Master Rosina Marzo 09 [2]

Patologie Immuni &
Malattie Orfane
Torino – 22-24 Gennaio 2009
22-

Entero Behçet
F. Rosina
PRESIDIO SANITARIO GRADENIGO
TORINO
S.C. Gastroenterologia & Epatologia

Behçet disease
Epidemiology of a rare disease

North 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

Far & Middle East 13,5 - 20/100.000


Behçet disease
Epidemiology of a common disease

Far & Middle East 13,5 - 20/100.000
Turkey 80 - 370 / 100,000


Behçet disease
Epidemiology of a common disease

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

Age 20-40 yrs

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

Severity More severe in Young Men
Middle & Far East


Behçet disease
Definition

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


Behçet disease
Clinical manifestations

100
100

90

80
75 75 75
70

60

50
50

40
33
30

20
20

10
10
1 1 1
0
ng
l

l
al
e
n
rs

ac
ar

I
is
ita

na

G
Ey
i

ur
rit
Sk
lce

ul

Lu
di
en

Re
th

Ne
sc

ar
lU

og

Ar

Va

C
ra

Ur
O


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 was performed.
(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 microcoils (Hong
YK, Yoo WH. Rheumatol Int 2008)


Behçet disease
Large Vessels Disease

Number of
patients
Venous disease
Deep venous thrombosis 221/728 (30%)
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)


Behçet
Small Vessels Disease: Entero Behçet

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


Behçet disease

Italy Turkey China Taiwan Korea Thai
Number of studied pts 137 2313 28 125 1527 23
• Oral ulcerations 99% 100% 95% NR 99% 100%
• Uro-genital lesions
Uro- 63% 85% 50% NR 83% 70%
• Cutaneous lesions 82% 80% 95% NR 84% 61%
• Ocular disease 61% 38% 50% NR 51% 52%
• Neurologic disease NR 3% NR NR NR 9%
• Vascular disease NR 25% NR NR NR 9%
• Arthritis NR 11% 45% NR NR NR
• Renal disease NR NR NR NR NR NR
• Cardiac disease NR NR NR NR NR NR
• Pulmonary disease NR 0,03% NR NR NR NR
Salvarani C et al. Arthritis Rheum 2007
Pipitone N et al. Clin Exp Rheumatol 2004
Tursen U et al. Int J Dermatol 2003
Ning Sheng L et al. Clin Rheumatol 2005
Chou SJ et al J Gastrointest Surg 2007
Ling J et al Yan Ke Xue Bao 2005
Bang D et al. J Korean Med Sci 2001


Behçet disease
Gastrointestinal

100
* 43% HP/NSAIDs neg.ve
90
Peptic ulcers
80
70 66
60
50
40 35
30
20
9 9
10
1,5 Salvarani C et al. Arthritis Rheum 2007
0
0 Pipitone N et al. Clin Exp Rheumatol 2004
Tursen U et al. Int J Dermatol 2003
Ning Sheng L et al. Clin Rheumatol 2005
ey

a
ly

an
ai

a*
re
Ita

Th
rk

iw
in
Ko
Tu

Ch

Ta

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


Entero Behçet
Natural History

Remitting relapsing disease complicated by
Intestinal perforation

Taiwan
125 Behçet’s disease cases
Follow-up 25 yrs
82/125 (66%) intestinal Behçet’s disease
22/82 (27%) intestinal perforation
Male/female 14/8 - Age 22-65 yrs
Surgery:
• Hemicolectomy 11
• Partial Ileum Resection 8
• Ileocecal Resection 3
Reperforation:3
Choi IJ et al. Dis Colon Rectum 2000
Kin Js et al. Endoscopy 2000


Entero Behçet
Treatment

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

Infliximab
3 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 Behçet
Diagnosis

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

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


Entero Behçet
Diagnosis

• Radiology

• Endoscopy
• Upper GI Endoscopy
• Colonoscopy
• Wireless Capsule Endoscopy

• Histology

• Serology

but ……


Entero Behçet
Diagnosis
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
Chung SY et alRadiographics 2001


Entero Behçet
Diagnosis

Crohn’s
• Endoscopy
• Colonoscopy
• Small Bowel Capsule Endoscopy
Behçet’s


Entero Behçet
Wireless Capsule Endoscopy

Barium-CT pos.ve / suspected Behçet (0/11 - 0%)
WCE pos.ve / suspected Behçet (10/11 - 91%)

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


Entero Behçet
Diagnosis

• Endoscopy
• Colonoscopy
• Small Bowel Capsule
Endoscopy

• Histology
does not discriminate
between Behçet and other
Gastrointestinal Vasculitis,
specific for IBD only when
early lesions are present

• Serology

Entero Behçet
Diagnosis

Serology

ASCA IgA & IgG

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

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


Entero Behçet
Diagnosis

Serology

ASCA IgA & IgG
Crohn Disease 42%
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 2005
Choi CH et al. Dis Colon Rectum 2006


Entero Behçet
Diagnosis

• Barium Studies

• Endoscopy
• Colonoscopy
• Small Bowel Capsule Endoscopy

• Biopsy

• Serology

• International Diagnostic Criteria


Entero Behçet
International 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
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)
International Study Group for Behcet's Disease. Lancet 1990


Entero Behçet
Sensitivity & specificity of Behçet Diagnostic criteria

Sensitivity Specificity

International 95% 100%

Japanese 100% 95%

Mason & Barnes 100% 94%

Tunc R etr al. Clin Exp Rheumatol 2001
Chang HK et al Clin Exp Rheumatol 2004


Entero Behçet
International 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
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)


Entero Behçet



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


Entero Behçet
Conclusions

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

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


Entero Behçet
Conclusions

Steroids
Azathioprine
Infliximab


Entero Behçet
Conclusions

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


Entero Behçet
Conclusions

Crohn’s Behçet’s

Steroids 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’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 lesions
Arthritis
Skin lesions Neurologic lesions
Family history

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

Entero Behçet



Japanese (Suzuki) 100% 95%




XIII Congresso Nazionale delle
Malattie Digestive
Corso AIGO-SIGE
AIGO-
“Hot topics in Gastroenterologia”
Palermo – 3 ottobre 2007

“Up date” su ….
Colangite Sclerosante
Primitiva
F. Rosina
Presidio Sanitario Gradenigo
Torino

Behçet disease
• 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)
• 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
20° Congresso Regionale ACOI , 31 ottobre 2008

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
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:
• 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
(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


Behçet disease

• Oral ulcerations (95-100%)
(95-
• Uro-genital lesions (75%)
Uro-
• Cutaneous lesions (>75%)
• Ocular disease (25-75%)
(25-
• Neurologic disease ( < 20%)
• large Vessel Vascular disease (33%)
• Arthritis (75%)
• Renal disease (uncommon)
• Cardiac disease (uncommon)
• Pulmonary disease (uncommon)
• Gastrointestinal Symptoms (common)
• Gastrointestinal Disease (more or less frequent depending on the geographical
area: infrequent in in Italy and middle east – common in far east)


Master Rosina Marzo 09 [2]

Recommandé

Recommandé

Contenu connexe

Similaire à Master Rosina Marzo 09 [2]

Similaire à Master Rosina Marzo 09 [2] (6)

Plus de cmid

Plus de cmid (20)

Dernier

Dernier (20)

Master Rosina Marzo 09 [2]