Continuing Education Activity

Vasculitis represents a diverse group of disorders defined by inflammation of blood vessels that can damage multiple organ systems. More than 30 forms of vasculitides exist, including large-, medium-, small-, and variable-vessel types, each with distinct presentations. This course reviews the clinical features of vasculitides and their associated manifestations, as this disorder may occur as primary systemic vasculitides or secondary to other conditions. The 1990 American College of Rheumatology (ACR) classification and the Chapel Hill Consensus Conference (CHCC) nomenclature, which remain central to diagnosis, are also reviewed, along with the 2022 criteria that refine definitions for ANCA-associated and large-vessel vasculitides. Early recognition and timely management are critical to preventing irreversible organ damage; therefore, participants will also gain an understanding of the need for a careful history, thorough examination, and targeted testing as the various forms of vasculitis often mimic common conditions. 

This course explores primary vasculitic syndromes, including their epidemiology, pathogenesis, clinical features, and treatment principles, as well as key disease patterns, integration of diagnostic tools, and appropriate management strategies. This activity for healthcare professionals is designed to enhance the learner's competence in identifying vasculitis, performing the recommended evaluation, and implementing an appropriate interprofessional approach when managing this condition, ultimately improving diagnostic accuracy, reducing treatment delays, and advancing patient outcomes and safety.

Objectives:

• Identify the diagnostic criteria used for primary systemic vasculitides.
• Differentiate the clinical presentations of the various types of vasculitis. 
• Apply evidence-based approaches to the management of vasculitis.
• Collaborate with interprofessional teams to optimize care and outcomes in patients with vasculitis.

Introduction

Vasculitis encompasses a heterogeneous group of diseases characterized by inflammation of blood vessels, resulting in subsequent end-organ tissue damage. These disorders share certain clinical, laboratory, and pathophysiologic features, yet manifestations vary widely depending on the site, size, and type of vessel involved.[1] More than 30 distinct vasculitides have been identified.[2] Vasculitis may arise as a primary process or develop secondary to another underlying condition.

When vasculitis occurs as the primary process, the diseases are classified as primary systemic vasculitides. The 1990 American College of Rheumatology (ACR) criteria established a framework for classifying systemic vasculitis.[3] The International Chapel Hill Consensus Conference (CHCC) nomenclature subsequently became the most widely applied system for defining vasculitic syndromes.[2] In 2022, new classification criteria were introduced for 3 antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides—granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)—and for 2 large-vessel vasculitides, giant cell arteritis (GCA) and Takayasu arteritis.[4][5][6][7][8] The various types of vasculitis include:

• Large vessel vasculitis

  • Giant cell arteritis (GCA)
  • Takayasu arteritis
• Medium vessel vasculitis

  • Kawasaki disease
  • Polyarteritis nodosa (PAN)
• Small vessel vasculitis

  • ANCA-associated vasculitis

    • Granulomatosis with polyangiitis (GPA)
    • Microscopic polyangiitis (MPA)
    • Eosinophilic granulomatosis with polyangiitis (EGPA)
  • Cryoglobulinemic vasculitis
  • IgA vasculitis
• Variable vessel vasculitis: Behçet disease

Etiology

The cause of vasculitis remains largely unknown, although growing evidence links disease incidence to geography, age, ethnicity, sex, genetics, and environmental exposures. These risk factors contribute to variations in susceptibility and clinical expression across different forms of vasculitis.

Large Vessel Vasculitis

Takayasu arteritis demonstrates strong associations with human leukocyte antigen (HLA) class I and II loci, particularly the HLA-B52 allele.[9] The incidence of giant cell arteritis (GCA) has risen over the past 50 years by a factor of 2 to 5.[10] Genetic studies have demonstrated that class II HLA alleles, including HLA-DRB1*0401 and HLA-DRB1*0101, increase the risk of developing GCA.[11]

Medium Vessel Vasculitis

Polyarteritis nodosa has a well-established association with hepatitis B infection.[12] Kawasaki disease appears to result from a combination of genetic susceptibility and infectious triggers. Epidemiologic studies suggest that bacterial superantigens and viral infections contribute to its pathogenesis.[13]

Small Vessel Vasculitis

The pathogenesis of ANCA-associated vasculitides—microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA)—overlaps significantly, with ANCA autoantibodies playing a central role. Genetic associations with the HLA-DP locus have been identified. Genome-wide association studies (GWAS) indicate that HLA-DPB1*04 is more prevalent in individuals of European ancestry with GPA, whereas HLA-DRB1*09:01 is more common in individuals of Asian ancestry with MPA.[14][15]

