- Email: [email protected]
Uncommon associations and catastrophic manifestation in Takayasu arteritis: an autopsy case report
Uncommon associations and catastrophic manifestation in Takayasu arteritis: an autopsy case report Abhijit Chougule, Amanjit Bal, Ashim Das, Sanjay Jain, Ajay Bahl PII: DOI: Reference:
S1054-8807(14)00052-0 doi: 10.1016/j.carpath.2014.04.005 CVP 6770
To appear in:
Cardiovascular Pathology
Received date: Revised date: Accepted date:
28 March 2014 25 April 2014 25 April 2014
Please cite this article as: Chougule Abhijit, Bal Amanjit, Das Ashim, Jain Sanjay, Bahl Ajay, Uncommon associations and catastrophic manifestation in Takayasu arteritis: an autopsy case report, Cardiovascular Pathology (2014), doi: 10.1016/j.carpath.2014.04.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT :
:
Abhijit Chougule Amanjit Bal Ashim Das
SC
*Sanjay Jain
T
AUTHORS
Uncommon associations and catastrophic manifestation in Takayasu arteritis: An autopsy case report
RI P
TITLE
MA NU
**Ajay Bahl
3
NUMBER OF TABLES:
0
:
CE
PT
INSTITUTION
ED
NUMBER OF FIGURES:
Departments of Histopathology, *Internal Medicine and **Cardiology Post Graduate Institute of Medical Sciences & Research, (PGIMER), Sector – 12, Chandigarh- 160012, INDIA
AC
ADDRESS OF CORRESPONDING: AUTHOR
Dr. Amanjit Bal Associate Professor Department of Histopathology, PGIMER Chandigarh-160012, INDIA E mail- [email protected]
Financial Disclosure: The authors have no funding, financial relationships, or conflicts of interest to disclose
ACCEPTED MANUSCRIPT Abstract Takayasu arteritis, a chronic inflammatory vasculitis affecting aorta and its major branches is complicated by stenosis, occlusion and aneurysm formation. The aneurysm formation and
T
subsequent complications such as heart failure, aortic regurgitation and aneurysm rupture can
RI P
be fatal. The aortic aneurysm rupture is a rare and fatal complication with only a few cases reported in the English literature. The involvement of coronary artery in Takayasu occurs in
SC
about 10% patients and the coronary artery aneurysm is the least common manifestation. Here we describe a case of Takayasu arteritis with abdominal aortic aneurysm rupture and coronary artery aneurysm. This patient also had associated systemic inflammatory diseases
MA NU
like sarcoidosis and Hashimoto’s thyroiditis.
Key Words: Takayasu arteritis, aneurysm, coronary, rupture, sarcoidosis
ED
Introduction
Takayasu arteritis (TA), first reported by Dr Mikito Takayasu is a chronic inflammatory vasculitis affecting aorta and its major branches characterised by stenosis, occlusion and
PT
aneurysm formation. The cases have been reported worldwide however it has highest prevalence in Asian countries and females younger than 40 years are affected more
CE
commonly than males. The disease is characterised by an acute phase followed the chronic phase which is dominated by vascular symptoms such as hypertension, diminished or absent
AC
pulses, limb claudication or localized pain. The long term prognosis of patients with TA is good however the aneurysm formation and subsequent complications such as heart failure, aortic regurgitation and aneurysm rupture can be fatal [1]. In addition to involvement of aorta and its major branches, small percentages of patients have coronary artery involvement in different forms of which aneurysm formation is rarest [2]. The present case describes the simultaneous occurrence of abdominal aortic aneurysm with rupture and coronary artery aneurysm. Additionally the patient had immune mediated associations in form of sarcoidosis and Hashimoto’s thyroiditis.
Case report A 38 year old female presented in the emergency in unconscious state. Three hours prior to the admission she complained of sudden abdominal pain followed by abdominal distension
ACCEPTED MANUSCRIPT and loss of consciousness. Her blood pressure and vitals were un-recordable with low Glasgow score. Cardiopulmonary resuscitation was carried out however patient could not be revived and was declared dead.
