3.4 Vasculitides and Peripheral Vascular Disease

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  1. What are causes of Vasculitis?
    • Infectious agents
    • Mechanical trauma
    • Radiation or toxins
    • Many cases - no specific etiology is determined
  2. What is Vasculitis?
    Autoimmune destruction (inflammation and necrosis) of systemic blood vessels
  3. What is the pathogenesis of Vasculitides?
    • 1. Deposition of immune complexes
    • 2. Direct attack on the vessels by circulating antibodies
    • 3. Various forms of cell-mediated immunity
    • The initial start is unknown but evidence shows that it may be associated w/ a viral infection
  4. What are the possible viruses, implicated in causing Vasculitides?
    • Hepatitis B virus - associated w/ some cases of Polyarteritis Nodosa (viral antigen antibody immune complexes are deposited in the vessel wall)
    • Others: Herpes simplex, CMV, Parvovirus B19 (DNA virus that causes Fifths disease - "Slap Cheek Syndrome" or Erythema Infectiosum)
  5. What is Anti-Neutrophil Cytoplasmic Antibodies (ANCA's)?
    • Associated w/ small vessel vasculitides (Wegener granulomatosis and Polyarteritis Nodosa)
    • Contribution of autoantibodies to the vasculitis not understood
    • May cause endothelial damage by activating neutrophils and antibody titers correlate w/ disease activity
  6. How are ANCA's detected?
    By indirect immunoflourescence assays using the pts serum and ethanol-fixed neutrophils
  7. What is the difference between indirect and direct immunoflourescence?
    • Indirect - taking pts serum and exposing kit
    • Direct - taking pts tissue and testing for a particular organism/ antibody/ enzyme
  8. What is the difference between C-ANCA's and P-ANCA's?
    • P-ANCA - Perinuclear immunoflourescence - only stains nuclei (popular in PAN - Polyarteritis Nodosa)
    • C-ANCA - Cytoplasmic immunoflourescence (more general) - staining just w/in the cytoplasm (popular in Wegener's)
    • Each indicates different vasculitides
    • Two have different patterns
  9. What are the general characteristics and pathophysiology of Polyarteritis Nodosa (PAN)?
    • Acute, necrotizing vasculitis that affects medium and smaller sized muscular arteries then systemic organs
    • More common in white males
    • Not as common as other vasculitides but much more devastating
  10. What is the pathology PAN?
    • Lesions in muscular arteries are patchy in distribution
    • May extend to renal, splenic, or coronary arteries
    • Most prominent feature of the affected artery is an area of fibrinoid necrosis in which the medial muscle and adj. tissue are fused into a eosinophilic mass of fibrin
    • A vigorous acute inflammatory response surrounds the area of necrosis and extends into all the other layers of the vessel
  11. What is the most prominent feature of PAN?
    • Area of fibrinoid necrosis in which the medial muscle and adjacent tissue are fused into a eosinophilic mass of fibrin
    • A vigorous acute inflammatory response surrounds the area of necrosis and extends into all the other layers of the vessel
  12. What are the complications of PAN?
    • Smaller arteries (more thrombotic) - Thrombosis is common and infarcts are usually found in involved organs
    • Larger arteries (more aneurysms) - Injury is associated w/ the formation of small aneurysms, particularly in the branches of the renal, coronary, and cerebral arteries
    • Both - Total destruction of wall leading to hemorrhage
  13. What are the chronic complications of PAN?
    • An aneurysm may rupture, and if located in a critical area, may cause a fatal hemorrhage
    • Many of the vascular lesions will show evidence of healing w/ fibrosis of the media and gaps in the elastic laminae, especially if corticosteroids have been administered
  14. What are the clinical presentations of PAN?
    • Highly variable depending on organs involved
    • Kidneys, heart, skeletal muscles, skin, and mesentery are most frequently involved, but lesions may also occur in any organ in the body
