Classification of and approach to the vasculitides in adults

Author
Gene G Hunder, MD
Section Editor
John H Stone, MD, MPH
Deputy Editor
Paul L Romain, MD

Disclosures
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last
updated: Tue Jun 28 00:00:00 GMT 2011(More)

INTRODUCTION The vasculitides are defined by the presence of inflammatory

leukocytes in vessel walls with reactive damage to mural structures. Loss of vessel integrity
may lead to bleeding. Compromise of the lumen leads to downstream tissue ischemia and
necrosis. In general, affected vessels vary in size, type, and location in association with the
specific vasculitic disorder. Vasculitis may occur as a primary process or may be secondary
to another underlying disease [1].

The exact mechanisms underlying these disorders are unclear. Three different pathogenic
models of disease have been advanced to help explain why the lesions of a particular
vasculitic syndrome are only found in specific vessels [2]:

The distribution of the antigen responsible for the vasculitis determines the pattern
of vessel involvement.

The recruitment and accumulation of the inflammatory infiltrate is determined by the

endothelial cell, including the expression of adhesion or other receptor molecules, the
secretion of peptides and hormones, and the specific interaction with inflammatory
cells. Some endothelial cells are therefore able to attract inflammatory cells, while
others are not.

Nonendothelial structures of the vessel wall are involved in controlling the

inflammatory process. In addition to the endothelial cells that provide costimulatory
function, other cellular components serve as antigen-presenting cells and contribute
proinflammatory mediators.

It is likely that elements of each model contribute to the pathogenesis of these diseases.

The vasculitides are often serious and sometimes fatal diseases that require prompt
recognition and therapy. Symptomatic involvement of affected organs may either occur in
isolation or in combination with multiple organs. The distribution of affected organs may
suggest a particular vasculitic disorder, but significant overlap is observed.

Fortunately, available treatments are helpful, particularly in the acute phase. However,
during maintenance therapy with glucocorticoids and immunosuppressive agents, the
adverse effects of drugs and superimposed infections may assume increasing importance.
Mortality data suggest that while early deaths in vasculitis are due to the active disease, late
deaths may be due to the complications of therapy [3].
This topic will review the classification and diagnostic manifestations 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 the
vasculitides in adults".)

CLASSIFICATION Classically, the vasculitic syndromes have been categorized by the

predominant sizes of the blood vessels and types of vessels most commonly affected among
patients with the disorder (table 1) [4,5]. The presence or absence of antineutrophil
cytoplasmic antibodies (ANCA) is a more recent addition to proposed classification criteria
[6,7].

Large vessel vasculitis

Takayasu arteritis Takayasu arteritis primarily affects the aorta and its primary
branches. The inflammation may be localized to a portion of the thoracic or abdominal aorta
and branches, or may involve the entire vessel. (See "Clinical features and diagnosis of
Takayasu arteritis".)

Giant cell arteritis Giant cell or temporal arteritis is a chronic vasculitis of large and
medium size vessels. Although it may be generalized, vessel inflammation most prominently
involves the cranial branches of the arteries originating from the aortic arch. (See "Clinical
manifestations of giant cell (temporal) arteritis".)

Medium sized vessel vasculitis

Polyarteritis nodosa Polyarteritis nodosa is a systemic necrotizing vasculitis that

typically affects the small and medium-sized muscular arteries. (See "Clinical manifestations
and diagnosis of polyarteritis nodosa".)

In some cases, however, only the smaller vessels are affected, a condition that has been
called microscopic polyarteritis or polyangiitis; this disorder is felt to be more closely
associated with granulomatosis with polyangiitis (Wegeners) than to classic polyarteritis
nodosa (see 'Microscopic polyarteritis' below and "Clinical manifestations and diagnosis of
granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis").

Kawasaki disease Kawasaki disease is an arteritis of large, medium, and small arteries,
particularly the coronary arteries. The disease usually occurs in children and is often
associated with a mucocutaneous lymph node syndrome. A small number of cases have also
been reported in adults [8]. (See "Kawasaki disease: Clinical features and diagnosis".)

