Transcript physical examination

IN THE NAME OF GOD
Three cases of Behcet`s disease
with vascular involvement
Gholamrezapoor, MD, resident of internal
medicine
&
Sasan Fallahi, MD, rheumatologist, Kerman
University of Medical Sciences
CASE PRESENTATION
FIRST CASE
A 48 years old female
HISTORY
• Chief complaint
Pain and swelling of the left lower limb
• Present illness
Patient’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.
HISTORY
• Past History
she 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.
HISTORY
• Family History
There was no significant point.
• Personal and Social History
She was not smoker and opium addict.
HISTORY
• Review of Systems
Oral painful lesions
–
–
–
–
Since 8 years ago
Interval 20 days
Duration 10-15 days
At the time of physical examination, the lesion was present.
Genital painful lesions
–
–
–
–
Since 4 years ago
Interval several months
Duration 5-7 days
At the time of physical examination, the lesion was not present.
Dysuria
– When genital lesion was present
HISTORY
• Review of Systems
Red eye, tearing and Pain in left eye since 20 years
ago intermittently.
No history of visual loss
Skin lesion in both lower limbs since 15 days ago
No history of headache and seizure
No history of GI problems such as abdominal pain
or diarrhea
No history of arthralgia or arthritis
PHYSICAL EXAMINATION
• General Survey
Patient is a middle age female, awake and
oriented, without any distress, she was thin and
pale.
• Vital Signs
PR:80
RR:15
BP:90/60 AxilaryT:37
PHYSICAL 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 adenopathy
• Chest & Cardiac & Axillary
NL
• Abdomen
Prominent veins were visible in epigastric zone, with flow
from down to up.
There was no distention, tenderness, hepatomegaly,
splenomegaly and ascites.
PHYSICAL 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
PHYSICAL 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.
DUPPLER 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.
DIANOSIS
DVT
LABORATORY TEST
• CBC
WBC:7500
RBC:3790000
HG:9.2
HCT:31.3
MCV:82.6
MCH:24.3
MCHC:24.4
Plat:360000
ESR:104
CRP:+3
RF: Neg
LABORATORY TEST
• Biochemistry
BS:86
Urea:15
Creat:0.89
AST:18
ALT:12
Al Ph:255
Bil Total:0.6
Bil Direct:0.16
LDH:435
• Electrolyte
Na:135
K:3.9
Ca:8.5
P:4.5
• Coagulative
PTT:41
PT:15
INR:1
LABORATORY TEST
• PBS
Hypochromic:+1
Anisocytosis:Mild
Poychilocytosis:+1
Ovalucytosis:Mild
Teardrop:Mild
Helmet:Mild
• Urine analysis
SG:1015
PH:7
Others: NL
ECHOCARDIOGRAPHY
• EF:60%
• PAP:NL
• There was no abnormal finding.
ABDOMINOPELVICE SONOGRAPHY
• Liver, biliary tract, pancreas and urinary tract
were normal
GYNECOLOGICAL CONSULT
• No aphthous, active lesion or scar in genital
area
OPHTHALMOLOGICAL CONSULT
• There was naso-lacrimal duct stenosis in left
eye.
• No evidence of uveitis or retinal vasculitis
SECOND CASE
A 36 years old male
HISTORY
• Chief complaint
Pain and swelling of the right lower limb since
two weeks ago
• Present 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
HISTORY
• 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.
HISTORY
• Family History
No significant point.
• Personal and Social History
No smoking and opium addiction
HISTORY
• Review of Systems
Oral painful lesions
– The first time appeared at 1375 and continued for 2 weeks and then
disappeared for 5 years
– Further started from 1380
– Interval 20 days
– Duration about 15 days
– At the time of physical examination, the lesion was present.
Genital painful lesions
– The first time appeared at 1380
And reoccurred several times .
– Duration 3-5 days
– At the time of physical examination, there was no lesion or scar.
HISTORY
• 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
PHYSICAL EXAMINATION
Patient is a young male, awake and oriented,
without any distress.
• Vital Signs
PR:84
RR:14
BP:120/80
AxillaryT:37.4
PHYSICAL EXAMINATION
• Head & Neck
-An aphthous lesion in anterior side of tongue was
noted.
-Trachea and thyroid were normal.
-No adenopathy
• Chest & Cardiac & Axillary
NL
• Abdomen
-No distention, tenderness, hepatomegaly,
splenomegaly and ascites
PHYSICAL 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.
PHYSICAL 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 .
DUPPLER SONOGRAPHY
• Thrombosis in popliteal vein
• CFV and SFV were normal.
• SMA, SMV, portal vein and IVC were normal.
DIAGNOSIS
DVT
LABORATORY TEST
• CBC
WBC:7400
RBC:5180000
HG:14.3
HCT:45
MCV:87
MCH:28
MCHC:32.1
Plat:374000
• Biochemistry
BS:207
Urea:31
Creat:1
AST:14
ALT:13
Al Ph:234
Bil Total:0.75
Bil Direct:0.16
Uric acid:4.8
LABORATORY TEST
• Electrolyte
Na:137
K:4.2
Ca:9.2
P:3.5
• Coagulative
PTT:31
PT:13
INR:1.1
Pathergy test
THIRD CASE
34 years old male
HISTORY
-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
HISTORY
-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.
HISTORY
• 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
THE FIRST CASE
Oral aphtous
+
Erythema nodosum
+
DVT
+
Positive pathergy test
Behcet’s disease
THE SECOND CASE
Oral aphtous
+
Pseudofolliculitis Lesions
+
DVT
+
Positive pathergy test
Behcet’s disease
THE THIRD CASE
Oral aphtous
+
Increased ICP, Cerebral venous sinus thrombosis and lower limb DVT
+
Arterial aneurysm
+
Positive pathergy test
Behcet’s disease
VIRCHOW'S TRIAD
• Proposes that VTE occurs as a result of
1. Alterations in blood flow (stasis)
2. Vascular endothelial injury
3. Alterations in the constituents of the blood
(inherited or acquired hypercoagulable state)
RISK FACTORS FOR VENOUS
THROMBOSIS
• Inherited thrombophilia
1. Factor V Leiden
mutation
2. Prothrombin gene
mutation
3. Protein S deficiency
4. Protein C deficiency
5. Antithrombin (AT)
deficiency
6. Rare disorders
Dysfibrinogenemia
RISK FACTORS FOR VENOUS
THROMBOSIS
• Acquired disorders
1. Malignancy
2. Surgery, especially
orthopedic
3. Trauma
4. Pregnancy
5. Oral contraceptives
6. Immobilization
7. Antiphospholipid antibody
syndrome
8. Myeloproliferative
disorders
–
Polycythemia vera
–
Essential thrombocythemia
9) Presence of a central
venous catheter
10) Congestive failure
11) Hormone replacement
therapy
12) Tamoxifen, Thalidomide,
Lenalidomide
13) PNH
14) IBD
15) Nephrotic syndrome
16) Behcet disease
SCREENING 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 members
• There is currently no consensus regarding who
to test for inherited thrombophilia
SCREENING FOR HYPERCOAGULABLE
STATE
Only patients with one or more of the following:
1. Initial thrombosis occurring prior to age 50 without an
immediately identified risk factor (ie, idiopathic or
unprovoked venous thrombosis)
2. A family history of venous thromboembolism (ie, firstdegree relatives with VTE prior to age 50)
3. Recurrent venous thrombosis
4. Thrombosis occurring in unusual vascular beds such
as portal, hepatic, mesenteric, or cerebral veins
5. A history of warfarin-induced skin necrosis, which
suggests protein C deficiency
THROMBOPHILIA WORK-UP
1.
2.
3.
4.
5.
6.
7.
8.
