VASCULITIS BLOOD VESSELS INFLAMMATION Primary vasculitis Secondary vasculitis (infections, viruses, tumors, collagen diseases: RA, Sjögren’s syndrome, SLE, SSc, Myositis)

VASCULITIS CLASSIFICATION LARGE-MEDIUM-SIZED VESSELS –Takayasu’s arteritis –Temporal arteritis MEDIUM-SMALL-SIZED VESSELS –Polyarteritis nodosa –Kawasaki’s disease –Churg-Strauss syndrome –Wegener’s granulematosis SMALL-SIZED VESSELS –Schonlein-Henoch syndrome –Cryoglobulinemia –Goodpasture’s (anti-GBM) disease –Immune complex vasculitis (SLE, Serum sickness) –Microscopic polyangiitis

VASCULITIS CLASSIFICATION MISCELLANEOUS SYNDROMES –Behcet’s syndrome –Pyoderma gangrenosum

VASCULITIS Pathogenesis - Immune complexes formation Ag Ab WBC Ag+Ab=IC C B-cell activation RBC

VASCULITIS Pathogenesis- Anti-neutrophile cytoplasmic Ab pANCA – myeloperoxidase cANCA-proteinase 3

VASCULITIS Pathogenesis – granuloma formation T lymphocyte accumulation T lymphocyte accumulation

Takayasu’s Arteritis Pulse-less disease Incidence: 2-5/ /year. Epidemiology: children+young women Japan, India, Africa, Asia, South America, Europe, US. F:M=7:1. Age 10-50years (90% <30y) Pathology: Involves aortic arch, descending aorta and its branches + AV involvement, coronary and pulmonary arteries Panarteritis with granuloma narrowed vessels and thrombus formation

Takayasu’s Arteritis Clinical features: General: malaise, fever, weight loss, arthralgia/arthritis Vascular: –arm claudication/numbness –pulses changes/discrepancy –hypertension –renal failure –Aortic regurgitation (AR) Laboratory: anemia, ESR/CRP elevation Diagnosis: angiography, MRI angiography Treatment: steroids, cytotoxic drugs, control of hypertension, arterial reconstruction, AVR Prognosis: 15 year survival 90%

Takayasu’s Arteritis

Giant Cell Arteritis/ Temporal arteritis

Polyarteritis Nodosa (PAN) Incidence: 5-9 to 80/ Epidemiology: M:F=2-3:1, young patients Pathology: fibrinoid necrosis, aneurysms formation, Ly/Eos infiltration, lumen thrombosis, fibrous obliteration of the lumen Primary or secondary (RA, Sjogren’s syndrome, SLE, Hepatitis B, Hepatitis C, HIV, FMF )

Polyarteritis Nodosa Clinical features: General: weight loss, mild to high fever, malaise Musculo-skeletal: arthralgia, asymmetric polyarthritis, myalgia Skin: palpable purpura, ulceration, ischemic necrosis Neural: peripheral neuropathy, mononeuritis multiplex, CVA

Polyarteritis Nodosa GIT: abdominal pain, mesenteric thrombosis, peritonitis, bleeding Kidney: hypertension, renal failure, proteinuria, hematuria – not glomerulonephritis Cardiac: CHF, MI Lung: very rare hemorrhage Eyes: retinal detachment, scleritis

Polyarteritis Nodosa Ischemic ulcers

Polyarteritis Nodosa Laboratory data: ESR , anemia, globulins , 40% HBS Ag+, aHCV+, 20-30% pANCA+, abnormal urine 40% HBS Ag+, aHCV+, 20-30% pANCA+, abnormal urine Diagnosis: biopsy, angiography Aneurysms formation Aneurysms formation

Polyarteritis Nodosa Prognosis: 5 year survival 15%-80% Treatment: Hepatitis neg : Steroids, Cyclophosphamide, Imuran, Methotrexate Hepatitis pos : Antiviral treatment (Interferon, plasmapheresis, Ribaverin)

Churg-Strauss Syndrome Incidence: 1-2/ Epidemiology: M:F=2:1 Pathology: allergic necrotizing angiitis, eosinophils infiltration, extra-vascular granulomas formation

Churg-Strauss Syndrome Prodromal period: bronchial asthma Second phase: eosinophiliaeosinophilia Lóffler s-me - eosinophilic pneumoniaLóffler s-me - eosinophilic pneumonia eosinophilic gastroenteritiseosinophilic gastroenteritis Third phase: systemic vasculitis

Churg-Strauss Syndrome Clinical features: General signs: fever, malaise, weight lossGeneral signs: fever, malaise, weight loss Lung involvement: asthma, lung infiltratesLung involvement: asthma, lung infiltrates GIT involvement: abdominal pain, diarrhea, bleedingGIT involvement: abdominal pain, diarrhea, bleeding NS involvement: neuropathy (motor/sensor)NS involvement: neuropathy (motor/sensor) Kidney involvement: GNKidney involvement: GN ArthritisArthritis

Churg-Strauss Syndrome Peripheral lung infiltrates

Churg-Strauss Syndrome Laboratory data: anemia, ESR , eosinophils/mm 3, IgE , pANCA + (70%) Diagnosis: biopsy Prognosis: 5 years survival-65% Treatment: Steroids, Cyclophosphamide, Imuran

Wegener’s Granulematosis Incidence: 4/ Epidemiology: M:F=1,2:1 Pathology: necrotizing granulomatosis and vasculitis, neutrophils accumulation: upper airways, lungs, kidney

