Overview of and approach to the vasculitides in adults

INTRODUCTION — The vasculitides are defined by the presence of inflammatory leukocytes in vessel walls with reactive damage to mural structures. Both loss of vessel integrity leading to bleeding, and compromise of the lumen may result in downstream tissue ischemia and necrosis. In general, affected vessels vary in size, type, and location in association with the specific type of vasculitis. Vasculitis may occur as a primary process or may be secondary to another underlying disease. The exact pathogenetic mechanisms underlying these diseases are unknown.

The vasculitides are often serious and sometimes fatal diseases that require prompt recognition and therapy. Symptomatic involvement generally reflects and follows the pattern of affected organs. The distribution of affected organs may suggest a particular type of vasculitis.

This topic will review the nomenclature of the different vasculitides and provide an overview of the approach to the patient with suspected vasculitis. An overview of the treatment of these disorders and detailed discussions of the individual disorders are presented separately. (See "Overview of the management of vasculitis in adults".)

NOMENCLATURE — The disease names and definitions of the vasculitides continue to evolve as our understanding of the pathogenesis advances. The international Chapel Hill Consensus Conference (CHCC) has developed one of the most widely used nomenclature systems which specifies the names and definitions for most forms of vasculitis [1-3]. The CHCC nomenclature system has changed over the past few decades, and definitions that were put forth by the CHCC in 1994 have since been revised in the 2012 CHCC (table 1 and table 2) with a specific addendum issued to cover the many forms of vasculitis of the skin [3].

Among the notable changes in the 2012 CHCC was the preferential use and adoption of new names for several diseases, consistent with the trend of replacing eponyms with disease names that reflect an increased pathophysiologic understanding of these conditions. Among the name changes are: eosinophilic granulomatosis with polyangiitis, abbreviated EGPA, in place of Churg-Strauss syndrome; granulomatosis with polyangiitis, abbreviated GPA, in place of Wegener's granulomatosis; immunoglobulin A (IgA) vasculitis (Henoch-Schönlein), abbreviated as IgAV, in place of Henoch-Schönlein purpura (HSP); anti-C1q vasculitis as an alternative name for hypocomplementemic urticarial vasculitis, abbreviated HUV; and use of the term "cryoglobulinemic vasculitis" in place of "essential cryoglobulinemic vasculitis." Furthermore, the 2012 CHCC formally adopted the term antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) for the group of three disorders that include microscopic polyangiitis (MPA), GPA, and EGPA, with additional categories also named to describe variable-vessel vasculitis and secondary forms of vasculitis. This nomenclature system is not meant to substitute for classification criteria, which include clinical observations that classify a specific patient into a category for research purposes. (See 'Classification criteria' below.)

MAJOR CATEGORIES OF VASCULITIS — Classification of the noninfectious vasculitides is primarily based upon the predominant size of the vessels involved (figure 1), although there may be some overlap in the size of arteries involved with all these diseases. Thus, large-vessel vasculitis, as its name suggests, mostly affects large arteries. The same principle is true for the medium- and small-vessel vasculitides in which medium-vessel vasculitis predominantly affects medium arteries and small-vessel vasculitis predominantly affects small arteries and capillaries. The Chapel Hill Consensus Conference (CHCC) also recognizes that some forms of vasculitis do not involve a single predominant size of vessel (variable-vessel vasculitis).

Large-vessel vasculitis

Takayasu arteritis — Takayasu arteritis (TAK) primarily affects the aorta and its major branches. The inflammation and damage is often localized to a portion of the affected vessels, but extensive involvement such as nearly pan-aortitis can be seen. The onset of disease usually occurs before the age of 30 years. (See "Clinical features and diagnosis of Takayasu arteritis".)

Giant cell arteritis — Giant cell arteritis (GCA), also known as temporal arteritis, predominantly affects the aorta and/or its major branches, with a predilection for the branches of the carotid including the superficial temporal artery. The onset of disease usually occurs in patients older than 50, with markedly increased incidence in the eighth and ninth decades of life. (See "Clinical manifestations of giant cell arteritis".)

