CE: Tripti; JCM-D-14-00057; Total nos of Pages: 3;
JCM-D-14-00057
Images in cardiovascular medicine
Restrictive cardiomyopathy and pseudoxanthoma elasticum skin lesions Maria B. Musumecia, Lorenzo Semprinia, Matteo Casenghia, Dalma Montesantia, Vittoria Mastromarinoa, Fabio Socciarellic, Massimo Volpea,b and Camillo Autorea We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively. Furthermore, the electron microscopic examination did not show all the peculiar histopathological findings of amyloid elastosis, precluding a final diagnosis of this disease. J Cardiovasc Med 2014, 15:000–000
A 46-year-old man, with no cardiovascular risk factors or family history of cardiovascular disease, was admitted to our hospital for a massive right-sided pleural effusion. Cardiovascular physical examination revealed gallop rhythm, severe elevation of jugular venous pressure and mild peripheral edema. The ECG showed a low voltage on the limb leads and a pseudoinfarct pattern in the peripheral leads; transthoracic echocardiogram revealed a symmetrical concentric left ventricular hypertrophy with normal ejection fraction, restrictive filling pattern and left atrial enlargement (Fig. 1a and b). N-terminal-pro-brain natriuretic peptide was significantly increased (6627 ng/ml), whereas cardiac troponin I was normal (0.06 ng/ml). Cardiac magnetic resonance (MRI) demonstrated a diffuse subendocardial late enhancement (Fig. 1c). On the basis of these features, we suspected an amyloidotic cardiomyopathy. A serum and urine immunofixation revealed a monoclonal l spike (167 mg/dl), increased serum free light chain levels (155 mg/l) with a reduced k/l ratio (0.06) and a BenceJones proteinuria. A minor salivary gland biopsy confirmed histologically the diagnosis of amyloid light chain (AL) amyloidosis. During hospitalization, we noted the presence of yellowish papulous skin lesions measuring 1–3 mm in diameter in a reticular pattern on the trunk and the arm. The patient claimed that these lesions had been present from 6 to 7 months. A skin biopsy was performed, which showed degenerated and irregular elastic fibers in the dermis (Fig. 1d). These lesions were compatible with a diagnosis of pseudoxanthoma elasticum (PXE). A cyclophosphamide-bortezomib1558-2027 ß 2014 Italian Federation of Cardiology
Keywords: AL amyloidosis, amyloid elastosis, pseudoxanthoma elasticum, restrictive cardiomyopathy a Cardiology, Clinical and Molecular Medicine Department, ‘Sapienza’ University of Rome, Rome, bIRCCS Neuromed, Pozzilli (IS), Italy and cPathology Department, ‘Sapienza’ University of Rome, Rome, Italy
Correspondence to Maria Beatrice Musumeci, MD, Cardiology Department, Clinical and Molecular ‘Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Ospedale Sant’Andrea, Via di Grottarossa 1035-1039, 00189 Rome, Italy Tel: +39 06 33775563; fax: +39 06 33775038; e-mail: [email protected] Received 22 January 2014 Revised 5 May 2014 Accepted 6 May 2014
dexamethasone (CyBorD) chemotherapy regimen was started for the treatment of amyloidosis. Nevertheless, we observed a rapid deterioration of the hematological and cardiac picture and the patient died suddenly in the context of severe and refractory heart failure. We described an unusual case of a patient with AL amyloidosis and PXE-like lesions. A rare form of systemic amyloidosis accompanied by PXE-like skin lesions has been previously described in only six studies.1 – 6 The major criterion for the diagnosis of the so-called amyloid elastosis is the presence of amyloid around the elastic fibers in the derma. In a post-hoc analysis, we performed an electron microscopic examination on the skin specimen of our patient, which failed to clearly show amyloid deposition in the derma; the immunohistochemistry analysis for immunoglobulin lambda chain showed extracellular matrix positivity compatible with an elastic fiber localization of the monoclonal component (Fig. 2). These findings have not been fully explained, but previous cases reported that amyloid deposition could be restricted to some elastic fibers only, completely sparing others in an apparently random manner.5 A concentric left ventricular hypertrophy was described only in a recent study of amyloid elastosis.6 Possibly, the severity of cardiomyopathy in our patient negatively influenced prognosis earlier than the appearance of amyloid deposition in the derma. In conclusion, we report a rare case of AL amyloidosis with PXE-like skin lesions and a severe restrictive cardiomyopathy. DOI:10.2459/JCM.0000000000000158
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00057; Total nos of Pages: 3;
JCM-D-14-00057
2 Journal of Cardiovascular Medicine 2014, Vol 00 No 00
Fig. 1
(a) ECG shows a low voltage in the limb leads and a pseudoinfarct pattern in the precordial leads. (b) Echocardiogram shows severe concentric left ventricular hypertrophy with a maximum wall thickness of 20 mm and left atrial enlargement. (c) Cardiac MR shows circumferential diffuse subendocardial late gadolinium enhancement. (d) The hematoxylin–eosin stain (H&E) shows deposition of basophilic collapsed and fragmented fibers in the derma (magnification 200). MR, magnetic resonance.
