Overview and Classification of Systemic Vasculitides

Overview and Classification of Systemic Vasculitides

Surya V. Seshan, MD

This schematic shows the predominant range of vascular involvement by different vasculitides, as described in the Chapel Hill Consensus Conference on Nomenclature of Systemic Vasculitis. Those that affect capillaries are most likely to cause glomerulonephritis (except for cutaneous leukocytoclastic angiitis). (Courtesy J.C. Jennette, MD.)



  • Primary systemic vasculitides


  • Pathological

    • Vasculitis is defined as inflammation of blood vessels with demonstrable structural injury such as disruption of elastic lamina ± fibrinoid necrosis

    • Often, occlusive changes due to inflammatory infiltrate or thrombosis are evident

  • Clinical

    • Clinical definition is not possible due to organ-specific or multisystemic disease

    • Rapid or prolonged evolution of clinical features over time may impede or delay definitive diagnosis

    • Thorough correlation with pathophysiologic mechanisms, serology, and imaging studies is essential


  • Vasculitis 1st described by Kussmaul and Maier in 1866; termed “periarteritis nodosa”

  • Giant cell arteritis described by Hutchinson in 1890

  • Multiple vessel involvement and transmural arterial inflammation led to term “polyarteritis nodosa” by Ferrari in 1903 and later by Dickson in 1908

  • Takayasu arteritis described by Takayasu in 1909

  • Granulomatosis with polyangiitis (Wegener) described by Klinger and Wegener in 1931 and 1934, respectively

  • Allergic granulomatosis and angiitis described by Churg and Strauss in 1951

  • Introduction of term “necrotizing angiitis” and attempt to classify vasculitis by Zeek in 1952

  • Vasculitis and mucocutaneous lymph node syndrome described by Kawasaki in 1966

  • Introduction of the term “microscopic polyangiitis” in 1994 by Jennette et al

Classification Considerations

  • No ideal classification

  • Vasculitides may be primary or secondary to systemic disease

  • Vasculitides can be localized to 1 organ or affect multiple organ systems

  • Consensus conferences have developed classifications and criteria based on demographics, clinical characteristics, and pathology



  • Most widely used classification system

  • Developed definitions and standardized diagnostic terminology

  • Classification is based on size of arterial vessel involved and type of inflammatory reaction

  • While size-specific vasculitides are identified, significant overlap in size exists between diagnoses, and ANCA testing may be helpful

  • Cutaneous leukocytoclastic angiitis is a separate category except for those with immune complex deposits or associated with positive ANCA serology

  • Pulmonary renal syndromes of pauci-immune small vessel vasculitides may have similarities and can be distinguished by ANCA serology

  • Pathological correlation with clinical and laboratory features may identify specific therapeutic groups

Large Vessel Vasculitis

  • Giant cell (temporal) arteritis

    • Granulomatous arteritis of the aorta and its major branches, with predilection for extracranial branches of carotid artery

    • Often involves temporal artery

    • Usually occurs in patients older than 50 and often is associated with polymyalgia rheumatica

  • Takayasu arteritis

    • Granulomatous inflammation of aorta and its major branches usually occurring in patients < 50 years

Medium-sized Vessel Vasculitis

  • Polyarteritis nodosa (classic polyarteritis nodosa)

    • Necrotizing inflammation of medium-sized, or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules

  • Kawasaki disease

    • Arteritis involving large, medium-sized and small arteries, and associated with mucocutaneous lymph node syndrome

    • Coronary arteries are often involved

    • Aorta and veins may be involved

    • Usually occurs in children

Small Vessel Vasculitis Including Capillaries, Venules, Arterioles, and Arteries

  • Granulomatosis with polyangiitis (Wegener)

    • Granulomatous inflammation involving respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels

    • Necrotizing glomerulonephritis is common

  • Churg-Strauss syndrome

    • Eosinophil-rich and granulomatous inflammation involving respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels; associated with asthma and eosinophilia

  • Microscopic polyangiitis (microscopic polyarteritis)

    • Necrotizing vasculitis with few or no immune deposits, affecting small and medium-sized vessels

    • Necrotizing glomerulonephritis is very common

    • Pulmonary capillaritis often occurs

  • Henoch-Schönlein purpura

    • Vasculitis with IgA-dominant immune deposits, affecting small vessels

    • Typically involves skin, gut, and glomeruli, and is associated with arthralgias or arthritis

  • Essential cryoglobulinemic vasculitis

    • Small vessel vasculitis with cryoglobulin immune deposits

    • Associated with cryoglobulins in serum

    • Skin and glomeruli are often involved

  • Cutaneous leukocytoclastic angiitis

    • Involves cutaneous leukocytoclastic angiitis without systemic vasculitis or glomerulonephritis


American College of Rheumatology (1990)

  • Criteria for diagnosis of vasculitides

    • Clinical criteria were developed to standardize cohorts of patients in almost all primary systemic vasculitides

    • Presence of 3 or more criteria were associated with high degree of sensitivity and specificity for diagnosis in appropriate context

