Presentation on theme: "Dr. Müge Bıçakçıgil Kalaycı"— Presentation transcript:
1 Dr. Müge Bıçakçıgil Kalaycı VasculitisDr. Müge Bıçakçıgil Kalaycı
2 VasculitisA heterogenous group of clinical syndromes characterized by inflammation of blood vesselsThe clinical picture is essentially dependent on the size and extent of vessel involvement
3 Vasculitis Ambiguity of clinical presentations Limited diagnostic testsDifficulty in obtaining diagnostic tissueTherefore, difficult to diagnoseAND classify
4 Incidence of Vasculitis Variable because of definitionsKawasaki seen almost exclusively in pediatric populationMost other vasculitides in the fifth decade of life
5 All blood vessels can be affected from the largest (Aorta) to the smallest blood vessels in the skin (capillaries)Blood Vessel InjuryIncreased permeabilityWeakening (Aneurysm +/-Hemorrhage)Intimal proliferation and thrombosis, obstruction and local ischemia
7 Classification of Vasculitis Vasculitis may be classified by:The size and type of vessel involvementThe histopathologic features (leukocytoclastic, granulomatous vasculitis, etc.)The pattern of clinical features
8 Classification of Vasculitis Important to classify the vasculitis since some types may be self-limited while others may be chronicHowever, initially it is important to determine the amount and extent of organ system involvement
9 Classification of Vasculitis Primary Vasculitis SyndromesWegener's granulomatosisChurg-Strauss syndromePolyarteritis nodosaMicroscopic polyangiitisGiant cell arteritisTakayasu's arteritisHenoch-Schönlein purpuraIdiopathic cutaneous vasculitisEssential mixedcryoglobulinemiaBehçet's syndromeIsolated vasculitis of the centralnervous systemCogan's syndromeKawasaki diseaseSecondary Vasculitis SyndromesDrug-induced vasculitisSerum sicknessVasculitis associated with otherprimary diseasesInfectionMalignancyRheumatic disease
10 Classification of Vasculitis Large VesselTakayasu arteritisGiant Cell ArteritisMedium VesselPANKawasaki’sIsolated CNS vasculitisSmall VesselChurg-StraussWegener’sMicroscopic PolyangiitisHSPEssential CryoglobulinemiaHypersensitivity vasculitisVasculitis 2nd to CTDVasculitis 2nd to viral infection
12 LARGE VESSEL VASCULITIS Giant Cell Arteritis (Temporal Arteritis)Takayasu’s Arteritis
13 Temporal (Giant-Cell) Arteritis Chronic granulomatous vasculitis affecting large arteries in older peopleInflammation of the walls of large arteriesCranial arteritis (most common):Temporal, occipital, ophthalmicSubclavian, iliac/femoralAorta
14 Temporal (Giant-Cell) Arteritis Most are >50 years of age (average 72)Women>menFemales 70%Gradual onset 64%Prevalence high in Scandinavian countriesVERY rare in Blacks and Hispanics
15 Fever/wasting syndrome Fever and chills Can sometimes present with Fever of Unknown Origin (FUO)Anorexia, weight lossNight sweatsWeaknessDepressionPain & Stiffness:Around shoulders and hips (polymyalgia rheumatica) – 15%
16 Cranial Arteries – most common Headaches…….severeScalp tenderness +/- thickened vesselsIschemic optic neuropathyLoss of vision-diplopiaJaw claudication in 50%Tongue claudicationCNS ischemiaStrokes
17 Large-vessel GCA/aortitis 10-15% Arm claudication…femoral is rarePulselessnessRaynaud’s phenomenonAortic aneurysmAortic insufficiencyPMROften lack cranial involvement
18 Scalp necrosisTongue gangreneCranial and peripheral neuropathiesRare, isolated organ involvement
19 Temporal (Giant-Cell) Arteritis Physical ExaminationVery tender over templesSwollen, rope like temporal arteryOptic disc swelling due to ischemia
25 Three of the following five criteria must be met to diagnosis GCA. 1-Age greater than 50 years2-new headaches3-abnormal temporal artery4-ESR≥50mm/h and5- positive temporal artery biopsy results for vasculitis
26 Therapy Relative EMERGENCY as patient can lose vision Urgent temporal artery biopsy (get the tissue) to confirm the diagnosisInitiate high-dose corticosteroids (40-60 mg per day)Relief DRAMATICTaper by 10% per 2 weeksDuration – 9-12 monthsSteorid sparing drugs- MTX 10 mg/wk - maybeLow dose ASA can be considered
28 Polymyalgia Rheumatica A clinical syndrome of the middle aged and elderly characterized by pain and stiffness in the neck, shoulder and pelvic girdles,often accompanied by constitutional symptoms.The clinical response to small doses of corticosteroids can be dramatic.
