master rosina marzo 09 [2]

Patologie Immuni & Patologie Immuni &

Malattie OrfaneMalattie OrfaneTorino Torino –– 2222--24 Gennaio 200924 Gennaio 2009

Patologie Immuni & Patologie Immuni &

Malattie OrfaneMalattie OrfaneTorino Torino –– 2222--24 Gennaio 200924 Gennaio 2009

Entero BehçetEntero BehçetEntero BehçetEntero Behçet

PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO TORINOTORINOTORINOTORINOTORINOTORINOTORINOTORINO

S.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & Epatologia

PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO PRESIDIO SANITARIO GRADENIGO TORINOTORINOTORINOTORINOTORINOTORINOTORINOTORINO

S.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & EpatologiaS.C. Gastroenterologia & Epatologia

F. RosinaF. RosinaF. RosinaF. RosinaF. RosinaF. RosinaF. RosinaF. Rosina

Entero BehçetEntero BehçetEntero BehçetEntero Behçet

Behçet disease Epidemiology of a rare disease

North America & North Europe 0,2 - 6,6 /100.000North America & North Europe 0,2 - 6,6 /100.000

12° Convegno Patologie Immuni & Malattie Orfane , Torino 22-24 gennaio 2009

Behçet disease Epidemiology of a not so rare disease

North America & North Europe 0,2 - 6,6 /100.000North America & North Europe 0,2 - 6,6 /100.000North America & North Europe 0,2 - 6,6 /100.000

Far & Middle East 13,5 - 20/100.000

North America & North Europe 0,2 - 6,6 /100.000

Far & Middle East 13,5 - 20/100.000


Behçet disease Epidemiology of a common disease

North America & North Europe 0,2 - 6,6 /100.000North America & North Europe 0,2 - 6,6 /100.000North America & North Europe 0,2 - 6,6 /100.000

Far & Middle East 13,5 - 20/100.000

Turkey 80 - 370 / 100,000

North America & North Europe 0,2 - 6,6 /100.000

Far & Middle East 13,5 - 20/100.000

Turkey 80 - 370 / 100,000


Behçet disease Epidemiology of a common disease

North America & North Europe 0,2-6,6/100.000Far & Middle East 13,5-20/100.000Turkey 80-370 / 100,000

Age 20-40 yrs

North America & North Europe 0,2-6,6/100.000Far & Middle East 13,5-20/100.000Turkey 80-370 / 100,000

Age 20-40 yrs

Sex Men prevalence(Middle East)Female prevalence(Far East & North Europe)

Severity More severe in Young MenMiddle & Far East

Sex Men prevalence(Middle East)Female prevalence(Far East & North Europe)

Severity More severe in Young MenMiddle & Far East


Behçet disease Definition

Behcet's disease is a chronic, relapsing vasculitis involving arterial and venous blood vessels of all sizes

Behcet's disease is a chronic, relapsing vasculitis involving arterial and venous blood vessels of all sizesand venous blood vessels of all sizesleading to several systemic manifestations….

and venous blood vessels of all sizesleading to several systemic manifestations….


Behçet disease Clinical manifestationsBehçet disease Clinical manifestations

100

75 75 75

60

70

80

90

100

50

33

20

1 1 1

10

0

10

20

30

40

50

60

Oral U

lcers

Uroge

nital

SkinArth

ritis

EyeVas

cular

Neura

l

Renal

Cardi

ac

Lung GI


Behçet disease Large Vessels Disease

Number of

patients

Arterial disease

Pulmonary artery occlusion or aneurysm 36/728 (5%)

Aortic aneurysm 17/728 (2%)

Extremity arterial occlusion or aneurysm 45/728 (6%)

Other arterial occlusion or aneurysm 42/728 (6%)

Right ventricular thrombus 2/728

Review of 728 cases from Koc, Y, Gullu, I, Akpek, G, et al. J Rheumatol 1992; 19:402.


Behçet disease Enteral Arterial disease

• Massive gastrointestinal bleeding due to aneurysmal

rupture of ileo-colic artery. After the failure of hemostasis

with arterial embolization, ileo-right colecctomy wa s performed.

