Presentation on theme: "Three cases of Behcet`s disease with vascular involvement"— Presentation transcript:
1Three cases of Behcet`s disease with vascular involvement IN THE NAME OF GODThree cases of Behcet`s disease with vascular involvementGholamrezapoor, MD, resident of internal medicine&Sasan Fallahi, MD, rheumatologist, Kerman University of Medical Sciences
4HISTORY Chief complaint Pain and swelling of the left lower limb Present illnessPatient’s problem has been started from four weeks ago, initially she had pain and subsequently swelling of the left lower limb.Swelling appeared initially in distal side of leg and then extended to proximal side of the left thigh.She also had history of fever, especially at the evening.No dyspnea, chest pain and hemoptysis.
5HISTORYPast Historyshe did not have any previous history of known illness, except admission for PID, 7 years ago.She also, had an abortion.No history of recent surgery, trauma, bed ridden or traveling.She used Prednisolone(5mg daily),Omeprazol, Doxepin and Loratadin since 4 weeks ago, but she did not used OCP.
6HISTORY Family History There was no significant point. Personal and Social HistoryShe was not smoker and opium addict.
7HISTORY Review of Systems Oral painful lesions Genital painful lesions Since 8 years agoInterval 20 daysDuration daysAt the time of physical examination, the lesion was present.Genital painful lesionsSince 4 years agoInterval several monthsDuration 5-7 daysAt the time of physical examination, the lesion was not present.DysuriaWhen genital lesion was present
8HISTORY Review of Systems Red eye, tearing and Pain in left eye since 20 years ago intermittently.No history of visual lossSkin lesion in both lower limbs since 15 days agoNo history of headache and seizureNo history of GI problems such as abdominal pain or diarrheaNo history of arthralgia or arthritis
9PHYSICAL EXAMINATION General Survey Patient is a middle age female, awake and oriented, without any distress, she was thin and pale.Vital SignsPR:80 RR:15 BP:90/60 AxilaryT:37
10PHYSICAL EXAMINATION Head & Neck -Mild conjunctivitis and tearing in left eye was noted(red eye).-Aphthous lesions in right and left side of tongue were noted-Trachea and thyroid were normal- No adenopathyChest & Cardiac & AxillaryNLAbdomenProminent veins were visible in epigastric zone, with flow from down to up.There was no distention, tenderness, hepatomegaly, splenomegaly and ascites.
11PHYSICAL EXAMINATION Upper extremities -No skin lesion -Bilateral radial arteries pulsation were normal and symmetric .-Active and passive motion of joints were normal.Force of proximal and distal muscles were near to normal for her sex and age
12PHYSICAL EXAMINATION Lower extremities -Swelling and pitting edema in left lower limb, specially in foot, ankle and distal side of leg-Size difference between circumference of two legs was about 2.5cm.-Red brownish colored nodule with tenderness (1.5 * 1.5 cm ) on lateral side and anterior surface of the left leg compatible with erythema nodosum-Dorsalis pedis and posterior tibialis arteries pulsation in left side were palpable but weaker than right side.Active and passive motion of joints were normal.Force of proximal and distal muscles were near to normal.
13DUPPLER SONOGRAPHY Thrombosis in CFV and SFV were noted. Venous thrombosis was extended to the left iliac vein and IVC.SMA, SMV, Portal vein and hepatic arteries were normal.
25HISTORY Chief complaint Pain and swelling of the right lower limb since two weeks agoPresent illness-Swelling has been appeared initially in right foot and then extended to the right leg and thigh.-No fever, dyspnea, chest pain and hemoptysis
26HISTORY Past History -known case of DM since six months, ago -No history of recent surgery, trauma or bed rest, but he had a trip by bus , 45 days ago.
27HISTORY Family History No significant point. Personal and Social HistoryNo smoking and opium addiction
28HISTORY Review of Systems Oral painful lesions Genital painful lesions The first time appeared at and continued for 2 weeks and then disappeared for 5 yearsFurther started from 1380Interval 20 daysDuration about 15 daysAt the time of physical examination, the lesion was present.Genital painful lesionsThe first time appeared at 1380And reoccurred several times .Duration 3-5 daysAt the time of physical examination, there was no lesion or scar.
