The Vasculitis Syndromes Definition Inflammation and damage of

The Vasculitis Syndromes

Definition § Inflammation and damage of blood vessels § Single organ→ skin § Several organ systems § Primary § Secondary § Heterogeneity § Overlap

Primary Vasculitis Syndromes § § § § Wegener´s granulomatosis Churg-Strauss syndrome Polyarteritis nodosa Microscopic polyangitis Giant cell arteritis Takayasu´s arteritis Henoch-Schönlein purpura Idiopthic cutaneous vasculitis Essential mixed cryoglobulinemia Behcet´s syndrome Isolated vasculitis of the CNS Cogan´s syndrome Kawasaki disease

Secondary Vasculitis Syndromes § § § Drug-induced vasculitis Serum sickness Vasculitis associted with other primary diseases, infection, malignancy, rheumatic disease

Pathophysiology and Pathogenesis § Immunpathogenic mechanisms § Pathogenic immune complex formation and/or deposition: Hepatitis B PAN, Hepatitis C Essential mixed cryoglob. § Production of antineutrophilic cytoplasmic antibodies: Wegener´s, Churg-Strauss, Microsc. polyang. § Pathogenic T lymphocyte responses and granuloma formation: Giant cell, Takayasu´s, Wegener, Churg-Strauss

Approach to the patient: Vasculitis § § § Unexplained systemic illness Angiogram of organs Definitive diagnosis→biopsy of involved tissue

Wegener´s granulomatosis

Incidence and Prevalence § § § § Prevalence: 3 per 100. 000 Age of onset: 40 years Primary vasculitis syndrome→ damage of vessels Immunopathogenic mechanisms ANCA= antineutrophil cytoplasmic antibody c-ANCA= cytoplasmic ANCA (diffuse, granular cytoplasmic staining by immunofluorescence microscopy) § Detectable antibodies to proteinase-3 § Granuloma formation

Pathology and pathogenesis § Necrotizing vasculitis of small arteries and veins + granuloma formation § Lung: multiple, bilateral, nodular cavitary infiltrates § Biopsy: necrotizing granulomatous vasculitis § Upper airway lasions: sinuses, nasopharynx § Kidney: rapidly progressive crescentic

Clinical manifestations § § § Upper airways 95% Purulent or bloody nasal discharge Nasal septal perforation Saddle nose deformity Serous oitis media, hearing loss Subglottic tracheal stenosis→severe airway obstruction Pulmonary involvement: hemoptysis, dyspnea 85 -90% Eye: scleritis, conjunctivitis, retroorbital mass laesion Skin: palpable purpura, papules, vesicles, subcutaneous nodules Heart: pericarditis, coronary vasculitis CNS: mononeuritis multiplex, cerebral vasculitis Kidney disease: 77%, proteinuria, hematuria, red blood cell casts, rapidly progressive renal failure

Laboratory findings § ESR↑ § Mild anemia, leukocytosis, thrombocytosis § 90% positive antiproteinase-3 c-ANCA

Diagnosis of WG § Tissue biopsy: necrotizing granulomatous vasculitis § c-ANCA positivity

Treatment of WG § Cyclophosphamide induction for severe disease: 2 mg/kg per day orally + steroids § Cyclophosphamide for 1 year following the induction of complete remission § Prednisone 1 mg/kg per day § Improvement: 90% § Complete remissions: 75% § Later relapses § Remission maintenance: Azathioprine, Methotrexate 2 years past remission

Treatment of WG 2 § Mycophenolate mofetil 1000 mg twice a day § Rituximab (anti-CD 20) § Trimethoprim-sulfamethoxazole

Churg-Strauss syndrome

Definition § Allergic angiitis and granulomatosis § Asthma, peripheral and tissue eosinophilia, extravascular granuloma formation, vasculitis of multiple organs

Incidence and Prevalence § 1 -3 cases per million § Onset: 48 years

Pathology and Pathogenesis § Necrotizing vasculitis § Small and medium-sized muscular erteries, capillaries, veins, and venules § Granuloma formation § Infiltration of the tissues with eosinophils § Lung, skin, heart, kidney. Peripheralnervous system, GI

Clinical and Laboratory Manifesttions § § § § Asthma, pulmonary infiltrates Mononeuritis multiplex Allergic rhinitis and sinusitis Skin lesions: purpura, subcutaneous nodules Eosinophilia ESR↑ p-ANCA = perinuclear ANCA (antimyeloperoxidase)

Diagnosis § § § Asthma Peripheral blood eosinophilia Biopsy

Treatment § § § Steroids Cyclophosphamide Survival rate: 72%

Polyarteritis nodosa

Definition § Multisystem, necrotizing vasculitis § Small and medium-sized muscular arteries § Renal and visceral arteries

Incidence and Prevalence § Very uncommon disease

Pathology and Pathogenesis § § Segmental lesions Bifurcations and branching of arteries Aneurysmal dilatations up to 1 cm in size Kidney: arteritis without glomerulonephritis § Hepatitis B antigenemia: 10 -30% § Circulating immune complexes composed of hepatitis B antigen

