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Vasculitis
Irene J. Tan, MD, FACR
image BASICS
DESCRIPTION
An inflammatory blood vessel disorder
  • Clinical features result from the destruction of blood vessel walls with subsequent thrombosis, ischemia, bleeding, and/or aneurysm formation.
  • Vasculitis consists of a large, heterogeneous group of diseases classified by the predominant size, type, and the location of involved blood vessels (1).
    • Small-vessel vasculitis
      • Microscopic polyangiitis (MPA)
      • Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis)
      • Eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome)
      • Antiglomerular basement membrane disease (anti-GBM)
      • Cryoglobulinemic vasculitis
      • IgA vasculitis (Henoch-Schönlein purpura [HSP])
      • Hypocomplementemic urticarial vasculitis
    • Medium-vessel vasculitis
      • Polyarteritis nodosa (PAN)
      • Kawasaki disease (KD)
    • Large-vessel vasculitis
      • Takayasu arteritis (TAK)
      • Giant cell arteritis (GCA)
  • Vasculitis occurs as a primary disorder or secondary to infection, a drug reaction, malignancy, or connective tissue disease.
    • Variable vessel vasculitis
      • Behçet disease
      • Cogan syndrome
    • Single-organ vasculitis
      • Cutaneous leukocytoclastic angiitis
      • Cutaneous arteritis
      • Primary CNS vasculitis
    • Vasculitis associated with systemic disease
      • Lupus vasculitis
      • Rheumatoid vasculitis
      • Sarcoid vasculitis
    • Vasculitis associated with other etiology
      • Hepatitis C-associated cryoglobulinemic vasculitis
      • Hepatitis B-associated vasculitis
      • Syphilis-associated aortitis
      • Drug-induced immune complex vasculitis
      • Drug-associated antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis
      • Cancer-associated vasculitis
  • Protean features often delay definitive diagnosis.
EPIDEMIOLOGY
Highly variable, depending on the particular syndrome
  • Hypersensitivity vasculitis is the most commonly encountered vasculitis in clinical practice.
  • KD, IgA vasculitis, and dermatomyositis are more common in children.
  • TAK is most prevalent in young Asian women. GPA, MPA, and EGPA are more common in middle-aged males.
  • GCA occurs exclusively in those >50 years of age and is rare in the African American population.
Incidence
Annual incidence in adults (unless otherwise specified)
  • IgA vasculitis: 200 to 700/1 million in children <17 years of age
  • GCA: 170/1 million
  • KD: depends on race/age; ˜170/1 million
  • PAN: 2 to 33/1 million
  • GPA: 4 to 15/1 million
  • MPA: 1 to 24/1 million
  • EGPA: 1 to 3/1 million
  • TAK: 2/1 million
  • Hypersensitivity vasculitis: depends on drug exposure
  • Viral-/retroviral-associated vasculitis: unknown; >90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C.
  • Connective tissue disorder-associated vasculitis: variable
ETIOLOGY AND PATHOPHYSIOLOGY
  • Three major immunopathogenic mechanisms
    • Immune-complex formation: systemic lupus erythematosus (SLE), IgA vasculitis (HSP), and cryoglobulinemic vasculitis
    • ANCAs: GPA, MPA, and EGPA
    • Pathogenic T-lymphocyte response: GCA and TAK
  • Pathophysiology best understood where known drug triggers have been identified (e.g., antibiotics, sulfonamides, and hydralazine)
Genetics
  • A number of the vasculitic syndromes have been linked to candidate genes.
  • No single gene has been found to cause vasculitis.
  • Angiotensin-converting enzyme insertion/deletion polymorphism is associated with susceptibility to vasculitis, especially in Behçet disease and IgA vasculitis.
RISK FACTORS
A combination of genetic susceptibility and environmental exposure likely triggers onset.
GENERAL PREVENTION
Early identification is the key to prevent irreversible organ damage in severe forms of systemic vasculitis.