    • Constitutional symptoms: fever, weight loss are common
  15. What is the tx of PAN?
    • Corticosteroids and Cyclophosphamide therapy may lead to remission
    • W/o tx, PAN is fatal
  16. What is Temporal Arteritis and what are some general characteristics?
    • Describes a focal, chronic, granulomatous inflammation of the temporal arteries that has systemic manifestations
    • Can involve additional cranial arteries, the aorta, and its branches, and other arteries
    • Avg age of onset is 70 years and rarely occurs in those younger than 50
    • Women slightly more affected
  17. What is the most common Vasculitis?
    Temporal Arteritis or Giant Cell Arteritis
  18. What is the etiology of Temporal Arteritis?
    • Obscure
    • Supports a genetic component
    • Presence of activated CD4+ T cells suggests an immunological rxn, and a cell-mediated response to arterial antigens has been reported in some cases
  19. What is the pathology of Temporal Arteritis?
    • Grossly - affected vessel is cord-like and exhibits nodular thickening
    • Lumen is reduced to a slit or may be obliterated by a thrombus
    • Microscopically - granulomatous inflammation of the media and intima, consisting of aggregates of macrophages, lymphocytes, and plasma cells w/ varying amounts of neutrophils and eosinophils
    • Giant cells (which tend to be distributed at the site of the elastic laminae) are present
    • Foci of necrosis are present in the elastic lamina w/ fragmentation
    • In advanced lesions, the elastic laminae may disappear
    • In the late stages, the intima is thickened and the media is fibrotic
    • Thrombosis may obliterate the lumen after which organization and canalization occurs
  20. What are the clinical features of Temporal Arteritis?
    • Benign and self-limited w/ the symptoms subsiding in 6-12 months
    • Pts present w/ h/a and throbbing temporal pain, sometimes along w/ malaise, fever, weight loss, and generalized muscular aching or stiffness in the shoulders and hips (polymyalgia rheumatica)
    • Visual symptoms occur in almost 1/2 of pts and may proceed from transient to permanent blindness (if internal more than external is involved)
    • Throbbing and pain over the temporal artery is accompanied by swelling, tenderness, and redness in the skin overlying the vessel
  21. How is the dx made for Temporal Arteritis?
    • Biopsy of the temporal artery may not disclose the disease as in many as 40% of pts w/ otherwise classic manifestations
    • Due to the focal nature of the disease
  22. What is the tx for Temporal Arteritis?
    Response to corticosteroid therapy is dramatic w/ symptoms subsiding w/in days
  23. What is another name for Kawasaki Disease?
    Mucocutaneous Lymph Node Syndrome
  24. What is Kawasaki Disease?
    • Acute, necrotizing vasculitis of infancy and early childhood
    • Only pediatric disease that can cause aneurysms to the coronary artery
  25. Which organs and tissues are involved in Kawasaki Disease?
    • Mucous
    • Skin
    • Lymph nodes
  26. What are the clinical features of Kawasaki Disease?
    • High fever, rash, conjunctival and oral lesions, lymphadenitis
    • Desquamation of the fingertips, soles, and palms
  27. What is the etiology of Kawasaki Disease?
    • Self-limited and although an infectious cause has been sought, none has been conclusively proved
    • Infection w/ Parvovirus B19 has been implicated in some cases, and there is evidence for various bacterial infections in others
  28. What are the complications of Kawasaki Disease?
    • 70% of pts have vasculitis that affects the coronary arteries and leads to the formation of coronary artery aneurysms
    • Such lesions are the cause of death in 1-2% of the cases
  29. What is Takayasu Artertitis and the vessels involved?
    Inflammatory disorder of large arteries (ie aortic arch and its major branches)
  30. Who is mainly affected in Takayasu Arteritis?
    World-wide distribution and primarily affects young women (90%), majority younger than 30 years of age
  31. What is the etiology of Takayasu Arteritis?
    Cause: Unknown (autoimmune?)
  32. What is the gross pathology of Takayasu Arteritis?
    • Grossly: aorta is thickened and the intima exhibits focal, raised plaques
    • Branches of aorta exhibit localized stenosis or occlusion, which interferes w/ blood flow and accounts for the synonym "Pulseless Disease" when the subclavian arteries are affected
    • Thoracic and abdominal aorta commonly show aneurysms
  33. What is "Pulseless Disease"?
    When Takayasu Arteritis has the subclavian arteries affected
  34. What is the microscopic findings of Takayasu Arteritis?
    Panarteritis (intima, media, adventia) with infiltrates of neuts, lymphs, and giant cells (granulomatous inflammation)
  35. What is the clinical presentation of Takayasu Arteritis?
    • Dizziness, visual disturbances, occasionally symptoms early in disease
    • As disease progresses, cardiac symptoms appear w/ claudication of the arms and legs
    • Asymmetrical differences in the BP may occur, and the pulse in 1 extremity may be absent
    • Majority eventually manifest CHF and visual defects, ranging from field defects to total blindness
  36. What is the tx for Takayasu Arteritis?
    • Early - steroids
    • Later - surgery to replace effected vessels
  37. What is Wegener Granulomatosis?
    Who is infected more and what is the etiology?
    • Systemic, necrotizing vasculitis of unknown etiology characterized by granulomatous lesions of the respiratory tract (nose, sinuses, and lungs) and renal glomerular disease
    • Men affected more usually in 50-60's
    • Etiology: Unknown and no infectious agents ID
    • (Necrotizing sinusitis in older males)
  38. Which ANCA is associated w/ Wegener Granulomatosis?
    • C-ANCA (90%)
    • Antibodies activate circulating neutrophils to attack the blood vessels
  39. What are the renal and pulmonary pathology and clinical features of Wegener Granulomatosis?
    • Renal - exhibit focal necrotizing glomerulonephritis, which progresses to Crescentic Glomerulonephritis (Rapidly Progressive Glomerulonephritis)
    • Pulmonary - persistent bilateral pneumonia w/ nodular infiltrates that undergo cavitation (similar to tuberculosis)
    • Chronic granulomatous sinusitis and ulcerations of the nasopharyngeal mucosa are common
  40. What is the microscopic pathology in Wegener's?
    • Lesions feature parenchymal necrosis, vasculitis, and a granulomatous inflammation composed of neuts, lymphs, plasma cells, macrophages, and eosinophils
    • The necrotizing granulomas in the lungs must be differentiated from those of TB (caseating granulomas)
    • Acute inflammation, necrotizing granulomatous inflammation and fibrinoid necrosis, all leading to medial thickening, intimal proliferation and narrowing of the lumen
  41. Which organs are most involved regarding Wegener's?
    Vasculitis involving the small arteries and veins may be found anywhere, but occur most frequently in the respiratory tract, kidney, and spleen
  42. What is the clinical presentation of Wegener's?
    • Symptoms related to the respiratory tract, particularly pneumonia and sinusitis. Lungs are eventually involved in >90% of cases
    • On CXR, multiple cavitating pulmonary infiltrates are prominent
    • Hematuria and proteinuria are common and the glomerular disease may progress to acute renal failure (from the rapidly progressive GN)
    • Rashes, muscular pains, joint involvement, neurologic symptoms
  43. What is the tx for Wegener's?
    • Cyclophosphamid produces a striking involvement w/ both complete remissions and substantial disease-free intervals in most pts
    • W/o tx pts die w/in a year of onset
  44. What is Churg-Strauss Syndrome and what is its other name?
    • "Allergic Granulomatosis and Angiitis"
    • Systemic vasculitis w/ prominent eosinophilia that occurs in young ppl w/ asthma
    • Widespread necrotizing vascular lesions of the small and medium sized arteries, arterioles, and veins of the lungs, spleen, kidney, heart, liver, and CNS
