Vasculitis in children: Management overview

INTRODUCTION — Vasculitis is defined as the presence of inflammation in a blood vessel that may occur as a primary process or secondary to an underlying disease. Clinical symptoms vary widely. The various vasculitic syndromes are defined by both the type of pathologic inflammation and the type and location of the predominantly involved vessels, which, in turn, determines which specific organs are affected [1,2].

The first priorities in management of a child with vasculitis are prompt recognition and timely treatment since many of the vasculitides can be severe and life threatening if not appropriately managed. Specific treatments are determined by the type of vasculitis, the severity of the inflammation, and the particular organ systems affected.

A general overview of the management of vasculitis in children is reviewed here. The classification and the approach to evaluating childhood vasculitis are discussed separately. (See "Vasculitis in children: Incidence and classification" and "Vasculitis in children: Evaluation overview".)

GENERAL PRINCIPLES OF MANAGEMENT — The following principles are important to consider when managing a child with vasculitis:

●Differentiating vasculitis from other diseases that can either mimic vasculitis or cause secondary vasculitis

●Defining disease activity and severity

●Weighing the benefits and risks of therapy

Differentiating vasculitis from other diseases — In treating a child with vasculitis, it is critical to distinguish primary vasculitis from other diseases that can mimic vasculitis, as well as from conditions causing secondary vasculitis, such as infections, drugs, malignancies, or connective tissue diseases (eg, systemic lupus erythematosus and juvenile dermatomyositis). Making an accurate diagnosis is necessary to ensure that the appropriate therapy is given and contraindicated medicines avoided. In children with secondary vasculitis, therapy is directed at treating the underlying disease (eg, infection or other rheumatic disorders). Thus, administration of immunosuppressive therapy may be appropriate in patients with primary vasculitis but may have adverse (even catastrophic) consequences in a patient with secondary vasculitis due to a systemic infection. The disorders that may mimic vasculitis or cause secondary vasculitis are discussed in greater detail separately. (See "Vasculitis in children: Evaluation overview", section on 'Differentiating primary vasculitis from other disorders'.)

Defining disease activity — Assessment of disease activity plays an important role in the treatment of the systemic vasculitides, both in interpreting the results of therapeutic studies and in directing the care for individual patients [3]. Patients may fall into one of three categories of active disease or may be in remission.

●Active disease – A patient has active disease when there is objective evidence of ongoing inflammation. However, determining this is not always straightforward, because there is a lack of reliable disease-activity markers for many types of systemic vasculitis. In addition, distinguishing active disease from chronic sequelae of the disease (irreversible damage), medication toxicity, and concomitant or secondary processes, such as infection, may be difficult. Because of the lack of reliable markers, assessment of disease activity often relies upon the clinical judgment of the treating clinician(s) based upon clinical findings (eg, signs, symptoms, disease tempo, and laboratory markers of inflammation, such as erythrocyte sedimentation rate or C-reactive protein). The ability to detect and quantify disease activity is important as it impacts upon therapeutic choices. (See 'Patient monitoring' below.)

The three categories of active disease are:

•New-onset disease – Disease at the time of diagnosis.

•Relapsing disease – When disease activity recurs following remission.

•Refractory disease – Worsening disease or persisting disease activity with limited improvement after a period of appropriate therapy (eg, within a few days for Kawasaki disease after two treatments with intravenous immune globulin [IVIG] or within 6 to 12 weeks of standard "remission induction" therapy for chronic diseases such as granulomatosis with polyangiitis [GPA]).

●Remission – A patient is in remission when there is persistently no evidence of active disease. There is no universally accepted duration of persistent inactivity required to define remission, and definitions vary considerably within the literature. In some studies, remission may be as long as three months for chronic vasculitides (eg, Takayasu arteritis) and as short as 24 to 48 hours for acute conditions (eg, Kawasaki disease). Remission may be further qualified as remission on or off medications.