Fig. 2
Immunohistochemistry for immunoglobulin lambda chain (400 magnification). There is an extracellular matrix positivity compatible with elastic fiber localization.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00057; Total nos of Pages: 3;
JCM-D-14-00057
Pseudoxanthoma elasticum skin lesions Musumeci et al. 3
References 1 2
3
Winkelmann RK, Peters MS, Venencie PY, Amyloid elastosis. A new cutaneous and systemic pattern of amyloidosis. Arch Dermatol 1985; 121:498–502. Sepp N, Pichler E, Breathnach SM, Fritsch P, Hintner H. Amyloid elastosis: analysis of the role of amyloid P component. J Am Acad Dermatol 1990; 22:27–34. Vecchietti G, Masouye´ I, Salomon D, et al. An unusual form of primary systemic amyloidosis: amyloid elastosis. Report of a case treated by haematopoietic cell transplantation. Br J Dermatol 2003; 148:154–159.
4
5
6
Bocquier B, D’Incan M, Joubert J, et al. Amyloid elastosis: a new case studied extensively by electron microscopy and immunohisto-chemistry. Br J Dermatol 2008; 158:858–860. Santos-Briz A, Canueto J, Antunez P, Bravo J, Garcia-Sanz R, De Unamuno P. Primary cutaneous localized amyloid elastosis. Am J Dermatopathol 2010; 32:86–90. Marchand A, Levaltier X, Croue´ A, Arbeille B, Ifrah N, Martin L. Cutaneous amyloid elastosis revealing multiple myeloma with systemic amyloidosis. Acta Derm Venereol 2013; 93:204–205.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
JCM-D-14-00057
Images in cardiovascular medicine
Restrictive cardiomyopathy and pseudoxanthoma elasticum skin lesions Maria B. Musumecia, Lorenzo Semprinia, Matteo Casenghia, Dalma Montesantia, Vittoria Mastromarinoa, Fabio Socciarellic, Massimo Volpea,b and Camillo Autorea We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively. Furthermore, the electron microscopic examination did not show all the peculiar histopathological findings of amyloid elastosis, precluding a final diagnosis of this disease. J Cardiovasc Med 2014, 15:000–000
A 46-year-old man, with no cardiovascular risk factors or family history of cardiovascular disease, was admitted to our hospital for a massive right-sided pleural effusion. Cardiovascular physical examination revealed gallop rhythm, severe elevation of jugular venous pressure and mild peripheral edema. The ECG showed a low voltage on the limb leads and a pseudoinfarct pattern in the peripheral leads; transthoracic echocardiogram revealed a symmetrical concentric left ventricular hypertrophy with normal ejection fraction, restrictive filling pattern and left atrial enlargement (Fig. 1a and b). N-terminal-pro-brain natriuretic peptide was significantly increased (6627 ng/ml), whereas cardiac troponin I was normal (0.06 ng/ml). Cardiac magnetic resonance (MRI) demonstrated a diffuse subendocardial late enhancement (Fig. 1c). On the basis of these features, we suspected an amyloidotic cardiomyopathy. A serum and urine immunofixation revealed a monoclonal l spike (167 mg/dl), increased serum free light chain levels (155 mg/l) with a reduced k/l ratio (0.06) and a BenceJones proteinuria. A minor salivary gland biopsy confirmed histologically the diagnosis of amyloid light chain (AL) amyloidosis. During hospitalization, we noted the presence of yellowish papulous skin lesions measuring 1–3 mm in diameter in a reticular pattern on the trunk and the arm. The patient claimed that these lesions had been present from 6 to 7 months. A skin biopsy was performed, which showed degenerated and irregular elastic fibers in the dermis (Fig. 1d). These lesions were compatible with a diagnosis of pseudoxanthoma elasticum (PXE). A cyclophosphamide-bortezomib1558-2027 ß 2014 Italian Federation of Cardiology
Keywords: AL amyloidosis, amyloid elastosis, pseudoxanthoma elasticum, restrictive cardiomyopathy a Cardiology, Clinical and Molecular Medicine Department, ‘Sapienza’ University of Rome, Rome, bIRCCS Neuromed, Pozzilli (IS), Italy and cPathology Department, ‘Sapienza’ University of Rome, Rome, Italy
Correspondence to Maria Beatrice Musumeci, MD, Cardiology Department, Clinical and Molecular ‘Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Ospedale Sant’Andrea, Via di Grottarossa 1035-1039, 00189 Rome, Italy Tel: +39 06 33775563; fax: +39 06 33775038; e-mail: [email protected] Received 22 January 2014 Revised 5 May 2014 Accepted 6 May 2014
dexamethasone (CyBorD) chemotherapy regimen was started for the treatment of amyloidosis. Nevertheless, we observed a rapid deterioration of the hematological and cardiac picture and the patient died suddenly in the context of severe and refractory heart failure. We described an unusual case of a patient with AL amyloidosis and PXE-like lesions. A rare form of systemic amyloidosis accompanied by PXE-like skin lesions has been previously described in only six studies.1 – 6 The major criterion for the diagnosis of the so-called amyloid elastosis is the presence of amyloid around the elastic fibers in the derma. In a post-hoc analysis, we performed an electron microscopic examination on the skin specimen of our patient, which failed to clearly show amyloid deposition in the derma; the immunohistochemistry analysis for immunoglobulin lambda chain showed extracellular matrix positivity compatible with an elastic fiber localization of the monoclonal component (Fig. 2). These findings have not been fully explained, but previous cases reported that amyloid deposition could be restricted to some elastic fibers only, completely sparing others in an apparently random manner.5 A concentric left ventricular hypertrophy was described only in a recent study of amyloid elastosis.6 Possibly, the severity of cardiomyopathy in our patient negatively influenced prognosis earlier than the appearance of amyloid deposition in the derma. In conclusion, we report a rare case of AL amyloidosis with PXE-like skin lesions and a severe restrictive cardiomyopathy. DOI:10.2459/JCM.0000000000000158
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00057; Total nos of Pages: 3;
JCM-D-14-00057
2 Journal of Cardiovascular Medicine 2014, Vol 00 No 00
Fig. 1
(a) ECG shows a low voltage in the limb leads and a pseudoinfarct pattern in the precordial leads. (b) Echocardiogram shows severe concentric left ventricular hypertrophy with a maximum wall thickness of 20 mm and left atrial enlargement. (c) Cardiac MR shows circumferential diffuse subendocardial late gadolinium enhancement. (d) The hematoxylin–eosin stain (H&E) shows deposition of basophilic collapsed and fragmented fibers in the derma (magnification 200). MR, magnetic resonance.
Fig. 2
Immunohistochemistry for immunoglobulin lambda chain (400 magnification). There is an extracellular matrix positivity compatible with elastic fiber localization.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00057; Total nos of Pages: 3;
JCM-D-14-00057
Pseudoxanthoma elasticum skin lesions Musumeci et al. 3
References 1 2
3
Winkelmann RK, Peters MS, Venencie PY, Amyloid elastosis. A new cutaneous and systemic pattern of amyloidosis. Arch Dermatol 1985; 121:498–502. Sepp N, Pichler E, Breathnach SM, Fritsch P, Hintner H. Amyloid elastosis: analysis of the role of amyloid P component. J Am Acad Dermatol 1990; 22:27–34. Vecchietti G, Masouye´ I, Salomon D, et al. An unusual form of primary systemic amyloidosis: amyloid elastosis. Report of a case treated by haematopoietic cell transplantation. Br J Dermatol 2003; 148:154–159.
4
5
6
Bocquier B, D’Incan M, Joubert J, et al. Amyloid elastosis: a new case studied extensively by electron microscopy and immunohisto-chemistry. Br J Dermatol 2008; 158:858–860. Santos-Briz A, Canueto J, Antunez P, Bravo J, Garcia-Sanz R, De Unamuno P. Primary cutaneous localized amyloid elastosis. Am J Dermatopathol 2010; 32:86–90. Marchand A, Levaltier X, Croue´ A, Arbeille B, Ifrah N, Martin L. Cutaneous amyloid elastosis revealing multiple myeloma with systemic amyloidosis. Acta Derm Venereol 2013; 93:204–205.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
