Takayasu arteritis associated with
hypercholesterolemia presenting with an abdominal
mass in a 9 Year-old boy
Alyaa A Kotby1, Ola A Elmasry1, Omneya I Youssef1, Mervat G Mansour1, Abdul R
Shahein2
1
Department of Pediatrics, Ain Shams University, 38 Abbassia, Cairo, Egypt
Department of Pediatrics, Hospital for Sick Children, 555 University Avenue, Toronto,
Ontario, Canada M5G 1X8
2
Corresponding author email address: abdulrahman.shahein@utoronto.ca or abdulrahman.shahein@sickkids.ca
Alyaa A Kotby
ABSTRACT
Introduction: Takayasu arteritis (TA) is a large vessel granulomatous
vasculitis that commonly affects the thoracic and abdominal Aorta with
unknown etiology. The majority of TA occurs between 10 -40 years of age
and present with hypertension and absent right femoral pul se. There is
limited information about the role of hypercholesterolemia in pediatric TA.
Case presentation: W e report a unique case of 9 year -old boy with
angiogram-proven
Takayasu
arteritis
associated
with
hypercholesterolemia. The initial clinical manifestations included high
erythrocyte sedimentation rate, right iliac fossa swelling and pulseless
right lower limb. He responded to oral steroids and surgical resection of
the
aneurysm.
We
discuss
the
possible
contribution
of
hypercholesterolemia in (pediatric) patient with TA Conclusion:
Hypercholesterolemia should be investigated for the possibility of
worsening the course of pediatric TA.
MANUSCRIPT TEXT:
Introduction:
Takayasu arteritis was first diagnosed by a Japanese ophthalmologist on
the year 1908. It is now considered a worldwide disease. Takayasu
arteritis is a large vessel granulomatous vasculitis that commonly affects
the thoracic and abdominal Aorta with unknown etiology. The mechanism
of arteritis has not been fully elucidated to date but a non specific cell
mediated inflamm atory process that progresses to fibrotic stenosis of the
aorta is widely accepted [ 1 ] .
TA passes into early inflammatory pre -pulseless and late arterial
occlusive pulseless phase. The inflammatory stage usually presents with
nonspecific low grade fever, tachycardia and easy fatigability with
hypertension and diminished upper extremities pulses. The most
commonly involved vessels include the left subclavian artery (50%), left
common carotid artery (20%), brachiocephalic trunk, renal arteries, celiac
trunk, superior mesenteric artery, and pulmonary arteries. Axillary,
vertebral, coronary and iliac arteries are infrequently involved [ 2 ] .
There are many molecular defects that cause hypercholesterolemia in
pediatric patients. Familial hypercholesterolemia whic h is an autosomal
dominant disorder of defective or grossly mal -functioning low density
lipoprotein (LDL) receptors comes on top of the list. More than 700
mutations have been identified to have a meaningful impact on the LDL
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receptor function [ 3 ] . Other identified molecular defects are familial
defective
apoB-100,
phytosterolemia
and
autosomal
recessive
hypercholesterolemia that cause no symptoms in childhood [ 4 ] .
W e report the first case of childhood Takayasu's arteritis in a 9 year old
boy, who also suffers from hypercholesterolemia and discussing the
potential impact of hypercholesterolemia.
Case Presentation:
A 9 year-old white Caucasian Egyptian male child, the 4 t h born to
consanguineous parents presented with gradual onset of non -radiatin g
dull-aching pain in the right thigh of one month duration. The pain
increased with active movement of the limb and decreased with resting.
There was neither history of trauma or back strain nor history of pervious
operations or hernias. The patient had n o fever, tachycardia, chest pain,
arthralgia, rashes or blurring of vision. Past medical and family histories
were unremarkable.
Physical examination revealed diminished right femoral, popliteal and
dorsalis pedis pulses with capillary perfusion from 2 -3 seconds. A deep
oval swelling in right iliac fossa measuring 5 centimeters in diameter was
palpated. The swelling was intra -abdominal, non-pulsating, firm in
consistency and tender with no fixation to the skin or muscle. Blood
pressure measured 111/72 (85 t h percentile) in the right upper limb.
A comprehensive laboratory (Table 1) and radiological assessment were
done in order to establish the diagnosis. A color coded duplex
examination of the right lower limb arterial system showed a partially
thrombosed aneurysm of the right common iliac artery with thrombus
matter occupying 50% of the arterial lumen and turbulent flow in the rest
of the lumen.