Antithrombin
Protein C
Protein S
Factor VIII level
Factor V Leiden
Antiphospholipid antibodies
Lupus anticoagulant
Prothrombin gene mutation
Thrombophilia workup:Effects of anticoagulant
therapy and acute thrombosis
Hypercoagulable
disorder for testing
Confounding Factors
Acute thrombosis
Heparin therapy
Coumadin therapy
Can be lowered
Lowered
NC; Rarely increased
Antiphospholipid
antibodies
NC
NC
NC
Factor V Leiden
NC
NC
NC
Antithrombin
(deficiency)
Factor VIII level
Acute phase reactant. Do not test while inflammation is still present.
Lupus anticoagulant
NC
Cannot measure
False positives
possible
Protein C (deficiency)
Can be lowered*
NC
Cannot measure•
Protein S (deficiency)
Can be lowered*
NC
Cannot measure•
NC
NC
NC
Prothrombin gene
mutation
BEHCET’S DISEASE
DEFINITION
• Behcet's disease is a multisystem autoimmune
disorder presenting with recurrent oral and
genital ulcerations as well as ocular
involvement.
EPIDEMIOLOGY
•
•
•
•
Affects young males and females
Males and females are affected equally
Males often have more severe disease
Mediterranean region, the Middle East, and the
Far East
• Prevalence ranges from 13.5 to 20 per 100,000
• Prevalence in the United States and Europe have
ranged from 0.12 to 7.5 per 100,000
PATHOGENESIS
The etiology and pathogenesis of this syndrome remain
obscure
• Increase of circulating autoantibodies
– Anti-Enolase of endothelial cells
– Anti-Selenium binding protein
– Anti-Saccharomyces cerevisiae antibodies
• Association of Behcet's disease with HLA-B*5, HLAB*51 and the MHC Class I region is confirmed
• An association with ILI0 and the IL23R-ILI2RB2 locus
were also observed
• Perhaps infectious acts as a immune activity trigger
PATHOLOGY
The classic Behçet’s lesion is
1. Necrotizing leukocytoclastic obliterative
perivasculitis
2. Venous thrombosis
3. Lymphocytic infiltration of capillaries, veins and
arteries of all sizes
• Cellular infiltration is often neutrophils and CD4+ T
lymphocytes
• In some patients, diffuse inflammatory disease,
involving all layers of large vessels and resulting
to formation of pseudoaneurysms, suggests
vasculitis of vasa vasorum.
CLINICAL FEATURES
Mucocutaneous
1. The recurrent aphthous ulcerations
–
–
–
–
–
–
Are a sine qua non for the diagnosis
The ulcers are usually painful
Are shallow or deep with a central yellowish necrotic base
Appear singly or in crops
Are located anywhere in the oral cavity
Less than 10 mm in diameter are seen in 85% of patients,
while large or herpetiform lesions are less frequent
– The ulcers persist for 1-2 weeks and subside without
leaving scars
CLINICAL FEATURES
2. The genital ulcers
– Are less common but more specific
– Painful
– Do not affect the glans penis or urethra
– Produce scrotal scars
3. Pseudofolliculitis
4. Erythema nodosum
5. Acne-like exanthem
CLINICAL FEATURES
Eye involvement
• Occurring in 50% of patients
• Is usually present at the onset but may also develop
within the first few years
• Includes
1. Anterior uveitis (Iritis )
2. Posterior uveitis
3. Bilateral pan uveitis with scarring
• Is the most dreaded complication, since it occasionally progresses
rapidly to blindness.