Wegener’s Granulematosis Clinical features: General signs: fever, malaise, weight lossGeneral signs: fever, malaise, weight loss Upper Respiratory Tract: sinusitis, otitis media, nasal ulcerationUpper Respiratory Tract: sinusitis, otitis media, nasal ulceration Low Respiratory Tract: Pulmonary infiltrates, nodules, cavities (cough, dyspnea, hemopthysis)Low Respiratory Tract: Pulmonary infiltrates, nodules, cavities (cough, dyspnea, hemopthysis) Kidney: Glomerulonephritis, hypertension, renal failureKidney: Glomerulonephritis, hypertension, renal failure Purpura  Necrotic ulcersPurpura  Necrotic ulcers Arthritis (50-70%)Arthritis (50-70%) Eyes: orbital damage, scleritis (20%)Eyes: orbital damage, scleritis (20%) NS: peripheral neuropathy, central (33%)NS: peripheral neuropathy, central (33%) Heart: CHF, MI, arrhythmiasHeart: CHF, MI, arrhythmias

Wegener’s Granulematosis Orbital and nasal granuloma Orbital and nasal granuloma Pulmonary nodes And cavitation

Wegener’s Granulematosis Laboratory data: leukocytosis, anemia, ESR , cANCA + (90%), abnormal urine Diagnosis: nasal biopsy, open lung biopsy Prognosis: 5 years survival % Treatment: Steroids + Cyclophosphamide, Imuran, MTX Trimethoprim Sulfamethoxazole (Resprim) Trimethoprim Sulfamethoxazole (Resprim)

Henoch-Schőnlein Purpura Incidence: 4-10/ Epidemiology: M:F=1,2:1, 4-14 years Pathology: necrotizing leukocytoclastic vasculitis, fibrinoid necrosis, IC, IgA and C3 deposition ( skin, gut, kidney [glomerrular& tubular]), MNC infiltration

Henoch-Schőnlein Purpura Clinical features: General signsGeneral signs Skin: purpura (100%), ulceration (rare)Skin: purpura (100%), ulceration (rare) Arthritis, arthralgia (60%)Arthritis, arthralgia (60%) GIT vasculitis (85%-abd. pain, diarrhea, bleeding)GIT vasculitis (85%-abd. pain, diarrhea, bleeding) Renal (IgA nephropathy) disease (10-40%) – segmental proliferative GN +/- crescents, IgA + C ³ deposition (Berger’s disease) – hematuria, proteinuriaRenal (IgA nephropathy) disease (10-40%) – segmental proliferative GN +/- crescents, IgA + C ³ deposition (Berger’s disease) – hematuria, proteinuria

Henoch-Schőnlein Purpura Purpura, Arthritis Ischemic colitis

Henoch-Schőnlein Purpura Laboratory data: elevated ESR/CRP, leukocytosis, mild anemia, hematuria, high IgA Diagnosis: clinical +/- biopsy Prognosis: good (except severe GIT vasculitis and IgA nephropathy) Treatment: rest, NSAID, Steroids, Cyclophosphamide

Cryoglobulinemic Vasculitis Immunoglobulins – reversibly precipitated by low temperature Type % Type % Type % Polyclonalmixed RF (IgM to IgG) Monoclonal mixed RF (IgM to IgG) Monoclonal IgM or IgG RA, SLE, SS, DM SBE, Strept GN Hepatitis C/B Collagen disease InfectionsLymphomaMyeloma Waldenström d-se Lymphoma

Cryoglobulinemic Vasculitis Hyperviscosity problems:Hyperviscosity problems: – visual problems –TIA – neuropathy Vasculitis:Vasculitis: –purpura –arthritis –kidney involvement glomerulonephritisglomerulonephritis progressive renal failureprogressive renal failure nephrotic syndromenephrotic syndrome

Cryoglobulinemic Vasculitis Laboratory data: anemia, high ESR/CRP, hyperglobulinemia, pos cryoglobulins, elevated creatinine, hematuria, proteinuria, liver enzymes elevation - pos anti HCV/HBV/HIV Ab Diagnosis: biopsy (leukocytoclastic vasculitis) with deposits of cryoglobulins, cryoglobulins, DPGN Prognosis: poor Treatment: plasmapheresis, antiviral therapy (Ribaverin + Interferon  ), Steroids + Cyclophosphamide

Behcet’s Disease Epidemiology: Japan, Meddle East (Silk rood) Family penetration Clinical feature: Oral aphthous ulcers (100%) – 3/yearOral aphthous ulcers (100%) – 3/year Genital ulcerations (80%)Genital ulcerations (80%) Eye inflammation (65%)-anterior/posterior uveitis, retinal vasculitisEye inflammation (65%)-anterior/posterior uveitis, retinal vasculitis Skin inflammation (70%)-(folliculitis-like, acne-like, erythema nodosum-like)Skin inflammation (70%)-(folliculitis-like, acne-like, erythema nodosum-like) Vasculitis (arterial-CNS, venous – thrombosis superficial and deep)Vasculitis (arterial-CNS, venous – thrombosis superficial and deep)

Behcet’s Disease Aphtha Aphtha Erythema nodosum Hypopion

Behcet’s Disease Laboratory data : HLA B 51 pos. Pathergy skin test Prognosis: serious in uveitis - blindness, CNS vasculitis, thrombosis Treatment: Colchicine CS +/- MTX, Imuran, Salazopyrine CS +/- MTX, Imuran, Salazopyrine CS +Neoral CS +Neoral Thalidomide Thalidomide Anticoagulants Anticoagulants

Pyoderma Gangrenosum Neutrophilic Dermatosis Inflammatory Bowel Diseases: Diseases: Crohn’s Disease Ulcerative colitis Myeloproliferative Diseases: Diseases: Polycythemia Vera MyelomaLeukemias