1. Vasculitis

2. Vasculitis
DEFINITION
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

3. 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.

4. 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.

5. 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

6. • . 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.

7. 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.
• .

8. Clinical Features of Vasculitis include
Constitutional symptoms Gastrointestinal
Bowel ischemia and ⁄or infarction
Fever
Weight loss Renal
Fatigue Glomerulonephritis
Nephrotic syndrome
purura
Renovascular involvement
Livido reticularis Hypertension
Digital infarction
Neurologic
Musculoskeletal Mononeuritis multiplex
Arthralgia Visual disturbance
Arthritis Stroke
Cardiovascular
pulselessness and ⁄or bruits Laboratory abnormalities
common in large vessel disease Anemia
Claudication Eosinophilia
Aneurysms Elevated acute phase reactions
Pulmonary Renal insufficiency
Alveolar hemorrhage Active urinary sediment
Nodules

9. • 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

10. 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

11. • 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

12. 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.

13. • 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

14. • 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.

15. Large Vessel Vasculitis
1- Giant cell arteritis
2- Polymyalgia rheumatica
3-Takayasu's arteritis

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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

22. • . 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.