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Overview of the management of vasculitis in adults

Overview of the management of vasculitis in adults
Literature review current through: Jan 2024.
This topic last updated: Jun 09, 2023.

INTRODUCTION — The vasculitides are defined by the presence of leukocytes in the vessel wall with reactive damage to mural structures. In general, affected vessels vary in size, type, and location in association with the specific vasculitic disorder. These conditions are often serious and sometimes fatal diseases that require prompt recognition and therapy.

Symptomatic involvement may occur in single or multiple organs. Specific clinical manifestations may suggest a particular vasculitic disorder, but significant overlap is observed among the vasculitides. The wide clinical spectrum of disease in the vasculitides presents particular challenges to management of these complex disorders.

This topic review will provide an overview of the approach to the management of the vasculitides. Treatment recommendations for specific forms of vasculitis are reviewed for each disorder separately (see 'Disease-specific treatments' below), and an overview of the classification and clinical manifestations of the different vasculitides and the approach to the patient with suspected vasculitis is presented separately. (See "Overview of and approach to the vasculitides in adults".)

APPROACH TO TREATMENT — The framework for the treatment of vasculitis is similar to that used for many other systemic autoimmune rheumatic disorders, while the specific therapeutic regimen depends upon the nature and severity of the particular disorder (see 'Disease-specific treatments' below). The management scheme for vasculitis generally includes the following components:

Remission induction – The goal of initial treatment is to induce remission of the disease. Initial management usually involves medium to high doses of glucocorticoids, with the addition of an immunosuppressive agent in most forms of disease. The initial presentation of vasculitis is often rapid, and delay in diagnosis or failure to recognize the extent of disease or arrest the disease process can lead to substantial morbidity and, in some forms of disease, mortality. The initial treatment phase may thus be more intensive than the subsequent phases of treatment, involving the use of higher doses or drugs with greater risk of toxicity.

Remission maintenance – The goals of the remission maintenance phase of therapy are to maintain control of disease activity, prevent disease recurrence following reduction or discontinuation of medications, and minimize the risks of drug toxicity, especially from glucocorticoids.

Once remission has been attained, the dose of glucocorticoids is usually steadily lowered, as tolerated, to limit the development of drug-induced toxicity. Both glucocorticoids and other immunosuppressive agents may be continued at a given dose for a period of time, depending upon the specific condition, then subsequently reduced or discontinued, sometimes after being tapered, according to disease-specific, protocol-based adjustments in therapy.

Monitoring – Patients require monitoring for both disease activity and drug toxicity during the active treatment phase, but patients with most forms of vasculitis will also require monitoring for disease recurrence subsequent to achieving drug-free remission. (See 'Monitoring' below.)

As examples:

In patients with giant cell (temporal) arteritis, the initial therapy is typically a high dose of prednisone (40 to 60 mg daily), which often results in control of symptoms within days; progressive tapering of the dose is started within two to four weeks of initiating therapy. In most patients with giant cell arteritis, the dose of glucocorticoids can be progressively reduced over 6 to 18 months if there are no ongoing signs of active disease, and the drugs are eventually discontinued. Some patients require chronic therapy with low-dose prednisone or other medications. Two randomized trials support the use of tocilizumab as adjunctive therapy in giant cell arteritis [1,2], and this drug is now often started from the onset of treatment. Methotrexate is another option as adjunctive therapy to glucocorticoids [3]. Patients are monitored for an extended period of time because recurrence is common, even several years later. Treatment of this condition is described in detail separately. (See "Treatment of giant cell arteritis".)

In granulomatosis with polyangiitis, remission is induced with high-dose glucocorticoids (eg, 1 mg/kg daily for severe disease, which is then tapered), in combination with either rituximab [4-7]; or three to four months of cyclophosphamide, followed by remission maintenance with rituximab, azathioprine, or methotrexate [8,9]. Methotrexate may be an appropriate initial therapy in combination with glucocorticoids in some patients with mild to moderate disease [5,6,10,11]. Patients require monitoring for recurrence every several months after discontinuing therapy. If the disease recurs, resumption of therapy is necessary. Long-term monitoring, possibly lifelong, is needed for this condition. The treatment of this condition is described in detail separately. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of disease resistant to initial therapy" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease".)

DISEASE-SPECIFIC TREATMENTS — Treatment regimens are based upon the specific diagnosis and the severity or extent of the disease. Classification of the vasculitides is based primarily upon the predominant size of the vessels involved, but the size of the involved vessel does not determine which medications or treatment regimen is usually most effective, or what type of monitoring is required. (See "Overview of and approach to the vasculitides in adults".)

