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