Residency · Residency · Internal Medicine

Vasculitis: Pattern Recognition and Urgent Management

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Alright, it’s 3 AM, and you’ve just been called about Mrs. Henderson, a 72-year-old with a new, severe headache, jaw pain when she chews, and she’s starting to see black spots in her vision. Her inflammatory markers are through the roof. You're exhausted, but this is one of those times you need to snap awake because waiting could mean permanent blindness for her. This sounds like giant cell arteritis, a large vessel vasculitis. The immediate decision? High-dose steroids, now. Don't wait for the temporal artery biopsy. That can come later, but saving her vision cannot. This is about recognizing a pattern and acting fast.

Then there's Mr. Chen, a 50-year-old who came in with coughing up blood and rapidly worsening kidney function. His urine shows red blood cell casts, and his creatinine has doubled in two days. This is a classic pulmonary-renal syndrome, a red flag for small vessel vasculitis, specifically ANCA-associated vasculitis like granulomatosis with polyangiitis or microscopic polyangiitis. Here, the urgency is also extreme. You’re looking at a multi-organ catastrophe if you don't hit it hard with pulse-dose steroids and either rituximab or cyclophosphamide. You need to get those ANCA labs and a renal biopsy, but the treatment starts even before all the results are back.

The key takeaway for tonight, and for any time you see a patient with widespread, unexplained inflammation hitting multiple organ systems, is to think vasculitis. Is it large vessel, like Mrs. Henderson’s temporal headache, or small vessel, like Mr. Chen’s lungs and kidneys? Is it ANCA-positive or ANCA-negative? Knowing these broad categories helps you prioritize the workup and, more importantly, initiate life- and organ-saving treatment without delay. We'll dive into the specifics, but remember those two scenarios – they'll guide many of your urgent management decisions.

Introduction

Vasculitis encompasses a group of disorders characterized by inflammation and destruction of blood vessel walls. The clinical presentation depends on the size and distribution of the affected vessels. Early recognition is critical because untreated vasculitis can lead to irreversible organ damage and death. The internist must recognize clinical patterns, initiate appropriate workup, and begin treatment while awaiting rheumatology consultation.

Classification by Vessel Size

Large-Vessel Vasculitis

• Giant cell arteritis (GCA): temporal artery and aortic branches; age > 50
• Takayasu arteritis: aorta and major branches; typically young women

Medium-Vessel Vasculitis

• Polyarteritis nodosa (PAN): renal, mesenteric, and peripheral arteries; NOT associated with ANCA
• Kawasaki disease: coronary arteries; pediatric population

Small-Vessel Vasculitis (ANCA-Associated)

• Granulomatosis with polyangiitis (GPA): upper/lower respiratory tract, kidneys; c-ANCA/PR3
• Microscopic polyangiitis (MPA): kidneys, lungs; p-ANCA/MPO
• Eosinophilic granulomatosis with polyangiitis (EGPA): asthma, eosinophilia, neuropathy; p-ANCA/MPO in ~40%

Small-Vessel Vasculitis (Immune Complex)

• IgA vasculitis (Henoch-Schonlein purpura): palpable purpura, arthritis, abdominal pain, nephritis
• Cryoglobulinemic vasculitis: associated with hepatitis C; purpura, arthralgia, glomerulonephritis

Giant Cell Arteritis

Clinical Features

• Age > 50; most common primary systemic vasculitis in older adults
• New-onset headache (temporal), scalp tenderness, jaw claudication
• Visual symptoms: amaurosis fugax, diplopia, irreversible vision loss if untreated
• Constitutional symptoms: fever, weight loss, fatigue
• Polymyalgia rheumatica (PMR) coexists in 40-60% of GCA patients

Diagnosis

• ESR and CRP: almost always markedly elevated; normal values make GCA unlikely
• Temporal artery biopsy: gold standard; obtain within 2 weeks of starting steroids (inflammation persists)
• Biopsy should be >= 1 cm; skip lesions can cause false negatives; consider bilateral biopsy
• Temporal artery ultrasound: halo sign; increasingly used as non-invasive alternative

Management

• Do NOT wait for biopsy to start treatment if clinical suspicion is high
• Prednisone 60 mg daily for uncomplicated GCA; taper over 12-24 months
• IV methylprednisolone (1 g daily for 3 days) if visual symptoms present
• Tocilizumab: steroid-sparing agent; FDA-approved for GCA; enables faster taper
• Low-dose aspirin for vascular event prevention

ANCA-Associated Vasculitis

Granulomatosis with Polyangiitis (GPA)

• Classic triad: upper airway disease (sinusitis, nasal crusting, saddle-nose deformity), pulmonary involvement (nodules, cavitary lesions, diffuse alveolar hemorrhage), glomerulonephritis
• Associated with c-ANCA (anti-PR3 antibodies)
• Can present with subglottic stenosis, orbital pseudotumor, mononeuritis multiplex

Microscopic Polyangiitis (MPA)

• Rapidly progressive glomerulonephritis and pulmonary capillaritis/alveolar hemorrhage
• Associated with p-ANCA (anti-MPO antibodies)
• No granulomatous inflammation (distinguishes from GPA)
• Renal biopsy shows pauci-immune crescentic glomerulonephritis