The rest of the arterial system was all patent, showing biphasic flow
pattern with average flow velocities and no evidence of arterial occlusion.
Left renal artery duplex showed mild stenosis with acceleration of 2.4
M/sec (N: > 3M/sec) and normal resistive index of 0.37 (N :< 0.7).
Electrocardiogram (ECG) and chest X -ray were normal. Both right and left
lower limbs deep venous systems were thrombosed. Contrasted
computerized tomography and angiogram of the abdomen and pelvis
showed right common iliac artery aneurysm displacing the right psoas
muscle (Figure 1 A and 1B).
A decision was made to surgically resect and bypass the thrombosed
aneurysm with saphenous graft. The limp perfusion and pain markedly
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improvement after the surgery. Methicillin resistant staph aureus (MRSA)
grown upon culturing the revealed thrombus. The infection was treated
with intravenous Vancom ycin 15mg/kg/dose q8hrs over 14 days. Patient
then was started on oral anticoagulant therapy (warfarin sodium 3mg/day)
and returned back home. He didn’t return back for the designed follow -up
for unknown reasons.
One year later, he presented to the emerge ncy room with a picture of
heart failure due to hypertensive cardiomyopathy. Blood pressure
measured 149/109 (> 95 t h percentile), 138/99, 128/98 and 162/115 in right
upper limb, left upper limb, right lower limb and left lower limb
respectively. Echo cardi ogram revealed left ventricular hypertrophy,
stenosed abdominal aorta with normal flow and anatomy of the
coronaries.
The (ECG) showed left heart axis deviation. Computerized tomography
angiogram (CTA) for the aorta and both lower limb arteries showed
multiple stenotic segments of the aorta and brachiocephalic trunk with
segments of relative dilatation. The left renal artery couldn’t be delineated
with complete occlusion of the right common iliac artery (Figure 2). Lipid
profile was done at this point and repeatedly showed mild
hypercholesterolemia although normal dietetic habits (Table 2). Both
erythrocyte sedimentation rate (ESR) and C -reactive protein (CRP) were
again elevated.
Patient was then strongly considered to have Takayasu arteritis with an
unusual presentation based on the previously described angiograms,
hypertension and the markedly elevated erythrocyte sedimentation rate.
The child was then started on oral prednisolone (2mg/kg/day divided
doses) in order to control disease activity. Blood pressure returned to the
75 t h centile on amlodepine, Carvidalol and spironolactone. His lipid profile
normalized on diet control and atorvastatin (20 mg/day).
Discussion:
Our patient first presented with right iliac mass and pulseless right lower
limb which was preliminary thought to be a thrombosed congenital right
common iliac artery aneurysm. Elevated (ESR) and (CRP) at this time
were explained by the on top infection. He improved after surgical
resection and intravenous antibiotics.
During the interim period between his first and second presentation, the
disease seems to continue evolving with blood pressure climbing up until
precipitated heart failure (diastolic failure). He was finally diagnosed with
takayasu arteritis (TA) in his second presenta tion and fulfilled the revised
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EULAR/PReS
(European
League
against
Rheumatism/Pediatric
Rheumatology European Society) criteria for TA, given (1) aortic and renal
narrowing on radiographic imaging, (2) undetectable right tibial pulses,
and (3) hypertension [ 5 ] .
The majority of TA cases occur between 10 -40 years of age [ 6 ] . The
youngest age of presentation was reported by W eiss et al. about an
eighteen month-old infant with TA proven by arterial autopsy and
presented with cerebral aneurysm [ 7 ] . TA is more common in females with
ratio varied from (6.6: 1) in Korea and (2.9: 1) in China as reported by
Park et al [ 8 ] and Zheng et al [ 9 ] respectively.
During his second presentation, the child showed persistent moderate
hypercholesterolemia
( 293
mg/dL).
Although
hypercholesterolemia
couldn’t explain the above findings solely but we suggested this increase
to contribute with the ongoing inflammation affecting the major blood
vessels with TA. This explanation was not studied before. DNA
sequencing for LDL receptor gene was not done due to lack of facilities.
In support for our suggestion, Parissis et al concluded in his study on a
cohort of hypertensive patients who proved to have elevated inflammatory
markers in their blood that hypertension could induce an inflammatory
process in blood vessels. He also added that the coexistence of
hypercholesterolemia may en hance this inflammatory process [ 1 0 ] .