(Kim SU et al Korean J Gastroenterol. 2007) (Kim SU et al Korean J Gastroenterol. 2007)

• Massive hemorrhage from ruptured small aneurysm on

the right ileocolic artery successfully treated with

superselective arterial embolization using microcoi ls (Hong

YK, Yoo WH. Rheumatol Int 2008)


Behçet disease Large Vessels Disease

Number of patients

Venous diseaseDeep venous thrombosis 221/728 (30%)

Subcutaneous thrombophlebitis 205/728 (28%)Subcutaneous thrombophlebitis 205/728 (28%)

SVC occlusion 122/728 (17%)

IVC occlusion 93/728 (13%)

Cerebral sinus thrombosis 30/728 (4%)

Budd-Chiari syndrome 17/728 (2%)

Other venous occlusion 24/728 (3%)

Review of 728 cases from Koc, Y, Gullu, I, Akpek, G, et al. J Rheumatol 1992; 19:402.


Behçet disease Large vessel Disease

Number of patients

Hepatic Vein Thrombosis 14/493 (3%)

Hepatic Vein (HV) Thrombosis Alone 4/14 (29%)

HV + Inferior Vena Cava (IVC) Thrombosis 8/14 (57%)

HV + IVC + Portal Vein Thrombosis 2/14 (16%)

Bayraktar Y et al.. Am J Gastroenterol 1997


Behçet disease Budd Chiari

• Acute — 20 % (5% with fulminant hepatic failure)

• Subacute — 40 % (signs or symptoms for less than six months and no evidence of liver cirrhosis)

• Chronic — 40 % (signs or symptoms for more than six months with evidence of portal hypertension and cirrhosis)

• Acute — 20 % (5% with fulminant hepatic failure)

• Subacute — 40 % (signs or symptoms for less than six months and no evidence of liver cirrhosis)

• Chronic — 40 % (signs or symptoms for more than six months with evidence of portal hypertension and cirrhosis)


BehçetSmall Vessels Disease: Entero Behçet

Symptoms • anorexia• nausea• abdominal pain • diarrhea

Symptoms • anorexia• nausea• abdominal pain • diarrhea

Lesions• “punched out” or “flask shaped” ulcers involving both the submucosa and the muscularis propria, especially in the ileo-ciecal region, less frequenltly in the esophagus and rarely in the stomach and duodenum

Lesions• “punched out” or “flask shaped” ulcers involving both the submucosa and the muscularis propria, especially in the ileo-ciecal region, less frequenltly in the esophagus and rarely in the stomach and duodenum

Griffin JW et al. South Med J 1982Anti M et al. J Clin Gastroenterol 1986Powderly WG et al. Ir J Med Sci 1987Stringer DA et al. Pediatr Radiol 198


Behçet disease Clinical manifestations

ItalyItaly TurkeyTurkey ChinaChina TaiwanTaiwan KoreaKorea ThaiThai

Number of studied ptsNumber of studied pts 137137 23132313 2828 125125 15271527 2323

•• Oral ulcerationsOral ulcerations 99%99% 100%100% 95%95% NRNR 99%99% 100%100%

•• UroUro--genital lesionsgenital lesions 63%63% 85%85% 50%50% NRNR 83%83% 70%70%

•• Cutaneous lesionsCutaneous lesions 82%82% 80%80% 95%95% NRNR 84%84% 61%61%

•• Ocular diseaseOcular disease 61%61% 38%38% 50%50% NRNR 51%51% 52%52%

•• Neurologic diseaseNeurologic disease NRNR 3%3% NRNR NRNR NRNR 9%9%

ItalyItaly TurkeyTurkey ChinaChina TaiwanTaiwan KoreaKorea ThaiThai

Number of studied ptsNumber of studied pts 137137 23132313 2828 125125 15271527 2323

•• Oral ulcerationsOral ulcerations 99%99% 100%100% 95%95% NRNR 99%99% 100%100%

•• UroUro--genital lesionsgenital lesions 63%63% 85%85% 50%50% NRNR 83%83% 70%70%

