Vasculitis

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[edit] Vasculitis

Leslie R. Harrold

David F. Giansiracusa

The vasculitides are a group of disorders in which inflammation and necrosis of blood vessel walls result in organ system abnormalities caused by thrombosis and hemorrhage.Since vasculitis can involve any vessel in the body, it can result in a wide variety of signs, symptoms, and laboratory abnormalities.The pattern of organ involvement is one of the criteria that help differentiate between vasculitic syndromes.The current classification scheme is based on the clinical presentation, size of involved vessels, histopathology, and associated conditions.If an underlying disease is the cause of the vasculitis, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), the blood vessel disorder is a secondary vasculitis.Otherwise, the vasculitis is primary (Table 138-1).

Table 138-1 Classification of Primary Vasculitides by Vessel Size and Histopathology

[edit] EPIDEMIOLOGY

Data on the epidemiology of vasculitic syndromes in the general population are limited.Most information is based on referral center cases, since the syndromes are sufficiently infrequent that population-based data are lacking.The incidence rates of temporal arteritis in persons over 50 years of age include 23.3 per 100,000 biopsy-proven cases in Denmark, 17.0 per 100,000 in Olmsted County, Minnesota, and 1.6 per 100,000 in Tennessee.For Takayasu's arteritis, a rare condition more often described in Asia, the estimated annual incidence in Olmsted County is 2.6 per 1 million.The annual incidence rate for polyarteritis nodosa (PAN) ranges from 4.6 per 1 million in England to 9.9 in Olmsted County,to 77 in a hepatitis B virus (HBV) hyperendemic population.The average age of patients with PAN is 40 to 60, and there is a strong association with HBV.The annual incidence of Wegener's granulomatosis in Rochester, Minnesota, is an estimated 0.4 cases per 100,000.The incidence rate for Kawasaki syndrome varies according to race.In the United States, children 8 years old or younger have an annual incidence of 19.54 per 100,000 for Asians, 1.03 per 100,000 for blacks, and 0.45 per 100,000 for whites.Henoch-Schönlein purpura, more common in the pediatric populations, has an estimated incidence rate of 13.5 per 100,000 in the pediatric population in Belfast annually.^[1] Although no population-based epidemiologic data exist on hypersensitivity vasculitic syndromes, including drug-related cutaneous vasculitis, these syndromes are likely the most common of all the vasculitides.^[2]

[edit] PATHOPHYSIOLOGY

No single pathophysiologic mechanism can explain all the disease manifestations of vasculitis.Several possible mechanisms have been delineated based on animal models and more recent understanding of immunologic phenomena.In a previously immunized animal an antigenic challenge will result in vasculitis caused by an immune complex–mediated process.Also, expression of adhesion molecules may account for the different pattern of organ involvement in vasculitis.The role of antibodies other than those present in immune complexes remains unclear.Two autoantibodies, antineutrophil cytoplasmic antibody (ANCA) and antiendothelial cell antibody (AECA), have been detected in association with some forms of vasculitis.Whether they are directly involved in the pathogenesis of vasculitis is not known at this time.Cytokines and growth factors secreted by activated inflammatory cells are responsible for the clinical symptoms, such as fever, malaise, and weight loss.They also have vasoactive, prothrombotic, and fibrogenic functions responsible for the clinical findings of thrombosis, vasospasm, intimal hyperplasia, and fibrosis.^[3]

[edit] PATIENT EVALUATION

[edit] History

Vasculitis should be suspected in any patient who presents with an unexplained systemic illness or has symptoms of organ-specific ischemia.Patients typically have a history of fever, fatigue, weight loss, myalgias, and arthralgias.Organ-specific symptoms depend on the size and location of the vessel involved in the vasculitic process.The involvement of large arteries may cause symptoms of headache, tongue or jaw claudication, and arm or leg claudication.When vasculitis affects medium and small arteries, hypertension, neurologic deficits suggestive of mononeuritis multiplex, abdominal pain, and hemoptysis are common manifestations.Vasculitides affecting arterioles and venules result in palpable purpura, maculopapular rash, livedo reticularis, abdominal pain, and bloody diarrhea.The one exception to the systemic vasculitides is primary angiitis of the central nervous system (CNS), which affects only blood vessels in the CNS.This entity usually presents with symptoms of severe headaches, progressive dementia, and symptoms of multifocal neurologic deficits (Table 138-2).

