http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; 25(3): 468–471 © 2013 Japan College of Rheumatology DOI: 10.3109/14397595.2013.843754
CASE REPORT
Multiple cerebral lesions as the unique complication of idiopathic retroperitoneal fibrosis Takashi Tani, Chikara Ishihara, Tomohiro Kaneko, Syuichi Tsuruoka, and Yasuhiko Iino Department of Nephrology, Nippon Medical School, Tokyo, Japan Abstract
Keywords
We present a case of idiopathic retroperitoneal fibrosis (IRF) complicated by severe renal failure and multiple intracranial lesions, which are probable results of cerebral vasculitis. IRF is an idiopathic hyperplasia of the retroperitoneal tissue that often entraps the ureters and causes post-renal failure. While the etiology of IRF is unclear, researchers consider IRF a systemic autoimmune disease complicated by immune-mediated vasculitides. The chief complaints of the patient were cognitive disorders, and brain MRI findings revealed multiple intracranial lesions with accompanying central degeneration. Given that vasogenic cerebral edemas derive from uremia, we speculated that the lesions in our case were related to more destructive changes such as aortic and periaortic inflammation. Details on this case manifesting rare cerebrovascular complications may help elucidate the pathogenesis of IRF.
Autoimmune diseases, Cerebral vasculitis, Idiopathic retroperitoneal fibrosis
Introduction Retroperitoneal fibrosis is a rare disease characterized by chronic inflammation and marked fibrosis of the retroperitoneal tissue leading to the entrapment or blockage of the ureters or other abdominal organs [1]. Idiopathic retroperitoneal fibrosis (IRF) is more than twice as frequent as retroperitoneal fibrosis derived from secondary causes (neoplasms, infections, trauma, radiotherapy, surgery and use of certain drugs) [2]. A histological examination often contributes directly to the differential diagnosis between IRF and secondary retroperitoneal fibrosis [3]. The pathogenesis of IRF is still unclear, but immunological and histological surveys implicate the involvement of systemic immunemediated vasculitides [1,3–5]. Corticosteroids promptly improve symptoms and often reduce the size of the retroperitoneal mass and resolve obstructive complications [1,3]. We present a case of IRF complicated by severe renal failure and multiple cerebral lesions in which adventitial and periadventitial inflammation appear to play a causal role.
Case report A 59-year-old man was admitted to our hospital for the evaluation of cognitive manifestations and lower back pain. He had a smoking habit, but had no medical history, and took no medicines or supplements. A month earlier he had begun to experience symptoms of memory disorder and apraxia. He reported difficulties in remembering computer passwords, using computers, water faucets and even dressing. His vital signs on physical examination were a temperature of 37.7°C, heart rate of 87 beats/minute and blood pressure of 142/86 mmHg. He was awake but manifested scattered attention and scored only 13/30 and 18/30 on the Hasegawa Dementia
Correspondence to: Takashi Tani, MD, Department of Nephrology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. Tel: ⫹ 81-3-3822-2131. Fax: ⫹ 81-3-5685-1795. E-mail: [email protected]
History Received 4 March 2013 Accepted 24 April 2013 Published online 31 October 2013
Scale (HDS-R) and Mini Mental Scale Examination (MMSE), respectively. Both legs were edematous and he complained of treatment-resistant lower back pain. The rest of his physical examination resulted normal. Laboratory data were as follows: white blood count, 10,000/μl with no left shift; hemoglobin, 12.3 g/dl; potassium, 7.7 mmol/l; uric acid, 11.4 mg/dl; creatinine, 31.86 mg/dl; urea, 133.3 mg/dl; β2-microglobulin, 2.6mg/dl; oxidized-low-density lipoproteins (LDL), 186mg/dl; C-reactive protein, 5.95 mg/dl; ferritin, 506.6 ng/ml; serum amyloid A protein, 86.4μg/ml; soluble interleukin-2 receptor(sIL-2R), 1502 U/ml; IgG, 386 mg/dl; IgG4, 12 mg/dl; BNP, 1181.9 pg/ml; and QuontiFERON-TB Gold was negative. No autoantibodies were positive including antinuclear antibody, anti-DNA antibody, cytoplasmic-anti-neutrophil cytoplasmic antibody (ANCA), perinuclear-ANCA and anti-glomerular basement membrane (GBM) antibody. Immunoelectrophoresis of patient’s blood showed no abundance of monoclonal antibody. Blood gas analysis showed uncompensated acidosis (room air): pH, 7.256; PaCO2, 18.4 Torr; PaO2, 64.2 Torr; bicarbonate, 8.0 mmol/l; and anion gap, 22 mEq/l. His urinalysis was normal. Abdominal CT showed a retroperitoneal mass surrounding the aorta, bilateral mid-ureter dilatation, hydronephrosis and no abnormal findings on other organs including pancreas and lymph nodes (Figure 1A). Abdominal MRI revealed the retroperitoneal mass, which showed mild hyperintensity on diffusion weighted image (DWI) and enhancement. Gallium scintigraphy also showed mild uptake in the retroperitoneal tissue, and abnormal uptake in abdominal aorta and bilateral iliac artery. These findings implied greater possibility of IRF as a result of vasculitides rather than secondary one (lymphoma, infections or other neoplasms). As cognitive disorders were the chief compliant of admission, brain MRI has been performed to find multiple lesions of abnormal hyperintensity on T2-weighted and fluid-attenuated inversion recovery images (T2WI and FLAIR), with accompanying central degeneration (Figure 2A). Brain MR angiography did not show evident stenosis, or abnormal narrowing in major branches of cerebral blood vessels (Figure 2B).