Primary central nervous system vasculitis Primary or isolated central nervous

system vasculitis affects medium and small arteries over a diffuse area of the central
nervous system, without symptomatic involvement of extracranial vessels. (See "Primary
angiitis of the central nervous system".)

Small vessel vasculitis

Churg-Strauss syndrome Churg-Strauss syndrome (also called allergic granulomatosis

and angiitis) is a vasculitis of the medium and small sized muscular arteries, and is often
found with vascular and extravascular granulomatosis. The vasculitis classically involves the
arteries of the lung and skin, but may be generalized. (See "Epidemiology, pathogenesis,
and pathology of Churg-Strauss syndrome (allergic granulomatosis and angiitis)".)

Granulomatosis with polyangiitis (Wegeners) Granulomatosis with polyangiitis

(Wegeners), abbreviated as GPA, is a systemic vasculitis of the medium and small arteries,
as well as the venules and arterioles. It typically produces granulomatous inflammation of
the upper and lower respiratory tracts and necrotizing, pauci-immune glomerulonephritis in
the kidneys. GPA is usually associated with antineutrophil cytoplasmic antibodies (ANCA).
(See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis (Wegener's)
and microscopic polyangiitis".)

Microscopic polyarteritis Microscopic polyarteritis or polyangiitis is a vasculitis that

primarily affects capillaries, venules, or arterioles. Involvement of small and medium-sized
arteries may also be present. This disorder is thought by some investigators to represent
part of a clinical spectrum that includes GPA, since both are associated with the presence of
ANCA and similar histologic changes outside the respiratory tract. (See "Clinical
manifestations and diagnosis of granulomatosis with polyangiitis (Wegener's) and
microscopic polyangiitis".)

Henoch-Schnlein purpura Henoch-Schnlein purpura (HSP) is a systemic vasculitis

that is characterized by the tissue deposition of IgA-containing immune complexes. Biopsy
of lesions reveals inflammation of the small blood vessels (most prominent in the
postcapillary venules). This disorder is considered a form of hypersensitivity vasculitis, but is
distinguished from other forms of hypersensitivity by the finding of prominent deposits of
IgA. (See "Clinical manifestations and diagnosis of Henoch-Schnlein purpura".)

Essential cryoglobulinemic vasculitis Essential cryoglobulinemic vasculitis is

characterized by the presence of cryoglobulins, which are serum proteins that precipitate in
the cold and dissolve upon rewarming. Cryoglobulins typically are composed of a mixture of
immunoglobulins and complement components. In this disorder, which is most often due to
hepatitis C virus infection, immune complexes are deposited in the walls of capillaries,
venules or arterioles, thereby resulting in small vessel inflammation. (See "Overview of
cryoglobulins and cryoglobulinemia" and "Clinical manifestations and diagnosis of essential
mixed cryoglobulinemia".)

Hypersensitivity vasculitis The term "hypersensitivity vasculitis" has been used by

some authors to include several forms of vasculitis of small blood vessels. These have
included HSP, mixed cryoglobulinemia, allergic vasculitis, and serum sickness. However, the
term "hypersensitivity vasculitis" is most properly used to refer to vasculitis that occurs as a
hypersensitivity reaction to a known or suspected substance such as a vasculitic drug
reaction. In hypersensitivity vasculitis, the presence of skin vasculitis with palpable
petechiae or purpura is typically a major finding. Biopsy of these lesions reveals
inflammation of the small blood vessels, called leukocytoclastic vasculitis, which is most
prominent in the postcapillary venules. (See "Hypersensitivity vasculitis in adults".)

Vasculitis secondary to connective tissue disorders A subset of patients with

systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, Behets
disease, and other connective tissue disorders may have or develop an associated vasculitis.
The vasculitic process in this setting most frequently involves the small muscular arteries,
arterioles, and venules. A propensity for involvement of particular organs varies with the
underlying autoimmune disorder. (See appropriate topic reviews).

