Management Of Systemic Vasculitis Research Articles

Management of primary vasculitides with biologic and novel small molecule medications.

Vasculitides can affect small, medium and/or large vessels, leading to end-organ damage, decreased quality of life and death. Glucocorticoids remain the backbone of treatment for systemic vasculitis but are associated with numerous toxicities. In recent years, the efficacy of glucocorticoid-sparing biologic and novel small molecule therapies has been demonstrated. In giant cell arteritis, tocilizumab was superior to glucocorticoid monotherapy in maintenance remission and cumulative glucocorticoid exposure and is now approved for the treatment of giant cell arteritis. In addition to the previously demonstrated efficacy of rituximab for remission induction in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, recent trials have also demonstrated its superiority for remission maintenance compared to alternative approaches. Mepolizumab is superior to standard of care alone with regard to remission rates and glucocorticoid-sparing effect in refractory eosinophilic granulomatosis with polyangiitis. Avacopan has shown significant promise in ANCA-associated vasculitis as part of a glucocorticoid-free induction regimen in a recently completed phase 3 trial. Use of biologics in rarer vasculitides remains guided by reports from small case series. Biologics and other novel therapies have an increasingly important role in the management of systemic vasculitis. Additional studies are needed to define their optimal use and to guide their use in more rare forms of vasculitis.

The Role of 18F Fluorodeoxyglucose Positron Emission Tomography Scanning in the Diagnosis and Management of Systemic Vasculitis.

Primary systemic vasculitis is a group of heterogeneous disorders, characterized by inflammation of blood vessels causing end organ damage from ischemia, aneurysm formation or dissection. Delay in the early diagnosis owing to non-specific symptoms, lack of definitive serological tests, limited availability of biopsy and standard imaging tests pose significant challenge in the management of these diseases. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning is being increasingly used in the management of systemic vasculitis, especially the large vessel vasculitides: giant cell arteritis (GCA) and Takayasu arteritis (TAK). FDG-PET involves detection of positron rays emitted by FDG, a fluorinated glucose analogue which is avidly taken up by metabolically active inflammatory cells in the walls of involved blood vessels. 18F-FDG-PET scan, especially when combined with computed tomography or magnetic resonance imaging (MRI) can give information about active inflammation as well as structural damage associated with vasculitis. In patients with GCA, FDG-PET has acceptable sensitivity and specificity for the early diagnosis in non-cranial GCA, cranial GCA with negative biopsy, assessment of immediate response to treatment, predicting prognosis, but has limited value in serial follow-up and prediction of relapses. In TAK, FDG-PET can be useful for early diagnosis and probably for serial assessment of disease activity. FDG-PET has a limited role in medium and small vessel vasculitis.

Vasculitides Throughout History and Their Clinical Treatment Today

Therapeutic management of the vasculitides is closely linked to modern rheumatologic advances, particularly as it relates to the discovery and first clinical use of glucocorticoids. These compounds were introduced in the late-1940s for the treatment of rheumatoid arthritis, but soon after, clinicians in Europe and the United States realized that they could have a significant positive impact in systemic vasculitides. However, once it was realized that glucocorticoid use was associated with a high degree of morbidity, the search for better immunosuppressive agents with similar efficacy but improved safety profiles was on. During the past several years, several agents have been utilized for the therapeutic management of systemic vasculitides, and the list keeps growing with the development of newer compounds that have retained efficacy but with a better safety profile.

An approach to the diagnosis and management of systemic vasculitis.

The systemic vasculitides are a complex and often serious group of disorders which, while uncommon, require careful management in order to ensure optimal outcome. In most cases there is no known cause. Multi-system disease is likely to be fatal without judicious use of immunosuppression. A prompt diagnosis is necessary to preserve organ function. Comprehensive and repeated disease assessment is a necessary basis for planning therapy and modification of treatment protocols according to response. Therapies typically include glucocorticoids and, especially for small and medium vessel vasculitis, an effective immunosuppressive agent. Cyclophosphamide is currently the standard therapy for small vessel multi-system vasculitis, but other agents are now being evaluated in large randomized trials. Comorbidity is common in patients with vasculitis, including the cumulative effects of potentially toxic therapy. Long-term evaluation of patients is important in order to detect and manage relapses.