T
At the age of 23 years in 1998, the patient first presented with pedal edema and was
RI P
diagnosed to have hypertension and was started on clonidine. On imaging she was found to have Takayasu disease based on asymmetric dilatation of aorta. Subsequent angiography
SC
showed bilateral renal artery stenosis for which left renal artery balloon dilatation and stenting was done. In year 2010 she was hospitalised for lower abdominal pain along with backache. On examination brachial pulse was weak with absent left radial pulse. Both side
of mercury in both upper limbs.
MA NU
popliteal and posterior tibial pulses were also absent. There was pressure difference of 20mm Per abdomen examination revealed prominent aortic
pulsations with aortic and left renal bruit. Non contrast enhancing computerized tomography (NCCT) scan showed presence of fusiform dilatation and thrombosis at the bifurcation of abdominal aorta, and small sized right kidney with multiple calculi (Fig. 1A). MR
ED
angiography showed fusiform dilatation with tortuosity of abdominal aorta with significant luminal narrowing in the proximal part. She was managed on anti-hypertensives and
PT
analgesics. Two years later on a routine outpatient follow up a visible pulsatile lump below umbilicus was noticed which was extending to left side. She was counselled for potential
CE
complications and endovascular repair surgery was advised. However because of financial constraints patient lost to follow up. In 2013 she was brought in unconscious state and died
AC
after brief hospital stay. Partial autopsy was performed after written consent from the patient’s relatives.
Autopsy findings: Peritoneal cavity on opening yielded 2 litres of blood with blood clots. Whole length of aorta and its main branches showed dense fibrosis with adhesions. The intima showed marked wrinkling with tree bark like appearance with superimposed atherosclerotic plaques, which were more prominent at the origin of branches. Skip lesions with relatively uninvolved areas in between were also seen in descending thoracic aorta. There was stenosis at the level of renal arteries while the post stenotic segment was markedly dilated. A large fusiform aneurysm measuring 10x7x5cm was present at the bifurcation which was extending into proximal part of right common iliac artery (Fig. 1B). The posterior surface of aneurysm showed a rupture site measuring 1.5x1.4cm (Fig. 1C). The aneurysmal sac showed a large fresh thrombus almost occluding the whole lumen. Microscopically the involved segments showed dense adventitial fibrosis with prominent vasa vasorum showing
ACCEPTED MANUSCRIPT intimal hyperplasia, medial thickening and moderate lymphoplasmacytic infiltrate (Fig. 1D). Few giant cell granulomas were also seen (Fig. 1E). The inflammatory infiltrate was extending to the media which was also showing marked fibrosis. The loss of elastic fibres and
T
thinning of media was highlighted on elastic von Gieson (EVG) stain (Fig. 1F). Intima
RI P
showed proliferation with luminal narrowing and superimposed atherosclerotic changes with and areas of calcification. All the major branches showed changes of chronicity in the form of adventitial fibrosis, moderate lymphoplasmacytic cell infiltrate and replacement fibrosis in
SC
the media.
Heart weighed 425grams and the epicardial surface on the right side showed a bulge
MA NU
at atrio-ventricular groove. On dissection it showed a fusiform aneurysm of right coronary artery starting from its origin and measuring 2cm in length. The aneurysmal sac showed a thrombus, however the lumen was patent. (Fig.2A-C). The left coronary artery and its branches showed mild luminal narrowing with atherosclerotic changes. There was significant left ventricular hypertrophy with reduction in the volume of cavity. Microscopically wall of
ED
the coronary artery showed similar changes as seen in aorta (Fig.2D-E). The heart showed
PT
patchy areas of interstitial fibrosis however no fresh myocardial infarction was noted. Lungs together weighed 675grams with focal areas of pleural dullness. Cut surface
CE
did not show any focal lesions and pulmonary arteries were unremarkable. Histologically many compact non-caseating interstitial granulomas were seen in the subpleural, paraseptal and bronchocentric location (Fig.3A). These were composed of epithelioid histiocytes,
AC
Langhans and foreign body type of giant cells, lymphocytes and scattered plasma cells. The ZN stain for acid fast bacilli was negative. These granulomas were T-cell rich with dominant CD4 positive helper T-cells. The right kidney was small and granular with dilated pelvicalyceal system containing few irregular calculi. Left kidney was of normal size with granular outer surface. A metallic stent was present at the origin of left renal artery while right renal artery showed atherosclerotic narrowing at the origin. Microscopically the renal parenchyma showed changes of benign arterionephrosclerosis. Thyroid was firm, fibrotic and weighed 21grams. Microscopically there was extensive lymphocytic infiltrate with lymphoid follicles causing destruction of thyroid follicles and dense interstitial fibrosis (Fig.3B). An incidental adenoma was also noted in right superior parathyroid gland composed of clear cells. The superior and inferior mesenteric arteries were
ACCEPTED MANUSCRIPT extensively involved by the disease process causing ischemic changes in the intestines in the form of submucosal fibrosis and fat infiltration.
