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An autopsy study of Takayasu arteritis in India
International Journal of Cardiology 66 (Suppl. 1) (1998) S85–S90
An autopsy study of Takayasu arteritis in India a, a b B.K. Sharma *, S. Jain , B.D. Radotra a
Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India b Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Abstract Autopsy findings of 10 patients with Takayasu arteritis (TA) are presented. These patients include six females and four males with a mean age of 22.6610.2 years. Hypertension was the commonest mode of presentation. On autopsy, the vascular lesions in the aorta comprised of stenosis (eight), dilatation (six), aneurysm (two) and dissection of aorta involving its arch, thoracic and abdominal aorta (one). Abdominal aorta was the commonest site of involvement (nine patients) and renal artery was involved in six patients. Histologically, the three types of lesions were identified — active, fibrotic and combination of active and fibrotic lesions. Active inflammatory lesions in the arterial circuit were present despite a clinically chronic (silent) phase of the disease. Cardiac involvement included left ventricular hypertrophy (nine), right ventricular hypertrophy (four), biventricular hypertrophy (three), myocarditis (two) (rheumatic and Takayasu’s myocarditis — one patient each) and involvement of coronary artery (one). The pulmonary artery was involved in two patients. Kidneys showed changes of malignant hypertension and benign nephrosclerosis in one patient each. Associated tuberculosis was present in four patients. The causes of mortality were congestive heart failure (four), chronic renal failure (two), intracranial bleed, aneurysmal rupture and pulmonary thromboembolism in one patient each. Thus, the major causes of morbidity and mortality in Indian patients with TA is due to severe uncontrolled hypertension and its effect on heart, kidney and brain. The disease appears to have a persistent activity for a prolonged period even when it appears to be clinically silent. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Takayasu arteritis; Autopsy; Histology; Hypertension; Heart failure
1. Introduction Takayasu arteritis (TA) is a chronic inflammatory disease that frequently involves the aorta and its major branches and occasionally the pulmonary and coronary arteries. It is the commonest cause of renovascular hypertension in India and other South Asian countries and the clinical manifestations of this disease are usually as a consequence of ischaemia of various organs and / or uncontrolled hypertension [1,2]. The present document is based on an analysis
*Corresponding author. Tel.: 191-172-541-031; Fax: 191-172-540401.
of 10 autopsy cases of TA during a 15-year period from 1982 to 1997.
2. Materials and methods Ten cases of TA diagnosed clinically and confirmed at autopsy have been analyzed. These patients were admitted at the Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh, India on an emergency basis. A detailed clinical examination with special emphasis on asymmetry or absence of arterial pulsations, presence of a bruit and blood pressure recording in all
0167-5273 / 98 / $ – see front matter 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00155-7
S86
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
Table 1 Clinical features in 10 patients with TA Clinical features
Number
Hypertension Inequality of pulses Dyspnoea Hypertensive retinopathy Vascular bruits Congestive heart failure Syncope Seizures Hemiplegia
9 6 6 4 3 3 2 2 1
four limbs were performed in all the patients. Baseline investigations including a complete hemogram, urinalysis and blood biochemistry were done in all patients. Of these 10 patients, there were six females and four males with a female to male ratio of 3:2. Their age ranged from 6 to 40 years with a mean of 22.6610.2 years. The commonest mode of presentation was hypertension (nine patients). Other clinical features included asymmetry of pulses (six), vascular bruits (three), breathlessness (six), palpitation (three), congestive heart failure (four), nausea / vomiting (three) and syncope and seizures (two each) (Table 1). An ophthalmic examination revealed hypertensive retinopathy in four patients — grade II and grade III hypertensive retinopathy in two patients each. One patient presented with hemiparesis. Laboratory investigation revealed a hemoglobin of less than 10 g% in six patients, an erythrocyte sedimentation rate of more than 20 mm in the first hour in five patients, a serum creatinine of more than 2 mg in three patients. The results of laboratory investigations are shown in Table 2. It is a routine in our hospital to carry out an aortogram in these patients but these patients were admitted with various complications and died before this could be done. The treatment of each patient was individualised.
After the death of the individual, informed consent was obtained from the next close relative for an autopsy.
