Vasculitis

VasculitisDEFINITION Vasculitis are a heterogeneous group of diseases characterized by Inflammation , necrosis and damage to blood vessel walls , often with associated organ involvement.

The vessel lumen is usually compromised, and this is associated with ischemia of the tissue supplied by the involved vessel. Any type, size, and location of blood vessel may be involved.

Vasculitis may be primary ( sole manifestation of a disease) or may be secondary( component of another primary disease)

Vasculitis may be confined to a single organ, such as the skin,or it may simultaneously involve several organ systems

Classification of Vascilites Large vessel.Giant cell arteritis &/or Polymyalgia rheumatica.• Takayasu's arteritis

Medium vessel Classical polyarteritis nodosa • Kawasaki disease (in childhood)

Small vessel • Microscopic polyangiitis • Wegener's granulomatosis • Churg-Strauss syndrome • Henoch-Schönlein purpura • Mixed essential cryoglobulinaemia

Others as Behcets disease.

PATHOPHYSIOLOGY AND PATHOGENESIS of Vasculitis

• Generally, most of the vasculitic syndromes are assumed to be mediated at least in part by immunopathogenic mechanisms that occur in response to certain antigenic stimuli

• it is unknown why some individuals might develop vasculitis in response to certain antigenic stimuli,whereas others do not.

• It is likely that a number of factors are involved in the ultimate expression of a vasculitic syndrome. These include the genetic predisposition, environmental exposures, and the regulatory mechanisms associated with immune response to certain antigens.

deposition of immune complexes in vessel walls is the most widely accepted pathogenic mechanism of vasculitis.

• The actual antigen contained in the immune complex has only rarely been identified in vasculitic syndromes.

• In this regard, hepatitis B antigen has been identified in some patients with systemic vasculitis, most notably in polyarteritis nodosa .

• The syndrome of essential mixed cryoglobulinemiais strongly associated with hepatitis C virus infection

• . The mechanisms of tissue damage in immune complex–mediated vasculitis

• antigen-antibody complexes are formed and are deposited in vessel walls .

• The deposition of complexes results in activation of complement components, particularly C5a, which is strongly chemotactic for neutrophils.

• These cells then infiltrate the vessel wall, phagocytose the immune complexes, and release their intracytoplasmic enzymes, which damage the vessel wall.

• As the process becomes subacute or chronic,mononuclear cells infiltrate the vessel wall.

• This will compromise of the vessel lumen with ischemic changes in the tissues supplied by the involved vessel.

Clinical features of Vasculitis• The clinical features of vasculitis are due to a combination of

local tissue ischaemia (caused by vessel inflammation and narrowing) and the systemic effects of widespread inflammation.

• Systemic vasculitis should be considered in any patient with

fever, weight loss, fatigue, evidence of multisystem involvement, rashes, raised inflammatory markers and abnormal urinalysis.

• Early diagnosis and management are essential to prevent irreversible organ damage.

• .

Clinical Features of Vasculitis include Constitutional symptoms FeverWeight lossFatigue pururaLivido reticularisDigital infarction

MusculoskeletalArthralgiaArthritis

Cardiovascular pulselessness and ⁄or bruits common in large vessel diseaseClaudicationAneurysms

PulmonaryAlveolar hemorrhageNodules

GastrointestinalBowel ischemia and ⁄or infarction

RenalGlomerulonephritisNephrotic syndromeRenovascular involvementHypertension

NeurologicMononeuritis multiplexVisual disturbanceStroke

Laboratory abnormalities AnemiaEosinophiliaElevated acute phase reactionsRenal insufficiencyActive urinary sediment

• Vasculitis may be difficult to distinguish from

- widespread malignancy.

- occult sepsis (particularly subacute bacterial endocarditis & meningococcal septicaemia).

- cholesterol emboli. - atrial myxoma . -antiphospholipid syndrome.

The key to recognition is the presence of multisystem involvement

Conditions That Can Mimic Vasculitis

• Infectious diseases• Bacterial endocarditis• Disseminated gonococcal infection• Pulmonary histoplasmosis• Coccidioidomycosis• Syphilis• Lyme disease• Rocky Mountain spotted fever

• Coagulopathies/thrombotic microangiopathies• Antiphospholipid antibody syndrome• Thrombotic thrombocytopenic purpura

• Neoplasms Emboli • Atrial myxoma cardiac emboli• Lymphoma cholestrol emboli• Carcinomatosis

• Drug toxicity• Cocaine• Amphetamines• Ergot alkaloids• Methysergide

• Others• Sarcoidosis• Goodpasture’s syndrome• Amyloidosis• Migraine• Cryofibrinogenemia

Investigations in Vasculitis

• If vasculitis is suspected, the diagnosis should ideally be confirmed by tissue biopsy.

