VASCULITIS. It means ―inflammation of the walls of thevessels‖ and can be associated to manydifferent clinical conditions.CLASSIFICATION.*Direct Infection.-Bacterial(Neisseria)-Rickettsial(spotted fever)-Spirochetal(Syphilis)-Fungal(aspergillosis)-Viral(herpes zoster)
GIANT CELL (TEMPORAL)ARTERITIS. A vasculitis of unknown etiology occurringprimarily in the elderly. Other termscommonly used include temporal arteritis,cranial arteritis and granulomatous arteritis. Is the MOST common form of systemicvasculitis in adults, acute or chronic, oftengranulomatous inflammation of large/smallsize. It affects temporal arteries, but alsovertebral, ophtalmic (blindness) and aorta(aneurysm) Involved arteries have nodular thickeningreduction of lumenthrombosis.Granulomatous inflammation in inner half ofmedia with mononuclear cells+ giant cells.
GIANT CELL (TEMPORAL)ARTERITIS. CLINICAL: old patients with:◦ fever,◦ fatigue,◦ loss of weight,◦ with or w/o facial pain and headache.
GIANT CELL (TEMPORAL)ARTERITIS. Others, with more severe form andinvolvement of ophtalmic arterydiplopiaor blindness of abrupt onset.Dx.: significantly elevated ESR + arterialbiopsy.
TAKAYASU ARTERITIS. Takayasu’s arteritis is a chronicinflammatory disorder of unknownetiology primarily affecting the aortaand its major branches. Predominant in females below 40´sw/probable autoimmune mechanism, Arteritis may also affects pulmonaryarteries in ½ of cases as well ascoronary/renal arteries.
Aortic archarteriogram in apatient withTakayasu‘s arteritis.Smooth taperedstenosis of bilateralcommon carotidarteries (upperarrows) and of theright subclavianartery (lower arrow)can be seen. There ispoststenoticdilatation beyond theleft common carotidnarrowed segment.Total involvement isseen along the
TAKAYASU ARTERITIS.(cont.) CLINICAL:◦ reduced brachial pulse,◦ difference in BP between R & L arm >10 mmHg,◦ Coldness + numbness of fingers,◦ bruising above a subclavia and/or aorta,◦ hypertension, visual defectsblindness.
POLYARTERITIS NODOSA Is a small/medium sized arteritis affectingmultiple organs (skin, peripheral nerves,gut, kidney and heart. Age of onset is from childhoodlateadulthood (average40´s) and it has been associatedw/Hepatitis B,C or both (most common ininjection drug abusers). Probably mediated by immune complexes(Igs + viral Ags)circulating anddeposited in inflammed vessels.
POLYARTERITIS NODOSA◦ diastolic pressure >90 mm Hg,◦ mononeuropathy or polyneuropathy◦ palpable purpura,◦ livedo reticularis,◦ digital gangrene or tender nodules
POLYARTERITIS NODOSA◦ Renal involvementhypertension.◦ In GI tract abdominal angina (hemorrhage,perforation).◦ In heart: myocarditis/myocardial infarction.◦ Eye: scleritis.
POLYARTERITIS NODOSA Dx.◦ Elevated BUN or creatinine◦ Proven hepatitis B/C virus infection◦ Angiographic signs ofaneuryms/vascularocclusion◦ Demonstration of granulocytes in smallor medium sized vessels (biopsy).
BUERGER´S DISEASE Also known as Thromboangiitis obliterans,is characterized by segmental thrombosis+ acute/chronic inflammation of mediumand small arteries MOSTLYtibial and radial arteries, and secondarilyinvolvement of veins and nerves of limbs. Apparently heavy cigarette-smokers areMOST frequently affected (endoth. cellshypersensitivity?)
BUERGER´S DISEASE Microscopically: acute + chronicinflammation in arterial walls +thrombosisorganization/recanalization. Also, thrombosis contains microabscesses+ granulomatous inflammationextensionto veins/nerves. Late complication: chronic ulceration oftoes or fingersgangrene.
