• infectious: direct invasion of bv by organism
  • Neisseria
  • mycobacteria
  • spirochetes (ex: treponema- syphillus)
  • rickettsia (ex: rocky mountain spotted fever)
  • fungi (Aspergillus, Zygomyces)
  • viruses (Herpes zoster)
• noninfectous- problem regulating the imune response, so native mediators of inflammation cause damage to bv
  • immune complex associated (MAJOR)
  • ANCA mediated
  • direct Ab mediated

1. complexes of Ab/Ag form in circulation and lodge in the walls of the bv's (Type III hypersensitivity)
2. initiate an inflammatory response in the vessel wall
3. activate cytokines, recruit inflammatory cells to area
4. Ab and complement found in the vessels (low sensitivity and specificity)

• SLE
• drug induced (ex: sulfa antibiotics)
• polyarteritis nodosa
• Henoch Schonlein purpura
• cyoglobulinemic
• rheumatoid
• serum sickness
• infection induced immune complex (ex: Hep B, C)
• paraneoplastic

• heterogenous group of Ab against enzymatic Ag's found in cytoplasmic granules of inflam. cells (ex: neutrophils, monocytes) and endothelial cells

• c-ANCA (against proteinase 3)- Wegner's granulomatosis
  • presence of Ab diffusely in cytoplasm of neutrophil
• p-ANCA (against myeloperoxidase)- microsopic polyangiitis, Churg-Strauss syndrome
  • presence of Ab in perinuclear distribution within the neutrophil

• definition- autoAb formed against Ag's within the vessel wall, including a direct immune response against vessel
• examples
  • Goodpasture's syndrome (anti-basement membrane Ab's)
  • Kawasaki disease (anti-endothelial cell Ab's)

based of size of vessel effected

• large vessel vasculitis- aorta and its major branches
  • ex: giant cell arteritis, Takayasu arteritis
• medium sized vessel vasculitis- aorta and its larger branches along with smaller arteries within parenchymal tissue
  • ex: polyarteritis nodosa, Kawasaki disease
• small vessel vasculitis- everything from larger arteries to veins)
  • ex: microscopic polyangiitis, Wegener granulomatosis

• epidemiology: men over 50 mainly, most common type of large vessel vasculitis
• arteries at risk: mainly all in head
  • temporal A.
  • opthalamic
  • vetebral
  • aorta
• major complications
  • blindness (affect on opthalamic artery)
    • if visual disturbances, treat immediately
  • neurologic defects (affect on vertebral artery)
  • thoracic aortic aneurysm (affect on aorta)
  • polymyalgia rheumatica- stiffness, aching, pain in muscles of shoulder, neck, lower back, hips, thights)

• gross

  • nodular, segmental thickening
  • mural fibrosis, narrowing of lumen, occasional thrombosis (seen in Takayasu's arteritis as well)
• microscopic
  • chronic granulomatous inflammation (seen in Takayasu's arteritis as well)
  • mononuclear infiltrates originating in inner half of media (ex: lymphocytes, macrophages, multinucleated giant cells)
  • collagenous thickening/fibrosis of vessel wall upon healing (destruction of internal elastic lamina)

• dx
  • elevated ESR (over 100 mm/hr) (normal is 25)
  • biopsy of temporal A. (thickening, nodularity found)- segmental lesion
    • negative biopsy doesnt rule out disease (disease is segmental, and they only take out a few cm of A.)
• tx- usually based on clinical findings before confirmatory biopsy scheduled
  • prognosis- good response to corticosteroids

• epidemiology: younger than 50
• affected arteries
  • aortic arch
  • subclavian A.
  • renal A.
  • carotid A.
  • vetebral A.
  • iliac A.
  • pulm. A.

• decrease bp with weak pulse in upper extremities (due to affecting aorta)
• ocular disturbance
• neuological defects (due to affect on vertebral A.)
• lower extremity claudication (due to affect on iliac A.)
• pulmonary HTN (due to pulm. A. effects)
• MI
• systemic HTN (due to affect on renal A.)
• coldness, numbness of fingers

• gross 
  • mural fibrosis, narrowing of lumen, occasional thrombosis (seen in giant cell arteritis as well)
• microscopic
  • chronic granulomatous inflammation (seenin Takayasu's arteritis as well)
  • inflammation mainly in media
    • could involve intima and adventitia in later stages
    • inflammation contains eosinophils and neutrophils in acute phase
  • advanced stage of disease- mural fibrosis with little inflammation

• mainly involves visceral arteries (ex: coronary, hepatic, renal)
  • pulm. A. rare

• epidemiology- usually for young adults
• arteries involved
  • renal, visceral, but RARELY pulm. A.
• dx- associated with Hep B and circulated immune complex 30% of time
• cause- immune complex mediated (type III hypersensitivity)
• tx- fatal if not treated, but responds well to corticosteroids

• HTN
• abdominal pain
• GI bleed
• diffuse muscular pain
• peripheral neuritis
• renal failure

