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Systemic Vasculitides (Medium-sized vessel vasculitis (Polyarteritis…
Systemic Vasculitides
heterogeneous group of disorders that is characterized by inflammatory destruction (necrosis) of blood vessels.
Symptoms depends on the size, distribution, and severity of the affected vessels.
can result in clinical syndromes that vary in severity from a minor self-limited rash to a life-threatening multisystem disorder.
Classification
Primary
Large-artery vasculitis (Giant cell arteritis, Takayasu arteritis)
Medium-vessel vasculitis (Polyarteritis nodosa, Kawasaki Disease)
Small-vessel vasculitis
•granulomatosis with polyangiitis - GPA ; (Wegener granulomatosis -WG)
•Microscopic polyangiitis (MPA)
•eosinophilic granulomatosis with polyangiitis –EGPA; (Churg-Strauss syndrome- CSS)
•anti–GBM antibody disease; (Goodpasture’s disease)
•Henoch-Schönlein Purpura (HSP)
•Essential cryoglobulinemic vasculitis
•Cutaneous leukocytoclastic angiitis, etc.
Secondary
•Connective tissue diseases
•infection(HIV, HBV, HCV, CMV)
•Neoplastic diseases (NHL, myeloproliferative diseases, solid tumors)
•Drug-induced
Drug induced vasculitis (DIV)
Most commonly after: Hydralazine, Propylthiouracyl, Metimazol, Carbamizol, Allopurinol, Penicylline, Streptokinaze, Monoclonal antibody, Carvedilol
Main symptoms (appear up to 21 days after drug administration)
1.Cutaneous small-vessel vasculitis
2.Joint pain
3.Rarely affect renal vessels (approx. 19%)
Paraneoplastic vasculitis
-More frequently with lymphoprolipherative diseases
-accompany neoplastic disease
-Most often as leukocytoclastic vasculitis, may also affect medium and large vessels
-< 5%
Solid tumors that are most often accompanied by vasculitis:
Non-small cell lung cancer Prostate cancer
Colon cancer Breast cancer Renal cell carcinoma
Pathomechanism
Self-existing or accompanying other autoimmune diseases.
infections or exposition to alergens
Antineutrophil cytoplasmatic antibody (ANCA) associated
Immune complexes disease
manifestation
depands on:
Vascular diameter
Localisation
Pathomechanism
Advancement in inflamatory and necrotic tissue changes, thrombosis of affected vessel and ischemia of tissue or organs
general (malaise, decrease body weight, fever, Joint pain, Muscle pain, Cutaneous lesions)
laboratory: ESR (Biernacki Reaction), CRP, anaemia, leukocytosis, eosinophilia, proteinuria, erythrocyturia, ANCA, EA Anti-GBM complexes
other: Bloody sputum, pneumonia, polyneuropathy, hypertension, Nephrotic syndrome, Renal insufficiency, Internal organs ischemia
Large-vessel vasculitis
Giant cell arteritis (GCA)
temporal artery - Horton disease
patients older than 50
more common among siblings
F>M
increase of incidence is observed
Pathogenesis
Genetic factors (HLA-DRB1
04, DRB1
01)
Connection with infections (parvovirus B19, mycoplasma, chlamydia)
„miniepidemy” – herpes and parainfluenza viruses
Cell-mediated immunity (macrophages, CD4)
Granulomatous aortitis and vasculitis of its main branches:
mainly extracranial branches of carotid artery
.