KAWASAKI DISEASE(Mucocutaneous lymph nodesyndrome). Is an arteritis that frequently affects coronaryarteries USUALLY in children/infants(about 80% are < 4 yrs old) Associated w/mucocutaneous lymph nodesyndrome of acute and self-limited evolution:◦ fever, conjunctivitis, sore throat,◦ generalized rash, redding of palms/soles,peeling of fingers/ toes and mucopurulentcervical lymphadenopathy. It is epidemic in Japan, Hawaii and US
KAWASAKI DISEASE Dx.:◦ Leukocytosis (PMN´s), thrombocytosis.◦ Some children have ANCA+ in plasmaand◦ Aprox.1/5 of patients involvement ofcoronary arteries/myocardium aneurysm/myocarditis that usuallyresolves spontaneously(mortality 2%).
Behçet’s Syndrome A systemic vasculitis of unknown causewith mucocutaneous and frequent ocularand musculoskeletal involvement. A marked geographic distribution ischaracterized by highest prevalence inTurkey, Iran and Japan.
Behçet’s Syndrome: Clinicalfeatures Recurrent oral and/or genital aphthousulceration. Chronic relapsing uveitis leading toblindness in 10% of all cases. A variety of skin manifestations, includingthe ‗pathergy‘ phenomenon. Musculoskeletal, neurologic, major arteryand vein involvement. An undulating course that generallyabates in intensity with the passage oftime.
MICROSCOPICPOLYANGIITIS It affects arterioles, capillaries andvenules (smaller than PAN) andthe leions are in the same stage. Typically presents as ―palpable purpura‖(skin), but also with mucous membranes,lungs, brain, heart, GI tract, kidneys,muscle, PNS.
MICROSCOPIC POLYANGIITIS CLINICAL:◦ Necrotizing GN (90%)hematuria◦ Lungshemoptysis◦ GI tractabdominal pain◦ Jointsarthralgias◦ Weight loss(>70%)◦ Nerve damage(60%)numbness/tingling inlimbs.◦ Chronically: muscle wasting◦ Skin: purpura(>60%) in legs, feet, buttocks
MICROSCOPIC POLYANGIITIS About 70% of patients may have a clearrelation with a recent immunologicreaction to an Ag (drugs, microrganisms,tumor Ags,etc) having + pANCAS. MPA is quite similar histologically to PANmicroscopic changes EXCEPT thatmuscular/largearteries are usually spared. It reminds Wegener vasculitis BUT w/ogranulomatosis.
CHURG-STRAUSS SYNDROME Asthma is the cardinal clinical feature of CSS (8-10 yrs BEFORE symptoms of vasculitis) with 8-10yrs of evolutionrespiratory failure. Eosinophilia(>10% in CBC) Allergy Mono/polyneuropathy(ocular symptoms) Lung hemorrhage, pleural effusion, pulmonaryinfiltrates Changes in paranasal sinuses Eosinophilic granulomatosis vasculitis/perivasc. Abdominal cramps/heart failure(myocarditis)
History of Wegener’s In 1936, Wegener first described a distinctsyndrome in three patients found to havenecrotizing granulomas involving theupper and lower respiratory tract. In 1954, seven more patients described,resulting in definite criteria
Criteria for Classification Nasal or oral inflammation◦ Development of painful or painless oral ulcers or purulentor bloody nasal discharge Abnormal chest radiograph◦ Chest radiograph showing the presence of nodules, fixedinfiltrates, or cavities Abnormal Urinary sediment◦ Microhematuria (>5 red blood cells per high power field)or red cell casts in urine sediment Granulomatous inflammation onbiopsy◦ Histologic changes showing granulomatous inflammationwithin the wall of an artery or in the perivascular orextravascular area (artery or arteriole)* For purposes of classification, a patient shall be said to haveWegeners granulomatosis if at least 2 of these 4 criteria arepresent. The presence of any 2 or more criteria yields a sensitivityof 88.2% and a specificity of 92.0%
