Vasculitides may involve small, medium-sized or large arteries. In small-vessel vasculitides imaging studies of lungs, nasal sinuses, cerebrum, heart and other organs are important for determining disease extension and disease activity. Aneurysms are a hallmark of medium-sized artery vasculitides. In large-vessel vasculitis, imaging studies depict homogeneous, circumferential wall swelling and smoothly tapered luminal narrowing. Ultrasound and high-resolution magnetic resonance imaging (MRI) show characteristic wall abnormalities in temporal and occipital arteries whereas ultrasound, MRI, MR angiography, computed tomography (CT), CT angiography and positron emission tomography delineate characteristic features in extra-cranial arteries that are affected in large-vessel giant cell arteritis, Takayasu arteritis and idiopathic aortitis. Conventional angiography has still its place for therapeutic interventions. Imaging has led to a better understanding of the nature and distribution of vasculitides. It significantly facilitates diagnosis of patients with suspected vasculitis.

The systemic vasculitides are a diverse set of diseases linked by the presence of blood-vessel inflammation and are often associated with life-threatening or critical complications, including glomerulonephritis, diffuse alveolar haemorrhage, pulmonary arterial hypertension and airway compromise. The protean manifestations of the systemic vasculitides make them challenging to diagnose. Early recognition, however, is crucial to improving outcomes. This article serves as an introduction to these complex diseases, reviewing the manifestations of systemic vasculitis that may be encountered in an intensive care setting, and outlines an overall approach to their treatment.

Despite the rarity of vasculitides, fertility and pregnancy outcome in the setting of vasculitis have become a major topic of interest within the past decade. The potential impact of vasculitis therapies, particularly cyclophosphamide, has been examined to some extent, but data are limited on the possible impact of the disease itself on fertility. Ideally, pregnancy should be planned when the vasculitis is in remission. The outcome for mothers and newborns is usually good when vasculitis is known before the pregnancy and is in remission, but every pregnant woman must be monitored by a specialised health-care team consisting of obstetricians specialised in high-risk births and internists/rheumatologists with expertise in managing these rare conditions. Most maternal complications during pregnancy are indeed due to vasculitis damage: hypertension in Takayasu arteritis (TAK) or granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA) with renal insufficiency, asthma or cardiac damage in eosinophilic granulomatosis with polyangiitis (EGPA) and subglottic and/or bronchial stenosis(es) in GPA. Pregnancy loss can occur in about 10% of cases in GPA, up to 20% in EGPA, 20-30% in Behçet's disease and up to 25% in TAK, and several studies found high rates of preterm births, at least with some vasculitides. Vasculitis manifestations in newborns from mothers with known vasculitis are very rare and usually transient.

The primary vasculitides are a life- and organ-threatening set of diseases with a course often marked by alternating periods of active vasculitis and remission. As opposed to clinical trials within the fields of cardiology and oncology, where treatment interventions have been tested in a controlled fashion using hard 'end' points, such as mortality and hospitalisation, surrogate 'end' points have to be used in randomised clinical trials (RCTs) in vasculitis. Given the multisystem nature of the vasculitides, their heterogeneous clinical presentations and rarity, outcome-measure development is a challenging task. The objective of this review is to summarise the data on how health-related quality of life is affected by vasculitis, to describe the currently used outcome measures and provide insight into future outcome-measures development. The primary focus is on anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, where the most data exist and outcome measure development is farthest along. Data on other vasculitides will also be briefly discussed.

Thrombo-embolic disease is an increasingly recognised complication of several vasculitides. A common observation is that thrombo-embolic complications coincide with periods of increased vasculitis disease activity, but the mechanism through which this happens is still unknown. Thrombo-embolic disease has been recognised for decades as a significant contributor to the morbidity and mortality of Behçet's disease, and the role of anticoagulation in its management is being minimised in favour of immunosuppression, although evidence from randomised controlled trials is lacking. Ancillary data from a randomised clinical trial and retrospective observational studies have confirmed an association between venous thrombo-embolic disease and vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCAs). An increased cardiovascular risk is now also recognised for vasculitides associated with ANCAs. Thrombosis plays a prominent role in the pathogenesis of thromboangiitis obliterans (Buerger's disease). The association of thrombosis with other vasculitides such as giant-cell arteritis and levamisole-induced vasculopathy is under investigation.

In this review, we summarise the current understanding of the potential link between cancer and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (Wegener's; GPA) and microscopic polyangiitis (MPA). As is true for many autoimmune or inflammatory rheumatic diseases, AAV diagnosis and therapy are associated with an increased risk of de novo cancer development, likely as a result of impaired immunosurveillance, direct oncogenicity of immunosuppressive agents and perhaps malignant degeneration of tissues undergoing chronic immune stimulation. Data from several studies suggest a standardised incidence ratio of cancer in AAV of 1.6-2.0 compared to the general population and a possibly higher risk in GPA than in MPA. The most prominent cancers observed in AAV include urinary tract cancer, leukaemia and non-melanoma skin cancer. The effect of individual therapeutic agents is difficult to dissect, but cyclophosphamide has emerged as a major contributor to cancer development because of its direct carcinogenic properties. Awareness of cancer risk in AAV calls for increased implementation of measures to prevent or screen for cancer and development of less carcinogenic therapies. Cancer has also been suggested as a potential trigger or cause of AAV. Although some studies found that prior or concomitant history of cancer increases the risk of AAV, available data are inconsistent and suggest that the fraction of AAV that might be attributable to cancer is at best small.

Patients with different forms of systemic vasculitis experience long-term morbidity and mortality caused by cardiovascular disease due to premature atherosclerosis. Epidemiologic reports of patients with GCA suggest that long-term mortality in this disease is not increased compared with the general population of the same age. The risk of a stroke, however, in particular in the vertebrobasilar territory, is increased. In addition, the occurrence of aortic aneurysmal disease and aortic dissection is also clearly increased in GCA. Mortality due to ischaemic heart disease, however, is not increased. In Takayasu arteritis accelerated atherosclerosis has been clearly documented both clinically and in autopsy reports. Atherosclerotic plaques in the carotid artery may be present in the carotid arteries especially in patients with a documented history of arteritis involving the carotid artery. It is controversial whether Kawasaki disease is associated with accelerated atherosclerosis. Young adults with a history of Kawasaki disease may have abnormal brachial artery reactivity, increased carotid IMT values and increased arterial stiffness. At autopsy examinations of KD patients, however, no significant atherosclerotic lesions are detected and carotid IMT measurements were found to be clearly different from those in young adults with familiar hypercholesterolaemia, suggesting that the remodeling process in KD is different from atherosclerosis. In ANCA-associated vasculitis (AAV), an increased mortality as a consequence of cardiovascular disease is well-documented. In these patients the relative risk for coronary heart disease is two- to fourfold that in control subjects. In addition, a similar relative risk has been found for stroke. Diabetes, hypertension, dyslipidemia, abdominal obesity (metabolic syndrome), impaired renal function, persistent proteinuria and increased production of C-reactive protein are common risk factors for premature atherosclerosis in patients with systemic vasculitis. Furthermore, cholesterol and its modifications play a pivotal role in the pathogenesis of accelerated atherosclerosis in vasculitis. The (preventive) therapy for accelerated atherosclerosis in systemic vasculitis is based on an aggressive approach against inflammation and against risk factors of premature atherosclerosis such as smoking, inactivity, obesity and unhealthy diet. In addition, patients should be treated with angiotensin-converting enzyme inhibitors and/or angiotensin receptor-1 blockers for hypertension and statins for dyslipidemia. Finally, low dose acetylsalicylic acid should be prescribed in patients with large vessel vasculitis, i.e., both in GCA and TA, who do not have contraindications for ASA.

Infections, mainly viral, are the cause of some vasculitides, like polyarteritis nodosa (hepatitis B virus) or mixed cryoglobulinemia (hepatitis C virus), and it has been hypothesized that others might be due to infectious agents (HIV, EBV, parvovirus...). Among etiologies of vasculitis, the responsibility of a Burkholderia-like strain has been recently demonstrated as the cause of giant-cell arteritis. On the other hand, patients frequently develop infections, mainly as a consequence of steroids, immunosuppressants and most immunomodulating treatments prescribed to treat vasculitides. Infections occur when patients receive steroids and immunosuppressants, especially in the long term. They are more frequently observed in elderly patients or in patients with poor general condition. Infection risk is not reduced when biotherapies are prescribed to induce or maintain remission. Patients, considered at higher risk for infections, should be followed closely and their immunological status monitored periodically. We recommend especially to monitor neutrophiles, lymphocytes and if needed CD3-, CD4- and CD8-cell counts in patients receiving steroids and cyclophosphamide or other cytotoxic agents. In patients treated with rituximab, CD19 and gammaglobulins should be monitored regularly. Prophylaxis are needed in patients at risk to develop infections.

Classification criteria have an important role and practical use in everyday rheumatology. Improvement in therapy and our understanding of the aetiopathogenesis of vasculitis have driven the need to have better descriptors and groupings of diseases. This in turn will allow newer therapy and further understanding to have a greater impact. The American College of Rheumatology (ACR) classification criteria have been an important advance but have limitations. There remains confusion between classification and diagnostic criteria and definitions. We hope to resolve this using evidence-based improvements in classification and diagnostic criteria. Further understanding of the underlying causative mechanisms could lead to diagnostic testing, eliminating the need for classification criteria.