Flashcards in Robbins pg. 348-355 Deck (61)
What are some symptoms associated with vasculitis?
Does vasculitis mostly affect larger or smaller vessels?
Although several forms of vasculitis have a predilection
for relatively large vessels (e.g., large or medium-sized
muscular arteries), most affect small vessels (arterioles,
capillaries, and venules)
The two most common pathogenic mechanisms of
vasculitis are what?
-Direct vascular invasion by infectious pathogens
The main immunologic mechanisms underlying noninfectious vasculitis are:
• Immune complex deposition
• Antineutrophil cytoplasmic antibodies
• Anti-endothelial cell antibodies
• Autoreactive T cells
What are some vasculitis conditions mediated by immune complex deposition?
Immunologic disorders such as SLE that are associated with autoantibody production.
Only rarely is the specific antigen responsible for immune complex formation known. While immune complexes are occasionally detected in the blood, in most instances it is not clear whether the pathogenic antigen-antibody complexes are deposited from the circulation or form in situ
Immune complex deposition is implicated in what vasculitides?
Drug hypersensitivity vasculitis. In some cases drugs (e.g.,
penicillin) act as haptens by binding to host proteins;
other agents are themselves foreign proteins (e.g., streptokinase). Regardless, antibodies directed against the
drug-modified proteins or foreign molecules result in immune complex formation. The clinical manifestations can be mild and self-limiting, or severe and even fatal; skin lesions are most common. It is always important to
consider drug hypersensitivity as a cause of vasculitis, since discontinuation of the offending agent usually leads to resolution.
Vasculitis secondary to infections. Antibody to microbial
constituents can form immune complexes that circulate
and deposit in vascular lesions. In up to 30% of patients with polyarteritis nodosa, the vasculitis is attributable to immune complexes composed of hepatitis B surface antigen (HBsAg) and anti-HBsAg antibody
How do ANCAs cause vasculitis?
Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called anti-neutrophil cytoplasmic antibodies (ANCAs).
What are ANCAs?
ANCAs are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cells.
ANCAs are very useful diagnostic markers; their titers generally mirror clinical severity, and a rise in titers after periods of quiescence is predictive of disease recurrence.
What are some important ANCAs?
• Antiproteinase-3 (PR3-ANCA), previously called c-ANCA. PR3 is a neutrophil azurophilic granule constituent that shares homology with numerous microbial peptides, possibly explaining the generation of PR3- ANCAs. PR3-ANCAs are associated with Wegener granulomatosis.
• Anti-myeloperoxidase (MPO-ANCA), previously called p-
ANCA. MPO-ANCAs are induced by several therapeutic agents, particularly propylthiouracil. MPO-ANCAs are associated with microscopic polyangiitis and Churg-Strauss syndrome
The close association between ANCA titers and disease
activity suggests a pathogenic role for these antibodies.
What can ANCAs do?
ANCAs can directly activate neutrophils, stimulating the release of reactive oxygen species and proteolytic enzymes; in vascular beds, this may lead to endothelial cell injury.
Where else are ANCAs found?
ANCA antigens (especially PR3) either are constitutively expressed at low levels on the plasma membrane or are translocated to the cell surface in activated and apoptotic leukocytes
Describe the mechanism for ANCA vasculitis.
• Drugs or cross-reactive microbial antigens induce
ANCA formation; alternatively, leukocyte surface expression or release of PR3 and MPO (in the setting of infections) incites ANCA development in a susceptible host.
• Subsequent infection, endotoxin exposure, or inflammatory stimulus elicits cytokines such as TNF that up regulate the surface expression of PR3 and MPO on
neutrophils and other cell types
• ANCAs bind these cytokine-activated cells, causing
further activation of neutrophils.
• ANCA-activated neutrophils cause endothelial cell
injury by releasing granule contents and reactive oxygen
T or F. The ANCA autoantibodies are directed against cellular constituents and do not form circulating immune complexes.
What is a condition that causes antibodies against endothelial cells?
What is Giant cell (temporal) arteritis?
The most common form of vasculitis among the elderly in developed countries. It takes the form of chronic, typically granulomatous, inflammation of large to small size arteries
What arteries are most affected by Giant cell arteritis?
mainly those supplying the head—especially the temporal arteries. Vertebral and ophthalmic arteries, as well as the aorta (giant cell aortitis), also can be involved.
Because ophthalmic artery involvement can lead to sudden
and permanent blindness, affected persons must be diagnosed and treated promptly
What causes giant cell arteritis?
The bulk of evidence suggests the culprit is a T cell–mediated immune response to an as-yet uncharacterized vessel wall antigen.
Pro-inflammatory cytokines (especially TNF) and
anti-endothelial cell antibodies also contribute.
Why is an immune etiology suggested for giant cell arteritis?
- characteristic granulomatous inflammation,
- the association with certain MHC class II haplotypes, and - the excellent therapeutic response to steroids
all are in favor of an immune etiology.
How does temporal arteritis present clinically?
- rare before 50.
- Signs and symptoms may be vague and constitutional—fever, fatigue, weight loss—or take the form of facial pain or headache, most intense along the course of the superficial temporal artery, which is painful to palpation.
- elevated ESR
How common is ocular involvement in temporal arteritis patients?
(associated with involvement of the ophthalmic artery)
abruptly appear in about 50% of patients; these range from diplopia to complete vision loss.
Diagnosis depends on biopsy and histology; however, because involvement in temporal arteritis is patchy a negative biopsy result does not exclude the diagnosis.
How is temporal arteritis treated?
Corticosteroid or anti-TNF therapies are effective treatments
What is Takayasu arteritis?
Takayasu arteritis is a granulomatous vasculitis of medium sized and larger arteries characterized principally by ocular
disturbances, upper body weakness, and marked weakening of the pulses in the upper extremities (hence the alternate name, pulseless disease).
Where does Takayasu arteritis typically affect?
Takayasu arteritis classically affects the aortic arch and arch vessels; a third of cases also involve the remainder of the aorta and its branches
Pulmonary arteries are involved in 50% of patients,
and renal and coronary arteries also can be affected
How is Takayasu arteritis differentiated from Temporal arteritis?
Made largely on the basis of a patient’s age; those older than 50 years are designated giant cell aortitis, and those younger than 50 years, Takayasu aortitis.
How does Takayasu arteritis present clinically?
- Constitutional symptoms
- With progression, vascular signs and symptoms appear and dominate the clinical picture.
- Distal aorta disease can manifest as leg claudication, and pulmonary artery involvement can cause pulmonary hypertension.
- Narrowing of the coronary ostia can lead to MI, and
- involvement of the renal arteries causes systemic hypertension in roughly half of the patients.
What vascular signs are common with Takayasu?
-reduced upper extremity blood pressure and pulse strength;
-neurologic deficits; and
-ocular disturbances, including visual field defects, retinal hemorrhages, and total blindness.
Prognosis of Takayasu?
Some cases rapidly progress, while others become quiescent after 1 to 2 years. In the latter scenario, long-term survival, albeit with visual or neurologic deficits, is possible
What is Polyarteritis nodosa (PAN)?
segmental transmural (involve only part of the vessel circumference) necrotizing inflammation of small or medium-sized muscular arteries that typically involves the
renal and visceral vessels and spares the pulmonary circulation.
What is PAN associated with?
There is no association with ANCAs, but a third of
the patients have chronic hepatitis B infection, which leads to the formation of immune complexes containing hepatitis
B antigens that deposit in affected vessels.