Case Study
Immunoglobulin G4-related aortitis mimicking an intramural hematoma
Asian Cardiovascular & Thoracic Annals 2015, Vol. 23(9) 1083–1086 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314533974 aan.sagepub.com
Daniel Z Tay, Peter YT Goh, Terence K Teo, Mee Leng Boey, Naresh Chachlani and Poo Sing Wong
Abstract Immunoglobulin G4-related systemic disease is a rare entity with various presenting symptoms. We report the case of a 34-year-old Chinese male who presented with immunoglobulin G4-related aortitis and the unusual symptom of hoarseness of voice. He underwent distal ascending aorta and total aortic arch replacement.
Keywords Aorta, thoracic, Aortic aneurysm, thoracic, Aortitis, Diagnosis, differential, Hematoma, Immunoglobulin G
Introduction Immunoglobulin G4 (IgG4)-related systemic disease is a newly recognized disease entity. Only a few cases of IgG4-related aortitis have been reported.1 We describe the case of a young Chinese man with IgG4-related aortitis presenting as an intramural hematoma.
Case report A 34-year-old Chinese male presented with a 3-month history of voice hoarseness. Other than childhood asthma and being a smoker, there was no significant past medical history. Physical examination was unremarkable. He underwent laryngoscopy which revealed left vocal cord palsy. A computed tomography (CT) study of the thorax showed eccentric wall thickening of the aortic arch, highly suggestive of an intramural hematoma (Figure 1). A dedicated CT aortogram and coronary angiogram revealed normal coronary arteries. The aortogram showed an apparent intramural hematoma involving the aortic arch. This extended from the distal ascending aorta proximally and ended just distal to the origin of the left subclavian artery. An incidental finding of infrarenal periaortic soft tissue at the level
of the inferior mesenteric artery was also noted. Electrocardiography showed normal sinus rhythm. Transthoracic echocardiography revealed normal ventricular and valvular function. The patient underwent a median sternotomy for distal ascending aorta and total aortic arch replacement with a 32-mm Hemashield Platinum 4-branched graft (Maquet Cardiovascular LLC, San Jose, CA, USA), using cardiopulmonary bypass and total circulatory arrest. Intraoperatively, no aortic dissection or intramural hematoma was found, but the aortic wall was thickened and firm. The left vagus nerve was invaded by the aorta at the level of the left recurrent laryngeal nerve origin. Frozen section analysis of the aortic wall showed a nodular aggregated infiltrate of lymphoid cells with focal fibrosis, suggestive of lymphoplasmacytic aortitis. Immunohistochemical staining revealed a fibroinflammatory lesion consistent with IgG4-related aortitis or periaortitis (Figure 2). Further investigations demonstrated normal C3
Mount Elizabeth Hospital (Orchard), Singapore Corresponding author: Daniel Z Tay, c/o 3 Mount Elizabeth #12-04, Mount Elizabeth Medical Centre, 228510, Singapore. Email: [email protected]
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
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complement levels, and C4 complement was slightly elevated at 0.48 g L 1. Anti-nuclear antibody was positive at 1:80 (speckled pattern). Anti-dsDNA antibody, anti-neutrophil cytoplasmic antibodies, and anti-ENA antibodies were all negative. Immunoglobulins IgM and IgE were normal, but IgG and IgA were elevated at 17.18 g L 1 (normal range 5.00–15.00 g L 1) and 6.89 g L 1 (normal range 0.80–4.00 g L 1), respectively. Of the IgG subclasses, only IgG subclass 2 was elevated at 7.93 g L 1 (normal range 0.64–7.00 g L 1). The patient was started on oral prednisolone 40 mg daily. One month later, positron-emission tomography/CT showed complete resolution of the aortic thickening and periaortic soft tissue in the infrarenal aorta (Figure 3).
Figure 1. Contrast-enhanced computed tomography demonstrating eccentric wall thickening of the aortic arch, suggestive of an intramural hematoma (white arrow).
