What is known about the epidemiology of the vasculitides?

The vasculitides are conditions of unknown aetiology. Until recently, relatively little was known about their incidence and prevalence, but there are now increasing data, especially from Europe. These are conditions of the extremes of age. Kawasaki disease occurs predominately in Asian children, with a peak annual incidence of 90/100,000 children aged under 5 years. Henoch-Schonlein purpura has an incidence of 70/100,000 in those aged 4-7 years and is also more common in Asians. Primary systemic vasculitis has a peak incidence 6/100,000 in those aged 65-74 years. Giant cell arteritis is most common in Caucasians aged over 70 years, with an incidence of 53/100,000. Vasculitis has been associated with malignancy, the association being strongest between haematological malignancies and cutaneous vasculitis. There is occasionally a temporal association; failure to respond appropriately to therapy should prompt a search for malignancy. Lesions suspicious of malignancy should be biopsied even if the diagnosis of vasculitis has been histologically proven.     

Epidemiology of large-vessel vasculidities

The systemic vasculitides are multisystem disorders characterised by the inflammation of blood vessels and tissue necrosis. Classified by the size of the vessels affected, the large vessel vasculitides include giant cell arteritis (GCA) and Takayasu's arteritis (TA). These are anatomically, epidemiologically and clinically distinct conditions. They are often associated with considerable morbidity and mortality. The classification of vasculitis has been an area of controversy for many years and current classification criteria remain suboptimal. Although intensive efforts are under way to improve them, a further understanding of the aetiology and pathogenesis of these diseases is required to develop more sensitive and specific diagnostic tests. These efforts, however, have been hampered by the low prevalence of these diseases. The establishment of national and international registries is encouraged to enhance valuable data collection. These are anatomically, epidemiologically and clinically distinct conditions. This article summarises the current classification systems for systemic vasculitis and their limitations. We also review the presently known epidemiology, risk factors and morbidity and mortality associated with GCA and TA.     

Epidemiology of the vasculitides

The epidemiology of systemic vasculitis is becoming increasingly well understood. Giant cell arteritis is the commonest type of vasculitis with an incidence that is highest in populations of Scandinavian descent, where the annual incidence reaches 15 to 35/100,000 aged > 50 years. Takayasu's arteritis has a relatively uniform global incidence of one to two/million. The ANCA-associated vasculitides have an overall incidence of 20/million with a peak age of onset at 65 to 74 years. Wegener's granulomatosis appears to be more common in northern Europe compared with microscopic polyangiitis, which seems to be more common in southern Europe. Henoch-Sch?nlein purpura is the commonest form of childhood vasculitis in the West with an incidence of 20/100,000 aged < 17 years, but it is much rarer in adults (13/million). Kawasaki disease is commonest in the childhood population of southeast Asia; in Japan the incidence is 500/million aged < 5 years, 50% of cases occur in those aged < 2 years. Beh?et's disease occurs along the Silk Road and in the Mediterranean littoral with a prevalence in Turkey of 380/100,000. The various types of vasculitis have very different geographical and ethnic distributions, which provide clues to the pathogenesis.     

Therapy insight: The recognition and treatment of retinal manifestations of systemic vasculitis

A variety of retinal signs can occur in patients who have systemic vasculitides, or who experience complications of these diseases or their treatment. Although treatment of these retinal manifestations is usually the treatment of the systemic disease, specific treatment is occasionally indicated to preserve vision. The more prevalent of the systemic vasculitides are giant cell arteritis, polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and systemic lupus erythematosus. Less frequently occurring vasculitides include Takayasu's arteritis, Goodpasture's disease, microscopic polyangiitis and Henoch-Sch?nlein purpura, as well as vasculitis secondary to scleroderma and rheumatoid arthritis. This article describes the pathogenesis, clinical features and treatment of retinal manifestations of systemic vasculitides.     

Difficult to diagnose manifestations of vasculitis: does an interdisciplinary approach help?

