Department of Internal Medicine, Tokyo Medical & Dental University, Tokyo, Japan
Takayasu arteritis is a chronic vasculitis mainly involving the aorta and its main branches, such as the brachiocephalic, carotid, subclavian, vertebral and renal arteries, as well as the coronary and pulmonary arteries.
It induces clinically varied ischaemic symptoms due to stenotic lesions or thrombus formation, including blindness, cataract and/or retinal haemorrhage, pulselessness, aortic regurgitation and/or congestive heart failure due to dilatation of the ascending aorta. More acute progression causes destruction of the media of the arterial wall, leading to the formation of aneurysms and/or dissecting aneurysm or rupture of the involved arteries [1].
Takayasu arteritis is characterized histologically as panarteritis, involving all layers of the arterial wall, including intimal fibrous thickening and/or typical atheromatous lesions, destruction of medial smooth muscles and elastic layers, cellular infiltration and collagenous fibrosis in the media and thickened adventitia with cellular infiltration around vasa vosorum [2, 3].
Almost all patients in Japan, for example, have ischaemic disorders due to cervical lesions, presenting with dizziness, syncope, visual disturbance, faint or absent pulse, or differences in systolic blood pressure between arms [4].
In Western countries this disease is also known as pulseless disease, because the pulse is frequently absent due to the obstruction of subclavian or brachial arteries [5]. The pathogenesis of this condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries [1, 6].
Autoimmune mechanisms induced by viruses have been suspected in the pathogenesis as HLA analysis demonstrated a statistically significant frequency of B*5201 (B52) B*3902 haplotype in these patients [7, 8].
History of Takayasu arteritis
Although this morbid condition is a vascular disease, it was first reported by a Japanese ophthalmologist. At the 12th Annual Meeting of the Japan Ophthalmology Society held in 1908 in Fukuoka, Mikito Takayasu (Fig. 1a) reported a case of a 21-yr-old woman whose eyegrounds exhibited coronary anastomosis, arteriovenous anastomosis around the papilla (Fig. 1b
). This abstract was published in 1908 in the Proceedings of the Japan Ophthalmology Society [911]. However, at this meeting, Katsutomo Onishi, Professor of Ophthalmology at Kyushu University and Tsurukichi Kagoshima, Professor of Ophthalmology at Kumamoto University, presented cases of eyegrounds showing the same features.
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Takayasu did not mention pulselessness in his patient in his presentation and indicated no abnormality in the medical examination. Some doctors, therefore, insist on the appellation of this disease as TakayasuOnishi disease. Soon afterwards, several cases were reported in Japan, including a report in 1939 by Yasuzo Shinmi who used the term Takayasu's Arteritis for the first time [12].
A 28-yr-old female patient complaining of delirium was hospitalized at the Department of Psychiatry at Tokyo University on 27 October 1939. The patient had experienced epileptic attacks since 1938 and it was recorded in her chart that she kept her head down to ward off dizziness sometimes accompanied by epileptic seizure. Examining this patient, her physician noticed and described that the pulses of both radial, brachial and carotid arteries were not palpable. After 1 week of hospitalization the patient died due to congestive heart failure. An autopsy was performed on 5 November 1938 by T. Okabayashi [11]. In his autopsy report, he pointed out that the patient had suffered from panarteritis of the aorta, both common, interna and externa carotid, subclavian and axillar arteries. The patient died of cerebromalacia and pulmonary congestion. Clinical diagnosis was Verschwinden des Radialis Pulsation mit Psychischer Storung.
Later, Kunio Oohta re-examined this case more precisely and systematically, and reported at the Japanese Pathological Society in 1940, emphasizing that the inflammatory changes were confined not only to the medial layer, but also in both the intima and adventitia of the arteries, which is equivalent to panarteritis [11, 13]. Oohta also pointed out for the first time that pulmonary arteries were involved in Takayasu arteritis. This was the first document that clearly established that this condition was caused by vasculitis involving mainly the aorta and its main branches and that characteristic ophthalmic findings reported by Takayasu resulted from the ischaemia of the cerebrovascular circulation.
Takayasu arteritis has been well known in foreign countries since Kentaro Shimizu and Keiji Sano, Department of Surgery at Tokyo University, introduced this disease in the English literature as pulseless disease [5]. They described the clinical features of pulselessness, coronary anastomosis in retinal vasculature, and accentuated carotid sinus reflex as the characteristic triad of this morbid condition in 1948. In addition, an introductory paper on the disease by Caccamize and Whiteman in the American Heart Journal contributed to the spread of information on Takayasu arteritis into Western countries. Caccamize obtained resources from Kunio Okuda [14].
