Vasculitides

Essentials

• Vasculitides are an uncommon and heterogeneous group of diseases characterized by inflammation and injury of a blood vessel wall. The vascular damage may cause narrowing of the vascular lumen, thrombosis, ischaemia, aneurysm or haemorrhage.
• The size and the location of the affected blood vessel determine the clinical picture and symptoms.
• Biopsy or imaging is used to diagnose vasculitis.
• In differential diagnosis, it is essential to exclude secondary vasculitis and pseudovasculitides.
• Vasculitides are often serious but still usually treatable disorders. Yet in some cases, delay of appropriate treatment may even be life-threatening.
• Vasculitis must be considered when the patient presents with unexpected multiple organ failure with systemic symptoms, progressing by increments, that could be explained by vascular wall damage.

Symptoms and signs of vasculitis

• Fever, fatigue, weight loss
• Palpable purpura, livedo reticularis, skin wounds and skin necrosis
• Myalgia, myositis, arthralgia, arthritis
• Dysfunction of the peripheral nervous system, headaches, cerebral infarction
• Epistaxis, persistent sinusitis, dyspnoea, haemoptysis, asthma
• Myocardial infarction, hypertension, intermittent claudication, weak peripheral pulses
• Abdominal pain, haematemesis, melaena
• Glomerulonephritis, renal failure
• Elevated ESR and CRP, anaemia, leucocytosis, thrombocytosis, proteinuria, haematuria, anti-nuclear cytoplasmic antibodies (ANCA)

Classification of the vasculitides

Giant cell arteritis (temporal arteritis)

• Giant cell arteritis is discussed in another article: see Giant Cell (Temporal) Arteritis.

Takayasu's arteritis

• Takayasu arteritis is a disease of women of childbearing age, and is rare in western countries, with inflammation mainly in the aorta and its main branches, such as the subclavian and carotid arteries.
• Coronary arteries may also be affected.
• Onset of the disease is insidious with nonspecific systemic symptoms: low-grade fever, fatigue, arthralgias and myalgias, and increased inflammatory markers.
• Signs of arterial narrowing develop gradually and there may be ischaemic pain and numbness of the upper extremities.
• Weakened pulses in the upper extremities and inter-arm blood pressure differential, bruits of inflamed arteries
• There may be vertigo, fainting and visual disturbances.
• Magnetic resonance angiography gives findings consistent with inflammation.

Polyarteritis nodosa (PAN)

• Damages medium-sized and small arteries of internal organs, leading to ischaemia or infarctions in target organs.
• The patients are mostly men aged 40 to 60 years.
• The incidence of PAN in Nordic countries is < 2/1 000 000.
• Systemic symptoms include fever, weight loss, malaise.
• Muscle and joint symptoms are common.
• As the disease becomes acute, intestinal haemorrhage or perforation, angina pectoris, myocardial infarction, hypertension, renal failure, mononeuritis multiplex, cerebral infarction
• Cutaneous manifestations such as livedo reticularis, subcutaneous nodules and necrosis
• Some patients have positive hepatitis B or C serology Viral Hepatitis.
• An association with underlying hairy cell leukaemia is also known.
• Magnetic resonance angiography will show arterial microaneurysms.
• Hereditary deficiency of adenosine deaminase 2 (DADA2) may be associated with PAN-type vasculitis.

ANCA-associated vasculitis

• Vasculitides associated with antineutrophil cytoplasmic antibodies
• Most cases are diagnosed in patients over 55 years.
• Common target organs include the lungs, nasal sinuses, renal corpuscle and skin.
• ANCA-associated vasculitis may also affect the nervous system or the conjunctiva of the eye.
• Rarer forms include subglottal stenosis, pachymeningitis, orbital pseudotumour.
• In addition to systemic symptoms, there are various symptoms depending on the target organ.
• In GPA and EGPA, there are granulomatous changes in addition to vasculitis.

IgA vasculitis (Henoch-Sch�nlein purpura)

• See article Henoch-Sch�nlein Purpura.
• IgA vasculitis (formerly Henoch-Sch�nlein purpura; pictures 1 2) 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 vasculitis symptoms by 1-3 weeks.
• The most typical symptom is palpable non-blanching purpura.
• Arthralgia, arthritis, abdominal pain, melaena, haematemesis and haematuria may occur.
• There is usually spontaneous remission within about a week but relapses may occur.
• A chronic glomerulonephritis develops rarely.
• The diagnosis is based on the clinical picture. Skin biopsy shows leukocytoclastic vasculitis with IgA precipitated in the vessel walls. Plasma IgA concentrations may 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 but some may be caused by hepatitis B virus and some may be essential forms.
• This is an immune complex vasculitis.
• General symptoms: fatigue, weakness
• Cutaneous manifestations in almost all patients: purpura Easy Bruising, Petechiae and Ecchymoses, Raynaud's phenomenon Raynaud's Phenomenon (Rp) or White Finger Disease, skin necrosis, leg ulcers
• Other manifestations include arthralgias, proteinuria, haematuria, renal failure, hypertension, hepatomegaly, mono- or polyneuropathy and abdominal pain.
• Laboratory findings include elevated ESR, a very high titre of rheumatoid factor and a low level of complement (particularly C4).

Hypocomplementaemic urticarial vasculitis syndrome (HUVS, anti-C1q vasculitis)

Goodpasture syndrome

• Rare immune complex vasculitis of small vessels, due to basement membrane antibodies targeted against renal and pulmonary capillary walls
• The annual incidence is 1-2/1 000 000.
• The initial symptoms are unspecific: myalgia, low-grade fever, microscopic haematuria.
• In a small proportion of patients, the disease begins with pulmonary haemorrhage that may lead to anaemia and haemoptysis.
• In glomerulonephritis, there is slow worsening of kidney function, at first, but as the disease progresses it may worsen very rapidly.
• More than 80% of patients have anti-glomerular basement membrane antibodies in their blood (anti-GBM antibodies).
• About 1 in 3 also have ANCA antibodies (mainly MPO antibodies).

Behҫet's syndrome

• A form of vasculitis that may involve arteries or veins of any size
• Most cases are seen in the Mediterranean area and in Japan.
• Severe disease is more common in men.
• The disease may involve symptoms of the skin, mucosa, eyes, joints and the circulatory system.
• Recurrent, painful mouth ulcers are the most typical symptom occurring in nearly all patients.
• In addition, genital ulceration, myalgia, arthralgia and unspecific skin symptoms are common.
• About half of patients have uveitis.
• The diagnosis is based on clinical findings.

Cogan syndrome

• A rare disease; exact prevalence not known
• Age at disease onset most typically 20-30 years
• Typical disease involves interstitial keratitis and sensorineural hearing loss.
• Other symptoms include headaches, tinnitus, vertigo, chronic conjunctivitis, uveitis, retinal vasculitis and intestinal symptoms.
• Neurological manifestations include peripheral neuropathy, TIA, cerebral infarction.
• One patient in three has systemic symptoms.
• The diagnosis is based on clinical findings.

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]