Vasculitis secondary to viral infection A number of viral infections may cause a

vasculitis of medium and/or small vessels [9]. This association is most commonly observed
with hepatitis B and C viruses, but may also be seen with HIV, cytomegalovirus, Epstein-
Barr virus, and Parvovirus B19. The clinical presentation may be similar to that of
polyarteritis nodosa or microscopic polyangiitis. Although the disorder is probably immune
complex mediated, it must be distinguished from non-viral associated vasculitides since
treatment consists of the administration of anti-viral, and not anti-inflammatory, regimens.

CLINICAL MANIFESTATIONS AND APPROACH TO DIAGNOSIS The presence of

vasculitis should be considered in patients who present with systemic symptoms in
combination with evidence of single and/or multiorgan dysfunction. Although neither
sensitive or specific, common complaints and signs of vasculitis include fatigue, weakness,
fever, arthralgias, abdominal pain, hypertension, renal insufficiency (with an active urine
sediment containing red and white cell and occasionally red cell casts), and neurologic
dysfunction.

Clinical features suggestive of vasculitis The diagnosis of vasculitis is often delayed

because the clinical manifestations can be mimicked by a number of other disorders.
However, the presence of certain signs is strongly suggestive. As examples:

Mononeuritis multiplex Mononeuritis multiplex (or asymmetric polyneuropathy) is

highly suggestive of vasculitis (particularly polyarteritis nodosa), since diabetic
neuropathy is the only other common cause of this problem in developed countries.
(See "Clinical manifestations of vasculitic neuropathy".)

Palpable purpura Patients with palpable purpura alone are likely to have cutaneous
leukocytoclastic vasculitis of the hypersensitivity vasculitis type (picture 1); if the
purpura is present with systemic organ involvement, such patients are likely to have
HSP or microscopic polyarteritis (polyangiitis). (See "Evaluation of adults with
cutaneous lesions of vasculitis", section on 'Cutaneous findings' and "Approach to the
patient with retiform (angulated) purpura", section on 'Vessel wall pathology'.)

Pulmonary-renal involvement The combination of hemoptysis and renal

involvement suggestive of glomerulonephritis suggests the diagnosis of
granulomatosis with polyangiitis (Wegeners) or microscopic polyangiitis. However,
certain other disorders, particularly anti-glomerular basement membrane (anti-GBM)
antibody disease, may cause an identical combination of findings. One report of 97
such patients, for example, found that 48 were ANCA-positive and presumably had
granulomatosis with polyangiitis (Wegeners) or microscopic polyangiitis, 7 had both
ANCA and anti-GBM antibodies, and six had anti-GBM antibody disease alone [10].
The remaining patients had a variety of disorders including pulmonary emboli,
infection, and lupus. (See "Acute glomerulonephritis and pulmonary hemorrhage".)
Because of the variability of the manifestations of vasculitic syndromes, it has not been
possible to outline a single uniform method of evaluating patients suspected of having one
of these conditions. Nevertheless, there are shared elements in the history, physical
examination, and laboratory evaluation of the patient suspected of having a vasculitis. In
addition, specific procedures are essential in some forms of vasculitis, such as arch
angiogram for Takayasu arteritis and temporal artery biopsy for giant cell arteritis.

Diagnostic approach

History A detailed history is important to assess whether the patient has recently been
administered drugs (which may produce hypersensitivity vasculitis), has a history of
hepatitis (hepatitis C virus is responsible for most cases of mixed cryoglobulinemia and
some cases of polyarteritis), or has been diagnosed with any disorder known to be
associated with a vasculitis (such as systemic lupus erythematosus).

The propensity of certain disorders to occur among certain age groups and/or in women
may favor the diagnosis of a specific vasculitic syndrome (table 1). In a review of 807
patients from the American College of Rheumatology cohort, the mean age at onset was
between 45 and 50 for granulomatosis with polyangiitis (Wegeners) and polyarteritis
nodosa compared with 17 and 26 years of age for HSP and Takayasu arteritis, and 69 years
for giant cell arteritis [4]. The last two disorders occurred primarily in women (86 and 75
percent, respectively).