  45. What is the pathology of Churg-Strauss Syndrome?
    Lesions are characterized by granulomas w/ an intense eosinophilic infiltrate in and around blood vessels, resulting in fibrinoid necrosis and thrombosis
  46. What is the ANCA involvement for Churg-Strauss Syndrome?
    Both C-ANCA and P-ANCA in 2/3 of pts
  47. What is the tx for Churg-Strauss Syndrome?
    • Corticosteriods
    • Untreated pts have a poor prognosis
  48. What is Thromboangiitis Obliterans and what is another name?
    • "Buerger Disease"
    • Occlusive, inflammatory disease of medium and small arteries in the distal arms and legs that occurs almost exclusively in middle-aged heavy smokers (stop smoking and there will be a remission; mechanism unknown)
  49. What are the general features of Thromboanglitis Obliterans?
    • Small microabscesses
    • Upper extremity affected lots
  50. What is the etiology of Thromboanglitis Obliterans?
    • Certain byproducts of tobacco elicit antibodies that can induce inflammation
    • Greater frequency in Japan, Israel, India (maybe genetic factors)
  51. What are the microscopic pathology of Thromboangiitis Obliterans?
    • Earliest changes is an acute inflammation of medium-sized and small arteries
    • PMN infiltrates extends to involve neighboring veins and nerves
  52. What are the complications of Thromboangiitis Obliterans?
    • Involvement of the endothelium in the inflamed areas leads to thrombosis and obliteration of the lumen
    • Small microabscesses of the vessel wall, w/ neutrophils and giant cells are prominent
    • Early lesions can be severe enough to result in gangrene of the extremities, the only tx being amputation
  53. Who is more likely to get Varicose Veins?
    • Individuals from families known to have a connective tissue weakness, and family histories
    • Professions that require long hours of standing
    • Pregnant women - ↑ BP in the pelvic veins compressed by the pregnant uterus and the subsequent stagnation of blood in the leg veins. Thrombotic occlusion of the veins (thrombophlebitis), prevents the outflow of venous blood, and also predisposes pts to varicosities
  54. What are the clinical findings of Thromboangiitis Obliterans?
    • Symptoms usually start between the 25-40 yo
    • Claudication (cramping pains in the muscles following exercise, which are quickly relieved by rest)
    • Pts often present w/ painful ulcerations of the digits, which can progress to the destruction of the tips of the involved digit
    • Continuation of smoking may lead to loss of both hands and feet
  55. What is the etiology of Varicose Veins?
    • Back pressure from the failing heart may ↑ the pooling of blood in the veins, w/ stagnation of blood
    • Dilated veins - veins have valves that oppose back flow of blood, but these venous valves easily become incompetent when the veins dilate
  56. What is the pathophysiology of Varicose Veins?
    • Once leg veins become dilated, they tend to remain so, and become varicose
    • Slow flow of blood to the veins predisposes an individual to clotting
    • Clotting is even more likely in dilated, varicose veins and those in which the back pressure from the failing heart causes stagnation
  57. What are complications of Varicose Veins?
    • Blood flow in the varicose veins are turbulent and slow, favoring clotting and thrombosis that may become loose and embolize to the lungs
    • Pooling of blood in the lower parts of the legs causes blood to leak from distended, small capillaries and veins into the tissues
  58. What are clinical features of Varicose Veins?
    • Brownish discoloration of the skin attributed to the accumulation of blood pigments (hemosiderin) in the subcutaneous tissue
    • Skin is dry, scaly, shows small pinpoint hemorrhages from ruptured capillaries called "Stasis Dermatitis"
    • Skin may necrotize and stasis ulcers may form
  59. Which disease has granulomas?
    • Giant Cell Arteritis
    • Takayasu Arteritis
    • Wegener's
    • Churg-Strauss Syndrome
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3.4 Vasculitides and Peripheral Vascular Disease
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