3. Results
3.1. Autopsy findings The main burden of the disease was seen in the aorta and its major branches. The various types of vascular lesions that were observed included stenosis (eight lesions), dilatation (five lesions), aneurysms (two lesions) and dissection of aorta including its arch, descending thoracic and abdominal aorta (one lesion) (Fig. 1). The distribution of vascular lesions in various branches of aorta is shown in Table 3. The abdominal aorta was involved in nine patients and renal artery was involved in six patients. Macroscopically, there was thickening and rigidity of the walls of the aorta with periarterial fibrosis in many cases (Fig. 2). ‘Skip lesions’ characterised by normal areas in between thickened inner surfaces were frequently seen. Occasionally, lesions of atherosclerosis were also present. On microscopy, there were three types of lesions:
Table 2 Labratory investigations in 10 patients with TA Investigation
Number
Haemoglobin,10 g% Total leukocyte count.11 000 / mm 3 ESR.20 mm / 1 h S. creatinine.2 mg% Urine alb. 21 ECG: LVH CxR: cardiomegaly
6 2 5 3 2 5 3
Fig. 1. Dissection of aorta with thrombus formation in Takayasu arteritis.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
S87
Table 3 Distribution of vascular lesions Artery
Number
Ascending aorta Aortic arch Brachiocephatic artery Right subclavian artery Left subclavian artery Thoracic aorta Abdominal aorta Celiac artery Renal artery Coronary artery Pulmonary artery
2 3 2 2 3 5 9 2 6 1 2
1. active lesions: characterised by perivascular mononuclear infiltrate in the vasa vasorum especially near the junction of adventitia and media (Fig. 3);
Fig. 3. Mononuclear cells infiltrate around vasa vasorum.
2. fibrotic lesions: characterised by scarring, destruction of media, perivascular fibrosis and fibrous thickening of media (Fig. 4); 3. combination of active and fibrotic lesions: few areas in the aorta had infiltration of mononuclear cells along with cicatricial lesions (Fig. 5). Besides the aorta, the disease also involved those arteries that are rich in elastic fibers including Fig. 4. Destruction of media and intimal thickening in Takayasu arteritis.
Fig. 2. Morphology of aorta-thickening, rigidity and periarterial fibrosis.
Fig. 5. Intimal thickening, infiltration of mononuclear cells in media and periadventitial fibrosis.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
S88
coronary artery (one patient) and pulmonary artery (two patients).
3.2. Cardiac findings In the heart, left ventricular hypertrophy was present in nine patients, right ventricular hypertrophy in four patients and biventricular hypertrophy in three patients. Causes of left ventricular hypertrophy were hypertension, aortic regurgitation and mitral regurgitation. Infiltration of mononuclear cells in the myocardium was seen in two patients and this could be attributed to rheumatic myocarditis (co-existing presence of rheumatic vegetations on mitral valve) in one patient and necrosis of myofibres associated with mononuclear cells infiltration consistent with Takayasu myocarditis (Fig. 6) in another. The coronary artery was involved in one patient.
3.3. Pulmonary findings The pulmonary artery was involved in two patients. Segmental branches in right upper and middle lobes of the lungs were involved in these two cases. Pulmonary thrombo-embolism was the cause of death in one patient. Other findings included interstitial pneumonia, pneumonic consolidation, lung haemorrhage and pulmonary oedema in one case each. An interesting association was capillary haemangiomatosis. Pulmonary tuberculosis (healed and active) was seen in three patients (Fig. 7) though none
Fig. 7. Tubercular granuloma in Takayasu arteritis.
had received anti-tuberculous drug therapy in the past.
3.4. Kidney lesions Kidneys were involved primarily due to uncontrolled and prolonged hypertension and ischaemic damage due to renal artery stenosis. Pathological changes of fibrinoid necrosis of small vessels and intraglomerular necrosis consistent with malignant hypertension were seen in one patient while one patient had small contracted kidney due to benign nephrosclerosis. Associated findings were active tubercular granulomas in interstitium of the kidney in one patient.
3.5. Associated tuberculosis Tuberculosis (active / healed) was present in four patients. The organs included miliary tuberculosis (lungs, lymph node, liver) in one patient, mediastinal lymph node, retroperitoneal lymph node and parenchyma of kidney in one patient each.
3.6. Brain
Fig. 6. Active myocarditis.
Massive introcerebral haemorrhage was the cause of death in one patient. Associated findings were dermoid cyst of ovary in one patient and squamous metaplasia in pelvi-calyceal lining of the kidney in one case each.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
3.7. Causes of death The causes of mortality were congestive heart failure (four patients), chronic renal failure (two patients), intracranial bleed, aneurysmal rupture and pulmonary thrombo-embolism in one patient each.