In the management of childhood vasculitis, treatment is determined by the phase of disease activity as follows:

●Induction therapy – Therapy is directed at stopping the inflammatory process in a newly diagnosed patient and putting the patient into remission.

●Maintenance therapy – Once the patient is in remission, therapy may be continued to maintain remission. In some cases, especially in diseases that are generally acute and self-limited (eg, Kawasaki disease), maintenance therapy may not be necessary, and the patient may be in remission off medications.

●Relapse therapy – Therapy that is required to treat a reactivation of the inflammatory process.

●Refractory therapy – Increased therapy requirement for patients not responding to standard therapy, which may include alternative or additional immunosuppression or biologic response modifiers. (See appropriate topic reviews for each specific vasculitis disorder.)

Weighing the benefits and risks of therapy — When deciding upon therapy for any given vasculitis, the benefits of a specific therapy and its potential adverse effects must be weighed against the consequences of allowing the vascular inflammation to follow its natural course. Treatment of the rarer types of chronic vasculitis is best supervised by clinicians (eg, pediatric rheumatologists) with knowledge of the diseases, medications used to treat them, and the implications of the disease and its treatment in a developing child. The importance of judiciously balancing the short- and long-term risks of treatment against the short- and long-term risks of untreated disease cannot be overstated.

Some vasculitides, such as immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura), are acute, usually self-limited, and uncomplicated. In these cases, it is usually unnecessary to even consider the use of potentially toxic therapies.

Other vasculitides, such as GPA, follow a chronic relapsing course with ongoing serious morbidity and mortality risk due to kidney disease and/or pulmonary involvement. In such patients, long-term immunosuppressive therapy is usually warranted in an attempt to minimize disease relapses and/or progression.

Children require special consideration regarding both short-term and long-term calculations of treatment risks and benefits. Both the disease and its treatments affect physical, social, educational, and emotional development and can have long-term consequences. Children are presumed to have a long life expectancy, so the significance of potentially lifesaving treatment is magnified. Children's developing organ systems are at risk of insidiously accruing a high toxic burden from therapies. With time, the potential long-term toxicities (eg, infertility, malignancy, osteoporosis, atherosclerosis) have a greater chance to manifest.

Determining what treatment is warranted — The treatment of primary vasculitic syndromes varies based upon the answers to the following key questions [4]:

●Is the disease active? Differentiate active disease from chronic sequelae of disease, medication toxicity, and other processes, particularly infection. For refractory disease, in particular, alternative or additional diagnoses/diseases should be considered. (See "Vasculitis in children: Evaluation overview", section on 'Differentiating primary vasculitis from other disorders' and 'Defining disease activity' above and 'Patient monitoring' below.)

●How severe is the active disease? Fulminant life-threatening disease or critical organ-threatening disease requires more aggressive management. (See 'Patient monitoring' below and "Vasculitis in children: Evaluation overview".)

●What organ sites are affected? Certain sites of organ involvement may not require or may not respond to systemic immunosuppressive therapy. As an example, subglottic stenosis in GPA may be more appropriately treated with local therapy (eg, local glucocorticoid injections and/or mechanical dilation) than with systemic medications.

●Is this an acute, self-limited disease such as Kawasaki disease where there is a short window of opportunity for preventing damage and long-term immunosuppressive treatment is not usually required, or is it IgA vasculitis, when no toxic therapy may be necessary?

●What accommodations should be made for unique characteristics of individual patients?

•Is there a history of medication toxicity or intolerability?

•Is there a contraindication to certain medications?

•Does the presence of previous organ damage restrict therapeutic options?

•Does the patient's age or sex constrain options?

•Do patient/caregiver preferences, tolerance of risk, or ability to comply with medication regimens strongly weigh for or against certain approaches?