IgA vasculitis exhibits a seasonal pattern, with a higher frequency from September to April and a lower frequency during the summer months.[16] Many patients report prior exposure to infections or environmental antigens. Group A Streptococcus, parainfluenza virus, and parvovirus B19 frequently precede disease onset, supporting the role of mucosal immune activation in the pathogenesis of these diseases.[16]

Cryoglobulinemic vasculitis develops in association with circulating serum cryoglobulins, immunoglobulins that reversibly precipitate at temperatures below 37 °C. Cryoglobulins have been divided into the following 3 subtypes:

• Type I: composed of monoclonal immunoglobulins (most often IgM, less commonly IgG or IgA)
• Type II: consisting of polyclonal IgG and monoclonal IgM with rheumatoid factor activity
• Type III: consisting of polyclonal IgG and polyclonal IgM with rheumatoid factor activity

Type II and III, considered mixed cryoglobulins, have the strongest associations with vasculitis. Chronic hepatitis C virus accounts for 70% to 90% of cases, followed by lymphoproliferative disorders and connective tissue disease.[17]

Variable Vessel Vasculitis

Behçet disease demonstrates a strong association with HLA-B*51, which increases both susceptibility and disease severity.[18] Evidence suggests that infections or alterations in the microbiome may contribute to the etiopathogenesis of disease by triggering immune dysregulation in genetically predisposed individuals.[19]

Epidemiology

The overall incidence of primary systemic vasculitis per annum is approximately 20 to 40 cases per million, according to studies in Europe and the United States.[18] 

Large Vessel Vasculitis

GCA affects individuals older than 50, and its incidence rises with age. GCA occurs predominantly in White populations.[20] This condition is the most common among the primary vasculitides, with an annual incidence (in individuals 50 years and older) of around 240 per million.[21] Furthermore, Takayasu arteritis primarily affects women younger than 50.[22][2] Takayasu is more common in females (a 9:1 ratio) than in males and is more prevalent in South Asian countries than in other regions. 

Medium Vessel Vasculitis

Kawasaki disease occurs at much higher rates in Asian populations, including Japan, Korea, and Taiwan.[13] Kawasaki disease preferentially affects children, mainly those younger than 5 years, but can also be seen in older children and occasionally in adults.[23]

PAN is extremely rare when not associated with hepatitis B, whose prevalence is declining globally. The estimated incidence of PAN ranges from 2 to 9 cases per million individuals in Europe and North America. The disease shows a slight male predominance and most commonly affects adults between 40 and 60 years of age.[24] 

Small Vessel Vasculitis

MPA is more common in Asian populations. GPA occurs predominantly in white populations.[20] GPA, MPA, and EGPA have been reported at an incidence of anywhere from 1 to 10 per million.[18]

IgA vasculitis is the most common form of vasculitis in children, affecting 20 children per 100,000 per year.[16] Conversely, IgA vasculitis is rare amongst adults, with an incidence of 0.8 to 2.2 per 100,000 persons per year. Incidence of IgA vasculitis does seem to differ across races, where Asian populations show the highest incidences and black populations show the lowest.[16] Cryoglobulinemic vasculitis is a rare disease with fewer than 5 cases per 10,000 persons.[2]

Variable Vessel Vasculitis

Behçet disease is more common among inhabitants of countries that border the ancient Silk Road.[18] Behçet disease also tends to cause more severe manifestations in men, with a higher frequency of advanced ocular disease.

Pathophysiology

The pathology of vasculitis primarily involves blood vessels—arteries, veins, and capillaries—leading to the characteristic clinical manifestations of each disease subtype, with few exceptions.

Large Vessel Vasculitis

In GCA and Takayasu arteritis, inflammation initially affects the vasovasorum of the adventitia and subsequently spreads into the other layers of the vessel wall.[19] Dendritic cells recognize unidentified antigens, activating both the innate immune system and CD4 T cells. Toll-like receptor (TLR) expression contributes to the recruitment of inflammatory cells and amplification of the immune response.[19] Takayasu arteritis shows a strong association with the HLA-B*52:01 allele across multiple ethnicities, including Asian, Turkish, Mexican, and North American populations. GCA susceptibility increases with variants in the plasminogen, prolyl 4-hydroxylase subunit alpha-2, and protein tyrosine phosphatase nonreceptor type 22 genes within the HLA class II region.[19]

Medium Vessel Vasculitis

Hepatitis B-associated PAN arises from immune complexes formed with viral particles that deposit in the vasculature, triggering the innate immune response and causing damage to the vessel wall. Classic PAN, unassociated with hepatitis B, may result from an imbalance between Th1 and Th17 cells.[25] Kawasaki disease likely results from a combination of genetic predisposition and infectious triggers, with deregulated immune responses central to pathogenesis. Loss of the T-cell inhibitor inositol 1,4,5-triphosphate 3-kinase plays a crucial role, while proinflammatory cytokines, including IL-1 and TNF-alpha, drive endothelial activation and vascular injury.[13][26][13]

Small Vessel Vasculitis

In ANCA-associated vasculitis (MPA, GPA, and EGPA), ANCAs directly contribute to endothelial injury. ANCAs prime neutrophils, enhance binding of proinflammatory cytokines (TNF, IL-1-beta, C5a), and trigger release of myeloperoxidase and proteinase-3, leading to endothelial damage through reactive oxygen species and enzymatic activity. The alternative complement pathway amplifies injury through the release of elevated C3a and C5a, while persistent neutrophil extracellular traps promote further ANCA formation.[19]

IgA vasculitis features the deposition of IgA within vessel walls, initiating an inflammatory cascade. An unidentified antigen activates T cells, which stimulate B cells to produce galactose-deficient IgA1 (GD-IgA1) and anti-GD-IgA1 autoantibodies. These immune complexes accumulate in organs, leading to tissue inflammation and damage.

Cryoglobulinemic vasculitis involves monoclonal and polyclonal IgMs with rheumatoid factor activity, forming immune complexes with other immunoglobulins and complement. Chronic hepatitis C drives antigen-dependent B-cell stimulation and cryoglobulin production, with antiviral therapy reducing circulating cryoglobulin levels and memory B-cell expansion.[27]

Variable Vessel Vasculitis

Behçet disease represents an autoimmune disorder with autoinflammatory features. Cytotoxic T cells, NK cells, and Th17 lymphocytes play central roles, targeting the endothelium and creating an imbalance in prostacyclin and nitric oxide that promotes thrombosis. Aberrant neutrophil activation contributes to the development of lesions, including aphthous ulcers, pustular cutaneous lesions, and erythema nodosum, highlighting the complex interplay between immune-mediated and inflammatory processes in vascular injury.

Histopathology

The identification of various subtypes of vasculitis can be assisted by histopathologic findings associated with each type (see Table. Vasculitis Histopathologic Findings).  

Table

Table. Vasculitis Histopathologic Findings.

History and Physical

General Clinical Features of Vasculitis

Systemic vasculitides are clinically heterogeneous, making it impossible to outline a single algorithm for evaluating patients suspected of having vasculitis. A thorough medical history, a complete physical examination, laboratory testing, and select additional diagnostic tests are essential for diagnosis. Some general features may overlap in all vasculitides. Because vasculitis is a systemic inflammatory condition, the history may include fevers, unexplained weight loss, malaise, and fatigue. 

The most significant barrier to diagnosing vasculitis is putting the diagnosis on the differential in the first place. Vasculitis should be a consideration in patients who present with systemic or constitutional symptoms in combination with evidence of single or multiorgan dysfunction, and a preexisting diagnosis with recurrent flare or uncontrolled symptoms. For example, a patient who presents to the emergency room with dyspnea, cough, and fever who is found to have an infiltrate on chest x-ray and treated with antibiotics 2 weeks prior, returns with similar lower respiratory symptoms but additionally, has a new lower extremity purpuric rash and hematuria on urinalysis, should be evaluated for ANCA-associated vasculitis. Additionally, an older adult who has a new-onset, new quality headache refractory to treatment for sinus disease and migraines over the past 2 months, who has now lost 10 lbs and is having some visual blurring in the left eye, should be evaluated for GCA. Vasculitis is a great mimicker of other common conditions; therefore, a detailed history and complete examination are vital for recognizing clinical clues that can help increase clinical suspicion. 

Subtype-Specific Clinical Features of Vasculitis

Giant cell arteritis

GCA presents in older adults, specifically those older than 50, and the incidence increases with age.[28] It can present with multiple symptoms depending on which vessel of the head and neck circulation is affected. Classically, if involving the temporal artery off the external carotid, headache is the most common manifestation. However, if vasculitis is affecting a branch of the ophthalmic artery, changes in monocular vision may occur. GCA should be suspected in any older adult with a new onset, new quality headache, or new visual disturbance- especially symptoms of vision loss or amaurosis fugax, jaw claudication, or fever of unknown origin, but in the setting of an elevated C-reactive protein and/or erythrocyte sedimentation rate. Patients may also exhibit signs of polymyalgia rheumatica, which can coexist with GCA in about one-third of patients. Exam findings may be nonspecific; however, a thorough vascular exam, including palpation for temporal artery tenderness and nodularity, auscultation for arterial bruits, and assessment of pulses, is essential to characterize any other vascular abnormalities.

