rheumatology1.2 Flashcards
Vasculitis
The vasculitides are a heterogeneous group of clinical disorders characterized by inflammation of blood vessels. Inflammation may involve arteries of any size: therefore, different vasculitic syndromes may have a spectrum of clinical and pathologic features. All of them mentioned here are type III.
Terminology/Classification of vasculitis
Vasculitis classification can be based on the size of the vessel involved, the type of pathologic change in the vessel wall, and/or the clinical presentation. Vasculitides can be primary occurring separately from any known underlying disease or secondary to infectious disorders such as hepatitis B or C and endocarditis, drug hypersensitivity, connective tissue diseases (RA, SLE, Sjögren’s), cryoglobulins, and malignancies.
Large-vessel vasculitis
includes giant cell and takayasu’s arteritis. More of t cell mediation
Giant cell arteritis
temporal arteries, vessels originating from the aortic arch, other arteries less common; temporal headache, jaw claudication, scalp tenderness, visual loss; giant cell arteritis with disruption of the internal elastic lamina
Takayasu’s arteritis
aortic arch and its branches, can involve any part of the aorta; claudication of upper > lower extremities, CNS events; granulomatous panarteritis. This leads to low blood flow and ischemia
Medium-vessel vasculitis
includes polyarteritis nodosa and kawasaki’s disease
Polyarteritis nodosa
small and medium-sized arteries; may affect any organ, but skin, joints, peripheral nerves, gut, and kidney are most commonly involved; focal but panmural necrotizing arteritis with a predilection for involvement at the vessel bifurcation. Often presents with abdominal pain
Kawasaki’s disease
small and medium-sized arteries; acute febrile illness primarily affecting infants and young children; fever, prominent mucocutaneous changes, cervical lymphadenopathy, polymorphous rash, erythema and edema of hands and feet, desquamation, myocarditis, coronary vasculitis; probable infectious vector resulting in cytokine-mediated endothelial damage
Small-vessel vasculitis
includes antineutrophil cytoplasmic antibody (ANCA) positive vasculitides and ANCA negative vasulitides
Antineutrophil cytoplasmic antibody (ANCA) positive vasculitides
includes granulomatosis with polyangiitis (wegener’s), eosinophilic granulomatosis with polyangiitis (churg-strauss), and microscopic polyangiitis (MPA).
Granulomatosis with polyangiitis (Wegener’s) (GPA)
small and medium-sized arteries; upper respiratory tract (sinuses), lungs, and kidneys, may affect other organs; pauci-immune, necrotizing, granulomatous arteritis usually associated with serum cytoplasmic-ANCA (c-ANCA to the PR-3). Noses collapses and patients often presents throws up blood with high creatinine.
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss):
ANCA positive. small arteries and venules; asthma, eosinophilia, multiorgan involvement – lungs, skin, peripheral nerves, gut, heart, renal (rare); necrotizing extravascular granulomas and vasculitis of small arteries and venules, eosinophils present in early stage
Microscopic polyangiitis (MPA)
arterioles, capillaries, and venules; pulmonary hemorrhage, glomerulonephritis, palpable purpura, peripheral neuropathy, joint and abdominal pain; pauci-immune, necrotizing vasculitis, serum perinuclear-ANCA (p-ANCA binds to MPO) common.
Antineutrophil cytoplasmic antibody (ANCA) negative vasculitides
includes Henoch-Schonlein Purpura (HSP), essential cryoglobulinemic vasculitis, and cutaneous leukocytoclastic angiitis.
Henoch-Schönlein Purpura (HSP)
arterioles and venules; palpable purpuric skin lesions lower extremities, arthritis, abdominal pain, hematuria; leukocytoclastic (neutrophilic perivascular/transmural infiltrate) or necrotizing vasculitis often with IgA deposition (the only one with IgA). ANCA negative.
Essential cryoglobulinemic vasculitis
cryoglobulins are immunoglobulins that are reversibly precipitated by reduced temperatures; cryoglobulins are deposited in small vessels including glomerulocapillaries; purpura, arthralgias, weakness, peripheral neuropathy, Raynaud’s phenomenon, glomerulonephritis, pulmonary hemorrhage possible; often rheumatoid factor and hepatitis C antibody positive; cryoglobulins deposited on the vascular wall stimulate complement activation and a cellular inflammatory response. ANCA negative
Cutaneous leukocytoclastic angiitis
arterioles and venules; palpable purpuric skin lesions, arthralgias, systemic symptoms may be present, usually secondary to an immune response [drugs, bugs (infections), connective tissue disease, malignancy]; leukocytoclastic vasculitis. ANCA negative
Signs/Symptoms of vasculitis
Common clinical features, including skin lesions, constitutional symptoms (fever, anorexia, weight loss, weakness, fatigue) and musculoskeletal symptoms (arthralgias, arthritis, myalgias, peripheral neuropathy) are found, to some extent, in all systemic vasculitides.