T
Discussion:
RI P
Since initial description of disease, many clinical and autopsy series have been published from Japan and other countries including India [1-3]. Stenosis of aorta due to fibrosis and aneurysm formation is seen in almost all patients with TA. The aneurysm formation is the
SC
major complication and indicates extreme activity and is generally found in older patients with prolonged duration of disease. The chronic inflammation present also leads to
MA NU
accelerated atherosclerosis, especially at the origin of branches further contributing to aneurysm formation. Most patients have favourable prognosis because of relatively indolent disease course however in some patients the aneurysm may increase at rapid rate leading to thrombosis or rupture. The exact incidence of aortic aneurysmal rupture is not known as it is very rare and only a few cases reported in English literature. First case of aneurysmal rupture
ED
and massive hemoperitoneum manifesting as initial presentation of TA was reported in 1987 [4]. It was seen in 65-year-old Caucasian women who showed segmental involvement
PT
confined to infra-renal abdominal aorta. Ishikawa and Maetani [5] followed 120 patients with TA prospectively for a median period of 13 years. They reported only one case of ruptured
CE
thoraco-abdominal aortic aneurysm, which occurred after left nephrectomy. Sueyoshi et al [6] reported 17 aortic aneurysms in 14 of their 31 patients with TA. Three of the aneurysms
AC
increased in size rapidly at a mean rate of 1.16 cm/year and ruptured during follow up period. Two of these were located in thoracic aorta while one was present in abdominal aorta. The rarity of aneurysmal rupture may be related to thickening of the wall because of marked fibrosis of media and adventitia [7]. Repair of aneurysms by endovascular technique is advised if they reach the size more than 5cm. This complication was explained to our patient, however due to monetary problems the same could not be done. The involvement of coronary artery in TA occurs in about 10% patients and is seen in three forms; narrowing or occlusion of origin; diffuse or focal coronary arteritis; and aneurysm formation [2]. Autopsy study from our institute has reported coronary artery stenosis in one out of 10 cases and abdominal aortic aneurysm in 2 cases [3]. Coronary aneurysms are rare and the incidence at autopsy is around 1 to 1.5% which is mostly caused by atherosclerosis in western world and Kawasaki disease in the Far East. The coronary artery aneurysm formation in patients with TA is very rare and only few cases have been
ACCEPTED MANUSCRIPT reported in the literature. Suzuki et al [8] described a giant coronary aneurysm of left main coronary artery in a 71-year-old Japanese woman with TA, who died of progressive left ventricular failure. The aneurysm measured 5x6x5cm and another saccular aneurysm
T
measuring 2cm in the proximal portion of right coronary artery was found at autopsy.
RI P
Myocardial infarction (MI) has been reported in young patients as an atypical presentation of TA due to coronary artery involvement. A young woman presented with anterior wall MI, and was found to have mixed aneurysmal and obstructive coronary artery disease involving
SC
the left anterior descending artery (LAD) and its diagonal branches [9]. In another case, rapid development of coronary artery aneurysm has also been reported following coronary arteritis
MA NU
causing MI [10]. Ouali et al [11] reported MI developing in a young Tunisian male who showed right coronary aneurysm and was subsequently treated with intravenous methylprednisolone followed by oral prednisolone because of high probability of TA. Other complications of coronary artery aneurysm include rupture leading to cardiac tamponade and sudden cardiac death. These complications can be avoided by surgical procedures which
ED
involve ligation and exclusion of aneurysmal segment followed by coronary artery bypass. In our patient, there were no signs and symptoms related to coronary artery involvement.