TREATMENT — The treatment of vasculitis depends upon the nature and severity of the disorder. Treatment options may include antihistamines, nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, or immunosuppressive agents (eg, cyclophosphamide, biologic response modifiers). While there are recommended, standardized protocols for initiating treatment of moderate-to-severe chronic vasculitis in adult patients, such protocols are seldom validated in pediatric patients. Accordingly, such protocols should be used as a suggested approach rather than firm guidelines for children and adolescents with vasculitis. In an effort to improve upon pediatric-specific treatment guidance, consensus-based recommendations for the management of rare chronic systemic pediatric vasculitides were published in 2019 [5]. Subsequently, consensus treatment plans (CTPs) for the treatment of severe pediatric antineutrophil cytoplasmic autoantibody (ANCA) associated vasculitis were published [6]. Such consensus-based recommendations and treatment protocols, ideally for use within a registry, represent an important step towards developing a pediatric-specific evidence base to guide management of these patients.

An overview of the general principles of the management of vasculitis is presented here. Specific recommendations, including dosing regimens and detailed discussions of the individual disorders, are presented separately. (See appropriate topic reviews for each specific type of vasculitis.)

As discussed above (see 'General principles of management' above), the treatment of primary vasculitic syndromes will vary based upon the following factors:

●Specific type of vasculitis [7,8] and, in particular, distinguishing primary from secondary vasculitis. In the latter case, therapy often is directed at treating the underlying disease (eg, infection or other rheumatic disorders). (See "Vasculitis in children: Incidence and classification" and "Vasculitis in children: Evaluation overview", section on 'Differentiating primary vasculitis from other disorders'.)

●Type, extent, and severity of organ involvement: Localized (eg, cutaneous) vasculitis versus systemic involvement.

●Acute self-limited (eg, IgA vasculitis and Kawasaki disease) versus chronic-relapsing systemic disorders (eg, granulomatosis with polyangiitis [GPA], Takayasu arteritis, polyarteritis nodosa, and microscopic polyangiitis).

Cutaneous vasculitis — Management consists mainly of supportive measures when vascular inflammation is limited to the skin (such as mild cases of IgA vasculitis or isolated cutaneous leukocytoclastic vasculitis). (See "IgA vasculitis (Henoch-Schönlein purpura): Management" and "Overview of cutaneous small vessel vasculitis", section on 'Treatment'.)

In patients with mild hypersensitivity vasculitis due to a drug reaction, discontinuation of the offending drug may be adequate. Other supportive measures include antihistamines, which may relieve the itching associated with urticaria, and NSAIDs, which may provide analgesia. (See "Hypersensitivity vasculitis in children", section on 'Treatment'.)

In cases of cutaneous vasculitis where the course is more prolonged, severe, or chronic, such as cutaneous polyarteritis nodosa, a trial of colchicine, dapsone, oral glucocorticoids, or azathioprine may be added to supportive measures [9].

Central nervous system vasculitis — Central nervous system (CNS) vasculitis refers to a broad spectrum of diseases characterized by inflammation of the blood vessels of the brain, spinal cord, and/or meninges. Childhood primary angiitis of the CNS (cPACNS) is a vasculitis that is confined to the CNS. Treatment protocols for the different types of cPACNS have been developed and are reviewed in greater detail separately. (See "Childhood primary angiitis of the central nervous system: Angiography-positive subtype".)

Systemic vasculitis — The treatment of primary systemic vasculitis in children varies depending upon whether the disorder is acute and self-limited or chronic with potentially frequent relapses.

Acute and self-limited disorders — The two most common primary vasculitides, IgA vasculitis and Kawasaki disease, typically present acutely and are usually characterized by a self-limited course. Management is based upon an understanding of the well-characterized course of these diseases, the risk of long-term sequelae, and the effectiveness of available therapy as follows:

●IgA vasculitis – Since IgA vasculitis is usually self-limited, without major long-term complications, patient management is primarily supportive, with therapy focused on symptomatic relief of arthritis and abdominal pain while systematically monitoring for kidney involvement. Glucocorticoids appear to improve joint and gastrointestinal symptoms in children with IgA vasculitis who do not respond to supportive therapy [10], but there is no strong evidence to suggest that they prevent the development of kidney disease [11,12]. However, treatment options for kidney disease, managed in consultation with a pediatric nephrologist, include glucocorticoids, angiotensin-converting enzyme (ACE) inhibitors, and/or other immune-suppressing agents [11,12]. (See "IgA vasculitis (Henoch-Schönlein purpura): Management".)