Laboratory features of vasculitis
reflect systemic inflammation – anemia of inflammatory disease, thrombocytosis, low albumin, elevated sedimentation rate and C-reactive protein, polyclonal gammopathy; possibly elevated liver enzyme tests, low complement levels, cryoglobulins
Diagnosis of vasculitis
history and physical exam to determine extent of organ involvement, detection of serum autoantibodies (RF, ANA, ANCA), biopsy of affected organ; if biopsy inaccessible, angiogram to show segments of smooth arterial stenosis alternating with areas of normal or dilated artery; tapered occlusions; thrombosis
Incidence of vasculitis
rare group of disorders with mean age of onset in the fifth decade of life, although can occur at extremes of age; approximately equal sex distribution except for a female predominance in Takayasu’s and giant cell arteritis
Ethnic associations of vasculitis
Although these disorders can occur in any population, there is a higher incidence of Takayasu’s arteritis in Japanese and Asian populations, and giant cell arteritis in populations of Northern European background, as well as in the northern latitudes.
Pathology of vasculitis
Considerable overlap exists in the patterns of pathologic involvement in the vasculitic syndromes. Vasculitic lesions tend to be both focal and segmental. The entire circumference of the vessel may not be involved.
Pathology of large and medium vessel vasculitis
typically panarteritis with infiltration to a varying degree of lymphocytes, monocytes, histiocytes, eosinophils, and polymorphonuclear leukocytes (PMNs) through the vessel wall; can be associated with granuloma or giant cell formation in some disorders (see Section I); disruption of the elastic lamina: intimal thickening results in narrowing or obliteration of the vessel lumen
Pathology of small vessel vasculitis
typically fibrinoid necrosis of the vessel wall with a transmural inflammatory reaction; often referred to as “leukocytoclastic” vasculitis – a pathologic term used to describe necrotizing vasculitis with PMN-derived nuclear debris that often accompanies the neutrophilic perivascular infiltrate of the vessel wall; immunoglobulin (IgM, IgA in HSP) and complement (C3) vascular deposition are often noted in the vasculitic lesions
Pathophysiology of vasculitis
No single pathophysiologic process accounts for the spectrum of pathology noted in the systemic vasculitides. Suspected mechanisms of vascular damage include immune complexes, antineutrophil cytoplasmic antibodies, antiendothelial antibodies, T cell dependent mediated endothelial cell injury, and infection of endothelial cells.
Immune complexes (IC) and vaculitis
Animal models of serum sickness, human serum sickness induced by horse immunoglobulins (anti-venoms), and the demonstration of hepatitis B surface antigen and IgM in an arterial wall of a patient with polyarteritis nodosa suggest that IC can mediate inflammatory vessel disease. In animal models, platelet activating factors and other vasoactive mediators released as part of the inflammatory and cytokine response probably induce vascular permeability. This is followed by deposition of circulating IC at the vascular endothelium, the activation of complement, and the attraction of PMNs. Indirect evidence suggests the IC-induced vasculitis may be involved in hypersensitivity vasculitis, HSP, cryoglobulinemia, and hepatitis B–associated vasculitis.
Antineutrophil Cytoplasmic Antibodies (ANCA)
ANCA are antibodies to antigens found in the cytoplasm of neutrophils. The cytoplasmic staining or c-ANCA (granulomatosis with polyangiitis) binds to proteinase 3 (PR3) found in the primary granules of the PMN. The perinuclear staining or p-ANCA (microscopic polyangiitis) binds to myeloperoxidase (MPO), another primary granule constituent which migrates to the perinuclear area with alcohol fixation of PMNs. Potentially, inflammatory cytokines induced by infections or other insults activate PMNs to release and express PR3 and MPO on the cell surface. The binding of ANCA to the neutrophil cell surface leads to further neutrophil activation and possibly enhanced binding to vascular endothelial cells with resultant vascular damage. PR3 and MPO have also been found on the surface of activated endothelial cells. Although ANCA may not be essential for the initiation of the vasculitis, they may play a role in amplifying the inflammatory vascular response.