There are other forms of large-vessel vasculitis that either do not have a specific name, such as idiopathic isolated aortitis, or are part of another form of vasculitis or systemic inflammatory condition, such as Cogan syndrome or relapsing polychondritis. (See "Clinical manifestations of giant cell arteritis", section on 'Large vessel involvement' and "Cogan syndrome", section on 'Systemic vasculitis' and "Clinical manifestations of relapsing polychondritis", section on 'Systemic vasculitis'.)

Medium-vessel vasculitis

Polyarteritis nodosa — Polyarteritis nodosa is a systemic necrotizing vasculitis that typically affects the medium- and small-sized arteries. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults".)

Kawasaki disease — Kawasaki disease is an arteritis that predominantly affects the medium and small arteries, but the aorta and large arteries may also be involved. The disease usually occurs in children and is often associated with a mucocutaneous lymph node syndrome. The coronary arteries may also be involved. A small number of cases have also been reported in adults [4]. (See "Kawasaki disease: Clinical features and diagnosis".)

Small-vessel vasculitis

ANCA-associated vasculitis — Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis that does not substantially involve the deposition of immune complexes. AAV predominantly affects small vessels and is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). Cases of ANCA-negative AAV do occur, especially in eosinophilic granulomatosis with polyangiitis (EGPA) but also to some extent in granulomatosis with polyangiitis (GPA). ANCA-negative AAV describes cases in which the patient otherwise fulfills the definition for AAV but has negative results on serologic testing for ANCA. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)

The major clinicopathologic variants of AAV include microscopic polyangiitis (MPA), GPA, and EGPA; additionally, AAV can occur in only a single organ, especially a subset referred to as renal-limited AAV.

Microscopic polyangiitis — MPA is a necrotizing vasculitis that primarily affects capillaries, venules, or arterioles, most commonly manifesting as necrotizing glomerulonephritis and/or pulmonary capillaritis. Involvement of medium- and small- sized arteries may also be present. Granulomatous inflammation is usually absent. ANCA is present in >90 percent of patients with MPA. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis".)

Granulomatosis with polyangiitis — GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (eg, capillaries, venules, arterioles, arteries, and veins). It typically produces granulomatous inflammation of the upper and lower respiratory tracts as well as necrotizing, pauci-immune glomerulonephritis. ANCA is present in >80 percent of patients with GPA. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis".)

While MPA and GPA continue be regarded as distinct entities within AAV, they have markedly overlapping manifestations and it can be sometimes extremely difficult to differentiate between these two diseases within a patient. Furthermore, there is a growing recognition that ANCA type (anti-MPO or anti-PR3) has more prognostic and clinical meaning rather than the disease type (MPA or GPA), leading some experts to refer to MPO-AAV or PR3-AAV, and many clinical trials in AAV now stratify enrollment by ANCA type (MPO or PR3) and report results for each subgroup.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) — EGPA is an eosinophilic-rich necrotizing vasculitis predominantly affecting small- to medium-sized vessels. Patients often have chronic rhinosinusitis, asthma, and prominent peripheral blood eosinophilia. ANCA is present in approximately 40 percent of patients with EGPA, usually anti-MPO ANCA. The presence of ANCA is more frequent in patients with glomerulonephritis. (See "Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)".)

Immune complex small-vessel vasculitis — Immune complex small-vessel vasculitis refers to vasculitis with moderate to marked vessel wall deposits of immunoglobulin and/or complement, predominantly affecting small vessels. Glomerulonephritis is often present. Medium-sized arterial involvement is much less common in immune complex vasculitis compared with AAV.

