VASCULITIS SYNDROMES

The vasculitides are a heterogeneous group of relatively uncommon

diseases that can arise as primary conditions or secondary to an
established disease such as rheumatoid arthritis (RA)
or systemic lupus erythematosus (SLE)
The vasculitides are linked by the presence of vascular inflammation,
which can lead to one of two common outcomes:
• vessel wall destruction , leading to aneurysm or rupture;
• stenosis , leading to tissue ischaemia and necrosis

In 1994, the Chapel Hill Consensus Conference (CHCC) developed a

standard nomenclature for the primary systemic vasculitides based on
clinical and laboratory features, and categorized by vessel size:
• large vessel: aorta and its major branches (‘great vessels’);
• medium vessel: main visceral arteries (e.g. renal, mesenteric);
• small vessel: capillaries, arterioles, and venules.
According to the size of the vessel affected, vasculitis can be classified into:[7][8].

 Large vessel vasculitis

Takayasu arteritis
Giant cell arteritis
 Medium sized vessel vasculitis
Polyarteritis nodosa
Kawasaki disease
 Small vessel vasculitis
Small vessel vasculitis
ANCA – associated vasculitis
Microscopic polyangiitis
Granulomatosis with polyangiitis (Wegener’s)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
Immune complex small vessel vasculitis
Anti-glomerular basement membrane antibody disease
Cryoglobulinemic vasculitis
IgA vasculitis (Henoch Schönlein)
Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
 Variable vessel vasculitis
Behçet’s disease
Cogan’s syndrome
 Singel-organ vasculitis
Cutaneous leukocytoclastic angiitis
Cutaneous arteritis
Primary central nervous system vasculitis
Isolated aortitis
Others
 Vasculitis associated with systemic disease
Lupus vasculitis
Rheumatoid vasculitis
Sarcoid vasculitis
Others
 Vasculitis associated with probable etiology
Hepatitis C virus – associated cryoglobulinemic vasculitis
Hepatitis B virus – associated vasculitis
Syphilis-associated aortitis
Drug-associated immune complex vasculitis
Drug-associated ANCA-associated vasculitis
Cancer-associated vasculitis
Others

Etiology and Pathogenesis

The unifying feature of all vasculitides is the activation of
inflammatory mediators within vessel walls. Virtually all
components of the effector arm of the immune system may
be affected. For instance, T-cell-mediated inflammation
has been implicated as a causative feature in giant cell
arteritis and Takayasu’s arteritis. In immune complex–
mediated vasculitides, circulating antibody-antigen complexes
deposit within the vessel wall or form within the
vessel wall itself (in situ immune complex formation).
Direct antibody binding to antigens integral to vessel
walls occur in Goodpasture’s syndrome secondary to anti–
glomerular basement antibodies, and in Kawasaki’s disease
because of antiendothelial antibodies. Regardless of how
they are deposited within the vasculature, immune complexes,
complement, coagulation, and kinin systems act as
infl ammatory (phlogistic) stimulants for neutrophils and
monocytes. These cells then release toxic oxygen metabolites
and enzymes that damage the vasculature.
Pauci-immune vasculitides are characterized by lacking
either immune complexes or direct antibody binding to the
vessel wall. They are closely associated with antineutrophil
cytoplasmic antibodies (ANCA). Although the role of
ANCA is not certain, a large body of evidence suggests
that these antibodies are pathogenic agents.
In the presence of stimulatory cytokines, ANCA antigens
(myeloperoxidase and proteinase 3) are translocated to the
surface of neutrophils and monocytes, allowing binding of
ANCA to their target antigens. Alternatively, release of
these antigens from leukocytes and endothelial cells may
result in damage from immune complex formation with
ANCA or by the direct effect of leukocyte serine protein,
causing endothelial cell death.

Takayasu’s arteritis

• Takayasu’s arteritis (TA) is a chronic granulomatous arteritis that

affects the aorta and the great vessels. The pulmonary arteries can also
be involved, although this is relatively uncommon..
• TA tends to affect women (90% of cases) with adolescents and
young adults between 20 and 40 years at greatest risk. Classification
criteria distinguish TA from giant cell arteritis (GCA) by age at onset
(i.e. TA <40 years, GCA >50 years).
• The hallmark of the disease is arteritic inflammatory infiltrates that
cause luminal narrowing or occlusion; clinically, this presents with
bruits, claudication, and diminished (or asymmetric) pulses.
• Light headedness, visual disturbance, and strokes can occur. Subclavian
steal can be an important cause of neurological symptoms.
• Hypertension may develop as a consequence of renal artery stenosis.
• Musculoskeletal symptoms, including arthralgias and myalgias, are not
uncommon.
• Cardiovascular complications are an important cause of morbidity,
and include aortic insufficiency, congestive heart failure, systemic
hypertension, and ostial involvement of the coronary arteries.
• Traditionally, the diagnosis of TA has depended on angiography
to demonstrate the characteristic changes of arterial dilatation,
thrombosis, and aneurysm formation. Conventional angiography has
the added benef t of allowing a comparison between central and
peripheral blood pressures; because subclavian stenosis is a common
consequence of this disease, a standard arm cuff blood pressure
reading may underestimate central hypertension.
• Magnetic resonance imaging/angiography (MRI/MRA) has excellent
resolution at the level of the large vessels, and may be the technique of
choice for some patients. MR can also demonstrate evidence of vessel
wall inflammation, which could support a diagnosis of TA.
• High-resolution ultrasonography is sensitive for detecting carotid
lesions.
• Positron emission CT (PET) scanning is useful for identifying the
presence of large vessel vasculitis, but it is not clear whether it can be
used to monitor response to therapy.
Treatment
• Initial medical treatment is with corticosteroids (prednisolone 1 mg/kg/
day). Most patients should also be treated with MTX 20–25 mg po per
week; patients with severe forms of the disease should be treated with
cyclophosphamide 2 mg/kg/day.
• An anti-TNF-α agent should be used for severe or resistant cases.
• Hypertension can be difficult to manage, and may require angioplasty
or surgery to address renal artery stenosis.
• Surgical management ranges from angioplasty to bypass procedures.
These are best performed during the inactive phase of disease.
Angioplasty is often a temporizing measure, and lesions tend to
restenose over time; when intervention is required, bypass is the
treatment of choice. Overall operative mortality is 4%, associated
mostly with aneurysm rupture.
• The prognosis depends mainly on the presence of hypertension
and aortic incompetence.

Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a multisystem disease which presents with nonspecific

complaints such as fever, malaise, weight loss, anorexia, and abdominal pain. The disease can
affect nearly any site in the body, except the lungs. It has a predisposition for organs such as
the skin, kidney, nerves, and GI tract.
• Peripheral neuropathies are very common: tingling, numbness, and/or pain in the
hands, arms, feet, and legs, and mononeuritis (e.g., foot drop).
• GI manifestations are common: abdominal pain and GI bleed (occasionally mistaken
for inflammatory bowel disease).
• Active hepatitis B infection is seen in a minority of patients.
Diagnosis is made by biopsy of involved organs (most commonly taken from skin, symptomatic
nerves, or muscle). The biopsy will show pathologic changes in medium-size arteries.
Angiogram of the abdominal vessels may also be helpful for diagnosing PAN, since aneurysms
affecting the arteries of the kidneys and/or GI tract are found.
Treatment is high doses of corticosteroids and immunosuppressive drugs (cyclophosphamide).
(Before these treatments were available, untreated PAN was usually fatal within weeks to
months, with most deaths occurring from kidney failure, or heart or GI complications.)
Wegener Granulomatosis (Granulomatosis with polyangiitis)
Wegener granulomatosis is a small vessel vasculitis. It typically affects the respiratory tract
(sinuses, nose, trachea, and lungs) and kidneys, but can involve any organ system.
The most common sign of Wegener granulomatosis is involvement of the upper respiratory
tract, which occurs in nearly all patients.
Symptoms include rhinitis, sinusitis, and, rarely, nasal ulcers.
• A common sign of the disease is chronic rhinitis that does not respond to usual
treatment and that becomes increasingly worse.
• Despite lack of symptoms, lungs are affected in most people; if symptoms are present, they
include cough, hemoptysis, and dyspnea.
• Kidney involvement (>80% of patients) (major cause of morbidity and mortality)
• Arthritis (60% of patients)
Diagnostics
• Presence of antineutrophil cytoplasmic antibodies (C-ANCA)
–– Although a positive ANCA test is useful to support a suspected diagnosis of
Wegener granulomatosis, it is never diagnostic.
–– The C-ANCA test may be negative in some people with active Wegener. The only
way to confirm the diagnosis is with a biopsy of an involved organ (usually nasal
septum), demonstrating the presence of vasculitis and granulomas.

Modified American College of Rheumatology 1990

classification criteria of Wegeners granulomatosis—diagnosis
requires 2 or more of the following:
1 Nasal or oral infl ammation: development of painful or painless oral ulcers or
purulent or bloody nasal discharge
2 Abnormal chest radiograph: the chest radiograph may show nodules, cavities,
or infi ltrate
3 Urinary sediment: microscopic hematuria or red cell casts
4 Histological changes of granulomatous infl ammation on biopsy
5 PR3-ANCA (C-ANCA) positivity
Standard treatment is combined glucocorticoid plus an immunosuppressive agent
(cyclophosphamide).
Henoch–Schцnlein purpura (IgA vasculitis)
• This tends to be regarded as a special form of allergic vasculitis. It
occurs most often in children, but can affect adults of any age. IgA is
usually detected in skin, gut, or renal biopsies.
• The classic presentation is with purpura, arthritis (50%), haemorrhagic
GI disease (40%), and glomerulonephritis (50%).
The rash may begin as macular erythema and urticarial lesions, but may progress rapidly to
purpura. The lower extremities and buttocks are the most common sites for the rash. Scrotal
and scalp edema can be seen, particularly in children. The joints are involved in 60% to 84% of
patients. The involvement is symmetrical and most commonly involves the ankles and knees,
which are usually swollen, warm, and tender. GI lesions may cause severe cramping, abdominal
pain, intussusception, hemorrhage, and, rarely, ileal perforation. Renal
involvement is seen in 50% of patients and is usually manifest as asymptomatic proteinuria and
hematuria.
However, more marked findings may occur, including nephrotic syndrome and acute renal
failure. IgAV is often acute in onset, and resolution is rapid and complete in 97% of cases,
except in a minority of patients (3% to 5%) with chronic renal disease. Persons of any age can
be affected, but IgAV occurs primarily in children between the ages of 2 and 10 years. Adults
have more severe disease with a higher frequency of renal involvement. Patients of any age
(especially adults) suspected of having IgAV for whom a skin biopsy is negative or IgA should
be evaluated for ANCA-associated vasculitis, anti-C1q disease, or IgA paraproteinemia.

Treatment
Corticosteroids given early may relieve joint and GI symptoms, but there is little
evidence that they prevent progression of renal disease or influence
overall outcome. If renal function is rapidly deteriorating, pulsed
methylprednisolone and/or plasmapheresis may be of benefit.
• Patients who present with a nephritic or nephrotic syndrome have
an increased lifetime prevalence of renal complications, including hypertension.
• Although most cases are self-limited, this can (rarely) become a chronic,
relapsing disease. Such patients should be evaluated for the presence of
a monoclonal IgA antibody, which may herald a pre-malignant lesion.