•• Cutaneous lesionsCutaneous lesions 82%82% 80%80% 95%95% NRNR 84%84% 61%61%

•• Ocular diseaseOcular disease 61%61% 38%38% 50%50% NRNR 51%51% 52%52%

•• Neurologic diseaseNeurologic disease NRNR 3%3% NRNR NRNR NRNR 9%9%

•• Vascular diseaseVascular disease NRNR 25%25% NRNR NRNR NRNR 9%9%

•• ArthritisArthritis NRNR 11%11% 45%45% NRNR NRNR NRNR

•• Renal diseaseRenal disease NRNR NRNR NRNR NRNR NRNR NRNR

•• Cardiac diseaseCardiac disease NRNR NRNR NRNR NRNR NRNR NRNR

•• Pulmonary diseasePulmonary disease NRNR 0,03%0,03% NRNR NRNR NRNR NRNR

•• Vascular diseaseVascular disease NRNR 25%25% NRNR NRNR NRNR 9%9%

•• ArthritisArthritis NRNR 11%11% 45%45% NRNR NRNR NRNR

•• Renal diseaseRenal disease NRNR NRNR NRNR NRNR NRNR NRNR

•• Cardiac diseaseCardiac disease NRNR NRNR NRNR NRNR NRNR NRNR

•• Pulmonary diseasePulmonary disease NRNR 0,03%0,03% NRNR NRNR NRNR NRNR

Salvarani C et al. Arthritis Rheum 2007Pipitone N et al. Clin Exp Rheumatol 2004

Tursen U et al. Int J Dermatol 2003Ning Sheng L et al. Clin Rheumatol 2005Chou SJ et al J Gastrointest Surg 2007

Ling J et al Yan Ke Xue Bao 2005Bang D et al. J Korean Med Sci 2001


Behçet disease Gastrointestinal

Behçet disease Gastrointestinal

66

60

70

80

90

100* 43% HP/NSAIDs neg.ve Peptic ulcers

0 1,5

9 9

35

0

10

20

30

40

50

60

Italy

Turke

y

Korea

Thai

China*

Taiwan

Salvarani C et al. Arthritis Rheum 2007Pipitone N et al. Clin Exp Rheumatol 2004

Tursen U et al. Int J Dermatol 2003Ning Sheng L et al. Clin Rheumatol 2005Chou SJ et al J Gastrointest Surg 2007

Ling J et al Yan Ke Xue Bao 2005Bang D et al. J Korean Med Sci 2001


Entero BehçetNatural History

Remitting relapsing disease complicated by Intestinal perforation

Taiwan125 Behçet’s disease cases Follow-up 25 yrsFollow-up 25 yrs82/125 (66%) intestinal Behçet’s disease 22/82 (27%) intestinal perforationMale/female 14/8 - Age 22-65 yrsSurgery:• Hemicolectomy 11• Partial Ileum Resection 8• Ileocecal Resection 3Reperforation:3

Chou SJ et al J Gastrointest Surg 2007Choi IJ et al. Dis Colon Rectum 2000

Kin Js et al. Endoscopy 2000


Entero BehçetTreatment

Glucocorticoids plus Azathiopine / 6-mercaptopurine• Prednisone 0.5 to 1.0 mg/kg daily• Azathioprine 2.5 – 2.5 mg/k / daily

Infliximab3 to 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks3 to 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks(Travis SP et al , Gut 2001; Kram MT et al, Dis Colon Rectum. 2003; Naganuma M et al, Inflamm Bowel Dis 2008; Lee JH et al Korean J Intern Med 2007))

Thalidomide 2 mg/kg per day, (Yasui K et al, J Pediatr 2003; Yasui K et al Inflamm Bowel Dis 2008)

Cyclosporin

Surgery


Entero BehçetDiagnosis

……the problem is not to assess the presence of GI involvement in a patient with a known Behçet disease, but ……

……the problem is not to assess the presence of GI involvement in a patient with a known Behçet disease, but …… a known Behçet disease, but ……

to make a diagnosis of Behçet syndrome in a patient with GI ulcers

a known Behçet disease, but ……

to make a diagnosis of Behçet syndrome in a patient with GI ulcers



• Radiology

• Endoscopy• Upper GI Endoscopy• Colonoscopy

Wireless Capsule Endoscopy

• Radiology

• Endoscopy• Upper GI Endoscopy• Colonoscopy

Wireless Capsule Endoscopy• Colonoscopy• Wireless Capsule Endoscopy

• Histology

• Serology

but ……

• Colonoscopy• Wireless Capsule Endoscopy

• Histology

• Serology

but ……



Small Bowel & Colon Barium Studies• mucosal fold thickening

• discrete ulcers • poor sensitivity and specificity

Small Bowel & Colon Barium Studies• mucosal fold thickening

• discrete ulcers • poor sensitivity and specificity

CT scans• bowel wall thickening• perienteric infiltration • polipoid bowel involvement• polipod mass-like lesions