Anti-glomerular basement membrane disease — Anti-glomerular basement membrane (GBM) disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with basement membrane deposition of anti-basement membrane autoantibodies. Lung involvement typically causes pulmonary hemorrhage, and renal involvement causes glomerulonephritis with necrosis and crescents. (See "Anti-GBM (Goodpasture) disease: Pathogenesis, clinical manifestations, and diagnosis".)

Cryoglobulinemic vasculitis — Cryoglobulinemic vasculitis, previously termed essential cryoglobulinemic vasculitis, is characterized by the presence of cryoglobulins, which are serum proteins that precipitate in the cold and dissolve upon rewarming. In this disorder, which is most often due to hepatitis C virus infection, cryoglobulin immune complexes are deposited in the walls of capillaries, venules, or arterioles, thereby resulting in inflammation in small vessels. Skin, glomeruli, and peripheral nerves are often involved. (See "Overview of cryoglobulins and cryoglobulinemia" and "Mixed cryoglobulinemia syndrome: Clinical manifestations and diagnosis".)

IgA vasculitis (Henoch-Schönlein purpura) — Immunoglobulin A (IgA) vasculitis is a systemic vasculitis characterized by the tissue deposition of IgA1-dominant immune complexes affecting mostly small vessels (predominantly capillaries, venules, or arterioles). IgA vasculitis typically affects the skin and gastrointestinal tract, and often causes arthritis. A glomerulonephritis indistinguishable from IgA nephropathy may be observed. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis".)

Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis) — Hypocomplementemic urticarial vasculitis (HUV) is a vasculitis associated with urticaria and hypocomplementemia, and predominantly affects small vessels. Glomerulonephritis, arthritis, obstructive pulmonary disease, and ocular inflammation may also be observed. The presence of anti-C1q antibodies is one of the most distinctive findings in HUV, and consideration of the name anti-C1q vasculitis for this entity has been suggested. (See "Urticarial vasculitis", section on 'Hypocomplementemic urticarial vasculitis'.)

Variable-vessel vasculitis

Behçet syndrome — The vasculitis occurring in patients with Behçet syndrome can affect any size artery or vein. Behçet syndrome is characterized by recurrent oral and/or genital aphthous ulcers as well as cutaneous, ocular, articular, gastrointestinal, and/or central nervous system involvement. Thrombosis and arterial aneurysms can also occur. (See "Clinical manifestations and diagnosis of Behçet syndrome", section on 'Vascular disease'.)

Cogan syndrome — Vasculitis occurring in patients with Cogan syndrome is characterized by ocular inflammatory lesions, including interstitial keratitis, uveitis, and episcleritis as well as inner ear disease (eg, sensorineural hearing loss and vestibular dysfunction). Vasculitis manifestations may include arteritis of any size vessel, aortitis, and aortic aneurysms. (See "Cogan syndrome".)

Single-organ vasculitis — Single-organ vasculitis refers to vasculitis in arteries or veins of any size in a single organ, and has no features suggesting it is a limited expression of a systemic vasculitis. The involved organ and vessel type should be included in the name (eg, primary central nervous system vasculitis [CNSV], cutaneous small vessel vasculitis [5], isolated aortitis). Some patients initially diagnosed with single-organ vasculitis may develop other disease manifestations, warranting reevaluation for another systemic vasculitis (eg, cutaneous arteritis later becoming polyarteritis nodosa).

Primary central nervous system vasculitis — Primary CNSV, or primary angiitis of the CNS (PACNS), refers to vasculitis affecting the medium and small blood vessels of the brain, spinal cord, and the meninges, without systemic (non-brain) involvement. (See "Primary angiitis of the central nervous system in adults".)

Vasculitis associated with systemic disease — Subsets of patients with systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, and other systemic rheumatic diseases may develop an associated vasculitis. The vasculitic process in this setting most frequently involves small muscular arteries, arterioles, and venules.