As examples, among the small-vessel vasculitides, the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis, and microscopic polyangiitis are treated with high-dose glucocorticoids and additional immunosuppressive medications, while immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura) may benefit from nonsteroidal antiinflammatory drugs (NSAIDs) or glucocorticoids for symptomatic relief, although these medications do not alter the typically self-limited disease course of this condition. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "IgA vasculitis (Henoch-Schönlein purpura): Management".)

Treatment protocols are based on different amounts and quality of evidence for different conditions. As examples, in patients with granulomatosis with polyangiitis, treatment regimens are based upon a series of randomized trials; in giant cell arteritis, the regimens are based upon a smaller number of trials; and in polyarteritis nodosa, the approach to treatment is based upon a combination of largely observational studies and indirect evidence from other better-studied vasculitides, such as granulomatosis with polyangiitis. Treatments of most forms of vasculitis are increasingly based upon data from randomized trials or large cohort studies [4-7,12-15]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Treatment of giant cell arteritis" and "Treatment and prognosis of polyarteritis nodosa".)

The treatments used for specific disorders are described in detail separately:

Large-vessel vasculitis – Large-vessel vasculitis includes vasculitides that predominantly involve the aorta and its major branches but may also include more "medium-sized" vessels, such as the ophthalmic artery. The major conditions included in this category are:

Giant cell arteritis (see "Treatment of giant cell arteritis")

Takayasu arteritis (see "Treatment of Takayasu arteritis")

Other systemic rheumatic diseases, such as relapsing polychondritis, Cogan syndrome, IgG4-related disease, spondyloarthritis, and others, may also be associated with an aortitis. Idiopathic aortitis is also a recognized entity in which aortitis is present but the case cannot be classified as one of the other named diseases.

Medium-vessel vasculitis – Medium-vessel vasculitis includes vasculitides that predominantly involve "medium-sized" arteries such as those arising from the celiac trunk or the coronary arteries. These vasculitides can also involve smaller arteries. The major forms of medium-vessel vasculitis are:

Polyarteritis nodosa, which like other medium-vessel vasculitides can affect both medium and small arteries (see "Treatment and prognosis of polyarteritis nodosa")

Kawasaki disease, which can also affect larger vessels (see "Kawasaki disease: Initial treatment and prognosis" and "Overview of and approach to the vasculitides in adults", section on 'Medium-vessel vasculitis')

Small-vessel vasculitis – Small-vessel vasculitis incudes vasculitides that predominantly involve small-sized/microscopic arteries, capillaries, and venules, and thus can impact many organs/tissues, especially eyes, kidneys, lungs, nerves, and skin. There are several major forms of vasculitis that primarily affect the small vessels:

ANCA-associated vasculitis – The ANCA-associated vasculitides include:

-Granulomatosis with polyangiitis and microscopic polyangiitis (see "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of disease resistant to initial therapy" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease")

-Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (see "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis")

IgA vasculitis (Henoch-Schönlein purpura) (see "IgA vasculitis (Henoch-Schönlein purpura): Management")

Cryoglobulinemic vasculitis (see "Mixed cryoglobulinemia syndrome: Treatment and prognosis")

Anti-GBM (Goodpasture) disease (see "Anti-GBM (Goodpasture) disease: Treatment and prognosis")

Rheumatoid vasculitis (see "Treatment of rheumatoid vasculitis")

Other systemic rheumatic diseases, such as systemic lupus erythematosus, relapsing polychondritis, and others, may also be associated with a small-vessel vasculitis.

Variable-vessel vasculitis – Several forms of vasculitis can involve vessels of varying size and no specific-sized arteries are predominantly affected:

Behçet syndrome (see "Treatment of Behçet syndrome")

Primary angiitis of the central nervous system, which can affect both medium and small arteries (see "Primary angiitis of the central nervous system in adults")

Cogan syndrome (see "Cogan syndrome", section on 'Treatment')

Drug-induced vasculitis – Drug-induced vasculitis (DIV) has been associated with almost every class of medication and many recreational drugs, and can involve small, medium, and occasionally large arteries. The principal treatment of DIV is discontinuation of the putative causative agent, and this may be sufficient, along with avoiding subsequent rechallenge. In patients with persistent and/or necrotizing skin lesions or other organ damage, treatment with glucocorticoids may be required. Infrequently, patients may require additional immunosuppressive medications for prolonged DIV. A notable subset of DIV is drug-induced ANCA-associated vasculitis. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Drug-induced ANCA-associated vasculitis' and "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Drug-induced ANCA-associated vasculitis'.)