Discussion IgG4-related systemic disease is a recently discovered disease with a predilection for middle-aged and elderly men.1–3 Its full clinical and pathophysiological nature is yet to be fully understood. There have been several possible causes of this condition, including molecular mimicry, autoimmunity, and Helicobacter pylori infection which is associated with autoimmune pancreatitis.2,6 Given that IgG4-related systemic disease affects a wide variety of organs,2,3 it is difficult to establish a set of criteria that applies to all affected locations. An elevated serum IgG4 level is currently the most sensitive noninvasive test; it is elevated in up to 86% of patients. However, false-positive results can occur in cancer and infection, and may even be a normal variant in up to 5% of the general population. Therefore, a diagnosis of IgG4-related systemic disease should not be based only on elevated serum IgG4 levels but correlated with clinical, radiologic and histologic findings. Guma and colleagues3 proposed a set of diagnostic criteria for IgG4-related systemic disease, based on clinical findings of visceral edema, elevated serum IgG4 concentrations, and specific histopathological findings. Histopathologic examination is crucial because patients may present without any clinical signs of inflammation.4 In our patient, the main presenting symptom of hoarseness of voice is extremely rare. This was due to involvement of the left recurrent laryngeal nerve at the distal aortic arch by the aortitis. Despite the potentially aggressive nature of this disease, IgG4-related systemic disease usually responds well to corticosteroid therapy. However, the optimal
Figure 2. (a) Cross-sectional view of the resected aorta. (b) Fibroinflammatory aortitis with predominance of a lymphoplasmacytic infiltrate. Hematoxylin and eosin stain, original magnification 1 (inset: hematoxylin and eosin stain, original magnification 40).
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Figure 3. (a) Arterial-phase computed tomography showing infrarenal periaortic wall thickening encasing the origin of the inferior mesenteric artery (solid white circle). (b) A positron-emission tomography/computed tomography study after one-month of immunosuppression showed complete resolution of periaortic soft tissue thickening (dashed circle) with (c) no evidence of a fluorodeoxyglucose-avid focus (white arrow).
dose and duration of treatment is unknown.2 In the light of its good response to steroids, it has been suggested that medical treatment be the first-line management for IgG4-related diseases.1 However, the decision to start steroids may be difficult without a histological diagnosis. In patients with recurrent or refractory disease, or those intolerant to corticosteroid use, rituximab can provide swift and significant results and avoid the complications of long-term corticosteroid usage.3,5 In some patients with aortitis, surgical repair needs to be considered, especially if an aneurysm has formed. While it can be lifesaving in the short term,4 the long-term prognosis is unknown. There have been reports of syphilitic aortitis that can predispose to aortic dissection,7 and this is particularly dangerous if there is retrograde dissection to the neck vessels and aortic root. Although IgG4-related systemic disease is rare,6 a high index of suspicion of inflammatory causes of aortic disease should be considered in young patients with unusual clinical manifestations, normal serology, and radiologic features of a thickened aortic wall.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement None declared.
References 1. Byeon K, Han J, Kim JS, et al. Immunoglobulin G4related periaortitis mimicking an intramural hematoma. Ann Thorac Surg 2011; 92: 1506–1508. 2. Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM and Stone JR. IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 2009; 60: 3139–3145. 3. Guma M and Firestein GS. IgG4-related diseases. Best Pract Res Clin Rheumatol 2012; 26: 425–438. 4. Pacini D, Leone O, Turci S, et al. Incidence, etiology, histologic findings, and course of thoracic inflammatory aortopathies. Ann Thorac Surg 2008; 86: 1518–2153.
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
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5. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB and Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore) 2012; 91: 57–66. 6. Kajander H, Paavonen T, Valo T, Tarkka M and Mennander AA. Immunoglobulin G4-positive ascending
thoracic aortitis may be prone to dissection. J Thorac Cardiovasc Surg 2012; 146: 1449–1455. 7. Park BS, Min HK, Kang do K, et al. Stanford type A aortic dissection secondary to infectious aortitis: a case report. J Korean Med Sci 2013; 28: 485–488.