CT scans• bowel wall thickening• perienteric infiltration • polipoid bowel involvement• polipod mass-like lesions

Chung SY et alRadiographics 2001



• Endoscopy• Upper GI Endoscopy• Colonoscopy• Small Bowel Capsule Endoscopy


Crohn’s


Behçet’s

Entero BehçetWireless Capsule Endoscopy


Thomson M et al. J Pediatr Gastroenterol Nutr 2007Hamdulay SS et al Rheumatology Oxford 2008

Barium-CT pos.ve / suspected Behçet (0/11 - 0%)

WCE pos.ve / suspected Behçet ( 10/11 - 91%)

Barium-CT pos.ve / suspected Behçet (0/11 - 0%)

WCE pos.ve / suspected Behçet ( 10/11 - 91%)



• Histology


• Histology • Histology does not discriminate

between Behçet and other Gastrointestinal Vasculitis, specific for IBD only when early lesions are present

• Serology

• Histology does not discriminate

between Behçet and other Gastrointestinal Vasculitis, specific for IBD only when early lesions are present

• Serology



Serology

ASCA IgA & IgG

Crohn Disease 42%Behçet Disease 4%

Serology

ASCA IgA & IgG

Crohn Disease 42%Behçet Disease 4%Behçet Disease 4%Ulcerative Colitis 4%Ankilosing Spondilitis 15%

Behçet Disease 4%Ulcerative Colitis 4%Ankilosing Spondilitis 15%

Fresko I et al. Clin Exper Rheumatol 2005Choi CH et al. Dis Colon Rectum 2006



Serology

ASCA IgA & IgG

Crohn Disease 42%Behçet Disease 4%

Serology

ASCA IgA & IgG

Crohn Disease 42%Behçet Disease 4%Behçet Disease 4%Ulcerative Colitis 4%Ankilosing Spondilitis 15%Enteral Behçet 44%

……..severity and relapse rates of intestinal Behçet's disease not associated with ASCA expression. ASCA pos.ve pts more likely to receive surgical treatment.

Behçet Disease 4%Ulcerative Colitis 4%Ankilosing Spondilitis 15%Enteral Behçet 44%

……..severity and relapse rates of intestinal Behçet's disease not associated with ASCA expression. ASCA pos.ve pts more likely to receive surgical treatment.

Fresko I et al. Clin Exper Rheumatol 2005Choi CH et al. Dis Colon Rectum 2006



• Barium Studies


• Barium Studies

• Endoscopy• Upper GI Endoscopy• Colonoscopy• Small Bowel Capsule Endoscopy• Colonoscopy• Small Bowel Capsule Endoscopy

• Biopsy

• Serology

• International Diagnostic Criteria

• Colonoscopy• Small Bowel Capsule Endoscopy

• Biopsy

• Serology

• International Diagnostic Criteria


Entero BehçetInternational Diagnostic Criteria

Recurrent Oral Aphthae (three times in one year)

plus two of the following in the absence of other systemic diseases:

• Recurrent genital aphthae

• Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit




• Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit • Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit

lamp examination, or retinal vasculitis, observed by an ophthalmologist)

• Skin lesions (including erythema nodosum, pseudo vasculitis, papulopustular

lesions, or acneiform nodules consistent with Behcet's)

• A positive pathergy test (a papule 2 mm or more in size developing 24 to

48 hours after oblique insertion of a 20 to 25 gauge needle 5mm into the skin,

generally performed on the forearm)

• Eye lesions (including anterior or posterior uveitis, cells in vitreous on slit


• Skin lesions (including erythema nodosum, pseudo vasculitis, papulopustular

lesions, or acneiform nodules consistent with Behcet's)




International Study Group for Behcet's Disease. Lancet 1990


Entero BehçetSensitivity & specificity of Behçet Diagnostic criteria

Sensitivity Specificity

International 95% 100%


International 95% 100%International 95% 100%

Japanese 100% 95%

Mason & Barnes 100% 94%


Japanese 100% 95%


International Study Group for Behcet's Disease. Lancet 199Tunc R etr al. Clin Exp Rheumatol 2001

Chang HK et al Clin Exp Rheumatol 2004


Entero BehçetInternational Diagnostic Criteria




• Eye lesions (including anterior or posterior Uveitis , cells in vitreous on slit