Vasculitis associated with probable etiology — Some of the vasculitides are associated with a specific etiology and the diagnosis should have a prefix specifying the underlying cause. Examples include hepatitis C virus-associated cryoglobulinemic vasculitis, hepatitis B virus-associated polyarteritis nodosa, and hydralazine-associated ANCA-associated vasculitis. Hematologic and solid organ neoplasms as well as clonal B cell lymphoproliferative disorders can also be associated with vasculitis.

CLASSIFICATION CRITERIA — The classification of the vasculitides has been a challenging problem for decades [6]. In 1990, the American College of Rheumatology (ACR) proposed criteria for several types of vasculitis [7-12]. These criteria have been widely applied to and are quite useful for clinical research. However, while the criteria can be used to help inform the diagnosis, they lack sufficient sensitivity and specificity to be used as diagnostic criteria [13].

In 2022, the ACR and European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) published a set of new validated classification criteria for the three types of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], and eosinophilic granulomatosis with polyangiitis [EGPA]) as well as two types of large-vessel vasculitis (giant cell arteritis [GCA] and Takayasu arteritis [TAK]) [14-23]. There were no prior criteria for MPA. Compared with the 1990 criteria, the 2022 ACR/EULAR classification criteria were developed using more sophisticated analytic methods, data from thousands of patients from many regions of the world, and incorporation of testing not available or routinely used in 1990 (eg, ANCA or magnetic resonance (MR)/computed tomography (CT) angiography). The 2022 criteria sets each use weighted parameters for clinical, laboratory, imaging, and biopsy features that are combined to derive a score.

The new classification criteria for the vasculitides are not intended for use as diagnostic criteria but are intended to delineate the type of vasculitis in a patient with an established diagnosis of vasculitis. The use of the criteria for making a diagnosis of vasculitis runs the risk of misdiagnosis.

The 2022 classification criteria can be found on the American College of Rheumatology website.

The European Medicines Agency (EMA) developed an algorithm that was designed to help classify the ANCA-associated vasculitides as well as polyarteritis nodosa for epidemiologic studies, but this also has its limitations [24]. The EMA algorithm is discussed in detail separately. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis", section on 'Classification criteria'.)

Although the ACR/EULAR criteria, the EMA algorithm, and the Chapel Hill Consensus Conference (CHCC) nomenclature system have each been used by clinical researchers and clinicians to help diagnose patients, each approach has limitations, and accurate diagnostic criteria for each of the vasculitides have yet to be developed.

CLINICAL FEATURES SUGGESTIVE OF SYSTEMIC VASCULITIS

Diagnostic approach — It is not possible to outline a single algorithm for evaluating patients suspected of having any one of the vasculitides because of the clinical heterogeneity of these diseases. Nevertheless, there are some elements of the medical history, physical examination, and laboratory evaluation that may be helpful when trying to identify a patient suspected of having a vasculitis. While each form of vasculitis is rare, the potential for severe organ damage or death from these diseases means it is appropriate to consider the possibility early in the evaluation of patients with any possible manifestations of vasculitis.

In general, the presence of vasculitis should be considered in patients who present with systemic or constitutional symptoms in combination with evidence of single and/or multiorgan dysfunction, and especially with some key manifestations as outlined below. The diagnosis of vasculitis is often delayed because the clinical manifestations can be mimicked by a number of other diseases.

The diagnosis of the individual vasculitides is generally based on patterns of organ injury, the size of the vessels affected, histopathologic features, and characteristic findings on diagnostic imaging. Refer to separate topic reviews for each of the individual vasculitides for a more detailed diagnostic approach once a specific type of vasculitis is suspected.

History — Although neither sensitive nor specific for the diagnosis of vasculitis, systemic symptoms such as fever, fatigue, weight loss, and arthralgias are often present in patients with vasculitis. A history of eye inflammation, particularly scleritis, are features sometimes observed in vasculitis. Persistent nasal crusting, epistaxis, or other upper airway disease is suggestive of granulomatosis with polyangiitis (GPA). The presence of acute foot drop or wrist drop may be due to a motor neuropathy from an ischemic process. Limb claudication, especially in the upper extremities or in a person at low risk for atherosclerosis, is suggestive of a large arterial occlusion from Takayasu arteritis (TAK) or giant cell arteritis (GCA).

