Chapter 137 - Vasculitis and other uncommon arteriopathies Flashcards
International Chapel Hill Consensus Conference Nomenclature
TABLE 137.1
Large vessel vasculitis examples
1) GCA (temporal) 2) Takayasu
Medium vessel vasculitis examples
1) Polyarteritis nodosa 2) Kawasaki disease
Small vessel vasculitis categories
1) Immune complex-mediated 2) antineutrophil cytoplasmic antibody mediated (ANCA-associated pauci-immune)
Immune complex-mediated small vessel vasculitis examples
1) Antiglomerular basement membrane disease (anti-GBM) 2) Cryoglobulinemic vasculitis 3) IgA vasculitis (Henoch-Schonlein purpura) 4) Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
Antineutrophil cytoplasmic antibody-mediated (ANCA-associated pauci-immune) small vessel vasculitis examples
1) Granulomatosis with polyangiitis (Wegener’s) 2) Microscopic polyangiitis 3) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
Variable-vessel vasculitis examples
1) Behcet 2) Cogan 3) Thromboangiitis obliterans (Buerger’s)
Single-organ vasculitis examples
1) Cutaneous leukocytoclastic vasculitis 2) Cutaneous arteritis 3) Primary CNS vasculitis (isolated angiitis of CNS) 4) isolated aortitis
Vasculitis associated with systemic disease examples
1) Lupus vasculitis 2) Rheumatoid vasculitis 3) Sarcoid vasculitis
Vasculitis secondary to other etiology examples
1) Hepatitis C-associated cryoglobulinemic vasculitis 2) Hepatitis B associated vasculitis 3) Syphilis-associated vasculitis 4) Drug-associated immune complex vasculitis (hypersensitivity vasculitis) 5) cancer-associated vasculitis
Typical presentation of large vessel vasculitis
1) limb claudication 2) vascular bruits 3) asymmetric blood pressure 4) absent pulses
Typical presentation of medium vessel vasculitis
1) cutaneous nodules and ulcers 2) livedo reticularis 3) digital gangrene 4) mononeuritis multiplex 5) renovascular hypertension
Typical presentation of small vessel vasculitis
1) palpable purpura 2) pulmonary-renal syndrome (glomerular nephritis, alveolar hemorrhage) 3) urticarial skin rash 4) scleritis
Histological findings of vasculitis
1) infiltration of vessel wall by neutrophil, mononuclear cells, giant cells 2) fibrinoid necrosis with pan-mural descruction 3) nuclear dust - from destruction of leukocytes
Angiographic finding of vasculitis
1) beading 2) irregular asymmetrical tapering 3) segmental stenosis 4) aneurysm formation
MRI and PET scans in vasculitis
1) Gadolinium in aortic wall indicate active inflammation 2) PET demonstrate enhancement in large vessel vasculitis
Giant cell arteritis epidemiology
1) Over 50 years of age 2) elderly more affected (80’s have 10x higher risk than 50’s) 3) 2:1 female:male
Cause of GCA
unknown but have theories 1) HLA-DRB1*04 and DRB1*01 2) T-cell cytokine IFN-gamma expression injury –> growth and angiogenic factors –> proliferation of myofibroblast –> new vessel formation –> thickening of arterial intima –> vessel occlusion
Symptoms of GCA
1) cranial symptoms: HA, scalp tender, jaw and tongue claudication, diplopia, blindness 20% 2) polymyalgia rheumatica 40% 3) fever and systemic symptoms without localizing symptoms 15% 4) claudication, cough, tenosynovitis 5%
Percentage of patients with polymyalgia rheumatica that develop GCA
10-20%
Percentage of elderly patients with fever of unknown origin that ends up being GCA
15%
Increased risk in GCA of developing thoracic and abdominal aneurysms
17x TAAA 2.4x AAA
Relative risk of blindness in GCA after amaurosis fugax
