Prof Gergely Péter Vascularitis

Active necrotizing vasculitis

Vasculitic scars

Vasculitis - HE

Classification of systemic vasculitis (Fauci et al, 1978) I. Polyarteritis nodosa group 1. Classic polyarteritis nodosa (PAN) 2. allergic granulomatosis (Churg-Strauss syndrome) 3. Overlap forms II. Hypersensitive vasculitis Special forms: - serum sickness - Henoch Schönlein’s purpura - mixed cryoglobulinemic vasculitis - vasculitis associtade with malignancy - vasculitis associtade with systemic autoimmune diseases III. Wegener’s granulomatosis IV. Lymphomatoid granulomatosis V. Giant cell angiitis 1. temporal arteritis (and polymyalgia rheumatica) 2. Takayasu’s arteritis VI. Other vasculitis 1. Thrombangiitis obliterans (Buerger’s disease) 2. Kawasaki disease Classification of systemic vasculitis (Fauci et al, 1978)

Classification of systemic vasculitis (Chapel Hill Consensus Conference, 1994) Large vessel vasculitis: Giant cell arteritis – vasculitis of aorta and larger branches – mainly on extracranial branches of aorta. Occurs over 50 ys. Frequently associated with polymyalgia rheumatica Takayasu’s arteritis – Granulomatous inflammation of aorta and larger branches. Occurs befora the age of 50 Medium sized vessel vasculitis PAN (classic PAN) – necrotizing inflammation of medium sized or small arteries. Without glomerulonephritis, arteriole, capillary and venule inflammation Kawasaki disease inflammation of large, medium sized and small arteries – with skin, lymph node and mucous membrane symptoms. Frequently affects coronaries, occurs mainly in small children Classification of systemic vasculitis (Chapel Hill Consensus Conference, 1994)

Small cell vasculitis: Wegener’s granulomatosis necrotizing inflammation primarily of airway vessels, frequently with necrotizing glomerulonephritis Churg-Strauss syndrome - eosinophile granulocytic necrotizing vasculitis, involving vessels of airways microscopic polyangiitis (microscopic polyarteritis) necrotizing inflammation of arterioles, capillaries, venules (may involve also medium sized arteries) pauci-immune (i.e. no IC deposit) frequent necrotizing glomerulonephritis and capillaritis of lungs Henoch-Schönlein’s purpura vasculitis localized to capillaries, venules, arterioles, with IgA deposition, with skin, intestinal and glomerular involvement essential cryoglobulinemic vasculitis cryoglobulin and cryoglobulin deposition cutaneous-leukocytoclastic vasculitis without visceral involvement Small cell vasculitis

Classification criteria of polyarteritis nodosa (ACR, 1990) 1 Weight loss  4 kg (since illness began, not due to dieting or other factors) 2 Livedo reticularis (mottled reticular pattern over the skin of portions of extremities or torso) 3 Testicular pain or tenderness (not due to infection, trauma or other causes) 4 Myalgias, weakness, or leg tenderness (diffuse myalgias, excluding shoulder and hip girdle, or weakness of muscles or tenderness of leg muscles) 5 Mono- or polyneuropathy 6 Hypertension (diastolic blood pressure >90 Hgmm) 7 Elevated BUN or creatinine 8 Hepatitis B virus (presence of virus antigen or antibody) 9 Arteriographic abnormality (aneurysms or occlusions of the visceral arteries, not due to other causes, e.g. arteriosclerosis, etc.) 10 Biopsy (granulocytes and/or granulocytes and mononuclear leukocytes in the artery wall) Diagnosis is based on the presence of at least 3 criteria. Classification criteria of polyarteritis nodosa (ACR, 1990)

Livedo reticularis

Livedo vasculitis

Livedo reticularis (racemosa)

PAN - aneurysms

Classification criteria of allergic granulomatosis (Churg-Strauss syndrome) (ACR, 1990) 1 Asthma (in the history) 2 Eosinophilia in WBC count (>10%) 3 Mono- or polyneuropathy 4 Non-fixed pulmonary infiltrates (migratory or transitory infiltrates on radiographs) 5 Paranasal sinus abnormality (history of acute or chronic paranasal sinus pain or tenderness or radiographic opacification) 6 Biopsy (artery, arteriole or venule, showing accumulation of eosinophils in extravascular area) Diagnosis is based on the presence of at least 4 criteria. Classification criteria of allergic granulomatosis (Churg-Strauss syndrome) (ACR, 1990)

Churg-Strauss syndrome - tissue eosinophilia

Classification criteria of Wegener’s granulomatosis (ACR, 1990) 1 Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge) 2 Abnormal chest radiograph (presence of nodules, fixed infiltrates, or cavities) 3 Urinary sediment (microhematuria, i.e. >5 red blood cell per high power field, or red cell casts in sediment) 4 Biopsy (granulomatous inflammation within the wall of an artery or in the peri- or extravascular area of artery or arteriole) Diagnosis is based on the presence of at least 2 criteria. In the absence of specific biopsy finding, hemoptysis can be used as a surrogate variable. Classification criteria of Wegener’s granulomatosis (ACR, 1990)

Wegener’s granulomatosis - lungs

Chest X ray in Wegener’s granulomatosis

Saddle nose deformity in Wegener’s granulomatosis

Classification criteria of hypersensitivity vasculitis (ACR, 1990) 1 Age at onset over 16 years 2 Medication at disease onset 3 Palpable purpura (slightly elevated purpuric rash over one or more areas of the skin; does not blench with pressure and is not related to thrombocytopenia) 4 Maculopapular rash (flat or raised lesions of various sizes over one or more areas of the skin) 5 Biopsy (granulocytes in a peri- or extravascular localisation) Diagnosis is based on the presence of at least 3 criteria. Classification criteria of hypersensitivity vasculitis (ACR, 1990)

Leukocytoclasis

Cutaneous leukocytoclastic vasculitis

Cryoglobulinemia

Cyoglobulinemia - HBsAg+

Vasculitis in RA

Classification criteria of Henoch-Schönlein purpura (ACR, 1990) 1 Palpable purpura 2 Age  20 years at disease onset 3 Bowel angina (diffuse abdominal pain, worse after meals, or bloody diarrhea) 4 Biopsy (granulocytes in the walls of arterioles and venules) Diagnosis is based on the presence of at least 2 criteria. Classification criteria of Henoch-Schönlein purpura (ACR, 1990)

H-S purpura – palpable purpura

H-S purpura

Classification criteria of giant cell arteritis (temporal arteritis) (ACR, 1990) 1 Age at onset  50 years 2 "New" headache (new onset or new type of localized pain) 3 Temporal artery abnormality (tenderness to palpation or decreased pulsation, unrelated to other causes, e.g. arteriosclerosis) 4 Elevated ESR (  50 mm/hr) 5 Abnormal artery biopsy (vasculitis with mononuclear cell infiltration or granulomatous inflammation with multinucleated giant cells) Diagnosis is based on the presence of at least 3 criteria. Classification criteria of giant cell arteritis (temporal arteritis) (ACR, 1990)

Arteritis temporalis – giant cells

Inflamed, painful arteria temporalis

Angiography in arteritis temporalis Angiography in arteritis temporalis

Diagnostic criteria of polymyalgia rheumatica (Healey, 1984) Absolute criterium: onset after 50 ys of age Other criteria: 1 Neck, shoulder or hip pain 2. Morning stiffness for at least 2 hrs 3 Elevated ESR (>40 mm/hr) 4 Rapid response to low dose corticosteroid <20 mg prednisolone/day) Diagnosis is based on the absolute criteria + 3 others Diagnostic criteria of polymyalgia rheumatica (Healey, 1984)

