Vasculitis

• Vasculitis arises when immune system mistakenly attacks blood vessels.

• What causes this attack isn't fully known, but it can result from infection or certain medications.

• Severe forms of vasculitis can be caused by the rare autoimmune diseases microscopic polyangiitis and granulomatosis with polyangiitis.

Vasculitis

• People with these conditions produce harmful antibodies (anti-neutrophil cytoplasmic antibodies, or ANCAs) that attack immune cells known as neutrophils.

• Resulting inflammation in small- to medium-sized blood vessels can cause severe organ damage and sometimes death.

Vasculitis • Diseases characterized by inflammation and

necorosis of artery

• Primary vasculitis: damage:

• Large vessels

• Medium vessels

• Small vessels

• Histological, patogenetic aspects and clinical feature

Vasculitis • Cranial arteritis • – prevalence 15-30/100 000• - incidence 18/100 000

Vasculitis

• Polyarteritis nodosa – medium and small vessels• Fever, fatigue, loss of weight, artritis, skin changes • Myalgia, polyneuropathy• Involvement of brain – cca 20%

• Wegener granulomatosis – small vessels• Nekrotisans granulomatomas – compression of cranial

nerves • Meningitis, hydrocephalus • Polyneuropathy, myelopathy, cerebrovascular diseases • Kidney, lung

Vasculitis • Churg-Strauss syndrom• CNS – 6-8% pacients• Stroke – ischemic, hemorrhage, SAH

• Behcet disease • Multisystem, chronic-relapsing vasculitis, damage

predominantly venous system • Oral ulcerations + genital ulcerations, uveitis, erythema

nodosum, • 30% - CNS – lesion of pyramidal tract, stroke, headache,

venous sinuses thrombosis

Therapy

• Combination of immunosuppressive drugs to control the inflammation.

• These drugs are commonly high dose steroids (prednisolone) and additional treatment with drugs such as cyclophosphamide or methotrexate may be given.

• The amount of steroid treatment will be reduced quickly over the first few weeks and then more slowly.

• The current standard of care for ANCA-related vasculitis requires daily doses of the harsh immunosuppressant drug cyclophosphamide for 3 to 6 months.

Therapy

• Daily doses of another immunosuppressant, azathioprine, then follow for a year or more.

• This standard therapy usually clears the vasculitis, but relapse is common.

• In addition, this treatment suppresses the immune system in a non-specific way and has potentially severe side effects.

• Rituximab is specifically targeted to deplete the type of immune cells thought to produce ANCA.

Primary CNS angiitis (PACNS)• Multifocal or diffuse damage of CNS with remittent or

progredient clinical course

• Leasion of the spinal cord

• CSF – increased elements, proteins

• AG – narroving and dilatation of the vessels

• MRI – ischemic, hemoragic, „tumor-like“ lesions, enhancement of meninges after gadolínium

• Brain biopsy

Primary CNS angiitis (PACNS)

Primary CNS angiitis (PACNS)

Primary CNS angiitis (PACNS)

• Therapy• Combined immunosuppressive therapy is the

treatment of choice for PACNS. • This therapy was initially proposed after its

success in patients with systemic vasculitis such as Wegner granulomatosis and polyarteritis nodosa

• but is not supported by evidence from controlled trials in PACNS.

Primary CNS angiitis (PACNS)

• An induction regimen for 9-12 weeks: Cyclophosphamide 2.5 mg/kg/d coupled with intravenous methylprednisolone, 1 g/d for 3 days, then oral prednisolone, 60 mg/d, to be decreased by 10 mg at weekly intervals to reach a dose of 10 mg/d, if possible.

• A maintenance regimen for further 10 months: Alternate day steroids (10-20 mg prednisolone) along with azathioprine, 2 mg/kg/d, substituted for cyclophosphamide.