●Kawasaki disease – The acute clinical manifestations of Kawasaki disease are generally self-limited. However, cardiac complications (particularly coronary artery aneurysms) may develop and lead to significant morbidity and mortality. As a result, patients with Kawasaki disease are treated during the acute phase of the disorder to reduce the risk of coronary artery aneurysms. In randomized clinical trials, the administration of intravenous immune globulin (IVIG), in conjunction with aspirin, dramatically reduced the risk of aneurysms in children with Kawasaki disease. For children who fail to respond to the initial standard therapy of IVIG and aspirin, other immunosuppressive agents may be used. The initial treatment of Kawasaki disease, refractory therapy, and cardiovascular complications of Kawasaki disease are discussed in detail separately. (See "Kawasaki disease: Initial treatment and prognosis" and "Refractory Kawasaki disease" and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

Chronic disorders — Unlike IgA vasculitis and Kawasaki disease, other primary systemic vasculitides (such as Takayasu arteritis, GPA, polyarteritis nodosa, microscopic polyangiitis, and eosinophilic GPA [Churg-Strauss syndrome]) are characterized by chronic, often relapsing, disease courses. Children with primary chronic systemic vasculitis should be cared for by experienced clinicians (eg, pediatric rheumatologists) who are familiar with the different primary vasculitides and their treatment. Management should always be based upon the best available evidence published in the literature while taking into consideration factors specific to individual patients such as disease activity, severity, and tolerance of medications. Glucocorticoids, with cyclophosphamide for more severe disease, have been the standard of care for many types of primary chronic vasculitides. Other immunosuppressive drugs, such as methotrexate and azathioprine, as well as biologic agents (eg, tumor necrosis factor [TNF] inhibitors, rituximab, and tocilizumab), have shown benefit in small studies of various pediatric systemic vasculitides and are increasingly being used [13].

Remission induction and remission maintenance therapy — The results of adult studies have important implications for children because they demonstrate that milder, more localized disease can be treated effectively with less aggressive treatment protocols. Glucocorticoid therapy alone may be sufficient initially for mild and limited disease, but an additional immunosuppressive agent is generally indicated for moderate-to-severe systemic disease that is life or organ threatening (eg, kidney, lung, or brain involvement). Patients with severe systemic vasculitis are usually treated in a staged treatment approach [14] with high-dose glucocorticoids plus a potent immunosuppressive agent to induce remission. Subsequently, remission is maintained with lower-dose glucocorticoids and continuing immunosuppressive therapy of lower potency/toxicity. Treatment protocols emphasize early administration of steroid-sparing agents in order to minimize exposure to glucocorticoids.

The standard initial glucocorticoid therapy for most of the systemic vasculitides is prednisone/prednisolone 1 to 2 mg/kg per day (maximum dose 60 mg per day), given for two to four weeks before systematically and gradually reducing the dose as symptoms improve. The goal is to reach low doses (0.2 mg/kg/day or 10 mg/day, whichever is lower) by six months [5,6,15]. In patients with severe or life-threatening disease, glucocorticoid treatment may begin with high pulsed doses of intravenous methylprednisolone (IVMP; ie, 30 mg/kg per day for one to three days, maximum dose of 1 gram/day) followed by oral therapy. Adult guidelines for treating GPA published in 2021 [16] advise cautionary use of pulsed IVMP because of its lack of proven efficacy and known side effects [17,18]; they also recommend early and more aggressive oral glucocorticoid wean based upon adult study data [15]. None of these adult glucocorticoid studies have been replicated in children.

