19.1 Vasculitis Classification, Large and Medium Vessel Disease

Systemic vasculitides and crystal arthropathies are prominent, high-yield components of the MRCP(UK) Part 1 curriculum. Candidates are expected to master the vessel-size classification of vasculitis, the immunological distinctions between ANCA autoantibodies, emergency sight-saving protocols, and the biophysical and therapeutic contrasts between monosodium urate and calcium pyrophosphate crystals.

1. Systemic Vasculitis: The Chapel Hill Consensus Classification

Systemic vasculitides are inflammatory diseases characterized by mural destruction, necrosis, and lumen occlusion of blood vessels. The standard international taxonomy is the 2012 Revised Chapel Hill Consensus Conference (CHCC) classification, which stratifies vasculitides primarily by the predominant calibre of blood vessel involved:

                  Chapel Hill Consensus Classification of Vasculitis
                                          |
         +--------------------------------+--------------------------------+
         |                                |                                |
    Large Vessel                    Medium Vessel                    Small Vessel
(Aorta & major branches)      (Main visceral arteries)         (Arterioles, capillaries, venules)
         |                                |                                |
- Giant Cell Arteritis        - Polyarteritis Nodosa           +-------------------+
  (Temporal arteritis, >50y)    (Spares lungs! Hep B linked)   |                   |
- Takayasu's Arteritis        - Kawasaki Disease         ANCA-Associated    Immune Complex
  (Pulseless disease, <40y)     (Children; coronary         (Pauci-immune)      (Deposition)
                                 aneurysms)                    |                   |
                                                         - GPA (c-ANCA/PR3) - IgA Vasculitis
                                                         - MPA (p-ANCA/MPO)   (HSP; purpura/GI)
                                                         - EGPA (p-ANCA/MPO - Cryoglobulinaemic
                                                           + eosinophils)     (HCV; low C4)

2. Large Vessel Vasculitides

Giant Cell Arteritis (GCA / Temporal Arteritis)

• Epidemiology: The most common systemic vasculitis in adults. Restricted to patients age > 50 years (incidence peaks between 70 and 80 years), with a female-to-male ratio of 3:1. Prevalent in populations of Northern European descent.
• Association with Polymyalgia Rheumatica (PMR): Approximately 50% of GCA patients exhibit symptoms of PMR (severe bilateral aching and morning stiffness in the shoulder and pelvic girdles lasting > 45 minutes, with normal muscle power and completely normal serum CK). Conversely, 15–20% of PMR patients harbor occult GCA.
• Clinical Features:
  • New-Onset Headache: Typically temporal or occipital, severe, boring or throbbing.
  • Scalp Tenderness: Pain when brushing hair or resting head on a pillow, reflecting ischemia of the superficial temporal and occipital arteries.
  • Temporal Artery Signs: Thickened, tortuous, tender, nodular, or pulseless superficial temporal artery.
  • Jaw Claudication: Fatigue, cramping pain, or aching in masseter and temporalis muscles during mastication (eating meat/bread) or speaking, secondary to ischemia of maxillary and facial arterial branches. Exam pearl: Jaw claudication has the highest positive likelihood ratio (~4.2) for biopsy-proven GCA.
  • Visual Loss (The Feared Emergency): Sudden, painless, unilateral or bilateral visual loss resulting from anterior ischaemic optic neuropathy (AION) secondary to granulomatous occlusion of the posterior ciliary arteries (branches of the ophthalmic artery supplying the optic nerve head). Fundoscopy reveals a pale, swollen, edematous optic disc with flame-shaped splinter hemorrhages. Alternatively, patients describe transient monocular visual loss (amaurosis fugax) as an ominous warning sign before permanent blindness.
  • Extracranial Large-Vessel Involvement: Aortitis causing thoracic aortic aneurysm, aortic dissection, or aortic branch claudication in up to 15%.
• Investigations:
  • Inflammatory Markers: Markedly elevated ESR (characteristically > 50 mm/h, frequently > 100 mm/h) and elevated CRP. Note: A normal ESR does not absolutely exclude GCA if clinical suspicion is high (up to 4% have normal ESR, but CRP is almost universally elevated).
  • Temporal Artery Ultrasound: Non-invasive first-line imaging. Shows a pathognomonic hypoechoic, circumferential wall thickening ("halo sign") representing mural oedema, which compresses with probe pressure.
  • Temporal Artery Biopsy (TAB): The definitive histological gold standard. Demonstrates transmural granulomatous inflammation, infiltration of macrophages and T-cells, fragmentation and disruption of the internal elastic lamina, and multinucleated giant cells (present in 50–75%). Because the inflammation is segmental with normal intervening arterial segments ("skip lesions"), the biopsy specimen must be at least 2 to 3 cm in length.
• Emergency Management Protocol:
  • CRITICAL EXAM RULE: Never delay systemic corticosteroid therapy while awaiting temporal artery biopsy or ultrasound! Corticosteroid therapy does not compromise biopsy histopathology if performed within 2 to 4 weeks of initiation.
  • Uncomplicated GCA (No Visual Symptoms): Immediate oral prednisolone 40–60 mg daily (or 1 mg/kg/day).
  • Complicated GCA (Evolving Visual Symptoms, Amaurosis Fugax, or Visual Deficit): Medical emergency! Requires immediate high-dose intravenous pulsed methylprednisolone (500–1,000 mg IV daily for 3 consecutive days) prior to converting to oral prednisolone, in an urgent attempt to salvage vision in the affected eye and prevent catastrophic spread to the contralateral eye.
  • Steroid-Sparing Biologic: Tocilizumab (anti-IL-6 receptor monoclonal antibody) is approved under UK NICE guidelines for relapsing or refractory GCA, significantly reducing cumulative corticosteroid toxicity.