PT
Underlying mechanism for development of aneurysms is thought to be due to chronic hypertension and extensive destruction of elastic tissue in the media causing vessel wall
CE
weakness and subsequent aneurysm formation. There are few case reports about association of TA with Sarcoidosis [12,13]. However in most of the cases the diagnosis of sarcoidosis preceded the diagnosis of Takayasu arteritis.
AC
Though the classic granulomas in sarcoidosis are non necrotising, focal areas of necrosis can be found in about 39% patients. Another granulomatous disorder; Crohn’s disease, has been reported in association with TA thus suggesting the possibility of a common basis of granulomatous disorders and TA. Takayasu arteritis is also known to be associated with other systemic inflammatory diseases like; rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and autoimmune disorders such as systemic lupus erythematosus, polymyositis, Hashimoto thyroiditis and scleroderma. Such associations strongly suggest that Takayasu aortitis is an autoimmune disease
Conclusion This case reports simultaneous occurrence of coronary artery aneurysm and abdominal aorta aneurysm. Presence of aortic aneurysm is a major complication in Takayasu arteritis, however aneurysm rupture causing massive hemothorax or hemoperitoneum leading to death
ACCEPTED MANUSCRIPT is rare. This case also highlights associated sarcoidosis and lymphocytic thyroiditis suggesting that these diseases may be related as they are characterized by non-specific,
AC
CE
PT
ED
MA NU
SC
RI P
T
immune-inflammatory abnormalities.
ACCEPTED MANUSCRIPT References
1. Matsumura K, Hirano T, Takeda K, et al. Incidence of aneurysms in Takayasu's
T
arteritis. Angiology. 1991;42:308-15.
RI P
2. Matsubara O, Kuwata T, Nemoto T, Kasuga T, Numano F. Coronary artery lesions in Takayasu arteritis: pathological considerations. Heart Vessels Suppl. 1992;7:26-31. 3. Sharma BK, Jain S, Radotra BD. An autopsy study of Takayasu arteritis in India. Int J
SC
Cardiol. 1998; 66: S85–S90.
4. Lie JT. Segmental Takayasu (giant cell) aortitis with rupture and limited dissection.
MA NU
Hum Pathol. 1987;18:1183-5.
5. Ishikawa K, Maetani S. Long-term outcome for 120 Japanese patients with Takayasu's disease. Clinical and statistical analyses of related prognostic factors. Circulation. 1994;90:1855-60.
6. Sueyoshi E, Sakamoto I, Hayashi K. Aortic aneurysms in patients with Takayasu's
ED
arteritis: CT evaluation. AJR Am J Roentgenol. 2000;175:1727-33. 7. Matsumura K, Hirano T, Takeda K, et al. Incidence of aneurysms in Takayasu's
PT
arteritis. Angiology. 1991;42:308-15. 8. Suzuki H, Daida H, Tanaka M, et al. Giant aneurysm of the left main coronary artery
CE
in Takayasu aortitis. Heart. 1999;81:214-7. 9. Al-Hulaimi N, Al-Saileek A, Ahmed T, Al-Zaibag M, Pai RG, El-Widaa H. Mixed aneurysmal and obstructive coronary artery disease causing acute myocardial
AC
infarction in a young woman with Takayasu’s arteritis. Can J Cardiol. 2001;17: 602-5. 10. Araszkiewicz A, Prech M, Hrycaj P, Lesiak M, Grajek S, Cieslinski A. Acute myocardial infarction and rapid development of coronary aneurysms in a young woman--unusual presentation of Takayasu arteritis? Can J Cardiol. 2007;23:61-3. 11. Ouali S, Kacem S, Ben Fradj F, et al. Takayasu arteritis with coronary aneurysms causing acute myocardial infarction in a young man. Tex Heart Inst J. 2011;38:183-6. 12. Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994;120:919-29. 13. Weiler V, Redtenbacher S, Bancher C, Fischer MB, Smolen JS: Concurrence of sarcoidosis and aortitis: case report and review of the literature. Ann Rheum Dis. 2000, 59:850-3.
