Vasculitis Flashcards
Types of vasculitis are organized by. . .
. . . the size of the blood vessels affected by the pathology
Vasculitis diagram: Where is the inflammation?
“Large” blood vessels
The aorta and its major branches
Medium blood vessels
Visible to the naked eye or by angiography, often named arteries that branch off of the “major” central arteries.
Small blood vessels
Arterioles, capillaries, and venules
Microscopic
Etiologies of large vessel vasculitis
- Giant cell arteritis
- Takayasu arteritis
Etiologies of medium vessel vasculitis
- Polyarteritis Nodosa
Etiologies of small vessel vasculitis
- ANCA-associated vasculitis
- Cryoglobulinemic vasculitis
- IgA vasculitis
Organs selectively affected by small vessel vasculitis and corresponding symptoms
- skin - purpura
- nerves - neuropathy
- lungs - coughing, nodules, hemoptysis
- kidneys - hematuria
- joints - synovitis, arthritis, arthralgia
- eyes - inflammatory symptoms
Organs affected by medium vessel vasculitis and associated symptoms
- Mesenteric - abdominal pain
- Renal - kidney infarct, kidney pain
- Nerves - neuropathy
- Skin - ulcers, livedo, gangrene
- associated w/ insidious presentation
Livedo
Organs affected by large vessel vasculitis and associated symptoms
- Brain - headache
- Eyes - blindness
- Muscles of face - Jaw claudication
- Fever
- Extremity claudication
Specific lab tests are available to test for ___.
Specific lab tests are available to test for small vessel vasculitis, but not medium or large vessel vasculitis.
Small vessel vasculitis may be due to an underlying ___.
Small vessel vasculitis may be due to an underlying connective tissue disease.
Tests for small vessel vasculitis
- Usually involve testing for glomerulonephritis
- Test for proteinuria
- Stain H and E for RBC casts
- Kidney biopsy for “crescent” of immune cells surrounding a glomerulus
- Full-body observation for purpura
- CT scan for diffuse alveolar hemorrhage
Leukocytoclastic vasculitis
- When white blood cells attack blood vessels
- General term for any small-vessel vasculitis
Small vesse vasculitis on H and E. Note the asterix in the vessel wall and extravasated RBCs (the histological equivalent to the finding of non-blanching erythema)
Asterix
Firboid necrosis in a vessel wall
Anti-neutrophil cytoplasmic antibodies (ANCA)
- Autoreactive antibodies against myeloperoxidase and proteinase-3
- Known to cause glomerulonephritis
Indirect immunofluorescence test for ANCA
- Anti-MPO stains perinuclearly (pANCA)
- Anti-PR3 stains cytoplasmically (cANCA)
- Minor ANCAs such as elastase, Lamp-2, or lactoferrin may confound results (usually pANCA)
- ELISA used to confirm following indirect immunofluorescence screening test
Three phenotypes of ANCA
- Microscopy polyangitis (MPA)
- MPO > PR3, necrotizing vasculitis
- Granulomatosis with polyangitis (GPA)
- PR3 > MPO, necrotizing vasculitis, granulomas
- Eosinophilic granulomatosis with polyangitis (EGPA)
- MPO only, necrotizing vasculitis, granulomas, eosinophilia
____ is central to ANCA
NETosis is central to ANCA
NETosis model for ANCA
Role of DNAse I in ANCA
Impaired DNAse I activity leads to NET persistence following physiological NETosis. This leads to some damage which is then associated with anti-PR3 and anti-MPO antibody development. These ANCAs then activate further NETosis via FcγRI binding.
The cycle goes on.
IgA vasculitis
- Non-ANCA-mediated small cell vasculitis, rather IgA immune complex mediated
- Generally preceded by the initiaton of a new medication (often antibiotics)
- General presentation of purpura, arthralgia/peri-arthralgia, abdominal pain (from interstitial vasculitis), glomerulonephritis
Diagnosing IgA vasculitis
Biopsy of area and direct immunofluorescence against IgA
Cryoglobulinemic vasculitis
- Characterized by overabundance of cryoglobulins
- May be primary, or may be secondary to: malignancy, connective tissue disease (steven-johnson syndrome), or Hep C infection
- Meltzer’s triad: purpura, arthralgias, myalgias
- Membranoproliferative glomerulonephritis presenting as hematuria
- Peripheral symmetric polyneuropathy (often painful)
- Reynaud’s phenomenon and acryocyanosis
Cryoglobulin
Igs characterized by their ability to precipitate at low temperatures
Acryocyanosis
Bluish or purple-coloring of the hands or feet caused by low circulation
Diagnosis of cryoglobulinemic vasculitis
- Serum cryoglobulin measurement (must be collected in warm serum tube)
- Hypocomplementemia (C4 depressed out of proportion to C3, due to C4 depletion)
- High-titer Rheumatoid factor
- Serum protein electrophoresis
- Serum free light chain measurement
Giant cell arteritis
- Form of large vessel vasculitis
- Most common vasculitis in adults
- Occurs more frequently w/ older age, almost all cases >50 yr old
- Majority of patients female Caucasian (due to HLA clustering)
- Distinct clinical phenotypes
- Headache, scalp tenderness, visual loss, jaw claudication
- Visible superficial arteries with pulsation (often temporal artery)
- Fever of unknown origin (likelihood increases w/ age)
- Polymyalgia rheumatica (widespread myalgia, aches, and flu-like symptoms)
Polymyalgia rheumatica
- Associated w/ giant cell arteritis (obsv. in 50% of GCA patients, but only 15-20% of PMR patients have GCA)
- 2nd most common rheumatic disease in elderly
- Symmetric >30 min morning stiffness and aching pain in neck, shoulders, hips
- Mostly due to bursitis, synovitis may be associated
- H and E of giant cell arteritis
- Characteristics:
- Trans-mural mononuclear inflammation (mostly MΦ and CD4)
- Occasional multinucleated giant cells
- Predilection for internal elastic lamina
- Intimal hyperplasia
Immune cell infiltrate characteristics in GCA
- Dominated by oligoclonal CD4 T cells
- Th1 and Th17 polarization
- Assocaition w/ HLA-DRB1*04 (note that this is the same family of HLA genes that predisposes to rheumatoid arthritis)
Giant cell arteritis diagram
CD4 T cell polarity
Th17 polarization diagram
Digital ischemia may be a presenting symptom of ___.
Digital ischemia may be a presenting symptom of medium vessel arteritis.
___ is a form of vasculitis associated with high titer rheumatoid factor.
Cryoglobulinemia is a form of vasculitis associated with high titer rheumatoid factor.
