16: Medium & Large Vessel Vasculitis Flashcards
What are the types of medium and large vessel vasculites?
- Medium vessel:
- Polyarteritis nodosa
- Kawasaki disease
-
Large vessel:
-
Giant cell arteritis
- Polymyalgia rheumatica
- Takayasu’s arteritis
-
Giant cell arteritis
What is polyarteritis nodosa (PAN)?
Multisystem, necrotizing vasculitis of small and medium-sized muscular arteries in which involvement of the renal and visceral arteries is characteristic; does not involve pulmonary arteries, although bronchial vessels may be involved; granulomas, significant eosinophilia, and an allergic diathesis are not observed
PAN affected vasculature
Primarily below the diaphragm
- SMA
- Celiac & hepatic arteries
- Renal arteries
- Musclar arteries of extremities
- Coronary arteries (uncommon)
PAN epidemiology
- 20-70yo
- No racial/ethnic predilection
- Incidence:
- 2-4/1,000K annually in US
- 70-80/1,000K annually in regions endemic for HBV
What is the association between PAN and HBV?
PAN occurs acutely in first 6mos following HBV infx; usually + for surface and e antigens
What does this image show?
Necrotizing arteritis of PAN; destruction of vessel wall –> aneurysm
What does this image show?
Extravasation of blood into surrounding tissue in PAN
PAN clinical manifestations
- Constitution
- Fatigue
- Fever
- Weight loss
- GI: abdominal pain
- Kidney: HTN (2/2 renal artery occlusion; NO glomerulonephritis)
- PNS: mononeuritis multiplex
- Skin: nodules/ulcers, livedo reticularis (mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin)
- Digital gangrene
What is livedo reticularis?
Enhanced prominence of the dermal or subcutaneous venous plexus due either to venodilatation and/or increased deoxygenation of the venous blood caused by regional ischemia secondary to reduced arteriolar blood flow.
What does this image show?
Livedo reticularis
PAN treatment
- Onset:
- Prednisone
- Cyclophosphamide
- Continue for at least one year
- If HBV+:
- Antiviral therapy (lamivudine)
What is kawasaki disease (mucocutaneous lymph node syndrome)?
Acute, febrile, multisystem disease of children characterized by nonsuppurative cervical adenitis and changes in the skin and mucous membranes such as edema; congested conjunctivae; erythema of the oral cavity, lips, and palms; and desquamation of the skin of the fingertips.
What are the clinical criteria for KD?
- Fever for more than five days, plus:
- 4 of 5 clinical criteria:
- B/l nonpurulent bulbar conjuctival injection (spares limbus)
- Oral mucous membrane inflammation
- Injected and/or fissured lips
- Nonpurulent erythematous pharynx
- Strawbery tongue
- Peripheral extremity abnormalities
- Edema of hands and feet (acute)
- Erythema of palms and soles
- Periungual (surounding nail) desquamation (convalescent)
- Polymorphous rash
- Cervical LAD (1 LN > 1.5cm)
What is the epidemiology of KD?
- >6mos to <5yo
- Population differences <5yo:
- Japanese: 112/100K
- Korean: 86.4/100K
- US: 9-33/100K
What does this image show?
Sheet-like desquamation of distal extremities; begins in periungual region of hands and feat; occurs during convalescent (resolution) phase
What is the etiology of KD?
- Infectious?
- ↑freq in household contacts
- seasonal distribution (winter & summer)
- occasionally occurs in epidemics
KD complications
- Coronary artery aneurysm 2/2 vasculitis occurring >10 days after onset of illness
- Resulting in:
- MI
- arrhythmias
- Frequency:
- Untx: 25-30%
- Tx: 5% (transient coronary artery dilatation); <1% (giant aneurysm >8mm)
- Resulting in:
What does this image show?
coronary arteritis in KD
- Panarteritis (all three layers of artery affected)
- Minimal evidence of fibrinoid necrosis despite aneurysm formation
KD treatment
- Intravenous immunoglobulin (IVIG)
- Aspirin
What is the mechanism of activation of IVIG in KD?