ACCEPTED MANUSCRIPT Figure Legends
Figure 1 A: Non-contrast computed tomography showed fusiform dilatation of abdominal
T
aorta and thrombosis at bifurcation of aorta and both iliac arteries B: Gross photograph
RI P
showing stenosis and dilatation of abdominal aorta with large aneurysm at the bifurcation. Adventitia is markedly thickened with adhesions to surrounding structures, C: Closer view to show the ruptured site on posterior wall. Photomicrographs showing: D: marked fibrosis of
SC
aortic adventitia and vasa vasorum showing concentric hypertrophy with perivascular lymphoplasmacytic cell infiltrate E: Giant cells in the media F: EVG stain highlighting
MA NU
break in internal elastic lamina.
Figure 2: A: Gross photograph showing bulge on right heart border B: Cut surface of aneurysm C: Transverse section of aneurysm showing lumen filled with organised thrombus D: Scanning image of whole coronary aneurysm showing thinning and thickening of wall thrombosis
E:
Adventitia
of
coronary
aneurysm
showing
fibrosis
and
ED
with
PT
lymphoplasmacytic cell infiltration.
CE
Figure 3: Photomicrographs showing: A: Widened alveolar interstitium showing compact non caseating granulomas with multinucleated giant cells showing inclusions B: Thyroid
AC
parenchyma showing destruction of follicles with dense fibrosis and many lymphoid follicles.
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
SC
RI P
T
Figure 1
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
SC
RI P
T
Figure 2
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
SC
RI P
T
Figure 3
S1054-8807(14)00052-0 doi: 10.1016/j.carpath.2014.04.005 CVP 6770
To appear in:
Cardiovascular Pathology
Received date: Revised date: Accepted date:
28 March 2014 25 April 2014 25 April 2014
Please cite this article as: Chougule Abhijit, Bal Amanjit, Das Ashim, Jain Sanjay, Bahl Ajay, Uncommon associations and catastrophic manifestation in Takayasu arteritis: an autopsy case report, Cardiovascular Pathology (2014), doi: 10.1016/j.carpath.2014.04.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT :
:
Abhijit Chougule Amanjit Bal Ashim Das
SC
*Sanjay Jain
T
AUTHORS
Uncommon associations and catastrophic manifestation in Takayasu arteritis: An autopsy case report
RI P
TITLE
MA NU
**Ajay Bahl
3
NUMBER OF TABLES:
0
:
CE
PT
INSTITUTION
ED
NUMBER OF FIGURES:
Departments of Histopathology, *Internal Medicine and **Cardiology Post Graduate Institute of Medical Sciences & Research, (PGIMER), Sector – 12, Chandigarh- 160012, INDIA
AC
ADDRESS OF CORRESPONDING: AUTHOR
Dr. Amanjit Bal Associate Professor Department of Histopathology, PGIMER Chandigarh-160012, INDIA E mail- [email protected]
Financial Disclosure: The authors have no funding, financial relationships, or conflicts of interest to disclose
ACCEPTED MANUSCRIPT Abstract Takayasu arteritis, a chronic inflammatory vasculitis affecting aorta and its major branches is complicated by stenosis, occlusion and aneurysm formation. The aneurysm formation and
T
subsequent complications such as heart failure, aortic regurgitation and aneurysm rupture can
RI P
be fatal. The aortic aneurysm rupture is a rare and fatal complication with only a few cases reported in the English literature. The involvement of coronary artery in Takayasu occurs in
SC
about 10% patients and the coronary artery aneurysm is the least common manifestation. Here we describe a case of Takayasu arteritis with abdominal aortic aneurysm rupture and coronary artery aneurysm. This patient also had associated systemic inflammatory diseases
MA NU
like sarcoidosis and Hashimoto’s thyroiditis.
Key Words: Takayasu arteritis, aneurysm, coronary, rupture, sarcoidosis
ED
Introduction
Takayasu arteritis (TA), first reported by Dr Mikito Takayasu is a chronic inflammatory vasculitis affecting aorta and its major branches characterised by stenosis, occlusion and
PT
aneurysm formation. The cases have been reported worldwide however it has highest prevalence in Asian countries and females younger than 40 years are affected more
CE
commonly than males. The disease is characterised by an acute phase followed the chronic phase which is dominated by vascular symptoms such as hypertension, diminished or absent
AC
pulses, limb claudication or localized pain. The long term prognosis of patients with TA is good however the aneurysm formation and subsequent complications such as heart failure, aortic regurgitation and aneurysm rupture can be fatal [1]. In addition to involvement of aorta and its major branches, small percentages of patients have coronary artery involvement in different forms of which aneurysm formation is rarest [2]. The present case describes the simultaneous occurrence of abdominal aortic aneurysm with rupture and coronary artery aneurysm. Additionally the patient had immune mediated associations in form of sarcoidosis and Hashimoto’s thyroiditis.