Table 138-2 Summary of Vasculitic Syndromes

[edit] Physical Examination

A comprehensive examination should be performed on all patients suspected of having a vasculitis.General appearance and vital signs, including temperature, are important; hypertension may suggest vascular involvement of the kidneys.Cutaneous examination may reveal livedo reticularis, a maculopapular rash, and palpable purpura.Palpation of the sinuses is performed to assess for sinus pressure.The ophthalmologic examination should include inspection of the sclera, conjunctiva, and the fundi to assess retinal vessels.All eye structures may be involved in vasculitis, particularly temporal (giant cell) arteritis and Behçet's syndrome.Inspection of the oral mucosa may reveal ulcerations, also a sign of Behçet's disease.A detailed examination for lymphadenopathy may aid in discriminating a primary vasculitis from other diseases associated with vasculitis, such as lymphoma.Auscultation of the lungs and heart may reveal clinical abnormalities because both structures may be affected by vasculitis, as well as by conditions that mimic vasculitis, such as bacterial endocarditis and atrial myxoma, both of which may present with fever, a heart murmur, and embolic phenomena.Abdominal examination focuses on palpation for masses and hepatosplenomegaly and testing for occult blood in the stool to assess for diseases that mimic vasculitis and to examine for vasculitis of the intestines.Inspection of the genitalia may reveal ulcerations, which may be present in Behçet's syndrome, or testicular involvement, which may occur in PAN.

Specific attention should be given to the skin, joint,vascular, and neurologic systems.A complete joint examination infrequently demonstrates frank synovitis.If polyarthritis is present, the differential is expanded to include systemic connective tissue diseases associated with vasculitis (e.g., SLE, RA).A general vascular examination is important to evaluate for atherosclerotic peripheral vascular disease, which may present as a systemic vasculitis in the setting of atheroembolization.Decreased or absent pulses may be present in Takayasu's arteritis and temporal arteritis.Full neurologic examination, including assessment of sensation, muscle strength, and cranial nerve function, is vital because mononeuritis multiplex, cranial neuropathies, and peripheral polyneuropathies are common manifestations of vasculitides and may suggest the size of the vessel involved.For example, medium-sized vasculitis tends to cause mononeuritis multiplex, whereas small-vessel involvement may cause peripheral polyneuropathies.Primary angiitis of the CNS can alter cognitive ability and cause focal deficits; mental status testing should be performed in these patients^[4](see Table 138-2).

[edit] LABORATORY STUDIES AND DIAGNOSTIC PROCEDURES

Patients with a suspected vasculitic syndrome should have routine laboratory studies, including a complete blood count, creatinine, and urinalysis.Findings such as leukocytosis, anemia of chronic disease, and thrombocytosis may be nonspecific markers of inflammation.Proteinuria, hematuria, and red cell casts suggest involvement of the kidneys.A chest radiograph may reveal pulmonary findings such as infiltrates, which may be asymptomatic.Complement levels may be suppressed by immune complex–mediated complement activation during the active phase of vasculitis.The ANCA test can also aid in making a diagnosis; 90% of patients with Wegener's granulomatosis have a positive cytoplasmic ANCA (c-ANCA), and 60% to 75% of patients with microscopic polyangiitis have a positive peripheral ANCA (p-ANCA).Positive c-ANCA is caused by antibodies to proteinase 3, a serine protease in azurophilic granules of neutrophils.Positive p-ANCA is caused by antibodies to elastase, myeloperoxidase, and other enzymes in the primary granules of neutrophils.If nerve involvement is suspected, an electromyogram (EMG) and nerve conduction studies may demonstrate mononeuritis multiplex, peripheral polyneuropathy, or myopathic process.Biopsy of affected tissues (or arteriography if biopsy is not feasible) may be necessary to confirm the diagnosis of vasculitis.Multiple arterial aneurysms on arteriography suggest a vasculitic process but are not pathognomonic.All patients should have age-specific and gender-specific cancer screening because malignancy may result in a secondary vasculitis (see Table 138-2).

