Systemic Vasculitis

Systemic vasculitis is inflammation and necrosis of blood vessel walls that impairs blood flow through the affected vessel, producing organ damage from ischemia rather than from the vessel wall itself. The diseases grouped under this heading share that mechanism but otherwise differ enormously in typical patient age, vessel calibre, organ targets, and treatment — which is exactly why the vessel-size framework below, from the 2012 Revised International Chapel Hill Consensus Conference (CHCC) Nomenclature of Vasculitides, is the organizing structure for this entire chapter rather than an optional preamble.^[1]

Two practical consequences follow directly from this framework. First, age is itself diagnostic: giant cell arteritis essentially never occurs under age 50, Takayasu arteritis classically presents under age 40, and IgA vasculitis is overwhelmingly a disease of childhood — a patient's age alone should narrow the differential before a single test is ordered. Second, vessel size predicts the dominant clinical picture: large-vessel disease produces claudication, bruits, and asymmetric pulses/pressures; medium-vessel disease produces mononeuritis multiplex, visceral microaneurysms, and skin nodules; small-vessel disease produces palpable purpura, glomerulonephritis, and pulmonary hemorrhage. Recognizing which pattern a patient fits is the single fastest route to the right diagnosis.

Why giant cell arteritis and ANCA-associated vasculitis anchor this chapter

Every vasculitis in this chapter matters, but two deserve to be treated as centrepieces because delay in recognizing and treating them causes irreversible harm on a timescale of hours to weeks rather than months: giant cell arteritis, where delayed glucocorticoid therapy causes permanent vision loss (see Red Flags & Refer and Choose Initial Treatment), and ANCA-associated vasculitis, where delayed or under-intensive immunosuppression allows progression to end-stage kidney disease or fatal pulmonary hemorrhage, while over-cautious avoidance of the necessary immunosuppression's real infection risk is itself a genuine, preventable cause of death (see Choose Initial Treatment and Special Populations).

Large-vessel vasculitis

Giant cell arteritis (GCA)

The most common systemic vasculitis in adults over 50, with incidence rising steeply with age and a genuine female predominance (roughly 2-3:1); most common in populations of Northern European ancestry.^[2] Classic features include a new, often temporal, headache; scalp tenderness (pain on combing hair or resting the head on a pillow); jaw or tongue claudication (pain with chewing that eases with rest — a genuinely specific finding, caused by ischemia of the muscles of mastication); and constitutional symptoms (fever, weight loss, malaise). Visual symptoms are the finding that changes everything — amaurosis fugax (transient monocular vision loss), diplopia, or any acute visual disturbance in this clinical context reflects arteritic anterior ischemic optic neuropathy or central retinal artery occlusion and is a direct precursor to permanent, irreversible blindness, sometimes within hours (see Red Flags & Refer). Roughly 40-60% of GCA patients have overlapping polymyalgia rheumatica (proximal shoulder and hip girdle pain and stiffness, worse in the morning) at diagnosis, and a patient presenting with apparently isolated polymyalgia rheumatica should always be screened for GCA symptoms specifically, since the two exist on a spectrum rather than as fully separate diseases.

Takayasu arteritis

A large-vessel vasculitis that is, in most other respects, GCA's younger mirror image: classically presenting under age 40, with a strong female predominance (roughly 8-9:1) and a materially higher incidence in patients of Asian ancestry, though it occurs worldwide.^[3] Early disease produces nonspecific constitutional symptoms that are easy to miss; the diagnosis becomes apparent as large-vessel stenosis, occlusion, or aneurysm develops, producing limb claudication (classically upper-limb, from subclavian involvement), a measurable blood pressure discrepancy of more than 10 mmHg between arms, diminished or absent peripheral pulses (the historical name "pulseless disease"), carotidynia, vascular bruits (subclavian, carotid, abdominal aorta), and, in more advanced disease, hypertension from renal artery involvement or aortic regurgitation from aortic root dilation. Because early symptoms are nonspecific and pulse/pressure asymmetry can be subtle, diagnosis is frequently delayed by months to years from symptom onset — a genuine, well-documented pattern that argues for actively checking bilateral blood pressures and pulses in any young patient with unexplained constitutional symptoms and elevated inflammatory markers.

