Vasculitis

Vasculitis - a group of inflammatory disorders that result in inflammation and necrosis of blood vessels with subsequent impairment of blood flow resulting in ischaemia and infarction of distal tissues.

Presentation

Large-vessel vasculitis: limb claudication, vascular bruits, asymmetric blood pressures, or absence of pulses
Medium-vessel vasculitis: cutaneous nodules and ulcers, livedo reticularis, digital gangrene, mononeuritis multiplex, and renovascular hypertension
Small-vessel vasculitis: palpable purpura, pulmonary-renal syndromes, urticarial skin rashes, and scleritis

Histologic findings:

Characteristic - infiltration of vessel wall by neutrophils/mononuclear cells/giant cells; fibrinoid necrosis with pan-mural destruction of the vessel wall; leukocytoclasis
Peri-vascular infiltration alone is quite non-specific and not necessarily reflective of vasculitis

Large-vessel vasculitis:

Takayasu arteritis
GCA/Temporal arteritis
- Epidemiology
  - Primarily >50yo, and increasing with age
  - Mostly caucasians
  - F:M 2:1
- Pathophysiology
  - Exact cause unknown
  - Probably in response to immunologic injury, the artery induces myofibroblasts which leads to new vessel formation and marked thickening of intima
  - This leads to vessel occlusion leading to symptoms of ischaemia
- Clinical
  - New-onset headache
  - Scalp tenderness
  - Reduced pulse and tenderness along temporal artery
  - Jaw and tongue claudication (specific)
  - Diplopia (specific)
  - Blindness
  - Systemic inflammation
  - PMR (although only 10-20% of patients with PMR develop GCA)
  - Check for bilateral pulses and BPs - 20% have large-vessel vasculitis
  - ICA and vertebral arteries can be involved, leading to stroke/seizure/acute hearing loss/vertigo/cerebral dysfunction and depression
- Diagnosis
  - Gold standard test if temporal artery biopsies
    - Up to 50% of biopsies show diffuse lymphocytic infiltrate without evidence of granulomatous inflammation or giant cells
    - Fraying of the internal elastic lamina is a non-specific finding of normal aging, and should be ignored in the absence of inflammation
- Medical treatment
  - Corticosteroid therapy - 40-60mg daily, maintaining the dose until inflammatory markers normalise
    - Reduce prednisolone by 5mg every 1-2 weeks down to 30mg/day, then 2.5mg every 1-2 weeks until 15mg per day, then 2.5mg every 4 weeks until 10mg, then 1mg every 4 weeks until the patient is off prednisolone
  - IV methylpred if visual loss is present for 3 days
  - Start on low-dose aspirin to reduce risk of cardiovascular events and blindness
- Surgical treatment
  - Revascularisation is rare required
Idiopathic aortitis
- Idiopathic retroperitoneal fibrosis
  - Presents 40-60yo
  - Pain in lower back, abdomen, flank and scrotum
  - Some have systemic symptoms
  - Most have elevated inflammatory markers
  - CT - homogenous mass around the aorta following the iliac bifurcation, with medialisation of ureters and associated hydronephrosis. Usually, lymphadenopathy is absent.
  - Pathophysiology unknown
  - Treat with high-dose prednisolone
- IgG4-related systemic disease
- Erdheim-Chester disease
  - Periaortic fibrosis ('coated aorta')
  - Hairy kidney
  - Main distinguishing factor from RPF/IgG4 is that bones are involved

Medium-vessel vasculitis

Polyarteritis nodosa
- Pathophysiology
  - Necrotising vasculitis or small and medium arteries
  - Characterised by the absence of glomerulonephritis and absence of ANCA antibodies
  - Can be idiopathic or secondary to HBV infection or other viral infections
  - Also seen as a paraneoplastic manifestation of haematology malignancy
- Diagnosis
- Presentation
  - Constitutional symptoms and organ dysfunction - see above
Thromboangitis obliterans (Buerger disease)
- See separate topic)
Kawasaki disease
- Acute vasculitis
- Typically seen in children
- Involvement of small/medium arteries, especially coronary arteries
- Main cause of death is MI
- Treat with high-dose aspirin and IVIg