4. Discussion The initial documents of autopsy findings in Takayasu arteritis have been reported by Ota in 1940 [3] and Nasu in 1963 [4]. Since then, it has been known that this disease is a panarteritis involving all the three layers — intima, media and adventitia of aorta and its major branches. A detailed description of autopsy cases of Japanese patients has been reported by Nasu in 1975 [5], Nagata in 1990 [6] and Hotchi in 1992 [7]. The ratio of 115 autopsy cases as reported by Hotchi in 1992 to all autopsy cases from 1975 to 1984 in Japan was 0.033% [7]. Singhal et al. in 1978 and Chopra et al. in 1983 have reported autopsy series of 11 and 14 cases, respectively, of this disease from North India [8,9]. The clinical profile of the patients with TA in the present series is nearly identical to the previous studies on TA as reported by us [1,10,11]. The average age of the patients at presentation in the present series was 22.6 years and a female to male ratio was 3:2. Previously, we have reported a mean age of 27 years amongst 106 patients of TA with a female to male ratio of 1.58:1 [11]. The majority of our patients had hypertension and its complications at the time of presentation. On autopsy, the characteristic lesions of TA were located in the media and adventitia of large vessels in the present series and has been reported by Hotchi earlier [7]. It is presumed that the inflammatory reaction is initiated through the vasa vasorum [7] although there are few studies on the initial phases of this disease. Saito has reported that neutrophils infiltrate into the media and adventitia resulting in abscesses, necrosis and destruction of elastic fibers [12]. Later a granuloma formation occurs comprising of multinucleated giant cells. Fibrous thickening of the intima occurs in relation to the destruction of media and
S89
adventitia. As a result of these phenomena, the lumen of the affected arteries gets narrowed and stenosing lesions develop. However, if the destructive lesions occur rapidly and fibrosis is delayed, aneurysmal formation occurs. An important observation in the present study was the presence of active inflammatory lesions in arterial circuit even in the seemingly chronic fibrotic phase of the disease. This confirms our belief that despite a clinically silent disease, the activity of the disease persists and new lesions in the arteries continue to develop. Clinical and laboratory parameters, at present, cannot possibly detect this histological activity. Cardiac complications, especially congestive heart failure, were the most important causes of mortality in the present series (40%). The various causes of congestive failure included uncontrolled severe hypertension, diastolic and systolic dysfunction of left ventricle, myocarditis and involvement of mitral and aortic valve [10,11]. It has been suggested that patients with TA and HLA BW 52 have a more severe left ventricular involvement [13]. Involvement of myocardium due to TA has been reported by Talwar et al. earlier [14] and a good response to immunosuppressive agents was documented by them. Pulmonary involvement of TA is due to pulmonary artery involvement [15,16]. It has been found in 41–100% of the cases and there is a predilection for involvement of vessels to the right lung. Other pathological lesions include oedema, hemorrhage, infarction, interstitial pneumonia and pneumonic consolidation. Unusual association of capillary haemangiomatosis in a patient with TA has not been reported in the English literature to the best of our knowledge. Stenosis recanalization (vessel-in-vessel) lesions as described by Matsubara et al. were also present in the present series [17]. Kidneys and brain are usually involved due to uncontrolled hypertension or stenosis of supplying arteries. Kidneys show a variety of lesions including benign nephrosclerosis, malignant nephrosclerosis and ischaemic scars. The association of tuberculosis in TA is very interesting. The relationship of tuberculosis and TA was suggested by a few studies from India and Mexico [18,19] but convincing evidence is lacking [1,2,11]. The presence of a thrombo-embolic phenomenon (thrombus in left ventricle, pulmonary
S90
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
thromboembolism) suggests a disturbance in coagulation profile in patients with TA. In conclusion, the autopsy study of patients with TA does confirm that the most important cause of mortality in Indian patients with TA is a result of severe uncontrolled hypertension and its effect on heart, kidney and brain. The study also suggests that the activity of the disease persists for a long time that cannot be detected clinically or by the present laboratory tests.