Case report A 38 year old female presented in the emergency in unconscious state. Three hours prior to the admission she complained of sudden abdominal pain followed by abdominal distension
ACCEPTED MANUSCRIPT and loss of consciousness. Her blood pressure and vitals were un-recordable with low Glasgow score. Cardiopulmonary resuscitation was carried out however patient could not be revived and was declared dead.
T
At the age of 23 years in 1998, the patient first presented with pedal edema and was
RI P
diagnosed to have hypertension and was started on clonidine. On imaging she was found to have Takayasu disease based on asymmetric dilatation of aorta. Subsequent angiography
SC
showed bilateral renal artery stenosis for which left renal artery balloon dilatation and stenting was done. In year 2010 she was hospitalised for lower abdominal pain along with backache. On examination brachial pulse was weak with absent left radial pulse. Both side
of mercury in both upper limbs.
MA NU
popliteal and posterior tibial pulses were also absent. There was pressure difference of 20mm Per abdomen examination revealed prominent aortic
pulsations with aortic and left renal bruit. Non contrast enhancing computerized tomography (NCCT) scan showed presence of fusiform dilatation and thrombosis at the bifurcation of abdominal aorta, and small sized right kidney with multiple calculi (Fig. 1A). MR
ED
angiography showed fusiform dilatation with tortuosity of abdominal aorta with significant luminal narrowing in the proximal part. She was managed on anti-hypertensives and
PT
analgesics. Two years later on a routine outpatient follow up a visible pulsatile lump below umbilicus was noticed which was extending to left side. She was counselled for potential
CE
complications and endovascular repair surgery was advised. However because of financial constraints patient lost to follow up. In 2013 she was brought in unconscious state and died
AC
after brief hospital stay. Partial autopsy was performed after written consent from the patient’s relatives.
Autopsy findings: Peritoneal cavity on opening yielded 2 litres of blood with blood clots. Whole length of aorta and its main branches showed dense fibrosis with adhesions. The intima showed marked wrinkling with tree bark like appearance with superimposed atherosclerotic plaques, which were more prominent at the origin of branches. Skip lesions with relatively uninvolved areas in between were also seen in descending thoracic aorta. There was stenosis at the level of renal arteries while the post stenotic segment was markedly dilated. A large fusiform aneurysm measuring 10x7x5cm was present at the bifurcation which was extending into proximal part of right common iliac artery (Fig. 1B). The posterior surface of aneurysm showed a rupture site measuring 1.5x1.4cm (Fig. 1C). The aneurysmal sac showed a large fresh thrombus almost occluding the whole lumen. Microscopically the involved segments showed dense adventitial fibrosis with prominent vasa vasorum showing
ACCEPTED MANUSCRIPT intimal hyperplasia, medial thickening and moderate lymphoplasmacytic infiltrate (Fig. 1D). Few giant cell granulomas were also seen (Fig. 1E). The inflammatory infiltrate was extending to the media which was also showing marked fibrosis. The loss of elastic fibres and
T
thinning of media was highlighted on elastic von Gieson (EVG) stain (Fig. 1F). Intima
RI P
showed proliferation with luminal narrowing and superimposed atherosclerotic changes with and areas of calcification. All the major branches showed changes of chronicity in the form of adventitial fibrosis, moderate lymphoplasmacytic cell infiltrate and replacement fibrosis in
SC
the media.