Takayasu arteritis

Takayasu arteritis often presents subacutely, resulting in delayed diagnoses in many cases. It presents mostly in younger women and may start with systemic symptoms, eg, fevers, unexplained weight loss, malaise, and fatigue. Patients may also experience arthralgia. Limb claudication is common but can be ameliorated by collateral circulation. On physical exam, findings associated with hypertension may be noted, as well as discrepancies in blood pressure between limbs. On the vascular exam, diminished or absent distal pulses, evidence of distal ischemia with pallor, and arterial bruits on auscultation may also be present. 

Polyarteritis nodosa

Patients with PAN typically have systemic symptoms and signs of organ involvement. Patients may present with skin lesions, including palpable purpura, livedo reticularis, and ulcerations. Skin involvement typically occurs on the lower extremities, although the upper extremities can also be affected. The patient can also experience digital and limb ischemia. The kidneys are frequently involved. This can be through renal artery vasculitis leading to infarction, or nonglomerular disease.

Malignant hypertension is often a key sign of renal involvement. Neurological involvement can cause a mononeuritis multiplex, characterized by both sensory and motor deficits, which tend to be asymmetric but may progress over time to involve multiple limbs. Exam findings may show evidence of a wrist or foot drop. Other organ systems may be the gastrointestinal tract with mesenteric vasculitis leading to bowel ischemia, the coronary arteries leading to myocardial ischemia, and the musculature leading to myalgias. 

Kawasaki disease

Kawasaki disease affects medium-sized arteries, but can also affect small arteries. Kawasaki disease occurs in children and, rarely, may affect adults. Fever is a hallmark of the disease and tends to be refractory to antipyretic agents, lasting 7 to 12 days. Conjunctival injection often occurs, and anterior uveitis may also develop. Patients may have cervical lymphadenopathy. Mucositis with fissuring, redness of the lips, and the presence of a "strawberry tongue" may appear. Rash, swelling of the extremities, redness of the palmar/plantar surfaces, and later, desquamation, can occur. Heart complications can involve coronary artery aneurysms. Patients may also develop arthritis and arthralgias. 

ANCA-associated vasculitis

GPA and MPA primarily affect older adults and usually cause systemic symptoms, eg, fevers, malaise, weight loss, and arthralgias. GPA tends to cause more manifestations than MPA in the head and neck, which include nasal crusting, epistaxis, hearing loss, and nasal and oral ulcerations. More patients with GPA develop saddle nose deformity as a long-term complication. In both diseases, lower airway symptoms may be present, including dyspnea, cough, and hemoptysis. Renal symptoms can cause lower extremity edema, hypertension, hematuria, and proteinuria from a necrotizing glomerulonephritis, and neurologic involvement can cause wrist or foot drop from a mononeuritis multiplex. The skin may also be involved, with palpable purpura typically occurring on the lower extremities. 

EGPA differs from GPA and MPA in terms of asthma and allergy symptoms, as well as the presence of prominent peripheral eosinophilia. Asthma symptoms typically predate the onset of vasculitis by several years. Pulmonary manifestations can include refractory asthma symptoms, pulmonary opacities, nodules, and pleural effusions with peripheral eosinophilia. Head and neck manifestations may include nasal polyps, chronic sinusitis, and otitis media. The skin may reveal painful ulcerations and nodules, palpable purpura, or urticaria. Cardiac involvement can cause electrical abnormalities, pericardial effusion, valve disease, myopericarditis, and heart failure. Neuropathy can occur, including mononeuritis multiplex, which may lead to foot or wrist drop. 

IgA Vasculitis

IgA vasculitis tends to cause diffuse palpable purpura predominantly in the lower extremities and manifests in individuals younger than age 21, though adults can also be affected. Patients may also have acute abdominal pain, nausea, vomiting, arthritis or arthralgias, and proteinuria and hematuria. The rash can occur in clusters and coalesce in gravity-dependent areas, including the buttocks. Bowel complications can occur rarely, including ischemia, intussusception, and other manifestations. Renal disease is more common in adults. 

Cryoglobulinemic Vasculitis

Patients with cryoglobulinemic vasculitis tend to develop systemic symptoms, including arthralgias, fatigue, palpable purpura, and sensory or motor deficits in the extremities (see Image. Urticarial Vasculitis). Rarely can the kidneys and gastrointestinal tract be involved. Renal disease is caused by membranoproliferative glomerulonephritis. Symptoms and disease manifestations can flare and remit spontaneously over time, although kidney disease may progress rapidly. Most cases are associated with chronic hepatitis C, though other viral infections, including hepatitis B, EBV, CMV, parvovirus, HIV, and bacterial infections, can be the cause. 