DOI 10.3109/14397595.2013.843754
Case report 469 Figure 1. (A) Abdominal CT showed a retroperitoneal mass surrounding the calcified aorta extending from the superior mesenteric artery to the iliac bifurcation. Bilateral mid-ureter dilatation and hydronephrosis were observed. (B) Retroperitoneal mass surrounding the aorta shrunk after immunosuppression therapy.
We commenced hemodialysis immediately because of severe renal dysfunction and hyperkalemia. Bilateral ureter stents were inserted, and his urine volume and serum creatinine levels improved. His post-renal failure remitted, and the hemodialysis was terminated on the 11th hospital day. CT-guided core biopsy of the mass performed on the 13th hospital day revealed sclerotic tissue with acute inflammatory cells, along with foam cell hyperplasia consistent with retroperitoneal fibrosis (Figure 3). Cluster of differentiation (CD) immunostaining of the mass showed no abundance of CD68, CD138 or CD20, and
no conspicuous presence of IgG4-positive cells. Finally, IRF was diagnosed based on the histological findings. Immunosuppression therapy with oral prednisolone (30 mg/ day) was commenced promptly after diagnosis, and his lower back pain vanished within a few days. An abdominal CT scan on the 20th day from the start of treatment showed a clear reduction of the peritoneal fibrosis (Figure 1B). The multiple T2WI hyperintensity lesions had shrunk on brain MRI (Figure 2C) and his cognitive difficulties abated. His HDS-R, MMSE and frontal assessment battery (FAB) scores were 25/30, 26/30 and 15/15 points after treatment,
Figure 2. (A) T2WI showed macular hyperintensity involving the subcortical white matter of bilateral hemispheres. Some of these abnormal intensity lesions showed peripheral hyperintensity on FLAIR images. (B) Brain MR angiography did not show abnormal narrowing in major branches of cerebral blood vessels. (C) Abnormal hyperintensity on T2WI and FLAIR images was reduced in frequency and size after treatment.
470
T. Tani et al.
Figure 3. The core biopsy showed sclerotic tissue with acute inflammatory cells, along with foam cell hyperplasia consistent with retroperitoneal fibrosis.
respectively. The patient is now doing well, is back at work, and remains on immunosuppression therapy with oral prednisolone (5 mg/day) and mizoribine (150 mg/day).
