Pathology Of Vascultiis Flashcards
Vasculitis definition
Generalized term for various types and causes of vessel wall inflammation
- there are 20 primary forms of vasculitis that are recognized
Common classifications include the following characteristics:
1) vessel diameter
2) immune complexes present or not
3) presence of specific antibodies
4) granuloma formation or not
5) organs being affected
6) population demographics
Clinical manifestations of vasculitis
Very widespread but usually are associated to specific affected vascular beds
Non-specific symptoms/signs include
- myalgia
- inflammation
- fever
- arthralgia
- malaise
Main immunologic mechanisms of non infectious vasculitis
Immune complex deposition
- henloch-purpura
- cyroglobinemic
- nodosa
Anti-Neutrophil Cytoplasmic Antibodies (ANCAs)
- GPA/ wegners
- MPA
- churgg Strauss/ eosinophilc
Anti-endothelial cell antibodies
- Kawasaki’s
Auto reactive T cells
- giant cell
- takayasu
Immune complex associated vasculitis
Immunologic disorders such as SLE and is associated with autoantibody production
Anti-Neutrophil cytoplasmic antibodies (ANCAs)
Vasculitis that produces antibodies that react with neutrophil cytoplasmic antigens.
- can directly activate neutrophils stimulating the release of ROS and proteolytic enzymes
There are two main types of ANCAs
- p-ANCA
- c- ANCA
Two main types of ANCAs
1) Anti-proteinase-3 (PR3-ANCA or (c-ANCA)
- azurophilic granule constituent antibody that is associated with granulomatosis w/ polyangiitis vasculitis.
2) Anti-myeloperoxidase (MPO-ANCA) or (p-ANCA)
- lysosomal granule constituent antibody that is associated with microscopic polyangiitis and churg-Strauss syndrome
- these antibodies directly attack and activate neutrophils without reason, causing ROS to rain on endothelial cells and cause inflammation and damage-> vasculitis*
Giant Cell (temporal) arteritis
Chronic inflammatory disorder w/ granulomatous inflammation
- affects large-small arteries of the head
Diagnosis is only done via biopsy of temporal arteries, however must treat it before diagnosis w/ corticosteroids or anti-TNF therapies.
- can also induce vertebral and ophthalmic arteries
- if not treated, causes sudden and permanent blindness and possibly death*
- MOST COMMON form among >50yrs old adults in developed countries*
Pathogenesis of Giant Cell arteritis
Unknown for sure, but likely occurs as a result of T-cell-mediated immune response to an uncharacterized vessel wall antigen
- often presents with granulomas in the facial arteries and large amounts of pro-inflammatory cytokines
Morphology of Giant Cell arteritis
Involved arterial segments exhibit Nodular intima thickening and overall marked reduction of vessel diameters which causes distal ischemia
- presence of granulomas w/ inflammation within the internal elastic lamina will also be present
note these morphological are patchy in appearance, so if biopsy comes back negative, this diagnosis can not be ruled out
Signs and symptoms and to of giant cell arteritis
Can be vague and constitutional
- abrupt vision issues
- painful temporal arteries/regions
- intermittent jaw claudication
- fever
- malaise and myalgia
- thickened temporal arteries
- treatment is immediate corticosteroids (even before biopsy) when suggested diagnosis, may also use TNF- inhibtors also*
Takayasu arteritis
Granulomatous vasculitis of medium and large sized arteries characterized with ocular dysfunctions and marked weakening of the pulses in the upper extremities
- often called “Pulseless disease”
Always manifests as transudate scarring and thickening of the aorta, usually found in the aortic arch, pulmonary arteries or/and great vessels with severe luminal narrowing
Major differences between takayasu arteritis and giant cell aortitis
They all have the same symptoms however the age of the patient is the primary differential factor
- > 50yrs = giant cell
- <50yrs = takayasu
Signs and symtpoms of takayasu arteritis
Nonspecific to begin with
- fever
- weight loss
- fatigue
Specific with progression
- marked reduction in radial and branchial pulses
- neurological symptoms
- ocular defects
Polyarteritis Nodosa (PAN)
Systemic vasculitis of small-medium sized muscular arteries
- typically includes renal, cardiac and visceral/GI vessels
- almost always NO pulmonary issues
Usually transumual necrotizing inflammation when inflammation occurs
often associated with chronic Hep B infections and deposit is hepatitis B antigens into affected vessels, causing mass inflammation, but can also be idiopathic
Clinical features and Tx of PAN
Most common in young adults but can be in any age
Symptoms are EPISODIC and include
- malaise
- fever
- weight loss
- rapidly accelerating HTN seen in kidney lesions*
- abdominal pain*
- blood stools via GI lesions*
- peripheral neuritis affecting motor nerves*
TX:
- immunosuppressive via corticosteroids
- no treatment often kills, Tx = 80% survival rate
Kawasaki disease
Acute, febrile, self-limited vasculitis of infants and children
- affects large-medium sized vessels
- can result in aneurysms that rupture or thromboses in the coronary arteries, often causing MIs in the case.