Physical examination A careful physical examination helps to determine the extent of

vascular lesions, the distribution of affected organs, and the presence of additional disease
processes. As mentioned above, certain findings, such as mononeuritis multiplex and
palpable purpura (picture 1), are highly suggestive of an underlying vasculitic process.

Laboratory tests Laboratory tests help ascertain the type of vasculitis, and the degree
and types of organs affected. Basic laboratory analysis should include serum creatinine and
muscle enzyme concentrations, liver function studies, erythrocyte sedimentation rate,
hepatitis serologies, urinalysis, chest x-ray, and electrocardiogram. Other tests that may be
warranted include cerebrospinal fluid analysis, central nervous system imaging, pulmonary
function testing, and blood and tissue culture. Although many of these tests are nonspecific,
they permit the initial assessment of organ involvement, and may suggest, include, or
exclude additional diagnostic possibilities, particularly infection.

Additional, more specific, laboratory testing may further aid in diagnosis:

ANA A positive antinuclear antibody test suggests the presence of an underlying

connective tissue disorder, particularly systemic lupus erythematosus.
(See "Measurement and clinical significance of antinuclear antibodies".)

Complement Low serum complement levels may be present in mixed

cryoglobulinemia and lupus but not most other vasculitis disorders. Among those
with cryoglobulins, infection with hepatitis C virus must be considered.
(See "Overview and clinical assessment of the complement
system" and "Extrahepatic manifestations of hepatitis C virus infection".)
 ANCA Although not diagnostic, the presence of ANCA directed against protease 3
strongly suggests a diagnosis of granulomatosis with polyangiitis (Wegeners), while
ANCA directed against myeloperoxidase favors a diagnosis of microscopic polyangiitis
[11,12]. Other ANCA associated disorders include drug-induced vasculitis and Churg-
Strauss vasculitis. (See "Clinical spectrum of antineutrophil cytoplasmic antibodies".)

Electromyography Electromyography is useful if a systemic vasculitis is suspected and

neuromuscular symptoms are present, such as a mononeuritis multiplex. (See "Clinical
neurophysiology".)

Tissue biopsy Biopsy examination of the most clinically involved tissue is essential for
diagnosis. The chances of obtaining a diagnostic specimen are greatest when a specimen is
taken from an involved portion of an affected organ and when the tissue sample is of
adequate size. A "blind" biopsy is less likely to be fruitful. Histologic findings evolve as
lesions progress and may vary from an acute inflammation to those due to healing and
repair (see 'Classification criteria' below and "Evaluation of adults with cutaneous lesions of
vasculitis", section on 'Biopsy').

Arteriography Arteriograms are helpful in identifying and characterizing a vasculitis of

large and medium-sized arteries, such as polyarteritis nodosa, Takayasu arteritis, and giant
cell arteritis with an aortic arch syndrome. In these conditions, angiographic abnormalities
may not be pathognomonic, but usually 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 (picture 2). In the patient suspected of having
polyarteritis nodosa in whom an obvious area for biopsy is absent, a mesenteric angiogram
should be considered, particularly in the presence of abdominal pain. In contrast,
angiography is unlikely to be helpful in assessing a small vessel vasculitis, such as
microscopic polyangiitis. The affected vessels in this disorder are below the resolution of
usual angiograms.

The decision to biopsy and/or perform angiography in a patient suspected of a vasculitis is

based upon an overall clinical assessment and the relative complications associated with
each procedure in a particular clinical setting. As an example, arteriography alone is usually
performed to confirm the diagnosis of Takayasu arteritis. The arteriographic changes tend to
be most pronounced in the region of the aortic arch and its primary branches, areas
relatively inaccessible for biopsy. In contrast, involvement of the skin is characteristic of
patients with a leukocytoclastic vasculitis; the skin is easily accessible for biopsy, a
procedure not associated with significant morbidity. However, the observed changes are not
specific unless there is IgA deposition, establishing the diagnosis of HSP.

