Vasculitis¶

Hannah Angle

Background¶

Large vessel vasculitis (aorta and its major branches)
- Takayasu arteritis:
  - Most commonly <30 years old, 80-90% cases in females, greatest prevalence in Asia
  - Branches of aorta/aortic arch (subclavian, innominate, carotid arteries)
- Giant cell arteritis (GCA)
  - Most commonly >50 years old, slight F > M predominance
  - Cranial arteries (temporal artery), aorta and its branches
Medium vessel vasculitis (muscular arteries that supply visceral organs)
- Polyarteritis nodosa (PAN)
  - Most often middle age/older adults (peaks in 5^th decade of life)
  - Necrotizing vasculitis of muscular arteries (renal, mesenteric, arteries supplying neurons and skin)
- Kawasaki’s: not addressed here, most often children
Small vessel vasculitis (arterioles, capillaries, and venules)
- ANCA-associated vasculitis:
- Granulomatosis with polyangiitis (GPA): granulomatous; classically involves nasopharynx, lungs, kidneys
- Microscopic polyangiitis (MPA): affects multiple organs but predilection for lungs and kidneys; in contrast to GPA, no nasopharynx involvement or granulomas
- Eosinophilic granulomatosis with polyangiitis (EGPA): granulomatous; predilection for heart and lungs; associated with eosinophilia, chronic rhinosinusitis, asthma; uncommon > 65 years old
  - Immune-complex vasculitis: not addressed here
  - Cryoglobulinemic vasculitis (see lab section)
  - IgA vasculitis
  - Anti-GBM disease

Takayasu Arteritis¶

Hannah Angle

Presentation¶

Subacute constitutional symptoms: fevers, arthralgias, myalgias, rash, weight loss
CVS: angina from coronary arteritis, HTN (renal a. involvement), discrepant BP between arms (arterial stenosis), diminished or absent pulses (“pulseless disease”), carotidynia (tenderness of the carotid a.), arterial bruits
Limb claudication
Neuro symptoms from carotid/vertebral arteritis: vertigo, headaches, syncope, strokes
GI symptoms from mesenteric ischemia

Evaluation¶

ESR/CRP: often elevated, though can be normal during active disease
Arteriography: MRA or CTA of head/neck, chest, and abdomen/pelvis

Management¶

New arterial stenosis or aorta/carotid artery involvement: 1mg/kg prednisone daily (max 60-80mg) for 2-4 weeks followed by steroid taper
Organ threatening disease (coronary artery involvement, critical stenosis of carotid/vertebral arteries): 500-1000mg IV methylprednisolone daily for 1-3 days, then 1mg/kg prednisone daily for 2-4 weeks followed by steroid taper

Giant Cell Arteritis¶

Lauren Waskowicz

Presentation¶

Always consider in pts >50 years old with new headache, abrupt vision changes (diplopia, amaurosis fugax), jaw claudication, temporal artery tenderness
~20% of pts have clinically significant extracranial large vessel disease
Sudden, typically permanent vision loss may develop due to anterior ischemic optic neuropathy (AION), which develops due to occlusion of the posterior ciliary a. supplying the optic nerve. Non-inflammatory conditions may cause this as well.
Polymyalgia rheumatica accompanies GCA in ~50% pts, classically with bilateral shoulder and hip pain/stiffness (with elevated ESR, but normal CK)
~15% of pts with polymyalgia rheumatica have GCA, but should be considered in all

Evaluation¶

ESR/CRP (almost always elevated), CK, TSH
Evaluate for any temporal artery abnormalities (tenderness to palpation, presence of nodules)
Ophthalmology evaluation if any concern for ocular involvement
Temporal a. biopsy by vascular surgery (typical in the US) OR temporal a. ultrasound (typical in Europe)
If high suspicion for GCA with negative biopsy or ultrasound, perform further imaging to evaluate for large vessel involvement (CT/CTA or MRI/MRA of aorta and/or branches)

Management¶

Treatment: increase glucocorticoid dosing + addition of steroid sparing agent
Start glucocorticoids as soon as GCA is suspected, do not delay while awaiting biopsy
No vision loss: prednisone 1mg/kg daily (max 60 mg) for 2-4 weeks followed by taper
Vision loss/diplopia: 500-1000mg IV methylprednisolone daily for 3 days, followed by prednisone 1mg/kg daily (max 60mg) for 2-4 weeks followed by steroid taper
Bisphosphonates will be commonly indicated for prevention of glucocorticoid induced osteoporosis. A bone density test should be obtained at baseline to assess if other anabolic therapies should be used in higher risk pts.
Consider tocilizumab (weekly or monthly injections) as adjunctive therapy with steroids to allow for faster steroid in pts at higher risk for glucocorticoid-related side effects (since most pts with GCA are elderly, this applies to most pts)

Polyarteritis Nodosa¶

Hannah Angle

Presentation¶

Constitutional symptoms: fatigue, weakness, fevers, arthralgias, myalgias, rash, weight loss
Evidence of multisystem involvement:
Asymmetric polyneuropathy with motor and sensory deficits (foot drop, radial/ulnar neuropathy)
Skin manifestations: livedo reticularis, palpable purpura, ulcers, tender erythematous nodules, bullae, vesicles
HTN (renal arteritis)
Abdominal pain and melena (mesenteric arteritis)
Ischemic cardiomyopathy (coronary arteritis)
Testicular pain (orchitis)
Classically spares the lungs (consider other dx if pulmonary complaints)