Behçet disease

Recurrent oral aphthous ulcers, in addition to genital ulcers, inflammatory eye lesions, or involvement of the skin, gastrointestinal tract, nervous system, vascular system, or musculoskeletal system, characterize Behçet disease. The ulcers tend to be painful, either in clusters or isolated, but are often deep and painful. Genital sores are very similar in appearance to oral aphthous ulcers and are extremely painful, typically occurring on the scrotum in males and the vulva in females. Skin lesions are prevalent, especially erythema nodosum. Pathergy is a unique characteristic of Behçet disease that manifests through a sterile pustule occurring at the site of local injury, eg, a needle stick. Ocular disease often manifests as uveitis, which can affect the entire uveal tract, a condition known as panuveitis. Neurological manifestations in BD can encompass multiple features, including diffuse encephalopathy, focal lesions, brainstem disease, and cognitive changes, among others. Vascular thrombosis is not uncommon, and inflammatory arthritis may also occur. 

Evaluation

Giant Cell Arteritis

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are essential laboratory tests for GCA, as both are typically elevated. Additional tests help exclude other systemic illnesses that may mimic vasculitis, eg, infection or malignancy. Temporal artery biopsy remains the gold standard for diagnosis. Ultrasound has emerged as a noninvasive diagnostic tool, though accuracy depends on operator skill, the influence of interpretation bias, and limited accessibility.[29] Ultrasound evaluation may reveal homogeneous, hypoechoic wall thickening in transverse scans, referred to as the "halo sign." Magnetic resonance imaging (MRI) or positron emission tomography (PET) can assess both cranial and extracranial arteries as alternative imaging modalities.[30]

Takayasu Arteritis

No specific blood tests confirm the diagnosis of Takayasu arteritis. ESR and CRP may be elevated but can normalize later in the disease course. Imaging serves as the primary diagnostic modality, with magnetic resonance angiography (MRA) preferred, or CT angiography (CTA) used to visualize stenotic and dilated segments of the aorta and its branches. Imaging also allows longitudinal monitoring. PET scans are increasingly used to identify ongoing disease activity, particularly when inflammatory markers are normal, thereby guiding immunosuppressive therapy.[30] Tissue biopsy is rarely performed unless obtained during urgent surgical interventions, eg, aneurysmal repair.

Polyarteritis Nodosa

No specific blood test confirms PAN. Markers of inflammation may be elevated but lack specificity. Hepatitis B and C serologies help evaluate for virus-associated PAN, while other tests rule out mimicking conditions. Vascular imaging, including conventional arteriography, CT angiography, or MR angiography, detects stenoses and aneurysmal dilations characteristic of PAN. A biopsy of skin lesions can exclude other causes of ulcers. When angiographic findings and clinical presentation are characteristic, biopsy may be unnecessary and potentially harmful.

Kawasaki Disease

Diagnosis relies on a detailed history and a thorough physical examination. Laboratory tests lack specificity but may show elevated inflammatory markers. Hematologic abnormalities, eg, leukocytosis, lymphopenia, thrombocytosis, and anemia may occur, along with transaminitis or sterile pyuria. Electrocardiography and echocardiography should be performed in all suspected cases to monitor for cardiac complications, including coronary artery aneurysms.

ANCA-Associated Vasculitis

Laboratory evaluation may reveal nonspecific signs of inflammation, including leukocytosis, thrombocytosis, anemia, and elevated ESR or CRP. Urinalysis may show hematuria and proteinuria in the presence of glomerulonephritis, with renal dysfunction possible. Detection of anti-neutrophil cytoplasmic antibodies (ANCA) aids diagnosis, present in 73% to 95% of GPA or MPA cases.[6][8] GPA ANCA (c-ANCA) typically associates with proteinase-3 in GPA, while MPA ANCA (p-ANCA) associates with myeloperoxidase in MPA, though up to 10% of cases demonstrate opposite patterns. Imaging, particularly CT scans, is critical for evaluating pulmonary and head/neck involvement. A biopsy may confirm the diagnosis and exclude mimicking conditions.

For EGPA, no specific blood test confirms the diagnosis; however, peripheral eosinophilia is expected, defined as an absolute eosinophil count of 1000 cells/mm³ or more, or greater than 10% of total leukocytes. Most patients also exhibit elevated IgE levels, though this lacks specificity. ANCA are present in 30% to 40% of patients, typically as p-ANCA against myeloperoxidase.[7] Imaging may reveal fluctuating pulmonary infiltrates on chest CT scans. Cardiac assessment via electrocardiogram, transthoracic echocardiography, and serum biomarkers is recommended for evaluation. Tissue biopsy demonstrates eosinophilic infiltrates, with or without vasculitic changes.

