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

Giant cell arteritis (temporal arteritis)

• Giant cell arteritis, i.e. temporal arteritis is discussed in another article: see Giant Cell (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 ) 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.