CLASSIFICATION CRITERIA Criteria for the classification of most of the major forms of
vasculitis have been established by the American College of Rheumatology (ACR) in 1990
and are presented below [4]. These criteria are based upon prospective data from patients
with vasculitis; they do not include all characteristics of a particular disorder, only those that
help to distinguish the disorder from other vasculitides. As noted above, the diagnosis of a
particular form of vasculitis is virtually always confirmed by tissue biopsy.
The inappropriate utilization of these classification criteria for the clinical diagnosis of
individual patients suspected to have vasculitis is associated with relatively low diagnostic
accuracy. As an example, the diagnostic accuracy of these criteria for four forms of vasculitis
was directly assessed in a prospective study of 198 patients referred for possible vasculitis
[13]. The reference diagnosis was the final diagnosis found in an audit of the patient's chart
performed two to eight months after presentation. For the diagnosis of granulomatosis with
polyangiitis (Wegeners), giant-cell arteritis, polyarteritis nodosa, and hypersensitivity
vasculitis, the positive predictive values of the ACR criteria were low: 17 to 29 percent for all
patients, and only 29 to 75 percent for those with a final diagnosis of vasculitis.

This study therefore confirms previous views that these classification criteria function poorly
when used for clinical diagnosis [14]. Separate criteria are therefore needed for both
classification and diagnosis. However, when used properly, the existence of standardized
criteria, which must change over time with the acquisition of new knowledge, permits the
comparison of patients from multiple centers, thereby enhancing our understanding of
complex diseases [14].

Takayasu arteritis The following classification criteria by the ACR for Takayasu arteritis
were primarily designed to distinguish this disorder from other forms of vasculitis (table
2) [15]:

Age at disease onset 40 years

Claudication of the extremities

Decreased pulsation of one or both brachial arteries

Difference of at least 10 mmHg in systolic blood pressure between the arms

Bruit over one or both subclavian arteries or the abdominal aorta

Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or

large arteries in the proximal upper or lower extremities, not due to arteriosclerosis,
fibromuscular dysplasia, or other causes

Patients are said to have Takayasu arteritis if at least three of the six criteria are present;
this classification yields a sensitivity and specificity of 90.5 and 97.8 percent, respectively.
(See "Clinical features and diagnosis of Takayasu arteritis".)

Giant cell arteritis The ACR criteria for the classification of giant cell arteritis (GCA)
were formed by comparing the symptoms and findings of 214 patients with the diagnosis of
GCA with the clinical findings of 593 patients with other forms of vasculitis [16]. In a patient
with vasculitis, the finding of three of the following five criteria was associated with a 94
percent sensitivity and a 91 percent specificity for the diagnosis of GCA:

Age 50 years at time of disease onset

 Localized headache of new onset

Tenderness or decreased pulse of the temporal artery

Erythrocyte sedimentation rate (ESR) greater than 50 mm/h (Westergren)

Biopsy that includes an artery, and reveals a necrotizing arteritis with a

predominance of mononuclear cells or a granulomatous process with multinucleated
giant cells (picture 3).

If an elevated ESR is excluded, but scalp tenderness and claudication of the jaw, tongue, or
with deglutition are added as criteria, sensitivity for the diagnosis is now 95 percent with a
specificity of 91 percent. (See "Clinical manifestations of giant cell (temporal) arteritis".)

Polyarteritis nodosa The ACR has established ten criteria for the classification of
polyarteritis nodosa in a patient with a vasculitis [17]:

Otherwise unexplained weight loss > 4 kg

Livedo reticularis

Testicular pain or tenderness

Myalgias (excluding that of the shoulder and hip girdle), weakness, or

polyneuropathy

Mononeuropathy or polyneuropathy

New onset diastolic blood pressure > 90 mmHg

Elevated levels of serum blood urea nitrogen (>40 mg/dL or 14.3 mmol/L) or
creatinine (>1.5 mg/dL or 132 mcmol/L)

Evidence of hepatitis B virus infection via serum antibody or antigen serology

Characteristic arteriographic abnormalities not resulting from noninflammatory

disease processes (picture 2)