6.3x
Cause of abrupt onset of painless blindness in GCA
arteritis of posterior ciliary branches of the ophthalmic arteries
Risk of blindness in GCA after steroids have been initiated
10%
Thrombocytosis of ophthalmic artery in GCA symptoms
1) iritis 2) conjunctivitis 3) scintillating scotoma 4) photophobia 5) glaucoma 6) opthalmoplegia (ischemia of extraocular muscles)
Diagnostic criteria of GCA
1990 American college of rheumatology 3/5 present = sensitivity 93.5 specificity 91.2
Principles of temporal artery biopsy
1) 2-3 cm 2) bilateral biopsy can be done 3) 50% show diffuse lymphocytic infiltration without granulomatous inflammation or GC 4) fragmentation and fraying of internal elastic lamina is normal aging 5) done within 7 days of steroids
Steroid treatment in GCA
1) initial dose 40-60 mg daily 2) if blindness then IV methylprednisolone 1g/day x 3 days 3) prednisone maintained until inflammatory markers normalize (takes > 1 month)
Prednisone tapering
1) reduce 5mg every 1-2 weeks until 30 mg/day 2) reduce 2.5 mg every 1-2 weeks until 15 mg/day 3) reduce 2.5 mg every 4 weeks until 10 mg/day 4) reduce 1 mg every 4 weeks until patient is off
Rate of spontaneous recurrence in GCA
50%
Other drugs used in GCA
1) ASA 2) anti-IL6 antibody Tocilizumab 3) biologic and non-biologic disease modifying antirheumatic drugs (DMARDS)
Ormond disease; what is it, epidemiology
1) Idiopathic retroperitoneal fibrosis 2) male:female 3:1 3) middle age 40-60
Symptoms of Ormond disease
1) systemic symptoms 2) HTN 75% 3) LE edema and phlebitis
Diagnosis Ormond - lab
serology negative, inflammatory marker elevated in 75%
Diagnosis Ormond - CT finding
1) Homogenous mass around aorta and iliac bifurcation 2) medial deviation of mid-part of ureter 3) secondary hydronephrosis
Treatment of Ormond
Prednisone 1-3 years Others: mycophenolate mofetil, tamoxifen, methotrexate
Disease recurrence in Ormond
10-30%
IgG4 related systemic disease epidemiology
Men > 50 years of age In people with history of allergic disease and atopy
Diagnosis of IgG4-related disease
1) tumor-like lesions with dense lymphoplasmacytic infiltrates with storiform fibrosis and obliterative phlebitis 2) lesions with IgG4/IgG positive ratio > 50% 3) elevated serum IgG4 60-80% 4) negative serology
IgG4-related disease specific types
1) Type 1 autoimmune pancreatitis 2) sclerosing cholangitis 3) salivary gland involvement (Mikulicz disease) 4) sclerosing sialadenitis (Kuttner tumor)
Treatment of IgG4
steroids with DMARDS Rituximab (B cell target)
Erdheim-Chester disease define
Rare histiocytic disease with 1) periaortic fibrosis 2) periarterial infiltration of coronary arteries 3) pericardial thickening and effusion 4) Hairy kidney 5) retroperitoneal mass like infiltrative lesion 6) bone lesions (juxtaarticular pain) - KEY FEATURE that differentiates it from others
Cause of Erdheim-Chester disease
Gain of function mutation in proto-oncogene BRAF BRAFV600E
Polyarteritis nodosa (PAN) define
Necrotizing vasculitis of small and medium arteries absence of glomerulonephritis and ANCA antibodies
Diagnosis of PAN
3/10 have to be present
Causes of PAN
1) idiopathic 2) Hep B associated (mean time 7 months) 3) other viral infections (HIV) 4) paraneoplastic manifestation (hairy cell leukemia)
Histology of PAN
1) focal segmental necrotizing vasculitis 2) medium sized arteries 3) fibrinoid necrosis of media 4) neutrophilic and lymphocytic infiltrate 5) active necrotizing lesions alongside healed fibrotic lesions