29 Polymyalgia Rheumatica: Clinical featuresThe musculoskeletal symptoms are usually bilateral and symmetrical.Morning Stiffness is the predominant featureMuscular pain is often diffuse and is accentuated by movement; pain at night is common.
30 Polymyalgia Rheumatica: Clinical featuresSystemic features include low-grade fever,fatigue, weight loss and an elevated ESR.Corticosteroid treatment is usually required for at least 2 years..
31 Increased ESR AND CRPNO pathognomonic testNo myopathy
32 All of the following criteria must be met to diagnose PMR: 1- Age greater than 50 years2-aching and stiffness for at least 1 month,affecting at least two of the three above mentioned areas(ie,shoulders,neck, and pelvic girdle)3-morning stiffness lasting at least 1 hour4-ESR>40 mm/h5-exclusion of other diseases except GCA and6-rapid response to prednisone(<20 mgd)
33 Treatment of PMR Prednisone 15 mg Slow taper over 12 to 18 months Possible mtx use as 2nd line agentLook for temporal arteritisConcept of benign outcome
35 Takayasu’s arteritisTakayasu’s arteritis is a chronic inflammatory disorder of unknown etiology primarily affecting the aorta and its major branches.Occurs most commonly in females under 40 years of age.
36 Takayasu’s Arteritis Pathophysiology Giant cells are seen invading the media & adventitia of affected vesselsBw52 or DR12Immunogenetics of TA are less well definedExposure to an unknown antigen precipitates an uncontrolled,inflammatory immune response that primarily targets large vessels
37 Takayasu’s Arteritis Clinical Picture TA had a triphasic course: 1. Early systemic complaints2. Followed by symptoms related to vascular inflammation3. Finally sequelae of vascular stenosis
38 Systemic phase:malaise, fever, night sweats and fatigue.Occlusive phase: upper limb claudication, headaches, postural dizziness and visual disturbances.Reduced or absent upper limb pulses.Arterial bruits over the carotid, abdominal and subclavian vessels
39 80% of patients had bruits most in the carotid arteries Elevated blood pressure occurred in 33%Diminished or absent extremity pulse occur over half of the patients with TANervous system symptoms occurred , in over half experienced dizzinessVisual disturbance affected 1/3 of the patients, always bilateral
42 Takayasu’s Arteritis Evaluation ESR > 20mm/hr Ultrasonography and MRI have been usedAngiography is considered the diagnostic gold standardLong stenotic lesions were seen in 98% of patients.Aneurysms were seen in 27%
43 Diagnosis - 3 of 6 criteria 1. onset age < 40 years2. Limb claudication3. decreased brachial artery pulse4.unequal arm BP(>10 mmHg)5.subclavian and artic bruit6.Angiographic evidence of narrowing or occlusion of aorta
44 Takayasu’s Arteritis Management Glucocorticoids are the mainstay of therapyOther immunosuppressive therapies are used for patients who fail to respond to steroid therapyAzathioprine and Methotrexate are frequently used & cyclophosphamide has been used with some
45 Beta-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors can be used to treat hypertensionPercutaneous coronary transluminal angioplasty (PCTA) successfully restores patency in as many as 80% of these patientsBypass surgery can be done.