A biopsy of small- or medium-sized artery containing polymorphonuclear cells

(picture 4)

A sensitivity and specificity for the diagnosis of polyarteritis of 82 and 87 percent,

respectively, has been found in the patient with a documented vasculitis in whom at least
three of the criteria are present. (See "Clinical manifestations and diagnosis of polyarteritis
nodosa".)
Kawasaki disease Guidelines for the diagnosis of Kawasaki disease were established by
Tomisaku Kawasaki in 1967. Diagnosis requires the presence of fever lasting five days or
more without any other explanation, combined with at least four of the five following
physical findings [18]:

Bilateral conjunctival injection (picture 5)

Oral mucous membrane changes, including injected or fissured lips, injected

pharynx, or strawberry tongue

Peripheral extremity changes, including erythema of palms or soles or edema of

hands or feet (acute phase), and periungual desquamation (convalescent phase)
(picture 6)

Polymorphous rash

Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)

As with all clinical criteria, these are imperfect guidelines with less than 100 percent
sensitivity and specificity. Children who do not meet the criteria may have an incomplete or
atypical form of Kawasaki disease (see below). In addition, some patients who manifest five
or six signs may have other conditions. (See "Kawasaki disease: Clinical features and
diagnosis".)

Churg-Strauss syndrome The following six criteria have been formulated by the ACR
for the diagnosis of the Churg-Strauss syndrome in a patient with documented vasculitis
[19]:

Asthma (a history of wheezing or the finding of diffuse high pitched wheezes on

expiration)

Eosinophilia of >10 percent on differential white blood cell count

Mononeuropathy (including multiplex) or polyneuropathy

Migratory or transient pulmonary opacities detected radiographically

Paranasal sinus abnormality

Biopsy containing a blood vessel showing the accumulation of eosinophils in

extravascular areas (picture 7A-B)

The presence of four or more of these criteria yields a sensitivity of 85 percent and a
specificity of 99.7 percent for the Churg-Strauss syndrome. (See "Clinical features and
diagnosis of Churg-Strauss syndrome (allergic granulomatosis and angiitis)", section on
'Diagnostic criteria'.)
Primary central nervous system vasculitis Specific criteria for a diagnosis of primary
central nervous system vasculitis (ICNSV) have not yet been formulated. PCNSV is a rare
disorder that is most commonly diagnosed in the patient with CNS symptoms and signs in
combination with evidence of a cerebral vasculitis by angiography and leptomeningeal
biopsy. (See "Primary angiitis of the central nervous system".)

Granulomatosis with polyangiitis (Wegeners) The ACR proposed four clinical

criteria for the classification of granulomatosis with polyangiitis (Wegeners), abbreviated as
GPA, in 1990, before the availability of ANCA testing [20]:

Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal
discharge).

Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities.

Abnormal urinary sediment (microscopic hematuria or red cell casts).

Granulomatous inflammation on biopsy of an artery or perivascular area.

The presence of two or more of these four criteria yielded a sensitivity of 88 percent and a
specificity of 92 percent. As a result, an abnormal chest radiograph or the findings of
granulomatous inflammation on biopsy are not absolute requirements to distinguish patients
with GPA from those with other forms of vasculitis.

Antineutrophil cytoplasmic antibodies At present, the diagnosis of GPA is suggested

from the clinical and laboratory findings and from the presence of circulating antineutrophil
cytoplasmic antibodies (ANCA) that are usually directed against proteinase 3 (C-ANCA)
(picture 8A-B). Almost all patients with active systemic GPA have a positive ANCA [21].
However, ANCA alone, including the presence of antiproteinase 3 antibodies which are more
specific for GPA, does not appear to be sufficiently accurate to preclude the need for tissue
biopsy. (See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis
(Wegener's) and microscopic polyangiitis".)