IgA Vasculitis

No specific blood test confirms IgA vasculitis; however, serum IgA levels may be elevated. ESR or CRP may be normal or elevated, and anemia may occur. Urinalysis may reveal hematuria and proteinuria. In cases with classic rash plus abdominal pain, renal involvement, or arthralgia, further testing may be unnecessary, though uncertain cases warrant skin biopsy with IgA staining. Renal biopsy with IgA staining should be considered when the diagnosis is unclear.

Cryoglobulinemic Vasculitis

Diagnosis requires testing for cryoglobulins, which must be collected at 37 °C and maintained at a warm temperature to prevent false negatives. Cryocrit measures the precipitate volume as a percentage of serum. Immunofixation identifies cryoglobulin components. Supporting labs include complement levels (particularly C4), rheumatoid factor, and testing for hepatitis C, hepatitis B, or Epstein-Barr virus. Chronic hepatitis C infection drives B-cell–mediated cryoglobulin production, with antiviral therapy reducing circulating cryoglobulins and memory B-cell expansion.

Behçet Disease

Diagnosis relies on clinical criteria, as no specific laboratory test confirms the disease. ESR and CRP may be elevated, accompanied by leukocytosis, thrombocytosis, anemia, or elevated ferritin levels. The International Criteria for Behçet Disease (ICBD) employs a scoring system: oral aphthosis, genital aphthosis, and ocular lesions each score 2 points, while other skin, neurological, and vascular findings each score 1 point. A total score of 4 or higher confirms the diagnosis.[31] Neuroimaging with brain MRI may evaluate neuro-Behçet. HLA-B51 associates with disease susceptibility but is not routinely used for diagnostic purposes.

Treatment / Management

Large Vessel Vasculitis Management

Giant cell arteritis

Treatment of GCA involves the prompt initiation of high-dose glucocorticoids, eg, prednisone 1 mg/kg/day. The use of a pulse dose is indicated in cases of vision loss or threatened vision loss, followed by a prolonged tapering of an oral steroid.[32][33] Steroids are typically tapered over a period of approximately 24 to 48 months; however, adverse effects can complicate this process. The GIACTA trial, published in 2017, demonstrated the steroid-sparing benefit of tocilizumab 162 mg subcutaneously weekly for inducing a steroid-free remission compared with standard therapy (steroids only) over 52 weeks. Potential adverse effects of tocilizimab over steroids included a higher risk of neutropenia and elevated nonfasting total cholesterol.[34] Combination therapy with steroids and tocilizumab or steroids and methotrexate is encouraged as initial therapy, given the benefit of steroid-sparing effects on patients.[33]

Takayasu arteritis 

Most medical therapy recommendations have been through small observational studies. High-dose oral glucocorticoids remain the first-line treatment for active and severe disease.[33] Methotrexate, azathioprine, and leflunomide, as steroid-sparing medications, have all been found to have some effectiveness in treating Takayasu arteritis.[35] TNF inhibitors are also partially effective in controlling the disease. More recently, tocilizumab has been shown to have a steroid-sparing benefit in patients with active Takayasu arteritis, and hydroxychloroquine may also play a role in preventing disease progression.[35] In some cases, the addition of antiplatelet therapy may be beneficial for patients at risk of stroke.[33]

Medium Vessel Vasculitis Management

Kawasaki disease

Intravenous immunoglobulin (IVIG) at a dosage of 2 g/kg is the primary therapy for Kawasaki disease.[36] Kawasaki disease is most effective when given within 10 days of the onset of illness and reduces the risk of coronary artery aneurysm formation. Concomitant aspirin is also recommended to treat the high fever, a common symptom of Kawasaki disease. Glucocorticoids are not typically used in Kawasaki disease except as an adjunct in patients at high risk for coronary artery lesions along with IVIG and aspirin.[37] 

Polyarteritis nodosa

The severity of the manifestation guides therapy for PAN. For mild-to-moderate disease, steroids with a steroid-sparing medication, eg, methotrexate or azathioprine, are recommended. For more severe disease, high-dose steroids with a more potent immunosuppressive, eg, cyclophosphamide, are advised.[38] Patients can typically be switched off of cyclophosphamide to a less toxic immunosuppressive as a maintenance steroid-sparing medication for the longer term, and then tapered off as clinical stability and remission are achieved.[39] 

Small Vessel Vasculitis Management

ANCA-associated vasculitis

While GPA and MPA are recognized as distinct diseases, management strategies generally follow a similar approach, as clinical trials often group patients with antibody–associated vasculitis together. Some differences exist, however, particularly in the choice of therapy based on disease severity and organ involvement. For both GPA and MPA with severe manifestations, rituximab is preferred over cyclophosphamide for induction of remission, administered alongside high-dose glucocorticoids.[40] In select cases, plasma exchange may provide benefit, especially in patients with severe renal involvement or diffuse alveolar hemorrhage.

