Vasculitis

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    Introduction

    • Inflammation of the vessel well causing vascular damage:
      • Narrowing
      • Occlusion
      • Aneurysm
      • Rupture
    • Vasculitis can cause tissue damage due to ischemia. 
    • Symptoms that suggest vasculitis are:
      • Palpable Purpuric rash
      • Chronic Inflammatory Sinusitis
      • Pulmonary Infiltrates
      • Glomerulonephritis or microscopic hematuria
      • Unexplained ischemic events (i.e. mononeuritis multiplex)

    Large Vessel

    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).

     

    Medium-Sized Vessel

    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

    nodulesPAN.jpgpalpablepurpura.jpglivedoReticulitis.jpg

     

    • 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
      • kawasaki.jpg

    • 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)

     

     

    Small Vessel

    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

    Mononeuritis Multiplex

    • Vasculitic disorder that affects vasa vasorum of nerve vascular supply.
    • Occurs in systemic inflammatory reactions (i.e. SLE, vascultis, etc..)
    • Peroneal nerve is most commonly affected.
    • Defined by: Abnormal findings in the territory of ≥2 nerves in separate parts of body.
      • I.e. patient with foot drop, normal reflexes (peroneal nerve), and wrist drop (radial nerve)
    • Diagnosis:
      • EMG/NCS to confirm a peripheral neuropathy.
        • This helps identify a nerve to biopsy prior to immunosuppression. 
    • Management:
      • Immunosuppression.

    Small Vessel

    • Features:
      • Palpable purpura
      • Vesicles
      • Chronic Urticaria
      • Superficial Ulcers

     

    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 multiplextest.jpg
         
         
    • 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

     

    ANCA Associated

    • Is positive ANCA a true positive?
      • C and P-ANCA immunofluorescence should always be confirmed by ELISAs for PR3-ANCA and MPO-ANCA.
      • ELISA PPV is 83%
      • Immunofluorescence PPV is 45%
      • ELISA+Immunofluorescence = PPV 88%
    •  
    • Microscopic polyangitis (MPA)
      • 70% are ANCA positive
      • Majority are MPO-ANCA
      • Cannot distinguish GPA from MPA on serology
      • ANCA useful to distinguish MPA from classic polyarteritis nodosa (PAN).
      • Pulmonary, GN
    • Eosinophilic Granulomatosis Polyangiitis (EGPA) aka Churg-Strauss Syndrome
      • pANCA (antigen: MPO)
      • Respiratory, asthma, eosinophilia, rare kidney involvement
    • Atypical ANCA
      • Drug Induced Systemic Vasculitis (commonly PTU - propylthiouracil, and other thyroid drugs).
    • IgA Nephritis (aka Henoch-Schonlein purpura (HSP))
      • Most common childhood vasculitis
      • IgA complex deposits in skin, GI tract, kidneys, joints, CNS, lungs
      • Sx:
        • Skin: Non-thrombocytopenic purura
        • GI: Abdo pain, intusussception
        • Joings: Arthritis, Arthralgia 
    • Essential cryoglobulinemic vasculitis
      • Cryoglobulin immune deposits.  Skin + glomeruli affected
    • Cutaneous leukocytoclastic angiitis
      • cutaneous leukocytoclastic angiitis w/o systemic effects

     

    •  
    1. Renal Limited Vasculitis
      • Pauci-immune vasculitis 
      • "Necrotizing glomerulonephritis with little or no deposition of immunoreactants (IgG, IgM, IgA, Complement)
      • Majority are ANCA positive (75-80% have MPO-ANCA)
      • Histology of kindey indistinguishable from GPA or MPA.
    2. Churg-Strauss Syndrome
      •  
    3. Anti-GBM Antibody Disease
      • Btwn 10-40% with anti-GBM are ANCA-positive at diagnosis.  (25% MPO-ANCA, 12% PR3-ANCA, 1% had both)
      • Double positive sera (Anti-GBM and ANCA)
        • Renal disease (100 percent), with a median serum creatinine concentration of 7.2 mg/dL (636 µmol/L). Seventy percent required dialysis within 48 hours of presentation.
        • Malaise and general weakness (44 percent)
        • Pulmonary hemorrhage (41 percent)
        • Rash (22 percent)
        • Other respiratory symptoms (19 percent)
        • Ear, nose, and throat or sinus symptoms (11 percent)
    4. Drug-induced ANCA vasculitis
    • Propylthiouracil
    • Hydralazine
    • Minocycline
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