Discussion We experienced a rare case of IRF, which seemed to have complicated cerebral vasculitis. The patient had a smoking habit and nontreated dyslipidemia, but these factors alone seemed insufficient to explain his severe complications. We therefore speculated that an autoimmune disorder, the presumed cause of the IRF, could also have triggered his intracranial lesions [5]. The pathogenesis of IRF is still unclear. The leading theory is that IRF is a consequence of a local inflammatory reaction to oxidized ceroid and LDL, two commonly observed components of atherosclerotic plaques of the abdominal aorta. These oxidized lipids trigger a fibro-inflammatory response when immunocompetent cells such as T lymphocytes and B lymphocytes encounter them in plaque macrophages [6]. Meanwhile, IRF is often accompanied by elevated concentrations of acute-phase reactants, positive testing for autoantibodies, and associated autoimmune diseases such as autoimmune thyroiditis. A number of reports, including some on autopsy cases, have described aortic and periaortic inflammations not only of the abdominal aorta, but also of the thoracic aorta, major branches such as the renal, mesenteric, and celiac arteries, and even the coronary arteries [7,8]. Autopsy studies report the presence of adventital inflammation in aortic section lacking periaortic fibrosis, which indicate that aortitis could precede the development of adventitial and periadventitial fibrosis [7]. Another study of 11 chronic periaortitis patients (10 IRF patients and one inflammatory aneurysm patient) has revealed significantly increased number of CECs (circulating endothelial cell concentrations) in comparison with healthy subjects, and they closely correlated with the degree of disease activity. This suggests that endothelial injury associated
Mod Rheumatol, 2015; 25(3): 468–471
with micro-vascular damage plays an important role in the pathogenesis of IRF [9]. Furthermore, RF is strongly associated with HLA-DRB1*03, an allele linked to prototypical autoimmune conditions such as type 1 diabetes, myasthenia gravis and autoimmune thyroiditis [10,11]. Given these findings, researchers now assume that IRF is more of an immune-mediated systemic vasculitis than of an exaggerated local reaction to atherosclerosis, resulting in adventitial and periadventitial fibrosis [1,3–5]. Our patient had a complication of intracranial lesions that could have been derived from cerebral vasculitis. Brain MRI findings showed multiple patches of degeneration surrounded by T2WI and FLAIR image hyperintensity. Brain MRI images in lymphoma, cardiogenic embolism, infective endocarditis, sepsis and some of collagen diseases can resemble those of this case, but cardiac ultrasound study and blood examination, and the histological findings denied all these disorders. Cerebral vasculitis sometimes appears as blood vessel stenosis, and narrowing in MR angiography showed, but it was negative in our case [12]. Cerebral angiography, not being performed due to his severe renal failure and invasiveness, may have revealed finer abnormalities with higher sensitivity. Another characteristic feature of his brain MRI findings is the reversible T2WI and FLAIR image hyperintensity. These findings can be explained not only by cerebral vasculitides, but also by uremia, or posterior reversible encephalopathy syndrome as a manifestation of vasogenic edema [13]. Yet central degeneration is reflective of more destructive changes such as aortic and periaortic inflammation. The success of the prednisolone immunosuppression therapy in arresting the degeneration implicates systemic vascular inflammation as well. An assumed pathophysiology implies that his abnormal findings on brain MRI can result from micro-vascular inflammations followed by vasogenic edema. Thus, we consider these findings the results of cerebral vasculitides, although striking evidence by imaging studies is lacking. While the reported vascular involvements of IRF are mainly large to medium vessels (the aorta and its major branches), some autopsy cases refer to small vessel vasculitis [14]. As the presumed etiology of IRF is an immune-mediated systemic vasculitis, vasculitides could take place on any vessels of human body. The vascular supplies of his multiple intracranial lesions are mainly small vessels, which are probably not detectable in MR angiography. Therefore, vasculitides observed in this case are expected to have taken place in large to small vessels. In accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of vasculitides, such vasculitides can be categorized into large vessel vasculitis (LVV) or variable vessel vasculitis (VVV) [15]. Immunological and histological investigations of IRF have revealed new features of the disease consistent with a systemic immune-mediated vasculitis [1,3–5]. Mindful of the recent theories about IRF, we concluded that our patient’s abnormal findings on brain MRI might have resulted from periaortic inflammation of the cerebral blood vessels. As far as we searched, this is the first report referring to cerebral vasculitides as the complication of IRF. If this was so, our case could be key to elucidating the pathogenesis of IRF. Thus, more latent symptom-free cases with cerebrovascular complications may be included among the patients suffering from IRF. We need to screen for the presence of such complications in further surveys of IRF patients.
Conflict of interest None.
References 1. Gilkeson GS, Allen NB. Retroperitoneal fibrosis: a true connective tissue disease. Rheum Dis Clin North Am. 1996;22(1):23–38.