Current State of Biologicals in the Management of Systemic Vasculitis

Conventional immunosuppressive treatment of systemic vasculitides has improved their often fatal outcome, but is burdened by cytotoxic side effects and frequent relapses. Recent advances in the therapy of systemic vasculitides with biologicals have helped to establish new options for patients resistant to conventional treatment. Moreover, early intervention aiming to interfere with specific targets important in the break of tolerance and/or persistence of the autoimmune response might further improve the prognosis of autoimmune vasculitides such as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). In vitro and in vivo studies suggest that the interaction of ANCA and cytokine (TNF-alpha, IL-1)-primed neutrophils results in premature neutrophil activation and degranulation, subsequent endothelial cell damage, and further leukocyte recruitment. For one of the AAV, Wegener's granulomatosis, recent ex vivo data have provided evidence that WG-granulomata might provide the necessary "proinflammatory environment" for the break of tolerance and display features of lymphoid-like tissue neoformation, in which autoimmunity to "Wegener's autoantigen" proteinase 3 PR3 could be sustained. Blocking TNF-alpha and eliminating autoreactive B cells seem promising treatment targets to interfere with these fundamental disease processes. While the recombinant TNF-alpha receptor/IgG1 fusion protein etanercept, in addition to standard therapy with subsequent tapering of standard medications, was found to be not effective for maintenance of remission, open clinical studies suggest a beneficial effect of the anti-TNF-alpha antibody infliximab in addition to standard therapy for the induction of remission in patients with refractory AAV. Peripheral B cell depletion with the anti-CD20 antibody rituximab also induced remissions in AAV in uncontrolled trials.

Management of systemic vasculitis.

The systemic vasculitides are a wide-ranging group of diseases that are characterized by the presence of blood vessel inflammation. Despite this common feature, each type of vasculitis has a unique variety of clinical manifestations that influences its degree of disease severity and ultimately its management. Immunosuppressive therapy forms the foundation of treatment for almost all forms of systemic vasculitis. Because of this, treatment can be associated with its own risk of morbidity, or even mortality, related to specific medication side-effects or infections which occur as a result of impaired host defences. This chapter seeks to review the approach to management in selected forms of systemic vasculitis. Questions examined include the following. When should one treat systemic vasculitis? How does the nature of the disease and its severity affect treatment decisions? What are the data regarding the effectiveness of individual therapeutic regimens?

Management of systemic vasculitis: contribution of scintigraphic imaging to evaluation of disease activity and classification

The use of radio-isotope-labelled leucocyte scans has become established as a non-invasive and accurate means of diagnosing a variety of inflammatory conditions. We report a retrospective study on leucocyte imaging in the management of 50 patients with systemic vasculitis. Leucocyte imaging was useful for detecting unsuspected sites of disease and monitoring disease activity. Scintigraphy was superior to conventional radiography or CT scanning for detecting and monitoring vasculitic involvement of the respiratory tract. The scans were useful for differentiating between Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). There was a close and statistically significant relationship between the clinical diagnosis of WG and nasal uptake on leucocyte scans (p < 0.01), whereas in patients with MPA it was rare. Anti-proteinase 3 autoantibody specificity correlated significantly with nasal uptake of labelled leucocytes (p < 0.03). Leucocyte imaging is a useful non-invasive investigation in patients with systemic vasculitis.

Pooled intravenous immunoglobulin in the management of systemic vasculitis.

Investigation into the therapeutic use of intravenous immunoglobulin (IVIg) in systemic vasculitis was prompted by the detection of anti-idiotype antibodies reactive with ANCA in IVIg and the proven ability of IVIg to reduce the incidence of coronary artery aneurysms in Kawasaki disease. The efficacy and safety of IVIg (Sandoglobulin) was assessed in an open study of 26 patients with active systemic vasculitis. Eight weeks after IVIg 13 patients were in full and 13 in partial remission, clinical benefit was maintained in 18 twelve months later and was reflected by changes in C-reactive protein and ANCA.

Infectious complications in the management of systemic vasculitis and rapidly progressive glomerulonephritis

Patients with microscopic polyarteritis and Wegener's granulomatosis are often elderly. At present 10-20% of these patients will die from infection in the first three months of immunosuppressive treatment. Therapeutic strategies initially must maximize anti-inflammatory and immunosuppressive effects and minimize the later in the longer term. Regimens with pulse MP combined with low dose prednisolone (ie 20 mg/day), together with oral or pulsed cyclophosphamide in the first weeks followed by maintenance treatment with azathioprine and prednisolone are suggested--with PE reserved for those requiring dialysis, lung haemorrhage, or uncontrolled vasculitis.

Sequential ANCA and C‐reactive protein estimations in the management of systemic vasculitis

Sequential ANCA and C‐reactive protein estimations in the management of systemic vasculitis