29HISTORY Review of Systems -45 days, ago a few skin pustular lesions appeared on right leg. only two small brownish papule remained.-No history of erythema nodosum-Swelling of right testis one month, ago-No history of visual loss, red eye and ocular pain-No history of headache and seizure-No history of GI problems such as abdominal pain or diarrhea-No history of arthralgia or arthritis
30PHYSICAL EXAMINATIONPatient is a young male, awake and oriented, without any distress.Vital SignsPR:84 RR: BP:120/ AxillaryT:37.4
31PHYSICAL EXAMINATION Head & Neck -An aphthous lesion in anterior side of tongue was noted.-Trachea and thyroid were normal.-No adenopathyChest & Cardiac & AxillaryNLAbdomen-No distention, tenderness, hepatomegaly, splenomegaly and ascites
32PHYSICAL EXAMINATION Upper extremities -No skin lesion -Bilateral radial arteries pulsation were normal and symmetric.-Active and passive motion of joints were normal.-Force of proximal and distal muscles were normal.
33PHYSICAL EXAMINATION Lower extremities -Swelling and pitting edema in right lower limb, specially in foot, ankle and distal side of leg-Size difference between circumference of two legs was about 1.5cm.-Two skin lesions (brownish colored pigmentation with 3 * 3mm in size )were visible on lateral side of the right leg (scars of pseudofolliculitis).Bilateral dorsalis pedis and posterior tibialis arteries pulsation were palpable, normal and symmetric.-Active and passive motion of joints were normal.-Force of proximal and distal muscles were normal .
34DUPPLER SONOGRAPHY Thrombosis in popliteal vein CFV and SFV were normal.SMA, SMV, portal vein and IVC were normal.
41HISTORY-Diplopia and visual loss since Farvardin, 1390 due to thrombosis of cerebral venous sinuses, increase of ICP and optic disk atrophy. -8 months, ago he had DVT in left lower limb for which Warfarin started. -Post prandial abdominal pain 6 months, ago
42HISTORY-Abdomino-pelvice CT scan: vascular aneurysm was suspected. -CT Angiography showed aneurysm in abdominal aorta and right common iliac artery. -Operation was done and Prednisolone,60mg daily and Cyclophosphamide, monthly were started.
43HISTORY Review of system -Oral aphthous since the age of eight -No history of genital lesions-No history of erythema nodozum or pseudofolliculitis-No history of arthritis
53Positive pathergy test THE FIRST CASEOral aphtous+Erythema nodosumDVTPositive pathergy testBehcet’s disease
54THE SECOND CASEOral aphtous + Pseudofolliculitis Lesions DVT Positive pathergy test Behcet’s disease
55THE THIRD CASE Oral aphtous + Arterial aneurysm Positive pathergy test Increased ICP, Cerebral venous sinus thrombosis and lower limb DVTArterial aneurysmPositive pathergy testBehcet’s disease
56VIRCHOW'S TRIAD Proposes that VTE occurs as a result of Alterations in blood flow (stasis)Vascular endothelial injuryAlterations in the constituents of the blood (inherited or acquired hypercoagulable state)
57RISK FACTORS FOR VENOUS THROMBOSIS Inherited thrombophiliaFactor V Leiden mutationProthrombin gene mutationProtein S deficiencyProtein C deficiencyAntithrombin (AT) deficiencyRare disorders Dysfibrinogenemia
58RISK FACTORS FOR VENOUS THROMBOSIS Acquired disordersMalignancySurgery, especially orthopedicTraumaPregnancyOral contraceptivesImmobilizationAntiphospholipid antibody syndromeMyeloproliferative disordersPolycythemia veraEssential thrombocythemiaPresence of a central venous catheterCongestive failureHormone replacement therapyTamoxifen, Thalidomide, LenalidomidePNHIBDNephrotic syndromeBehcet disease
59SCREENING FOR HYPERCOAGULABLE STATE Screening for a hypercoagulable state is not generally recommended unless the results are likely to change subsequent therapy for the patient or family membersThere is currently no consensus regarding who to test for inherited thrombophilia