Miscellaneous Joints◦ Arthritis can occur, with joint swelling andpain Nerves◦ Peripheral nerve involvement leads tonumbness, tingling, shooting pains in theextremities, and sometimes to weakness ina foot, hand, arm, or leg Meninges Prostate gland Genito–urinary tract Constitutional symptoms of fatigue, low–grade fever, and weight loss
Incidence of symptomsSymptom At OnsetTotal ENT 75% 95% Lung 50 85 Joints 30 70 Fever 25 50 Kidney 20 75 Cough 20 50 Eye 15 50 Skin 15 45 Weight Loss 10 35 Nervous System (Central/Peripheral) 0 10/15One-third of patients may be without symptoms at onset ofdisease
PathogenesisANCA ANCAs may be not only markers forWegeners granulomatosis and relateddisorders, but they may also be actors inpathogenesis Neutrophils exposed to cytokines such asTNF, express PR3 & MPO (the targets forANCAs) Adding ANCAs to these cytokine-primedneutrophils causes them to generateoxygen radicals and release enzymescapable of damaging blood vessels.
Diagnosis Nasal or oral inflammation◦ Development of painful or painless oral ulcers orpurulent or bloody nasal discharge Abnormal chest radiograph◦ Chest radiograph showing the presence of nodules, fixedinfiltrates, or cavities Abnormal urinary sediment◦ Microhematuria (>5 red blood cells per high power field)or red cell casts in urine sediment Granulomatous inflammation onbiopsy◦ Histologic changes showing granulomatous inflammationwithin the wall of an artery or in the perivascular orextravascular area (artery or arteriole)Criteria for Classification
Management Vasculitides are often serious andsometimes fatal- require prompt recognition and therapy Treatment – helpful- particularly in the acute phase During maintenance therapy- adverse effects- superimposed infections
Management cont. Early deaths – due to active diseaseLate deaths – may be due to thecomplications of therapy The risk-versus-benefit ratio of anytherapeutic approach should be weighedcarefully
Management cont. Glucocorticoides and/orimmunosuppressive therapy should beinstituted immediately in diseases whereirreversible organ system dysfunction andhigh morbidity and mortality have beenclearly established Aggressive therapy should be avoided forvasculitic manifestations that rarelyresults in irreversible organ systemdysfunction and that usually do notrespond to such therapy
Management cont.Treatment of aggressive small vessel vasculitis1. Induction of remission2. Maintenance of remission3. Treatment of relapseInduction therapy (to 3 months after remission, usually 6months from diagnosis) Cyclophosphamide 2.0mg/kg/day (maximum200mg/day)Age > 60years, reduce dose by 25%> 75years, by 50% Prednisolone 1mg/kg/day (maximum 80mg/day)reduced weekly to 25mg/day by 8 weeks and thenmore slowly to 10mg/day by 6 months
Management cont.In severe, life threatening disease(pulmonary haemorrhage, severecrescentic glomerulonephritis withcreatinine > 500μmol/L) consider,◦ Plasma exchange, 7-10 treatments over14 days or◦ Three pulses of methylprednisolone,15mg/kg/day for 3 days
Management cont.Maintenance therapy (to 18-24 months, longerif clinically indicated) Azathioprine, 2.0mg/kg/day (maximum200mg/day)Age > 60yrs, reduce dose by 25%> 75yrs, by 50%Relapse therapy Major relapse: return to induction therapy Minor relapse: increase dose of corticosteroid
Management cont. Stop cyclophosphamide or azathioprine ifWBC < 4x109/L. Restart with a dose reduced by at least 25mgwhen WBC > 4x109/L on 2 consecutive tests.
Management cont. Most of other systemic vasculitides need atleast corticosteroidsUsual dose is 1mg/kg at the inductionGradual tapering during the remission