Description

Vasculitis is an inflammatory disease of the blood vessels:

• Clinical features result from the destruction of blood vessel walls, with subsequent thrombosis, ischemia, bleeding, and/or aneurysm formation.
• Consists of a large, heterogeneous group of diseases classified by the predominant size, type, and the location of the blood vessels involved:
  • Small-vessel vasculitis:
    • Churg-Strauss syndrome
    • Wegener granulomatosis
    • Microscopic polyangiitis
    • Henoch-Schönlein purpura
    • Essential cryoglobulinemic vasculitis
    • Hypersensitivity vasculitis
    • Viral-/retroviral-associated vasculitis
    • Connective tissue disorder–associated vasculitis
  • Medium-vessel vasculitis:
    • Polyarteritis nodosa
    • Kawasaki disease
    • Isolated CNS vasculitis
  • Large-vessel vasculitis:
    • Takayasu arteritis
    • Giant cell arteritis
• Occurs as primary disorders or secondary to infection, a drug reaction, malignancy, or connective tissue disorder
• Protean features often delay the diagnosis.

Epidemiology

• Hypersensitivity vasculitis is the most commonly encountered vasculitis in clinical practice.
• Kawasaki disease, Henoch-Schönlein purpura, and dermatomyositis are more common in children.
• Takayasu arteritis is most prevalent in young Asian women.
• Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are more common in middle-aged males.
• Giant cell arteritis occurs exclusively in those >50 years of age and is rare in the African American population.

• Hypersensitivity vasculitis: Depends on drug exposure patterns
• Connective tissue disorder–associated vasculitis: Variable
• Henoch-Schönlein purpura: 200–700/1 million in children <17 years of age
• Giant cell arteritis: 170/1 million
• Kawasaki disease: Depends on race/age; ~170/1 million
• Polyarteritis nodosa: 2–33/1 million
• Wegener granulomatosis: 4–15/1 million
• Microscopic polyangiitis: 1–24/1 million
• Churg-Strauss arteritis: 1–3/1 million
• Viral-/retroviral-associated vasculitis: Unknown; >90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C.
• Polyarteritis nodosa: 2–33/1 million
• Takayasu arteritis: 2/1 million

Risk Factors

A combination of genetic susceptibility and environmental exposure is presumed to play a role in disease onset.

• 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's disease and Henoch-Schönlein purpura (1)[A]

General Prevention

None

• Early identification is the key to prevent irreversible organ damage in severe forms of systemic vasculitis.

Pathophysiology

3 major immunopathogenic mechanisms have been proposed:

• Immune-complex formation: Systemic lupus erythematosus (SLE), polyarteritis nodosa, and essential mixed cryoglobulinemia
• Antineutrophil cytoplasmic antibodies (ANCAs): Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome
• Pathogenic T-lymphocyte response: Giant cell arteritis and Takayasu arteritis

Etiology

Not well understood in most forms of vasculitis, except where known drug triggers have been identified (e.g., antibiotics, sulfonamides, and hydralazine)

Commonly Associated Conditions

Hepatitis C (essential cryoglobulinemic vasculitis), hepatitis B (polyarteritis nodosa [PAN]), SLE, rheumatoid arthritis (RA), Sjögren syndrome, mixed connective tissue disease (MCTD), dermatomyositis, ankylosing spondylitis, Behçet disease, relapsing polychondritis (CTD-associated vasculitis), HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C (viral-/retroviral-associated vasculitis), respiratory tract methicillin-resistant Staphylococcus aureus (MRSA) (Wegener granulomatosis [WG]).

History

• Consider patient's age, sex, and ethnicity.
• Note the organs affected and estimate the size of blood vessels involved.
• Use the pattern of demographics, clinical features, and the predominant vessel size/organ involvement to narrow down the specific type of vasculitis.

Physical Exam

• Constitutional symptoms: Fever, weight loss, malaise, fatigue, diminished appetite, sweats
• Skin findings: Palpable purpura, livedo reticularis, nodules, ulcers, gangrene, nail bed capillary changes
• CNS findings: Mononeuritis multiplex, polyneuropathy, headaches, visual loss, tinnitus, stroke, seizure, encephalopathy
• Heart/Lung findings: Myocardial infarction, cardiomyopathy, pericarditis, arrhythmia, cough, chest pain, hemoptysis, dyspnea
• Renal manifestations: Hypertension, proteinuria, hematuria, renal insufficiency
• GI manifestations: Abdominal pain, hematochezia, perforation
• Musculoskeletal manifestations: Arthralgia, myalgia
• Miscellaneous: Unexplained ischemic or hemorrhagic events, chronic sinusitis, scleritis, episcleritis, and recurrent epistaxis

Diagnostic Tests and Interpretation

ALERT
Clinically silent kidney involvement warrants both a routine serum creatinine and urinalysis with microscopy for underlying glomerulonephritis.

Labs are required to exclude alternate diagnosis, which has major treatment implications.

• Routine tests:
  • CBC
  • Liver enzymes
  • Serum creatinine
  • Urinalysis with microscopy
• Serology:
  • Antinuclear antibodies (ANA)
  • Rheumatoid factor (RF)
  • Rapid plasma reagin/venereal disease reaction level (RPR/VDRL)
  • Rocky Mountain spotted fever (RMSF titer)
  • Lyme test
  • Complements C3,C4
  • ANCA titer
  • Hepatitis screen for B and C
  • Antiglomerular basement membrane titer
  • HIV
  • Serum protein electrophoresis
• Miscellaneous:
  • Drug screen
  • ESR
  • C-reactive protein
  • Creatine kinase (CK)
  • Blood culture
  • ECG

Imaging
Chest x-ray (CXR), CT scan, MRI, and arteriography may be required to delineate extent of organs involved.

