Vasculitides — Medicine Library

Summary

Vasculitides are a heterogeneous group of rare autoimmune diseases characterized by blood vessel inflammation (vasculitis). Inflammation can lead to ischemia, necrosis, and/or hemorrhage, with subsequent end-organ damage. Vasculitides are either primary (idiopathic) or secondary to an underlying disease (e.g., HBV infection, cancer, systemic lupus erythematosus) or drug use. Vasculitides are further classified based on the size of the affected vessels: small-, medium-, or large-vessel vasculitis, or variable vessel vasculitis. Diagnosing vasculitides is often challenging, as symptoms are usually nonspecific; vasculitides should be considered in patients presenting with constitutional symptoms and signs of multisystem disease (e.g., palpable purpura, pulmonary infiltrates, unexplained ischemic 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 immunosuppressive therapy to avoid organ damage and death. Treatment of the underlying cause (e.g., with antiviral drugs) and/or symptomatic management (e.g., with NSAIDs) 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

Types of vasculitis

Approach to management [1]

Vasculitis should be suspected in patients with constitutional symptoms 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., constitutional symptoms, elevated inflammatory markers).

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.

Polymyalgia rheumatica and giant cell arteritis fact sheet Temporal arteritis Great vessel stenoses External carotid artery stenosis Takayasu arteritis

**Temporal arteritis**
Temporal artery biopsy specimen (Van Gieson stain)
The vessel lumen is narrowed as the tunica intima is thickened and inflamed (yellow overlay). Disruption of the internal elastic lamina (examples indicated by arrowheads) is also visible.
These histological changes are typically seen in temporal arteritis.
Blue overlay: lymphocytic inflammation; dashed overlay: giant cells

Source: © IMPP

**Great vessel stenoses**
Angiography thoracic aorta (left anterior oblique view) of a patient with Takayasu arteritis
Stenoses (examples indicated by white arrows) are seen in the innominate (I), left common carotid (C), and left subclavian (S) arteries. An injection catheter is seen in the dilated ascending aorta (green overlay).

Source: "File:Takayasu Arteritis.jpg", Justin Ly, Wikimedia Commons licensed under Public Domain

**External carotid artery stenosis**
CT angiography neck (left carotid artery) of a patient with Takayasu arteritis
The external carotid artery shows a 50–60% stenosis (arrowheads). Mural thickening (green overlay) and irregularity of the left common carotid artery are also present.

Source: “First case of childhood Takayasu arteritis with renal artery aneurysms” by Tahar Gargah, Mouna Ben Harrath, Haythem Bachrouche et al., Pediatric Rheumatology, licensed under CC BY 2.0. Modifications: Arrows and bracket removed. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Takayasu arteritis**
MRI angiography aorta (A: with contrast; sagittal plane. B: inversion recovery dark blood sequence; axial plane)
The descending aorta shows luminal dilatation and irregularity (A: green overlay), with multiple areas of wall thickening (B: examples indicated by red dimension lines).
These features are characteristic of Takayasu arteritis.

© AMBOSS. This image was adapted from the image “Figure 4, in: CMR in inflammatory vasculitis” by Raman SV, Aneja A, Jarjour WN, Journal of Cardiovascular Magnetic Resonance, licensed under CC BY 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

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.

Clinical features of Kawasaki disease Typical findings in Kawasaki disease Renal artery microaneurysms Muscle involvement in polyarteritis nodosa

© Massachusetts Medical Society. All rights reserved. AMBOSS SE, exclusive licensee.

**Renal artery microaneurysms**
Angiography abdominal (kidneys; arterial phase) of a patient with polyarteritis nodosa
Selective contrast injections of the right and left renal arteries show microaneurysms in both kidneys (examples indicated by arrows).