Ross and McKusick, after Frovig's paper reporting a 21-yr-old woman with bilateral obliteration of the common carotid artery [15], summarized over 100 cases in which absent or diminished pulses in the arm and neck were observed, and they used the term aortic arch syndrome in which the cause of this condition was due to stenoses or obstruction near the origin of the great vessels from the arch of the aorta. They described many cases and classified them according to their causative factors, such as syphilic aortitis, atheromatosis, congenital anomalies, and trauma thrombophilia [16, 17]. They also mentioned four similar cases in the literature, reported by Frovig as young female arteritis, pointing out that all these patients were young females and that they showed cerebral and ocular manifestations.
In 1963, Hideo Ueda, Professor of Internal Medicine at Tokyo University, through studies of many cases of Takayasu arteritis, confirmed that it is due to aortitis involving the aorta, its main branches, pulmonary, and coronary arteries and called it panaortitis syndrome. He suggested that it could be induced by an autoimmune mechanism [18]. Afterwards, he changed this name to aortitis syndrome because of potential misunderstandings whereby pan would be taken to mean the whole area of the aorta. In 1975, the research committee of the Department of Health and Welfare in Japan proposed the use of Takayasu arteritis in memory of the first reporter, Mikito Takayasu.
Before Takayasu
Researching old documents in relation to Takayasu arteritis, two papers have been found.
In 1856, Savory reported a case of a 22-yr-old female whose main arteries of both upper extremities and the left side of the neck were completely obliterated, causing loss of vision in the left eye. At first, Savory suspected that the condition of the patient's arteries was due to inflammation [19, 20]. In the Western literature some name him as the first author [21]. However, the patient's clinical course revealed that she was suffering from an ulcer of the cornea which proceeded to invade the scalp and, finally, a portion of the brain. From this clinical description it is very unlikely that she was suffering from Takayasu arteritis. The author himself called it a degenerative condition in her autopsy report [19]. In the Japanese literature, in 1830 Rokushu Yamamoto published a book entitled Kitsuo-Idan, meaning Medical records of my private hospital under the big orange tree (Fig. 2). In it, Yamamoto, who practised Japanese oriental medicine, described a 45-yr-old man who initially visited him for high fever. One year later the patient presented with pulselessness in the right radial artery and a very weak pulse in the left radial artery. Moreover, Yamamoto described in this book the clear presence of the pulse in both lower extremities. Later, both carotid arteries become weaker and weaker and finally became non-palpable. The patient gradually emaciated and complained of dyspnoea, and suddenly died in the 11th year of follow-up. Yamamoto noted that, when he mentioned this patient to Tokaku Wada in Kyoto, Wada said that he also had examined two patients with the same symptoms. This may be the oldest description of Takayasu arteritis found in the literature [11].
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After Takayasu
The cause of Takayasu arteritis is still unknown and in Japan the disease is classified as one of the intractable diseases [6].
Female predominance and ethnic difference are characteristics of this disease. This author, who observed very similar vascular changes in cholesterol-fed rabbits treated with a large dose of oestrogen, advocated hyperoestrogenism as one of the causative factors [22, 23]. Nowadays, it is widely believed that this morbid condition is multifactorial. In fact, most young females get sick in their teens or twenties and urinary hyper-secretion of oestrogen in patients with Takayasu arteritis was reported, as compared with age-matched healthy controls. In 1974, Victor Deutsch, studying 22 patients with Takayasu arteritis and their ethnic distribution, pointed out that all of the four Jewish patients were Sephardic Jews while none were Ashkenazi Jews, although the ratio of these two Israeli populations is nearly equal. Furthermore, he noticed the possible different regional involvement due to ethnic differences [11, 24, 25].
Numano encountered twin sisters suffering from Takayasu arteritis in 1972 [26], and therefore suspected participation of a hereditary factor in the aetiology of this condition. In 1978, Numano reported a significantly increased frequency of a haplotype, A24-B52-DR2 (then described as A24-BW52-DW12) in Takayasu arteritis. Furthermore, he reported a higher frequency of HLA B52 in familial cases as compared with that in a population study [7, 27, 28]. Akira Kimura also confirmed, in his DNA-derived HLA typing studies, the close association of B*5201 and B*3901 in Japanese patients with Takayasu arteritis [8].
Afterward, Kimura also found a close association of MICA genes with the disease and we are currently exploring the participation of genes between the HLA B locus and MIC gene locus in chromosome 6 [29, 30].
Summary
At first, Takayasu arteritis was reported as an eye disease and soon after it was confirmed as a vasculitis. The aetiology of the disease is still unknown. However, its characteristic clinical features suggest multiple causative factors. Recent progress in vascular biology and immunology is elucidating the pathological process of the vasculitis and, at the same time, suggesting common pathways with other vasculitides, such as Bürger, Beh&çet and inflammatory abdominal aortic aneurysms. In the near future, the aetiology of these vasculitides could be elucidated and their clinical classification changed.
References
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