    • Application of criteria for individual patients may not be entirely helpful

International Pediatric Consensus Conference (2006)

  • Childhood vasculitis

    • Criteria for childhood PAN include histopathological evidence of necrotizing vasculitis or angiographic abnormality along with 1 clinical finding

Birmingham Vasculitis Activity Scores (BVAS)

  • BVAS and vascular damage index (VDI) are applied to assess clinical activity and severity in patients with vasculitis



  • Depends on specific types of vasculitis and associated primary or secondary systemic diseases

Ethnicity and Distribution

  • Takayasu arteritis and Kawasaki disease most common in Asia and Far East countries

  • Granulomatosis with polyangiitis (Wegener) and Churg-Strauss syndrome have predilection for North America and Northern Europe, mainly in Caucasians

  • Higher incidence of microscopic polyangiitis in Asia



  • Immune complexes

    • Mixed cryoglobulinemia

    • Lupus erythematosus

    • Henoch-Schönlein purpura (presumed)

    • Possibly other vasculitides

  • Autoantibodies

    • ANCA

      • Polyangiitis

      • Granulomatosis with polyangiitis (Wegener)

      • Churg-Strauss syndrome

    • Possibly other vasculitides

  • Idiopathic

    • Takayasu arteritis

    • Kawasaki disease

    • Giant cell arteritis

  • Other factors

    • Infections

      • Bacteria, viruses, fungi, rickettsia, parasites

    • Drug reaction


Clinical Presentation

  • General constitutional symptoms are common with all forms of vasculitis in initial or acute stage

  • Specific signs and symptoms depend on several factors

    • Single or multiple organ system involvement

    • Size and type of vessel involved

    • Pathogenetic mechanisms

    • Pathological findings

    • Severity of disease

  • Specific presenting symptoms of complications of vasculitis

    • Vascular narrowing

    • Stenosis

    • Occlusion

    • Aneurysm formation with rupture

  • Symptoms can be acute, subacute, or chronic

  • Clinical features of vasculitis can mimic vasculitis-like diseases, vasculopathies, and, rarely, nonvascular diseases

  • Renal findings in vasculitis

    • Hematuria

    • Proteinuria

    • Acute renal insufficiency or failure

    • Rapidly progressive renal failure

    • Slowly progressive renal failure

    • Chronic renal failure

    • Benign or malignant hypertension

Laboratory Findings

  • Acute phase response is associated with active vasculitis

    • Rise in C-reactive protein

    • Elevated erythrocyte sedimentation rate

    • Increased plasma viscosity

  • Complete blood counts

    • Varied granulocytosis or lymphocytosis

    • Thrombocytosis

    • Anemia

  • Specific organ function tests

    • Kidney, lung, heart, liver, pancreas, endocrine

  • Serologic tests

    • Various types of infections

    • Autoantibodies

      • Antineutrophil cytoplasmic antibodies

      • Antinuclear antibodies

      • Rheumatoid factor

      • Antiglomerular basement membrane

      • Other less frequent but specific antibodies

    • Complement levels

      • C3, C4, C1q

    • Urinalysis

      • Hematuria

      • Proteinuria

      • Casts

      • Cells

Imaging Findings

  • Most useful in large and medium-sized vessel vasculitides

  • Specific types of vessel involvement contribute toward definitive diagnosis

  • Each diagnostic category may have several vascular patterns by imaging studies

  • Variety of imaging modalities may be used to identify specific vascular abnormal patterns

    • Plain x-ray

    • Angiography

      • Computed tomogram

      • Magnetic resonance

    • Doppler studies

    • Tc-99m DMSA scanning


  • Vasculitides range from self-limiting to relapsing disease involving different organs

  • Significant diagnostic delays occur due to frequent clinical overlap and nonspecific findings leading to worse prognosis

  • Varied morbidity and mortality

    • Specific organ involvement

    • Severity of vasculitis

    • Complications

  • Sequelae of vasculitis contribute to further organ damage (stenosis, occlusion)

  • Infectious complications secondary to immunosuppressive treatment are not uncommon


  • Ideally, therapeutic approaches should be based on etiology &/or pathophysiology of the vasculitides

    • Corticosteroid therapy alone is useful for giant cell arteritis and Churg-Strauss syndrome without renal involvement

  • Clinical heterogeneity and varied immune-mediated pathogenetic mechanisms prompt empirical form of initial therapy

  • A number of treatment protocols are in use for primary and secondary vasculitides

    • Cyclophosphamide and steroids in small vessel vasculitides

    • Plasmapheresis and anti-CD20 antibody in severe disease

    • Several immunosuppressive agents including oral steroids, methotrexate, and azathioprine are employed for maintenance of remission


General Features

  • Large and medium-sized vessel vasculitides display distinctive gross characteristics from specimens obtained following excision during surgery or autopsy specimen

  • Gross findings of renal vasculitides of all sizes include segmental or total infarction and progressive atrophy in renal artery stenosis

  • Cortical petechial hemorrhages in small vessel vasculitides


General Features

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Overview and Classification of Systemic Vasculitides

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