Unexplained hemoptysis should always raise concern for alveolar hemorrhage and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Similarly, any patients with suspected glomerulonephritis must be evaluated for possible vasculitis, especially AAV or anti-glomerular basement membrane (GBM) disease. The combination of lung hemorrhage and renal insufficiency (often referred to as "pulmonary-renal syndrome") should immediately raise concern for vasculitis [25].

A detailed history is also important to assess whether the patient has recently (up to at least some time in the prior 6 to 12 months) been exposed to specific medications or cocaine which may be associated with drug-induced vasculitis, has a history of hepatitis, or has been diagnosed with any disorder known to be associated with a vasculitis (such as systemic lupus erythematosus). (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Drug-induced ANCA-associated vasculitis' and "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Cocaine and levamisole'.)

The propensity of certain disorders to occur among certain age groups and/or in women may favor the diagnosis of a specific vasculitides (table 3). In a review of 807 patients from the American College of Rheumatology (ACR) cohort, the mean age at onset was between 45 and 50 for GPA and polyarteritis nodosa compared with 17 and 26 years of age for immunoglobulin A (IgA) vasculitis and TAK and with 69 years for GCA [7]. GCA and especially TAK are observed more frequently in women.

Physical examination — A careful physical examination helps identify potential sites of vasculitis and determine the extent of vascular lesions, the distribution of affected organs, and the presence of additional disease processes. Certain findings, such as diminished sensation to touch and motor weakness of the extremities due to neuropathic changes consistent with mononeuritis multiplex and palpable purpura (picture 1), are highly suggestive of an underlying vasculitic process.

●Findings of a sensory and/or motor neuropathy – Both subtle and extensive neuropathies can occur in many forms of vasculitis. These include classical mononeuritis multiplex and peripheral symmetric or asymmetric polyneuropathy. (See "Clinical manifestations and diagnosis of vasculitic neuropathies".)

●Palpable purpura – Palpable purpura is a strong sign of cutaneous leukocytoclastic vasculitis (picture 1) and is a common finding in many small-vessel vasculitides as well as polyarteritis nodosa (see "Approach to the patient with retiform (angulated) purpura", section on 'Vessel wall pathology' and "Evaluation of adults with cutaneous lesions of vasculitis", section on 'When to suspect cutaneous vasculitis'). However, it is important to recognize that not all purpura is vasculitis and not all vasculitis in the skin is represented as purpura.

●Absent, diminished, or tender pulses, bruits, or blood pressure discrepancies – A careful and full vascular examination is extremely helpful in identifying signs of large-vessel vasculitis [26]. The vascular examination should include palpation for pulses in multiple areas including, but not limited to, the radial, brachial, carotid, femoral, popliteal, posterior tibial, and dorsalis pedis arteries, and auscultation for bruits in the regions of the carotid, subclavian, renal, and femoral arteries and the thoracic and abdominal aorta.

Laboratory tests — Some laboratory tests may help identify the type of vasculitis, the degree of organ involvement, or identify another disease. The initial laboratory evaluation of a patient suspected of having vasculitis should include a complete blood cell count (CBC), serum creatinine, liver function studies, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), serologies for viral hepatitis, serum cryoglobulins, and a urinalysis with urinary sediment. Blood cultures should be drawn to help exclude infection (eg, infective endocarditis).

Additional, more specific laboratory testing that is guided by the clinical presentation and may further aid in the diagnosis include:

●Antinuclear antibody (ANA) – A positive ANA test may support the presence of an underlying systemic rheumatic disease such as systemic lupus erythematosus. (See "Measurement and clinical significance of antinuclear antibodies".)