60SCREENING FOR HYPERCOAGULABLE STATE Only patients with one or more of the following:Initial thrombosis occurring prior to age 50 without an immediately identified risk factor (ie, idiopathic or unprovoked venous thrombosis)A family history of venous thromboembolism (ie, first-degree relatives with VTE prior to age 50)Recurrent venous thrombosisThrombosis occurring in unusual vascular beds such as portal, hepatic, mesenteric, or cerebral veinsA history of warfarin-induced skin necrosis, which suggests protein C deficiency
61THROMBOPHILIA WORK-UP AntithrombinProtein CProtein SFactor VIII levelFactor V LeidenAntiphospholipid antibodiesLupus anticoagulantProthrombin gene mutation
62Thrombophilia workup:Effects of anticoagulant therapy and acute thrombosis Confounding FactorsHypercoagulable disorder for testingCoumadin therapyHeparin therapyAcute thrombosisNC; Rarely increasedLoweredCan be loweredAntithrombin (deficiency)NCAntiphospholipid antibodiesFactor V LeidenAcute phase reactant. Do not test while inflammation is still present.Factor VIII levelFalse positives possibleCannot measureLupus anticoagulantCannot measure•Can be lowered*Protein C (deficiency)Protein S (deficiency)Prothrombin gene mutation
64DEFINITIONBehcet's disease is a multisystem autoimmune disorder presenting with recurrent oral and genital ulcerations as well as ocular involvement.
65EPIDEMIOLOGY Affects young males and females Males and females are affected equallyMales often have more severe diseaseMediterranean region, the Middle East, and the Far EastPrevalence ranges from 13.5 to 20 per 100,000Prevalence in the United States and Europe have ranged from 0.12 to 7.5 per 100,000
66PATHOGENESISThe etiology and pathogenesis of this syndrome remain obscureIncrease of circulating autoantibodiesAnti-Enolase of endothelial cellsAnti-Selenium binding proteinAnti-Saccharomyces cerevisiae antibodiesAssociation of Behcet's disease with HLA-B*5, HLA-B*51 and the MHC Class I region is confirmedAn association with ILI0 and the IL23R-ILI2RB2 locus were also observedPerhaps infectious acts as a immune activity trigger
67PATHOLOGY The classic Behçet’s lesion is Necrotizing leukocytoclastic obliterative perivasculitisVenous thrombosisLymphocytic infiltration of capillaries, veins and arteries of all sizesCellular infiltration is often neutrophils and CD4+ T lymphocytesIn some patients, diffuse inflammatory disease, involving all layers of large vessels and resulting to formation of pseudoaneurysms, suggests vasculitis of vasa vasorum.
68CLINICAL FEATURES Mucocutaneous The recurrent aphthous ulcerations Are a sine qua non for the diagnosisThe ulcers are usually painfulAre shallow or deep with a central yellowish necrotic baseAppear singly or in cropsAre located anywhere in the oral cavityLess than 10 mm in diameter are seen in 85% of patients, while large or herpetiform lesions are less frequentThe ulcers persist for 1-2 weeks and subside without leaving scars
69CLINICAL FEATURES The genital ulcers Pseudofolliculitis Are less common but more specificPainfulDo not affect the glans penis or urethraProduce scrotal scarsPseudofolliculitisErythema nodosumAcne-like exanthem
70CLINICAL FEATURES Eye involvement Occurring in 50% of patients Is usually present at the onset but may also develop within the first few yearsIncludesAnterior uveitis (Iritis )Posterior uveitisBilateral pan uveitis with scarringIs the most dreaded complication, since it occasionally progresses rapidly to blindness.Retinal vessel occlusionsOptic neuritis
71CLINICAL FEATURES Articular involvement Seen in a 50% of patients Non-deforming arthritis or arthralgiaAffects knees and ankles