References [1] Sharma BK, Sagar S, Chugh KS, Sakhuja V, Rajachandran A, Malik N. Spectrum of renovascular hypertension in the young in North India: a hospital based study on occurrence and clinical features. Angiology 1985;36:370–8. [2] Chugh KS, Jain S, Sakhuja V, et al. Renovascular hypertension due to Takayasu’s arteritis among Indian patients. Q J Med 1992;85:833–43. [3] Ota K. Ein Seltener Fall Von beiderseitigem Carotis — Subclavia verschluss. Em Beitrag zur Pathologie der Anastomosis peripapillaris des Auges mit fehlendem Radialpuls. Trans Soc Path Jpn 1940;30:680–90. [4] Nasu T. Pathology of pulseless disease. A systematic study and critical review of twenty-one autopsy cases reported in Japan. Angiology 1963;14:225–42. [5] Nasu T. Takayasu’s truncoartertis in Japan: a statistical observation of 76 autopsy cases. Pathol Microbiol 1975;43:140–6. [6] Nagata S. Present state of autopsy cases of Takayasu’s arteritis (aortitis syndrome) in Japan. J Jpn Coll Angiol 1990;30:1303–8.
[7] Hotchi M. Pathological studies on Takayasu arteritis. Heart Vessels 1992;Suppl 7:11–17. [8] Singhal V, Jain SL, Chopra P. Non-specific aortoarteritis — an autopsy analysis. Indian J Med Res 1978;68:322–34. [9] Chopra P, Datta RK, Das Gupta A, Bhargava S. Non-specific aortoarteritis (Takayasu’s disease) — an immunological and autopsy study . Jpn Heart J 1983;24:549–56. [10] Sharma BK, Sagar S, Singh AP, Suri S. Takayasu’s arteritis in India. Heart Vessels 1992;Suppl 7:37–43. [11] Jain S, Kumari S, Ganguly NK, Sharma BK. Current status of Takayasu arteritis in India. Int J Cardiol 1996;54:S111–6. [12] Saito K. Pulmonary arteritis in Takayasu’s arteritis. Jpn J Chest Dis 1988;47:655–65. [13] Kasuya K, Hashimoto Y, Numano F. Left ventricular dysfunction and HLABw 52 antigen in Takayasu arteritis. Heart Vessels 1997;Suppl 7:116–119. [14] Talwar KK, Chopra P, Narula J, et al. Myocardial involvement and its response to immunosuppressive therapy in non-specific aortoarteritis (Takayasu’s disease): a study by endomyocardial biopsy. Int J Cardiol 1988;23:323–34. [15] Lupi EH, Sanchez GT, Horwitz S, Gutierrez E. Pulmonary artery involvement in Takayasu’s arteritis. Chest 1975;67:69–74. [16] Sharma S, Kamala KT, Rajani M, Talwar KK, Shrivastava S. The incidence and patterns of pulmonary artery involvement in Takayasu’s arteritis. Clin Radiol 1990;42:177–81. [17] Matsubara O, Yoshimura N, Tamura A et al. Pathological features of the pulmonary artery in Takayasu arteritis. Heart Vessels 1992;Suppl 7:18–25. [18] Sen PK, Kinare SG, Kelkar MD, Parulkar GB. Non-specific aortoarteritis. Tata McGraw Hill, Bombay, 1972. [19] Lupi-Herrera E, Sanchez TG, Marcushamer J, Mispareta J, Horwitz E, Espino J. Takayasu’s arteritis: clinical study of 102 cases. Am Heart J 1997;93:94–103.