Medium-vessel vasculitis

Polyarteritis nodosa (PAN)

A necrotizing vasculitis of medium-sized muscular arteries that is, critically, not ANCA-associated and does not cause glomerulonephritis — both genuinely important distinguishing points from the small-vessel ANCA-associated vasculitides covered below, since PAN spares the glomerular capillaries even as it can produce severe hypertension from renal artery microaneurysms and infarction.^[1] Classic features include mononeuritis multiplex (asymmetric, stepwise sensorimotor neuropathy — a foot drop or wrist drop appearing over days is a hallmark), livedo reticularis, tender subcutaneous nodules along artery courses, testicular pain (from testicular artery involvement — a finding that should prompt vasculitis workup rather than reflexive urologic referral alone), and gastrointestinal ischemia that can progress to bowel infarction or perforation. A genuinely important subset is hepatitis B-associated PAN, historically responsible for a substantial proportion of cases before universal HBV vaccination reduced its incidence; every new PAN diagnosis should include hepatitis B surface antigen testing, since HBV-associated disease is managed with a fundamentally different, antiviral-led strategy rather than the immunosuppression used for idiopathic disease (see Choose Initial Treatment).

Kawasaki disease — cross-reference

Kawasaki disease is the medium-vessel vasculitis of childhood under the Chapel Hill classification and this platform's existing Kawasaki Disease chapter covers its full diagnostic criteria, IVIG and aspirin dosing, and coronary-artery-aneurysm surveillance pathway in complete detail — that content is not repeated here.

Small-vessel ANCA-associated vasculitis (AAV)

The three AAV subtypes share pauci-immune small-vessel inflammation (minimal immune-complex deposition on biopsy, distinguishing them from IgA vasculitis) but differ meaningfully in organ pattern and typical ANCA serology (see Assessment & Diagnosis for the full serology table).

Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis)

Defined by granulomatous inflammation of the respiratory tract in addition to small-vessel vasculitis. Upper airway disease is genuinely distinctive: chronic sinusitis unresponsive to usual therapy, saddle-nose deformity from destruction of nasal cartilage, subglottic stenosis producing stridor or voice change, and otitis media/mastoiditis. Lower respiratory tract disease produces pulmonary nodules (which can cavitate) and, in severe disease, diffuse alveolar hemorrhage. Renal disease is pauci-immune crescentic glomerulonephritis, often clinically silent until advanced. Roughly 90% of active generalized GPA is PR3-ANCA/c-ANCA positive.^[4]

Microscopic polyangiitis (MPA)

Small-vessel vasculitis without the granulomatous upper-airway disease that defines GPA. The classic, genuinely dangerous presentation is a pulmonary-renal syndrome — simultaneous diffuse alveolar hemorrhage (hemoptysis, dyspnea, falling hemoglobin) and pauci-immune crescentic glomerulonephritis (rising creatinine, active urinary sediment) — which is a medical emergency requiring immediate, aggressive treatment (see Red Flags & Refer). Roughly 70% of MPA is MPO-ANCA/p-ANCA positive.^[4]

Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome)

The AAV subtype most likely to be missed early, because it begins as apparent severe, late-onset asthma rather than as obvious vasculitis. EGPA classically evolves through overlapping phases: a prodromal allergic phase (adult-onset asthma, allergic rhinitis, nasal polyps, sometimes for years before diagnosis); an eosinophilic phase (peripheral eosinophilia and eosinophilic tissue infiltration — pulmonary infiltrates, eosinophilic gastroenteritis); and a vasculitic phase (mononeuritis multiplex, palpable purpura, and, most consequentially for mortality, eosinophilic myocarditis and cardiomyopathy). Only roughly 30-40% of EGPA is ANCA-positive (usually MPO/p-ANCA when positive), and this serologic split is not incidental: ANCA-positive EGPA behaves more like a genuine vasculitis, with more renal and neurologic involvement, while ANCA-negative EGPA behaves more like a severe eosinophilic organ-infiltrative disease, with more cardiac and pulmonary involvement — a distinction that increasingly shapes treatment choice (see Choose Initial Treatment).