• Skin biopsies are easily obtained.• Nasal septal tissue can be taken from areas of ulceration or

granulation. • Muscle biopsy is positive in about 50% of patients with muscle

pain.

. The most important bedside test is the urine dip test for protein and blood, and subsequent microscopy, since the prognosis of vasculitis is often determined by the degree of renal involvement. In patients with abnormal renal function and active urinary sediment, renal biopsy should be considered.

• Visceral angiography to detect microaneurysms (e.g. classical polyarteritis nodosa)

is most useful where involved tissue is not available to biopsy.

• ESR usually elevated in vasculitis• CRP• C-ANCA & p-ANCA

• Antineutrophil cytoplasmic antibodies (ANCA) • are directed against enzymes present in neutrophil granules. • Two main patterns of immunofluorescence are distinguished:

cytoplasmic (c-ANCA) and perinuclear (p-ANCA).

• c-ANCA are usually directed against proteinase 3 and are particularly associated with Wegener's granulomatosis and Churg-Strauss syndrome.

• p-ANCA are usually directed against myeloperoxidase and associate with microscopic polyangiitis.

• However, positive ANCAs occur in many other diseases, including malignancy, infection (bacterial and HIV), inflammatory bowel disease, RA, lupus and pulmonary fibrosis. Therefore, the diagnosis of these conditions cannot be made or refuted on the ANCA test alone.

Large Vessel Vasculitis

1- Giant cell arteritis2- Polymyalgia rheumatica3-Takayasu's arteritis

GIANT CELL ARTERITIS (GCA)(Temporal Arteritis)

• GCA also known as temporal arteritis or cranial arteritis

• is a large vessel vasculitis predominately affecting branches of the temporal and ophthalmic arteries.

• The mean age of onset is 70 years .

• 4:1 female:male ratio.

Clinical features of Giant cell arteritis

• The onset of symptoms may be abrupt but is often insidious over the course of several weeks or months.

• The most important clinical features are: 1- Headache. This is usually the first symptom and is often

localised to the temporal or occipital region, with scalp tenderness.

2- Jaw pain. This is brought on by chewing or talking and is due to ischaemia of the masseters.

3-Visual disturbance.The most important complication of GCA is monocular blindness

which is almost never reversible The optic nerve head is supplied by the posterior ciliary

artery, vasculitis of which leads to occlusion and acute anterior ischaemic optic neuropathy.

Damage to the optic nerve results in loss of visual acuity and field, reduced colour perception and pupillary defects.

Sudden visual symptoms in one eye, leading rapidly to blindness, constitute the most common pattern.

On fundoscopy the optic disc may appear pale and swollen with haemorrhages, but these changes may take 24-36 hours to develop.

Once blindness has occurred corticosteroids have a negligible effect but are indicated to prevent blindness in the other eye.

4- There may be associated constitutional symptoms of anorexia, fatigue, weight loss, fever, depression and general malaise.

5- Occasionally presentation is with neurological complications that include transient ischaemic attacks, brain-stem infarcts and hemiparesis.

Investigations• The ESR usually elevated above 50 mm/hour in 90% of cases. ( in some

cases the ESR may be normal mainly in those with acute presentationis , in the this situation the CRP may be more helpful ,& usually elevated ).

• Temporal artery biopsy should be obtained. corticosteroid treatment should not be delayed whilst the biopsy is

organised. Characteristic biopsy findings are fragmentation of the internal elastic

lamina with necrosis of the media in combination with a mixed inflammatory cell infiltrate (lymphocytes, plasma cells and eosinophils).

However, 'skip' lesions are common and a negative biopsy does not exclude the diagnosis.

Management of GCA

• If GCA is suspected, systemic corticosteroid (prednisolone 60 mg daily) should be started immediately to prevent visual loss.

• Steroid reduction should be guided by symptoms and ESR, aiming for approximately 10 mg daily by 6 weeks. Thereafter, doses should be reduced by 1 mg per month

• Maintenance therapy is required for at least 1 year, and occasionally for the rest of the patient's life.

• Relapse occurs in 30%, and is an indication to restart high-dose steroids with additional immunosuppressive agents, typically azathioprine or methotrexate

• . Patients with known GCA should be advised to take 60 mg prednisolone and seek prompt medical advice should they experience any recurrence of headache or visual disturbance.