4. Retinal vessel occlusions
5. Optic neuritis
CLINICAL FEATURES
Articular involvement
• Seen in a 50% of patients
• Non-deforming arthritis or arthralgia
• Affects knees and ankles
CLINICAL FEATURES
Vascular involvement
1. Venous involvement
– SVT or DVT is seen in 30% of patients
– The superior vena cava is obstructed occasionally
– Pulmonary emboli are a rare complication
2. Arterial involvement
– Occurs in less than 5% of patients
– Presents with
•
•
•
•
Aortitis
Peripheral arterial aneurysm
Arterial thrombosis
Pulmonary artery vasculitis presenting with dyspnea, cough, chest
pain, hemoptysis, and infiltrates on chest roentgenograms has been
reported in 5% of patients
• Behcet’s disease involve blood vessels of all
sizes - small, medium, and large - both arteries
and veins
CLINICAL FEATURES
Neurologic involvement
• 5-10%
1. Mainly in the parenchymal form (80%) it is
associated with brain stem involvement
– IL-6 is persistently raised in CSF of these patients
2. Dural sinus thrombi (20%) are associated
with headache and increased ICP
CLINICAL FEATURES
Gastrointestinal involvement
• Is seen more frequently in patients from Japan
• Consists of mucosal ulcerations of the gut,
resembling Crohn's disease
Genital tract involvement
• Epididymitis is seen in 5% of patients
PATHERGY TEST
• Nonspecific skin inflammatory reactivity to
any scratches or intradermal saline injection is
a common and specific manifestation
• A 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
DIFFERENTIAL DIAGNOSIS
• Differential diagnosis of recurrent oral ulcers includes
–
–
–
–
–
–
–
–
–
–
–
Herpes simplex
Benign aphthous ulcers
Inflammatory bowel disease
Stevens-Johnson syndrome
SLE
Dental prosthetics
Oral hygiene products
Medications such as methotrexate can cause oral ulcers
Pemphigoid, pemphigus vulgaris, cicatricial pemphigoid,
Lichen planus
Linear IgA disease
DIFFERENTIAL DIAGNOSIS
• Differential diagnosis of genital ulcers include:
– HSV
– Syphilis
– Chancroid
– Lymphogranuloma venereum
– Fixed drug reactions
– Neoplasms
– Trauma
DIFFERENTIAL DIAGNOSIS
• Other causes of inflammatory eye disease, neurologic
disease, vascular disease, arthritis, are included
–
–
–
–
–
–
–
–
–
–
–
–
SLE
IBD
Sarcoidosis
Reactive arthritis
Psoriatic arthritis
Ankylosing spondylitis
Juvenile idiopathic arthritis
FMF
MS
Tuberculosis
HIV
Malignancies
DIAGNOSIS
• Diagnosis is clinical and based on
internationally agreed diagnostic criteria
• Recurrent oral ulceration plus two of the
following:
1. Recurrent genital ulceration
2. Eye lesions
3. Skin lesions
4. Pathergy test
LABORATORY FINDINGS
• Laboratory findings are mainly nonspecific
indices of inflammation, such as
1. Leukocytosis
2. Elevated erythrocyte sedimentation rate
3. Elevated C-reactive protein levels
TREATMENT
• Mucocutaneouce involvement
1. Topical glucocorticoids (triamcinolone) in the form
of mouthwash or paste
2. Topical Sucralfate 1g/5mL four times daily as a
mouthwash
3. Colchicine
4. In more serious cases, Thalidomide (l00 mg/d)
5. 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
TREATMENT
• Uveitis
– Prednisone(I mg/kg per day) and azathioprine (2-3
mg/kg per day)
• Sight-threatening uveitis
– Cyclosporin (5mg/kg) +/- azathioprine
• Panuveitis refractory or intolerant to other
immunosuppressives
– Anti-TNF therapy
TREATMENT
• Arthritis
1. Colchicine 1 to 2 mg/day, administered in
divided doses
2. NSAIDs
3. Prednisone 10 mg/day is an appropriate starting
dose
• Joint complaints not controlled by colchicine
TREATMENT
• CNS-Behcet's syndrome
– Prednisone(I mg/kg per day) and azathioprine (2-3
mg/kg per day)
PROGNOSIS
• Behçet’s disease typically has a waxing and
waning course characterized by exacerbations
and remissions
• The disease appears to be more severe in young,
male, and Middle Eastern or Far Eastern patients
• The severity of the syndrome usually abates with
time
• Apart 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
Oral aphthous on tongue
Oral aphthous
Dilated superficial veins
Erythema nodosum
Oral aphthous