DISCUSSION
Takayasu arteritis is a chronic inflammatory disease of medium and large
arteries, also known as ‘pulseless disease’. The aorta and its branches,
pulmonary, coronary, and renal arteries are primarily affected. It is
known to have a female preponderance and tends to manifest most commonly
in the second to third decades of life [1]. It occurs worldwide with
the highest prevalence in Japan. In India, it is one of the common
causes of renovascular hypertension. In Indian female patients with TA,
the aortic arch and its branches are more commonly involved.
The disease has been attributed to various causes such as genetics,
infections (namely, Mycobacterium tuberculosis), and autoimmune,
although the exact etiopathogenesis is still unknown [1]. The result
of the process is vessel wall inflammation and chronic fibrosis with the
formation of inflammatory aneurysms [4] and eventually, stenosis and
thrombosis of affected arteries [5] which gives rise to symptoms of
ischemia.
The symptomatology of the disease varies by geographical region [6].
For example, India has higher rates of hypertension, abdominal aorta
involvement, and higher occurrence among the male population as compared
to Japan [6]. The patient may be asymptomatic to start with, as seen
in the above case, which often leads to a delay in diagnosis. Most
common symptoms are non-specific such as fever, myalgia, easy
fatigability, weight loss, and arthralgia [7]. With advancing
vascular damage, symptoms such as headache, claudication, carotidynia,
dizziness, diminution of vision, angina, etc. can occur [8].
Our patient who is a 29-year-old female, gravida 4 para 3 with 2 live
issues with no abortion, presented to the department of obstetrics and
gynecology (OBGYN) at 40 weeks of gestation with the finding of
oligohydramnios (AFI < 3cm) on ultrasonography (USG) and was
taken up for emergency lower segment caesarean section (LSCS). During
her evaluation, she was found to have an absent radial pulse
bilaterally. There were no intra-natal or postnatal complications; both
mother and baby were in good health. The patient was asymptomatic till
the second postnatal day when she developed an acute onset headache and
was further evaluated by the Medicine department. The most common
complications associated with TA are reported to be hypertension,
retinopathy, aortic regurgitation, and the development of aneurysm
[9]. Other devastating complications include stroke, intestinal
ischemia [10], and limb gangrene.
Clinical examination, laboratory tests, artery biopsy, and imaging are
the available modalities of diagnosis, imaging being the most important
diagnostic method as clinical examination and laboratory tests are
unreliable [11] and biopsy of the large vessels is impractical
[6]. Absent pulses, blood pressure discrepancies between limbs, and
arterial bruits are signs frequently present on examination. Our patient
had absent bilateral radial, bilateral brachial, and left dorsalis pedis
pulses. Blood pressure was not recordable in both upper limbs whereas it
was measured as 160/100 mmHg, post-delivery, in bilateral lower limbs,
suggestive of hypertension. A loud second pulmonary sound (P2) and
carotid bruit were heard on auscultation.
Laboratory tests such as erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP) are not specific for TA and the elevation in
ESR and CRP levels, seen in 80% and 60% of cases respectively, only
indicate underlying inflammation [12], although there are other
markers such as interleukin-6, RANTES [13, 14] and tissue inhibitor
of metalloproteinases-1 (TIMP-1) [15] which show some specificity
for TA. Based on the clinical manifestations of the patient and levels
of acute phase reactants such as ESR and CRP, the Indian Takayasu
Arteritis Clinical Activity Score was developed in 2010 (ITAS / ITAS-A
2010) [16]. The blood workup of our patient showed an erythrocyte
sedimentation rate of 130 mm at the end of an hour which is elevated.
Conventional angiography is still the gold standard for diagnosis and
treatment, although non-invasive techniques such as USG, computed
tomography (CT), and magnetic resonance imaging (MRI) are routinely used
[12]. In TA, mural thickening, vascular stenosis or occlusion or
dilatation, and surrounding edema can be made out [17]. The Macaroni
sign has been described as a pathognomonic sign for TA which can be seen
on the transverse cut of B mode USG [18]. According to the site and
extent of involvement of arteries on angiography, Numano et al have
classified TA into 5 patterns of disease [19], with the most common
pattern being type V [20, 21]. For our patient, USG doppler showed
diffuse intimal thickening of the proximal segment of the left common
carotid artery with stenosis of 60% and CT aortogram was characteristic
of type V TA (Numano classification), pointing towards the involvement
of the entire aorta and branches of the aortic arch. Thereby, she was
diagnosed to have active TA (ITAS-A, score: 5, 2010).
The majority of the population
affected by diseases of autoimmune etiology tend to be women and TA is
one of the primary systemic vasculitides likely to occur among women in
the childbearing age group [22]. So, the interaction between TA and
pregnancy becomes an area of attention. During pregnancy, the maternal
immune system bends to accommodate the growing fetus which is
potentially a foreign tissue. The severity of autoimmune diseases or the
risk of its relapse is reduced during pregnancy, especially in the case
of those autoimmune diseases which are mediated by Th1 cells as it is
postulated that there is a shift to Th2-based immunity in pregnancy
[23]. This mechanism has not been well studied in the context of
coexisting TA.
Studies have conflicting conclusions as to the effect of pregnancy on
TA. It has been reported in patients with TA on assessing the level of
inflammation and hemodynamic changes that ameliorate during pregnancy,
with hypertension being one of the complications which shows
deterioration, especially in the perinatal period [24, 25]. The
patient presented to us at term and was asymptomatic throughout
pregnancy. The first symptom of TA was headache which manifested two
days following delivery, although she had telltale signs of TA on
examination even before delivery.
Coming to the effect of TA on pregnancy, various studies report
different outcomes of pregnancy in patients with TA but the majority of
them worldwide and in India found that obstetric complications are
highly likely and are higher in pregnancies after the diagnosis of TA
was made than in those before its diagnosis [2]. Vascular damage of
TA combined with the normal physiological changes in hemodynamics during
pregnancy can act as a catalyst for adverse maternal and fetal outcomes
[5]. The most common complication is hypertension in the form of
gestational hypertension, preeclampsia, or eclampsia, though different
studies show varying percentages. Vessel involvement is likely to
reflect on the dynamics between TA and pregnancy as fetal complications
such as IUGR and oligohydramnios are associated with renal artery
stenosis, due to increased renin activity and resultant elevation of
blood pressure and uteroplacental insufficiency [26]. A fetal
Doppler scan done in the 3rd trimester also showed abnormalities in the
umbilical artery and middle cerebral artery circulation. The patient is
currently on maintenance dose steroid therapy using prednisolone and
Azathioprine, and is advised for regular follow-up.