Vasculitides

Last updated: June 9, 2023

Summary

Vasculitides are a heterogeneous group of rare autoimmune diseases characterized by blood vessel inflammation (vasculitis). Inflammation can lead to

, , and/or hemorrhage, with subsequent . Vasculitides are either primary () or secondary to an underlying disease (e.g., , cancer, ) or drug use. Vasculitides are further classified based on the size of the affected vessels: small-, medium-, or , or variable vessel vasculitis. Diagnosing vasculitides is often challenging, as symptoms are usually nonspecific; vasculitides should be considered in patients presenting with and signs of multisystem disease (e.g., palpable , pulmonary infiltrates, unexplained events). Laboratory studies, imaging, and histopathology are often required to confirm the diagnosis. Management should involve a multidisciplinary team (e.g., rheumatology, ophthalmology, neurology) and aims to promptly prevent the progression of vascular inflammation with to avoid organ damage and death. Treatment of the underlying cause (e.g., with antiviral drugs) and/or symptomatic management (e.g., with ) is often necessary.

General principles

Etiology ^[1]

Primary (
idiopathic
)
Secondary to another disease or drug use, e.g.:
- Infectious diseases
  - Viral infection: e.g.,
    HBV
    ,
    HCV
    ,
    HIV
  - Infectious endocarditis
  - Tuberculosis
  - Syphilis
- Drugs: e.g.,
  hydralazine
  ,
  cocaine
- Malignancy
  : e.g.,
  multiple myeloma
  , lymphoproliferative disorders
- Autoimmune diseases: e.g.,
  systemic lupus erythematosus
  (
  SLE
  ),
  Sjogren syndrome
  ,
  sarcoidosis
  ,
  IBD

Classification ^[2]

Based on the 2012 Chapel Hill Consensus Nomenclature
Classification is based on the size of the vessel predominantly affected:
- Large-vessel vasculitis
- Medium-vessel vasculitis
- Small-vessel vasculitis
  - ANCA-associated vasculitis of small vessels
  - Non-ANCA-associated vasculitis of small vessels
- Variable vessel vasculitis

Preview thumbnail for image: Types of vasculitis

Approach to management ^[1]

Vasculitis should be suspected in patients with

and multisystemic inflammatory disease. Specific manifestations depend on the vessels affected.

Tailor the approach to the suspected disease and/or affected organ or system.
Rule out other (more common) diagnoses (e.g., infections, cancer, other autoimmune diseases).
Assess for secondary causes of vasculitis (see “Etiology”).
Consult a rheumatologist and/or other specialists as required.
Start management based on disease severity and the affected organ or system.

Most patients with vasculitis present with nonspecific features (e.g.,

, elevated ).

Initial evaluation

Perform a thorough history and physical examination; ≥ 1 of the following clinical features are usually found in patients with vasculitis
:
- Typical cutaneous lesions (e.g., palpable
  purpura
  ,
  livedo reticularis
  , digital
  gangrene
  )
- Pulmonary-renal syndromes
  (e.g.,
  asthma
  ,
  hemoptysis
  ,
  glomerulonephritis
  )
- Limb
  claudication
  , asymmetric pulses and/or blood pressure measurements,
  bruits
- Temporal
  headache
  , visual loss,
  mononeuritis multiplex
Findings suggestive of vasculitis on routine studies include:
- CBC
  :
  anemia of chronic disease
  ,
  thrombocytosis
  ,
  eosinophilia
- Inflammatory markers
  : ↑
  ESR
  , ↑
  CRP
- Infectious diseases workup: positive
  hepatitis B testing
  or hepatitis C testing
- Autoimmune diseases workup: negative
  ANAs
  and
  aPL antibodies
- Chest x-ray
  : lung involvement (e.g.,
  ground glass opacity
  , nodular lesions)

Vasculitis has a wide variety of signs and symptoms; there is no single typical presentation.

Additional evaluation

Consider further diagnostics guided by clinical suspicion to:

Determine the extent of the disease, e.g.:
- Urine studies and chest CT to evaluate for kidney and lung involvement
- Nerve conduction studies
  ,
  electromyography
  , and
  creatine kinase
  levels
Establish the type of vasculitis: e.g., ↓
ANCAs
and ↑
cryoglobulins
indicates
cryoglobulinemic vasculitis
Confirm the diagnosis: with imaging (e.g.,
MRA
,
CTA
) or histological studies

Management

Immunosuppressive therapy
is generally indicated.
Surgical therapy may be required in specific cases (e.g., those with limb
ischemia
).
Supportive care
- Provide pain management.
- Prevent complications of glucocorticoid therapy.
- Monitor adverse effects of immunosuppressants.
- Consider PCP prophylaxis.

Large-vessel vasculitis

Overview of large-vessel vasculitides
	Clinical features	Diagnostics	Management
Giant cell arteritis ^[3]	Most commonly affects women > 50 years of age Visual impairment: may result in blindness New-onset headache Tender temporal artery Jaw claudication Associated with polymyalgia rheumatica	↑ ESR (≥ 50 mm/hour), ↑ CRP Negative autoantibody studies Duplex sonography : halo sign around the vessel ^[4] Temporal artery biopsy (gold standard): granulomatous inflammation	High-dose glucocorticoids to prevent permanent vision loss See “ Giant cell arteritis ” for more information.
Takayasu arteritis ^[3]^[5]	Most commonly affects Asian women < 40 years of age Disparity in blood pressure between arms ( Takayasu arteritis is also known as pulseless disease ) Bruit over the subclavian artery or abdominal aorta Syncope and angina pectoris	↑ ESR , ↑ CRP MR angiography (preferred study): vascular wall thickening with luminal stenosis or occlusion of the aorta and major branches ^[6] Angiography : stenosis of the aortic arch and proximal great vessels Biopsy : granulomatous inflammation of the aorta and its major branches ^[5]	Glucocorticoids PLUS a glucocorticoid-sparing agent (e.g., methotrexate , azathioprine , infliximab ) See “ Takayasu arteritis ” for more information.

Preview thumbnail for image: Giant cell arteritis Preview thumbnail for image: Temporal arteritis Preview thumbnail for image: External carotid artery stenosis

Medium-vessel vasculitis

Overview of medium-vessel vasculitides
	Clinical features	Diagnostics	Management
Kawasaki disease	Most often occurs in children < 5 years of age "CRASH ( Conjunctivitis , Rash, Adenopathy , Strawberry tongue , Hand-foot changes) and BURN (≥ 5 days of fever )”	↑ ESR , ↑ CRP , thrombocytosis Echocardiography : coronary artery aneurysms	High-dose aspirin PLUS IVIG See “ Kawasaki disease ” for more information.
Polyarteritis nodosa	Most often occurs in adults 45–65 years of age; ♂ > ♀ Fever , malaise Abdominal, muscle, and joint pain Renal impairment Neurological dysfunction (e.g., polyneuropathy , stroke ) Rash, ulcerations , nodules Spares the lungs	Associated with positive HBV and/or HCV studies ANCA : negative Muscle biopsy : transmural vasculitis	Glucocorticoids PLUS cyclophosphamide See “ Polyarteritis nodosa ” for more information.

Preview thumbnail for image: Typical findings in Kawasaki disease Preview thumbnail for image: Renal artery microaneurysms Preview thumbnail for image: Muscle involvement in polyarteritis nodosa Preview thumbnail for image: Polyarteritis nodosa

Small-vessel vasculitis

ANCA-associated small-vessel vasculitis

Overview of ANCA-associated small-vessel vasculitides
	Clinical features	Diagnostics	Management
Granulomatosis with polyangiitis	Most often occurs in adults 40–60 years of age; ♂ > ♀ Chronic sinusitis / rhinitis , saddle nose deformity Chronic otitis media and mastoiditis Treatment-resistant pneumonia -like symptoms such as cough, dyspnea , and hemoptysis Rapidly progressive glomerulonephritis	PR3-ANCA Biopsy of the affected organs: granulomatous, necrotizing vasculitis, glomerulonephritis , lung involvement Chest x-ray or CT: multiple bilateral cavitating nodular lesions	Glucocorticoids PLUS methotrexate OR cyclophosphamide OR rituximab See “ Granulomatosis with polyangiitis ” for more information.
Eosinophilic granulomatosis with polyangiitis	Severe allergic asthma , sinusitis Skin manifestations (e.g., tender nodules ) Peripheral neuropathy Gastrointestinal, cardiac, and/or renal involvement	MPO / p-ANCA (∼ 40% of patients) Peripheral blood eosinophilia ↑ IgE Biopsy ( confirmatory test ): tissue eosinophilia , necrotizing granulomas	Glucocorticoids PLUS cyclophosphamide OR rituximab See “ Eosinophilic granulomatosis with polyangiitis ” for more information.
Microscopic polyangiitis	Pauci-immune glomerulonephritis Hypertension Palpable purpura Similar to granulomatosis with polyangiitis but spares the nasopharynx	MPO / p-ANCA Biopsy : inflammation, no granulomas	Glucocorticoids PLUS rituximab OR cyclophosphamide See “ Microscopic polyangiitis ” for more information.

is the 'C' disease: Curvy nose (), Chronic , Cough, Conjunctivitis and Corneal , Cardiac , non-Caseating on , c, Corticosteroids and Cyclophosphamide as treatment.

Preview thumbnail for image: Pulmonary manifestation of granulomatosis with polyangiitis Preview thumbnail for image: Cytoplasmic pattern of antineutrophil cytoplasmic antibodies (c-ANCA) Preview thumbnail for image: Multifocal ground-glass opacities Preview thumbnail for image: Eosinophilic granulomatosis with polyangiitis

Non-ANCA-associated small-vessel vasculitis

Overview of non- ANCA-associated small-vessel vasculitides
	Clinical features	Diagnostics	Management
IgA vasculitis	Most often affects children (90% of patients are < 10 years of age) Palpable purpura on lower limbs Arthritis and/or arthralgia Abdominal pain Hematuria if IgA nephropathy is present Often secondary to URTIs	↑ IgA in serum Biopsy : leukocytoclastic vasculitis with IgA and C3 immune complex deposition	Mild cases: symptomatic treatment (e.g., with NSAIDs ) Severe cases: glucocorticoids PLUS IV hydration See “ IgA vasculitis ” for more information.
Cryoglobulinemic vasculitis	Fatigue Arthralgia Palpable purpura Glomerulonephritis Most cases are secondary to cryoglobulinemia due to HCV infection.	Cryoglobulinemia in serum Cutaneous or renal biopsy	Mild cases: symptomatic treatment (e.g., with NSAIDs ) Moderate or severe cases: glucocorticoids PLUS either rituximab OR cyclophosphamide Treatment of the underlying etiology (e.g., DAAs for HCV infection ) See “ Cryoglobulinemic vasculitis ” for more information.
Cutaneous small-vessel vasculitis ^[7]^[8]	Palpable purpura Causes Idiopathic in 45–50% of cases Drug-induced Infections	Skin biopsy : leukocytoclastic vasculitis	Management of the underlying etiology (e.g., discontinuation of inciting drugs, initiation of antivirals) Severe and/or chronic cases: glucocorticoids ± glucocorticoid-sparing agents (e.g., colchicine , dapsone ) See “ Cutaneous small-vessel vasculitis ” for more information.

Preview thumbnail for image: Purpura in IgA vasculitis Preview thumbnail for image: Leukocytoclastic vasculitis

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