Microscopic polyangiitis Some patients have equivalent vasculitic lesions to those

observed in GPA, but, at least at presentation, do not have symptomatic or histologic
respiratory involvement; such individuals are considered to have microscopic polyarteritis.
However, two observations suggest that this disorder is closely related to GPA and should be
considered similarly: some patients subsequently develop classic respiratory tract lesions
[22]; and ANCA are typically present [23,24]. (See "Clinical manifestations and diagnosis of
granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis".)

Hypersensitivity vasculitis The ACR proposed the following five criteria for the
classification of hypersensitivity vasculitis in a patient with vasculitis [25]:

Age >16

Use of a possible offending drug in temporal relation to the symptoms

 Palpable purpura (picture 1)

Maculopapular rash

Biopsy of a skin lesion showing neutrophils around an arteriole or venule (picture 9A-
B)

The presence of three or more of these criteria had a sensitivity and specificity of 71 and 84
percent, respectively.

Henoch-Schnlein purpura However, these criteria do not distinguish hypersensitivity

vasculitis from Henoch-Schnlein purpura (HSP). As noted above, HSP is characterized by
the additional finding of the deposition of IgA on skin or renal biopsy. There are also clinical
criteria that can help to distinguish between the two disorders [26]:

Palpable purpura

Bowel angina

Gastrointestinal bleeding

Hematuria

Age at onset 20 years lesion

No new medications

The presence of three or more of the six criteria yielded a correct classification of HSP in 87
percent of cases in which a consensus of experienced clinicians concluded that was the
correct diagnosis [26]. The presence of two or fewer criteria yielded a correct classification
of hypersensitivity vasculitis in 74 percent. (See "Clinical manifestations and diagnosis of
Henoch-Schnlein purpura".)

Essential cryoglobulinemic vasculitis Specific criteria for a diagnosis of essential

cryoglobulinemic vasculitis have not yet been formulated. The diagnosis is typically made
from the history, skin purpura, low complement levels, demonstration of circulating
cryoglobulins, and histology showing small vessel inflammation with immune deposits found
in the vascular walls. (See "Clinical manifestations and diagnosis of essential mixed
cryoglobulinemia".)

Vasculitis secondary to connective tissue disorders The diagnostic criteria for

vasculitis secondary to an underlying connective tissue disorder, and not a primary
disorder, rests upon histologic evidence of a vasculitis in combination with a firm diagnosis
of a connective tissue disorder. Discussions of the criteria for the diagnosis of those
connective tissue disorders in which vasculitis may emerge is presented in the appropriate
topic reviews.
DIFFERENTIAL DIAGNOSIS Patients with nonvasculitic disease processes may present
with symptoms and findings that closely mimic those of the various vasculitides. Perhaps
most common are systemic rheumatic diseases such as systemic lupus erythematosus.
Other disorders that should be considered in selected patients include [27]:

Fibromuscular dysplasia (predominantly affects the aorta and its primary branches)

Cholesterol emboli

Atrial myxoma with emboli

Infective endocarditis

Malignancies, such as lymphomatoid granulomatosis/polymorphic reticulosis,

angioimmunoblastic T cell lymphoma, and intravascular lymphoma

Mycotic aneurysm with embolization (predominantly with arteriole, capillary, and

venule involvement)

Bacteremia

Rickettsial infection

Ergotism (principally affects medium and small sized muscular arteries)

Thrombocytopenia and other processes associated with purpura

Radiation fibrosis (radiation-induced vasculopathy)

Neurofibromatosis

Congenital coarctation of the aorta

Amyloidosis

Livedoid vasculopathy (livedo reticularis)

Malignant atrophic papulosis (Degos disease or syndrome)

Necrotic arachnidism (Loxosceles species spider bites) (see "Bites of recluse spiders")

Cocaine abuse

Hereditary disorders, including Marfan syndrome, Ehlers-Danlos syndrome, Loey-

Dietz syndrome, Grange syndrome, and pseudoxanthoma elasticum
 Segmental arterial mediolysis

Atherosclerosis

Vasospasm

Conditions that mimic true CNS vasculitis include vasospastic disorders; hypercoagulable
states; infections (syphilis, Lyme disease, Bartonella, tuberculosis, Varicella, hepatitis B and
C, human immunodeficiency virus, and fungal disease); other arterial diseases; embolic
disease; malignancy; stroke-like syndromes; leukoencephalopathies; and cerebral
hemorrhage.