Cyclophosphamide is the traditional first-choice immunosuppressive agent, in addition to glucocorticoids, to induce remission in moderate-to-severe chronic vasculitis (eg, polyarteritis nodosum and antineutrophil cytoplasmic antibody [ANCA] associated vasculitides [AAVs] such as GPA, microscopic polyangiitis, and eosinophilic GPA). The use of cyclophosphamide in children is based upon improved remission rates and survival in trials of adults with these diseases [14,19-23]. Takayasu arteritis, on the other hand, often responds to methotrexate or biologic response modifiers [24-26]. Less potent and less toxic than cyclophosphamide, methotrexate is increasingly used as initial therapy for less severe early disease [21,27-30], and both methotrexate and azathioprine are frequently used for maintenance therapy [14,31-33].

Adult studies suggest that rituximab, a monoclonal antibody that depletes B cells, is as safe and effective as cyclophosphamide for inducing [34-36] and maintaining [37-40] remission, leading to greater use of this drug for induction therapy in children with AAV in the US [41]. The risk for prolonged hypogammaglobulinemia post-rituximab therapy recognized in adults [42] may be higher in children. At least 4 percent of children require prophylactic intravenous immune globulin (IVIG) to prevent infection, but the true extent and duration of this problem are still being characterized [43-46]. The long-term consequences of this may impact treatment choices for children versus adults. In the absence of pediatric-specific data about the longer-term risks of rituximab, guidelines recommend its use in patients with refractory disease who have failed cyclophosphamide, have relapsing disease, or when specific concerns exist regarding cyclophosphamide toxicity [5].

Therapy for refractory or relapsing disease — In severe systemic vasculitides, many agents may successfully induce disease remission, but well over half of patients relapse. Such relapses can cause cumulative, irreversible end-organ damage resulting in significant morbidity over time. The cumulative toxicity from repeated courses of cyclophosphamide can also lead to significant morbidity; hence, alternative agents are being tested for remission maintenance.

In adult trials, rituximab dosed every six months appears to effectively maintain disease remission in AAV with minimal side effects other than a dose-dependent risk of hypogammaglobulinemia [37-40]. Similarly, maintenance therapy with anti-tumor necrosis factor (TNF) agents and anti-interleukin (IL) 6 monoclonal antibodies in Takayasu arteritis may offer an effective alternative to more conventional immunosuppressive agents [26,38,47-50]. No comparable trials have been conducted in pediatric systemic vasculitis, although such biologic response modifiers are increasingly used to treat pediatric patients with disease that is refractory to conventional treatment (cyclophosphamide and glucocorticoids) or those with relapsing disease [51]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease" and "Treatment of Takayasu arteritis".)

Adjunctive therapy for severe disease — There is no evidence to support the routine use of plasmapheresis in the treatment of AAV. Earlier studies in adults had suggested that plasma exchange may reduce the risk of dialysis dependence and end-stage kidney disease [52,53]. However, there was no apparent survival benefit. Results from the Plasma Exchange and Glucocorticoid Dosing in the Treatment of ANCA-Associated Vasculitis (PEXIVAS) trial evaluating the role of plasmapheresis in AAV showed that plasma exchange does not reduce the risk of end-stage kidney disease or death in patients with AAV [15].

Supportive care — Some manifestations of vasculitis (eg, neuropathy) may take months to recede because of the slow recovery of end-organ damage, even when the underlying vasculitis is no longer active. In other cases, end-organ damage is irreversible, resulting in permanent clinical abnormalities. For example, patients in remission may continue to have seizures or learning disabilities due to residual brain damage or hypertension due to kidney damage, both of which were incurred during the period of active vasculitis. These and other chronic complications need to be addressed and treated accordingly with both pharmacologic and nonpharmacologic therapies.