Occurs with polymyalgia rheumatica
In temporal arteritis: headache, mandibula pain with chewing (claudication), cervicalgia
Ophthalmic artery– sudden blindness due to narrowing of the ophthalmic or posterior ciliary arteries (PCA more common); can a ect both eyes
Symptoms and signs
Headache, Hypersensitivity of head skin, Fever, vision disturbance, Blindness, Polymyalgia rheumatica, Vertigo, No pulse on temporal artery, Thoracic and abdominal aortic aneurysm and dissection, stroke
Diagnostic cryteria
Diagnosed if 3 or more of the above 5 criteria present
Begenning of disease > 50 years of age
Head pain
Tenderness and loss of pulse on temporal artery
ESR > 50 mm/h
Temporal artery biopsy (vasculitis, mononuclear cells infiltration, granulomatous inflamation with giant cells)
Treatment
prednisone1mg/kg.
low dose ASA to help decrease visual loss
Takayasu disease (TKA)
Essentials of Diagnosis
Causes vasculitis of the aorta and its major branches.
Affects young women.
presents with
absent pulse
, bruit, claudication, hypertension, or fever of unknown origin.
Erythrocyte sedimentation rate is usually elevated.
Most patients respond to prednisone.
commonly in Asia and Mexico.
affects women eight times more than men
average age of diagnosis is in the mid-20s but the disease may begin as early as age 7 or as late as age 70
Symptoms and signs
Vascular: Bruit, Claudication (pain caused by obstruction of artery), Hypertension, Unequal arm blood pressures, Aortic regurgitation.
CNS: headache, Visual abnormality, Stroke
Musculoskeletal: Chest wall pain, Joint pain, Myalgia
Malaise, Fever, Weight loss
Diagnostic criteria
Diagnosis: 3 out of 6
Onset < 40 years of age
Limb claudication
Lower pulse amplitude on arm artery
Blood pressure difference between arms > 10 mm Hg
Murmur over subclaviane artery or abdominal aorta
Improper result of arteriography (narrowing or oclussion of aorta or its main branches)
Medium-sized vessel vasculitis
Polyarteritis Nodosa (PAN)
Rare disease
Usually occurs in middle-aged men
Occasional association with hepatitis B antigenemia
Pathologically: fibrinoid necrosis of vessel walls with microaneurysm formation, thrombosis and infarction
Clinical features
Renal – haematuria and proteinuria, hypertension, chronic renal failure
Cardiac – myocardial infarction, heart failure
Skin – subcutaneous haemorrhage and gangrene, livedo reticularis, nodules
Neurological – mononeuritis multiplex due to arteritis of the vasa nervorum
Abdominal – pain due to arterial involvement of the abdominal viscera, mimicking acute cholecystitis, pancreatitis or appendicitis, gastrointestinal haemorrhage
Differential diagnosis of PAN and MPA
Segmental, non-granulomatous necrotizing inflammation Unknown etiology in most cases, leading to “rosary sign”, any age (average 40-50s), M>F
Classification Criteria for PAN*
Investigations
• blood work: CBC, ESR, Cr, BUN, p-ANCA, hepatitis B serology
• imaging: angiography
• arterial biopsy
Treatment
• prednisone 1mg/kg/d PO and cyclophosphamide 2mg/kg/d PO
• ± anti-viral of hepatitis B virus
KAWASAKI
check
Paediatrics
DD
Features of Medium Vessel Vasculitis
• Livedo reticularis
• Erythema nodosum
• Raynaud’s phenomenon
• Nodules
• Digital infarcts
• Ulcers
Small vessel vasculitis
ANCA -ve
Immune complex-mediated (most common mechanism)
CUTANEOUS VASCULITIS
Etiology
■ drug exposure (allopurinol, gold, sulfonamides, penicillin, phenytoin)
■ viral or bacterial infection
■ idiopathic causes
Signs and Symptoms
palpable purpura ± vesicles and ulceration, urticaria, macules, papules, bullae, subcutaneous nodules
renal or joint involvement may occur, especially in children
Investigations: skin biopsy
Treatment
• stop possible ofendingdrug
