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.