●Complement – Low serum complement levels, especially low C4, may be present in mixed cryoglobulinemia and systemic lupus erythematosus but not in most other forms of vasculitis. (See "Overview and clinical assessment of the complement system" and "Overview of cryoglobulins and cryoglobulinemia".)

●ANCA – Although not fully diagnostic on its own, the presence of ANCA directed against either proteinase 3 (PR3) or myeloperoxidase (MPO) is extremely specific (often >95 percent) for a diagnosis of AAV in patients with some reasonable pre-test suspicion. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)

Additional tests — Additional testing should be guided by the clinical presentation. Examples of such studies include:

●A chest radiograph or high-resolution computed tomography (HRCT) of the chest is indicated in patients with respiratory symptoms and/or hemoptysis.

●Electromyography is useful if symptoms of neuromuscular disease are present, such as findings suggestive of a mononeuritis multiplex. (See "Overview of electromyography".)

●A lumbar puncture with cerebral spinal fluid analysis should be considered in patients with symptoms suggestive of primary angiitis of the central nervous system (PACNS). (See "Primary angiitis of the central nervous system in adults", section on 'Lumbar puncture'.)

Biopsy — Biopsy examination of the involved tissue is essential for diagnosis of many vasculitides, but is not possible in all cases. For example, a temporal artery biopsy should be considered in cases of suspected GCA and is a generally a straightforward procedure (see "Temporal artery biopsy technique"). Similarly, skin biopsies of purpuric lesions and renal biopsies in patients with suspected glomerulonephritis have high diagnostic yields. However, for patients with suspected TAK, except in cases where surgical repair was conducted, tissue from the aortic arch and its primary branches is not feasible and the diagnosis is based on other clinical and radiographic findings.

Vascular imaging — Magnetic resonance imaging (MRI), MR angiograms, CT angiograms, vascular ultrasound, and positron emission tomography (PET) may be used to detect large artery lesions and, especially CT and MRI, have become the standard approach to screening for large-vessel vasculitis. There is increasing adoption of using ultrasound to detect possible giant cell arteritis, especially in countries and centers with the experience and expertise to conduct ultrasound of the temporal arteries. PET is sometimes useful in identifying potential inflammatory disease in the aorta and its branches. However, while more invasive imaging studies generally can be avoided, conventional catheter-based angiography remains an important diagnostic test in some situations. It is important to realize that no angiographic abnormalities are themselves pathognomonic for vasculitis, but they can be used to support a diagnosis when combined with other clinical data. Angiograms of mesenteric or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall irregularities (image 1). By contrast, angiography is unlikely to be helpful in assessing a small-vessel vasculitis because the affected vessels are below the resolution of usual angiograms.

DIFFERENTIAL DIAGNOSIS — Patients with nonvasculitic disease processes may present with symptoms and findings that closely mimic various vasculitides. Perhaps most common are systemic rheumatic diseases, such as systemic lupus erythematosus, atherosclerotic disease, drug reactions, and vaso-occlusive processes. Among the most important diseases to exclude are infections and malignancies, since the immunosuppressive therapy could worsen these conditions and a delay in diagnosis can be extremely dangerous. While it is beyond the scope of this review to provide a comprehensive list of all possible alternative diagnoses, we present several categories of mimics of vasculitis in a table (table 4) [27-29].

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Here is the patient education article that is relevant to this topic. We encourage you to print or e-mail this topic to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Polyarteritis nodosa (The Basics)" and "Patient education: Vasculitis (The Basics)")

●Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●General principles – The vasculitides are defined by the presence of inflammatory leukocytes in vessel walls with reactive damage to mural structures. Both loss of vessel integrity leading to bleeding, and compromise of the lumen may result in downstream tissue ischemia and necrosis. In general, affected vessels vary in size, type, and location in association with the specific type of vasculitis. Vasculitis may occur as a primary process or may be secondary to another underlying disease. (See 'Introduction' above.)