DOI 10.3109/14397595.2013.843754
2. Koep L, Zuidema GD. The clinical significance of retroperitoneal fibrosis. Surgery. 1977;81(3):250–7. 3. Vaglio A, Buzio C. Chronic periaortitis: a spectrum of diseases. Curr Opin Rheumatol. 2005;17(1):34–40. 4. Kottra JJ, Dunnick NR. Retroperitoneal fibrosis. Radiol Clin North Am. 1996;34(6):1259–75. 5. Vaglio A, Pipitone N, Savarani C. Chronic periaortitis: a large vessel vasculitis? Curr Opin Rheumatol. 2011;23(1):1–6. 6. Parums DV, Chadwick DR, Mitchinson MJ. The localisation of immunoglobulin in chronic periaortitis. Atherosclerosis. 1986; 61(2):117–23. 7. Mitchinson MJ. The pathology of idiopathic retroperitoneal fibrosis. J Clin Pathol. 1970;23(8):681–9. 8. Cohle SD, Lie JT. Inflammatory aneurysm of the abdominal aorta, aortitis, and coronary arteritis. Arch Pathol Lab Med. 1988;112(11):1121–5. 9. Moroni G, Del Papa N, Moronetti LM, Vitali C, Maglione W, Comina DP, et al. Increased levels of circulating endothelial cells in chronic periaortitis as a marker of active disease. Kidney Int. 2005;68(2):562–8.
Case report 471 10. Martorana D, Vaglio A, Greco P, Zanetti A, Moroni G, Salvarani C. Chronic periaortitis and HLA- DRB1*03: another clue to an autoimmune origin. Arthritis Rheum. 2006;55(1): 126–30. 11. Klein J, Sato A. The HLA system: second of two parts. N Engl J Med. 2000;343(11):782–6. 12. Ghinoi A, Zuccoli G, Pipitone N, Salvarani C. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving the central nervous system: case report and review of the literature. Clin Exp Rheumatol. 2010;28(5):759–66. 13. Lamy C, Oppenheim C, Méder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging. 2004; 14(2):89–96. 14. Doi M, Hoshikawa M, Ono A, Honjo K, Ariizumi Y, Koike J, et al. An autopsy case of idiopathic retroperitoneal fibrosis (In Japanese). Shindan Byouri. In press. 15. Jennette J, Falk R, Bacon P, Basu N, Cid M, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11.
Copyright of Modern Rheumatology (Informa Healthcare) is the property of Informa Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CASE REPORT
Multiple cerebral lesions as the unique complication of idiopathic retroperitoneal fibrosis Takashi Tani, Chikara Ishihara, Tomohiro Kaneko, Syuichi Tsuruoka, and Yasuhiko Iino Department of Nephrology, Nippon Medical School, Tokyo, Japan Abstract
Keywords
We present a case of idiopathic retroperitoneal fibrosis (IRF) complicated by severe renal failure and multiple intracranial lesions, which are probable results of cerebral vasculitis. IRF is an idiopathic hyperplasia of the retroperitoneal tissue that often entraps the ureters and causes post-renal failure. While the etiology of IRF is unclear, researchers consider IRF a systemic autoimmune disease complicated by immune-mediated vasculitides. The chief complaints of the patient were cognitive disorders, and brain MRI findings revealed multiple intracranial lesions with accompanying central degeneration. Given that vasogenic cerebral edemas derive from uremia, we speculated that the lesions in our case were related to more destructive changes such as aortic and periaortic inflammation. Details on this case manifesting rare cerebrovascular complications may help elucidate the pathogenesis of IRF.
Autoimmune diseases, Cerebral vasculitis, Idiopathic retroperitoneal fibrosis
Introduction Retroperitoneal fibrosis is a rare disease characterized by chronic inflammation and marked fibrosis of the retroperitoneal tissue leading to the entrapment or blockage of the ureters or other abdominal organs [1]. Idiopathic retroperitoneal fibrosis (IRF) is more than twice as frequent as retroperitoneal fibrosis derived from secondary causes (neoplasms, infections, trauma, radiotherapy, surgery and use of certain drugs) [2]. A histological examination often contributes directly to the differential diagnosis between IRF and secondary retroperitoneal fibrosis [3]. The pathogenesis of IRF is still unclear, but immunological and histological surveys implicate the involvement of systemic immunemediated vasculitides [1,3–5]. Corticosteroids promptly improve symptoms and often reduce the size of the retroperitoneal mass and resolve obstructive complications [1,3]. We present a case of IRF complicated by severe renal failure and multiple cerebral lesions in which adventitial and periadventitial inflammation appear to play a causal role.