46 Takayasu’s Arteritis Prognosis 5-10 years survival rates are in the range of 80-97%Myocardial infarction, stroke, cardiac failure, aneurismal rupture are causes of death
53 PAN -Clinical Manifestations GastrointestinalAbdominal pain-intestinal angina( postprandial abd. pain)Abdominal catastrophes,shock secondary to aneurysmal rupture and resultant hemorrhageShock secondary to sepsis from intestinal ischemia or infarctionHepatomegaly
54 PAN -Clinical Manifestations Kidney (40%)-renal and interlobar arteries, rarely arcuate and interlobular arteriesHypertensionRenal InsufficiencyRenal Vasculitis,Rarely proteinuria and hematuria -paucimmune GNAngiography; microaneurysms with in kidney or large, wedge shaped infarctions
55 PAN -Clinical Manifestations Peripheral Nervous SystemMononeuritis multiplex (e.g. wrist drop,foot drop)Central Nervous SystemEncephalopathy and strokesSkinNodules or ulcersPurpuraDigital gangrene
56 PAN -Clinical Manifestations HeartPericarditisCongestive heart failureArrhythmiasMyocardial infarctiontesticular
63 PAN-Treatment 5 yr survival untreated: 13% Disease onset Prednisone 1 mg/kg q dOral cyclophosphamide 2 mg/kg q dDuration of treatmentAt least one year+HBV PANInterferon-αLamivudine
64 Kawasaki Disease An acute febrile eruptive disease occurring most commonly in infants and children under 5 years of age.Vasculitis, especially involving coronary arteries, is a serious complication.
65 Kawasaki Disease Clinical Features Fever of unknown etiology lasting 5 days or more.Bilateral conjunctival congestion.Dry and red lips, reddening of oral cavity.
66 Kawasaki Disease-Clinical Features Acute nonpurulent swelling of the cervical lymph nodes.Polymorphous exanthema of the trunk without vesicles or crusts.Red palms and soles.
67 Bleeding and crustformation on the lipsand cervicallymphadenopathy inKawasaki disease.
68 Polymorphousexanthema on thelimbs and trunk of aninfant with Kawasakidisease.
72 Treatment and Management recommended treatment for KD patients is a single, intravenously administered dose of immunoglobulin (IVIG, 2 g/kg) in conjunction with high-dose aspirin ( mg/kg/day).The aspirin is continued until the ESR and platelet count have returned to the normal range.IVIG resistance -have included a second infusion of IVIG, a single infusion of infliximab, corticosteroids, and plasmapheresis.
76 Anti-Neutrophil Cytoplasmic Antibody (ANCA) A collection of antibodies directed against components of granules inside the neutrophilDetected in the laboratory by Immunofluorescence Assay and by ELISA methods for specific antibodies
80 Wegener’s Granulomatosis (Granulomatous polyangitis)(GPA) Necrotizing vasculitis of arterioles,capillaries, and postcapillary venulesAssociated with anti-neutrophil cytoplasmic antibodies (ANCA)
81 GranulomaNodular aggregate of macrophages or cells derived from the monocyte-lineage, which is typically surrounded by a “rim” of lymphocytes,and commonly associated with the presence of multinucleated giant-cells
82 GPA -Vasculature involved Upper respiratory tract arterioles and capillariesLung arterioles and capillariesPulmonary “capillaritis”KidneyGlomerulonephritis (“pauci immune”)SkinPeripheral Nervous system
83 Epidemiology of Wegener’s Granulomatosis Age: years-oldNo racial or ethnic predilectionPrevalence: 5-7/100,000
84 NOSE, SINUSIS, AND EARS 90% of patients have nasal involvement, often as the first manifestation of disease.symptoms includepersistant rhinorrhea,unusually severe nasal obstruction,epistaxis, andbloody or brown nasal crusts.
85 NOSE, SINUSIS, AND EARSCartilaginous inflammation lead to perforation of the nasal septum and collapse of the nasal bridge(a ‘’saddle-nose’’ deformity).Bony erosions of the sinus cavities are characteristicbut only develop after long standing diseaseBoth conductive and sensorineural hearing loss
86 “Saddle-nose” deformity resulting from collapse of the nasal cartilage
88 EYES Present with a variety of inflamatory lesions of the eye. Orbital pseudotumors behind the eye may lead to proptosis and visual loss through ischemia of the optic nerve.Scleritis causes photophobia and pain, scleral erythema.
89 Computed tomography scan of a patient with a left orbital mass. This was causing proptosis and visual loss through compression of the optic nerve.