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
Immunoglobulin G4-related aortitis mimicking an intramural hematoma
Asian Cardiovascular & Thoracic Annals 2015, Vol. 23(9) 1083–1086 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314533974 aan.sagepub.com
Daniel Z Tay, Peter YT Goh, Terence K Teo, Mee Leng Boey, Naresh Chachlani and Poo Sing Wong
Abstract Immunoglobulin G4-related systemic disease is a rare entity with various presenting symptoms. We report the case of a 34-year-old Chinese male who presented with immunoglobulin G4-related aortitis and the unusual symptom of hoarseness of voice. He underwent distal ascending aorta and total aortic arch replacement.
Keywords Aorta, thoracic, Aortic aneurysm, thoracic, Aortitis, Diagnosis, differential, Hematoma, Immunoglobulin G
Introduction Immunoglobulin G4 (IgG4)-related systemic disease is a newly recognized disease entity. Only a few cases of IgG4-related aortitis have been reported.1 We describe the case of a young Chinese man with IgG4-related aortitis presenting as an intramural hematoma.
Case report A 34-year-old Chinese male presented with a 3-month history of voice hoarseness. Other than childhood asthma and being a smoker, there was no significant past medical history. Physical examination was unremarkable. He underwent laryngoscopy which revealed left vocal cord palsy. A computed tomography (CT) study of the thorax showed eccentric wall thickening of the aortic arch, highly suggestive of an intramural hematoma (Figure 1). A dedicated CT aortogram and coronary angiogram revealed normal coronary arteries. The aortogram showed an apparent intramural hematoma involving the aortic arch. This extended from the distal ascending aorta proximally and ended just distal to the origin of the left subclavian artery. An incidental finding of infrarenal periaortic soft tissue at the level
of the inferior mesenteric artery was also noted. Electrocardiography showed normal sinus rhythm. Transthoracic echocardiography revealed normal ventricular and valvular function. The patient underwent a median sternotomy for distal ascending aorta and total aortic arch replacement with a 32-mm Hemashield Platinum 4-branched graft (Maquet Cardiovascular LLC, San Jose, CA, USA), using cardiopulmonary bypass and total circulatory arrest. Intraoperatively, no aortic dissection or intramural hematoma was found, but the aortic wall was thickened and firm. The left vagus nerve was invaded by the aorta at the level of the left recurrent laryngeal nerve origin. Frozen section analysis of the aortic wall showed a nodular aggregated infiltrate of lymphoid cells with focal fibrosis, suggestive of lymphoplasmacytic aortitis. Immunohistochemical staining revealed a fibroinflammatory lesion consistent with IgG4-related aortitis or periaortitis (Figure 2). Further investigations demonstrated normal C3
Mount Elizabeth Hospital (Orchard), Singapore Corresponding author: Daniel Z Tay, c/o 3 Mount Elizabeth #12-04, Mount Elizabeth Medical Centre, 228510, Singapore. Email: [email protected]
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
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complement levels, and C4 complement was slightly elevated at 0.48 g L 1. Anti-nuclear antibody was positive at 1:80 (speckled pattern). Anti-dsDNA antibody, anti-neutrophil cytoplasmic antibodies, and anti-ENA antibodies were all negative. Immunoglobulins IgM and IgE were normal, but IgG and IgA were elevated at 17.18 g L 1 (normal range 5.00–15.00 g L 1) and 6.89 g L 1 (normal range 0.80–4.00 g L 1), respectively. Of the IgG subclasses, only IgG subclass 2 was elevated at 7.93 g L 1 (normal range 0.64–7.00 g L 1). The patient was started on oral prednisolone 40 mg daily. One month later, positron-emission tomography/CT showed complete resolution of the aortic thickening and periaortic soft tissue in the infrarenal aorta (Figure 3).
Figure 1. Contrast-enhanced computed tomography demonstrating eccentric wall thickening of the aortic arch, suggestive of an intramural hematoma (white arrow).