Small-vessel immune-complex vasculitis

IgA vasculitis (Henoch-Schönlein purpura)

IgA vasculitis is the most common vasculitis of childhood, with a peak incidence between ages 3 and 15 and a generally self-limited course that stands in deliberate contrast to the chronic, relapsing, immunosuppression-dependent adult AAV subtypes above — this distinction should shape expectations and counselling from the first visit.^[5] It follows an upper respiratory infection in a substantial proportion of cases and is mediated by IgA1 immune-complex deposition in small vessels, rather than ANCA. The classic tetrad is palpable purpura (non-thrombocytopenic, classically on the buttocks and lower extremities, sometimes with associated edema), arthralgia or arthritis (usually large joints, non-deforming), abdominal pain (from bowel wall edema and hemorrhage, which can be severe and is a recognized precipitant of intussusception in children — see Red Flags & Refer), and renal involvement (hematuria with or without proteinuria, histologically and pathophysiologically continuous with IgA nephropathy — see the platform's IgA Nephropathy and Glomerulonephritis chapters for the shared renal workup). Most children recover fully within 4-6 weeks without any disease-modifying therapy; the renal trajectory, not the skin or joint findings, is what determines long-term prognosis and the small minority of patients who progress to chronic kidney disease.

A more severe case of IgA vasculitis (Henoch-Schönlein purpura), showing the characteristic non-thrombocytopenic palpable purpura extending onto the foot, leg, and arm. The lower-extremity/buttock distribution shown here is the classic pattern. (Okwikikim, Public Domain, Wikimedia Commons)

• Age over 50 — an essentially required feature of giant cell arteritis; GCA in a patient under 50 should prompt diagnostic reconsideration rather than acceptance.^[2]
• Age under 40, female sex, and Asian ancestry — the classic Takayasu arteritis demographic, though the disease occurs across ancestries.^[3]
• A history of polymyalgia rheumatica — a genuine risk marker for concurrent or subsequent GCA, not a separate, unrelated diagnosis.
• Northern European ancestry, for GCA specifically.
• Hepatitis B infection — the defining risk factor for the HBV-associated PAN subset, now uncommon in populations with high HBV vaccination coverage but still worth actively excluding in every new PAN diagnosis.
• A personal history of adult-onset asthma, allergic rhinitis, or nasal polyps — the prodromal-phase risk pattern that precedes eosinophilic granulomatosis with polyangiitis, sometimes by years.
• Childhood age (peak 3-15 years) and a preceding upper respiratory infection — the typical IgA vasculitis risk pattern; a minority of cases follow a specific medication exposure or streptococcal infection.
• PR3-ANCA/c-ANCA positivity specifically — associated with a higher relapse rate than MPO-ANCA/p-ANCA-positive disease across the AAV spectrum, a genuine prognostic distinction that should inform the intensity and duration of maintenance therapy (see Choose Initial Treatment and Monitoring & Follow-Up).^[6]

Beyond the GCA visual emergency, the following also demand urgent, same-day escalation rather than routine follow-up:

• Hemoptysis with a rising creatinine or active urinary sediment in a patient with suspected or known AAV — this pulmonary-renal syndrome pattern (classically MPA, but seen in GPA as well) reflects diffuse alveolar hemorrhage plus rapidly progressive glomerulonephritis and requires immediate hospital-based, specialist-directed treatment.
• A rapidly rising creatinine or new active urinary sediment (dysmorphic red cells, red cell casts) in any patient with known or suspected AAV — treat as rapidly progressive glomerulonephritis until proven otherwise; delay materially worsens the chance of renal recovery.
• A new, stepwise mononeuropathy (foot drop, wrist drop, or similar) in a patient with a systemic illness consistent with PAN or EGPA — this is mononeuritis multiplex until proven otherwise and warrants urgent specialist assessment.
• New or worsening limb ischemia, a new bruit with an ischemic limb, or evidence of aortic dissection or severe aortic regurgitation in a patient with known or suspected Takayasu arteritis.
• Acute abdominal pain with peritoneal signs in a patient with PAN or severe IgA vasculitis — evaluate urgently for bowel ischemia or perforation.
• Severe, colicky abdominal pain in a child with IgA vasculitis, particularly with vomiting or blood in the stool — evaluate for intussusception, a recognized and specifically actionable complication.
• New chest pain, dyspnea, or arrhythmia in a patient with EGPA, especially ANCA-negative disease — evaluate urgently for eosinophilic myocarditis, the leading driver of EGPA mortality.
• Fever in any patient on cyclophosphamide, rituximab, or high-dose glucocorticoids — treat as a potential serious infection in an immunosuppressed host until proven otherwise, given the genuine infection risk this therapy carries (see Choose Initial Treatment and Special Populations).

Giant cell arteritis

ESR and CRP are markedly elevated in the great majority of GCA cases and remain a reasonable first-line screen, but a normal ESR does not exclude the diagnosis — a small but genuine minority (on the order of a few percent) of biopsy-confirmed GCA presents with a normal ESR, so a compelling clinical picture should not be dismissed on inflammatory markers alone.^[2] Temporal artery biopsy remains the diagnostic reference standard, but two practical points matter more clinically than the biopsy result itself: first, glucocorticoid therapy should never be delayed to obtain it (see Choose Initial Treatment), and second, biopsy sensitivity is preserved for roughly two weeks after starting glucocorticoids, so treating first and biopsying promptly after does not meaningfully compromise diagnostic yield. Skip lesions mean a negative unilateral biopsy does not fully exclude GCA; a longer biopsy segment (at least 1-2 cm), contralateral biopsy in a persistently high-suspicion patient, or vascular ultrasound demonstrating the "halo sign" (a hypoechoic ring around the temporal artery lumen from wall edema) as either an adjunct or, where locally validated, an alternative to biopsy are all reasonable per current guidance.^[2] The 2022 ACR/EULAR classification criteria require age 50 or older at diagnosis plus a cumulative score of 6 or more points across weighted clinical, laboratory, and imaging/biopsy items (examples include morning stiffness in shoulders/neck, sudden visual loss, jaw/tongue claudication, new temporal artery abnormality on examination, ESR ≥50 or CRP ≥10 mg/L, and a positive biopsy or halo sign on ultrasound), though this tool is intended for research classification and structured clinical reasoning rather than as a bedside diagnostic checklist that overrides clinical judgment.^[7]

Takayasu arteritis

Diagnosis rests on vascular imaging — CT angiography, MR angiography, or PET-CT — demonstrating wall thickening, stenosis, occlusion, or aneurysm of the aorta or its major branches, together with the clinical/examination findings in Recognize the Condition (pulse and blood pressure asymmetry, bruits, claudication).^[3] Inflammatory markers are frequently, but not universally, elevated and correlate imperfectly with actual disease activity on imaging — a genuinely important limitation, since normal inflammatory markers do not reliably indicate quiescent vessel disease in Takayasu arteritis specifically. The 2022 ACR/EULAR classification criteria require age 60 or younger at diagnosis, evidence of vasculitis on imaging, plus a weighted point total from clinical and imaging criteria (examples include female sex, angina, limb claudication, bruits, pulse or blood pressure asymmetry, and the specific pattern of arterial involvement on imaging).^[3]

ANCA serology — the central diagnostic tool for small-vessel ANCA-associated vasculitis

ANCA testing combines indirect immunofluorescence (which yields the classic c-ANCA/p-ANCA staining pattern) with antigen-specific ELISA testing for proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies; current practice relies primarily on the ELISA result, with the immunofluorescence pattern as a supportive, historically named correlate.^[4]

Renal biopsy showing pauci-immune (minimal immune deposit) crescentic glomerulonephritis is the confirmatory test where renal involvement is present and is often pursued even in ANCA-positive disease to establish a baseline chronicity/activity index that guides both initial treatment intensity and prognosis.