• Electromyography with nerve conduction studies may be useful for documenting neuropathy and to target affected nerve for biopsy.
• Biopsy of the affected tissue/organ is essential to substantiate 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.

Pathological Findings
Immune cell infiltration into the blood vessel wall layers with varying degrees of necrosis and granuloma formation, depending on the type of vasculitis

Differential Diagnosis

• Fibromuscular dysplasia
• Embolic disease (atheroma, cholesterol emboli, atrial myxoma, mycotic aneurysm with embolization)
• Vasospasm, drug-induced (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, RMSF, bacteremia)
• Malignancy (lymphomatoid granulomatosis, angioimmunoblastic T-cell lymphoma, intravascular lymphoma)
• Miscellaneous (Goodpasture syndrome, sarcoidosis, amyloidosis, Whipple disease, congenital coarctation of aorta)

Medication (Drugs)

First Line
Corticosteroids are the initial systemic anti-inflammatory agent (2)[A],(3)[C] with rapid onset of action.

Second Line
Cytotoxic medications (e.g., cyclophosphamide (4,5)[A], methotrexate, azathioprine (5)[A], mycophenolate mofetil, and rituximab) are often required in combination with corticosteroids for rapidly progressive vasculitis with significant organ involvement or inadequate response to corticosteroids.

Additional Treatment

• Discontinue the offending drug for hypersensitivity vasculitis.
• Simple observation for mild cases of Henoch-Schönlein purpura.

• 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 gross hemoptysis

• IVIG and aspirin for Kawasaki disease, but corticosteroids are contraindicated
• Plasma exchange appears to improve recovery of patients with severe acute renal failure secondary to vasculitis (6)[A] and pulmonary hemorrhage.

Surgery/Other Procedures

Rarely, corrective surgery is required to repair tissue damage as a result of aggressive vasculitis.

In-Patient Considerations

• If pulmonary hemorrhage is present, life-saving measures may include mechanical ventilation, plasmapheresis, and immunosuppression.
• If acute renal failure is present, electrolyte and fluid balance as well as plasma exchange and immunosuppression should be considered.
• If signs of intestinal ischemia, patient should be NPO and be considered for plasmapheresis, immunosuppression, and parenteral nutrition.

Admission Criteria
Hemoptysis, acute renal failure, intestinal ischemia, any organ-threatening symptoms or signs, and/or need for biopsy

Discharge Criteria
Stabilization or resolution of potential life-threatening symptoms

Follow-Up Recommendations

If significant coronary artery disease is involved in Kawasaki disease, moderate activity restriction may be of benefit.

Patient Monitoring
Frequent clinical follow-up supported by patient self-monitoring is the key to the timely identification of disease relapse.

Diet

Special diet for patients with renal involvement, or ones with hyperglycemia/dyslipidemia as a result of therapeutic corticosteroids

Prognosis

Prognosis is good, particularly vasculitis with limited organ involvement. Relapsing courses, renal or extensive lung involvement portend the worst prognosis.

Complications

• Varying degrees of persistent organ dysfunction may be the result of the disease, medications, or scarring in the more serious forms of vasculitis.
• Early death is due to active vasculitic disease, and late death may be from complications of therapy (corticosteroids and cytotoxic medications).

See Also

• National Heart Lung and Blood Institute Diseases and Conditions Index: Vasculitis: http://www.nhlbi.nih.gov/health/dci/Diseases/vas/vas_whatis.html
• The Vasculitis Foundation: http://www. vasculitisfoundation.org/

ICD-9

• 446.0 Polyarteritis nodosa
• 446.4 Wegener's granulomatosis
• 447.6 Arteritis, unspecified
• 446.5 Giant cell arteritis
• 273.2 Other paraproteinemias
• 287.0 Allergic purpura
• 446.1 Acute febrile mucocutaneous lymph node syndrome [MCLS]
• 446.20 Hypersensitivity angiitis, unspecified
• 446.7 Takayasu's disease

ICD-10

• I77.6 Arteritis, unspecified
• M31.30 Wegener's granulomatosis without renal involvement
• D69.0 Allergic purpura
• M31.6 Other giant cell arteritis
• D89.1 Cryoglobulinemia
• M30.1 Polyarteritis with lung involvement [Churg-Strauss]
• M30.3 Mucocutaneous lymph node syndrome [Kawasaki]
• M31.0 Hypersensitivity angiitis
• M31.31 Wegener's granulomatosis with renal involvement
• M31.4 Aortic arch syndrome [Takayasu]
• M31.5 Giant cell arteritis with polymyalgia rheumatica

SNOMED

• 31996006 Vasculitis (disorder)
• 195353004 Wegener's granulomatosis (disorder)
• 155441006 Polyarteritis nodosa (disorder)
• 191306005 Henoch-Schonlein purpura (disorder)
• 190815001 Cryoglobulinemic vasculitis
• 359789008 Takayasu's disease (disorder)
• 414341000 giant cell arteritis (disorder)
• 60555002 Hypersensitivity angiitis (disorder)
• 75053002 Acute febrile mucocutaneous lymph node syndrome (disorder)
• 82275008 Allergic granulomatosis angiitis (disorder)