●Nomenclature – The international Chapel Hill Consensus Conference (CHCC) has developed one of the most widely used nomenclature systems, which specifies the names and definitions for most forms of vasculitis (table 2). (See 'Nomenclature' above.)

●Major categories of vasculitis – Classification of the noninfectious vasculitides is primarily based upon the predominant size of the vessels involved (figure 1), although some overlap in the size of arteries involved occurs among the major size-based categories. There are also some forms of vasculitis that do not involve a single predominant size of vessel (variable-vessel vasculitis) (see 'Major categories of vasculitis' above). The major categories of the vasculitides include:

•Large-vessel vasculitis – Takayasu arteritis (TAK) and giant cell arteritis (GCA) (see 'Large-vessel vasculitis' above)

•Medium-vessel vasculitis – Polyarteritis nodosa and Kawasaki disease (see 'Medium-vessel vasculitis' above)

•Small-vessel vasculitis – Microscopic polyangiitis, granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss), anti-glomerular basement membrane (GBM) disease, cryoglobulinemic vasculitis, immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura [HSP]), and hypocomplementemic urticarial vasculitis (anti-C1q-vasculitis). (See 'Small-vessel vasculitis' above.)

•Variable-vessel vasculitis – Behçet syndrome and Cogan syndrome (see 'Variable-vessel vasculitis' above)

•Single-organ vasculitis – Primary central nervous system vasculitis (CNSV) (see 'Single-organ vasculitis' above)

•Vasculitis associated with systemic disease such as systemic lupus erythematosus, rheumatoid arthritis, and relapsing polychondritis (see 'Vasculitis associated with systemic disease' above)

•Vasculitis associated with probable etiology such as hepatitis C virus-associated cryoglobulinemic vasculitis, hepatitis B virus-associated polyarteritis nodosa, and hydralazine-associated antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (see 'Vasculitis associated with probable etiology' above)

●Classification criteria – The 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for vasculitides offers fully revised criteria and will become the new standard for clinical research. The European Medicines Agency (EMA) classification system is also used. The CHCC nomenclature system is also a widely referenced naming system for vasculitides.

Although each of these systems may inform clinicians about the diagnosis of vasculitis, they all lack sufficient sensitivity and specificity to be used as diagnostic criteria. (See 'Classification criteria' above.)

●Clinical features suggestive of vasculitis – In general, the presence of vasculitis should be considered in patients who present with systemic or constitutional symptoms in combination with evidence of single and/or multiorgan dysfunction. The diagnosis of the individual vasculitides is generally based on patterns of organ injury, the size of the vessels affected, histopathologic features, and characteristic findings on diagnostic imaging. (See 'Clinical features suggestive of systemic vasculitis' above and 'Diagnostic approach' above.)

●Diagnostic evaluation – Diagnostic evaluation for a case of possible vasculitis should include a detailed history, including drug use, infectious disease exposure, and symptoms of manifestations that may characterize or exclude a suspected diagnoses; a careful physical examination to identify potential sites of involvement of vasculitis and determine the extent of vascular lesions; general laboratory testing to help identify the degree of organ involvement and exclude another disease; additional laboratory testing, depending on the suspected diagnosis and findings, such as tests for antinuclear antibodies (ANA), complement levels, ANCA; a chest radiograph or high-resolution computed tomography (HRCT) of the chest; electromyography; a lumbar puncture; a biopsy of the involved tissue if possible; and vascular imaging. (See 'Diagnostic approach' above.)

●Vasculitis mimics – Patients with nonvasculitic disease processes may present with symptoms and findings that closely mimic various vasculitides. Perhaps most common are systemic rheumatic diseases, such as systemic lupus erythematosus, atherosclerotic disease, drug reactions, and vaso-occlusive processes. Among the most important diseases to exclude are infections and malignancies since immunosuppressive therapy could worsen these conditions and a delay in diagnosis can be extremely dangerous. We present several categories of mimics of vasculitis in a table (table 4). (See 'Differential diagnosis' above.)