Polyarteritis nodosa

ANCA serology is characteristically negative in PAN — a genuine, clinically useful distinguishing feature from the AAV subtypes above.^[1] Diagnosis rests on conventional angiography demonstrating the classic microaneurysms and areas of stenosis in medium-sized visceral arteries (renal, mesenteric, hepatic), or biopsy of clinically involved tissue (sural nerve, skin, muscle) showing necrotizing arteritis of medium vessels without glomerulonephritis. Hepatitis B surface antigen testing is mandatory in every new diagnosis, since it fundamentally changes the treatment approach (see Choose Initial Treatment).

Eosinophilic granulomatosis with polyangiitis

Peripheral eosinophilia (typically >1.5 x 10⁹/L, or >10% of the differential) in a patient with the asthma/allergic-rhinitis prodrome described in Recognize the Condition is the key laboratory clue; biopsy of an accessible involved site (skin, nerve, lung) showing eosinophilic tissue infiltration with or without frank vasculitis supports the diagnosis. Cardiac assessment (ECG, troponin, and echocardiography or cardiac MRI where myocarditis is suspected) is warranted given its outsized contribution to mortality, particularly in ANCA-negative disease.

IgA vasculitis

Diagnosis in a child with the classic tetrad (palpable purpura, arthralgia, abdominal pain, renal involvement) is usually clinical, without requiring biopsy. The EULAR/PRINTO/PRES (Ankara 2008) criteria require palpable purpura (mandatory) plus at least one of: abdominal pain, histopathology showing typical leukocytoclastic vasculitis with predominant IgA deposition (or proliferative glomerulonephritis with IgA deposition), arthritis or arthralgia, or renal involvement (hematuria and/or proteinuria).^[5] Skin biopsy with immunofluorescence for IgA deposition is reserved for atypical presentations (adult onset, atypical distribution, or diagnostic uncertainty) rather than routine practice. Urinalysis for hematuria/proteinuria at diagnosis and through follow-up is essential in every case, since renal involvement — not the skin or joint findings — determines long-term outcome (see Monitoring & Follow-Up, and the platform's IgA Nephropathy and Glomerulonephritis chapters for the shared renal workup).

• Prevent irreversible vision loss in giant cell arteritis by starting high-dose glucocorticoid therapy immediately upon clinical suspicion, without waiting for biopsy confirmation — the single most time-critical target in this chapter (see Choose Initial Treatment).
• Induce remission in ANCA-associated vasculitis promptly and completely, using an intensity matched to disease severity, to prevent progression to end-stage kidney disease or fatal pulmonary hemorrhage.
• Transition every AAV patient from induction to a distinct, lower-intensity maintenance regimen rather than continuing induction-intensity immunosuppression indefinitely, balancing relapse prevention against cumulative treatment toxicity.
• Minimize cumulative glucocorticoid exposure across every vasculitis in this chapter through the fastest safe taper and, where evidence supports it, an early steroid-sparing agent (tocilizumab in GCA; rituximab, methotrexate, or azathioprine in AAV) — cumulative steroid toxicity is itself a major, preventable source of long-term morbidity.
• Proactively prevent infection during induction-intensity immunosuppression, with Pneumocystis jirovecii pneumonia prophylaxis as the single most specific, actionable pharmacist-level intervention (see Choose Initial Treatment).
• Recognize hepatitis B-associated polyarteritis nodosa as a distinct disease requiring an antiviral-led, not immunosuppression-led, strategy.
• Support the generally self-limited course of pediatric IgA vasculitis without over-treating it as though it were adult AAV, while still monitoring the renal trajectory that determines its minority of genuinely chronic outcomes.

Patient self-monitoring and red-flag education

Every GCA patient — and anyone on a glucocorticoid taper for it — needs explicit, repeated counselling to seek same-day care for any new visual symptom, since this is the single intervention most likely to prevent permanent vision loss outside of the initial treatment decision itself. AAV patients need equivalent counselling on the pulmonary-renal syndrome symptoms in Red Flags & Refer, and on fever as a possible serious infection rather than a routine viral illness given their immunosuppressed state.