Source: “Figure 2, in: Bilateral Spontaneous Perirenal Hemorrhage due to Initial Presentation of Polyarteritis Nodosa” by Hyung-Il Choi, Yang-Gyun Kim, Se-Yun Kim, Da Wun Jeong, Ki-Pyo Kim, Kyung-Hwan Jeong, Sang-Ho Lee, and Ju-Young Moon, Case Reports in Medicine, licensed under CC BY 3.0. Modifications: increased size. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Muscle involvement in polyarteritis nodosa**
Photomicrograph of a muscle biopsy specimen (H&E stain; medium power magnification)
The artery (top right) shows a transmural inflammatory infiltrate (blue overlay), fibrinoid necrosis (yellow overlay; identifiable as the eosinophilic region within the arterial wall), and an intraluminal thrombus (blue hatched overlay). The skeletal muscle fibers (bottom left) appear normal.
Transmural necrotizing inflammation of small- and medium-sized arteries is a characteristic feature of polyarteritis nodosa.

Source: © IMPP

**Polyarteritis nodosa**
Photomicrograph of a muscle biopsy sample with a medium-sized arterial vessel (H&E stain; low magnification)
There is transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis.
These findings are characteristic of polyarteritis nodosa.

Source: © IMPP

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.

Granulomatosis with polyangiitis is the 'C' disease: Curvy nose (saddle nose deformity), Chronic sinusitis, Cough, Conjunctivitis and Corneal ulceration, Cardiac arrhythmias, non-Caseating granulomas on biopsy, cANCA, Corticosteroids and Cyclophosphamide as treatment.

Granulomatosis with polyangiitis fact sheet Pulmonary manifestation of granulomatosis with polyangiitis Cytoplasmic pattern of antineutrophil cytoplasmic antibodies (c-ANCA) Multifocal ground-glass opacities 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.

IgA vasculitis fact sheet Purpura in IgA vasculitis Leukocytoclastic vasculitis

**Granulomatosis with polyangiitis fact sheet**
© AMBOSS

**Cytoplasmic pattern of antineutrophil cytoplasmic antibodies (c-ANCA)**
Indirect immunofluorescence of c-ANCA on ethanol-fixed neutrophils (high magnification)
Fluorescently labeled antibodies bind to c-ANCA, forming an extensive, granular pattern of fluorescence within the entire cytoplasm. The unlabeled areas in the center of the neutrophils are the lobulated nuclei. Alternative fluorescence patterns include the perinuclear ANCA (p-ANCA) pattern and the abnormal ANCA (a-ANCA) pattern. Fluorescence patterns are associated with specific antigens and, therefore, the pattern can help determine the underlying disease.
The c-ANCA pattern often suggests the presence of autoantibodies against proteinase 3, which is a characteristic finding in granulomatosis with polyangiitis.

Source: "Immunofluorescence pattern produced by binding of ANCA to ethanol-fixed neutrophils, from a person with GPA", Malittle, Wikimedia licensed under Public Domain

**Pulmonary manifestation of granulomatosis with polyangiitis**
Photograph of a macroscopic preparation of a lung
Round, solitary and nodular changes (green overlay) with centrally necrotic cavities (arrows) can be recognized in the left lung.
These pathological changes are typically seen in granulomatosis with polyangiitis.

Source: “Wegener's granulomatosis” by Yale Rosen, Flickr, licensed under CC BY-SA 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 2.0.

**Multifocal ground-glass opacities**
CT chest (high resolution; axial plane; lung window) of a patient with symptoms of asthma and eosinophilia
Scattered ground-glass opacities (examples indicated by red arrows) are present in both lungs, especially in the periphery.
In conjunction with the clinical symptoms, the CT findings are compatible with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).
Eosinophilic granulomatosis with polyangiitis frequently manifests with peripheral or randomly distributed ground-glass or consolidative opacities. Bronchial wall thickening, septal thickening, and nodules may also be seen.

Source: “Fig. 6C, in: COVID-19 pneumonia: the great radiological mimicker” by Duzgun SA, Durhan G, Demirkazik FB, Akpinar MG, Ariyurek OM, Insights Imaging, licensed under CC BY 4.0. Modifications: Image was cropped.

