Vasculitis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Vasculitis is an inflammatory disease of the blood vessels.

  • Disease presentation results from the destruction of blood vessel walls, with subsequent aneurysm formation, bleeding, thrombosis, or ischemia in the various vascular beds and organs.
  • Diagnosis should be considered whenever a patient has a persistent, unexplained systemic illness or focal signs as listed below.
  • Consists of a heterogeneous group of diseases depending on size, type, and location of the blood vessel involved.
    • Small-vessel vasculitis:
      • Churg-Strauss arteritis
      • Wegener granulomatosis
      • Microscopic polyangiitis
      • Henoch-Schönlein purpura
      • Essential cryoglobulinemic vasculitis
      • Hypersensitivity vasculitis
      • Viral-associated vasculitis
      • Rheumatic-associated vasculitis
    • Medium-vessel vasculitis:
      • Polyarteritis nodosa
      • Kawasaki disease
      • Isolated CNS vasculitis
    • Large-vessel vasculitis:
      • Takayasu arteritis
      • Giant cell arteritis
  • Occurs in primary and secondary as well as acute and chronic forms.

Epidemiology

Highly variable, depending on the vasculitic syndrome:

  • Hypersensitivity vasculitis is the most commonly encountered vasculitis in clinical practice.
  • The secondary vasculitic syndromes associated with rheumatic diseases (e.g., systemic lupus erythematosus [SLE]) are more common than the primary vasculitides.
  • Giant cell arteritis, Wegener granulomatosis, and microscopic polyangiitis are the most common adult primary vasculitic syndromes in the US.
  • Kawasaki disease, Henoch-Schönlein purpura, dermatomyositis, polyarteritis nodosa, and hypersensitivity vasculitis are the most common forms that occur in children and adolescents.
  • Takayasu arteritis is most prevalent in adolescent girls and young women.
  • Giant cell arteritis occurs exclusively in those >50 years of age and is rare in the black population.

Incidence

The annual incidence in adults unless otherwise specified:

  • Hypersensitivity vasculitis: Depends on drug exposure patterns
  • Rheumatic-associated vasculitis: SLE association is the most common at 400–500/1 million.
  • 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-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.

Genetics

A number of the vasculitic syndromes have been linked to candidate genes. Establishing the role of each candidate gene in these complex diseases is ongoing. No single gene has been found to be sufficient to cause vasculitis.

General Prevention

Current understanding of the causes of this heterogeneous set of diseases limits preventive measures. Early identification is the primary mode of preventing irreversible organ damage in the forms that are not self-limiting and that may require immunotherapy.

Pathophysiology

Three major immunopathogenic mechanisms have been proposed:

  • Immune-complex formation: 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)

Diagnosis

History

The time course from start of disease complaint and presentation to medical care is often prolonged because of the nonspecific, protean nature of complaints.

Physical Exam

May be highly variable and depend on the vascular bed that is inflamed.

  • Constitutional symptoms: Malaise, fatigue, decreased appetite, sweats, and weight loss
  • Skin findings: Palpable purpura, livedo reticularis, nodules, ulcers, gangrene, nail bed capillary changes
  • CNS findings: Mononeuritis multiplex, polyneuropathy, stroke, seizure encephalopathy
  • Heart/lung findings: Cardiomyopathy, pericarditis, arrhythmia, cough, chest pain, hemoptysis, breathlessness
  • Renal manifestations: Hypertension, proteinuria, hematuria, and renal failure
  • GI manifestations: Abdominal pain, bleeding, perforation
  • Musculoskeletal manifestations: Nonspecific joint complaints
  • Miscellaneous: Unexplained ischemic events, chronic sinusitis, scleritis, episcleritis, and recurrent epistaxis
  • A careful physical examination helps to determine the extent of vascular lesions and the distribution of affected organs. The physical exam can be normal. However, findings such as mononeuritis multiplex and palpable purpura are highly suggestive of an underlying vasculitic process.

Diagnostic Tests & Interpretation

Alert

It is imperative to determine whether there is renal involvement with vasculitis because it may be symptom-free. Prognosis is generally worse when renal vasculitis is present. Both a serum creatinine and a urinalysis with microscopic evaluation are required to rule out renal involvement.

Lab

Labs are required to eliminate alternate diagnoses. A few serologic tests are helpful for suggesting a particular vasculitic syndrome, but not every test is needed on all patients.

  • Serology: RPR, RMSF titer, Lyme test, antinuclear antibody, anti-double-stranded DNA, ANCA titer, hepatitis screen for B and C, antiglomerular basement membrane titer, C3, C4
  • Hematology: Complete blood count with differential
  • Microbiology: Blood culture
  • Miscellaneous: Drug screen, erythrocyte sedimentation rate, C-reactive protein, blood urea nitrogen, and creatinine; routine urinalysis with microscopic examination for abnormal sediment

Imaging

CXR, CT scan, MRI, and arteriogram may be required to localize affected vessels.

Diagnostic Procedures/Surgery

  • Diagnostic criteria have been proposed for a number of vasculitic syndromes, but these often allow only a presumptive diagnosis.
  • Nerve conduction studies may be useful for documenting neuropathy.
  • Biopsy of the affected tissue/organ will be the most precise way to substantiate the diagnosis.
  • With hemoptysis, a bronchoscopy may be required to differentiate pulmonary infection from potentially life-threatening hemorrhagic vasculitis.

Pathological Findings

Immune cell infiltration into the blood vessel wall layers will be noted with varying degrees of necrosis and granuloma formation depending on the type of vasculitis.

