Definition
In clinical use, vasculitis refers to inflammation and/or necrosis that is predominantly centered on blood vessels.
Classification
There are many ways that vasculitis can be classified. None are ideal, since there is considerable overlap between the clinical presentations, histology and etiologies. The classification below is based on size of the vessel involved. However, it is the clinical presentation and distribution that defines the disease and the histology confirms the presence of vasculitis. Only for a few diseases are the histologic features distinct enough to diagnose the type of vasculitis (e.g. Wegener's granulomatosis, Churg-Strauss syndrome).
Classification of Vasculitis:
1. Large vessel vasculitis
i) Takayasu arteritis
ii) Infectious Aortitis (e.g. syphilitic aortitis)
iii) Giant cell arteritis
a) Temporal arteritis
b) Primary granulomatous arteritis of the CNS
iv) Large vessel arteritis associated with autoimmune disease
(rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, relapsing polychondritis, Cogan's syndrome).
2. Medium size vessel vasculitis
i) Thromboangiitis obliterans (Buerger's disease)
ii) Polyarteritis nodosa (PAN)
iii) Churg-Strauss syndrome
iv) Wegener's granulomatosis
v) Kawasaki's disease
vi) Vasculitis associated with collagen vascular diseases.
3. Small vessel vasculitis (hypersensitivity vasculitis, leukocytoclastic vasculitis).
Frequency
Temporal arteritis is the most common type of the vasculitis, representing about 40% of the histologically diagnosed cases with an incidence of 1-20 cases/100,000 people per year. Polyarteritis nodosa, small vessel vasculitis, Wegener's granulomatosis, vasculitis associated with collagen vascular diseases, and thromboangiitis obliterans each represent 5-10% of the reported cases of vasculitis. Takayasu's arteritis, Kawasaki's disease, primary granulomatous arteritis of the CNS, and Churg-Strauss disease are rare.
Etiology
Medium and small vessel vasculitis occur in animal models of vasculitis (e.g. dermal Arthus reaction, serum sickness) induced by the deposition of antigen-antibody immune complexes. In human diseases, immune complexes may also play a major role. Ten to 50% of those with PAN have or have had measurable Hepatitis B surface antigen (HBsAg) in their serum. Deposition of this antigen with the associated antibody can precipitate a type III immune injury. Reduction of serum complement levels and the presence of circulating immune complexes in some cases of vasculitis implicate this mechanism. However, the presence of immune complexes is not universal. Microscopic PAN, Wegener's, Temporal arteritis, Takayasu's, Buerger's disease characteristically show no specific evidence of immunoglobulin deposition. The etiology in these diseases is not well defined. Antibody deposition may be present, but in insufficient amounts to detect with conventional techniques (immunofluorescence or electron microscopy).
Anti-neutrophil cytoplasmic antibodies
The presence of two autoantibodies seen in some cases of vasculitis is of diagnostic importance:
1) c-ANCA [cytoplasmic-antineutrophil cytoplasmic antibodies) is relatively specific for Wegener's granulomatosis and a microscopic form of PAN. c-ANCA titres parallel disease activity and rising titres may herald relapse of disease.
2) p-ANCA (perinuclear-ANCA) is seen in a wide variety of vasculitides and is of much less clinical utility.
Polyarteritis Nodosa
Classic presentation:
1) Necrotizing vasculitis of small and medium sized muscular arteries;
2) Involves the vessel of the kidney, viscera, peripheral nerves, joints and skin;
3) Relative sparing of the lungs (vs. Wegener's and Churg-Strauss);
4) 10-50% of cases associated with HBsAg.
Clinical: The earliest feature is a multisystem disease with the classic presentation being a vasculitic skin lesion, mononeuritis and renal disease.
Histology. The vasculitis tends to be multifocal so that along the length of an affected artery there are acutely inflamed necrotic segments adjacent to relatively normal segments. In addition, affected areas show lesions of differing age. Early lesions show fibrinous necrosis of the vessel wall with a mixed cellular infiltrate, including neutrophils. Some areas show segmental, rather than circumferential destruction, which results in the formation of microaneurysms. Older lesions may show resolution of the inflammation with fibrosis.
Churg-Strauss syndrome
Characteristic features:
1) History of asthma;
2) Peripheral eosinophilia;
3) Characteristically affects the lungs (like Wegener's, unlike classic PAN);
4) Histology: necrotlzing vasculitis associated with eosinophils and multinucleated giant cells.
Churg-Strauss is considered to be a variant of PAN, but with a distinct presentation.
Churg-Strauss syndrome is very rare.
Wegener's Granuiomatosis
Wegener's is a necrotizing and granuiomatous vasculitis that manifests as a distinctive triad of organ involvement:
1) Ear, nose and/or throat;
2) Lung;
3) Kidney.
While the triad defines Wegener's, the disease is still a systemic necrotizing vasculitis involving many organs. The presence of c-ANCA in the serum of these patients is closely linked to the disease and virtually specific.
"ELK": The classic presentation of Wegener's has all three of key areas: ENT, Lung and Kidney. However, presentation may only involve one or two of these target organs and is referred to by some as "limited" Wegener's (e.g. EK, EL, LK).