Diagnosis

• ANCA testing: c-ANCA/PR3 for GPA; p-ANCA/MPO for MPA
• Urinalysis: dysmorphic RBCs, RBC casts, proteinuria
• Renal biopsy: pauci-immune crescentic GN is characteristic
• CT chest: nodules, cavitary lesions, ground-glass opacities
• Tissue biopsy when possible for definitive diagnosis

Urgent Management

• Organ-threatening disease (pulmonary hemorrhage, RPGN): pulse IV methylprednisolone + rituximab or cyclophosphamide
• Rituximab is preferred for induction in most cases (RAVE trial: noninferior to cyclophosphamide)
• Plasma exchange: consider in severe renal disease (creatinine > 5.7 mg/dL) or diffuse alveolar hemorrhage (PEXIVAS trial showed mortality benefit uncertain but used in practice)
• Avacopan (complement C5a receptor inhibitor): approved as adjunctive therapy; may reduce glucocorticoid exposure

Maintenance Therapy

• Rituximab every 6 months or azathioprine: for remission maintenance
• Duration: minimum 2 years; relapse is common, especially in PR3-positive disease
• Monitor ANCA titers, renal function, and urinalysis regularly

Polyarteritis Nodosa

• Medium-vessel vasculitis; ANCA-negative
• Associated with hepatitis B in some cases
• Mesenteric ischemia, renal artery aneurysms, mononeuritis multiplex, livedo reticularis, skin nodules
• No glomerulonephritis or pulmonary capillaritis (distinguishes from ANCA-associated vasculitis)
• Diagnosis: angiography showing microaneurysms; tissue biopsy
• Treatment: corticosteroids +/- cyclophosphamide; treat hepatitis B if associated

When to Suspect Vasculitis

• Multisystem disease without a unifying diagnosis
• Unexplained constitutional symptoms with end-organ damage
• Palpable purpura, mononeuritis multiplex, unexplained renal failure with active sediment
• Pulmonary-renal syndrome (alveolar hemorrhage + glomerulonephritis)
• New headache or visual symptoms in a patient > 50 with elevated inflammatory markers

Key Clinical Pearls

• Start high-dose corticosteroids immediately for suspected GCA with visual symptoms; do not wait for biopsy
• ANCA-associated vasculitis presenting with pulmonary-renal syndrome is a medical emergency
• PAN is ANCA-negative and does not cause glomerulonephritis or pulmonary capillaritis
• Rituximab is noninferior to cyclophosphamide for ANCA-associated vasculitis induction and is preferred for most patients
• Always check urinalysis and creatinine in suspected vasculitis; silent renal involvement is common

References

1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1-11.
2. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE). N Engl J Med. 2010;363(3):221-232.
3. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47.
4. Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33(8):1122-1128.

For the intern

When called at 3am for suspected vasculitis, assess for vision changes in patients >50 (possible giant cell arteritis) and pulmonary-renal syndrome (hemoptysis with rising creatinine suggests ANCA vasculitis). Start prednisone 60 mg immediately for suspected GCA—never delay for biopsy if vision is threatened. For pulmonary hemorrhage or rapidly progressive glomerulonephritis, give IV methylprednisolone 1 g, check ANCA, get urgent renal consultation, and arrange ICU transfer if respiratory compromise exists. Order ESR, CRP, urinalysis with microscopy, creatinine, CBC, chest X-ray, and ANCA panel. Non-urgent evaluation (constitutional symptoms, rash, neuropathy without airway compromise) can wait until morning rounds with attending review, but obtain basic labs and urinalysis overnight.

Common pitfalls

• Waiting for temporal artery biopsy before starting steroids in suspected GCA—irreversible vision loss can occur within hours; biopsy remains positive for 2 weeks after treatment initiation
• Assuming negative ANCA excludes ANCA-associated vasculitis—10-20% of active disease is ANCA-negative; tissue biopsy showing pauci-immune crescentic glomerulonephritis confirms diagnosis
• Missing renal involvement—always check urinalysis and creatinine even without urinary symptoms; silent glomerulonephritis is common and progresses rapidly
• Confusing polyarteritis nodosa with ANCA vasculitis—PAN is ANCA-negative and doesn't cause glomerulonephritis or pulmonary capillaritis despite being severe systemic vasculitis

Make it stick

Imagine you're on call overnight and get a page about a 68-year-old patient presenting with a new, severe headache, jaw pain with chewing, and transient vision loss in one eye. Your gut says "GCA." Remember, this is a true ophthalmic emergency. While you order the ESR and CRP, and make a plan for a temporal artery biopsy the next day, the absolute priority is to start high-dose steroids (prednisone 60mg daily, or IV methylprednisolone if vision loss is more pronounced) immediately. Waiting for biopsy results could mean permanent blindness for the patient. You can always taper steroids if the biopsy is negative, but you can't reverse vision loss.

If you remember one thing

For Giant Cell Arteritis (GCA), never delay steroids for biopsy if vision is threatened; prompt treatment can prevent irreversible blindness. For ANCA-associated vasculitis, recognize the urgency of pulmonary-renal syndrome and initiate high-dose steroids and consult specialists immediately.

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