An autopsy study of Takayasu arteritis in India a, a b B.K. Sharma *, S. Jain , B.D. Radotra a
Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India b Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Abstract Autopsy findings of 10 patients with Takayasu arteritis (TA) are presented. These patients include six females and four males with a mean age of 22.6610.2 years. Hypertension was the commonest mode of presentation. On autopsy, the vascular lesions in the aorta comprised of stenosis (eight), dilatation (six), aneurysm (two) and dissection of aorta involving its arch, thoracic and abdominal aorta (one). Abdominal aorta was the commonest site of involvement (nine patients) and renal artery was involved in six patients. Histologically, the three types of lesions were identified — active, fibrotic and combination of active and fibrotic lesions. Active inflammatory lesions in the arterial circuit were present despite a clinically chronic (silent) phase of the disease. Cardiac involvement included left ventricular hypertrophy (nine), right ventricular hypertrophy (four), biventricular hypertrophy (three), myocarditis (two) (rheumatic and Takayasu’s myocarditis — one patient each) and involvement of coronary artery (one). The pulmonary artery was involved in two patients. Kidneys showed changes of malignant hypertension and benign nephrosclerosis in one patient each. Associated tuberculosis was present in four patients. The causes of mortality were congestive heart failure (four), chronic renal failure (two), intracranial bleed, aneurysmal rupture and pulmonary thromboembolism in one patient each. Thus, the major causes of morbidity and mortality in Indian patients with TA is due to severe uncontrolled hypertension and its effect on heart, kidney and brain. The disease appears to have a persistent activity for a prolonged period even when it appears to be clinically silent. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Takayasu arteritis; Autopsy; Histology; Hypertension; Heart failure
1. Introduction Takayasu arteritis (TA) is a chronic inflammatory disease that frequently involves the aorta and its major branches and occasionally the pulmonary and coronary arteries. It is the commonest cause of renovascular hypertension in India and other South Asian countries and the clinical manifestations of this disease are usually as a consequence of ischaemia of various organs and / or uncontrolled hypertension [1,2]. The present document is based on an analysis
*Corresponding author. Tel.: 191-172-541-031; Fax: 191-172-540401.
of 10 autopsy cases of TA during a 15-year period from 1982 to 1997.
2. Materials and methods Ten cases of TA diagnosed clinically and confirmed at autopsy have been analyzed. These patients were admitted at the Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh, India on an emergency basis. A detailed clinical examination with special emphasis on asymmetry or absence of arterial pulsations, presence of a bruit and blood pressure recording in all
0167-5273 / 98 / $ – see front matter 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00155-7
S86
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
Table 1 Clinical features in 10 patients with TA Clinical features
Number
Hypertension Inequality of pulses Dyspnoea Hypertensive retinopathy Vascular bruits Congestive heart failure Syncope Seizures Hemiplegia
9 6 6 4 3 3 2 2 1
four limbs were performed in all the patients. Baseline investigations including a complete hemogram, urinalysis and blood biochemistry were done in all patients. Of these 10 patients, there were six females and four males with a female to male ratio of 3:2. Their age ranged from 6 to 40 years with a mean of 22.6610.2 years. The commonest mode of presentation was hypertension (nine patients). Other clinical features included asymmetry of pulses (six), vascular bruits (three), breathlessness (six), palpitation (three), congestive heart failure (four), nausea / vomiting (three) and syncope and seizures (two each) (Table 1). An ophthalmic examination revealed hypertensive retinopathy in four patients — grade II and grade III hypertensive retinopathy in two patients each. One patient presented with hemiparesis. Laboratory investigation revealed a hemoglobin of less than 10 g% in six patients, an erythrocyte sedimentation rate of more than 20 mm in the first hour in five patients, a serum creatinine of more than 2 mg in three patients. The results of laboratory investigations are shown in Table 2. It is a routine in our hospital to carry out an aortogram in these patients but these patients were admitted with various complications and died before this could be done. The treatment of each patient was individualised.
After the death of the individual, informed consent was obtained from the next close relative for an autopsy.
3. Results
3.1. Autopsy findings The main burden of the disease was seen in the aorta and its major branches. The various types of vascular lesions that were observed included stenosis (eight lesions), dilatation (five lesions), aneurysms (two lesions) and dissection of aorta including its arch, descending thoracic and abdominal aorta (one lesion) (Fig. 1). The distribution of vascular lesions in various branches of aorta is shown in Table 3. The abdominal aorta was involved in nine patients and renal artery was involved in six patients. Macroscopically, there was thickening and rigidity of the walls of the aorta with periarterial fibrosis in many cases (Fig. 2). ‘Skip lesions’ characterised by normal areas in between thickened inner surfaces were frequently seen. Occasionally, lesions of atherosclerosis were also present. On microscopy, there were three types of lesions:
Table 2 Labratory investigations in 10 patients with TA Investigation
Number
Haemoglobin,10 g% Total leukocyte count.11 000 / mm 3 ESR.20 mm / 1 h S. creatinine.2 mg% Urine alb. 21 ECG: LVH CxR: cardiomegaly
6 2 5 3 2 5 3
Fig. 1. Dissection of aorta with thrombus formation in Takayasu arteritis.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
S87
Table 3 Distribution of vascular lesions Artery
Number
Ascending aorta Aortic arch Brachiocephatic artery Right subclavian artery Left subclavian artery Thoracic aorta Abdominal aorta Celiac artery Renal artery Coronary artery Pulmonary artery
2 3 2 2 3 5 9 2 6 1 2
1. active lesions: characterised by perivascular mononuclear infiltrate in the vasa vasorum especially near the junction of adventitia and media (Fig. 3);
Fig. 3. Mononuclear cells infiltrate around vasa vasorum.