Vaccination

Confirm routine immunization is current before starting significant immunosuppression wherever timing allows, since vaccine response is blunted once therapy (particularly rituximab or cyclophosphamide) is under way; avoid live vaccines during active immunosuppressive therapy. Annual influenza and age-appropriate pneumococcal vaccination are particularly relevant given the added respiratory infection risk this population carries.

Bone health

Every patient anticipated to need more than a brief glucocorticoid course should have baseline fracture-risk assessment and, where indicated, bone-protective therapy started proactively rather than reactively (see Drug Tables) — this applies across every vasculitis in this chapter given how central glucocorticoids are to initial treatment.

Smoking cessation

Genuinely relevant across the large- and medium-vessel vasculitides specifically, given the added vascular risk smoking carries in a patient already dealing with arterial inflammation and stenosis.

Fertility counselling

Discuss fertility preservation options before cyclophosphamide therapy wherever the clinical urgency allows for it, given its dose-dependent gonadotoxicity (see Special Populations) — this conversation is easy to defer under time pressure but should happen proactively rather than only when specifically raised by the patient.

Psychosocial support

The chronic, relapsing course of AAV and Takayasu arteritis in particular carries a genuine, often under-acknowledged burden — long-term immunosuppression, relapse anxiety, and, in Takayasu arteritis, a young age at diagnosis facing a lifelong disease. Proactively screen for and address mental health alongside physical disease management, and connect patients with vasculitis-specific patient-support organizations.

Pediatric IgA vasculitis — reassurance and graded activity

Most families need reassurance that this is a generally self-limited illness rather than a lifelong disease, together with clear, specific guidance on the red-flag symptoms in Red Flags & Refer (severe abdominal pain, blood in stool or urine, joint swelling limiting mobility) that should prompt reassessment. Activity can generally continue as tolerated; strict bed rest is not required and does not improve outcomes.

Pregnancy

Cyclophosphamide and methotrexate are both teratogenic and should be avoided, with treatment substituted for a pregnancy-compatible alternative (glucocorticoids, azathioprine) wherever the clinical situation allows planning in advance. Takayasu arteritis specifically affects women of reproductive age; pregnancy is generally manageable with careful blood pressure control and multidisciplinary maternal-fetal medicine involvement, though active, uncontrolled disease or significant aortic involvement carries genuine additional risk and warrants pre-conception counselling wherever possible. Rituximab crosses the placenta later in pregnancy and is generally avoided in the third trimester specifically because of the risk of neonatal B-cell depletion, though it is not absolutely contraindicated earlier in pregnancy when clinically necessary.

Fertility

Cyclophosphamide's gonadotoxicity is genuinely dose-dependent and age-dependent (higher risk with cumulative dose and older reproductive age); discuss fertility preservation options before starting wherever clinical urgency allows, rather than only when specifically raised by the patient (see Non-Pharmacologic Treatment).

Hepatitis B and C screening before rituximab

Screen hepatitis B surface antigen, core antibody, and hepatitis C antibody before starting rituximab in every patient, given a genuine reactivation risk with B-cell depletion; a patient with evidence of prior hepatitis B exposure needs antiviral prophylaxis or close monitoring per current infectious diseases guidance before and during rituximab therapy, not simply routine follow-up.

Renal impairment

Cyclophosphamide requires dose reduction in renal impairment; NSAIDs (used for IgA vasculitis arthralgia) should be avoided with any degree of active renal involvement given both the added nephrotoxicity risk and the diagnostic confusion an NSAID-related creatinine rise can cause in a patient already being monitored for vasculitis-related renal disease.

Elderly patients (giant cell arteritis)

Since GCA is overwhelmingly a disease of older adults, high-dose glucocorticoid therapy in this population carries a genuinely elevated risk of falls, fracture, delirium, and glucose destabilization; proactive bone protection, glucose monitoring, and a structured taper plan are especially important here, and this is exactly the population where an early steroid-sparing agent (tocilizumab) offers the most meaningful benefit in reducing cumulative exposure.

