Vasculitis

Giant Cell Arteritis

• AKA "Temporal Arteritis"
• Affects LARGE vessels that contain internal eastic membranes.
  • Usually extra-cranial of head & neck (intracranial is rare!)
  • Thoracic aorta + major branches
• Pathophysiology
  • Transmural lymphocytic infiltrate in vessel wall (disrupts internal elastic lamina)
  • Often find multinucleated giant cells in vessel section (wall or adventitia)
• Epidemiology
  • Occurs in pts >50yo
  • Women > Men (2:1)
• Clinical Features
  • Consider GCA in ALL patients > 50yo with a new onset headache
  • Constitutional Sx: fever, fatigue,...
    • (Consider in Fever of Unknown Origin or new onset headaches in >50yo pts)
  • Polymyalgia Rheumatic Sx (stiffness/pain in hip/shoulder girdle) - PMR can occur with GCA
  • Cranial Vessels:
    • Jaw Claudication (cranial vessel involvement - masseter and temporalis ischemia)
    • Scalp Tenderness
    • Temporal/Occipital Headache
  • Ophthalmic Artery
    • Optic nerve ischemia (blindness)
  • Subclavian vessels
    • Upper limb claudication
    • Subclavian steal
  • Aorta
    • Aortic Regurg
• Physical Exam:
  • Tenderness/thickening over temporal arteries
  • Carotid/subclavian bruits (neck, supraclavicular fossa)
  • May lose radial pulse (ipsilateral)
• Labs:
  • CBC: Anemia, thrombocytosis
  • ESR + CRP
  • Rule Out Other Causes: Glucose, Creatinine, urinalysis, Ca, ALP, Rh, Anti-CCP, LFTs, TSH, CK, Vitamin D
• Diagnosis/Workup

  • Diagnosis of GCA: Temporal Artery Biopsy demonstrating characteristic histologic features Can be performed up to 2 weeks after treatment started Biopsy can be negative! (skip lesions common) May require multiple biopsies (i.e. can repeat on contralateral side) Sometimes made clinically based on presentation (clinical, acute phase reactants, response to treatment)   Diagnostic Criteria: (need 3/5 criteria)    1. Age > 50    2. New onset headache    3. Temporal Artery tenderness/abnormality on palpation    4. ESR > 50    5. Abnormal temporal artery biopsy

  • CT/MR angiography if:
    • Cranial artery symptoms absent, temporal bx negative
      OR:
    • Physical findings suggest carotid/subclavian involvement.
• Association with PMR - similar pathophysiology, except PMR affects bursae and synovium. 
• Treatment
  • High Dose Steroids to prevent vision loss
  • Corticosteroids (1mg/kg/day prednisone - 60-80mg/day x1mo followed by slow taper)
    • Response to treatment helps diagnostically
    • Treat immediately when suspect GCA to avoid visual loss (do not wait temporal artery bx!)
    • Biopsy findings do not change x2-4 weeks (can still biopsy post-tx)
  • Continue prednisone --> taper after 4-6w (drop 10% q2weeks) -> monitor ESR/CRP
    • can relapse during taper --> increase by 10mg that previously controlled disease.
  • If repeated flares during tapering: (use steroid-sparing tx, but not proven)
    • Methotrexate
    • Azathioprine
    • Mycophenolate mofetil
  • Low-Dose ASA recommended -->  minimizes cerebral infarcts
  • Follow for aortic aneurysms.
  • NOTE: IF visual loss: methylprednisolone 500-1000mg daily IV x3d followed by prednisone

Takayasu Arteritis

• Aorta and branches
• Sx: fever, arthralgias, myalgias, malaise, weight loss, vascular insufficiency
  • claudication, decreased peripheral pulses, bruits, hypertension, BP differences in extremitis
• Dx: Imaging studies show great vessel narrowing (typically most marked at aortic branch points).

Polyarteritis Nodosa

• Pathophysiology
  • Inflammation and necrosis of medium-sized and small muscular artery walls
• Risk Factors:
  • Peak age 40-60
  • Recent Hepatitis B infection (50% of cases)
• Clinical Features
  • Fever, arthralgia, myalgia, abdo pain, weight loss
  • Peripheral nerves (2/3 of pts): Mononeuropathy / mononeuritis multiplex
  • Renal Artery Involvement (1/3 of pts)
  • Other Featurse:
    • GU: Testicular pain (1/3)
    • Cardio: Coronary arteries (rare)
    • Skin:
      • Painful cutaneous nodules
      • Skin Ulcers
      • Palpable Purpura
      • Livedo reticularis