Case report A 59-year-old man was admitted to our hospital for the evaluation of cognitive manifestations and lower back pain. He had a smoking habit, but had no medical history, and took no medicines or supplements. A month earlier he had begun to experience symptoms of memory disorder and apraxia. He reported difficulties in remembering computer passwords, using computers, water faucets and even dressing. His vital signs on physical examination were a temperature of 37.7°C, heart rate of 87 beats/minute and blood pressure of 142/86 mmHg. He was awake but manifested scattered attention and scored only 13/30 and 18/30 on the Hasegawa Dementia
Correspondence to: Takashi Tani, MD, Department of Nephrology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. Tel: ⫹ 81-3-3822-2131. Fax: ⫹ 81-3-5685-1795. E-mail: [email protected]
History Received 4 March 2013 Accepted 24 April 2013 Published online 31 October 2013
Scale (HDS-R) and Mini Mental Scale Examination (MMSE), respectively. Both legs were edematous and he complained of treatment-resistant lower back pain. The rest of his physical examination resulted normal. Laboratory data were as follows: white blood count, 10,000/μl with no left shift; hemoglobin, 12.3 g/dl; potassium, 7.7 mmol/l; uric acid, 11.4 mg/dl; creatinine, 31.86 mg/dl; urea, 133.3 mg/dl; β2-microglobulin, 2.6mg/dl; oxidized-low-density lipoproteins (LDL), 186mg/dl; C-reactive protein, 5.95 mg/dl; ferritin, 506.6 ng/ml; serum amyloid A protein, 86.4μg/ml; soluble interleukin-2 receptor(sIL-2R), 1502 U/ml; IgG, 386 mg/dl; IgG4, 12 mg/dl; BNP, 1181.9 pg/ml; and QuontiFERON-TB Gold was negative. No autoantibodies were positive including antinuclear antibody, anti-DNA antibody, cytoplasmic-anti-neutrophil cytoplasmic antibody (ANCA), perinuclear-ANCA and anti-glomerular basement membrane (GBM) antibody. Immunoelectrophoresis of patient’s blood showed no abundance of monoclonal antibody. Blood gas analysis showed uncompensated acidosis (room air): pH, 7.256; PaCO2, 18.4 Torr; PaO2, 64.2 Torr; bicarbonate, 8.0 mmol/l; and anion gap, 22 mEq/l. His urinalysis was normal. Abdominal CT showed a retroperitoneal mass surrounding the aorta, bilateral mid-ureter dilatation, hydronephrosis and no abnormal findings on other organs including pancreas and lymph nodes (Figure 1A). Abdominal MRI revealed the retroperitoneal mass, which showed mild hyperintensity on diffusion weighted image (DWI) and enhancement. Gallium scintigraphy also showed mild uptake in the retroperitoneal tissue, and abnormal uptake in abdominal aorta and bilateral iliac artery. These findings implied greater possibility of IRF as a result of vasculitides rather than secondary one (lymphoma, infections or other neoplasms). As cognitive disorders were the chief compliant of admission, brain MRI has been performed to find multiple lesions of abnormal hyperintensity on T2-weighted and fluid-attenuated inversion recovery images (T2WI and FLAIR), with accompanying central degeneration (Figure 2A). Brain MR angiography did not show evident stenosis, or abnormal narrowing in major branches of cerebral blood vessels (Figure 2B).
DOI 10.3109/14397595.2013.843754
Case report 469 Figure 1. (A) Abdominal CT showed a retroperitoneal mass surrounding the calcified aorta extending from the superior mesenteric artery to the iliac bifurcation. Bilateral mid-ureter dilatation and hydronephrosis were observed. (B) Retroperitoneal mass surrounding the aorta shrunk after immunosuppression therapy.