72CLINICAL FEATURES Vascular involvement Venous involvement SVT or DVT is seen in 30% of patientsThe superior vena cava is obstructed occasionallyPulmonary emboli are a rare complicationArterial involvementOccurs in less than 5% of patientsPresents withAortitisPeripheral arterial aneurysmArterial thrombosisPulmonary artery vasculitis presenting with dyspnea, cough, chest pain, hemoptysis, and infiltrates on chest roentgenograms has been reported in 5% of patients
73Behcet’s disease involve blood vessels of all sizes - small, medium, and large - both arteries and veins
74CLINICAL FEATURES Neurologic involvement 5-10% Mainly in the parenchymal form (80%) it is associated with brain stem involvementIL-6 is persistently raised in CSF of these patientsDural sinus thrombi (20%) are associated with headache and increased ICP
75CLINICAL FEATURES Gastrointestinal involvement Is seen more frequently in patients from JapanConsists of mucosal ulcerations of the gut, resembling Crohn's diseaseGenital tract involvementEpididymitis is seen in 5% of patients
76PATHERGY TESTNonspecific skin inflammatory reactivity to any scratches or intradermal saline injection is a common and specific manifestationA papule or pustul 2 mm or more in size developing 24 to 48 hours after oblique insertion of a 20 to 25 gauge needle 5mm intra-demal, generally performed on the forearm
77DIFFERENTIAL DIAGNOSIS Differential diagnosis of recurrent oral ulcers includesHerpes simplexBenign aphthous ulcersInflammatory bowel diseaseStevens-Johnson syndromeSLEDental prostheticsOral hygiene productsMedications such as methotrexate can cause oral ulcersPemphigoid, pemphigus vulgaris, cicatricial pemphigoid,Lichen planusLinear IgA disease
78DIFFERENTIAL DIAGNOSIS Differential diagnosis of genital ulcers include:HSVSyphilisChancroidLymphogranuloma venereumFixed drug reactionsNeoplasmsTrauma
79DIFFERENTIAL DIAGNOSIS Other causes of inflammatory eye disease, neurologic disease, vascular disease, arthritis, are includedSLEIBDSarcoidosisReactive arthritisPsoriatic arthritisAnkylosing spondylitisJuvenile idiopathic arthritisFMFMSTuberculosisHIVMalignancies
80DIAGNOSISDiagnosis is clinical and based on internationally agreed diagnostic criteriaRecurrent oral ulceration plus two of the following:Recurrent genital ulcerationEye lesionsSkin lesionsPathergy test
81LABORATORY FINDINGSLaboratory findings are mainly nonspecific indices of inflammation, such asLeukocytosisElevated erythrocyte sedimentation rateElevated C-reactive protein levels
82TREATMENT Mucocutaneouce involvement Topical glucocorticoids (triamcinolone) in the form of mouthwash or pasteTopical Sucralfate 1g/5mL four times daily as a mouthwashColchicineIn more serious cases, Thalidomide (l00 mg/d)Prednisone starting dose is 15 mg/day, with tapering to 10 mg/day after one week and discontinuation of prednisone entirely over two to three weeks period
83TREATMENT Uveitis Sight-threatening uveitis Prednisone(I mg/kg per day) and azathioprine (2-3 mg/kg per day)Sight-threatening uveitisCyclosporin (5mg/kg) +/- azathioprinePanuveitis refractory or intolerant to other immunosuppressivesAnti-TNF therapy
84TREATMENTArthritisColchicine 1 to 2 mg/day, administered in divided dosesNSAIDsPrednisone 10 mg/day is an appropriate starting doseJoint complaints not controlled by colchicine
85TREATMENT CNS-Behcet's syndrome Prednisone(I mg/kg per day) and azathioprine (2-3 mg/kg per day)
86PROGNOSISBehçet’s disease typically has a waxing and waning course characterized by exacerbations and remissionsThe disease appears to be more severe in young, male, and Middle Eastern or Far Eastern patientsThe severity of the syndrome usually abates with timeApart from the patients with CNS-Behcet's syndrome and major vessel disease, the life expectancy seems to be normal and the only serious complication is blindness