• NSAID, low dose corticosteroids
■ immunosuppressive agents in resistant cases
• usuallyself-limiting
known as hypersensitivity/leukocytoclastic vasculitis
small vessels involved (post-capillary venules most frequently)
ANCA positive
Microscopic polyangiitis (MPA)
Clinical manifestation
Kidneys: hematuria, proteinuria, renal failure
Peripheral neuropathy
Central nervous system involvement (strokes)
Heart: aseptic endocarditis, valvular destruction
Alimentary system: pain, hemorrhage, perforation
Respiratory system:
Bloody sputum, cough, dyspnea, infiltrations (alveolar capillarities),
Pulmonary-renal syndrome (massive pulmonary hemorrhage + RPG)
Bronchitis bronchostenosis, Subglottis stenosis
Solid infiltrations in lung, Pulmonary fibrosis
Lung structure damage
ENT:
Nasal hemorrhage, Nasal cartilage destruction
Eustachian tube disfunction, Inner ear disfunction
Deafness
Eye
Episcleritis
Retinal perfusion disfunction
Retinal vein thrombosis
Retinitis, Blindness
Retrobulbar granulomas
GRANULOMATOSIS WITH POLYANGIITIS
(GPA, formerly known as Wegener’s Granulomatosis)
granulomatous inflammation of vessels that may affect the upper airways (rhinitis,sinusitis), lungs (pulmonary nodules, in ltrates), and kidneys (glomerulonephritis, renal failure)
C-ANCA and PR3 antibodies are specific
Investigations
• blood work: anemia (normal MCV), increased WBC, increased Cr, increased ESR, elevated platelet count, ANCA (PR3 > MPO)
• urinalysis: proteinuria, hematuria, RBC casts
• CXR: pneumonitis, lung nodules, infiltration.
• biopsy: renal (segmental necrotizing glomerulonephritis), lung (granulomas, tracheobronchial erosion)
• c-ANCA and ESR correlate with disease activity and used to monitor response to treatment in some patients
Classification Criteria for GPA
Nasal or oral inflammation Development of painful or painless oral ulcers or purulent or bloody nasal discharge
Abnormal chest radiograph Chest radiograph showing the presence of nodules, fixed infiltrates, or cavities
Urinary sediment Microhematuria (>5 red blood cells per high power field) or red cell casts in urine sediment
Granulomatous inflammation on biopsy. Histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area (artery or arteriole)
(if at least 2 of these 4 criteria are present)
eosinophilic granulomatosis with polyangiitis –EGPA; (Churg-Strauss syndrome-CSS)
Granulomatous inflammation of vessels with hypereosinophilia and eosinophilic tissue infiltration, frequent lung involvement (asthma, allergic rhinitis), associated with MPO-ANCA in 40-50% of cases. Other manifestations include peripheral neuropathy (70%), GI involvement, myocarditis and rarely coronary arteritis; average age 40s
Churg-Strauss Triad
• Allergic rhinitis and asthma (often quiescent at time of vasculitis)
• Eosinophilic infiltrative disease resembling pneumonia
• Systemic vasculitis often mononeuritis multiplex/peripheral neuropathy and peripheral eosinophilia
Diagnostic criteria
Features of Small Vessel Vasculitis
• Palpable purpura
• Vesicles
• Chronic urticaria
• Superficial ulcers (erosions)
Treatment of vasculitis with kidney
involvement
Remission induction
a.Combined treatment:
metylprednisolon 0,5 -1,0 g i.v.3 days→ prednison 60 mg/d 4 weeks
Cyclophosphamide i.v. 0,75 g/m2/m-c or 2-3 mg/day p.o. b.Plasmapheresis 5-6x (Goodpasture’s syndr..,cryoglobulinemia, W.G)
c. Second line therapy; Rituximab; dzień 1, 15 – 1000 mg iv
Maintenance treatment
prednisone 6010 mg
Cyclophosphamide or AZA after 3 months
Adiuvant teratment:
trimetoprim/sulfametoksazol, pentoksyfilina.
Alternatively to Cyclophosphamide :
AZA 2 mg p.o., CsA 5mg/kg, MMF 2x 0,5
In some cases:
immunoglobulins 0,4g/kg/d for 5 days
schemes