COMMONLY ASSOCIATED CONDITIONS
Hepatitis C (cryoglobulinemic vasculitis), hepatitis B (PAN), cytomegalovirus (CMV), Epstein-Barr virus (EBV), HIV (viral-/retroviral-associated vasculitis), SLE, rheumatoid arthritis (RA), Sjögren syndrome, mixed connective tissue disease (MCTD), dermatomyositis, ankylosing spondylitis, Behçet disease, relapsing polychondritis (CTD-associated vasculitis), respiratory tract methicillinresistant Staphylococcus aureus (MRSA) (GPA)
image DIAGNOSIS
PHYSICAL EXAM
  • Vital signs: blood pressure (hypertension) and pulse (regularity and rate)
  • Skin: palpable purpura, livedo reticularis, nodules, ulcers, gangrene, nail bed capillary changes
  • Neurologic: cranial nerve exam, sensorimotor exam
  • Ocular exam: visual fields, scleritis, episcleritis
  • Cardiopulmonary exam: rubs, murmurs, arrhythmias
  • Abdominal exam: tenderness, organomegaly
DIFFERENTIAL DIAGNOSIS
  • Fibromuscular dysplasia
  • Embolic disease (atheroma, cholesterol emboli, atrial myxoma, mycotic aneurysm with embolization)
  • Drug-induced vasospasm (cocaine, amphetamines, ergots)
  • Thrombotic thrombocytopenic disorders (disseminated intravascular coagulation [DIC], thrombotic thrombocytopenic purpura [TTP], antiphospholipid syndrome, heparin- or warfarin-induced thrombosis)
  • Systemic infection (infective endocarditis, fungal infections, disseminated gonococcal infection, Lyme disease, syphilis, Rocky Mountain spotted fever [RMSF], bacteremia)
  • Malignancy (lymphomatoid granulomatosis, angioimmunoblastic T-cell lymphoma, intravascular lymphoma)
  • Miscellaneous (Goodpasture syndrome, sarcoidosis, amyloidosis, Whipple disease, congenital coarctation of aorta)
DIAGNOSTIC TESTS & INTERPRETATION
  • Initial tests to exclude alternate diagnosis and guide appropriate therapy
  • Routine tests
    • CBC
    • Liver enzymes
    • Serum creatinine
    • Urinalysis with microscopy
  • P.1109

  • Specific serology
    • Antinuclear antibodies (ANA)
    • Rheumatoid factor (RF)
    • Rapid plasma reagin/venereal disease reaction level (RPR/VDRL)
    • RMSF titer
    • Lyme titer
    • Complement levels C3, C4
    • ANCA
    • Antiproteinase 3 antibodies (anti-PR3)
    • Antimyeloperoxidase antibodies (anti-MPO)
    • Hepatitis screen for B and C
    • Cryoglobulin
    • Anti-GBM titer
    • HIV
    • Serum and urine protein electrophoresis
  • Miscellaneous
    • Drug screen
    • ESR
    • C-reactive protein
    • Creatine kinase (CK)
    • Blood culture
    • ECG
  • CXR, CT scan, MRI, and arteriography may be required to delineate extent of organs involved.
Diagnostic Procedures/Other
  • Electromyography with nerve conduction can document neuropathy and target nerve for biopsy.
  • Biopsy of affected site confirms diagnosis (e.g., temporal artery, sural nerve, renal biopsy).
  • If biopsy is not practical, angiography may be diagnostic for large- and medium-vessel vasculitides.
  • Bronchoscopy may be required to differentiate pulmonary infection from potentially life-threatening hemorrhagic vasculitis in patients with hemoptysis.
Test Interpretation
Blood vessel biopsy shows immune cell infiltration into vessel wall layers with varying degrees of necrosis and granuloma formation, depending on the type of vasculitis
image TREATMENT
GENERAL MEASURES
  • Discontinue offending drug (hypersensitivity vasculitis)
  • Simple observation for mild cases of IgA vasculitis
  • ANCA-associated vasculitis has 2-phase treatment: initial induction followed by maintenance (steady tapering of corticosteroids with immunosuppressants or immunomodulators)
MEDICATION
First Line
Corticosteroids are initial anti-inflammatory of choice.