Pediatric patients

IgA vasculitis is primarily a pediatric disease and is managed as detailed throughout this chapter; Kawasaki disease is covered in the platform's dedicated Kawasaki Disease chapter. GPA, MPA, and EGPA are rare but do occur in children, managed by pediatric rheumatology using the same general induction/maintenance principles as adult disease, with attention to growth and development-specific glucocorticoid and cyclophosphamide toxicity considerations.

• Giant cell arteritis: clinical symptoms and ESR/CRP at each visit during the taper; explicit, repeated screening for any new visual symptom at every contact, not only when volunteered by the patient.
• Takayasu arteritis: periodic vascular imaging (interval per specialist judgment, since inflammatory markers correlate imperfectly with actual disease activity on imaging) plus bilateral blood pressure and pulse assessment at every visit.
• ANCA-associated vasculitis: renal function and urinalysis serially throughout induction and maintenance; ANCA titer can be followed as one data point, but should not, on its own, drive a treatment change — titer correlates imperfectly with disease activity, and treating a rising titer in an otherwise asymptomatic patient with no other objective evidence of relapse is a genuine, avoidable overtreatment error (see Common Errors to Avoid).^[6]
• Cyclophosphamide: CBC regularly during therapy for cytopenias; track cumulative lifetime dose given its relationship to bladder cancer and myelodysplasia risk; urinalysis for hematuria as a possible hemorrhagic cystitis or, longer-term, bladder malignancy signal.
• Rituximab: CD19/CD20 B-cell counts and immunoglobulin levels periodically, particularly with repeated dosing, given the hypogammaglobulinemia and associated infection risk that can accumulate over multiple cycles.
• Azathioprine and methotrexate: periodic CBC and liver enzymes per each agent's standard immunosuppressive monitoring schedule.
• Tocilizumab: periodic CBC, liver enzymes, and lipid panel, consistent with its monitoring requirements in this platform's other chapters where it appears.
• Bone density (DEXA) at baseline and periodically for any patient on a prolonged glucocorticoid course.
• IgA vasculitis: urinalysis (and blood pressure) at diagnosis, then periodically for at least 6-12 months even after skin and joint symptoms resolve, since renal involvement can emerge or evolve after the presenting features have settled — this follow-up should not be abandoned once the child "looks better."
• Vaccination status review at every visit involving a change in immunosuppressive intensity.

1. Recurrent GCA symptoms during a glucocorticoid taper: increase the glucocorticoid dose back toward the last effective level and reassess the taper pace; add tocilizumab if not already started, specifically to allow a more sustainable subsequent taper rather than repeating the same cycle.
2. AAV relapse on maintenance azathioprine: switching to rituximab is a reasonable, evidence-supported next step given its demonstrated superiority in this exact scenario (MAINRITSAN); reassess whether the relapse reflects genuinely inadequate maintenance intensity or a missed alternative explanation (infection, non-adherence) first.
3. Severe or refractory AAV despite standard induction: this is a specialist-directed escalation (dose/agent intensification, reassessment for an overlapping process) rather than an isolated primary-care or community-pharmacy decision; do not reach for avacopan as a next step given its current regulatory status (see Choose Initial Treatment).
4. Relapsing or refractory EGPA with prominent eosinophilic/asthma features: add mepolizumab, provided any genuinely vasculitic organ involvement is separately and adequately addressed.
5. HBV-associated PAN not responding to antiviral-led therapy: specialist (infectious diseases and rheumatology) reassessment of both viral suppression adequacy and disease activity, rather than empirically escalating immunosuppression, which risks worsening viral replication.
6. Persistent or worsening proteinuria/hematuria in IgA vasculitis after the acute presentation has resolved: nephrology referral for consideration of biopsy and disease-modifying therapy following the platform's Glomerulonephritis and IgA Nephropathy chapters' approach, rather than continued observation alone.
7. Steroid-refractory or steroid-dependent Takayasu arteritis: add or switch the steroid-sparing agent (methotrexate, tocilizumab, a TNF-alpha inhibitor) per specialist judgment, and reassess for a revascularization indication once inflammation is controlled.