• it will never cause glomerulonephritis or pulm. disease (unless pulm. A. involved)
• it cannot involve these diseases because by definition, this is a necrotizing vasculitis that will only effect arteries and no other vessel smaller than arteries

• microscopic
  • transmural mixed inflammation
    • numerous neutrophils
    • some eosinophils
    • monocytes (predom. later on)
  • fibrinoid necrosis
  • during healing stage, fibrous thickening
• gross
  • visible nodules on vesel wall (due to segmental inflammation and necrosis producing a pseudoaneurysm)

Difference: polyarteritis nodosa has co-existing early and healing lesions

• mucocutaneous lymph node syndrome
  • self limiting and acute
  • fever
  • conjunctaval and oral erythema and/or erosion
  • edema of hands and feet
  • erythema of palms, soles
  • desquamative skin rash
  • enlarged cervical lymph nodes

• epidemiology
  • childhood and infants
  • far more common in Japan than in US
  • acute febrile illness
• artery most frequently involved (affects everything from large to small arteries)
  • coronary A: cause coronary thrombosis, aneurysm, MI, sudden death
  • NO assoc. glomeruloneph. or pulm. disease
• tx- IV Ig's

• prediliction for small vessles like arterioles, capillaries, venules
• leads to involvement of alveoli and glomeruli

• ANCA related
  • c-ANCA: Wegner granulomatosis
  • p-ANCA: microscopic polyangiits
• immune complex related
  • SLE
  • cryoglobulin
  • IgA (Henoch-Schonlein Purpura)

• two different pathogenesis mechanisms
  • anti myeloperoxidase Ab (pANCA)
  • immune complex mediated

• segmental transmural inflammation
  • neutrophilic infiltration (could be accompanied by eosinophils)
  • leukocytoclasia
• fibrinoid necrosis

Like with all ANCA associated vasculitis, there will be no immunoglobulin demonstrated on histology

remember, affects capillaries, arterioles, venules

• clinical signs/symptoms

  • skin- leukocytoclastic vasculitis (purpuric rash: aka palpable purpura)

    • purpuric rash is distinguishing factor from Wegners and Churg-Strauss
  • kidney- glomerulonephritis (proteinuria, hematuria)
  • lung- pulm. capillaries hemoptysis
    • alveolar hemorrhage
    • inflam. of alveolar septal capillaries (capillaritis)
  • abdominal pain
  • muscle pain, weakness
• prognosis- respond to steroids and cyclophosphamide

Remember, it involves necrotizing vasculitis of medium and small sized vessels.

• clinical signs/symptoms
  • upper resp. tract
  • lower resp. tract
  • kidney (glomerulonephritis)
• pathogenesis: anti-PR3 Ab (cANCA)
• prognosis- fatal if untreated, but responds to steroids, cyclophosphide

• microscopic
  • necrotizing inflammation w/ large areas of geographic necrosis with a rim of histiocytes, fibrobblasts, and occasional multinucleated giant cells
  • lesions in lung that are cavitary and localized (mimic tumors, other infectious pulm. lesions)
  • capillaritis, vascularitis with associated geographic tissue necrosis and fibrohistocytic proliferations
  • renal lesions same as those in polymicroscopic angiitis
• gross
  • if necrosis bad enough
    • perforation in palate or nasal septum
    • destroy sinus walls
    • involve orbit

• vessels involved- pulmonary capillaries and glomeruli
• pathogenesis- direct Ab binding to component of collagen IV, which is present in large amounts on BM's of kidneys, lungs
• associated with hemoptysis
• key pathological feature- linear immunostaining pattern of IgG along basement membranes

• Remember, the main feature is immunostaining of IgG along BM's
• microscopic
  • pulmonary lesions- with pulm. hemorrhage with no histologically discernable capillaritis
  • glomerular lesions- segmental or global glomerular proliferation and necrosis, with crescent formation

• pathogenesis- IgA dominant immune deposits in small vessels (arterioles, capillaries, venules)
• tissue affected
  • skin
  • GI tract
  • kidneys
  • RARE lungs
• associated conditions
  • arthralgia
  • arthritis
• pathological features
  • characteristic lesion- leukocytoclastic angiitis with focal necrosis of vessel walls
  • karyorrhexis of infiltrated neutrophils
  • kidney can have crescents identical to IgA nephropathy
• dx- IgA dominant immune complexes upon immunohistology in injured and uninjured vessels

• cryoglobulins: proteins which precipitate in serum at low temperatures and redissolve when warmed up
• pathogenesis- in vivo, deposit in small vessels, frequently involving skin and glomeruli
• clinical signs symptoms
  • indirect pulm. symptoms (rare direct)
    • radiographic evidence of alveolar septal thickening
  • strong assoc. with Hep C
• pathological features
  • similar histopath to HSP
  • hyaline thrombi present within capillary lumina (represents aggreagates of cryoglobulins and complement)

• all necrotizing vasculitis enters final common pathway of inflammation and scarring
• transformation of sclerotic lesions with a predominance of infiltrating T lymphocytes and macrophages occurs as quickly as 1-2 wks after initial injury