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TomPettersson

Vasculitides

Essentials

  • Vasculitis has to be taken into account when the patient presents with systemic symptoms or ischaemic organ damage.

General

  • The vasculitides are a rare and heterogenous group of clinical syndromes characterized by inflammation and injury of blood vessels. The vascular damage may cause narrowing of the vascular lumen, thrombosis, ischaemia, aneurysm or haemorrhage.
  • They are often serious but still treatable disorders.
  • Because of a variable clinical picture the diagnosis may be delayed.
  • The size and the localization of the affected blood vessel determine the clinical picture.

Symptoms and signs of vasculitis

  • Fever and weight loss
  • Palpable purpura, livedo reticularis, skin wounding and skin necrosis
  • Myalgia, myositis, arthralgia, arthritis
  • Mononeuritis multiplex, stroke
  • Epistaxis, sinusitis, haemoptysis, pneumonitis, asthma
  • Myocardial infarction, hypertension, intermittent claudication, weak peripheral pulses
  • Abdominal pain, melena
  • Glomerulonephritis
  • Elevated ESR, high serum CRP value, anaemia, leucocytosis, thrombocytosis, proteinuria, haematuria, anti-nuclear cytoplasmic antibodies (ANCAs)

Classification of the vasculitides

Large vessel vasculitis

Medium-sized vessel vasculitis

Small vessel vasculitis

  • Vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA-associated vasculitis)
    • Microscopic polyangiitis
    • Granulomatosis with polyangiitis (formerly Wegener's granulomatosis)
    • Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
  • Immune complex vasculitis
    • IgA vasculitis (formerly Henoch-Schönlein purpura Henoch-Schönlein Purpura
    • Cryoglobulinaemic vasculitis
    • Hypocomplementaemic urticarial vasculitis
    • Goodpasture syndrome

Giant cell arteritis (temporal arteritis)

Takayasu's arteritis

  • Most common in young women of Asian descent. Damages the aorta and its main branches.
  • In the early phases, nonspecific symptoms such as malaise, arthralgias and myalgias are frequent. Increased ESR and serum CRP concentration.
  • Signs of narrowing of the arteries develop gradually.
  • Weakened pulses in the upper extremities and difficulty measuring the blood pressure.
  • Central nervous system manifestations
  • The diagnosis is based on confirmation of arterial stenosis by clinical examination and by angiography.

Polyarteritis nodosa

  • A serious disease that most frequently affects middle-aged males
  • General symptoms: fever, weight loss, malaise
  • Arthralgia and myalgia occur frequently.
  • Gastrointestinal symptoms, such as vomiting, diarrhoea and abdominal pain are seen in about half of the patients. Haematemesis, melena and intestinal perforation may occur.
  • Coronary arteritis may lead to myocardial infarction or heart failure.
  • Renal disease, most often renal arteritis, which manifests as haematuria, proteinuria, renal insufficiency and hypertension
  • Mononeuritis multiplex is the most typical neurological manifestation and occurs in one-half or more of all cases.
  • Cerebral haemorrhage occurs in 10% of patients.
  • Occasionally eye manifestations, such as episcleritis, uveitis and retinal haemorrhages are present.
  • Cutaneous manifestations, such as exanthema and purpura are seen in 30% of all cases.
  • The ESR and serum CRP level are elevated. Anaemia, neutrophilic leucocytosis, thrombocytosis, proteinuria, haematuria and a raised serum creatinine concentration are frequent findings.
  • In the classic form of the disease anti-nuclear cytoplasmic antibodies are not found.
  • Hepatitis B surface antigen and antibody have been found in more than 15% of patients.
  • The diagnosis is based on the clinical picture and on evidence of vasculitis obtained at biopsy or arteriography.

Microscopic polyangiitis

  • A vasculitis that preferentially affects small arteries and arterioles.
  • In more than 90% of the cases there is a focal segmental necrotizing glomerulonephritis, which may be the only manifestation of the disease.
  • Other manifestations include lung infiltrates, haemoptysis, arthralgia, myalgia, mononeuritis multiplex, purpura and fever.
  • ANC-antibodies (most commonly p-ANC/MPO antibodies) are found in most patients. Findings in blood and urine tests are otherwise similar to those in granulomatosis with polyangiitis.
  • The diagnosis is based on the clinical picture, biopsy findings and a positive ANCA test.

Granulomatosis with polyangiitis (Wegener's granulomatosis)

  • Patients typically present with fever, weight loss and upper respiratory tract symptoms such as sinusitis and bloody nasal discharge.
  • There may be episcleritis, conjunctivitis and arthritis or arthralgia.
  • During the course of the disease, a cough with purulent or bloody sputum develops. Chest radiographs show single or multiple nodular infiltrates.
  • Renal involvement is common and varies from mild focal segmental glomerulonephritis to rapidly progressive crescentic glomerulonephritis.
  • Skin manifestations include palpable purpura, subcutaneous nodules and skin ulcerations.
  • The most typical symptom of the peripheral nervous system is mononeuritis multiplex.
  • A typical but rather rare symptom is proptosis, i.e. protrusion of the eyeball out of the orbita.
  • Destructive lesions like septal perforation or the so-called saddle-back deformation may develop in the nose.
  • Obstructive inflammation may occur in the trachea and in the bronchi.
  • The ESR and serum CRP concentration are elevated.
  • Anaemia, neutrophilic leucocytosis and thrombocytosis are found.
  • Urinalysis suggests glomerulonephritis.
  • c-ANC/PR3-antibodies are remarkably specific for granulomatosis with polyangiitis. Determination of these antibodies has made it possible to establish the diagnosis and commence the treatment earlier.
  • The diagnosis is based on the clinical picture, the ANCA test and biopsy findings.
    • Biopsy of the nasal mucosa or of the lung may show a vasculitis and a granulomatous inflammation.
    • Histological examination of a kidney biopsy typically shows a focal segmental necrotising glomerulonephritis.
  • The ANCA test should not be used as a screening test in cases where the probability of granulomatosis with polyangiitis is low.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

  • A rare disease, which occurs in patients with asthma or a history of allergy.
  • General symptoms: fever and weight loss
  • Glomerulonephritis and joint symptoms are more rare than in microscopic polyangiitis or in granulomatosis with polyangiitis.
  • Mono- and polyneuropathies
  • Coronary arteritis, myocarditis
  • Marked blood eosinophilia and an elevated plasma CRP concentration and ESR. ANC-antibodies of the p-ANC/MPO type are detected in about 40% of the patients.
  • Lung infiltrates on chest radiograph
  • The diagnosis is based on the clinical picture, a history of asthma or allergy, blood eosinophilia, lung infiltrates and typical biopsy findings.

IgA vasculitis (Henoch-Schönlein purpura)

  • See Henoch-Schönlein Purpura.
  • IgA vasculitis (formerly Henoch-Schönlein purpura; pictures 1 2 3 4) is most commonly seen in children, but may also occur in adults.
  • In 90% of all patients an upper respiratory tract infection has preceded the vasculitic symptoms by 1-3 weeks.
  • Arthralgia, arthritis, abdominal pain, melaena, haematemesis and haematuria may occur.
  • There is usually a spontaneous remission within a week but relapses may occur.
  • A chronic glomerulonephritis occurs rarely.
  • The diagnosis is based on the clinical picture. Skin biopsy shows a leucocytoclastic vasculitis with IgA precipitated in the vessel walls. The serum IgA concentration tends to be high.

Cryoglobulinaemic vasculitis

  • There may be an underlying infection, connective tissue disease, lymphoproliferative disease or liver disease.
  • The great majority of these are caused by hepatitis C virus. Hepatitis B virus may be the causative agent in a minority of cases and some are essential forms.
  • Mixed cryoglobulins have the properties of an immune complex vasculitis.
  • General symptoms: fatigue, weakness
  • Cutaneous manifestations in almost all patients: purpura, Raynaud's phenomenon, skin necrosis, leg ulcers
  • Other manifestations include arthralgias, proteinuria, haematuria, renal failure, hypertension, hepatomegaly, mono- or polyneuropathy and abdominal pain.
  • Elevated ESR, high titre of rheumatoid factor and low concentration of complement (particularly C4).

Differential diagnosis: secondary and pseudovasculitides

  • Infections such as septicaemia Sepsis, endocarditis Infective Endocarditis, Lyme borreliosis Lyme Borreliosis (LB), miliary tuberculosis
  • Systemic connective tissue diseases
  • Vasculitis associated with malignant tumours
  • Vasculitis associated with pharmaceuticals
  • Diseases of the vascular wall, e.g. arteriosclerosis, Buerger's disease, amyloidosis, calciphylaxis, vitamin C deficiency (scurvy)
  • Embolizations, such as atheromatous cholesterol embolization, endocarditis, mycotic aneurysms, atrial myxoma
  • Blood coagulation disorders such as DIC, TTP, HUS and the antiphospholipid syndrome
  • Vasospastic conditions, e.g drug abuse, phaeochromocytoma
  • Hypereosinophilic syndrome, hyperviscosity syndrome

Treatment principles Interventions for Renal Vasculitis in Adults, Interventions for Preventing and Treating Kidney Disease in Iga Vasculitis (Henoch-Schönlein Purpura)

  • If you suspect a vasculitis, refer the patient to specialized care for further investigations and treatment, as an emergency if necessary.
  • As for treatment, it is important to bear the possibility of secondary vasculitides or pseudovasculitides in mind. These should be excluded before the diagnosis of a primary vasculitis is established. There are different specific treatment options for these conditions according to the aetiology, like antimicrobial treatment for the triggering infection.
  • Vasculitides are treated with immunosuppressive agents, either glucocorticoids alone or together with cytotoxic drugs or B cell depleting biological drugs. In severe cases, the treatment is commenced with large-dose intravenous methylprednisolone and plasmafereses.
  • Hepatitis C virus -associated cryoglobulinemic vasculitis has been treated successfully with new virus-specific drugs without concurrent immunosuppression.
  • Vasculitides are treated in specialized hospital units.

References

  • 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. [PubMed]

Evidence Summaries