In the early stages of disease, primary systemic vasculitides often present with non-specific symptoms that make early diagnosis a challenge. The variety of clinical manifestations found in systemic vasculitis is huge, and some manifestations are frequently not clinically overt at first presentation. A logical implication of the often non-specific and sometimes subclinical presentation of vasculitis is that a systematic diagnostic work-up is necessary. This requires a multidisciplinary approach involving the expert opinion of specialists from many disciplines, such as neurology, radiology, respiratory medicine, pathology and microbiology. There are no generally accepted diagnostic criteria for primary systemic vasculitides, and the application of classification criteria as diagnostic criteria is not feasible and may even be misleading. The demonstration of vasculitis on biopsy is still the gold standard for the diagnosis of vasculitis. In cases where biopsies cannot be obtained, surrogate parameters of vasculitis (e.g. glomerular hematuria or mononeuritis multiplex), along with serology and imaging, can support a clinical diagnosis of vasculitis. This review discusses the approach to the diagnosis of central nervous system and pulmonary manifestations of primary systemic vasculitis. These two examples of difficult to diagnose manifestations of vasculitis illustrate the necessity of an interdisciplinary approach to the diagnostic work-up.     

Do vasculitis categorization systems really matter?

The diagnosis of systemic vasculitides is challenging for many reasons. The etiology and pathogenesis of most vasculitides are unknown or incompletely known. Vasculitides have protean and overlapping clinical and pathologic features. There are conflicting if not contradictory approaches to diagnostic categorization. In spite of these challenges, precise diagnostic categorization is essential for appropriate treatment. This overview reviews the history behind the modern approach to diagnosis of selected vasculitides, including giant cell arteritis, Takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Evidence is provided that the categorization for systemic vasculitis really does matter.     

Systemic vasculitis in adults in northwestern Spain, 1988-1997. Clinical and epidemiologic aspects.

The vasculitides constitute a heterogeneous group of diseases characterized by blood vessel inflammation and necrosis with different but frequently overlapping clinical and pathologic manifestations. The incidence of these conditions is frequently controversial. To further investigate the incidence and clinical manifestations of vasculitides, we reviewed the spectrum of these diseases in an unselected population of adults (age > 20 years) from northwestern Spain during a 10-year period. From January 1988 through December 1997, 267 adults were diagnosed as having vasculitis. The overall average annual incidence rate of vasculitis in the region of Lugo, Spain, between 1988 and 1997 for the population older than 20 years was 141.54/million. Primary vasculitis (115.04/million for the population older than 20 years; 81.3%), especially giant cell arteritis (GCA) was the most common group. Small vessel primary vasculitis (hypersensitivity vasculitis and Henoch-Sch?nlein purpura) was the second most common group. Both GCA and small vessel primary vasculitis had a good outcome. However, although less common, patients with medium and small vessel primary vasculitis, in particular those with polyarteritis nodosa, had a high mortality related to the systemic manifestations of the disease or to the immunosuppressive therapy. Among the group of adults with secondary vasculitis (26.51/million; 18.7%), rheumatic diseases and specifically those occurring in the context of rheumatoid arthritis were the most common group. Patients with secondary vasculitis had clinical or laboratory data that may suggest the presence of an underlying disease. In summary, systemic vasculitides are somewhat more common than previously considered. As in other western countries, GCA constitutes the most common type of vasculitis in northwestern Spain. Better physician awareness may contribute to the progressive increase in the recognition of these conditions.     

Ophthalmological diagnosis in systemic vasculitis

Ocular manifestations of systemic vasculitides are extraordinarily pleomorph and have been described for many decades. In the introduction the special interaction of the immune system and the eye is outlined. Thereafter diagnostic procedures of patients suffering from systemic vasculitides are shown from an ophthalmological view point. Many examples, which show multiple possibilities of ocular manifestations on systemic vasculitides, are given. With regard to the anatomy of the eye, a review is given on the involvement of the 1) outer eye and a tear film, 2) lacrimal duct diseases, 3) diseases of the lid, 4) diseases of conjunctiva, 5) diseases of sclera, 6) diseases of the cornea, 7) diseases of the lens, 8) intraocular inflammation, 9) retinal affections, 10) optic nerve inflammation, and 11) orbiota involvement. Frequencies of these structures involved in the various systemic vasculitides are outlined. Principally every systemic vasculitis can induce every eye manifestation; however, larger patient groups show characteristic features of eye manifestations in systemic vasculitides. Special reference is given to Wegener's granulomatosis, giant-cell arteritis and Behcet vasculitis.     