Clinical manifestations § § § § § Fever, weight loss Kidney→renal failure, hypertension Joint→arthritis, arthralgia, myalgia Peripheral neuropathy, mononeuritis multiplex GI→abdominal pain, bleeding, bowel infarction and perforation, liver infarction, pancreatic infarction Skin→purpra, nodules, cutaneous infarcts, livedo reticularis Heart→congestive heart failure, myocardial infarction, pericardiis Testicular and ovarian pain CNS→cerebral vascular accident, seizure, altered mental status

Laboratory tests § § § Leukocyte count↑ ESR↑ Anemia of chronic disease Hypergammaglobulinemia HBs. Ag pozitivity 30%

Diagnosis § Vasculitis on biopsy material of involved organs § Angiography→aneurysms of small and medium-sized arteries

Treatment § § § Steroid Cyclophosphamide PAN + Hepatitis B virus pozitivity: Antiviral drugs+ steroid+plasma exchange

Microscopic polyangitis § § § § Glomerulonephritis→renal failure Pulmonary capillaritis→hemoptysis Mononeuritis multiplex GI vasculitis Cutaneous vasculitis Age of onset: 57 years p. ANCA positivity 75%

Diagnosis and Treatment § Kidney, lung: histologic evidence of vasculitis § Steroid +Cyclophosphamide

Giant cell arteritis and Polymyalgia rheumatica

Definition § Temporal arteritis or Cranial arteritis § Inflammationof medium- and large-sized arteries § Temporal artery § Aorta and its main branches § Polymyalgia rheumatica: pain in the muscles of the neck, shouldersm lower back § >50 years

Clinical and Laboratory Manifestations § § § Fever, anemia ESR↑ Headache Temporal artery→tender, thickened, nodular Ischemic optic neuropathy→visual loss→blindness § Increased risk of aortic aneurysm→ dissection

Diagnosis § Biopsy of the temporal artery § Giant cell arteritis

Treatment § Steroid: Prednisone 40 -60 mg/day 1 month § Treatment for≥ 2 years § ESR↓ § Polymyalgia rheumatica: Prednisone 1020 mg/day § ESR↓

Takayasu´s arteritis § Inflammatory and stenotic disease of medium- and large-sized arteries § Aortic arch and its branches § =Aortic arch syndrome § Incidence: 1 -2 cases/million/year § Angiography

Frequency of angiographic abnormalities § § § § Subclavian: 93% Common carotid: 58% Abdominal aorta: 47% Aortic arch: 35% Vertebral: 35% Pulmonary: 10 -40% Coronary < 10%

Clinical manifestetions § Panarteritis with inflammatory mononuclear cell infiltrates § Narrowing of the lumen § Pulses absent § ESR↑, anemia, gammaglobulin↑

Diagnosis § § § Young woman Decrease or absence ofperipheral pulses Discrepancies in blood pressure Arterial bruits Arteriography→irregular vessel walls, stenosis, poststenotic dilatation, aneurysm formation, occlusion, evidence of increased collateral circulation

Treatment § § § Steroid: prednisone 40 -60 mg/day Methotrexate 25 mg/week Surgical correction of stenosed arteries

Henoch-Schönlein purpura § Anaphylactoid purpura § Palpable purpura over the buttocks and lower extremities § Arthralgias § GI signs→colicky abdominal pain, melena/hematochesia § Glomerulonephritis→proteinuria, microscopic hematuria, red blood cell casts § Small-vessel vasculitis § Children 4 -7 years § Immune-complex deposition § Serum Ig. A↑

Diagnosis § Clinical symptoms § Skin biopsy→ leukocytoclastic vasculitis

Treatment § Do not require therapy § Steroids: Prednisone 1 mg/kg/day

Idiopathic cutaneous vasculitis § § =Hypersensitivity vasculitis =Cutaneous leukocytoclastic vasculitis Dermis, small vessels Only skin involvement→palpable purpura, chronic urticaria § Diagnosis: biopsy→vasculitis § Etiology: drug, infection, underlying disease § Treatment: microbe→antimicrobal therapy, steroids

Essential mixed cryoglobulinemia § Cryoglobulins: cold-precipitable monoclonal or polyclonal immunoglobulins § Cutaneous vasculitis, palpable purpura, arthralgias, glomerulonephritis § Hepatitis C infection § Treatment: IFN-α, Ribavirin

Behcet´s syndrome § Recurrent, painful aphthous oral ulcerations in the oral cacity § Recurrent genital ulcers § Iritis § Cutaneous lesions § Treatment: topical steroids, Prednisone

Isolated vasculitis of the CNS § Severe headache, focal neurologic defects § Abnormal MRI of the brain § Abnormal liquor § Abnormal cerebral angiogram→vasculitis § Brain biopsy § Treatment: Prednisone+Cyclophosphami de

Kawasaki disease § § § =Mucocutaneous lymph node syndrome Nonsuppurative cervical adenitis Children > 2 years Coronary artery aneurysms 25% Treatment: IVIG+ Aspirin

Raynaud´s Phenomenon § § § § Episodic vasoconstriction inthe fingers and toes Tip of the nose and earlobes Cold exposure pallor→cyanosis→erythema rewarming of the fingers, vasoconstriction→ischemia→reperfusion Normal population: 3 -5%, women Primary and/or secondary Nailbed cutaneous capillaries viewed stereoscopic microscope

Treatment § Dress warmly, calcium channel blockers, ARBs (angiotensin II receptor blockers) Losartan, iv. prostaglandins, low-dose aspirin