Lab testing for PAN
no specific serologic test available
PAN symptoms
1) constitutional symptoms 2) organ dysfunction 3) skin: palpable purpura, livedo, necrotic lesions, digital infarcts 4) peripheral neuropathy and mononeuritis multiplex 5) abd pain from mesenteric vasculitis 6) HTN 7) microscopic hematuria and proteinuria 8) skeletal muscle myalgia
Renal biopsy in PAN
not helpful since no glomerular involvement
Key difference between PAN and ANCA-associated vasculitides
PAN does not affect lungs or upper respiratory tract
Treatment for PAN
1) antiviral first if infection 2) steroids 3) DMARDS 4) cyclophosphamide
Methotrexate cannot be used in which patients
Renal disease or hepatitis
Cyclophosphamide side effect
1) cytopenia 2) gonadal failure 3) hemorrhagic cystitis 4) malignancy
Patients with high dose steroid and DMARDS need prophylaxis against this
pneumocystis jirovecii (PJP)
Survival of PAN without treatment and with treatment
13% without treatment 80% with treatment 5 year
Factors associated with poor survival in PAN
1) Age > 65 2) cardiac symptoms 3) GI involvement 4) renal insufficiency Cr > 170
PAN recurrence in transplanted kidney
13%
Segmental arterial mediolysis (SAM) key points
1) rare 2) nonatherosclerotic, noninflammatory disease 3) affect muscular arteries and mimic PAN 4) variant of fibromuscular dysplasia
Segmental arterial mediolysis affects different parts at different ages
Aorta is spared Elderly - splanchnic arteries Adults - basilar cerebral Young - coronary
Other disease that mimic PAN
1) SAM 2) pseudoxanthoma elasticum 3) neurofibromatosis 4) vascular type Ehlers Danlos 5) adenosine deaminase-2 deficiency
Thromboangiitis obliterans define and epidemiology
1) Buerger’s disease 2) Age 18-50 3) men > woman 4) middle east and far east 5) related to smoking
Diagnosis of thromboangiitis obliterans
1) diagnosis of exclusion 2) rule out scleroderma first 3) echo and arteriogram
Arteriography features of TO
1) bilateral focal segmental stenosis/occlusion with relatively normal intervening vessels 2) tree-root/spiderweb/corkscrew collaterals 3) normal proximal artery
Pathologic findings of TO
1) cellular thrombosis and microabscesses 2) panvasculitis 3) internal elastic lamina preserved (KEY FATURE) 4) vein sparing
treatment of TO
1) stop smoking 2) calcium channel blocker 3) pentoxifylline 4) iv iloprost 5) sympathectomy
Risk of amputation in smokers that continue to smoke in TO
50%
Kawasaki disease definition and key points
1) children (most < 5 years) 2) small and medium sized (coronary most common) 3) coronary dilatation/aneurysm 20-29% 4) female 1.5: male 1 5) high grade fever 6) death by MI
Treatment of Kawasaki
1) high dose aspirin 2) IVIG
ANCA define
Antibiotics directed against specific proteins in granules in the cytoplasm of neutrophils and lysosomal proteins in monocytes
ANCA vasculitis classes
GPA: granulomatosis with polyangiitis (Wegener) MPA: microscopic polyangiitis EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
GPA epidemiology
1) mean age 41 2) 16% present in childhood 3) caucasian 7:1 black
GPA subclassification
Generalized GPA: upper and lower respiratory tract and kidney Limited GPA: resp track only
GPA symptoms
pulmonary involvement 50% at presentation, 90% eventual enal involvement 15-30% at presentation, 50-80% eventual 1) chronic sinusitis 2) epistaxis 3) chronic purulent nasal drainage 4) chronic inflammation of auditory canal (suppurative and chronic serous otitis media 5) laryngeal and tracheal inflammation (hoarseness, subglottic stenosis) 6) mononeuritis multiplex 7) chronic pachymenigitis, cranial neuropathies, pituitary involvement, brainstem and spinal cord lesions
