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Journal Presentation
case records of the massachusetts general hospital

An 80-Year-Old Man with Shortness of Breath, Edema, and Proteinuria

Fathia Rachmatina

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Present History
An 80-year-old man was admitted to the hospital because of shortness of breath, pleuraleffusions, and edema of the legs.

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Past History
Atrial fibrillation had developed seven years earlier, with bradycardia and syncope, a pacemaker had been placed. Angina developed two and a half years before admission and was treated with threevessel coronary-artery bypass grafting.

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 urinalysis revealed 3+ proteinuria, an increase from 1+ one year earlier. Nine months before admission, a subtotal colectomy was performed because of ischemic colitis with bleeding.

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 Bilateral pleural effusions, pulmonary edema, and cardiomegaly were noted on chest radiography. Five months before admission, an increase in exertional fatigue and shortness of breath developed. A chest radiograph showed small pleural effusions, diffuse irregular opacities, cardiomegaly, and pulmonary venous hypertension. . Page 6

 The patient received treatment with furosemide, and there was improvement in his symptoms and radiographic findings

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 A fine-needle aspiration biopsy of an abdominal fat pad was performed; a Congo red stain for amyloid was negative.

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Habitual History
He did not drink alcohol,smoke cigarettes,. He had not traveled recently, was retired, and lived with his wife

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Family and Medication History

Both parents and several uncles had had coronary artery disease. His medications were warfarin sodium and furosemide

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Physical Examination
He appeared fatigued, with increased respiratory effort. The temperature was 36.1C, the pulse was irregular at 77 beats per minute, the respiratory rate was 22 breaths per minute. The blood pressure was 80/40 mm Hg. The oxygen saturation was 93 percent while the patient was breathing two liters of oxygen with the use of a nasal cannula
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 The tongue was enlarged and had a whitish shallow ulceration on the right side. The neck was supple with a jugular venous pressure of 7 cm of water. Therewere decreased breath sounds two thirds of the way up the posterior chest on the right side and halfway up on the left side, with dullness to percussion
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 There were irregular first and second heart sounds. The abdomen was normal, and there was pitting edema (+++) of the legs from the feet to the knees

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Laboratory Findings
Table 1. Laboratory Data.* Variable On Admission Glucose (mg/dl) Sodium (mmol/liter) Potassium (mmol/liter) Chloride (mmol/liter) Carbon dioxide (mmol/liter) Urea nitrogen (mg/dl) Creatinine (mg/dl) Calcium (mg/dl) Phosphorus (mg/dl) Magnesium (meq/liter) Protein (g/dl) Albumin Globulin Bilirubin (mg/dl) Direct Total 119 130 3.8 93 32 29 0.9 8.4 3.5 1.8 6.8 3.0 4.3

0.2 0.5

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Creatine kinase isoenzymes (g/liter) 6.7 Troponin I (g/liter) 0.05 Alkaline phosphatase (U/liter) 455 Aspartate aminotransferase (U/liter) 63 Alanine aminotransferase (U/liter) 47 Uric acid (mg/dl) 6.9 Total urinary protein (mg/24 hr) 5180 Urinary creatinine (mg/24 hr) 1050 24-hr urine volume (ml) 1000

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Chest X-Ray

Figure 1. Chest Radiograph. Two weeks before admission, a posterioranterior chest radiograph revealed a large right-sided pleural effusion extending to the level of the right hilum, a small left-sided pleural effusion, pulmonary venous hypertension, and persistent diffuse irregular parenchymal opacities. Page 16

Transthoracic Echocardiogram.

RV

RV

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Figure 2. Transthoracic Echocardiogram. A four-chamber view shows mild symmetric left ventricular hypertrophy, left atrial enlargement, thickening of the mitral and tricuspid valves, and a small pericardial effusion (Panel A) (RV right ventricle, LV left ventricle, LA left atrium, RA right atrium). A four-chamber view shows moderate mitral regurgitation (MR) (Panel B). Pulsedwave Doppler evaluation of the mitral inflow gives information about the diastolic filling properties of the left ventricle and is expressed by two waves (Panel C).The E wave corresponds to rapid early diastolic filling of the left ventricle, whereas the A wave corresponds to atrial contraction. (The A wave is not present in this patient because of the presence of atrial fibrillation.) When left ventricular diastolic pressure is elevated, the equalization of pressures between the ventricular and atrial chambers is rapid, and the deceleration time (dec time) of early transmitral filling is shortened. A deceleration time of less than 150 msec indicates a restrictive filling pattern. In this patient, the deceleration time was 120 msec

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Diagnosis

Amyloidosis, AL type

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Anatomical Diagnosis
Systemic amyloidosis involving the heart and colon,in the setting of a monoclonal gammopathy; probably AL amyloidosis

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Organ Dysfunction in Systemic Amyloidosis

The kidney is the most frequent site of amyloid fibril deposition in both immunoglobulin light chain (AL) amyloidosis and serum amyloid A (AA) amyloidosis,and this condition is typically manifested as the nephrotic syndrome, as we see in this patient.
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 The proteinuria can be massive, and the accompanying edema can be resistant to diuretics, as in this case. The glomerular filtration rate may be normal, but progressive renal impairment typically follows unless new amyloid production can be reduced or eliminated

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Table 3. Clinical or Laboratory Findings in This Patient That Might Be Due to Amyloidosis. Kidney Nephrotic syndrome Heart Restrictive cardiomyopathy Valve thickening Conduction-system abnormalities Gastrointestinal tract Colonic bleeding or ischemia Liver Elevation of alkaline phosphatase and aminotransferase levels Lung Refractory pleural effusions Parenchymal opacifications Autonomic nervous system Hypotension

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Pathological Discussion
The presence of amyloid in tissue is not always readily apparent, and pathologists frequently do not recognize it on examination of sections routinely stained with hematoxylin and eosin. Examination of slides from the resected colon revealed the presence of amyloid in the walls of blood vessels in the submucosa and serosa
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Figure 3. Right Ventricular Endomyocardial-Biopsy Specimen. There is amorphous extracellular material present in a vascular distribution (Panel A, hematoxylin and eosin). With Congo red staining (Panel B), the deposits have a pinkorange color; under plane-polarized light (Panel C), the deposits display apple-green birefringence, which is indicative of the presence of amyloid.Page 26

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