2. fibrotic lesions: characterised by scarring, destruction of media, perivascular fibrosis and fibrous thickening of media (Fig. 4); 3. combination of active and fibrotic lesions: few areas in the aorta had infiltration of mononuclear cells along with cicatricial lesions (Fig. 5). Besides the aorta, the disease also involved those arteries that are rich in elastic fibers including Fig. 4. Destruction of media and intimal thickening in Takayasu arteritis.
Fig. 2. Morphology of aorta-thickening, rigidity and periarterial fibrosis.
Fig. 5. Intimal thickening, infiltration of mononuclear cells in media and periadventitial fibrosis.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
S88
coronary artery (one patient) and pulmonary artery (two patients).
3.2. Cardiac findings In the heart, left ventricular hypertrophy was present in nine patients, right ventricular hypertrophy in four patients and biventricular hypertrophy in three patients. Causes of left ventricular hypertrophy were hypertension, aortic regurgitation and mitral regurgitation. Infiltration of mononuclear cells in the myocardium was seen in two patients and this could be attributed to rheumatic myocarditis (co-existing presence of rheumatic vegetations on mitral valve) in one patient and necrosis of myofibres associated with mononuclear cells infiltration consistent with Takayasu myocarditis (Fig. 6) in another. The coronary artery was involved in one patient.
3.3. Pulmonary findings The pulmonary artery was involved in two patients. Segmental branches in right upper and middle lobes of the lungs were involved in these two cases. Pulmonary thrombo-embolism was the cause of death in one patient. Other findings included interstitial pneumonia, pneumonic consolidation, lung haemorrhage and pulmonary oedema in one case each. An interesting association was capillary haemangiomatosis. Pulmonary tuberculosis (healed and active) was seen in three patients (Fig. 7) though none
Fig. 7. Tubercular granuloma in Takayasu arteritis.
had received anti-tuberculous drug therapy in the past.
3.4. Kidney lesions Kidneys were involved primarily due to uncontrolled and prolonged hypertension and ischaemic damage due to renal artery stenosis. Pathological changes of fibrinoid necrosis of small vessels and intraglomerular necrosis consistent with malignant hypertension were seen in one patient while one patient had small contracted kidney due to benign nephrosclerosis. Associated findings were active tubercular granulomas in interstitium of the kidney in one patient.
3.5. Associated tuberculosis Tuberculosis (active / healed) was present in four patients. The organs included miliary tuberculosis (lungs, lymph node, liver) in one patient, mediastinal lymph node, retroperitoneal lymph node and parenchyma of kidney in one patient each.
3.6. Brain
Fig. 6. Active myocarditis.
Massive introcerebral haemorrhage was the cause of death in one patient. Associated findings were dermoid cyst of ovary in one patient and squamous metaplasia in pelvi-calyceal lining of the kidney in one case each.
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
3.7. Causes of death The causes of mortality were congestive heart failure (four patients), chronic renal failure (two patients), intracranial bleed, aneurysmal rupture and pulmonary thrombo-embolism in one patient each.