Classification criteria of Takayasu’s arteritis (ACR, 1990) 1 Onset before 40 ys of age 2 Claudication of extremities (pain or dyscomfort on movement, mostly in upper extremities) 3 Decreased brachial artery pulse (decreased pulsation of one or both brachial arteries) 4 More than 10 mm Hg difference in systolic blood pressure between arms 5 Bruit over subclavian arteri(es) or (abdominal) aorta 6 Arteriogram abnormality (occlusion or narrowing of the aorta, its branches or large arteries, not due to other cause, e.g. arteriosclerosis, etc.) At least 3 criteria are required for a definite diagnosis. Classification criteria of Takayasu’s arteritis (ACR, 1990)

Takayasu’s arteritis Takayasu’s arteritis

Diagnostic criteria of Kawasaki disease (American Heart Association, 1990): 1. Fever, persisting 5 days or more (with no other cause) 2. At least four of the followings: a) Non exudative conjunctival congestion b) Oropharyngeal signs: mucosal erythema, or reddening of lips, or strawberry tongue c) Peripheral extremities: reddening of palms and soles, in- durative edema, membranous desquamation of fingertips d) Polymorphous exanthema e) Acute nonpurulent cervical lymphadenopathy (one or more lymph nodes with at least 1.5 cm diameter) Diagnosis requires at least 4 criteria. In case of coronary involvement and less than 4 criteria, atypical Kawasaki disease diagnosis may be made. Diagnostic criteria of Kawasaki disease (American Heart Association, 1990):

Reddened lips and strawberry tongue in Kawasaki disease

Enlarged lymph nodes in Kawasaki disease

Membranous desquamation of fingertips in Kawasaki disease

Classification criteria of Behçet’s syndrome (ISG 1990) ARecurrent (>3/year) aphthae in the mouth B1. Recurrent genital ulcers 2. Ocular symptoms (uveitis, retinal vasculitis) 3. Skin symptoms (erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules) 4. Positive pathergic test (papular/pustular reaction after an aseptic needle prick) Diagnosis = A + 2 B criteria (exclude all other diseases!) Other: aphthous stomatitis, Crohn’s disease, Takayasu’s arteritis, polychondritis. Classification criteria of Behçet’s syndrome (ISG 1990)

Oral ulceration - Behcet

Erythema nodosum

Therapy 1. Periarteritis (PAN), Wegener’s granulomatosis, and microscopic polyangiitis: Starting with 1-4 mg/kg/day corticosteroid (CS) mg/day p.o. cyclophospgamide (CTX), followed by CTX monotherapy (generally for 2 years). In case of intolerance, azathioprine (100 mg/day) or methotrexate (MTX) (25 mg/week) adható. In mild Wegener’s co- trimoxazol (Sumetrolim) therapy may be sufficient. 2. Schönlein-Henoch purpura: mg/kg/day CS. Arthritis will respond to NSAID, long-term prognosis is determined by kidney disease. 3. Cryoglobulinemia: in “idiopathic”, hepatitis C virus positive cases, complex antiviral treatment (interferon-alpha + ribavirin) is required, CS, or CS+azathioprine therapy affects only arthritis and purpura, but not glomerulonephritis.

Therapy (cont’d) 4. Temporal arteritis: in mild cases 0.5 mg/kg/day CS, or NSAID may be sufficient. In more severe cases 1-2 mg/kg/day CS is recommended. If inflammation last for longer, azathioprine may be added to CS. 5. Polymyalgia rheumatica: In general 0.5 mg/kg/day CS (25 mg/day prednisolon or 20 mg methylprednisolon) is sufficient. 6. Takayasu’s arteritis: only in early active stage: 1 mg/kg/day CS and/or CTX for ½-1 year. In later stage: surgery. 7. Kawasaki betegség: in mild cases NSAID, in case of coronaritis high dose intravenous immune globulin (IVIG) (0.4 mg/kg/dose). 8. Behçet’s syndrome. In skin and mucous membrane involvation: 1-2 mg/kg/day CS, or colchicin, NSAID. In case of uveitis, retina vasculitis 1-2 mg/kg/day CS mg/kg/day cyclosporine! In arthritis NSAID, 1 mg/kg/day CS, azathioprine, or CTX may be required. In thrombophlebitis esetén: heparin, or warfarin. Therapy (cont’d)