscectomized, or left intact and served as controls. Articular cartilage degeneration was evaluated in detail using India ink staining, routine histology, immunochemistry for denatured (Col2-¾M) and cleaved (Col2-¾Cshort) type II collagen, Mankin’s grading system, and cartilage thickness measurements. Results: Histologically, fibrillation and substantial immunohistochemical staining for both denatured and cleaved type II collagen were found in all three treatment groups. The cartilage of the three groups showed identical degradation patterns. In the 24 months implant group, degradation appeared to be more severe when compared to the 6 months implant group and meniscectomy group. Significantly more cartilage damage (India ink staining, Mankin’s grading system, and cartilage thickness measurements) was found in the 24 months implant group compared to the 6 months implant group and meniscectomy group. Conclusion: Degradation of the cartilage matrix was the result of both mechanical overloading as well as localized cell-mediated degradation. The degeneration patterns were highly variable between animals. Clinical application of a porous polymer implant for total meniscus replacement is not supported by this study.

The highly accurate anteriolateral portal for injecting the knee

<p>Abstract</p> <p>Background</p> <p>The extended knee lateral midpatellar portal for intraarticular injection of the knee is accurate but is not practical for all patients. We hypothesized that a modified anteriolateral portal where the synovial membrane of the medial femoral condyle is the target would be highly accurate and effective for intraarticular injection of the knee.</p> <p>Methods</p> <p>83 subjects with non-effusive osteoarthritis of the knee were randomized to intraarticular injection using the modified anteriolateral bent knee versus the standard lateral midpatellar portal. After hydrodissection of the synovial membrane with lidocaine using a mechanical syringe (reciprocating procedure device), 80 mg of triamcinolone acetonide were injected into the knee with a 2.0-in (5.1-cm) 21-gauge needle. Baseline pain, procedural pain, and pain at outcome (2 weeks and 6 months) were determined with the 10 cm Visual Analogue Pain Score (VAS). The accuracy of needle placement was determined by sonographic imaging.</p> <p>Results</p> <p>The lateral midpatellar and anteriolateral portals resulted in equivalent clinical outcomes including procedural pain (VAS midpatellar: 4.6 ± 3.1 cm; anteriolateral: 4.8 ± 3.2 cm; p = 0.77), pain at outcome (VAS midpatellar: 2.6 ± 2.8 cm; anteriolateral: 1.7 ± 2.3 cm; p = 0.11), responders (midpatellar: 45%; anteriolateral: 56%; p = 0.33), duration of therapeutic effect (midpatellar: 3.9 ± 2.4 months; anteriolateral: 4.1 ± 2.2 months; p = 0.69), and time to next procedure (midpatellar: 7.3 ± 3.3 months; anteriolateral: 7.7 ± 3.7 months; p = 0.71). The anteriolateral portal was 97% accurate by real-time ultrasound imaging.</p> <p>Conclusion</p> <p>The modified anteriolateral bent knee portal is an effective, accurate, and equivalent alternative to the standard lateral midpatellar portal for intraarticular injection of the knee.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00651625">NCT00651625</a></p

Androgen Receptor Function Links Human Sexual Dimorphism to DNA Methylation

Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aber