TA is usually treated by Corticosteroids to achieve remission. Although
more than 50% of these patients flare with tapering [ 1 1 ] . There are case
reports of treatment with methotrexate, azathioprine, infliximab [ 1 2 , 1 3 ] and
adalimumab [ 1 4 ] . The use of Cyclophosphamide is reserved for severe
systemic involvement and frequent relapses [ 1 5 ] .
Assessing response t o treatment in takayasu arteritis is challenging. Prior
studies have shown that clinical signs and symptoms of disease and
elevated acute phase reactants are poorly correlated with disease activity.
In the presence of hardware or clips from aneurismal repa ir, non -invasive
studies such as magnetic resonance angiogram (MRA) and (CTA) are
limited due to artifact. One recent report discussed the utility of non invasive measurement of aortic arterial elastic properties with M -mode
echocardiographic images in chi ldren with TA. Furthermore, the optimal
interval for serial imaging during remission is uncertain [ 1 6 ] .
Conclusion:
Hypercholesterolemia might worsen pediatric TA through promoting the
inflammatory process.
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CONFLICTS OF INTEREST
The Authors declare they don’t have any conflict of interest.
SUPPORTING INFORMATION
We included 2D echocardiogram videos showing the narrowing of the abdominal aorta
with a mass that looks to have a different echogenicity from the wall of the aorta in long
and cross sections.
REFERENCES
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aneurysms in an 18 month old: A case report. Pediatrics
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and angiographic features. Heart Vessel – Suppl 1992, 7:55 -59.
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9. Zheng D, Fan D, Liu L: Takayasu's arteritis in China: A report of 530
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FIGURES AND FIGURE CAPTIONS
Figure 1A
Figure 1B
Figure 1 (A) Contrasted computerized tomography of the abdomen; a
roughly rounded heterogeneous right iliac soft tissue density mass lesion
anterolateral to L5 measuring 6x4x4 cm and displacing the right psoas
muscle with breaking down and thrombosis of right iliac ve in (arrowhead).
(B) Computerized tomography angiogram of the abdomen and pelvis; right
common iliac artery aneurysm (dashed arrowhead).
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Figure 2 Multi-slice CT angiography for the aorta; marked irregular
thickening of the aortic wall affecting who le course of abdominal aorta, till
just proximal to the origin of inferior mesenteric artery with multiple
stenotic and relatively dilated segments. Mild stenotic segments are also
noted at the brachiocephalic trunk, right subclavian and both common
carotid arteries (solid arrowheads). No flow in right iliac artery (dashed
arrowhead).
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TABLES AND TABLE TITLE
Table 1: Laboratory evaluation of the patient
Test
Result
Blood picture and non specific
inflammatory markers
Total leukocytic count
Lymphocytes
Neutrophils
Hemoglobin
8.1 x 103/uL (N: 4.0-11.0)
2.7 x 103/uL (N: 1.0-4.0)
5.0 x 103/uL (N: 2.0-7.7)
10.9 gm/dL (N: 12.0-17.5)
Red cell Distribution width
Platelet count
International normalization Ration
Prothrombin Time
16.6% (N: 12-15)
311 103/uL (N: 150-400)
1.1
38 (Control: 28-40 seconds)
Mean corpuscular volume
Erythrocyte sedimentation rate (1st hour)
C-reactive protein
66.2 fL (N: 82-98)
100 mm (N:0-10mm)
96 mg/dl (N: < 6 mg/dl)
Thrombophilia workup
Antiphospholipid IgM
Antiphospholipid IgG
Anticardiolipin IgM
Anticardiolipin IgG
Factor V
Anti-thrombin III
Protein C
Protein S
Factor XIII activity
Serum Homocystine level
10.0 U/mL (N: up to 10.0)
3.0 U/mL (N: up to 10.0)
9.0 MPL U/mL (N: up to 11.0)
3.20 GPL U/mL (N: up to 23.0)
105% (N: 70-120)
23.00 mg/dL (N: 19.00-31.00)
99.0% (N: 72-160)
120.00% (N: 60.00-150.00)
Normal (No lysis after 24 hours)
12.57 umol/L (N: 3.7-13.9)
Systemic Lupus markers
Anti Nucleic Antibodies (ANA)
Anti double stranded DNA antibodies
Anti-Sm antibodies
Negative
Negative
Negative
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Table 2: Lipid profile during second presentation
Test
Result
Serum Cholesterol
Serum Triglycerides
HDLc
LDLc
VLDL
293 mg/dL (N: < 200)
118 mg/dL (N: up to 150)
138 mg/dL (N: > 40)
168 mg/dL (N: up to 100)
24 mg/dL (N: up to 32)
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