MONITORING

Principles — Patients require monitoring for both disease activity and drug toxicity during the active treatment phase; patients with most forms of vasculitis will also require monitoring for recurrent disease subsequent to achieving control of disease activity and even drug-free remission. Monitoring relies upon some, but not all, of the procedures used in diagnosis, including close clinical follow-up, monitoring of vital organ function (especially blood pressure and renal function when clinically relevant), selective reimaging of involved areas, and occasionally repeat biopsy. Patients are a key factor in monitoring for relapse of vasculitis; patients must be well educated about their disease and the need to report new clinical problems rapidly to the clinicians who treat the vasculitis. (See 'Clinical features' below and 'Laboratory tests' below and 'Imaging and biopsy' below.)

The particular features that should be assessed depend upon the specific diagnosis, but there are common principles that apply to monitoring most forms of vasculitis:

Patients should be evaluated for the recurrence of disease manifestations, as well as other features characteristic of the patient's type of vasculitis, whether or not these features were previously present. This is necessary because relapses of vasculitis may involve features of disease that were not present at the time of diagnosis, including potentially severe disease manifestations, in addition to those manifestations that the patient had experienced prior to disease remission [16].

Most forms of vasculitis can relapse, and flares of vasculitis, defined as new or worsening manifestations of active disease, can occur many years after initial presentation and prolonged remission. Thus, ongoing monitoring is indicated, which for most types of vasculitis may be for many years. Monitoring may be facilitated by the utilization of a standardized approach to disease assessment when such measures are available for a given form of vasculitis, such as one of the versions of the Birmingham Vasculitis Activity Score (BVAS), which may be useful in patients with granulomatosis with polyangiitis and microscopic polyangiitis [17,18]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Assessment of disease severity'.)

The other long-term concern besides relapse, once remission has been attained, is that vascular injury during the acute phase can heal with scarring and narrowing of the affected vessels, potentially leading to signs of ischemia that do not reflect recurrent active disease. For example, a stenosis of the subclavian artery in a patient with Takayasu arteritis may result in upper extremity claudication even if the vasculitis is not active. Thus, a change in the patient's findings may represent a disease exacerbation, but can also result from drug toxicity or damage from scarring due to prior disease activity; each of these alternative explanations should be considered in the differential diagnosis of a disease flare, as the distinction between them may not be readily apparent.

Patients can benefit from extra support and encouragement while waiting for the gradual improvement to occur with certain manifestations. As an example, neuropathy may take months to recede even after the underlying vasculitis has abated, while other manifestations may be permanent. Additionally, some patients read lay or medical publications concerning vasculitis and become discouraged about their lack of rapid improvement and possible poor outcome.

It is important that patients with vasculitis be followed and treated for the comorbidities that can result from, or be exacerbated by, the vasculitis and/or treatment of vasculitis, such as hypertension, possibly accelerated atherosclerosis, anemia, infertility, premature ovarian failure, and the many complications of glucocorticoids. (See "General principles of the use of cyclophosphamide in rheumatic diseases", section on 'Infertility risk' and "Major adverse effects of systemic glucocorticoids".)

Clinical features — Certain symptoms, signs, and other clinical features, such as headache, jaw claudication, skin lesions, and renal function, are easily monitored by history, physical examination, and basic laboratory tests. By comparison, other features, such as symptoms and/or signs of mesenteric lesions in polyarteritis nodosa or asymptomatic large arterial stenoses, are more difficult to detect.

Laboratory tests — In addition to their utility in monitoring for drug toxicity (eg, complete blood counts in patients receiving cyclophosphamide or aminotransferases in patients on methotrexate), various laboratory tests have been proposed to help clinicians monitor disease activity in vasculitis. Testing to detect changes in organ function may be particularly useful for some disorders, such as monitoring of renal function in patients with diseases potentially affecting the kidneys (eg, polyarteritis nodosa, granulomatosis with polyangiitis, or microscopic polyangiitis). However, several tests that may be helpful in diagnosis are not as helpful for monitoring of disease activity. As examples:

Acute phase reactants such as the erythrocyte sedimentation rate (ESR) and the serum C-reactive protein (CRP) concentration should not be used as the sole criteria for determining disease activity, as the acute phase response is nonspecific, and such studies provide, at best, corroborative evidence of disease activity. Furthermore, some drugs, such as tocilizumab, may substantively impact levels of acute phase reactants, rendering these tests even less helpful when patients are taking these medications.

Antineutrophil cytoplasmic antibody (ANCA) titers have little role in disease management in patients with granulomatosis with polyangiitis or microscopic polyangiitis after a diagnosis is established. Neither the persistence of ANCA positivity nor a rise in ANCA titers reliably predicts subsequent flares of disease for an individual patient [19]. Thus, clinicians should not initiate prophylactic therapy based upon ANCA titers (see "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease", section on 'Monitoring by the clinician'). Nonetheless, the role of ANCA titers in disease management is an area of active investigation and some controversy; combining ANCA testing with other clinical and lab-based biomarkers may improve the utility of ANCA testing in this setting.