Pulmonary involvement of GPA
1) nodules and infiltrates 2) granuloma in alveolar septa
ANCA level in GPA
1) ANCA positive in 90% with generalized GPA and 60% limited GPA 2) 80-90% have cANCA positive with PR3 specificity 3) correlate with GPA flare if highly elevated
Specificity of PR3-ANCA for GPA
98%
Treatment for GPA
1) IV methylprednisolone 1g/day 2) rituximab and cyclophosphamide 3) plasmaphoresis milder 4) prednisone 5) methotrexate
Maintenance phase of GPA treatment
Azathioprine has less side effect than cytoxan
Relapse of GPA
50%
Microscopic polyangiitis (MPA) define
1) systemic necrotizing vasculitis of small vessels 2) ANCA formation 3) no immune deposits on histology (pauci-immune) 4) no granuloma formation
MPA epidemiology
1) men = women 2) age 30-50
Lab finding of MPA
pANCA in 60% can still have cANCA with specificity against PR3
How to differentiate MPA from GPA
MPA does not have upper resp involvement
Histopathology of MPA
1) segmental necrotizing glomerulonephritis with crescent formation 2) pulmonary capillaritis with negative immunofluorescence 3) skin = leukocytoclastic vasculitis
Treatment of MPA
1) IV steroid 2) oral prednisone 3) cyclophosphamide or rituximab 4) IVIG and plasmaphoresis (if acute pulmonary hemorrhage
Relapse of MPA
33% 20% need dialysis
5 year survival of MPA
70-75%
Eosinophilic granulomatosis with polyangiitis define
1) Churg-Strauss Syndrome 2) granulomatous vasculitis of small and medium-sized vessel with eosinophilia 3) history of allergic disease with rhinitis 70% or adult-onset asthma 95%
Diagnostic criteria of EGPA
4/6 sen 85% spe 99.7% 1) asthma 2) eosinophilia > 10% 3) mono or poly-neuropathy 4) nonfixed pulmonary infiltrates 5) paranasal sinus abnormalities 6) biopsy with eosinophilic infiltrates
Pathophysiology of EGPA
1) cytokine pathway IL5 stimulate eosinophil 2) leukotriene inhibitor contribute to pathogenesis 3) extravascular necrotizing granuloma near small artery and vein
Difference of EGPA from other granulomatous lesions
Eosinophilic core rather than basophilic core radially surrounded by macrophages and giant cells
Triphasic process of EGPA
1) Prodromal phase (28 months up to 7 years) - allergic rhinitis, asthma, nasal polyposis - 50% recurrent fever 2) Eosinophilia - shifting pulmonary infiltrates - chronic eosinophilic pneumonia - eosinophilic gastroenteritis 3) systemic vasculitis (3 years after onset) - myocarditis, valvular insufficiency - vasculitic peripheral neuropathy - eosinophilic gastroenteritis, purpura and testicular pain
Lab finding in EGPA
Eosinophilia > 1500 cells/mcL pANCA with anti MPO specificity positive RF
Treatment of EPGA
1) IV glucocorticoids 2) oral prednisone 3) cyclophosphamide 4) rituximab
Behçet disease define
systemic vasculitis of unknown etiology Vascular complication with high venous thrombosis rate and 1-7% arterial thrombosis 1) genital ulcers 2) uveitis 3) skin lesions 4) vascular manifestations
Venous thrombosis in Behcet disease
1) superficial and deep vein thrombosis 2) thrombosis of large central vein including SVC and IVC 3) Hepatic vein thrombosis = Budd Chiari syndrome 4) intracranial thrombosis in dural sinus
Unique feature of venous thrombosis in Behcet disease
clot adherent to vessel wall thrombosis can progress despite anticoagulation