• Eye lesions (including anterior or posterior Uveitis , cells in vitreous on slit • Eye lesions (including anterior or posterior Uveitis , cells in vitreous on slit


• Skin lesions (including Erythema Nodosum , pseudo vasculitis,

papulopustular lesions, or acneiform nodules consistent with Behcet's)




• Eye lesions (including anterior or posterior Uveitis , cells in vitreous on slit


• Skin lesions (including Erythema Nodosum , pseudo vasculitis,

papulopustular lesions, or acneiform nodules consistent with Behcet's)




International Study Group for Behcet's Disease. Lancet 1990





Japanese 100% 95%



Japanese 100% 95%


… inclusion of pts with Crohn disease and Ulcerative Colitis did not

substantially change sensitivity & specificity of ISG (International Study

Group) diagnostic score


… inclusion of pts with Crohn disease and Ulcerative Colitis did not

substantially change sensitivity & specificity of ISG (International Study

Group) diagnostic score




Entero BehçetConclusions

.....if you have still some doubt on your diagnosis……......if you have still some doubt on your diagnosis…….

…. just rule out infective colitis and feel comfortable since …….…. just rule out infective colitis and feel comfortable since …….



Steroids

Azathioprine

Steroids

Azathioprine


InfliximabInfliximab


Steroids

Azathioprine

Steroids

Azathioprine


Infliximab

…… are perfectly fitting with both Behçet’ and Crohn’s diseases

Infliximab

…… are perfectly fitting with both Behçet’ and Crohn’s diseases


Crohn’s Behçet’s

Steroids OK OK

Crohn’s Behçet’s

Steroids OK OK


Azathioprine OK OK

Infliximab OK OK

Azathioprine OK OK

Infliximab OK OK

…if you still have some doubt on the diagnosis,

Just rule out infective colitis and fell confortable since …….

Crohn’s Behçet’sCrohn’s Behçet’s

Steroids OK OK

Azathioprine OK OK

Infliximab OK OK

….. Perfectly fitting for both Behçet’s and Crohn’s disease.


The Mason–Barnes Criteria

Major Symptoms Minor Symptoms

Buccal ulcerations Gastrointestinal lesions

Genital ulcerations Thrombophlebitis

Ocular lesions Cardiovascular lesionsOcular lesions Cardiovascular lesions

Skin lesions

Arthritis

Neurologic lesions

Family history

Three major or two major and two minor criteria are required to establish the diagnosis of Behçet’s disease





International 95% 100%International 95% 100%

Japanese (Suzuki) 100% 95%



Japanese (Suzuki) 100% 95%





XIII Congresso Nazionale delle XIII Congresso Nazionale delle

Malattie DigestiveMalattie Digestive

Corso AIGOCorso AIGO--SIGESIGE

“Hot topics in Gastroenterologia”“Hot topics in Gastroenterologia”Palermo Palermo –– 3 ottobre 20073 ottobre 2007

XIII Congresso Nazionale delle XIII Congresso Nazionale delle

Malattie DigestiveMalattie Digestive

Corso AIGOCorso AIGO--SIGESIGE

“Hot topics in Gastroenterologia”“Hot topics in Gastroenterologia”Palermo Palermo –– 3 ottobre 20073 ottobre 2007

“Up date” su …. Colangite Sclerosante “Up date” su …. Colangite Sclerosante Colangite Sclerosante PrimitivaColangite Sclerosante Primitiva

F. RosinaPresidio Sanitario GradenigoTorino

F. RosinaPresidio Sanitario GradenigoTorino


• Oral ulcerations (95-100%)• Uro-genital lesions (75%)• Cutaneous lesions (>75%)• Ocular disease (25-75%)• Neurologic disease ( < 20%)• Vascular disease (33%)• Arthritis (75%)• Renal disease (uncommon)• Cardiac disease (uncommon)• Pulmonary diasease (uncommon)• Gastrointestinal Symptoms (common)

20° Congresso Regionale ACOI , 31 ottobre 2008

• Gastrointestinal Symptoms (common)• Gastrointestinal disease (more or less frequent depending on the geographical area: unfrequent in in Italy and middle east – common in far east (Japan, Korea)•Severity is generally greater in men. The greatest morbidity and mortality occurs with ocular disease (affecting up to two-thirds of patients), vascular disease (affecting up to one-third of patients), and central nervous system disease (affecting 10 to 20 percent of patients). Cutaneous and articular manifestations are common. Renal disease and peripheral nervous system involvement are less common than in other vasculitides