Histology: Wegener's is a necrotizing vasculitis. Classic lesion involves necrosis of medium size vessels with infiltration by neutrophils and multinucleated giant cells. In the upper airvvay, nonspecific vasculitis and necrosis are the predominant features. Granulomatous inflammation can be seen, but is uncommon. In the lung, the necrosis takes on a "geographic" pattern and the classic necrotizing granulomatous vasculitis is found. A small vessel capillaritis and intraalveolar hemorrhage may also be seen. In the kidney, the ischemic injury is seen predominantly in the glomeruli where there is a crescentic glomerulonephritis.
Prognosis: Untreated (or unrecognized), the disease is almost uniformly fatal. With treatment with cyclophosphamide, 90% of cases can be put into remission.
Temporal arteritis (Giant Cell Arteritis)
Temporal arteritis is one of the most common forms of vasculitis. While a systemic vasculitis, this disease mainly affects large and medium size branches of the carotid artery. The characteristic clinical features are as follows (with the presence of the first 3 being diagnostic):
1) Headache - localized, sharp aching and throbbing;
2) Claudication of muscles of mastication;
3) Palpable tenderness over the temporal artery with thickening;
4) Visual symptoms;
5) Systemic malaise.
Morbidity: Morbidity is associated with involvement of the ophthalmic artery with ischemic retinal injury and blindness.
Pathology: As with polyarteritis nodosa, the lesions are focal and segmental. The temporal artery is most often examined because of ease of access with a minimum of complication. Grossly, abnormal segments provide the best diagnostic yield. The classic histology is a mixed infiltrate of neutrophils and lymphocytes in the intima and muscularis. Characteristically, the internal elastic lamina is fragmented and frayed. Multinucleated giant cells are often seen (but not essential). Older lesions show the hallmarks of previous injury with intimal thickening and fibrosis of the wall. The fragmented elastica never returns to its normal architecture.
Buerger's disease [thromboangiitis obliterans]
Characteristic features:
1) Vasculitis of veins and arteries of the distal limbs with proximal progression with time; 2) Predominantly males, less than 40 years old;
3) Smoking history.
Buerger's disease is less systemic than the other vasculitic syndromes discussed here. The disease progresses proximally over months to 1-2 years, resulting in claudication or ischemic changes beginning with the digits. These changes can be accompanied by Raynaud's phenomenon and superficial migratory thrombophlebitis.
Histology: Involves veins and arteries. The acute lesions show predominantly a mixed-infiltrate in the vessel wall. Characteristically, the lumen is filled with thrombus that contains collections of neutrophils ("microabscess") and possibly giant cells.
Prognosis: Etiology of the disease is unknown. Stopping the progression of the disease is dependent on the complete cessation of smoking. lschemic changes are treated medically with vasodilators, but amputation may be necessary.
Kawasaki syndrome [mucocutaneogs lymph node syndramel
Kawasaki syndrome is an acute self limited disease of young children, whose descriptive name, mucocutaneous lymph node syndrome, summarizes the characteristic features:
1) Mucocutaneous symptoms:
a) reddening of the lips;
b) strawberry tongue;
c) diffuse injection of the oral and pharyngeal mucosa;
d) intense reddening of the palms and soles;
e) edema of palms and soles;
f) peeling of the palms and soles;
g) polymorphous rash;
h) conjunctival injection
2) Acute cervical lymphadenopathy;
3) High persistent (>5d) fever.
Kawasaki syndrome is typically a disease of young children (>5 years old), with a higher incidence in orientals and in Japan. It generally runs a benign course, requiring only symptomatic treatment. However, there is a 2% mortality associated with coronary arteritis and thrombosis in untreated cases. Therapy is directed at the prevention of the coronary complication.
Histology: Non-specific arteritis similar to that in PAN. While most patients are asymptomatic, 20% of patients have evidence of arteritis of the coronary vessels by ultrasound.
Etiology: Unknown. There is a seasonal variation in the disease with community outbreaks being described. Infectious and other environmental factors have been suggested but not proven.
Takayasu's arteritis
Characteristic features:
1) Granulomatous and sclerosing arteritis involving media and adventia of the aorta and its major branches;
2) Typically involves young adults (< 40 years old);
3) Associated with limb ischemia with the characteristic reduction of the peripheral pulses ("pulseless disease").
Involvement of the carotid vessels may be manifest by visual symptoms associated with ischemia (like the more common temporal arteritis)
"Pulseless disease in a young oriental female"; this popular patient stereotype is found in less than 10% of cases in North America.
Prognosis: The disease course is variable with some response to corticosteroids. For those with minimal symptoms, the overall survival is excellent. Those with active and severe disease have a 50% 6-year survival.
Small vessel vasculitis (hypersensitivity vasculitis, leukocytoclastic vasculitis)
This is not a disease with a unique etiology, but the skin manifestation of IC deposition. It may be a feature of any disease where immune complexes are deposited in the small vessel of the skin.
Histology: The affected small vessels (arterioles, capillaries and venules) are destroyed [fibrinoid necrosis) by an infiltrate of neutrophils.
COURTESY:Dr. B. Walker
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