Introduction,epidemiology and classification of vasculitis

Classification of the vasculitides has been traditionally based on vessel size. The American College of Rheumatology (ACR) criteria were developed in the 1980s and published in 1990 before the development of ANCA testing and modern imaging techniques such as MRI and PET scanning, and therefore, these criteria are not fit for use in 2010s. The Chapel Hill Consensus Conference provided a framework for defining various types of vasculitis. In the next two years, new classification criteria will be published from the DCVAS study, which will provide a modern system for the classification of vasculitis for clinical studies.The epidemiology of vasculitides is increasingly well studied; however, there remain gaps in our knowledge of the occurrence of vasculitis in many populations, especially from the third world or those with health care systems that do not permit ready collection of accurate epidemiological data. Giant cell arteritis presents in the elderly and those of Northern European ancestry; ANCA-associated vasculitis appears to have a consistent overall occurrence, but there are differences in the occurrence of MPO and PR3 vasculitis between populations. Kawasaki disease occurs most commonly in Asian populations, especially Japanese, and in those aged less than 5 years. It is currently the most common cause of acquired cardiac disease in those populations.     

Imaging procedures in rheumatology: imaging in vasculitis

In small vessel vasculitides, imaging studies aid in determining disease extent and activity, localization for biopsy, and for disease monitoring. They do not directly delineate the vasculitic lesion. Imaging studies focus on the upper and lower respiratory tract. Cranial magnetic resonance imaging (MRI) shows upper respiratory and retrobulbar granuloma in Wegener's granulomatosis. Furthermore, MRI depicts both mastoiditis and mucosal inflammation of the ear, nose, and throat. It is sensitive but not specific for the detection of cerebral vasculitis. Computed tomography (CT) reliably detects osseous facial lesions. Chest radiography in two planes remains the standard method of investigation for the lower respiratory tract. High-resolution CT aids in detecting further interstitial pathologies. Medium-sized vasculitides frequently occur with aneurysms. The classification criteria for polyarteritis nodosa involve the angiographic detection of visceral aneurysms. Patients with Kawasaki disease may develop coronary aneurysms that may be described by echocardiography or angiography according to diagnostic criteria. In large-vessel vasculitides such as temporal arteritis (giant cell arteritis) and Takayasu arteritis, MRI, MR-angiography, CT, CT-angiography, and duplex sonography delineate characteristic homogenous wall thickening with or without stenoses in the aorta and other arteries. There is a high correlation with angiography and positron emission tomography. Duplex sonography of the temporal arteries has a high sensitivity and specificity for the diagnosis. Data on temporal artery MRI in giant cell arteritis have recently been published.     

Systemic vasculitides

The vasculitides are a heterogeneous group of diseases that are characterized by blood vessel inflammation and necrosis. They have a wide spectrum of manifestations due to the involvement of arteries and other vessels of various sizes and locations. Classification criteria are useful in improving our understanding of the epidemiology of these conditions but they are not diagnostic criteria. In recent years a progressive increase in incidence has been reported. Both giant cell arteritis and Wegener's granulomatosis are more common in the Northern hemisphere. Environmental factors have been implicated in the pathogenesis of these syndromes. Recent studies in patients with large and small-sized vasculitides support a genetic influence in disease susceptibility. They have confirmed the association of giant cell arteritis and Henoch-Sch?nlein purpura with HLA-DRB1 alleles. Moreover, the polymorphisms of other genes, such as interleukin-1 receptor antagonist, seem to be implicated in disease severity in patients with cutaneous vasculitis.     

A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature

OBJECTIVE: To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. METHODS: To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month's duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). RESULTS: The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener's granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Sch?nlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener's granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. CONCLUSIONS: The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener's granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener's granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener's patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.     