• Waiting for temporal artery biopsy before starting glucocorticoids in suspected GCA — the single most dangerous, avoidable error in this chapter; biopsy sensitivity is preserved for roughly two weeks after treatment starts, so there is no clinical scenario where delay is justified.^[2]
• Dismissing a compelling GCA presentation because the ESR is normal — a genuine minority of biopsy-confirmed cases present with normal inflammatory markers.
• Assuming a negative ANCA excludes AAV — up to 60-70% of EGPA and a meaningful minority of GPA/MPA are ANCA-negative; diagnosis in that setting rests on the clinical and histologic picture.
• Adjusting AAV immunosuppression based on a rising ANCA titer alone, without corroborating clinical or laboratory evidence of relapse — titer correlates imperfectly with actual disease activity.^[6]
• Omitting Pneumocystis jirovecii pneumonia prophylaxis during cyclophosphamide or high-dose glucocorticoid induction — a specific, easily overlooked, genuinely actionable gap.
• Skipping hepatitis B surface antigen testing in a new PAN diagnosis, and consequently missing the fundamentally different antiviral-led treatment strategy HBV-associated disease requires.
• Skipping hepatitis B/C screening before starting rituximab, risking a genuine reactivation event.
• Treating PAN and ANCA-associated vasculitis as interchangeable — PAN is characteristically ANCA-negative and does not cause glomerulonephritis, both genuine distinguishing features that change the diagnostic and treatment approach.
• Continuing induction-intensity immunosuppression indefinitely instead of transitioning to a distinct, lower-intensity maintenance regimen once remission is achieved.
• Presenting avacopan as a routine or default AAV treatment option without checking its current regulatory status, given the June 2026 trial retraction and the ongoing Health Canada/FDA review.
• Using an NSAID for IgA vasculitis arthralgia without first confirming normal renal function via urinalysis.
• Missing intussusception as a cause of severe abdominal pain in a child with IgA vasculitis, and attributing it reflexively to the disease's expected GI involvement.
• Discontinuing follow-up urinalysis in IgA vasculitis once the skin and joint findings resolve, missing renal involvement that emerges or evolves afterward.
• Deferring fertility-preservation counselling before cyclophosphamide until after treatment has already started, when earlier discussion was genuinely feasible.

Glucocorticoids — the foundation of initial treatment across this chapter

In suspected giant cell arteritis, the first dose should never be delayed pending biopsy confirmation.

ANCA-Associated Vasculitis — Induction Immunosuppression

Combined with glucocorticoids above; choice between cyclophosphamide and rituximab is individualized (see Choose Initial Treatment).

ANCA-Associated Vasculitis — Maintenance Immunosuppression

A distinct, lower-intensity regimen started once remission is achieved, generally continued at least 18-24 months.

Giant Cell Arteritis / Takayasu Arteritis — Steroid-Sparing Biologic

Eosinophilic Granulomatosis with Polyangiitis — Targeted Biologic

Under Regulatory Review — Not a Routine Option

Avacopan's pivotal ADVOCATE trial was retracted by NEJM on June 29, 2026; Health Canada's July 7, 2026 advisory directs prescribers not to initiate it in new patients while its data-integrity review is ongoing. The entry below is included for reference only, per this project's drug-link-integrity rule that a published catalogue slug is linked wherever mentioned — it is not a treatment recommendation.

Infection Prophylaxis During Induction-Intensity Immunosuppression

Pneumocystis jirovecii pneumonia prophylaxis is recommended for the duration of cyclophosphamide therapy, and for at least 6 months after the last rituximab dose with significant concurrent glucocorticoid exposure.

Bone Protection During Long-Term Glucocorticoid Therapy

Start proactively, not reactively, in any patient anticipated to need a prolonged glucocorticoid course.

IgA Vasculitis — Symptomatic Management

Reserve NSAIDs for a patient with confirmed normal renal function; avoid with any active renal involvement.