Vasculitis Syndromes
Polymyalgia Rheumatica,Giant Cell
Arteritis, Wegener’s Granulomatosis,
Polyarteritis Nodosa
What is Vasculitis?
• Disease characterized by inflammation of
blood vessel walls, leading to altered blood
flow through obstructed walls. This causes
ischemia and tissue damage.
• In addition there is an intense inflammatory
rxn causing further systemic signs and
symptoms
• Can be fatal
You Should Suspect Vasculitis
•
•
•
•
•
•
•
•
•
•
•
Unexplained signs and sxs
Multisystem disease
Unexplained elevated ESR/CRP
Skin lesions (palpable purpura)
Ischemic vascular changes (Raynaud’s, gangrene, livedo,
claudication)
Glomerulonephritis
Mononeuritis multiplex
Intestinal angina
Inflammatory ocular diease
Arthalgias/arthritis, myalgias
Sudden visual loss/headache
Select Vasculitides
• Polymyalgia Rheumatica
• Giant Cell or Temporal Arteritis
• Wegener’s Granulamatosis
• Polyarteritis Nodosa
Polymyalgia Rheumatica (PMR)
• Most ‘benign‘ of the group
• Common: 50/100,000, age > 50, average age
75. Highest prevalence in northern European
ancestry, females>>males
• Cause unknown
PMR Clinical Presentation
• Usually abrupt onset
• Intense morning stiffness and pain that can last
all day involving the shoulders and hip girdle area
• No small joint involvement
• Muscle strength normal
• Fatigue and anorexia common
• Elevated CRP and ESR; anemia of chronic disease,
elevated platelets
• 15% get GCA (more later)
PMR Treatment
• Low Dose Steroids (10-20 mg/day)
– The only drug that works
– Look to normalize the CRP and ESR; if they
continue to be elevated, rethink the dx
(?paraneoplastic syndrome or GCA)
– Usually self-limited: 65% of patients able to taper
off Prednisone by 1 year, >85% in 2 years
– Disease flares not uncommon as prednisone is
tapered and may require dose adjustments
Giant Cell Arteritis
•
•
•
•
•
Can occur exclusively but often seen with PMR
Rare: 15/100,000
Age >50
Cause unknown
Involves the medium/large blood vessels of
the head and neck including the blood vessels
that supply the optic nerve
GCA Pathophysiology
• Unknown trigger causes inflammatory
response with the release of IL-1 and IL-6.
• This leads to systemic symptoms and the
infiltration of inflammatory cells into the
adventitia of the temporal and other involved
arteries
• Typical histologic pattern: Giant Cells
GCA Clinical Presentation
•
•
•
•
•
•
•
Variable
Scalp tenderness
Temporal headaches
Jaw Claudication
Sudden loss of vision
+/- PMR sxs
Rare- upper extremity claudication due to subclavian
involvement
• Constitutional sxs: FUO, wt loss, fatigue
• Bounding OR absent temporal artery pulses
• Rarely subclavian bruits
GCA Diagnostic Studies
• Temporal Artery Biopsy is the gold standard
• Elevated ESR and CRP, usually levels higher
than in PMR
• Anemia
• Elevated LFTs not uncommon
Treatment of GCA
• High dose Steroids (60 mg/day) is the only
drug that works
• Slow taper over time usually 1-2 years. Some
patients require low dose (<10 mg/day)
chronically
GCA Complications
•
•
•
•
Blindness
Scalp Necrosis
Lingual Infarction
Aortic Dissection/Aneurysm
• Complications from high dose steroids:
osteoporosis, cataracts, elevated blood sugars,
wt. gain etc.
Wegener’s Granulomatosis (WG)
• Potentially fatal vasculitis involving small
vessels
• Rare: 3-14/million, more common in whites,
any age but rare in children
• Pathology shows necrotizing granulomas
usually in upper airways, lungs and kidneys
WG Pathophysiology
• Complex immunopathogenic events in which
the production and activity of ANCAs (usually
c-ANCA) play a central role. These
autoantibodies interact with primed
neutrophils to cause vascular injury and
necrosis.
• Histologic lesions show granulomas
WG Clinical Presentation
• Variable, multisystem involvement
• Organs:
– Eyes: episcleritis/scleritis, proptosis due retro-orbital mass
– CNS: rare mass lesion
– Upper airway: otitis media, nasal chondritis, sinusitis with
purulent drainage and epistaxis, ulcerations, subglottic stenosis
– Kidney: neprotic syndrome, proteinuria, renal failure
– Skin: palpable purpura due to leukocytoclastic vasculitis,
pyoderma gangrenosum, panniculitis
– Lung: cough, hemoptysis, hemorrhage, resp failure
– Cardiac: pericarditis, conduction abnormalities
– Systemic: fever, night sweats, wt loss, fatigue
Palpable Purpura
Eye Involvement
Face Involvement
WG Diagnostic Studies
• Presence of c-ANCA (cytoplasmic staining
pattern antineutrophil cytoplasmic antibodies
+ clinical picture is often enough to make the
diagnosis. It is + 80-90% of generalized WG.
• If the c-ANCA is -, tissue biopsy of lung or
kidney is recommended.
• “Limited” refers to disease limited to the
airways; c-ANCA often is -.
Additional labs
•
•
•
•
Elevated CRP and ESR
Anemia, leukocytosis, & thrombocytosis
Elevated Cr
Active urine sediment with red cell casts,
hematuria and proteinuria
WG Clinical Course/Progression
• Prior to immunosuppression therapies, WG
was uniformly fatal. Now survival rates almost
90% with aggressive treatment.
• High dose steroids and Cyclophosphamide are
cornerstone of therapy. Methotrexate or
Azathioprine sometimes used as steroid
sparing agents.
Polyarteritis Nodosa (PAN)
•
•
•
•
Medium vessel vasculitis
Can be caused by Hep B
5/million cases
Peak incidence 50’s & 60’s, slightly more
common in males
PAN Pathophysiology
• In Hep B assoc cases immune complexes play
significant role
• In non Hep B cases, the pathophysiology is
less understood
PAN Clinical Presentation
• Systemic: fever, fatigue, wt loss
• Abdominal pain due to mesenteric
angina/ischemia
• Mononeuritis multiplex
• Myalgias/arthalgias/mild arthritis
• Hypertension
• Skin: livedo reticularis, palpable purpura,
fingertip ulceration, subcutaneous nodules
• Testicular pain or tenderness
Livedo reticularis
Subcutaneous Nodules
Complications of PAN
•
•
•
•
Chronic renal failure
Bowel perforation
Stroke/cerebral hemorrhage due to HTN
Foot/wrist drop
Wrist Drop
Labs of PAN
• Elevation of acute phase reactants (ESR, CRP
etc)
• Absence of ANCA
• Elevated transaminases, decreased albumin
• +/- Hep B
• Urine: proteinuria and hematuria without
casts
Imaging Studies of PAN
• Mesenteric and/or renal angiography is the
test of choice
• Biopsies seldom done
Angiogram
PAN Treatment
• High dose steroids and Cyclophosphamide
• Methotrexate or Azathioprine is used as
steroid sparing agents later once the disease is
controlled
• Treatment for Hep B with antivirals.
Sometimes plasma exchange is used to
remove immune complexes