We commenced hemodialysis immediately because of severe renal dysfunction and hyperkalemia. Bilateral ureter stents were inserted, and his urine volume and serum creatinine levels improved. His post-renal failure remitted, and the hemodialysis was terminated on the 11th hospital day. CT-guided core biopsy of the mass performed on the 13th hospital day revealed sclerotic tissue with acute inflammatory cells, along with foam cell hyperplasia consistent with retroperitoneal fibrosis (Figure 3). Cluster of differentiation (CD) immunostaining of the mass showed no abundance of CD68, CD138 or CD20, and
no conspicuous presence of IgG4-positive cells. Finally, IRF was diagnosed based on the histological findings. Immunosuppression therapy with oral prednisolone (30 mg/ day) was commenced promptly after diagnosis, and his lower back pain vanished within a few days. An abdominal CT scan on the 20th day from the start of treatment showed a clear reduction of the peritoneal fibrosis (Figure 1B). The multiple T2WI hyperintensity lesions had shrunk on brain MRI (Figure 2C) and his cognitive difficulties abated. His HDS-R, MMSE and frontal assessment battery (FAB) scores were 25/30, 26/30 and 15/15 points after treatment,
Figure 2. (A) T2WI showed macular hyperintensity involving the subcortical white matter of bilateral hemispheres. Some of these abnormal intensity lesions showed peripheral hyperintensity on FLAIR images. (B) Brain MR angiography did not show abnormal narrowing in major branches of cerebral blood vessels. (C) Abnormal hyperintensity on T2WI and FLAIR images was reduced in frequency and size after treatment.
470
T. Tani et al.
Figure 3. The core biopsy showed sclerotic tissue with acute inflammatory cells, along with foam cell hyperplasia consistent with retroperitoneal fibrosis.
respectively. The patient is now doing well, is back at work, and remains on immunosuppression therapy with oral prednisolone (5 mg/day) and mizoribine (150 mg/day).
Discussion We experienced a rare case of IRF, which seemed to have complicated cerebral vasculitis. The patient had a smoking habit and nontreated dyslipidemia, but these factors alone seemed insufficient to explain his severe complications. We therefore speculated that an autoimmune disorder, the presumed cause of the IRF, could also have triggered his intracranial lesions [5]. The pathogenesis of IRF is still unclear. The leading theory is that IRF is a consequence of a local inflammatory reaction to oxidized ceroid and LDL, two commonly observed components of atherosclerotic plaques of the abdominal aorta. These oxidized lipids trigger a fibro-inflammatory response when immunocompetent cells such as T lymphocytes and B lymphocytes encounter them in plaque macrophages [6]. Meanwhile, IRF is often accompanied by elevated concentrations of acute-phase reactants, positive testing for autoantibodies, and associated autoimmune diseases such as autoimmune thyroiditis. A number of reports, including some on autopsy cases, have described aortic and periaortic inflammations not only of the abdominal aorta, but also of the thoracic aorta, major branches such as the renal, mesenteric, and celiac arteries, and even the coronary arteries [7,8]. Autopsy studies report the presence of adventital inflammation in aortic section lacking periaortic fibrosis, which indicate that aortitis could precede the development of adventitial and periadventitial fibrosis [7]. Another study of 11 chronic periaortitis patients (10 IRF patients and one inflammatory aneurysm patient) has revealed significantly increased number of CECs (circulating endothelial cell concentrations) in comparison with healthy subjects, and they closely correlated with the degree of disease activity. This suggests that endothelial injury associated
Mod Rheumatol, 2015; 25(3): 468–471
with micro-vascular damage plays an important role in the pathogenesis of IRF [9]. Furthermore, RF is strongly associated with HLA-DRB1*03, an allele linked to prototypical autoimmune conditions such as type 1 diabetes, myasthenia gravis and autoimmune thyroiditis [10,11]. Given these findings, researchers now assume that IRF is more of an immune-mediated systemic vasculitis than of an exaggerated local reaction to atherosclerosis, resulting in adventitial and periadventitial fibrosis [1,3–5]. Our patient had a complication of intracranial lesions that could have been derived from cerebral vasculitis. Brain MRI findings showed multiple patches of degeneration surrounded by T2WI and FLAIR image hyperintensity. Brain MRI images in lymphoma, cardiogenic embolism, infective endocarditis, sepsis and some of collagen diseases can resemble those of this case, but cardiac ultrasound study and blood examination, and the histological findings denied all these disorders. Cerebral vasculitis