Vasculitis

 

• Background

  • Vessel inflammation leads to vessel wall damage, and in turn bleeding, stenosis, and ischaemia. Aneurysms may develop around stenosed segments.
  • Categorised by size, but some overlap between size categories.
  • Giant cell arteritis and granulomatosis with polyangiitis (GPA) are the commonest primary vasculitides.

  Classification

  Large vessel vasculitis:

  • Generally very dangerous due to the risks of impaired blood flow in such large vessels.
  • Conditions: giant cell arteritis (aka temporal arteritis), takayasu's arteritis.

  Medium vessel vasculitis:

  • Conditions: polyarteritis nodosa (PAN), Kawasaki's disease.

  Small vessel vasculitis:

  • Affects the arterioles, venules, and/or capillaries.
  • Types: immune-complex related vasculitis, ANCA-associated vasculitis (also affect medium vessels), anti-GBM disease, cryoglobulinaemic vasculitis, IgA vasculitis (Henoch-Schonlein purpura).

  Variable vessel vasculitis:

  • Behcet's disease.
  • Cogan's syndrome.

• Vasculitic purpura

  The most common symptom seen across all vasculitides is a palpable, painful, purpuric rash.

  In vasculitis, purpura occur because of vessel wall damage leading to blood leakage. The other cause of purpura are clotting problems, either thrombocytopenia or clotting factor deficiencies (e.g. DIC).

  Distinguishing features of vasculitic purpura:

  • Feel: vasculitic purpura are raised and palpable – due to inflammatory infiltrate – while coagulopathic purpura are flat.
  • Distribution: vasculitic purpura are more often localised, especially in the shins, versus a more widespread rash seen in clotting problems.
  • Progression: vasculitic purpura often blister, then may necrose and ulcerate, while retaining an actively-inflamed, purple/red edge.
  • Size: numerous small lesions suggests small vessel disease. Few big lesions suggests large vessel disease.

  Livedo reticularis:

  • Swelling of medium vessels in cold temperature to give a corn-beef look to skin.
  • It may be a feature of medium-vessel vasculitis, especially if patchy and with ulceration, but is usually idiopathic and benign.

• Investigations

  • There is rarely a single specific diagnostic test, but rather a combination of symptoms, biopsy, serology, and imaging (for large vessels).
  • Bloods include inflammatory markers, ANCA, and U&E (renal involvement).
  • Urinalysis is also performed to assess renal involvement.
  • Consider investigating secondary causes of vasculitis e.g. echo (endocarditis), LP (meningococcal disease).
  • Biopsies should target the most affected organ; lung and kidney are most likely to yield a diagnosis, but skin and mucosa may also be useful.
  • Birmingham vasculitis activity score (BVAS) can be used for monitoring.

• Immune-complex related vasculitis

  Pathophysiology

  • Type 3 hypersensitivity: immune-complex deposition, which attracts neutrophils and complement leading to vessel wall damage.
  • Characterised by palpable purpura, especially on the shins.

  Hypersensitivity vasculitis

  • Aka allergic vasculitis.
  • There is a lot of ambiguity and confusion about terminology here. The term hypersensitivity vasculitis sometimes refers specifically to an idiopathic or drug-induced vasculitis, while in a broader definition, it is synonymous with all immune-complex vasculitides.
  • It is also sometimes synonymous with leukocytoclastic vasculitis, which is a non-specific pathological term describing neutrophil infiltration and destruction of small vessels, seen in immune-complex vasculitis, some ANCA-associated vasculitis, and PAN.
  • Drug-induced vasculitis is most commonly due to antibiotics (penicillins and cephalosporins), diuretics (loop and thiazide), phenytoin, or allopurinol.
  • Skin involvement is a defining feature of hypersensitivity vasculitis, and when it is limited to the skin the term cutaneous leukocytoclastic angitis/vasculitis or cutaneous small-vessel vasculitis is used. This has a good prognosis, relative to the poorer prognosis of systemic vasculitis involving internal organs such as the kidney. No specific treatment is usually needed.

  Other immune-complex vasculitides

  • Cryoglobulinaemic vasculitis. Often due to hepatitis C.
  • Henoch-Schonlein purpura.
  • Septic vasculitis: infective endocarditis, meningococcal disease.
  • Connective tissue disease vasculitis: SLE, RA, Sjogren's.
  • Behcet's
  • Serum sickness vasculitis.

• Takayasu's arteritis

  Pathophysiology and epidemiology

  • Granulomatous inflammation affecting the aorta or its proximal branches.
  • Causes stenosis and aneurysms.
  • Commoner in young females and Asians.

  Signs and symptoms

  • Systemic symptoms early on: fatigue, fever, weight loss, headache, myalgia.
  • Uneven BP between arms. Radial and brachial pulse may be absent on one side.
  • Bruits: carotid, subclavian, brachial, abdominal aorta.
  • Aortic regurgitation.
  • Limb claudication.
  • Hypertension due to renal artery stenosis.
  • Subclavian steal syndrome: lesion proximal to vertebral artery origin causing neuro symptoms.

  Management

  • Corticosteroids (e.g. prednisolone) are 1st line. Add methotrexate or azathioprine if needed.
  • Angioplasty or valve replacement may be needed in some.

• Polyarteritis nodosa (PAN)

  Pathophysiology and epidemiology

  • Necrotizing vasculitis of medium and small arteries, causing aneurysms, bleeds, and thrombosis.
  • ANCA -ve and does not cause glomerulonephritis.
  • Very rare, but commonest in middle-aged and in men.
  • 20% are triggered by hepatitis B or C.

  Signs and symptoms

  • Constitutional: general malaise, fever, weight loss, arthralgia, myalgia.
  • Skin: palpable purpura, ulcerations, tender nodules, livedo reticularis.
  • Neuro: asymmetric peripheral neuropathy (including mononeuritis multiplex), TIA.
  • Renal impairment due to ischaemia, with haematuria and proteinuria.
  • Abdominal pain from visceral vasculitis.

  Management

  • Corticosteroids (e.g. prednisolone) are 1st line. Add methotrexate or azathioprine if needed.
  • Cyclophosphamide if organ involvement.