**Eosinophilic granulomatosis with polyangiitis**
Photomicrograph of eosinophilic vasculitis (H&E stain; high magnification)
Two blood vessels (white outlines) with necrotizing vasculitis with eosinophil infiltration of the media (indicated by arrows in the detail) are visible. Extravascular accumulations of eosinophils cause the characteristic tissue eosinophilia (examples indicated by arrowheads).
These findings are consistent with eosinophilic granulomatosis with polyangiitis.

Source: “Churg-Strauss syndrome - high mag” by Michael Bonert ("Nephron"), Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Purpura in IgA vasculitis**
Maculopapular, reddish, non-blanching, palpable skin lesions (purpura) are seen on both the distal right arm and leg. On the lower leg, the lesions are partially confluent and present with scaling and erosion.

Source: "Purpura2", Okwikikim, Wikimedia Commons licensed under Public Domain

**Leukocytoclastic vasculitis**
Photomicrograph of a skin tissue sample (H&E stain; high magnification)
There is focal neutrophilic inflammation (neutrophils indicated by arrowheads) neighboring a small blood vessel (marked by blue line) of the skin with the typical appearance of fragmented neutrophilic nuclei (leukocytoclasia, examples marked by arrows).
These findings are suggestive of small-vessel leukocytoclastic vasculitis (leukocytoclastic vasculitis).

Source: “Leukocytoclastic vasculitis -- high mag.jpg” by Nephron, Libre Pathology, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

Variable vessel vasculitis

Overview of variable vessel vasculitides
	Clinical features	Diagnostics	Management
Behcet disease	Most commonly occurs in individuals from Turkey, the Middle East, and Japan Oral and genital ulcers Uveitis Erythema nodosum	Positive pathergy test	Glucocorticoids PLUS other immunosuppressive agents based on the type and severity of manifestations See “Behcet disease” for more information.
Cogan syndrome [2][9]	Inflammatory ocular lesions, e.g.: Interstitial keratitis Uveitis Episcleritis Inner ear disease, e.g.: Sensorineural hearing loss Acute vestibular syndrome Vasculitis, e.g.: Aortitis Aortic aneurysms Valvulitis of the aortic or mitral valves	Clinical diagnosis	Glucocorticoids

Differential diagnoses

Infectious diseases
Thrombotic disorders, e.g.:
- Antiphospholipid syndrome
- Thrombotic thrombocytopenic purpura
- Sickle cell disease
Thromboangiitis obliterans
Amyloidosis
Scurvy
Ergotamines

The differential diagnoses listed here are not exhaustive.

References

Younger DS. "Overview of the Vasculitides". Neurol Clin. 37(2). :171-200. (2019)
Espígol-Frigolé G, Prieto-González S, Alba MA, et al. "Advances in the Diagnosis of Large Vessel Vasculitis". Rheumatic Disease Clinics of North America. 41(1). :125-140. (2015)
Kim ESH, Beckman J. "Takayasu arteritis: challenges in diagnosis and management.". Heart. 104(7). :558-565. (2018)
Bardi M, Diamantopoulos AP. "EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice summary". Radiol Med (Torino). 124(10). :965-972. (2019)
Suresh E. "Diagnostic approach to patients with suspected vasculitis". Postgrad Med J. 82(970). :483-488. (2006)
Jennette JC, Falk RJ, Bacon PA, et al. "2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides". Arthritis & Rheumatism. 65(1). :1-11. (2012)
Micheletti RG, Pagnoux C. "Management of cutaneous vasculitis". Presse Med. 49(3). :104033. (2020)
Goeser MR, Laniosz V, Wetter DA. "A Practical Approach to the Diagnosis, Evaluation, and Management of Cutaneous Small-Vessel Vasculitis". Am J Clin Dermatol. 15(4). :299-306. (2014)
A. Greco, A. Gallo, M. Fusconi, et al. "Cogan's syndrome: An autoimmune inner ear disease". Autoimmun Rev. 12(3). :396-400. (2013)