Transcript DIAGNOSTIC DILEMMA

DIAGNOSTIC DILEMMA
• PRESENTATION
• A 39-year-old Haitian woman arrived in the
emergency department for evaluation of a
severe headache and shortness of breath. She
had been experiencing chest pain, both at rest
and with exertion for several months.
• Episodes lasted for 10-15 minutes and were
substernal , very severe and squeezing in
nature and were intermittently associated
with dyspnea and nausea. The patient had
been limiting her physical activity because she
was afraid of precipitating chest discomfort.
• A review of systems was otherwise notable for
frequent headaches, a 5-10 pound
unintentional weight gain, fatigue, and
orthopnea. Exertion produced increased
fatigue, dyspnea, and bilateral leg pain and
“heaviness”. She denied lower-extremity
edema, new skin rashes, nodules, fevers, or
night sweats.
• Five years earlier, the patient, who had been
in the United States for 10 years, had been
diagnosed with hypertension during a
pregnancy. Her home medications included
lisinopril, 40 mg daily, and
hydrochlorothiazide, 25 mg daily, although she
had not taken either for about 1 month prior
to presentation.
• She smokes about 3 cigarettes per day but
denied use of alcohol, illicit drugs, or herbal
supplements. Her mother died from
complications of hypertension. There was no
known family history of early CAD, sudden
cardiac death, or rheumatologic diseases.
• ASSESSMENT
• The patient was afebrile with a regular heart
rate of 85 beats per minute, equal in both
arms blood pressure of 235/106 mmHg, a
respiratory rate of 16 breaths per minute, and
an oxygen saturation of 98% on ambient air.
• She appeared comfortable and in no apparent
distress. Her lungs were clear to auscultation
bilaterally, and her jugular venous pressure
was 10 cm of water.
• A cardiac examination identified a regular rate
and rhythm and a harsh III/VI systolic murmur
at the apex with radiation to her axilla and
back.
• Her abdomen was mildly obese and
nontender without hepatosplenomegaly.
• No abdominal bruits were evident. Femoral
pulses were absent bilaterally. The remainder
of her examination was normal.
• Laboratory analysis revealed a normal basic
metabolic panel with no electrolyte
abnormalities. The patient’s hemoglobin was
11.1 g/dL with a MCV of 90.8 mm3. Her Nterminal pro- BNP level was 2594 pg/mL
(reference range, 0-449 pg/mL).
• TSH was assessed at 1.65 mlU/L, and a urine
pregnancy test was negative. Renin level was
measured at 31 ng/mL/h (normal, <24
ng/ml/h). Urinalysis disclosed 2 protein and 3
blood. Urine toxicology testing was negative
for cocaine, amphetamines, and other
substances.
• An ECG indicated marked left ventricular
hypertrophy with repolarization
abnormalities, while a chest x-ray showed a
tortuous aorta and cardiomegaly. A work-up
for secondary causes of hypertension ensued.
• Transthoracic echocardiography demonstrated
moderate concentric left ventricular
hypertrophy and an estimated ejection
fraction of 60%. Mild left atrial enlargement
was detected. No significant valvular
abnormalities were seen. The aortic root size
was normal, measuring 2.6 cm at the sinuses.
• Because femoral pulses were absent,
additional imaging of the aorta was
performed.
• Figure 1 shows MRI of the abdomen and CTA
of the abdomen and pelvis.
• Figure 2 shows CTA of the chest .
• A tuberculin PPD test showed 8-9 mm of
induration in the setting of prior BCG
vaccination. A serum interferon gamma
release assay for Mycobacterium tuberculosis
was positive. Rapid plasma regain testing for
syphilis was negative.
• An ACE level was within normal limits. Tests
for ANA, p-ANCA and c-ANCA were negative.
An ESR was 46 mm/hr , and CRP was
elevated to 11.4 mg/L . The patient’s LDL level
was 200 mg/dL , and the HDL level was 47
mg/dL .
• Positron emission tomography (PET) was
carried out with the tracer fludeoxyglucose18F (FDG) (Figure 3).
• A core needle biopsy of a 1.4-cm, FDG-avid
axillary lymph node showed no pathologic
changes. An acid-fast bacilli (AFB) stain and
culture were both negative.
• DIAGNOSIS
• Our patient was given a diagnosis of Takayasu
arteritis with concomitant coronary artery
disease.
• This rare large-vessel vasculitis involves the
aorta and its primary branches. It typically
affects young women, with the greatest
prevalence in Asia and South America. The
pathogenesis of Takayasu arteritis remains
poorly understood, but the disease is
postulated to resemble giant cell arteritis
with cell-mediated granulomatous changes.
• Initially, inflammation occurs mostly in the
adventitia and media of arteries, leading to
thickening of the walls.3 With continued
inflammation, reactive intimal hyperplasia and
adventitial fibrosis may result in vascular
stenoses. Reactive intimal hyperplasia also
puts patients at risk for secondary
atherosclerosis.
• Authors found a high probability of Takayasu
arteritis when 2 major criteria, 1 major and 2
minor criteria, or 4 minor criteria were
fulfilled.
• Our patient met 1 major criterion in that she
had characteristic symptoms for at least 1
month. She also fulfilled 3 minor criteria: high
ESR , hypertension, and a descending thoracic
aorta lesion .
• Giant cell arteritis is the other most common
cause of large vessel vasculitis but this was an
unlikely diagnosis, given our patient’s young
age and the lack of ocular symptoms.
• She had no upper respiratory tract symptoms
to suggest granulomatosis with polyangiitis,
and tests for antineutrophil cytoplasmic
antibodies, proteinase 3 antibodies, and
myeloperoxidase antibodies were negative.
• Her negative rapid plasma reagin test ruled
out syphilitic aortitis; similarly, a normal
angiotensin-converting enzyme level made
sarcoidosis unlikely.
• Notably, our patient’s PPD test and interferon
gamma release assay were positive, raising
the possibility of tuberculous aortitis.
However, tuberculous involvement of large
vessels is exceedingly rare, with its mention in
the literature limited to case reports and case
series .
• Also, tuberculous aortitis is characterized
almost always by aneurysm formation. It is
usually secondary to contiguous spread from
adjacent infected lymph nodes, or less
commonly, it is due to disseminated
tuberculosis with vascular seeding.
• Although tuberculous aortitis could not be
definitively ruled out in our patient, the
absence of signs and symptoms of active
tuberculosis, her imaging findings, and her
subsequent improvement with
immunosuppression made Takayasu arteritis
the leading diagnosis.
• Several studies have identified a possible
association between Takayasu arteritis and
tuberculosis.7-10 An increased frequency of
positive tuberculin skin tests has been
observed in Takayasu arteritis patients,
although the association is difficult to prove
because many affected patients live in
endemic countries.
• MANAGEMENT
• Systemic corticosteroids are the backbone of
therapy for active Takayasu arteritis. Other
immunosuppressive agents, including
azathioprine, cyclophosphamide,
mycophenolate mofetil, and antagonists of
tumor necrosis factor alpha often are used in
combination with corticosteroids or as an
alternative to corticosteroids, but there are no
randomized clinical trials evaluating these
regimens.
• High-dose corticosteroids were administered
with a plan to initiate infliximab after she
completed 9 months of isoniazid for latent
tuberculosis. She also underwent stenting of
the significant descending aortic stenosis, a
procedure that afforded marked improvement
in her blood pressure control.
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