Milder disease, which occurs more commonly in GPA, may be managed with methotrexate as a steroid-sparing agent instead of rituximab. Long-term maintenance therapy may include rituximab, azathioprine, or methotrexate, with the choice guided by clinical factors, potential adverse effects, and patient preferences.[40] Avacopan, a C5a receptor inhibitor, demonstrates a significant steroid-sparing effect in antibody–associated vasculitis when used in conjunction with background therapy and is recommended as a potential first-line option by the EULAR 2022 and KDIGO 2024 guidelines.[41]

Eosinophilic granulomatosis with polyangiitis 

For patients with severe active EGPA, high-dose glucocorticoids as an IV pulse or oral are recommended as initial therapy, followed by a taper as appropriate. Steroid-sparing medication, including rituximab or cyclophosphamide, may also be used to induce remission.[40] Other drugs, including methotrexate or azathioprine, can also be used as steroid-sparing medications. Beyond cytotoxic medications, biologics targeting IL-5, eg, mepolizumab or benralizumab, have been shown to have an added steroid-sparing effect in patients with active but nonsevere EGPA.[40][42][43]

Cryoglobulinemic vasculitis

Cryoglobulinemic vasculitis from active hepatitis C can be managed by treating hepatitis C with direct-acting antiviral medications, plus immunosuppressive medications, depending on the manifestations of the vasculitis. For severe disease manifestations, the use of glucocorticoids, plasma exchange, or rituximab may be necessary to control end-organ damage from cryoglobulinemic vasculitis.[44] Treatment plans should be individualized depending on the severity of cryoglobulinemic vasculitis manifestations and the etiology of the cryoglobulinemia. 

IgA vasculitis

Treatment of IgA vasculitis has been controversial, mainly due to the heterogeneous course of the disease. IgA vasculitis may take a relatively benign and spontaneously remitting path or a more severe course. Most of the treatments studied in IgA vasculitis have been done in children. For mild manifestations, eg, arthralgias and purpura, rest and analgesia are recommended. NSAIDs are generally avoided due to the increased risk for toxicity on the gastrointestinal tract and kidneys. For organ or life-threatening manifestations, eg, renal disease or gastrointestinal bleeding, glucocorticoids with immunosuppressive drugs may be used, but this remains controversial, especially in children.[45] 

For adult patients with IgA vasculitis affecting the kidneys, which is treated similarly to IgA nephropathy, and mild proteinuria without significant renal compromise, treatment with oral high dose corticosteroids, tapered over time, may lead to better renal outcomes and improved proteinuria than observant management but needs to be individualized depending on the severity and progression of the disease, presence of other comorbid conditions, and risk benefit ratio of immunosuppressive therapy.[46] Other nonimmunosuppressive therapies that play an important role in slowing down proteinuria and the progression to end-stage kidney disease include renal angiotensin system (RAS) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibition. Sparsentan, an endothelin type A and angiotensin II type 1 receptor blocker, has been shown to reduce proteinuria in patients with IgA nephropathy significantly.[47] Medication management in the treatment of IgA vasculitis and nephropathy is undergoing rapid changes.

Variable Vessel vasculitis

Behçet disease

The severity of manifestations guides treatment for Behçet disease. Mucocutaneous disease can be treated by colchicine, but azathioprine, thalidomide, TNF inhibitors, and aprimilast may also be used in refractory cases.[48] Eye involvement in the form of uveitis and panuveitis can be very severe and is typically treated with oral CS first, followed by initiation of a TNF inhibitor with or without a cytotoxic agent (eg, azathioprine or cyclosporine). An experienced ophthalmologist should guide the management of eye complications.