Second Line
Cytotoxic medications, immunomodulatory, or biologic agents (e.g., cyclophosphamide (2)[B],(3,4)[A] methotrexate (4,5)[A], azathioprine (4,5)[A], leflunomide (4)[A], mycophenolate mofetil (2)[B],(4)[A], and rituximab (3,4)[A], are often required in combination with corticosteroids for rapidly progressive vasculitis with significant organ involvement or inadequate response to corticosteroids.
ISSUES FOR REFERRAL
  • Rheumatology referral for complicated cases where newer or more toxic treatments are required.
  • Nephrology referral for persistent hematuria or proteinuria, rising creatinine, or a positive ANCA titer
  • Pulmonary referral for persistent pulmonary infiltrate unresponsive to antibiotic therapy or if gross hemoptysis
ADDITIONAL THERAPIES
  • IVIG and aspirin for KD, but corticosteroids are contraindicated.
  • Plasma exchange appears to improve recovery of patients with severe acute renal failure secondary to vasculitis and pulmonary hemorrhage (4)[A].
SURGERY/OTHER PROCEDURES
Rarely, corrective surgery is required to repair tissue damage as a result of aggressive vasculitis.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Hemoptysis, acute renal failure, intestinal ischemia, any organ-threatening symptoms or signs, and/or need for biopsy
  • Initial therapy is guided by the organ system involved.
    • If pulmonary hemorrhage is present, life-saving measures may include mechanical ventilation, plasmapheresis, and immunosuppression.
    • If acute renal failure is present, attend to electrolyte and fluid balance and consider plasma exchange and immunosuppression.
    • If signs of intestinal ischemia are present, make NPO and consider plasmapheresis, immunosuppression, and parenteral nutrition.
Discharge Criteria
Stabilization or resolution of potential life-threatening symptoms
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
If significant coronary artery disease is involved in KD, moderate activity restriction may be of benefit.
Patient Monitoring
Frequent clinical follow-up supported by patient selfmonitoring to identify disease relapse
DIET
Alter diets for patients with renal involvement or hyperglycemia/dyslipidemia
PROGNOSIS
Prognosis is good for patients with vasculitis and limited organ involvement. Relapsing courses, renal, intestinal, or extensive lung involvement have a poorer prognosis.
REFERENCES
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1-11.
2. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112.
3. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232.
4. Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010;11:12.
5. Bosch X, Guilabert A, Espinosa G, et al. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298(6):655-669.
Additional Reading
&NA;
  • Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis. 2008;67(2):195-205.
  • Gatto M, Iaccarino L, Canova M, et al. Pregnancy and vasculitis: a systematic review of the literature. Autoimmun Rev. 2012;11(6-7):A447-A459.
  • Lee YH, Choi SJ, Ji JD, et al. Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to vasculitis: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2012;13(1):196-201.
  • National Heart Lung and Blood Institute Diseases and Conditions Index: Vasculitis. www.nhlbi.nih.gov/health/dci/Diseases/vas/vas_whatis.html
  • Vasculitis Foundation: www.vasculitisfoundation.org/
Codes
&NA;
ICD10
  • I77.6 Arteritis, unspecified
  • M31.30 Wegener's granulomatosis without renal involvement
  • M30.0 Polyarteritis nodosa
Clinical Pearls
&NA;
  • Suspect vasculitis in patients with a petechial rash, palpable purpura, glomerulonephritis, pulmonaryrenal syndrome, intestinal ischemia, or mononeuritis multiplex.
  • Exclude silent renal involvement by routinely obtaining serum creatinine and urinalysis with microscopy.
  • Vasculitis has “skip” lesions, which may complicate diagnostic biopsy.
  • In patients with vasculitis, look for a primary underlying process such as infection, thrombosis, or malignancy.