The impact of these chronic disorders and their treatments upon the physical, educational, and psychosocial development of a growing child or adolescent should not be underestimated. It represents an additional arena of morbidity compared with adults with vasculitis. Important areas of potential concern include reduced physical fitness, excessive or inadequate weight gain, delayed puberty, reduced growth, impaired academic performance and career potential, limited participation in extracurricular activities, and depression.

In addition to the pharmacologic management of immunosuppression by the clinician, children with severe systemic vasculitis are best cared for by a multidisciplinary team. Other medical subspecialists and health care professionals including nurses, physical and occupational therapists, social workers, and psychologists are team members who provide clinical care, counseling, referral to community services, and communication with the primary care clinician and school.

PATIENT MONITORING — The goal of initial therapy is to induce remission of the disease. Once this has been accomplished, a balance must be achieved between maintaining remission and minimizing treatment-related toxicities. In order to do this, patients must be monitored on a regular basis for signs of disease activity as well as medication side effects. It is important to remember that most forms of primary systemic vasculitis (except for IgA vasculitis and Kawasaki disease) tend to be chronic and relapsing. Distinguishing among active disease, chronic sequelae of disease, and treatment-related side effects can be challenging. Therefore, thorough and regular follow-up evaluations are necessary, even when the patient appears entirely well.

Patient monitoring relies upon some, but not all, of the procedures used in diagnosis including clinical findings, laboratory tests, imaging studies, and tissue biopsy. (See "Vasculitis in children: Evaluation overview".)

Clinical features — Depending upon the organ predilection of a patient's vasculitis, certain symptoms and signs may provide reliable evidence of active disease, and, therefore, they are included in routine monitoring. Worsening kidney function or deteriorating pulmonary function tests may herald a relapse of AAV, seizures or behavioral changes may indicate reactivation of childhood primary angiitis of the central nervous system (cPACNS), and bruits and new sites of claudication may result from progressive Takayasu arteritis. Other features are not always attributable to vascular inflammation, and other signs and symptoms, such as headaches, fatigue, and worsening hypertension, are less clearly attributable to the active inflammation of vasculitis. In addition, vessel damage may progress in some types of vasculitis despite a complete lack of symptoms and entirely normal acute-phase reactants [54]. In these settings, monitoring disease activity with the aid of laboratory tests, repeat imaging studies, or formal cognitive or pulmonary function testing is often essential.

Laboratory tests — The following laboratory tests are used to monitor disease activity:

●Acute-phase reactants – Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and platelet count, among others, are nonspecific markers of inflammation. Elevations of these tests may be indicative of increased disease activity. Acute changes in conjunction with other clinical findings or persistent abnormalities not accounted for by intercurrent illnesses or other factors must be investigated carefully.

●Urinalysis – Monitoring with urinalyses on a regular basis can detect changes in the urinary sediment that may reflect active disease in vasculitides that target the kidneys. Changes in the urinary sediment may also be due to persistent kidney damage from earlier active disease or medication toxicity, such as hematuria from cyclophosphamide-associated hemorrhagic cystitis.

●Antineutrophil cytoplasmic antibody (ANCA) titers – The utility of ANCA titers to predict active disease or risk of flares in ANCA-positive vasculitides remains controversial and is an area of ongoing study. Total ANCA levels do not seem to correlate with disease activity, but specific antigenic targets of antineutrophil cytoplasm antibodies (such as proteinase 3 [PR3] and myeloperoxidase [MPO] ANCA) may more closely reflect active vasculitis. Based upon available data, ANCA titers should not be used in isolation when making treatment decisions. This question is discussed in greater detail separately. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease", section on 'Monitoring by the clinician'.)

●Von Willebrand factor (VWF) antigen – VWF antigen, and perhaps other markers of endothelial cell disruption, may be useful for following damage to blood vessels, as occurs in vasculitis. In certain cases, such proteins may provide a more specific marker of disease activity than other acute-phase reactants [55,56].

Laboratory tests are also ordered for the purpose of monitoring medication toxicity, such as reduced cell counts in patients receiving immunosuppressive therapy, or elevated transaminases in those taking methotrexate.