Takayasu's Arteritis

• Epidemiology: Chronic granulomatous panarteritis targeting the aorta, its primary branches (subclavian, common carotid, renal), and pulmonary arteries. Strongly affects young females < 40 years (peak age 15–30), particularly of East Asian, Indian, and Hispanic origin.
• Clinical Presentation: Biphasic course: (1) Early systemic/pre-pulseless phase: fever, night sweats, fatigue, arthralgias, weight loss, carotidynia (tenderness over carotids); (2) Late occlusive/pulseless phase: "Pulseless disease"—absent or diminished radial/brachial pulses, limb claudication (forearm or calf pain upon exertion), blood pressure discrepancy > 10 mmHg between arms, vascular bruits (carotid, subclavian, abdominal aorta), renovascular hypertension (secondary to renal artery stenosis), and aortic regurgitation.
• Diagnosis: CT/MR angiography demonstrates smooth, long, circumferential arterial wall thickening, segmental stenosis, occlusion, or post-stenotic aneurysm formation involving the aorta and primary branches.
• Management: High-dose systemic corticosteroids; csDMARDs (methotrexate, leflunomide) or biologics (tocilizumab, infliximab). Surgical or endovascular revascularization (bypass grafting, angioplasty) must be delayed until active systemic vascular inflammation is completely suppressed.

3. Medium Vessel Vasculitides

Polyarteritis Nodosa (PAN)

Polyarteritis nodosa is a systemic necrotizing vasculitis that characteristically targets medium-sized and small muscular arteries, sparing arterioles, venules, and capillaries.

• CRITICAL EXAM PEARL — PULMONARY SPARING: Polyarteritis nodosa strictly spares the pulmonary circulation. There are no pulmonary infiltrates, no cavitating nodules, and no alveolar haemorrhage (pulmonary involvement categorically points to an ANCA-associated vasculitis instead).
• Association with Hepatitis B Virus: Between 10% and 30% of classic PAN cases are directly linked to active Hepatitis B virus (HBV) infection (HBsAg-positive), driven by deposition of HBsAg-anti-HBs immune complexes in arterial walls; can also rarely associate with Hepatitis C.
• Clinical Features:
  • Systemic: Fever, weight loss, severe myalgias, arthralgias.
  • Cutaneous: Livedo reticularis (violaceous, reticulated net-like cyanotic vascular mottling), painful subcutaneous erythematous nodules (representing inflamed, thrombosed subcutaneous arteries), deep punched-out skin ulcers, and digital ischemia/gangrene.
  • Neurological: Mononeuritis multiplex occurs in > 50–70% of patients—asymmetric, asynchronous, painful sensorimotor neuropathy affecting non-contiguous peripheral nerves (e.g. acute right wrist drop [radial nerve] followed days later by left foot drop [peroneal nerve]), caused by necrotizing arteritis of the vasa nervorum.
  • Renal: Ischemia, renal microinfarctions, and severe renovascular hypertension secondary to renal artery stenoses. Crucial point: Classic PAN does NOT cause glomerulonephritis because it targets medium muscular arteries rather than glomerular capillaries.
  • Gastrointestinal: Severe postprandial abdominal pain ("abdominal angina"), mesenteric ischemia, bowel infarction, and cholecystitis.
  • Orchitis: Unilateral or bilateral testicular pain and tenderness.
• Diagnostic Investigations:
  • Serology: ANCA is characteristically NEGATIVE in classic PAN. Screening for Hepatitis B (HBsAg, HBeAg, HBV DNA) and Hepatitis C is mandatory.
  • Catheter Angiography (Renal / Mesenteric): Demonstrates diagnostic saccular or fusiform microaneurysms (1–5 mm) alternating with focal segmental stenoses, producing the classical "string of beads" (rosary sign) appearance.
  • Biopsy (Deep Skin / Sural Nerve / Testis): Transmural, focal, segmental necrotizing arteritis with fibrinoid necrosis and dense pleomorphic infiltration of neutrophils and mononuclear cells, with destruction of the internal elastic lamina. Healed lesions display fibrous endarteritis obliterans without granulomas.
• Management:
  • Idiopathic (Non-HBV) PAN: High-dose systemic corticosteroids combined with intravenous cyclophosphamide for organ-threatening disease.
  • HBV-Associated PAN: Corticosteroids must be limited to a short, tapering course to control acute life-threatening inflammation, combined with plasma exchange (to clear circulating immune complexes) and immediate antiviral therapy with potent reverse-transcriptase inhibitors (entecavir or tenofovir). Long-term immunosuppression is strictly avoided as it fuels fulminant HBV replication.

Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)

Acute, self-limiting necrotizing medium-vessel vasculitis occurring almost exclusively in infants and young children (< 5 years). Characterized by high prolonged fever (> 5 days) plus at least 4 of: bilateral non-purulent conjunctivitis, strawberry tongue / cracked lips, polymorphous rash, indurative oedema of hands/feet with periungual desquamation, and unilateral cervical lymphadenopathy. Major complication: Coronary artery aneurysms (in 20–25% of untreated cases). Managed with single high-dose intravenous immunoglobulin (IVIG 2 g/kg) plus high-dose aspirin (the rare pediatric condition where aspirin is indicated despite Reye's syndrome risk).