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Facial Signs Leading to the Diagnosis of Cardiac Amyloidosis
CLINICAL COMMUNICATION TO THE EDITOR
Facial Signs Leading to the Diagnosis of Cardiac Amyloidosis To the Editor: Cardiac amyloidosis is still challenging to diagnose nowadays but is often associated with other organ involvement, which should alert physicians. We report a case of congestive heart failure related to cardiac amyloidosis, which was strongly evoked on periorbital ecchymoses and macroglossia. A 75-year-old man was hospitalized for recurrent episodes of cardiac insufficiency. He had taken clopidogrel for a long time. Physical examination revealed dyspnea, jugular venous turgescence, hepatojugular reflux, lower limbs swelling, and pulmonary crackles. The patient also had a long history of bilateral carpal tunnel syndrome. Concomitant spontaneous erythematosus to violaceous ecchymoses of both eyelids and macroglossia (Figure) were noted. Together, these physical symptoms indicated systemic amyloidosis. Accordingly, serum and urinary monoclonal free lambda light chain was observed, suggesting AL amyloidosis (primary amyloidosis). Seric immunoglobulin levels were within normal range. Other biological analysis revealed renal insufficiency (creatininemia to 180 mol/L), low albuminemia (28 g/L), low proteinemia (59 g/L), and proteinuria (3 g/day). Blood cell count showed only mild renal-related anemia. Coagulation tests were normal. Brain natriuretic peptide level was very high (3500 ng/L, N ⬍100). Electrocardiogram recording was unremarkable. Transthoracic Doppler echocardiography showed characteristic features of cardiac amyloidosis. Immunoglobulin light-chain amyloidosis (AL) was confirmed by salivary gland biopsy showing a strong positivity of Red Congo staining associated with positive staining of amyloid deposits with anti-lambda light chain antibodies. A good outcome was observed after an increase in furosemide dose. AL amyloidosis is the most frequent type of systemic amyloidosis and occurs mostly in patients older than 40 years of age.1 Cardiac involvement is observed in 1/3 to 1/2 of patients and is associated with the worst prognosis (6-8 months median survival according to historical series).1-3 Common cardiovascular features include congestive heart failure, arrhythmias, Funding: None. Conflict of Interest: All authors declare no conflict of interest with regard to this work. Authorship: All authors had access to the material published and a role in writing the article. Requests for reprints should be addressed to Brigitte Granel, MD, Service de médecine interne, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (AP-HM), Université de la Méditerranée, Marseille 13915, France. E-mail address: [email protected]
0002-9343/$ -see front matter © 2009 Published by Elsevier Inc.
Figure
Periorbital ecchymoses and macroglossia.
and hypotension.2 Echocardiographic abnormalities are observed mostly in the end stage of the disease.1 Consequently, cardiac amyloidosis is often underdiagnosed or associated with a delayed diagnosis. Echocardiography should be performed by an aware operator. Extracardiac manifestations are various and led here to the diagnosis of systemic amyloidosis.2 They included periorbital ecchymoses, macroglossia, and carpal tunnel syndrome. Periorbital ecchymoses, almost pathognomonic of the disease, are reported to appear in a minority of patients with amyloidosis.2 Bleeding diathesis is a common complication of systemic amyloidosis. It is supposed to be related to deposition of amyloid within blood vessel walls, leading to vascular fragility, and rarely to factor X deficiency, resulting from the binding of factor X to amyloid fibrils.4 In our case, a drug-induced thrombopathy could have worsened the ecchymoses. Macroglossia is defined by an enlargement of the tongue that protrudes at rest beyond the teeth or alveolar ridge. The diagnosis is usually based on this sign and comparison with an apparently normal tongue because objective measurements of size are unreliable. Macroglossia is the most common oral manifestation of amyloidosis and is present in about 27% of patients with primary AL amyloidosis.2 Some organ involvements in AL amyloidosis are indistinguishable from other systemic amyloidosis. Thus, it is crucial to determine the nature of the protein involved, as treatment and prognosis differ between them.5 Cardiac amyloidosis must be considered in the etiology of heart insufficiency in the elderly, especially when appearance of restrictive cardiomyopathy on echocardiography is observed. Associated extracardiac manifestations
e2
The American Journal of Medicine, Vol 122, No 9, September 2009
such as periorbital ecchymoses and macroglossia are useful diagnosis features of systemic amyloidosis. Karim Aissi, MD Pascal Rossi, MD, PhD Fanny Bernard, MD Brigitte Granel, MD Yves Frances, MD Service de Médecine Interne Hôpital Nord Assistance Publique-Hôpitaux de Marseille (AP-HM) Université de la Méditerranée Marseille, France
doi:10.1016/j.amjmed.2009.02.027
References 1. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112:2047-2060. 2. Dubrey SW, Cha K, Anderson J, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. Q J Med. 1998;91:141-157. 3. Gertz MA, Kyle RA. Primary systemic amyloidosis—a diagnostic primer. Mayo Clin Proc. 1989;64:1505-1519. 4. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood. 2001;97:1885-1887. 5. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346: 1786-1791.