Imaging studies — Imaging studies of vessels or of major organs, such as the brain or lungs, may be necessary to distinguish whether clinical symptoms reflect active disease or prior damage. These studies, which include ultrasonography, echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI), may be used at regular intervals, even in the absence of symptoms, in order to monitor disease progression and response to treatment. As previously discussed, many laboratory markers are nonspecific and/or may not reliably correlate with disease activity. Thus, it is often necessary to use imaging as part of follow-up evaluations. Other types of studies evaluating end-organ function, such as pulmonary function tests, may also be helpful.

Although conventional angiography may be necessary in the initial diagnostic evaluation of some systemic vasculitides, less invasive modalities, such as ultrasonography or magnetic resonance angiography, are preferred for continued routine monitoring, reserving more invasive testing for those situations in which more accurate imaging is required for critical therapeutic decisions.

Tissue biopsy — If the patient had an initial biopsy and the findings were diagnostic, often little more is to be learned by repeating the procedure as part of ongoing monitoring. On the other hand, if the patient's original diagnosis is in question, a new illness is suspected, or ongoing disease activity must be distinguished from manifestations of irreversible damage, repeat biopsies may be useful. This is particularly likely to be the case with kidney involvement, although involvement of other organs also must be assessed in this way on occasion.

Disease-activity scoring — Formalized scoring tools, such as the Birmingham Vasculitis Activity Score (BVAS), that are used to determine disease activity at the time of diagnosis are increasingly used to monitor disease activity and response to therapy. Fluctuations in scores are used to adjust medication dosing or choice of therapy for adults with vasculitis, both in the investigational and clinical practice setting. These tools are sometimes used for children with or without some pediatric-specific adaptations, although most of these tools have not been validated for use in pediatrics. As an example, the Pediatric Vasculitis Activity Score (PVAS), an adaptation of the BVAS, was internally validated [57]. Although external validation of this tool on an independent dataset would be valuable, it has already been used as a standard measure of disease in one pediatric vasculitis clinical trial.

OUTCOMES — Outcomes are dependent upon numerous factors including the specific diagnosis, disease severity, involvement of major organs, response to treatment, and damage caused by treatment.

The majority of children with primary vasculitis have a good outcome because the two most common disorders, Kawasaki disease and IgA vasculitis, are usually self-limited, and only a small minority of children have long-term sequelae from either damage or ongoing disease activity. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Prognosis' and "IgA vasculitis (Henoch-Schönlein purpura): Management", section on 'Prognosis'.)

For the other primary systemic vasculitides, immunosuppressive therapy has improved survival and remission rates. As an example, prior to the introduction of the regimen of high-dose glucocorticoids and cyclophosphamide, granulomatosis with polyangiitis (GPA) was fatal in almost all reported pediatric [58] and adult cases. The reported median survival time was five months in untreated adults [59]. The combination of glucocorticoids and cyclophosphamide or other remittive agents has greatly improved patient outcomes. Similar therapeutic strategies have proven beneficial in the treatment of other systemic vasculitides. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Treatment and prognosis of polyarteritis nodosa" and "Treatment of Takayasu arteritis".)

A 2008 systematic review of mortality risk in patients with systemic vasculitis that included both adult and pediatric patients reported the following five-year survival rates: GPA (approximately 75 percent), microscopic polyangiitis (45 to 75 percent), eosinophilic GPA (68 to 100 percent), IgA vasculitis (75 percent in adult onset, greater in childhood onset), medium vessel vasculitis including polyarteritis nodosa (75 to 80 percent), Kawasaki disease (greater than 99 percent at five years), and Takayasu arteritis (70 to 93 percent) [60].

One study of early outcomes in 105 children with antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) reported remission rates of 42 percent and improvement rates of 92 percent at 12 months [61]. Unfortunately, more than half of the cohort had evidence of damage at 12 months despite high improvement rates and aggressive treatment. No patients in the cohort died during the 12-month follow-up period.