Heart weighed 425grams and the epicardial surface on the right side showed a bulge
MA NU
at atrio-ventricular groove. On dissection it showed a fusiform aneurysm of right coronary artery starting from its origin and measuring 2cm in length. The aneurysmal sac showed a thrombus, however the lumen was patent. (Fig.2A-C). The left coronary artery and its branches showed mild luminal narrowing with atherosclerotic changes. There was significant left ventricular hypertrophy with reduction in the volume of cavity. Microscopically wall of
ED
the coronary artery showed similar changes as seen in aorta (Fig.2D-E). The heart showed
PT
patchy areas of interstitial fibrosis however no fresh myocardial infarction was noted. Lungs together weighed 675grams with focal areas of pleural dullness. Cut surface
CE
did not show any focal lesions and pulmonary arteries were unremarkable. Histologically many compact non-caseating interstitial granulomas were seen in the subpleural, paraseptal and bronchocentric location (Fig.3A). These were composed of epithelioid histiocytes,
AC
Langhans and foreign body type of giant cells, lymphocytes and scattered plasma cells. The ZN stain for acid fast bacilli was negative. These granulomas were T-cell rich with dominant CD4 positive helper T-cells. The right kidney was small and granular with dilated pelvicalyceal system containing few irregular calculi. Left kidney was of normal size with granular outer surface. A metallic stent was present at the origin of left renal artery while right renal artery showed atherosclerotic narrowing at the origin. Microscopically the renal parenchyma showed changes of benign arterionephrosclerosis. Thyroid was firm, fibrotic and weighed 21grams. Microscopically there was extensive lymphocytic infiltrate with lymphoid follicles causing destruction of thyroid follicles and dense interstitial fibrosis (Fig.3B). An incidental adenoma was also noted in right superior parathyroid gland composed of clear cells. The superior and inferior mesenteric arteries were
ACCEPTED MANUSCRIPT extensively involved by the disease process causing ischemic changes in the intestines in the form of submucosal fibrosis and fat infiltration.
T
Discussion:
RI P
Since initial description of disease, many clinical and autopsy series have been published from Japan and other countries including India [1-3]. Stenosis of aorta due to fibrosis and aneurysm formation is seen in almost all patients with TA. The aneurysm formation is the
SC
major complication and indicates extreme activity and is generally found in older patients with prolonged duration of disease. The chronic inflammation present also leads to
MA NU
accelerated atherosclerosis, especially at the origin of branches further contributing to aneurysm formation. Most patients have favourable prognosis because of relatively indolent disease course however in some patients the aneurysm may increase at rapid rate leading to thrombosis or rupture. The exact incidence of aortic aneurysmal rupture is not known as it is very rare and only a few cases reported in English literature. First case of aneurysmal rupture
ED
and massive hemoperitoneum manifesting as initial presentation of TA was reported in 1987 [4]. It was seen in 65-year-old Caucasian women who showed segmental involvement
PT
confined to infra-renal abdominal aorta. Ishikawa and Maetani [5] followed 120 patients with TA prospectively for a median period of 13 years. They reported only one case of ruptured
CE
thoraco-abdominal aortic aneurysm, which occurred after left nephrectomy. Sueyoshi et al [6] reported 17 aortic aneurysms in 14 of their 31 patients with TA. Three of the aneurysms
AC
increased in size rapidly at a mean rate of 1.16 cm/year and ruptured during follow up period. Two of these were located in thoracic aorta while one was present in abdominal aorta. The rarity of aneurysmal rupture may be related to thickening of the wall because of marked fibrosis of media and adventitia [7]. Repair of aneurysms by endovascular technique is advised if they reach the size more than 5cm. This complication was explained to our patient, however due to monetary problems the same could not be done. The involvement of coronary artery in TA occurs in about 10% patients and is seen in three forms; narrowing or occlusion of origin; diffuse or focal coronary arteritis; and aneurysm formation [2]. Autopsy study from our institute has reported coronary artery stenosis in one out of 10 cases and abdominal aortic aneurysm in 2 cases [3]. Coronary aneurysms are rare and the incidence at autopsy is around 1 to 1.5% which is mostly caused by atherosclerosis in western world and Kawasaki disease in the Far East. The coronary artery aneurysm formation in patients with TA is very rare and only few cases have been
ACCEPTED MANUSCRIPT reported in the literature. Suzuki et al [8] described a giant coronary aneurysm of left main coronary artery in a 71-year-old Japanese woman with TA, who died of progressive left ventricular failure. The aneurysm measured 5x6x5cm and another saccular aneurysm
T
measuring 2cm in the proximal portion of right coronary artery was found at autopsy.