90 Exophthalmos (patient's right eye). Enophthalmos (patient's left eye),both resulting from orbital pseudotumors
91 EYESNecrotizing scleritis may lead to scleral thinning, scleromalacia perforans , and visual loss.Peripheral keratitis lead to the syndrome of ‘’corneal melt’’.Episcleritis and conjunctivitisless serious ocular complications,they are very common
92 MOUTHPainful tongue ulcers occurAn intense gingivitis known as “strawberry gums” is also characteristic of WG.
93 TRACHEA subglottic stenosis, tracheal inflammation and scarring below vocal cords,a potentially disabling manifestationlargely specific to WG(relapsing polychondritis can also cause this lesion).
94 Subglottic stenosis. A web of scar tissue is evident just below the vocal chords, leading to narrowing of the subglottic area and inspiratory stridor.
95 LUNGSapproximately 80% of patients have pulmonary lesions during the course of their disease.pulmonary symptoms includecough, hemoptysis, dyspnea, and sometimes pleuritic chest pain.Lung lesions are often asymptomaticmay be detected only chest imaging is performed.
96 LUNGS radiolographic findings are pulmonary infiltrates and nodules.The infiltrates, which may wax and wane, are often misdiagnosed initially pneumonia.Nodules are usually multiple and bilateral and often cavitary.Pulmonary capillaritis may lead to hemoptysis and rapidly changing pulmonary infiltrates.
97 LUNGSPulmonary capillaritis may lead to alveolar hemorrhage, hemoptysis, and rapidly changing alveolar infiltratesDiffuse alveolar hemorrhage is an immediately life-threatening complication.Large airway disease leading to a cobblestone appearance of the mucosal surface and bronchial narrowing (similar to subglottic stenosis)sometimes leading to postobstructive pneumonia.
98 Multiple bilateral pulmonary nodules can be seen, many of which have cavitated
99 Alveolar hemorrhage in a patient with Wegener granulomatosis. This has resulted in rapidly changing pulmonary infiltrates.There is also a nodular lesion in the right lung.
101 KIDNEYSrenal involvement is present in approximately 20% of patients at the time of diagnosis,develops in nearly 80% of patients at some point during the course of the disease.the clinical presentation of renal disease is rapidly progressive glomerulonephritis
102 KIDNEYS rapidly progressive glomerulonephritis: -- hematuria,red blood cell casts,proteinuria (usually non-nephrotic), andrising serum creatinine.Without appropriate therapy, loss of renal function may ensue within days or weeks.
103 OTHER ORGANSConstitutional symptoms - fever and weight loss, common in WG, serve as important indicators of an active inflammatory process.Nonspecific arthralgias and frank arthritisoften occur early in the course of WG.arthritis of WG is migratory in naturemay assume a variety of joint patterns,from a pauciarticular syndrome of lower extremity joints to a polyarthritis of the small joints of the hands.
104 OTHER ORGANS involvement of brain paranchyma has been reported, meningeal inflammation - more typicalpresenting as excruciating headaches andcranial neuropathiesMononeuritis multiplex may also accompany WGbut is less characteristic of this disease than others(eg, polyarteritis nodosa, microscopic polyangiitis, and the Churg- strauss syndrome)
105 Mononeuritis multiplex. Wasting of the interosseous muscle between the thumb and first finger,caused by peripheral nerve infarction.(b) A patient with weakness bilaterally of foot dorsiflexion (“foot drop”),left greater than right.
106 OTHER ORGANSneuroendocrine complications - panhypopituitarism and diabetes insipidusWG rarely affects the heart, gastrointestinal tract, parotid gland, pulmonary artery, breast, or genitourinary organs.
107 ANCA associated> 90% have elevated titers of antineutrophil cytoplasmic antibodies
108 Anti-Neutrophil Cytoplasmic Ab (ANCA) Cytoplasmic reactivity (C-ANCA)Antigenic target = Proteinase 3Assay: Anti-proteinase 3 Ab titers (ELISA)
109 Wegener’s Granulomatous (2/4 - ACR) Nasal or oral inflammation, Abnormal chest filmPositive urinary sediment – RBC’s or RBC castsBiopsy -- necrotizing granulomatous vasculitisANCA – Ab to proteinase 3, myelloperoxidase
113 Treatment RegimenPrednisone mg/kg q d (tapered) pluscyclophosphamide 2 mg/kg q d for approximately one year85-90% response rate75% complete remission30-50% at least one relapse
114 Churg-Strauss syndrome (CSS) is a primary, multisystem, eosinophilic vasculitis associated with upper and lower respiratory tract disease and antineutrophil cytoplasmic antibodies (ANCAs).Clinical features include asthma, rhinitis, and sinusitis, with eosinophilia progressing to systemic vasculitis with cutaneous, cardiac, neurologic, gastrointestinal, and renal disease.