Imaging and biopsy — The performance of imaging studies for the evaluation of vascular anatomy or other tissues, and of biopsies for histopathologic examination, may be useful in certain situations. Issues related to such studies include the following:

Ultrasound and magnetic resonance (MR) angiography of areas of large-artery involvement are helpful for following progression and may reveal new areas of involvement.

Repeated computed tomography (CT) scanning should be avoided because of the risk from cumulative radiation doses.

The role of positron emission tomography (PET) in following disease activity in large-vessel vasculitis is an area of active investigation. There is increasing use of PET to aid in the diagnosis of giant cell arteritis and Takayasu arteritis. There is less consensus on this test's usefulness as a measure of disease activity.

Repeat catheter-based angiograms are usually not necessary for disease monitoring, unless used to image smaller vessels not seen by MR or CT. However, catheter-based arteriography can be performed in association with interventions (eg, angioplasty) or to more precisely assess vascular anatomy and arterial function in advance of surgery. In large-vessel vasculitis, catheter-based procedures also provide an opportunity to establish accurate core blood pressure readings when arterial stenosis in the extremities preclude accurate measurement of blood pressure.

Repeat biopsies, subsequent to establishing a diagnosis, should not be used for routine follow-up of patients with established vasculitis, but may have a role in selected situations. As an example, a common reason for repeating a renal biopsy is to differentiate active glomerulonephritis from scarring or another cause of renal dysfunction in patients with a falling glomerular filtration rate. Biopsy may also be useful when it is not possible to determine without histopathology whether a new manifestation (eg, a pulmonary nodule) is due to vasculitis, infection, or malignancy.

PROGNOSIS — The limited data available reveal a good outcome for many patients with vasculitis, but the prognosis is highly dependent upon the diagnosis, and during both the acute remission-induction phase and the subsequent maintenance phase of therapy, the adverse effects of drugs, especially the occurrence of infections, contribute to the morbidity of the illness. Mortality data suggest that deaths in vasculitis are due to both active vasculitic disease and complications of therapy [20], and progress in long-term outcomes have been seen over the last several decades [21]. Irreversible vascular and other damage may also occur in some disorders.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vasculitis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Vasculitis (The Basics)")

Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Approach to treatment – The approach to the treatment of vasculitis is similar to that used for many other systemic autoimmune rheumatic disorders, involving remission induction followed by remission maintenance. Initial management usually involves use of medium to high doses of glucocorticoids, with the use of an additional immunosuppressive agent in most forms of disease. (See 'Approach to treatment' above.)

Disease-specific treatments – Treatment regimens are based upon the specific diagnosis and the severity or extent of the disease. Classification of the vasculitides is based primarily upon the size of the vessels predominantly involved, but the size of vessel does not determine which medications or treatment regimen is usually most effective, or what type of monitoring is required. (See 'Disease-specific treatments' above.)

Monitoring – Patients require monitoring for both disease activity and drug toxicity during the active treatment phase, and patients with most forms of vasculitis will also require monitoring for recurrent disease subsequent to achieving control of disease activity and even drug-free remission. (See 'Principles' above and 'Clinical features' above and 'Laboratory tests' above and 'Imaging and biopsy' above.)

Clinical features – Certain symptoms, signs, and other clinical features, such as headache, jaw claudication, skin lesions, and renal function, are easily monitored by history, physical examination, and basic laboratory tests. By comparison, other features, such as symptoms and/or signs of mesenteric lesions in polyarteritis nodosa or asymptomatic large arterial stenoses, are more difficult to detect. (See 'Clinical features' above.)

Laboratory tests – In addition to their utility in monitoring for drug toxicity, various laboratory tests have been proposed to help clinicians monitor disease activity in vasculitis. Testing to detect changes in organ function may be particularly useful for some disorders, such as monitoring of renal function in patients with diseases potentially affecting the kidneys. However, several tests that may be helpful in diagnosis, such as acute phase reactants and antineutrophil cytoplasmic antibody (ANCA), are not as helpful for monitoring of disease activity. (See 'Laboratory tests' above.)

Imaging and biopsy – Imaging studies, such as ultrasound or magnetic resonance (MR) angiography, and positron emission tomography (PET), may be helpful for monitoring involvement of large vessels in selected patients, while repeat biopsies are generally avoided unless a patient's symptoms change dramatically for the worse or a new illness is suspected. (See 'Imaging and biopsy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Gene Hunder, MD, who contributed to an earlier version of this topic review.

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