RI P
Myocardial infarction (MI) has been reported in young patients as an atypical presentation of TA due to coronary artery involvement. A young woman presented with anterior wall MI, and was found to have mixed aneurysmal and obstructive coronary artery disease involving
SC
the left anterior descending artery (LAD) and its diagonal branches [9]. In another case, rapid development of coronary artery aneurysm has also been reported following coronary arteritis
MA NU
causing MI [10]. Ouali et al [11] reported MI developing in a young Tunisian male who showed right coronary aneurysm and was subsequently treated with intravenous methylprednisolone followed by oral prednisolone because of high probability of TA. Other complications of coronary artery aneurysm include rupture leading to cardiac tamponade and sudden cardiac death. These complications can be avoided by surgical procedures which
ED
involve ligation and exclusion of aneurysmal segment followed by coronary artery bypass. In our patient, there were no signs and symptoms related to coronary artery involvement.
PT
Underlying mechanism for development of aneurysms is thought to be due to chronic hypertension and extensive destruction of elastic tissue in the media causing vessel wall
CE
weakness and subsequent aneurysm formation. There are few case reports about association of TA with Sarcoidosis [12,13]. However in most of the cases the diagnosis of sarcoidosis preceded the diagnosis of Takayasu arteritis.
AC
Though the classic granulomas in sarcoidosis are non necrotising, focal areas of necrosis can be found in about 39% patients. Another granulomatous disorder; Crohn’s disease, has been reported in association with TA thus suggesting the possibility of a common basis of granulomatous disorders and TA. Takayasu arteritis is also known to be associated with other systemic inflammatory diseases like; rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and autoimmune disorders such as systemic lupus erythematosus, polymyositis, Hashimoto thyroiditis and scleroderma. Such associations strongly suggest that Takayasu aortitis is an autoimmune disease
Conclusion This case reports simultaneous occurrence of coronary artery aneurysm and abdominal aorta aneurysm. Presence of aortic aneurysm is a major complication in Takayasu arteritis, however aneurysm rupture causing massive hemothorax or hemoperitoneum leading to death
ACCEPTED MANUSCRIPT is rare. This case also highlights associated sarcoidosis and lymphocytic thyroiditis suggesting that these diseases may be related as they are characterized by non-specific,
AC
CE
PT
ED
MA NU
SC
RI P
T
immune-inflammatory abnormalities.
ACCEPTED MANUSCRIPT References
1. Matsumura K, Hirano T, Takeda K, et al. Incidence of aneurysms in Takayasu's
T
arteritis. Angiology. 1991;42:308-15.
RI P
2. Matsubara O, Kuwata T, Nemoto T, Kasuga T, Numano F. Coronary artery lesions in Takayasu arteritis: pathological considerations. Heart Vessels Suppl. 1992;7:26-31. 3. Sharma BK, Jain S, Radotra BD. An autopsy study of Takayasu arteritis in India. Int J
SC
Cardiol. 1998; 66: S85–S90.
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Figure 1 A: Non-contrast computed tomography showed fusiform dilatation of abdominal
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aorta and thrombosis at bifurcation of aorta and both iliac arteries B: Gross photograph
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showing stenosis and dilatation of abdominal aorta with large aneurysm at the bifurcation. Adventitia is markedly thickened with adhesions to surrounding structures, C: Closer view to show the ruptured site on posterior wall. Photomicrographs showing: D: marked fibrosis of
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aortic adventitia and vasa vasorum showing concentric hypertrophy with perivascular lymphoplasmacytic cell infiltrate E: Giant cells in the media F: EVG stain highlighting
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break in internal elastic lamina.
Figure 2: A: Gross photograph showing bulge on right heart border B: Cut surface of aneurysm C: Transverse section of aneurysm showing lumen filled with organised thrombus D: Scanning image of whole coronary aneurysm showing thinning and thickening of wall thrombosis
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lymphoplasmacytic cell infiltration.
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Figure 3: Photomicrographs showing: A: Widened alveolar interstitium showing compact non caseating granulomas with multinucleated giant cells showing inclusions B: Thyroid
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parenchyma showing destruction of follicles with dense fibrosis and many lymphoid follicles.
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