Evaluation¶

ESR/CRP, CK, TSH
Hepatitis panel (HBV/HCV can cause secondary PAN)
Arteriography: MRI, CT, or angiogram with classic “string of pearls” appearance
Biopsy: segmental transmural inflammation of muscular arteries, fibrinoid necrosis of arterial wall (no granulomas, presence suggests another process)

Management¶

Mild disease (e.g. isolated cutaneous disease): prednisone 1mg/kg daily (max 60-80mg) for 4 weeks followed by steroid taper
Moderate disease: cyclophosphamide + prednisone 1mg/kg daily (max 60-80mg) for 4 weeks followed by steroid taper
Severe/life-threatening disease (renal failure, significant proteinuria, GI/cardiac/neurologic involvement): cyclophosphamide + 500-1000mg IV methylprednisolone daily for 3 days, followed by prednisone 1mg/kg daily (max 60mg) for 4 weeks followed by steroid taper

Granulomatosis with Polyangiitis (GPA)¶

Hannah Angle

Background¶

Necrotizing vasculitis of small vessels characterized by granulomatous inflammation

Presentation¶

Constitutional symptoms: fevers, fatigue, weight loss
Vasculitis: pulmonary hemorrhage, mononeuritis multiplex, glomerulonephritis (hematuria, proteinuria)
Granulomatous inflammation: sinus and/or middle ear involvement, rhinorrhea, epistaxis, pulmonary nodule, cavitary pulmonary lesions (dyspnea, cough, hemoptysis)

Evaluation¶

ANCA + (typically PR3-cANCA)
ESR/CRP, ANA, anti-GBM, C3/C4, cryoglobulins, HBV/HCV, HIV
UA with microscopy (hematuria, proteinuria, RBC casts, dysmorphic RBCs)
CT chest if pulmonary symptoms
Biopsy: necrotizing granulomatous vasculitis, pauci-immune glomerulonephritis
Clinical Pearl: If you suspect renal disease (elevated Cr, hematuria), ask the renal or rheum fellow to help spin the urine to evaluate for RBC casting or dysmorphic cells. Quick way to confirm active GN, since renal biopsy takes time to arrange.

Management¶

Mild-moderate disease: MTX + prednisone 0.5 mg/kg/day followed by steroid taper
Severe disease: rituximab (first line) + prednisone 1mg/kg/day (60-80mg max)
If failed response to rituximab, cyclophosphamide can be used.
For pts with RPGN, pulmonary hemorrhage, mononeuritis multiplex or optic neuritis: IV methylprednisone 7-15mg/kg/d (1000mg max) x3d for induction therapy
DVT ppx (high risk for DVT/PE)

Microscopic Polyangitis¶

Hannah Angle

Presentation¶

Similar to GPA, but without granulomatous involvement (no upper respiratory tract involvement or pulmonary nodules); classically only involves lungs and kidneys

Evaluation¶

ANCA + (typically MPO-pANCA)
ESR/CRP, ANA, anti-GBM, C3/C4, cryoglobulins, HBV/HCV, HIV
UA with microscopy (hematuria, proteinuria, RBC casts, dysmorphic RBCs)
CT chest if pulmonary symptoms
Biopsy: necrotizing vasculitis (no granulomas), pauci-immune glomerulonephritis

Management¶

Same as GPA, see above

Eosinophilic Granulomatosis with Polyangitis (EGPA)¶

Hannah Angle

Presentation¶

Similar to GPA/MPA. Predominant symptoms include atopic symptoms (asthma, rhinosinusitis) and peripheral eosinophilia.
Vasculitis manifestations are more rare, and when they occur, mononeuritis multiplex is the most common, unlike pulmonary hemorrhage or renal involvement in GPA/MPA.
Cardiac involvement (accounts for 50% deaths from EGPA): coronary arteritis, myocarditis, heart failure, arrhythmias
Skin involvement (>50%): tender subcutaneous nodules

Evaluation¶

ANCA + (typically MPO-pANCA, positive in about 50-60% of pts)
Peripheral eosinophilia
IgE, ANA, RF, C3/C4
Biopsy: necrotizing granulomatous vasculitis, eosinophilic infiltrates with fibrinoid necrosis, pauci-immune glomerulonephritis

Management¶

Mild-moderate disease: prednisone 0.5-1 mg/kg/day for 6-12 weeks followed by steroid taper
Severe: cyclophosphamide + prednisone 0.5-1 mg/kg/day for 6-12 weeks followed by steroid taper
For pts with life-threatening multiorgan involvement (cardiac, pulmonary, renal, neurologic): IV methylprednisone 1000mg daily x 3 days for induction therapy
ACR guidelines now also recommend mepolizumab for non-severe disease (instead of rituximab or cyclophosphamide) plus steroids as initial induction therapy. Severe disease still requires rituximab or cyclophosphamide)
DVT ppx (high risk for DVT/PE)