Despite improved remission and survival rates, relapse is still common, especially when therapy is weaned or stopped [62-64]. Flares of GPA occur in up to 83 percent of pediatric patients as treatment is weaned [62,64]. A high rate of relapse (approximately 75 percent) is also seen in patients with polyarteritis nodosa [64]. Lower relapse rates are seen in eosinophilic GPA and microscopic polyangiitis (50 and 33 percent, respectively). As a result, maintenance immunosuppression is commonly used in these disorders. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Maintenance therapy'.)

Irreversible tissue damage is another crucial index of outcome. Measurement tools, such as the Vasculitis Damage Index (VDI), are widely used in adult chronic vasculitis to formally quantify damage due to either disease or treatment [65]. These tools, modified to incorporate measurements of damage unique to development and growth in children, are essential for the better understanding of childhood outcomes. A pediatric adaptation of the VDI (pVDI) has been developed, although it is not yet validated.

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 5^th to 6^th 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 10^th to 12^th 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)")

SUMMARY AND RECOMMENDATIONS

●Vasculitis is defined as the presence of inflammation in a blood vessel, which may occur as a primary process or secondary to an underlying disease. Prompt recognition and treatment of these disorders are important as they can be severe and even life-threatening conditions without timely therapy. (See 'Introduction' above.)

●Principles that are important in managing a child with vasculitis include differentiating primary vasculitis from other conditions that may mimic vasculitis or cause secondary vasculitis, defining disease activity and severity, and weighing the benefits and risks of therapy. (See 'General principles of management' above.)

●Management decisions, including which therapy to use in an individual patient, are based upon answers to key questions regarding the specific type of vasculitis; the course, activity, and severity of the disease; the type and extent of organ involvement; and unique patient characteristics/preferences. (See 'Determining what treatment is warranted' above.)

●The treatment of vasculitis depends upon the nature and severity of the disorder (see 'Treatment' above):

•In children with secondary vasculitis, therapy is directed at treating the underlying disease (eg, infection, malignancy, or other rheumatic disorders).

•In children with cutaneous vasculitis (ie, vascular inflammation limited to the skin), supportive measures are generally all that is required. This includes the use of antihistamines, which relieve urticarial itching, and nonsteroidal antiinflammatory drugs (NSAIDs), which provide analgesia. (See 'Cutaneous vasculitis' above.)

•In children with acute, self-limited systemic vasculitides, particularly immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura) and Kawasaki disease (the two most common types of primary vasculitis in children), treatment choice is based upon understanding the well-characterized course of the specific disease, the risk of long-term sequelae, and the effectiveness of available therapy. (See 'Acute and self-limited disorders' above.)

•In children with chronic or frequently relapsing vasculitis, immunosuppressive therapy is used to induce and maintain remission. Glucocorticoids are the mainstay of therapy and may be sufficient as monotherapy in patients with mild or limited disease. However, in patients with severe or life-threatening disease, additional immunosuppressive agents or biologic response modifiers are generally needed. For refractory or frequently relapsing disease following standard induction therapy, rituximab is an option in children with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, and infliximab or tocilizumab are options in children with Takayasu disease. (See 'Chronic disorders' above.)

●Once the patient is in remission, monitoring on a regular basis is required to detect signs of disease reactivation and/or drug toxicity. Follow-up measures include monitoring clinical manifestations of disease (eg, fever, claudication, skin lesions, or headache), laboratory testing (eg, acute-phase reactants and urinalysis), and imaging studies of vessels or of major organs to detect active disease versus residual damage. Tissue biopsy is usually not needed to monitor disease activity. (See 'Patient monitoring' above.)

●The outcome of childhood vasculitis is dependent upon the specific diagnosis, disease severity, whether major organs are involved, response to treatment, and damage caused by treatment. (See 'Outcomes' above.)