Arterial aneurysm formation in Behcet disease order of frequency and vessel type
Aorta > pulmonary > femoral> popliteal > brachial > iliac
Epidemiology of Behcet disease
1) Turkey and Mediterranean basin, Middle and Far East along the historic silk road trade route 2) age 20-40 3) genetic, infectious and immunologic factors 4) HLA-B51 genotype
Treatment of Behcet
1) glucocorticoid 2) steroid-sparing DMARD agents 3) colchicine for mucocutaneous lesions 4) Thalidomide for genital and oral ulcers 5) high dose steroids and cytotoxic agents for vasculitis
SLE define
Chronic multisystem autoimmune disease with autoantibody to various nuclear antigens
Rate of SLE with vasculitis
1/3 of SLE patients
Most commonly affected vessel in SLE vasculitis
Small vessel of skin Leukocytoclastic vasculitis
Treatment of vasculitis in SLE
Steroids and DMARDS Anticoagulation and Hydroxychloroquine if antiphospholipid antibodies present
Rheumatoid vasculitis rate
10-15% of RA
Relapsing polychondritis define
Rare autoimmune disease with recurrent inflammation of cartilaginous tissue Can lead to large vessel aortitis and aneurysms
Cogan’s syndrome define
Large and medium vasculitis (like Takayasu) Immune-mediated characterized by: 1) interstitial keratitis 2) vestibular dysfunction 3) sensorineural hearing loss
Epidemiology of Cogan’s syndrome
mean age 30’s Equal men and women No racial predilection Ear and eye involvement develop within 6 months of each other
Interstitial keratitis manifestations
1) redness 2) pain 3) photophobia 4) increase lacrimation
Vestibular dysfunction manifestation
1) tinnitis 2) vertigo 3) sensorineural hearing loss deaf in 50% of Cogan’s syndrome
Pseudoxanthoma elasticum define
1) inherited systemic disease causing early and diffuse arteriopathy 2) small and medium vasculitis
Pseudoxanthoma elasticum symptoms
1) claudication 2) coronary artery 3) internal mammary 4) GI and GU rupture
Exercise-related external iliac arteriopathy define
1) competitive cyclists with 8000-33000 km/year 2) men + women 3) external iliac artery 4) repetitive bending
Exercise-related EIA arteriopathy mechanism
Psoas branch, circumflex iliac and internal iliac cause fibrosis and thickening of EIA SMC migration and intimal thickening
Treatment of endofibrosis in EIA
1) bypass 2) endarterectomy 3) POBA 4) stenting
Radiation arteritis mechanism
1) endothelial damage, intimal thickening, smooth muscle loss with fibrosis 2) calcification and typical atherosclerosis 3) bulky stenosis 4) medial necrosis 5) vasa vasorum obliteration with adventitial scarring
Neurofibromatosis Type 1 key points
1) autosomal dominant disorder 2) loss of function mutation of tumor suppressor NF-1 3) affects 1:3000 4) neurofibroma, schwannoma, pheochromocytoma 5) 0.4-6.4% get vascular manifestation
NF1 vascular manifestations
1) saccular/fusiform aneurysms 2) stenotic lesions 3) AVM 4) extrinsic compression from neurofibromas
Drug induced (hypersensitivity) vasculitis caused by
1) chemotherapeutic agents 2) growth factors 3) interferons 4) antithyroid drugs 5) hydrochlorthiazide 6) hydralazine 7) minocycline 8) penicillamine 9) vaccine 10) beta blocker - mild vasospasm and exacerbate Raynauds 11) Ergot - vasospasm 12 Cocaine
Cocaine with levamisole vasculitis
1) skin necrosis (nose, ears, breast, digits 2) tissue loss 3) palpable purpura into cookie cutter edge 4) multicentric and doesn’t conform to vascular territory 5) painful worse with elevation