Pathogenesis: immunogenetic factors

The occurrence, albeit infrequent, of systemic vasculitis in closely related family members suggests that both environmental and genetic factors may play a role in the pathogenesis of these diseases. Malfunction of immune regulation in the systemic vasculitides may indicate a role for genes that encode molecules critical to the immune responses. The extremely polymorphic sequences of MHC molecules may provide a structural basis for associations of MHC genes and systemic vasculitis. This review summarizes recent reports of MHC associations, mechanisms by which MHC may play a role in certain vasculitides, and also examines the role for genes encoding non-MHC molecules, such as Fcgamma receptors, cytokines and T cell co-stimulators. Data suggest that the pathogenesis of systemic vasculitides such as giant-cell arteritis, Takayasu's arteritis and Wegener's granulomatosis might be governed by multiple genes encoding host defence molecules, in conjunction with environmental factors.     

Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010

Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4–7.0), idiopathic inflammatory myopathies 1.9 (0.5–5.0), systemic sclerosis 4.4 (2.0–8.3), mixed connective tissue disease 1.0 (0.1–3.5), Sjögren’s syndrome 10.7 (6.7–16.1) and undifferentiated connective tissue disease 13.6 (9.0–19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3–4.3), central nervous system vasculitis 0.5 (0–2.7) and Henoch-Schönlein purpura 1.5 (0.3–4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2–14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.     

Neues zur Pathogenese prim?r systemischer Immunvaskulitiden

Primary systemic vasculitides are defined according immunopathological features and the size of the involved vessels. Three anti-neutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitides (Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis) can be distinguished from the so-called Non-ANCA-associated vasculitides, i.e. granulomatous vasculitides of large vessels (giant cell arteritis, Takayasu arteritis) and immune complex-mediated vasculitides of medium-sized and small vessels (Polyarteriitis nodosa, Kawasaki disease and Henoch-Schönlein purpura, cryoglobulinemic vasculitis, cutaneous leukocytoklastische angiitis). Predisposing genetic and other endogenous and exogenous factors facilitate the activation of innate immunity and induce persisting inflammatory reactions resulting in different forms of (auto)-immune vasculitides.     

Vasculitis of the central nervous system

Central nervous system (CNS) vasculitis occurs in a variety of clinical settings. Some exhibit a distinct age preference; others a tissue tropism. Most frequently encountered are giant cell arteritis (temporal arteritis) and vasculitis secondary to infections. The CNS may be involved in the systemic vasculitides, and neurologic abnormalities occasionally appear as a presenting manifestation of disease. Isolated angiitis of the CNS, a rare form of vasculitis restricted to the CNS, must be distinguished from other causes of CNS inflammation and from noninflammatory vascular disease. We are learning a great deal about the cellular mechanisms of vascular inflammation in the brain. Some manifestations of the clinical disease result from histologic features of the infiltrate and the size of affected vessel. However, the local consequences of inflammation such as increased coagulation and altered vasomotor tone, as well as the systemic consequences such as activation of the central noradrenergic systems, trigeminovascular system, and hypothalamic pituitary adrenal axis contribute to both pathogenesis of disease and recovery. Two central issues that confront us now are improving the accuracy of the diagnosis (including identifying any underlying infectious causes) and limiting the long-term damage both from disease and its therapies.     

Hautmanifestationen der verschiedenen Vaskulitiden

The skin not only represents the organ which often reveals the first signs of systemic vasculitis, but also the organ which is most frequently involved in vasculitis. These diseases encompass systemic vasculitides and those which appear to involve the skin only. Among those vasculitides restricted to the skin, some are yet typically associated with other systemic diseases, such as nodular vasculitis, which often occurs during infections by M. tuberculosis, or erythema elevatum diutinum in patients with gammopathy. The type and localization of skin lesions give valuable indications as to the type of vasculitis. Subcutaneous nodules which ulcerate and are surrounded by livedo racemosa are suggestive of polyarteritis nodosa, a palpable purpura with predilection for the lower legs is almost pathognomonic for immune complex vasculitis (e.g. IgA vasculitis or cutaneous leukocytoclastic vasculitis), hemorrhagic papules and necrotic plaques which occur in acral areas after cooling indicate cryoglobulinemic vasculitis, hemorrhagic papules and macules which develop in patients who start to feel worse and develop fever should arouse suspicion of septic vasulitis, while the simultaneous presence of ulcerating nodules and hemorrhagic papules without predilection for the lower legs will suggest ANCA-associated vasculitis. The different morphology of the cutaneous signs of the various vasculitides depends to a large extent on the size of the vessels primarily involved. In this review the cutaneous signs of vasculitides will be presented with reference to the revised nomenclature of the Chapel Hill Consensus Conference from 2012.     