115 Churg-Strauss syndrome (CSS) characterized by respiratory tract and systemic vasculitis, eosinophilia, and extravascular granulomas.Also termed allergic granulomatosis and angiitisThe mean age at diagnosis is 55 years with an equal sex incidence.
116 CSS-HistologyEosinophil infiltrates, extravascular granulomas, and vasculitis of small and medium vessels are characteristic features of CSS.Arteries, arterioles, venules, and veins may be involved in both the pulmonary and systemic circulations, and vasculitis can occur without granulomas.The pulmonary features combine focal necrotizing vasculitis with features of eosinophilic pneumonia.
117 Clinical Features three phases of CSS: an allergic prodromal phase, an eosinophilic phase, anda final vasculitic phase.The prodrome may last many years and comprises asthma, nasal allergy and polyposis, or other allergic manifestations.The majority of CSS patients have a history of allergy
118 Clinical FeaturesThe eosinophilic phase ;comprises a circulating eosinophilia and eosinophilic manifestations such as eosinophilic pneumonia, endomyocarditis, or eosinophilic gastroenteritis.This phase may fluctuate without therapy;after a variable period, features of systemic vasculitis emerge, including constitutional disturbance with fevers, weight loss, polyarthralgia, and polymyalgia.
119 Pulmonary disease asthma is a diagnostic criterion, Other pulmonary manifestations are infiltrates, caused by localized granulomatous vasculitis, pulmonary hemorrhage, pleural effusions, and the pulmonary consequences of cardiac disease.Chest radiography and computed tomographic assessment reveals parenchymal infiltrates in 75%.
120 Pulmonary diseaseOther abnormalities include small nodules, ground-glass opacities, bronchial wall thickening, and consolidation.Pulmonary manifestations respond to glucocorticoid and immunosuppressive therapy with reduction of asthma and resolution of radiologic changes
121 Ear, nose, and throat involvement symptoms of “allergic” rhinitis, nasal obstruction by polyps, deafness due to otitis media, and sinusitis often precede the diagnosis by several years.Sensorineural deafness either caused by inner ear inflammation or vasculitis of the auditory nerveLaryngeal involvement has been reported.
122 Cardiac involvement Cardiac involvement occurs in 50%, more frequently than with other vasculitides,is the major vasculitic cause of early death.Endomyocarditis leads to a cardiomyopathy and myocardial infarctionboth supraventricular and ventricular dysrhythmias occur and can result in sudden death.Pericardial effusion.
123 Renal disease The kidney is affected in 27% of patients hematuria with proteinuria, and a pauci-immune crescentic, necrotizing glomerulonephritis are the same as for the other ANCA-associated vasculitides.
124 Gastrointestinal involvement Intestinal involvement causes abdominal pain and can lead to perforation and peritonitisis an adverse prognostic factor for survival.Neurologic involvementPeripheral neuropathy occurs in over 50% of CSS patients, more frequent than in the other ANCA-associated vasculitides.an asymmetric mononeuritis multiplexOnset is usually with sudden motor deficit and can be painful.
125 Cutaneous features Purpura, reflecting small vessel vasculitis A specific lesion for CSS is the subcutaneous nodule.livedo reticularis,Digital gangrene of both the hands and feet has been seen
127 Treatment Subgrouping for treatment is done according to prognosis: prednisolone alone or with methotrexate or azathioprine is used for those without poor prognostic factors,with prednisolone with cyclophosphamide for those with poor prognostic factors.Relapse occurs in 75%.Intravenous methylprednisolone, intravenous immunoglobulin, interferon alfa, or rituximab is used for refractory or relapsing disease.
142 Conclusion Vasculitis 2 Think of Arteritis, if– old, PMR, headache, fever (GCA)– young and large vessel disease (TA)• Joint involvement always possible• ANCA will help in a subset• Wherever possible go for histology