Although sometimes difficult, an accurate diagnosis is essential among patients suspected

having a vasculitis. As an example, the administration of immunosuppressive therapy to the
patient with an undiagnosed infection may result in death.

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Beyond the Basics topic (see "Patient information: Vasculitis")

SUMMARY AND RECOMMENDATIONS

The vasculitides are defined by the presence of inflammatory leukocytes in vessel

walls with reactive damage to mural structures. Loss of vessel integrity may lead to
bleeding, and compromise of the lumen leads to downstream tissue ischemia and
necrosis. In general, affected vessels vary in size, type, and location in association
with the specific vasculitic disorder, which may occur as a primary process or be
secondary to another underlying disease. The distribution of affected organs may
suggest a particular vasculitic disorder, but significant overlap is observed.
(See 'Introduction' above.)

Classically, the vasculitic syndromes have been categorized by the predominant sizes
of the blood vessels and types of vessels most commonly affected among patients
with the disorder. The presence or absence of antineutrophil cytoplasmic antibodies
(ANCA) is a more recent addition to proposed classification criteria. The vasculitides
include: (See 'Classification' above.)
 Large vessel vasculitis Takayasu arteritis and giant cell arteritis (see 'Large vessel
vasculitis' above)
Medium sized vessel vasculitis Polyarteritis nodosa, Kawasaki disease, primary
central nervous system vasculitis (see 'Medium sized vessel vasculitis' above)
Small vessel vasculitis Churg-Strauss syndrome, granulomatosis with polyangiitis
(Wegeners), microscopic polyarteritis, Henoch-Schnlein purpura, essential
cryoglobulinemic vasculitis, hypersensitivity vasculitis, vasculitis secondary to
connective tissue disease, and vasculitis secondary to viral infection (see 'Small
vessel vasculitis' above)

The presence of vasculitis should be considered in patients who present with

systemic symptoms in combination with evidence of single and/or multiorgan
dysfunction. Although neither sensitive or specific, common complaints and signs of
vasculitis include fatigue, weakness, fever, arthralgias, abdominal pain, hypertension,
renal insufficiency (with an active urine sediment containing red and white cell and
occasionally red cell casts), and neurologic dysfunction. Certain signs are strongly
suggestive of vasculitis, including mononeuritis multiplex, palpable purpura, and
combined pulmonary and renal involvement. (See 'Clinical manifestations and
approach to diagnosis' above and 'Clinical features suggestive of vasculitis' above.)

The diagnostic evaluation should consider age and gender, which may help direct the
evaluation (table 1); a detailed history, including drug use, infectious disease
exposure, and symptoms of manifestations that may characterize or exclude
suspected diagnoses; general laboratory testing to help identify the type of disorder
and degree and type of organ involvement; and additional testing, depending on the
suspected diagnosis and findings, including tests for antinuclear antibodies,
complement levels, and ANCA; electromyography; tissue biopsy; and arteriography.
(See 'Diagnostic approach' above and 'History' above and 'Physical
examination' above and 'Laboratory tests' above and 'Electromyography' above
and 'Tissue biopsy' above and 'Arteriography' above.)

Criteria for the classification of most of the major forms of vasculitis have been
established; they do not include all characteristics of a particular disorder, only those
that help to distinguish the disorder from other vasculitides. The classification criteria
function poorly when used for clinical diagnosis, but are useful in epidemiologic and
clinical research. The diagnosis of a particular form of vasculitis is virtually always
confirmed by tissue biopsy. (See 'Classification criteria' above.)

Patients with nonvasculitic disease processes may present with symptoms and
findings that closely mimic those of the various vasculitides. Perhaps most common
are systemic rheumatic diseases such as systemic lupus erythematosus. Numerous
other disorders should be considered in selected patients, depending upon the
specific signs and symptoms that are present. (See 'Differential diagnosis' above.)

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