Deep vein thrombosis associated with Behçet disease is typically caused by inflammation of the vessel wall, and most experts agree that it should be treated with immunosuppressive therapy rather than anticoagulation. The medications used in this scenario are azathioprine, cyclophosphamide, and cyclosporine. Arterial involvement with vasculitis and aneurysms requires high-dose glucocorticoids and typically cyclophosphamide. Neuro-Behçet is managed with high-dose glucocorticoids and cytotoxic agents, including azathioprine, cyclophosphamide, or a tumor necrosis factor inhibitor (TNFi).[49] A more recent study demonstrated that infliximab is superior to cyclophosphamide in managing severe Behçet disease manifestations; however, the study was an open-label trial.[50]

Differential Diagnosis

Vasculitis has several mimics, therefore, careful evaluation of the following differential diagnoses should be considered:

• Drugs and toxins

  • Amphetimines
  • Minocycline
  • Cocaine
  • Levamisol
  • Injection drug use
  • Ergotism
• Infections

  • Hepatitis C
  • Hepatitis B
  • Endocarditis
  • Mycotic aneurysm
  • HIV
  • COVID-19
  • Adenovirus
  • Gonococcal infection
  • Histoplasmosis
• Other

  • Embolic disease (atrial myxoma, cholesterol crystals)
  • Lymphoma
  • Anti-glomerular basement membrane disease
  • Thrombotic disorders, eg, antiphospholipid syndrome, thrombotic thrombocytopenic purpura (TTP)
  • Radiation fibrosis
  • Degos disease
  • Segmental arterial mediolysis
  • Connective tissue disorders, eg, Ehlers-Danlos, Marfan syndrome
  • Fibromuscular dysplasia
  • Malignant hypertension
  • Adenosine deaminase deficiency (ADA)
  • VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)

Prognosis

Long-term survival of patients with vasculitis highly depends on the diagnosis, response to therapy, and adverse effects of drugs, including the occurrence of infections. In a study assessing long-term survival in ANCA-associated vasculitis, the 1-, 2-, and 5-year survival rates were 88%, 85%, and 78%, respectively. The mortality rate was 2.6 times that of the general population.[51] Mortality reports derive from both active vasculitic disease and complications of therapy.

Complications

Complications of vasculitis depend on the size and type of vessel affected. Large- and medium-vessel vasculitides, eg, GCA, Takayasu arteritis, and Kawasaki disease, can result in acute myocardial infarction, stroke, ischemia of cranial arteries, vision loss, mesenteric ischemia, aortic syndromes including dissection or intramural hematoma, and limb ischemia.[52][53] Small-vessel vasculitis often produces life-threatening complications, eg, alveolar hemorrhage, renal failure, and intestinal ischemia.[54]

Aneurysm formation frequently develops in patients with polyarteritis nodosa and Behçet disease.[53] Deep venous thrombosis and pulmonary embolism occur more often in antineutrophil cytoplasmic antibody–associated vasculitis and Behçet disease compared with other vasculitides.[18] Additional complications arise from toxicities related to systemic medications, particularly immunosuppressive therapy, with infectious complications representing a major risk.

Deterrence and Patient Education

The vasculitides are rare diseases. For patients diagnosed with vasculitis, patient education on the type of vasculitis and various clinical manifestations that may arise from the vasculitis is critical to ensuring good patient outcomes. Because vasculitis may be difficult to treat and can flare through medication therapy, patients should be asked to immediately report new or recurrent symptoms that may be related to the vasculitis to their clinicians. Other reasons to contact a patient's clinician are for symptoms of an infection as a complication of immunosuppressant therapy or for an adverse effect of a medication. Successful management of vasculitis is in part achieved through regular follow-up with the patient's clinicians, typically led by the rheumatologist, but also involving other interprofessional members, adherence to regular laboratory monitoring, and medication therapy. 

Enhancing Healthcare Team Outcomes

Vasculitis encompasses a heterogeneous group of disorders characterized by inflammation of blood vessels, which can damage multiple organ systems and mimic more common diseases. Accurate diagnosis relies on a thorough history, physical examination, laboratory testing, and selective imaging or biopsy. Evidence-based treatment emphasizes early recognition, timely initiation of immunosuppressive therapy, and careful monitoring for toxicity. Most vasculitides are chronic systemic illnesses that require sustained, coordinated care from an interprofessional team to prevent irreversible organ injury and optimize long-term outcomes.

Effective management demands a broad set of skills and responsibilities across disciplines. Rheumatologists and advanced practitioners guide diagnosis, systemic therapy, and coordination of subspecialty input, while nephrologists, pulmonologists, dermatologists, ophthalmologists, and neurologists address organ-specific complications. Pathologists and radiologists provide diagnostic confirmation, and pharmacists ensure safe medication management with complex immunosuppressive regimens. Nurses deliver patient education, monitor treatment response, and offer vital support. Strong communication, care coordination, and shared decision-making among all team members are essential to enhance patient-centered care, improve outcomes, reduce safety risks, and strengthen overall team performance.

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Disclosure: Shraddha Jatwani declares no relevant financial relationships with ineligible companies.

Disclosure: Marissa Blum declares no relevant financial relationships with ineligible companies.