Differential Diagnosis

  • Infectious diseases:
    • Bacterial endocarditis
    • Disseminated gonococcal infection
    • Pulmonary histoplasmosis
    • Coccidioidomycosis
    • Syphilis
    • Lyme disease
    • Rocky Mountain spotted fever
    • Whipple disease
  • Neoplasms
  • Drug toxicity:
    • Cocaine
    • Amphetamines, ergot alkaloids
    • Methysergide
    • Arsenic
  • Sarcoidosis
  • Atheroembolic disease
  • Goodpasture syndrome
  • Amyloidosis

Treatment

Medication

  • Initial therapy often includes nonsteroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief of pain; however, long-term use of these agents may be detrimental to the GI tract and kidney.
  • Immunosuppressive agents often are required for more extensive vasculitic syndromes.

First Line

Glucocorticoids are the initial anti-inflammatory agent (1)[A],(2)[C].

Second Line

Treatment with immunosuppressive medications other than glucocorticoids (e.g., cyclophosphamide (3,4,5)[A], methotrexate, azathioprine (4)[A], mycophenolate, tumor necrosis factor (TNF) blockers, and rituximab) is generally reserved for patients with significant organ involvement and/or patients who have had an inadequate response to glucocorticoids. Subspecialty care is usually necessary to escalate care to this point.

Additional Treatment

General Measures

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If the vasculitic syndrome is believed to be drug-related, removal of the offending agent may be curative.

Issues for Referral

Early referral to subspecialty care may be required to assist with diagnosis and to devise an optimal treatment plan.

  • Nephrology referral for persistent hematuria or proteinuria, rising creatinine, or a positive ANCA titer
  • Rheumatology referral for persistent joint and skin complaints
  • Pulmonary referral for persistent pulmonary infiltrate unresponsive to antibiotic therapy

Additional Therapies

Plasma exchange appears to improve recovery in patients with severe acute renal failure secondary to vasculitis (5,6)[A] and pulmonary hemorrhage.

Surgery/Other Procedures

A surgical procedure may be required to obtain tissue for diagnosis. Rarely, corrective surgery is required to repair the tissue damage resulting from aggressive vasculitis.

In-Patient Considerations

Initial Stabilization

Initial therapy is guided by the organ system involved.

  • If pulmonary hemorrhage is present, lifesaving measures may include mechanical ventilation, immunosuppression, plasmapheresis, and even procoagulants.
  • If acute renal failure is present, attention to electrolyte and fluid balance will be required.
  • When GI disease is manifest, therapy may consist simply of making the patient NPO and sustaining nutrition intravenously.

Admission Criteria

Hemoptysis, acute renal failure, and/or need for biopsy are the usual indications for admission.

Nursing

No special nursing is required.

Discharge Criteria

Stabilization or resolution of potential life-threatening symptoms

Ongoing Care

Follow-Up Recommendations

  • In general, restriction of activity is not required.
  • If significant coronary artery disease is involved in Kawasaki disease, there may be benefit from a moderate activity restriction.

Patient Monitoring

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

Diet

Unless renal involvement has occurred and the patient requires a special diet for electrolyte or fluid control, no special diet is required.

Prognosis

Prognosis is good, particularly with hypersensitivity vasculitis and in those syndromes where a single episode occurs. Relapsing courses, renal involvement, and extensive lung involvement portend the worst prognosis.

Complications

Varying degrees of persistent organ dysfunction are common in the more serious forms of vasculitis.

References

1. Weiss PF, Feinstein JA, Luan X, et al. Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review. Pediatrics. 2007;120:1079–87.

2. Wood L, Tulloh R. Kawasaki disease: diagnosis, management and cardiac sequelae. Expert Rev Cardiovasc Ther. 2007;5:553–61.

3. 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;67:195–205.

4. Bosch X, Guilabert A, Espinosa G, et al. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298:655–69.

5. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev.2008:CD003232.

6. Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010;11:12.

Additional Reading

Appel GB, Contreras G, Dooley MA, et al. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis. J Am Soc Nephrol. 2009.

See Also (Topic, Algorithm, Electronic Media Element)

  • 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/

Codes

ICD9

  • 446.0 Polyarteritis nodosa
  • 446.1 Acute febrile mucocutaneous lymph node syndrome (MCLS)
  • 447.6 Arteritis, unspecified
  • 446.20 Hypersensitivity angiitis, unspecified
  • 446.4 Wegener granulomatosis
  • 446.5 Giant cell arteritis
  • 446.6 Thrombotic microangiopathy
  • 446.7 Takayasu disease
  • 287.0 Allergic purpura
  • 437.4 Cerebral arteritis

Snomed

  • 31996006 vasculitis (disorder)
  • 155441006 polyarteritis nodosa (disorder)
  • 75053002 acute febrile mucocutaneous lymph node syndrome (disorder)
  • 60555002 hypersensitivity angiitis (disorder)
  • 195353004 Wegener granulomatosis (disorder)
  • 414341000 giant cell arteritis (disorder)
  • 126729006 thrombotic microangiopathy (disorder)
  • 359789008 Takayasu disease (disorder)
  • 21148002 allergic purpura (disorder)
  • 28366008 cerebral arteritis (disorder)

Clinical Pearls

  • A vasculitic syndrome should be suspected whenever the patient has a persistent, unexplained systemic illness.
  • Regardless of the vasculitic syndrome, patients with renal involvement have the worst prognosis.
  • Determination of optimal treatment plan depends on accurately assigning a patient to a particular vasculitic syndrome.
  • Look for clinically silent kidney involvement with serum creatinine and urinalysis with microscopy.

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