Different epidemiologic profiles of systemic vasculitis between Brazil and Peru—preliminary results in two referral centers from both countries

Clinical Rheumatology - Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two...     

Technology Insight: the role of color and power Doppler ultrasonography in rheumatology

An increasing number of rheumatologists have access to ultrasound equipment that provide both color and power Doppler modes, which can be used to investigate musculoskeletal and vascular pathologies. Musculoskeletal Doppler ultrasonography can be used to estimate levels of inflammation, to document the anti-inflammatory effect of agents such as corticosteroids and tumor necrosis factor inhibitors, to differentiate between inflammatory and degenerative disease, and to distinguish between normal and inflamed joints in cases of minor synovial swelling. Vascular Doppler ultrasonography can be used to determine organ involvement in small-vessel vasculitides, to delineate aneurysms in vasculitides of medium-sized arteries, and to assess the characteristic findings in large-vessel vasculitis. Numerous studies, including a meta-analysis, have been published on the use of temporal-artery ultrasonography for the diagnosis of giant cell arteritis. Duplex ultrasonography is a sensitive approach for detecting characteristic edematous wall swellings in active temporal arteritis and for assessing vasculitis of the axillary arteries (large-vessel giant cell arteritis) in patients with suspected temporal arteritis, polymyalgia rheumatica, or fever of unknown origin. Duplex ultrasonography can also be used to assess vasculitis of subclavian and carotid arteries in younger patients with Takayasu's arteritis and acute finger artery occlusions in patients with small-vessel vasculitides.     

Use of ultrasonography and positron emission tomography in the diagnosis and assessment of large-vessel vasculitis

PURPOSE OF REVIEW: Ultrasonography and positron emission tomography have been increasingly studied and, in part, introduced in clinical practice to diagnose large-vessel vasculitides, such as temporal arteritis, Takayasu arteritis, large-vessel giant cell arteritis, and isolated aortitis. RECENT FINDINGS: Ultrasonography reveals characteristic homogenous, concentric wall thickening in vasculitis, often combined with stenoses and, less frequently, with acute occlusions. Thirteen studies describe sensitivities of 40 to 100% (median, 86%) for temporal artery vessel wall edema compared with histology, and of 35 to 86% (median, 70%) compared with clinical diagnosis. If wall edema, stenoses, and occlusions are included, sensitivities increase to 91 to 100% (median, 95%) compared with histology, and to 83 to 100% (median, 88%) compared with clinical diagnosis. Specificities for wall edema are 68 to 100% (median, 93%) compared with histology, and 78 to 100% (median, 97%) compared with clinical diagnosis. One should be aware of large-vessel giant cell arteritis in all patients with temporal arteritis and polymyalgia rheumatica. Ultrasonography reveals characteristic wall thickening, particularly of the distal subclavian, axillary, and proximal brachial arteries. Findings in Takayasu arteritis are similar, but the vessel wall swelling is usually brighter. Positron emission tomography reveals vasculitis in arteries with a diameter of more than 4 mm. Ultrasonography and positron emission tomography agreed completely in the anatomic distribution of changes in patients with large-vessel giant cell arteritis. It reveals asymptomatic large-vessel vasculitis in giant cell arteritis and Takayasu arteritis. Positron emission tomography is not suitable for the assessment of temporal arteries. SUMMARY: Ultrasonography and positron emission tomography are new, promising techniques to assess large-vessel vasculitides.