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

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 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

Pretomanid for tuberculosis treatment: an update for clinical purposes

Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB

Comparison of three treatment protocols with intra-articular low or intermediate molecular weight hyaluronic acid in early symptomatic knee osteoarthritis

Introduction: Viscosupplementation with hyaluronic acid (HA) is indicated for non-responders to non-pharmacological therapy, to analgesics or when non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated. The aim of this study is to compare the efficacy, safety and costs of three different HA treatments (Sinovial® Forte, sinovial one and hyalgan). Patients and methods: Ninety patients with grade I/II Kellgren–Lawrence knee osteoarthritis were included in three groups, the first was treated with hyalgan (weekly for 5 weeks), the second with Sinovial® Forte (weekly for 3 weeks) and the third group with a single injection of sinovial one. Results: All three treatments were effective, with an average reduction in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score of 18.9 points for hyalgan, 18.04 points for Sinovial® Forte and 17.92 points for sinovial one. The comparison of the three groups did not show any statistical difference in terms of efficacy. National health system (NHS) and social costs are, respectively, €419.12 and €853.43 for hyalgan, €338.64 and €599.22 for Sinovial® Forte, €221.56 and €308.42 for sinovial one. Conclusion: All three treatments were equally effective with no statistically significant differences; thus, the treatment with sinovial one may be considered as clinically effective as the other two regimens, but with a very efficient cost profile in early symptomatic knee osteoarthritis

Tenascin expression in normal and pathological conditions of the musculoskeletal system

Tenascin is an extracellular matrix protein with highly regulated expression and uncertain functions. It is prominently expressed during musculoskeletal embryogenesis. The pattern of distribution of tenascin in healthy adult musculoskeletal tissues is spatially and temporally restricted. It can be only detected in a small amount in the muscle-tendon junctions, tendons, perichondrium, periosteum, endosteum, the superficial layer of articular cartilage and the subintimal connective tissue of synovium. Elevated tenascin expression is found in inflammatory, degenerative and neoplastic lesions of the musculoskeletal system. The peculiar pattern of tenascin expression suggests it may play a role in the regulation of cell behavior at the interfaces between different elements of the musculoskeletal system and in various pathological processes, in particular those involving attachment and or detachment of cells from the extracellular matrix and their proliferation and collagenase secretion.Biomedical Reviews 1996; 6: 83-94

Systematic analysis of the literature in search of defining systemic sclerosis subsets

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. METHODS: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions. RESULTS: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. CONCLUSION: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting