Cardiovascular Pathology 23 (2014) 363–365
Contents lists available at ScienceDirect
Cardiovascular Pathology
Clinical Case Report
A case of aortic and mitral valve involvement in granulomatosis with polyangiitis Olivier Espitia a,⁎, Laure Droy b, Sabine Pattier c, Frédérique Naudin d, Antoine Mugniot e, Arnaud Cavailles d, Mohamed Hamidou a, Patrick Bruneval f, Christian Agard a, 1, Claire Toquet b, 1 a
Department of Internal Medicine, University Hospital of Nantes, France Department of Pathology, University Hospital of Nantes, France Department of Cardiology, University Hospital of Nantes, France d Department of Pulmonary Medicine, University Hospital of Nantes, France e Department of Thoracic and Cardio-vascular Surgery, University Hospital of Nantes, France f Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France b c
a r t i c l e
i n f o
Article history: Received 8 May 2014 Received in revised form 28 July 2014 Accepted 28 July 2014 Keywords: Granulomatosis with polyangiitis Wegener’s granulomatosis Valve disease Polymorphous microabscesses Epithelioid granuloma
a b s t r a c t Granulomatosis with polyangiitis (GPA) (Wegener’s) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2 years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Granulomatosis with polyangiitis (GPA) is a systemic necrotizing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis which typically involves the upper respiratory tract, kidneys, and lungs. Cardiac manifestations are rare and might be underdiagnosed when typical clinical signs are lacking. Pericarditis and coronary vasculitis are the most frequent findings of cardiac involvement in GPA (half of cases); myocarditis and conduction block are also described. In GPA, cardiac valvular disease seems to be very uncommon [1]. We report an exceptional case of dual valvular involvement during GPA with well-documented histopathological analysis. 2. Case report In 2005, a 60-year-old woman with a history of arterial hypertension, chronic obstructive pulmonary disease, and active smoking initially Conflicts of interest: The authors declare that they have no conflict of interest. Funding source: No external funding was secured for this report. ⁎ Corresponding author. Department of Internal Medicine, Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes, 1 place Alexis Ricordeau 44093 Nantes, France. Tel.: +33 240 083 146; fax: +33 240 083 379. E-mail address: [email protected] (O. Espitia). 1 Christian Agard and Claire Toquet contributed equally to this report as co-last author. http://dx.doi.org/10.1016/j.carpath.2014.07.007 1054-8807/© 2014 Elsevier Inc. All rights reserved.
developed weight loss, dyspnea, arthritis, and inflammatory syndrome [C-reactive protein (CRP) 150 mg/l]. She had no treatment. Computed tomographic (CT) scan found multiple thoracic lung nodules with compression of the right upper lobe bronchus. Lung nodules were explored by biopsy which showed necrosis surrounded by inflammatory infiltrates composed of some epithelioid and giant cells, mononuclear cells, and polymorphous microabscesses without any pathogens. Blood tests including ANCA, enzyme-linked immunosorbent assay antimyeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies, blood culture, mycobacterial investigations, and viral serology were negative. Electrocardiogram was normal; echocardiography found septal kinetics disorder without valvular involvement; left ventricular ejection fraction (LVEF) was 63%. Based on these findings, ANCA-negative GPA was diagnosed. At diagnosis, there was neither renal (serum creatinine 63 μmol/l, proteinuria 0.14 g/l, no hematuria) nor upper respiratory tract involvement, and Birmingham Vasculitis Activity Score (BVAS) was 13. She was treated with six cyclophosphamide (CYC) monthly pulses (600 mg/m2) followed by oral azathioprine (100 mg daily) associated with corticosteroids (prednisone 1 mg/kg/d). Remission was achieved, and treatment was discontinued after 2 years; oral corticosteroids were replaced by inhaled corticosteroids. The patient was followed every 6 months; CRP remained normal and ANCA negative. Four years later, she complained of isolated progressive dyspnea and pulmonary edema due to aortic and mitral regurgitation. CRP was
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O. Espitia et al. / Cardiovascular Pathology 23 (2014) 363–365
92 mg/l. She had no other systemic symptoms. Search for p-ANCA was positive (perinuclear pattern) with ANCA anti-MPO (35 UI/ml). Thoracic CT scan found no active lesion. Echocardiography showed an aortic regurgitation (4/4), a restrictive mitral regurgitation (2/4), a 50% LVEF, and a dilated left atrium (27 cm 2). Transesophageal echocardiography showed thickening of aortic annulus, thickening of anterior mitral valve, and restriction of posterior mitral valve; no vegetation was present on the valves. Coronary angiography showed a very irregular, calcified, and dominant right coronary artery with an old occlusion in proximal segment. Aortic and mitral valve replacements associated with coronary artery bypass were performed. Macroscopically, aortic valve was tricuspid; cups appeared diffusely thickened. Mitral valve’s leaflet appeared also thickened; chordae tendineae displayed no abnormalities. A few calcified deposits were observed closed to the mitral annulus. No vegetations were seen.
Blood and valves cultures were negative. Histopathological analysis of the aortic and mitral valve specimens showed extensive typical lesions of GPA, namely, a granulomatous inflammation and polymorphonuclear microabscesses with minute and remarkable geographic necrosis (Fig. 1). This necrosis was sometimes referred to as “dirty necrosis” because it contained cellular debris and dead polymorphonuclear cells, or “eosinophilic necrosis” when it was devoid of cellular debris. The necrosis was surrounded by a granulomatous infiltrate composed of macrophages, giant cells, lymphocytes, and plasma cells. This infiltrate, mainly deeply located in the central layer of the valve, could also be observed superficially underlying an intact endothelial layer. This endothelial layer could be focally interrupted, and surface erosions could be observed. However, neither vegetation nor fibrin deposit was seen. Areas of fibrosis were observed. There were numerous vessels surrounded by the inflammatory infiltrate. Very
Fig. 1. Mitral and aortic valves. (A, B) Mitral valve: Involvement of (A) the leaflet (central layer) and (B) the chordae tendineae by the inflammatory infiltrate (hematoxylin eosin staining [HES]; magnification ×20). (C) Aortic valve: thickening of the valve; diffuse inflammatory infiltrate, and “geographic” necrosis involving the different layers of the valve (*) (HES; magnification ×20). (D) Eosinophilic and “dirty” necrosis surrounded by granulomatous infiltrate with palissading macrophages, lymphocytes, and plasma cells (HES; magnification ×200). (E) Granulomatous infiltrate with giant cells (arrows) with polymorphous microabscesses (*) (HES; magnification ×200). (F) “Dirty” necrosis within fibrosis’ areas (HES; magnification ×200).
O. Espitia et al. / Cardiovascular Pathology 23 (2014) 363–365
rare lymphocytes could infiltrate their wall, but it was considered as a nonspecific finding. Stains (periodic acid–Schiff, Gram–Weigert, and Ziehl) for fungi, bacteria, or other organisms were negative. The patient felt better after surgery and did not receive any specific treatment of necrotizing vasculitis (BVAS 6). Seven months later, she presented with right eye papillitis, inflammatory syndrome, arterial hypertension, increase in serum creatinine 92 μmol/l, proteinuria 0.05 g/d, no hematuria, wheezing, and arthralgia arising with antiMPO ANCA persistence (24UI/ml). Considered as a relapse of GPA (BVAS 19), she received three new courses of CYC with prednisone 1 mg/kg/d followed by rituximab as a maintenance therapy, with clinical remission and ANCA decrease (5.6 UI/ml). 3. Discussion We report a rare case of dual valvular involvement during GPA with well-documented histopathological analysis. The diagnosis was based on clinical history, histopathological findings, and rise of ANCA. Although GPA is a systemic disorder, clinical evidence of cardiac involvement is uncommon. In a large cohort of 595 patients with periarteritis nodosa, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), 14% of patients had congestive cardiac failure at diagnosis [2]. Frequency of heart involvement in GPA is about 25% in autopsy study and 8% in clinical study. Half of patients with GPA heart involvement had pericarditis; 25%, myocarditis; 21%, valvular involvement; 17%, conduction block; and 11%, myocardial infarction. In a series of 21 patients with GPA heart valve involvement, aortic valve was involved in 57.1% of case; mitral valve, 14.3%; and both aortic and mitral valves, 28.6%. Aortic regurgitation is the main manifestation; other manifestations are rare: mitral regurgitation, aortic stenosis, valvular vegetations, mass involving a mitral leaflet, and multiple atrial masses [3]. In the cases of GPA-specific valvular involvement, 50% of valvular lesions were present at diagnosis, and 19% were observed after the first year of the vasculitis diagnosis [3]. Our literature review found 16 cases of documented valvular GPA involvement [3,4]: 10 GPA aortic valve involvement, and 3 mitral and 3 aortic/mitral involvements. Including this report, mean age at diagnosis of valvular involvement was 48.3 years. ANCA were positive in 10/12 patients: 6 patients with c-ANCA, 2 with p-ANCA, and 2 with unknown specificity. Anti-PR3 was positive in three cases and antiMPO in two cases. Six cases of valvular involvement occurred after the diagnosis of GPA: two cases occurred without immunosuppressive (IS) treatment; two cases, under IS treatment. In our case, microscopic examination of the valves demonstrated a typical GPA histopathological pattern based on two major histological criteria: polymorphous microabscesses with minute and remarkable geographic necrosis and a granulomatous inflammation. Neovascularization was present but without any obvious signs of vasculitis. Moreover, a major part of the infiltrate was located in the central layer of the valve, but it could also underlie the endothelial layer or a surface erosion. There were no vegetations and no fibrin deposit on the valve’s
365
surface. All these findings provided arguments in favor of an active GPA. However, in any cases, presence of microabscesses requires special stainings to rule out a bacterial/ fungal valves’ secondary infection. In all these cases, extensive valve samples are required to perform the correct diagnosis especially when the patient is under IS therapy. In a very few cases, histological lesions within valvular tissue were specific, characterized by granulomatous inflammation with minute or large necrosis and polymorphous microabscesses as described above. In most cases (12 cases on 16), pathological findings were nonspecific, without argument for active valve involvement. The lesions included insignificant inflammatory infiltrate, myxomatous change, or degeneration of collagen. Some other cases displayed neovascularization and fibrosis with no significant inflammatory infiltrate. These lesions are nonspecific but can be the only manifestation of underlying GPA and considered as “scarring” lesions. Infectious diseases of cardiac valves should be mentioned because cardiac valvular involvement in GPA is uncommon. Subacute bacterial endocarditis (SBE) has first to be ruled out based on negative blood cultures, intracellular pathogens search (with serology and bacterial polymerase chain reaction), and absence of microorganism on pathologist’s examination. In the present report, blood cultures were negative and p-ANCA anti-MPO positive. However, this type of valvular involvement associated with ANCA may be encountered in SBE [5]. c-ANCA are most often encountered in SBE, but p-ANCA are also described. Recently, among 109 infective endocarditis cases, 18% had c- or p-ANCA, and 8% had anti-PR3 or anti-MPO [5]. This report illustrates a diagnostic difficulty between SBE and specific involvement of GPA with no classical systemic symptoms. Clinical, biological, and pathological data must be taken into account to propose final diagnosis. To conclude, we report an exceptional case of severe GPA with aortic and mitral valves specific involvement whose diagnosis was only established at pathological analysis. Clinicians should be aware of such involvement in GPA that may occur as a sole sign of a relapse. ANCA should be monitored regularly even in patients with initial ANCA-negative GPA. Our case illustrates the need of a close collaboration between clinicians and pathologists in order to assess such difficult diagnosis.
References [1] Goodfield NE, Bhandari S, Plant WD, Morley-Davies A, Sutherland GR. Cardiac involvement in Wegener’s granulomatosis. Br Heart J 1995;73:110–5. [2] Bourgarit A, Le Toumelin P, Pagnoux C, Cohen P, Mahr A, Le Guern V, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg–Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore) 2005;84:323–30. [3] Lacoste C, Mansencal N, M’rad M Ben, Goulon-Goeau C, Cohen P, Guillevin L, et al. Valvular involvement in ANCA-associated systemic vasculitis: a case report and literature review. BMC Musculoskelet Disord 2011;12:50–6. [4] Shakil O, Matyal R, Khabbaz K, Wang A, Mahmood F. Intracardiac Wegener’s granulomatosis. Ann Thorac Surg 2012;94:e105. [5] Mahr A, Batteux F, Tubiana S, Goulvestre C, Wolff M, Papo T, et al. Prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol 2014; 66(6):1672–7.
Contents lists available at ScienceDirect
Cardiovascular Pathology
Clinical Case Report
A case of aortic and mitral valve involvement in granulomatosis with polyangiitis Olivier Espitia a,⁎, Laure Droy b, Sabine Pattier c, Frédérique Naudin d, Antoine Mugniot e, Arnaud Cavailles d, Mohamed Hamidou a, Patrick Bruneval f, Christian Agard a, 1, Claire Toquet b, 1 a
Department of Internal Medicine, University Hospital of Nantes, France Department of Pathology, University Hospital of Nantes, France Department of Cardiology, University Hospital of Nantes, France d Department of Pulmonary Medicine, University Hospital of Nantes, France e Department of Thoracic and Cardio-vascular Surgery, University Hospital of Nantes, France f Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France b c
a r t i c l e
i n f o
Article history: Received 8 May 2014 Received in revised form 28 July 2014 Accepted 28 July 2014 Keywords: Granulomatosis with polyangiitis Wegener’s granulomatosis Valve disease Polymorphous microabscesses Epithelioid granuloma
a b s t r a c t Granulomatosis with polyangiitis (GPA) (Wegener’s) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2 years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Granulomatosis with polyangiitis (GPA) is a systemic necrotizing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis which typically involves the upper respiratory tract, kidneys, and lungs. Cardiac manifestations are rare and might be underdiagnosed when typical clinical signs are lacking. Pericarditis and coronary vasculitis are the most frequent findings of cardiac involvement in GPA (half of cases); myocarditis and conduction block are also described. In GPA, cardiac valvular disease seems to be very uncommon [1]. We report an exceptional case of dual valvular involvement during GPA with well-documented histopathological analysis. 2. Case report In 2005, a 60-year-old woman with a history of arterial hypertension, chronic obstructive pulmonary disease, and active smoking initially Conflicts of interest: The authors declare that they have no conflict of interest. Funding source: No external funding was secured for this report. ⁎ Corresponding author. Department of Internal Medicine, Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes, 1 place Alexis Ricordeau 44093 Nantes, France. Tel.: +33 240 083 146; fax: +33 240 083 379. E-mail address: [email protected] (O. Espitia). 1 Christian Agard and Claire Toquet contributed equally to this report as co-last author. http://dx.doi.org/10.1016/j.carpath.2014.07.007 1054-8807/© 2014 Elsevier Inc. All rights reserved.
developed weight loss, dyspnea, arthritis, and inflammatory syndrome [C-reactive protein (CRP) 150 mg/l]. She had no treatment. Computed tomographic (CT) scan found multiple thoracic lung nodules with compression of the right upper lobe bronchus. Lung nodules were explored by biopsy which showed necrosis surrounded by inflammatory infiltrates composed of some epithelioid and giant cells, mononuclear cells, and polymorphous microabscesses without any pathogens. Blood tests including ANCA, enzyme-linked immunosorbent assay antimyeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies, blood culture, mycobacterial investigations, and viral serology were negative. Electrocardiogram was normal; echocardiography found septal kinetics disorder without valvular involvement; left ventricular ejection fraction (LVEF) was 63%. Based on these findings, ANCA-negative GPA was diagnosed. At diagnosis, there was neither renal (serum creatinine 63 μmol/l, proteinuria 0.14 g/l, no hematuria) nor upper respiratory tract involvement, and Birmingham Vasculitis Activity Score (BVAS) was 13. She was treated with six cyclophosphamide (CYC) monthly pulses (600 mg/m2) followed by oral azathioprine (100 mg daily) associated with corticosteroids (prednisone 1 mg/kg/d). Remission was achieved, and treatment was discontinued after 2 years; oral corticosteroids were replaced by inhaled corticosteroids. The patient was followed every 6 months; CRP remained normal and ANCA negative. Four years later, she complained of isolated progressive dyspnea and pulmonary edema due to aortic and mitral regurgitation. CRP was
364
O. Espitia et al. / Cardiovascular Pathology 23 (2014) 363–365
92 mg/l. She had no other systemic symptoms. Search for p-ANCA was positive (perinuclear pattern) with ANCA anti-MPO (35 UI/ml). Thoracic CT scan found no active lesion. Echocardiography showed an aortic regurgitation (4/4), a restrictive mitral regurgitation (2/4), a 50% LVEF, and a dilated left atrium (27 cm 2). Transesophageal echocardiography showed thickening of aortic annulus, thickening of anterior mitral valve, and restriction of posterior mitral valve; no vegetation was present on the valves. Coronary angiography showed a very irregular, calcified, and dominant right coronary artery with an old occlusion in proximal segment. Aortic and mitral valve replacements associated with coronary artery bypass were performed. Macroscopically, aortic valve was tricuspid; cups appeared diffusely thickened. Mitral valve’s leaflet appeared also thickened; chordae tendineae displayed no abnormalities. A few calcified deposits were observed closed to the mitral annulus. No vegetations were seen.
Blood and valves cultures were negative. Histopathological analysis of the aortic and mitral valve specimens showed extensive typical lesions of GPA, namely, a granulomatous inflammation and polymorphonuclear microabscesses with minute and remarkable geographic necrosis (Fig. 1). This necrosis was sometimes referred to as “dirty necrosis” because it contained cellular debris and dead polymorphonuclear cells, or “eosinophilic necrosis” when it was devoid of cellular debris. The necrosis was surrounded by a granulomatous infiltrate composed of macrophages, giant cells, lymphocytes, and plasma cells. This infiltrate, mainly deeply located in the central layer of the valve, could also be observed superficially underlying an intact endothelial layer. This endothelial layer could be focally interrupted, and surface erosions could be observed. However, neither vegetation nor fibrin deposit was seen. Areas of fibrosis were observed. There were numerous vessels surrounded by the inflammatory infiltrate. Very
Fig. 1. Mitral and aortic valves. (A, B) Mitral valve: Involvement of (A) the leaflet (central layer) and (B) the chordae tendineae by the inflammatory infiltrate (hematoxylin eosin staining [HES]; magnification ×20). (C) Aortic valve: thickening of the valve; diffuse inflammatory infiltrate, and “geographic” necrosis involving the different layers of the valve (*) (HES; magnification ×20). (D) Eosinophilic and “dirty” necrosis surrounded by granulomatous infiltrate with palissading macrophages, lymphocytes, and plasma cells (HES; magnification ×200). (E) Granulomatous infiltrate with giant cells (arrows) with polymorphous microabscesses (*) (HES; magnification ×200). (F) “Dirty” necrosis within fibrosis’ areas (HES; magnification ×200).
O. Espitia et al. / Cardiovascular Pathology 23 (2014) 363–365
rare lymphocytes could infiltrate their wall, but it was considered as a nonspecific finding. Stains (periodic acid–Schiff, Gram–Weigert, and Ziehl) for fungi, bacteria, or other organisms were negative. The patient felt better after surgery and did not receive any specific treatment of necrotizing vasculitis (BVAS 6). Seven months later, she presented with right eye papillitis, inflammatory syndrome, arterial hypertension, increase in serum creatinine 92 μmol/l, proteinuria 0.05 g/d, no hematuria, wheezing, and arthralgia arising with antiMPO ANCA persistence (24UI/ml). Considered as a relapse of GPA (BVAS 19), she received three new courses of CYC with prednisone 1 mg/kg/d followed by rituximab as a maintenance therapy, with clinical remission and ANCA decrease (5.6 UI/ml). 3. Discussion We report a rare case of dual valvular involvement during GPA with well-documented histopathological analysis. The diagnosis was based on clinical history, histopathological findings, and rise of ANCA. Although GPA is a systemic disorder, clinical evidence of cardiac involvement is uncommon. In a large cohort of 595 patients with periarteritis nodosa, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), 14% of patients had congestive cardiac failure at diagnosis [2]. Frequency of heart involvement in GPA is about 25% in autopsy study and 8% in clinical study. Half of patients with GPA heart involvement had pericarditis; 25%, myocarditis; 21%, valvular involvement; 17%, conduction block; and 11%, myocardial infarction. In a series of 21 patients with GPA heart valve involvement, aortic valve was involved in 57.1% of case; mitral valve, 14.3%; and both aortic and mitral valves, 28.6%. Aortic regurgitation is the main manifestation; other manifestations are rare: mitral regurgitation, aortic stenosis, valvular vegetations, mass involving a mitral leaflet, and multiple atrial masses [3]. In the cases of GPA-specific valvular involvement, 50% of valvular lesions were present at diagnosis, and 19% were observed after the first year of the vasculitis diagnosis [3]. Our literature review found 16 cases of documented valvular GPA involvement [3,4]: 10 GPA aortic valve involvement, and 3 mitral and 3 aortic/mitral involvements. Including this report, mean age at diagnosis of valvular involvement was 48.3 years. ANCA were positive