• Labs:
  • CBC: Anemia, elevated WBC, thrombocytosis
  • ESR!
• Diagnosis:
  • Biopsy: Necrotizing arteritis of medium-size arteries
    • Bx Sites: involved site (Skin if rash, symptomatic muscles, sural nerve if NCS)
    • Do NOT biopsy kidneys, arteriolar aneurysms can hemorrhage.
• Management:
  • High Dose Steroids (1mg/kg/day of prednisone) x several weeks.
    • Taper slowly when clinical + lab inflammation improved.
  • Cyclophosphamide indicated for:
    • Poor response to steroids
    • Kidney/GI/Cardiac/Neurologic involvement.
  • Hepatitis B-associated PAN
    • Short course (1-2w) of steroids with antiviral therapy (i.e. entecavir)
    • 50% of pts with HepB E-antigen positive PAN --> treating both treats arteritis and HepB E seroconversion.

Kawasaki Disease

• Involves medium-sized to small arteries
  • Occurs exclusively in children
  • Case resports of adults with HIV
• Clinical Features
  • Fever ≥5 days, ≥4 of following
    • 1. Non-exudative conjunctivitis
    • 2. Mucous membrane changes (strawberry tongue, erythema, fissured lips)
    • 3. Pleomorphic erythematous rash 
    • 4. Changes in hands + feet (erythema, edema, desquamation)
    • 5. Cervical lymphademopathy (usually unilateral)
  • (eventually desquamates in periungal areas + proximally on hands/feet)
  • Oligoarticular or polyarticular inflammatory arthritis

  • 

• Main Complication:
  • Coronary Artery Aneurysms (ACS!) (20-25% of untreated)
  • Peripheral vascular occlusion
• Labs:
  • CBC: Anemia, high WBC, high platelets,
  • Urine: Sterile pyuria
• Management
  • IVIG (2g/kg single infusion) + high dose ASA (80-100mg/kg in 4 doses /day)
    • Then: Low dose ASA x6-8wks if no coronary problems on echo.  Stay on ASA if coronary artery problems.
  • Steroids only if does not respond to above
  • Needs ECHO! (r/o coronary artery aneurysms)

Becet's Disease

• Small vessel vasculitis
• Symptoms:
  • Mouth: Oral ulcers!
  • Eyes: Panuveitis, Retinal Vasculitis
  • Skin: Erythema Nodosum
  • Pulmonary Artery Aneurysms
  • Other Visceral Organs:
    • Gastrointestinal, pulmonary, musculoskeletal, and neurologic manifestations also may be present

Churg-Strauss Syndrome

• Eosinophilic Granulomatosis with Polyangiitis
• Autoimmune small-vessel vasculitis 
• Presents with:
  • Peripheral Eosinophilia
  • Involves Lungs (such as asthma)
  • Purpura on hands & sensory/motor neuropathy

HSP

Under Construction

• Usually in kids, but in adults, it is less common and typically is more severe.
• Adults
  • Adult HSP runs a self-limited course
  • More likely to experience severe disease and to accumulate irreversible organ damage before the acute disease resolves.
• Organ Systems Involved:
  • Gastrointestinal tract
• Treatment:
  • Prednisone

Granulomatosis with Polyangiitis

• 80-90% are PR3-ANCA positive (cANCA)
• Clinical Features
  • upper airway (70% of cases): sinusitis, nasal, inner ear, laryngotrachea, saddle nose
  • pulmonary (90% of cases): cough, hemoptysis, pleurisy, pulmonary nodules, diffuse alveolar hemorrhage
  • renal (80% of cases): usually preceded by pulmonary disease
  • eyes: scleritis, keratitis, uveitis, retro-orbital pseudotumor
  • skin: pupura, nodules, ulcers
  • nerves: mononeuritis multiplex
     
     
• Histology
  • lung: vasculitis, necrosis, or granulomatous inflamation
  • renal: necrotizing focal segmental glomerulonephritis, no immune deposition (i.e. pauci-immune)
    • renal biopsy not needed in classic presentation (upper + lower airway, hematuria, anti-PR3) involvement
• Treatment
  • high dose corticosteroid with 3-6 month cyclophosphamide PO
    • switch cyclophosphamide to azathioprine or methotrexate once in remission for at least 18 months total
  • other:
    • methotrexate only if mild disease (high rate of recurrence)
    • rituximab shown to be as effective as cyclophosphamide
• Prognosis
  • 90% remission rate
  • relapse 30% while on treatment, another 30% recurrence after complete treatment