Discussion IgG4-related systemic disease is a recently discovered disease with a predilection for middle-aged and elderly men.1–3 Its full clinical and pathophysiological nature is yet to be fully understood. There have been several possible causes of this condition, including molecular mimicry, autoimmunity, and Helicobacter pylori infection which is associated with autoimmune pancreatitis.2,6 Given that IgG4-related systemic disease affects a wide variety of organs,2,3 it is difficult to establish a set of criteria that applies to all affected locations. An elevated serum IgG4 level is currently the most sensitive noninvasive test; it is elevated in up to 86% of patients. However, false-positive results can occur in cancer and infection, and may even be a normal variant in up to 5% of the general population. Therefore, a diagnosis of IgG4-related systemic disease should not be based only on elevated serum IgG4 levels but correlated with clinical, radiologic and histologic findings. Guma and colleagues3 proposed a set of diagnostic criteria for IgG4-related systemic disease, based on clinical findings of visceral edema, elevated serum IgG4 concentrations, and specific histopathological findings. Histopathologic examination is crucial because patients may present without any clinical signs of inflammation.4 In our patient, the main presenting symptom of hoarseness of voice is extremely rare. This was due to involvement of the left recurrent laryngeal nerve at the distal aortic arch by the aortitis. Despite the potentially aggressive nature of this disease, IgG4-related systemic disease usually responds well to corticosteroid therapy. However, the optimal
Figure 2. (a) Cross-sectional view of the resected aorta. (b) Fibroinflammatory aortitis with predominance of a lymphoplasmacytic infiltrate. Hematoxylin and eosin stain, original magnification 1 (inset: hematoxylin and eosin stain, original magnification 40).
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
Tay et al.
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Figure 3. (a) Arterial-phase computed tomography showing infrarenal periaortic wall thickening encasing the origin of the inferior mesenteric artery (solid white circle). (b) A positron-emission tomography/computed tomography study after one-month of immunosuppression showed complete resolution of periaortic soft tissue thickening (dashed circle) with (c) no evidence of a fluorodeoxyglucose-avid focus (white arrow).
dose and duration of treatment is unknown.2 In the light of its good response to steroids, it has been suggested that medical treatment be the first-line management for IgG4-related diseases.1 However, the decision to start steroids may be difficult without a histological diagnosis. In patients with recurrent or refractory disease, or those intolerant to corticosteroid use, rituximab can provide swift and significant results and avoid the complications of long-term corticosteroid usage.3,5 In some patients with aortitis, surgical repair needs to be considered, especially if an aneurysm has formed. While it can be lifesaving in the short term,4 the long-term prognosis is unknown. There have been reports of syphilitic aortitis that can predispose to aortic dissection,7 and this is particularly dangerous if there is retrograde dissection to the neck vessels and aortic root. Although IgG4-related systemic disease is rare,6 a high index of suspicion of inflammatory causes of aortic disease should be considered in young patients with unusual clinical manifestations, normal serology, and radiologic features of a thickened aortic wall.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement None declared.
References 1. Byeon K, Han J, Kim JS, et al. Immunoglobulin G4related periaortitis mimicking an intramural hematoma. Ann Thorac Surg 2011; 92: 1506–1508. 2. Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM and Stone JR. IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 2009; 60: 3139–3145. 3. Guma M and Firestein GS. IgG4-related diseases. Best Pract Res Clin Rheumatol 2012; 26: 425–438. 4. Pacini D, Leone O, Turci S, et al. Incidence, etiology, histologic findings, and course of thoracic inflammatory aortopathies. Ann Thorac Surg 2008; 86: 1518–2153.
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
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5. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB and Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore) 2012; 91: 57–66. 6. Kajander H, Paavonen T, Valo T, Tarkka M and Mennander AA. Immunoglobulin G4-positive ascending
thoracic aortitis may be prone to dissection. J Thorac Cardiovasc Surg 2012; 146: 1449–1455. 7. Park BS, Min HK, Kang do K, et al. Stanford type A aortic dissection secondary to infectious aortitis: a case report. J Korean Med Sci 2013; 28: 485–488.
Downloaded from aan.sagepub.com at CMU Libraries - library.cmich.edu on October 20, 2015