Small-vessel vasculitis

Antineutrophil cytoplasmic antibody-associated vasculitis
Granulomatosis with polyangiitis
- Previously Wegener granulomatosis
- Granulomatous vasculitis of the upper and lower respiratory tract
- Also causes pauci-immune focal, segmental, crescentic glomerulonephritis
- Clinical presentation
  - Chronic sinusitis
  - Epistaxis
  - Chronic purulent nasal drainage
  - Chronic inflammation of the auditory canal - acute suppurative otitis media and chronic serous otitis media
  - Hoarseness, subglottic stenosis
- Investigations
  - 90% ANVA positive
- Treatment - steroids
Microscopic polyangiitis
- Systemic necrotising vasculitis of small vessels
- Associated with ANCA formation
- No granulomas
Eosinophilic granulomatosis with polyangiitis
- Previously known as Churg-Strauss syndrome
- Associated with eosinophilia - 70% of patients have a history of some sort of atopic disease

Vasculitis secondary to connective tissue disease

Behcet disease
- Systemic vasculitis of unknown aetiology
- Classically presents with oral and genital ulcers, uveitis, skin lesions, vascular manifestations
- Vascular manifestations - aneurysms at unusual locations (especially pulmonary arteries), arterial and venous thrombosis including Budd-Chiari syndrome
SLE
- Chronic multisystem autoimmune disease characterised by autoantibodies to various nuclear antigens
- Vasculitis occurs in 30% of SLE patients - most commonly affects small vessels of the skin
- Tender punctate lesions on fingertips and palms
- Inflammatory vasculitis in SLE merits escalation of therapy with steroids and DMARDs
- Ischaemic events related to the antiphospholipid syndrome may mimic vasculitis in SLE, and should be considered when SLE patients present with digital and skin ulcerations
Rheumatoid vasculitis
Relapsing polychondritis
Cogan syndrome
Pseudoxanthoma elasticum
Exercise-related external iliac arteriopathy

Vascular mimics

Fibromuscular dysplasia
- Non-inflammatory vascular disease, most commonly affecting the carotid and renal arteries, but can affect any vascular bed
Radiation arteritis
- Particularly common in carotid arteries
- Reasonable results from stenting
Neurofibromatosis type 1
- Autosomal dominant disorder that results in a loss-of-function mutation of the tumour suppressor gene NF-1
- Neurofibromas, schwannomas, phaechromocytomas
- Vascular lesions are rare but can resemble FMD
Drug-induced vasculitis
- Chemotherapeutic agents, growth factors, interferons, antithyroid drugs, hydrochlorothiazide, hydralazine, minocycline, penicillamine, vaccines

Vasculitis affecting GIT

Presentation
- Mesenteric ischaemia
- Ischaemic colitis
- NOMI
- Strictures
- Ischaemic hepatitis
When to suspect
- Patients with symptoms of bowel ischaemia, but no risk factors for macrovascular disease
Diagnosis
- Specific serologic testing
- CT angiogram will usually pick something up

Aortitis -

'inflammatory aortic conditions that cannot be attributed to atherosclerosis alone.'

Periaortitis - 'inflammatory process arising from the adventitia of the aortic wall and extending into the surrounding periaortic space'. Mostly affects lower abdominal aorta and CIAs. Consider idiopathic retroperitoneal fibrosis.

Clinically - usually back or flank pain, which is usually persistent, not exacerbated by movement or palpation. It transiently responds to NSAIDs. Ureteral symptoms can ensue.

Pathophysiology

Involves the media and/or intima, and sometimes the adventitia too

Aetiology

Infectious
- Septic emboli (typically infective endocarditis)
- As a complication of bacteraemia
- Most commonly Salmonella, Staphylococci and Pneumococci
- Can be bacterial, viral or fungal
Non-infectious (far more common)
- Large-vessel vasculidites
  - GCA
  - Takayasu arteritis
- Complication of many rheumatological diseases
  - ANCA-associated vasculitis
  - SLE
  - RA
  - Ankylosing spondylitis
  - Behcet disease

Retroperitoneal fibrosis: