DESCRIPTION

• Injury to the walls of blood vessels from inflammation:
  • Ischemia and necrosis
  • Aneurysms and hemorrhage
  • Immunopathologic mechanisms:
    • Deposition of circulating antigen–antibody complex and complement fixation
    • Cell-mediated hypersensitivity
    • Granulomatous tissue reaction from persistent inflammation and formation of epithelioid giant cells
• The vasculitides represent a wide group of disorders:
  • Multisystem disease with constitutional symptoms and inflammatory lab indices
  • Secondary to another disorder or trigger, or primary if vasculitis is the principal feature and the cause is unknown
  • Multiple factors determine presentation:
    • The size of the affected blood vessels
    • The specific distribution, severity, and duration of the inflammation
    • Degree of permeability or occlusion of the affected vessels
• 1 out of 2,000 adults has some form of vasculitis

ETIOLOGY

• Classification is evolving and is increasingly based on presence or absence of antineutrophil cytoplasmic antibodies (ANCA).
• Traditional classification is based on vessel size.
• Large vessel vasculitides:
  • Temporal (giant cell) arteritis:
    • Granulomatous arteritis of the aorta and its major branches often involving the temporal artery
    • Patients > 50 yr
  • Takayasu arteritis:
    • Granulomatous inflammation of the aorta and its major branches
    • Usually occurs in patients < 50 yr
• Medium vessel vasculitides:
  • Polyarteritis nodosa (PAN):
    • Small- and medium-sized arteritis
    • Common distribution includes vessels supplying the muscles, joints, intestines, nerves, kidneys, and skin
    • Most common in middle age
  • Kawasaki disease (mucocutaneous lymph node syndrome):
    • Coronary arteries are often involved and involves large-, medium-, and small-sized arteries
    • Usually occurs in children
  • Isolated CNS vasculitis
• Small vessel vasculitides:
  • Granulomatosis with polyangiitis (Wegener granulomatosis):
    • Necrotizing vasculitis affecting small- to medium-sized vessels
    • Granulomatous inflammation of the upper and lower respiratory tract and glomerulonephritis
  • Microscopic polyangiitis:
    • Necrotizing affecting small vessels
    • Glomerulonephritis is very common.
    • Pulmonary capillaritis often occurs.
  • Churg–Strauss syndrome (allergic granulomatosis):
    • Small- and medium-sized arteries
    • Mainly lungs, GI, and nerves
    • Can also involve heart, skin, and kidney
  • Henoch–Schönlein purpura:
    • Most patients < 20 yr
  • Buerger disease (thromboangiitis obliterans):
  • Hypersensitivity vasculitis:
    • Recurring inflammation and thrombosis of small and medium arteries and veins of the hands and feet
    • Typically between 20 and 40 yr and male
  • Secondary vasculitides:
    • Bacterial infections:
      • Streptococcal, tuberculous, staphylococcal, Lyme disease, leprosy
    • Viral infections:
      • Hepatitis B or C, CMV, HSV, HIV
    • Rickettsial infections
    • Drug related
    • Connective tissue disease:
      • Systemic lupus erythematosus
      • Rheumatoid arthritis
      • Behçet disease
    • Malignancy:
      • Hairy cell leukemia
      • Lymphoma
    • Mixed cryoglobulinemia
    • Goodpasture syndrome
    • Serum sickness

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• Systemic complaints are common early in the presentation of vasculitis, before vascular-related complications occur:
  • Fever, fatigue, weight loss, diffuse aches and pains
• Signs of arterial insufficiency:
  • Ischemic pain:
    • Angina, abdominal angina, claudication, jaw claudication
  • Neurologic ischemia:
    • Headache, TIA, stroke, visual and sensorineural hearing loss, hallucinations, neuropathy, vision loss
  • Renal ischemia:
    • Severe or resistant HTN
  • Dermatologic ischemia:
    • Classic skin findings include palpable purpura.
    • Nodular lesions, ulcers, livedo reticularis, and digital ischemia may also be seen
  • Oligoarthritis
  • Ocular ischemia:
    • Diplopia, retinal hemorrhages, scleritis, and episcleritis
  • Respiratory tract:
    • Sinusitis, epistaxis, nasal and oral ulcerations, strawberry tongue
  • GI ischemia:
    • Hematochezia, melena, hematemesis, peritonitis, hepatitis
  • Cardiac:
    • Coronary artery aneurysms, myocarditis, pericarditis, valvular disease, CHF

History

• Suspect vasculitis with general systems and signs of arterial insufficiency:
  • Claudication, angina, abdominal angina, or TIA, in a young patient
  • Prolonged systemic illness with multiorgan dysfunction
  • History of glomerulonephritis, peripheral neuropathy, or autoimmune disease
• Diagnostic clues to the etiology:
  • Age, gender, ethnicity, travel history
  • Specific complaints that suggest the size of the involved vessel and organs
  • Recent infections
  • Connective tissue disorders
  • Medications that may cause vasculitis:
    • Levsamisole (as a cocaine adulterant), phenytoin, carbamazepine, isoniazid, methimazole, minocycline, penicillamine, propylthiouracil, sulfasalazine

Physical Exam

Classify vasculitis:

• Large arteries:
  • Diminished pulses and bruits over several large arteries
  • BP discrepancy > 10 mm Hg between left and right limbs
  • Pulse discrepancy > 30 mm Hg between the left and right limbs
  • Cool extremities due to claudication and ulceration
• Medium and small arteries:
  • Palpable purpura (nodules, ulcers, livedo papules)
  • Skin ulcers
  • Digital ischemia

ESSENTIAL WORKUP

• History and physical exam
• CBC, ESR, CRP, urinalysis, BUN, creatinine

DIAGNOSIS TESTS & INTERPRETATION

Lab

• CBC:
  • Leukocytosis
  • Eosinophilia
  • Anemia
• Creatinine
• LFT
• CRP
• ESR
• ANA
• ANCA
• Complement
• CPK
• Urinalysis:
  • Proteinuria and hematuria

Imaging

• CXR:
  • PAN usually has a nonspecific patchy alveolar infiltration.
• CT scan:
  • Sinus CT for suspected granulomatosis with polyangiitis (Wegener)
• CTA:
  • Coronary artery aneurysms in Kawasaki
• Echocardiography:
  • Coronary artery aneurysms in Kawasaki
• MRI and MRA:
  • Positron emission tomography (PET) scan for suspected Takayasu and Kawasaki
• ECG:
  • Indications:
    • Suspected Takayasu and Kawasaki
• US:
  • Temporal artery US for suspected giant cell arteritis
  • Use pretest probability in interpretation of results
• Arteriography

Diagnostic Procedures/Surgery

• EKG:
  • Pericarditis, conduction disturbances
• Endoscopy, sigmoidoscopy, and colonoscopy for GI tract involvement
• Tissue biopsy

DIFFERENTIAL DIAGNOSIS

• Endocarditis
• Adverse drug reaction
• Viral infections (e.g., enterovirus)
• Scarlet fever
• Staphylococcal scalded skin syndrome
• Toxic shock syndrome
• Stevens–Johnson syndrome
• Rocky Mountain spotted fever
• Leptospirosis
• Antiphospholipid antibody syndrome
• Disseminated intravascular coagulation
• Cholesterol emboli
• Calciphylaxis

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

Stabilization of cerebrovascular complications

ED TREATMENT/PROCEDURES

• Treatment for vasculitis is determined by the underlying cause or the specific disease and is best initiated by rheumatology.
• Kawasaki: Aspirin, IVIG
• Giant cell arteritis: Corticosteroids
• PAN: Steroids, cyclophosphamide
• Takayasu arteritis: Corticosteroids, methotrexate, azathioprine, cyclophosphamide
• Wegner granulomatosis: Corticosteroids:
  • Cyclophosphamide, azathioprine may be substituted
  • Plasma exchange may be helpful in severe disease.

MEDICATION

• Azathioprine: 2 mg/kg/d PO
• Cyclophosphamide:
  • IV: 0.5–1 mg/m² body surface area
  • PO: 2 mg/kg/d (up to 4 mg/kg) (peds: dose as per consultant)
• IVIG: 1–2 g/kg IV
• Methylprednisolone: 0.25–1 mg/d IV
• Methotrexate: 7.5–15 mg/wk PO
• Prednisolone: 1 mg/kg/d PO
• Prednisone: 40–60 mg/d (peds: 1–2 mg/kg/d) PO

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

• Patients with evidence of severe disease and end-organ dysfunction should be admitted.
• Consult for procedures to revascularize ischemic organs.

Discharge Criteria

Less-symptomatic patients without evidence of end-organ involvement

Issues for Referral

• Any patient suspected of vasculitis and being managed as an outpatient should be referred as soon as possible to a rheumatologist for the definitive diagnosis and treatment.
• Consult appropriate specialties based on the severity of the end-organ damage.

FOLLOW-UP RECOMMENDATIONS

Stress the need for close follow-up with general symptoms to confirm the diagnosis and initiate therapy that will be life-saving on a long-term basis.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Drug therapy may be toxic; do not prescribe without specialist consultation.
• Patients may be immunosuppressed and at risk for opportunistic pathogens.
• Do not miss subacute bacterial endocarditis as a mimic of vasculitis.
• Temporal (giant cell) arteritis does not occur before age 50 yr.
• Nodular lesions are the skin changes most likely to yield a diagnosis of vasculitis.

ICD9

• 446.0 Polyarteritis nodosa
• 446.5 Giant cell arteritis
• 447.6 Arteritis, unspecified

ICD10

• I77.6 Arteritis, unspecified
• M30.0 Polyarteritis nodosa
• M31.6 Other giant cell arteritis

[Outline]

• ICD9
• ICD10

• Langford CA. Vasculitis. J Allerg Clin Immunol. 2010;125(2 suppl 2):S216–S225.
• Lapraik C, Watts R, Bacon P, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford). 2007;46(10):1615–1616.
• Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310–317.
• Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114(6):1708–1733.
• Semple D, Keogh J, Forni L, et al. Clinical review: Vasculitis on the intensive care unit-part 1: Diagnosis. Crit Care. 2005;9(1):92–97.
• Semple D, Keogh J, Forni L, et al. Clinical review: Vasculitis on the intensive care unit-part 2: Treatment and prognosis. Crit Care. 2005;9(2):193–197.

See Also (Topic, Algorithm, Electronic Media Element)

• Erythema Nodosum
• Henoch–Schönlein Purpura
• Hepatitis
• Reiter Syndrome
• Systemic Lupus Erythematosus

Richard S. Klasco