[edit] DIFFERENTIAL DIAGNOSIS

It is important to differentiate between diseases that may mimic vasculitis and a true vasculitis (Box 138-1).A thorough history and physical examination help to identify the appropriate laboratory and radiographic procedures that should be pursued.Attempting to biopsy involved tissues, if feasible, should be strongly considered.In temporal arteritis, 50% of affected persons will have negative biopsies because the inflammation may not be widespread.When biopsies are negative or unattainable, treatment decisions are made based on the clinical presentation.Any atypical features need to be thoroughly investigated.

Once the diagnosis of vasculitis is made, the physician must determine whether it is a primary vasculitis or secondary to an underlying condition.Systemic rheumatic conditions (e.g., RA, SLE, Sjögren's syndrome) may have vasculitis involving either medium or small vessels as one of the manifestations of the underlying condition.^[5] Infection with HBV or hepatitis C has been associated with PAN and with cryoglobulinemia, which is a leukocytoclastic vasculitis similar to Henoch-Schönlein purpura.Leukocytoclastic vasculitis may also occur with inflammatory bowel disease, primary biliary cirrhosis, multiple myeloma, Waldenström's macroglobulinemia, lymphoma, leukemia, and carcinomas.

[edit] MANAGEMENT

The therapy of vasculitis depends on the size of the vessels involved and the specific clinical presentation.Treatment of patients with Takayasu's arteritis or temporal arteritis begins with prednisone, initiated at 1 mg/kg/day, about 60 mg in the typical patient.In approximately 40% of patients with Takayasu's arteritis, cytotoxic agents are necessary because of failure to respond to glucocorticoids or relapse on tapering glucocorticoids.Methotrexate and cyclophosphamide are most often used in these patients.The vast majority of patients with temporal arteritis respond to treatment with glucocorticoid therapy alone.One month after clinical parameters have returned to normal, tapering of the dose may begin.Most patients need to be treated with prednisone for 1 to 2 years.

Patients with PAN, Wegener's granulomatosis, and microscopic angiitis are initially treated with prednisone (1 mg/kg/day) and cyclophosphamide.Traditionally, cyclophosphamide is given orally (2 mg/kg/day) for 1 to 2 years after the patient is in remission.Intravenous “pulse” cyclophosphamide therapy is an option for patients at risk for side effects of the oral therapy.Churg-Strauss syndrome has beenthought to be more glucocorticoid responsive than PAN or microscopic polyangiitis.If patients with Churg-Strauss vasculitis fail treatment with glucocorticoids or relapse with tapering, however, the addition of a cytotoxic agent may be necessary.Such treatment is the same as the regimen for PAN.Azathioprine and methotrexate are alternative cytotoxic agents if patients are unable to tolerate cyclophosphamide, but are less effective.

Kawasaki disease (syndrome) is treated with aspirin and high-dose intravenous gamma globulin given over 4 or 5 days or as a one-time dose.Patients with hypersensitivity vasculitis or Henoch-Schönlein purpura usually require only symptomatic and supportive care.^[6] If organ-or life-threatening visceral disease is present, however, aggressive immunosuppressive therapy is initiated.

[edit] PROGNOSIS

The prognosis of a patient with vasculitis depends on the specific type and course of the vasculitic syndrome.Approximately half of patients with temporal arteritis experience resolution within 6 to 12 months.The remainder may require 3 or 4 years of treatment.The disease course of Takayasu's arteritis is poorly understood in the United States given the rarity of the condition.Many patients have a prolonged course, however, with significant morbidity and mortality from stenosis of the vessels involved.PAN, Wegener's granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis carry a poor prognosis.Although many patients may improve with treatment and achieve a state of remission, recurrence and therapy-related morbidity often occur.In contrast, Kawasaki disease has a good prognosis, with only a 1% to 2% acute mortality rate.The overall prognosis of hypersensitivity vasculitis and Henoch-Schönlein purpura is excellent because both processes tend to be self-limited, especially in hypersensitivity vasculitis when the underlying cause, such as infection or drug use, is treated or removed (Box 138-2).

[edit] REFERENCES