4. Discussion The initial documents of autopsy findings in Takayasu arteritis have been reported by Ota in 1940 [3] and Nasu in 1963 [4]. Since then, it has been known that this disease is a panarteritis involving all the three layers — intima, media and adventitia of aorta and its major branches. A detailed description of autopsy cases of Japanese patients has been reported by Nasu in 1975 [5], Nagata in 1990 [6] and Hotchi in 1992 [7]. The ratio of 115 autopsy cases as reported by Hotchi in 1992 to all autopsy cases from 1975 to 1984 in Japan was 0.033% [7]. Singhal et al. in 1978 and Chopra et al. in 1983 have reported autopsy series of 11 and 14 cases, respectively, of this disease from North India [8,9]. The clinical profile of the patients with TA in the present series is nearly identical to the previous studies on TA as reported by us [1,10,11]. The average age of the patients at presentation in the present series was 22.6 years and a female to male ratio was 3:2. Previously, we have reported a mean age of 27 years amongst 106 patients of TA with a female to male ratio of 1.58:1 [11]. The majority of our patients had hypertension and its complications at the time of presentation. On autopsy, the characteristic lesions of TA were located in the media and adventitia of large vessels in the present series and has been reported by Hotchi earlier [7]. It is presumed that the inflammatory reaction is initiated through the vasa vasorum [7] although there are few studies on the initial phases of this disease. Saito has reported that neutrophils infiltrate into the media and adventitia resulting in abscesses, necrosis and destruction of elastic fibers [12]. Later a granuloma formation occurs comprising of multinucleated giant cells. Fibrous thickening of the intima occurs in relation to the destruction of media and
S89
adventitia. As a result of these phenomena, the lumen of the affected arteries gets narrowed and stenosing lesions develop. However, if the destructive lesions occur rapidly and fibrosis is delayed, aneurysmal formation occurs. An important observation in the present study was the presence of active inflammatory lesions in arterial circuit even in the seemingly chronic fibrotic phase of the disease. This confirms our belief that despite a clinically silent disease, the activity of the disease persists and new lesions in the arteries continue to develop. Clinical and laboratory parameters, at present, cannot possibly detect this histological activity. Cardiac complications, especially congestive heart failure, were the most important causes of mortality in the present series (40%). The various causes of congestive failure included uncontrolled severe hypertension, diastolic and systolic dysfunction of left ventricle, myocarditis and involvement of mitral and aortic valve [10,11]. It has been suggested that patients with TA and HLA BW 52 have a more severe left ventricular involvement [13]. Involvement of myocardium due to TA has been reported by Talwar et al. earlier [14] and a good response to immunosuppressive agents was documented by them. Pulmonary involvement of TA is due to pulmonary artery involvement [15,16]. It has been found in 41–100% of the cases and there is a predilection for involvement of vessels to the right lung. Other pathological lesions include oedema, hemorrhage, infarction, interstitial pneumonia and pneumonic consolidation. Unusual association of capillary haemangiomatosis in a patient with TA has not been reported in the English literature to the best of our knowledge. Stenosis recanalization (vessel-in-vessel) lesions as described by Matsubara et al. were also present in the present series [17]. Kidneys and brain are usually involved due to uncontrolled hypertension or stenosis of supplying arteries. Kidneys show a variety of lesions including benign nephrosclerosis, malignant nephrosclerosis and ischaemic scars. The association of tuberculosis in TA is very interesting. The relationship of tuberculosis and TA was suggested by a few studies from India and Mexico [18,19] but convincing evidence is lacking [1,2,11]. The presence of a thrombo-embolic phenomenon (thrombus in left ventricle, pulmonary
S90
B.K. Sharma et al. / International Journal of Cardiology 66 ( Suppl. 1) (1998) S85 –S90
thromboembolism) suggests a disturbance in coagulation profile in patients with TA. In conclusion, the autopsy study of patients with TA does confirm that the most important cause of mortality in Indian patients with TA is a result of severe uncontrolled hypertension and its effect on heart, kidney and brain. The study also suggests that the activity of the disease persists for a long time that cannot be detected clinically or by the present laboratory tests.
References [1] Sharma BK, Sagar S, Chugh KS, Sakhuja V, Rajachandran A, Malik N. Spectrum of renovascular hypertension in the young in North India: a hospital based study on occurrence and clinical features. Angiology 1985;36:370–8. [2] Chugh KS, Jain S, Sakhuja V, et al. Renovascular hypertension due to Takayasu’s arteritis among Indian patients. Q J Med 1992;85:833–43. [3] Ota K. Ein Seltener Fall Von beiderseitigem Carotis — Subclavia verschluss. Em Beitrag zur Pathologie der Anastomosis peripapillaris des Auges mit fehlendem Radialpuls. Trans Soc Path Jpn 1940;30:680–90. [4] Nasu T. Pathology of pulseless disease. A systematic study and critical review of twenty-one autopsy cases reported in Japan. Angiology 1963;14:225–42. [5] Nasu T. Takayasu’s truncoartertis in Japan: a statistical observation of 76 autopsy cases. Pathol Microbiol 1975;43:140–6. [6] Nagata S. Present state of autopsy cases of Takayasu’s arteritis (aortitis syndrome) in Japan. J Jpn Coll Angiol 1990;30:1303–8.
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