Behçet disease Epidemiology

Behcet's disease is more common (and often more severe) along the ancient silk road, which extends from eastern Asia to the Mediterranean [4]. It is most common in Turkey (80 to 370 cases per 100,000) while the prevalence ranges from 13.5 to 20 per 100,000 in Japan, Korea, China, Iran, Iraq, and Saudi Arabia [4]. By comparison, the prevalence is from 1:15,000 to 1:500,000 in Northern American (Olmsted County, Minnesota) and Northern European countries. It is somewhat more common in men in the eastern Mediterranean area and in women in north


more common in men in the eastern Mediterranean area and in women in north European countries, and typically affects young adults 20 to 40 years of age. The disease appears to be more severe in young, male, and Middle Eastern or Far Eastern patients

FARE TABELLA IMPOSTANDOLA TUTTA SU UN RAPPORTO …./100.000

clinical manifestations vary among different patients and populations. Men and women have different propensities to develop the disease, but this varies among populations. As an example, Behcet's is more common in men in the Middle East and in women in Japan and Korea [6].

Behçet disease Vascular disease

Most clinical manifestations of Behcet's disease are due to vasculitis involving:

Most clinical manifestations of Behcet's disease are due to vasculitis involving:


vasculitis involving:

• blood vessels of all sizes

• arterial and venous

vasculitis involving:

• blood vessels of all sizes

• arterial and venous

Behçet disease Budd Chiari etiology Myeloproliferative diseases

Malignancy

Hepatocellular carcinoma

Infections and benign lesions of the liver

Oral contraceptives

Pregnancy

Hypercoagulable states


Hypercoagulable states(Factor V Leiden mutation, Prothrombin gene mutation, Antiphospholipid antibody syndrome, Antithrombin III deficiency, Protein C deficiency, Protein S deficiency )

Paroxysmal nocturnal hemoglobinuria

JAK2 mutations

Behcet's disease

Membranous webs of the inferior vena cava and/or the hepatic veins

Miscellaneous conditions

Idiopathic


•• Oral ulcerationsOral ulcerations (95(95--100%)100%)•• UroUro--genital lesionsgenital lesions (75%)(75%)•• Cutaneous lesionsCutaneous lesions (>75%)(>75%)•• Ocular diseaseOcular disease (25(25--75%)75%)•• Neurologic diseaseNeurologic disease ( < 20%)( < 20%)

•• Oral ulcerationsOral ulcerations (95(95--100%)100%)•• UroUro--genital lesionsgenital lesions (75%)(75%)•• Cutaneous lesionsCutaneous lesions (>75%)(>75%)•• Ocular diseaseOcular disease (25(25--75%)75%)•• Neurologic diseaseNeurologic disease ( < 20%)( < 20%)


•• Neurologic diseaseNeurologic disease ( < 20%)( < 20%)•• large Vessel large Vessel Vascular diseaseVascular disease (33%)(33%)•• ArthritisArthritis (75%)(75%)•• Renal diseaseRenal disease (uncommon)(uncommon)•• Cardiac diseaseCardiac disease (uncommon)(uncommon)•• Pulmonary diseasePulmonary disease (uncommon)(uncommon)•• Gastrointestinal SymptomsGastrointestinal Symptoms (common)(common)•• Gastrointestinal DiseaseGastrointestinal Disease (more or less frequent depending on the geographical (more or less frequent depending on the geographical

area: infrequent in in Italy and middle east area: infrequent in in Italy and middle east –– common in far east)common in far east)

•• Neurologic diseaseNeurologic disease ( < 20%)( < 20%)•• large Vessel large Vessel Vascular diseaseVascular disease (33%)(33%)•• ArthritisArthritis (75%)(75%)•• Renal diseaseRenal disease (uncommon)(uncommon)•• Cardiac diseaseCardiac disease (uncommon)(uncommon)•• Pulmonary diseasePulmonary disease (uncommon)(uncommon)•• Gastrointestinal SymptomsGastrointestinal Symptoms (common)(common)•• Gastrointestinal DiseaseGastrointestinal Disease (more or less frequent depending on the geographical (more or less frequent depending on the geographical

area: infrequent in in Italy and middle east area: infrequent in in Italy and middle east –– common in far east)common in far east)

master rosina marzo 09 [2]

Health & Medicine