in 10/12 patients: 6 patients with c-ANCA, 2 with p-ANCA, and 2 with unknown specificity. Anti-PR3 was positive in three cases and antiMPO in two cases. Six cases of valvular involvement occurred after the diagnosis of GPA: two cases occurred without immunosuppressive (IS) treatment; two cases, under IS treatment. In our case, microscopic examination of the valves demonstrated a typical GPA histopathological pattern based on two major histological criteria: polymorphous microabscesses with minute and remarkable geographic necrosis and a granulomatous inflammation. Neovascularization was present but without any obvious signs of vasculitis. Moreover, a major part of the infiltrate was located in the central layer of the valve, but it could also underlie the endothelial layer or a surface erosion. There were no vegetations and no fibrin deposit on the valve’s
365
surface. All these findings provided arguments in favor of an active GPA. However, in any cases, presence of microabscesses requires special stainings to rule out a bacterial/ fungal valves’ secondary infection. In all these cases, extensive valve samples are required to perform the correct diagnosis especially when the patient is under IS therapy. In a very few cases, histological lesions within valvular tissue were specific, characterized by granulomatous inflammation with minute or large necrosis and polymorphous microabscesses as described above. In most cases (12 cases on 16), pathological findings were nonspecific, without argument for active valve involvement. The lesions included insignificant inflammatory infiltrate, myxomatous change, or degeneration of collagen. Some other cases displayed neovascularization and fibrosis with no significant inflammatory infiltrate. These lesions are nonspecific but can be the only manifestation of underlying GPA and considered as “scarring” lesions. Infectious diseases of cardiac valves should be mentioned because cardiac valvular involvement in GPA is uncommon. Subacute bacterial endocarditis (SBE) has first to be ruled out based on negative blood cultures, intracellular pathogens search (with serology and bacterial polymerase chain reaction), and absence of microorganism on pathologist’s examination. In the present report, blood cultures were negative and p-ANCA anti-MPO positive. However, this type of valvular involvement associated with ANCA may be encountered in SBE [5]. c-ANCA are most often encountered in SBE, but p-ANCA are also described. Recently, among 109 infective endocarditis cases, 18% had c- or p-ANCA, and 8% had anti-PR3 or anti-MPO [5]. This report illustrates a diagnostic difficulty between SBE and specific involvement of GPA with no classical systemic symptoms. Clinical, biological, and pathological data must be taken into account to propose final diagnosis. To conclude, we report an exceptional case of severe GPA with aortic and mitral valves specific involvement whose diagnosis was only established at pathological analysis. Clinicians should be aware of such involvement in GPA that may occur as a sole sign of a relapse. ANCA should be monitored regularly even in patients with initial ANCA-negative GPA. Our case illustrates the need of a close collaboration between clinicians and pathologists in order to assess such difficult diagnosis.
References [1] Goodfield NE, Bhandari S, Plant WD, Morley-Davies A, Sutherland GR. Cardiac involvement in Wegener’s granulomatosis. Br Heart J 1995;73:110–5. [2] Bourgarit A, Le Toumelin P, Pagnoux C, Cohen P, Mahr A, Le Guern V, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg–Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore) 2005;84:323–30. [3] Lacoste C, Mansencal N, M’rad M Ben, Goulon-Goeau C, Cohen P, Guillevin L, et al. Valvular involvement in ANCA-associated systemic vasculitis: a case report and literature review. BMC Musculoskelet Disord 2011;12:50–6. [4] Shakil O, Matyal R, Khabbaz K, Wang A, Mahmood F. Intracardiac Wegener’s granulomatosis. Ann Thorac Surg 2012;94:e105. [5] Mahr A, Batteux F, Tubiana S, Goulvestre C, Wolff M, Papo T, et al. Prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol 2014; 66(6):1672–7.