sometimes appears as blood vessel stenosis, and narrowing in MR angiography showed, but it was negative in our case [12]. Cerebral angiography, not being performed due to his severe renal failure and invasiveness, may have revealed finer abnormalities with higher sensitivity. Another characteristic feature of his brain MRI findings is the reversible T2WI and FLAIR image hyperintensity. These findings can be explained not only by cerebral vasculitides, but also by uremia, or posterior reversible encephalopathy syndrome as a manifestation of vasogenic edema [13]. Yet central degeneration is reflective of more destructive changes such as aortic and periaortic inflammation. The success of the prednisolone immunosuppression therapy in arresting the degeneration implicates systemic vascular inflammation as well. An assumed pathophysiology implies that his abnormal findings on brain MRI can result from micro-vascular inflammations followed by vasogenic edema. Thus, we consider these findings the results of cerebral vasculitides, although striking evidence by imaging studies is lacking. While the reported vascular involvements of IRF are mainly large to medium vessels (the aorta and its major branches), some autopsy cases refer to small vessel vasculitis [14]. As the presumed etiology of IRF is an immune-mediated systemic vasculitis, vasculitides could take place on any vessels of human body. The vascular supplies of his multiple intracranial lesions are mainly small vessels, which are probably not detectable in MR angiography. Therefore, vasculitides observed in this case are expected to have taken place in large to small vessels. In accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of vasculitides, such vasculitides can be categorized into large vessel vasculitis (LVV) or variable vessel vasculitis (VVV) [15]. Immunological and histological investigations of IRF have revealed new features of the disease consistent with a systemic immune-mediated vasculitis [1,3–5]. Mindful of the recent theories about IRF, we concluded that our patient’s abnormal findings on brain MRI might have resulted from periaortic inflammation of the cerebral blood vessels. As far as we searched, this is the first report referring to cerebral vasculitides as the complication of IRF. If this was so, our case could be key to elucidating the pathogenesis of IRF. Thus, more latent symptom-free cases with cerebrovascular complications may be included among the patients suffering from IRF. We need to screen for the presence of such complications in further surveys of IRF patients.
Conflict of interest None.
References 1. Gilkeson GS, Allen NB. Retroperitoneal fibrosis: a true connective tissue disease. Rheum Dis Clin North Am. 1996;22(1):23–38.
DOI 10.3109/14397595.2013.843754
2. Koep L, Zuidema GD. The clinical significance of retroperitoneal fibrosis. Surgery. 1977;81(3):250–7. 3. Vaglio A, Buzio C. Chronic periaortitis: a spectrum of diseases. Curr Opin Rheumatol. 2005;17(1):34–40. 4. Kottra JJ, Dunnick NR. Retroperitoneal fibrosis. Radiol Clin North Am. 1996;34(6):1259–75. 5. Vaglio A, Pipitone N, Savarani C. Chronic periaortitis: a large vessel vasculitis? Curr Opin Rheumatol. 2011;23(1):1–6. 6. Parums DV, Chadwick DR, Mitchinson MJ. The localisation of immunoglobulin in chronic periaortitis. Atherosclerosis. 1986; 61(2):117–23. 7. Mitchinson MJ. The pathology of idiopathic retroperitoneal fibrosis. J Clin Pathol. 1970;23(8):681–9. 8. Cohle SD, Lie JT. Inflammatory aneurysm of the abdominal aorta, aortitis, and coronary arteritis. Arch Pathol Lab Med. 1988;112(11):1121–5. 9. Moroni G, Del Papa N, Moronetti LM, Vitali C, Maglione W, Comina DP, et al. Increased levels of circulating endothelial cells in chronic periaortitis as a marker of active disease. Kidney Int. 2005;68(2):562–8.
Case report 471 10. Martorana D, Vaglio A, Greco P, Zanetti A, Moroni G, Salvarani C. Chronic periaortitis and HLA- DRB1*03: another clue to an autoimmune origin. Arthritis Rheum. 2006;55(1): 126–30. 11. Klein J, Sato A. The HLA system: second of two parts. N Engl J Med. 2000;343(11):782–6. 12. Ghinoi A, Zuccoli G, Pipitone N, Salvarani C. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving the central nervous system: case report and review of the literature. Clin Exp Rheumatol. 2010;28(5):759–66. 13. Lamy C, Oppenheim C, Méder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging. 2004; 14(2):89–96. 14. Doi M, Hoshikawa M, Ono A, Honjo K, Ariizumi Y, Koike J, et al. An autopsy case of idiopathic retroperitoneal fibrosis (In Japanese). Shindan Byouri. In press. 15. Jennette J, Falk R, Bacon P, Basu N, Cid M, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11.
Copyright of Modern Rheumatology (Informa Healthcare) is the property of Informa Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