- ↓cytokines
- neutralize bacterial superangtigens
- augment T-cell suppressor activity
- modulate endothelial cell function
- reduce production of NO by neutrophils
- Fc receptor blockade
- anti-idiotypic inhibition of endothelial Abs
What is giant cell arteritis (temporal arteritis)?
Inflammation of medium- and large-sized arteries, characteristically involving one or more branches of the carotid artery, particularly the temporal artery
What vasculature is involved in GCA?
Above the diaphragm!
- Thoracic aorta and major branches:
- Carotid artery extra-cranial branches:
- Temporal a.
- Occipital a.
- Facial a.
- Ophthalmic a.
- Posterior ciliary a.
- Subclavian/axillary artery
- Carotid artery extra-cranial branches:
GCA epidemiology
- >50yo (loss of inhibitory funct. of immune mech?)
- Racial/ethnic background annual incidence:
- 20/100K N. Europe
- 2/100K AfAm & Hispanics
- <1/1,000K Asians
What does this image show?
Giant cell arteritis
GCA clinical manifestations
- Constitutional
- Fatigue
- Weight loss
- Fever
- H/A (66%): commonly temporal, but frontal or occiptal possible
- Jaw pain (claudication: more pain with activity) (50%)
- Visual loss (2/2 involvement of optic nerve)
- Acute onset
- Partial/complete visual field loss in 15-20% pts
- Arm claudication (2/2 involvement of subclavian & axillary aa.) (15%)
GCA pathogenesis
- Unknown initial factor (perhaps a viral or other infection) activates dendritic cells located in the adventitia in medium and large blood vessel walls, initiating an adaptive immune response
- TLR ligands recruit CD4 T cells which invade deeply into wall, causing panarteritis, whereas dendritic cells support perivascular infiltrates
- Recruited cells cause further inflammation, tissue destruction and induction of repair mechanisms
- Giant cells release vascular endothelial growth factor into intima, leading to luminal stenosis
GCA laboratory abnormalities
- ↑acute phase reactants
- ESR
- CRP
- IL-6
GCA diagnosis
- Temporal artery bx
- ↑ESR & CRP
GCA treatment
- **prednisone **tapering over 4-6mos
- >30% relapse at dose of <15mg/day
- in elderly, steroids assoc’d w/ ↑risk mortality, thus remove ASAP or use steroid-sparing agents
What is polymyalgia rheumatica?
Inflammatory rheumatic condition characterized by aching and morning stiffness in the shoulders, hip girdle, and neck; can be associated with GCA
PMR clinical manifestations
- Intense pain and stiffness of musculature surrounding shoulders and pelvic girdle, typically b/l
- Muscle strength normal
- Fatigue & weight loss
- ↑ESR or CRP
PMR epidemiology
- >50yo
- Incidence at >50yo:
- 113/100K N. Europeans
- 2-3x more common than GCA
- <2/100K Japanese
- 113/100K N. Europeans
What is the connection between PMR and GCA?
- 10% of pts dx w/ PMR eventually develop features of GCA
- 20-30% of pts dx w/ GCA eventually develop features of PMR
NB: monitoring for the two important b/c corticosteroid dosage differs
PMR treatment
-
prednisone
- prompt & dramatic response w/in 24-72hrs
What is takayasu arteritis (pulseless disease)?
Inflammatory and stenotic disease of medium- and large-sized arteries characterized by a strong predilection for the aortic arch and its branches
What vasculature is involved in TA?
Above and below the diaphragm
- Thoracic aorta
- Common carotid a.
- Vertebral a.
- Subclavian a.
- Abdominal aorta
- Celial a.
- SMA
- Renal a.
- Iliac a.
- Pulmonary artery
TA epidemiology
- Annual incidence 1.2-2.6/million
- 15-25yo
- F>M
- ↑incidence Asians
List the arteriographic abnormalities and their clinical symptoms in TA
- Subclavian (93%): arm claudication, raynaud’s
- Common carotid (58%): stroke, TIA, vision changes
- Abdominal aorta (47%): abdominal pain
- Renal (38%): HTN, renal failure
- Aortic arch (35%): aortic insufficiency, CHF
- Vertebral (35%): vision changes, dizziness
TA treatment
- prednisone
- secondary immunosuppresive agents:
- cyclophosphamide
- methotrexate
- azathioprine
- infliximab