Facial Signs Leading to the Diagnosis of Cardiac Amyloidosis To the Editor: Cardiac amyloidosis is still challenging to diagnose nowadays but is often associated with other organ involvement, which should alert physicians. We report a case of congestive heart failure related to cardiac amyloidosis, which was strongly evoked on periorbital ecchymoses and macroglossia. A 75-year-old man was hospitalized for recurrent episodes of cardiac insufficiency. He had taken clopidogrel for a long time. Physical examination revealed dyspnea, jugular venous turgescence, hepatojugular reflux, lower limbs swelling, and pulmonary crackles. The patient also had a long history of bilateral carpal tunnel syndrome. Concomitant spontaneous erythematosus to violaceous ecchymoses of both eyelids and macroglossia (Figure) were noted. Together, these physical symptoms indicated systemic amyloidosis. Accordingly, serum and urinary monoclonal free lambda light chain was observed, suggesting AL amyloidosis (primary amyloidosis). Seric immunoglobulin levels were within normal range. Other biological analysis revealed renal insufficiency (creatininemia to 180 mol/L), low albuminemia (28 g/L), low proteinemia (59 g/L), and proteinuria (3 g/day). Blood cell count showed only mild renal-related anemia. Coagulation tests were normal. Brain natriuretic peptide level was very high (3500 ng/L, N ⬍100). Electrocardiogram recording was unremarkable. Transthoracic Doppler echocardiography showed characteristic features of cardiac amyloidosis. Immunoglobulin light-chain amyloidosis (AL) was confirmed by salivary gland biopsy showing a strong positivity of Red Congo staining associated with positive staining of amyloid deposits with anti-lambda light chain antibodies. A good outcome was observed after an increase in furosemide dose. AL amyloidosis is the most frequent type of systemic amyloidosis and occurs mostly in patients older than 40 years of age.1 Cardiac involvement is observed in 1/3 to 1/2 of patients and is associated with the worst prognosis (6-8 months median survival according to historical series).1-3 Common cardiovascular features include congestive heart failure, arrhythmias, Funding: None. Conflict of Interest: All authors declare no conflict of interest with regard to this work. Authorship: All authors had access to the material published and a role in writing the article. Requests for reprints should be addressed to Brigitte Granel, MD, Service de médecine interne, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (AP-HM), Université de la Méditerranée, Marseille 13915, France. E-mail address: [email protected]
0002-9343/$ -see front matter © 2009 Published by Elsevier Inc.
Figure
Periorbital ecchymoses and macroglossia.
and hypotension.2 Echocardiographic abnormalities are observed mostly in the end stage of the disease.1 Consequently, cardiac amyloidosis is often underdiagnosed or associated with a delayed diagnosis. Echocardiography should be performed by an aware operator. Extracardiac manifestations are various and led here to the diagnosis of systemic amyloidosis.2 They included periorbital ecchymoses, macroglossia, and carpal tunnel syndrome. Periorbital ecchymoses, almost pathognomonic of the disease, are reported to appear in a minority of patients with amyloidosis.2 Bleeding diathesis is a common complication of systemic amyloidosis. It is supposed to be related to deposition of amyloid within blood vessel walls, leading to vascular fragility, and rarely to factor X deficiency, resulting from the binding of factor X to amyloid fibrils.4 In our case, a drug-induced thrombopathy could have worsened the ecchymoses. Macroglossia is defined by an enlargement of the tongue that protrudes at rest beyond the teeth or alveolar ridge. The diagnosis is usually based on this sign and comparison with an apparently normal tongue because objective measurements of size are unreliable. Macroglossia is the most common oral manifestation of amyloidosis and is present in about 27% of patients with primary AL amyloidosis.2 Some organ involvements in AL amyloidosis are indistinguishable from other systemic amyloidosis. Thus, it is crucial to determine the nature of the protein involved, as treatment and prognosis differ between them.5 Cardiac amyloidosis must be considered in the etiology of heart insufficiency in the elderly, especially when appearance of restrictive cardiomyopathy on echocardiography is observed. Associated extracardiac manifestations
e2
The American Journal of Medicine, Vol 122, No 9, September 2009
such as periorbital ecchymoses and macroglossia are useful diagnosis features of systemic amyloidosis. Karim Aissi, MD Pascal Rossi, MD, PhD Fanny Bernard, MD Brigitte Granel, MD Yves Frances, MD Service de Médecine Interne Hôpital Nord Assistance Publique-Hôpitaux de Marseille (AP-HM) Université de la Méditerranée Marseille, France
doi:10.1016/j.amjmed.2009.02.027
References 1. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112:2047-2060. 2. Dubrey SW, Cha K, Anderson J, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. Q J Med. 1998;91:141-157. 3. Gertz MA, Kyle RA. Primary systemic amyloidosis—a diagnostic primer. Mayo Clin Proc. 1989;64:1505-1519. 4. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood. 2001;97:1885-1887. 5. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346: 1786-1791.