Mostly results from viral triggers to people who are genetically disposed to the disease
- also can result from delayed hypersensitivity reactions in response to cross-reactive vascular antigens. (This causes antibodies to be produced for ECs and SMCs where the vasculitis is occurring)
Clinical features of Kawasaki disease
Strawberry tongue
Red swollen feet/hands bilaterally
Enlargement of cervical lymph nodes
Systemic blistering
Edema in extremities
Rash around eyes and face
Conjunctiva without discharge
Tx of Kawasaki disease
Intravenous immunoglobulin (IVIG) infusions and aspirin - must give together
- note the aspirin can cause Reyes potentially, but Kawasaki’s is more dangerous so still use asparin*
Microscopic polyangiitis
Necrotizing vasculitis that affects capillaries and small arterioles/venules
- can occur in mucous membranes, lungs, heart, GI, kidneys and brain
Usually occurs via obscure antibody responses to antigens from drugs, infections or tumors
MOST COMMON is necrotizing glomerulonephritis and pulmonary capillaries (90%)
- most commonly effects lungs and kidneys
Most cases are associated w/ MPO-ANCA antibodies
Clinical features and Tx of microscopic polyangiitis
Specific symptoms depends on the vascular bed involves
Non specific is the following
- extreme hematuria and proteinuria
- abdominal pain/bleeding
- myalgia
- palpable cutaneous purpura
Tx:
- immunosuppression via corticosteroids and treatment of the offending agent
(Note: this cant be done in widespread renal or CNS involvement microscopic polyangiitis)
Granulomatosis w/ Polyangiitis (GPA) or Wegener granulomatosis
Necrotizing vasculitis with a classic triad of symptoms
1) necrotizing granulomas of the upper-respiratory tract and lower-respiratory tract
2) necrotizing or granulomatous vasculitis affecting small vessels in the pulmonary system
3) crescentic glomerulonephritis
Is initiated via a cell-mediated hypersensitivity via inhaled infectious agents of pollutants.
ALL cases present with PR3-ANCAs and is the cardinal marker for the disease
Morphology of GPA
Upper respiratory tract lesions are always present in mucous membranes
- can be ulcerative in extreme cases
- most often shows granulomatous nodules though
Renal lesions are also present
Clinical features of GPA
Typical patient is a middle aged man (but women can also get this)
Classic presentation is the following symptoms
- bilateral pneumonitis w/ nodules and cavitation lesions
- chronic sinusitis
- mucosal ulcerations of the nasopharynx
- renal diseases (hematuria and proteinuria with high creatine)
Untreated = 1 year mortality within 80% of patinets
Tx =. Steroids, cyclophosphamide, and TNF inhibtors
- use rituximab if severe
NOTE: treatment almost certainly provides survivalists, but relapse rates are high
Chung-Strauss syndrome (allergic granulomatosis and angiitis)
Is a rare small vessel necrotizing vasculitis often presenting w/ allergic symptoms:
- asthma
- allergic runny nose
- lung infiltrates
- peripheral high eosinophilla
- extravascular granulomas
Also presents with the following symptoms that are non-allergic
- palpable purpura
- GI bleeding
- renal diseases
- Cardiomyopathies
Thromboangiitis Obliterans (Buerger Disease)
Segmental thrombosis acute and chronic inflammation of medium sized arteries
- most common sites are tibial and radial arteries with
- almost exclusively found in heavy tobacco smokers and usually develops before 35 yrs of age*
- ethnic groups of Israeli, Indian and Japanese are more predisposed
Clinical features and Tx of Thromboangiitis Obliterans (Buergers Disease)
Early manifestations includes:
- cold-induced Raynaud’s phenomenon (pain occurs when warming up the extremities)
- foot pain induced by exercise (instep claudication) and superficial nodular phlebitis
Late manifestations include:
- severe pain even at rest
- chronic ulcerations
Tx:
- early = stop smoking
- late = stop smoking and treat the ulcerations
