A 72-year-old man goes to his general practitioner (GP) complaining of painless swelling of both legs which he first noted approximately 2 months ago. The swelling started at the ankles but now his legs, thighs and genitals are swollen. His face is puffy in the mornings on getting up. His weight is up by about 10kg over the previous 3 months. He has noticed that his urine appears to be frothy in the toilet. He has noted gradual increasing shortness of breath, but denies any chest pain. He has also developed spontaneous bruising over the past 6 months. He is a retired heavy goods vehicle driver. He had hypertension diagnosed 13 years ago, and a myocardial infarction 4 years previously. He lives with his wife and has no children. He continues to smoke 30 cigarettes a day, and drinks about 30 units of alcohol a week. His medication consists of atenolol 50mg once a day.
Examination On examination there is pitting oedema of the legs which is present to the level of the sacrum. There is also massive oedema of the penis and scrotum. There is bruising on the forearms and around the eyes. There are no signs of chronic liver disease. His pulse rate is 72/min and regular. Blood pressure is 166/78mmHg. His jugular venous pressure is raised at 5cm. His apex beat is not displaced, and auscultation reveals normal heart sounds and no murmurs. There is dullness to percussion and reduced air entry at both lung bases. The liver, spleen and kidneys are not palpable, but ascites is demonstrated by shifting dullness and fluid thrill. Neurological examination is unremarkable.
Normal Haemoglobin 10.7g/dL 13.3–17.7g/dL Mean corpuscular volume (MCV) 95fL 80–99fL White cell count 4.7 109/L 3.9–10.6 109/L Platelets 176 109/L 150–440 109/L Sodium 138mmol/L 135–145mmol/L Potassium 4.9mmol/L 3.5–5.0mmol/L Urea 7.4mmol/L 2.5–6.7mmol Creatinine 112amol/L 70–120amol/L Glucose 4.7mmol/L 4.0–6.0mmol/L Albumin 16g/L 35–50g/L Cholesterol 15.2mmol/L 3.9–6.0mmol/L Triglycerides 2.7mmol/L 0.55–1.90mmol/L Clotting screen: normal Urinalysis: protein; no blood INVESTIGATIONS
Questions • What is the cause of this patient’s oedema? • What is the likely underlying diagnosis? • How would you further examine, investigate and manage this patient?
Peripheral oedema may occur due to local obstruction of lymphatic or venous outflow, or because of cardiac, renal, pulmonary or liver disease. Unilateral oedema is most likely to be due to a local problem, whereas bilateral leg oedema is usually due to one of the medical conditions listed above. Pitting oedema needs to be distinguished from lymphoedema which is characteristically non-pitting. This is tested by firm pressure with the thumb for approximately 10s. If the oedema is pitting, an indentation will be present after pressure is removed. This man has a subacute onset of massive pitting oedema. The major differential diagnoses are cardiac failure, renal failure, nephrotic syndrome, right heart failure (cor pulmonale) secondary to chronic obstructive airways disease or decompensated chronic liver disease. The frothy urine is a clue to the diagnosis of nephrotic syndrome and is commonly noted by patients with heavy proteinuria. On examination there were no clinical signs to suggest chronic liver disease. The jugular venous pressure would be expected to be more raised, and there should have been signs of tricuspid regurgitation (prominent ‘v’ wave, pansystolic murmur loudest on inspiration) and cardiomegaly if the patient had cor pulmonale or biventricular cardiac failure. The patient has signs of bilateral pleural effusions which may occur in nephrotic syndrome, if there is sufficient fluid retention. The bruising and peri-orbital purpura is classically seen in patients with nephrotic syndrome secondary to amyloidosis. The investigations are consistent with the diagnosis of nephrotic syndrome. Nephrotic syndrome is defined by the triad of hypoalbuminaemia (30g/L), proteinuria (3g/24h), and hypercholesterolaemia. The normochromic, normocytic anaemia is typical of chronic disease and is a clue to the underlying diagnosis of amyloidosis. Patients with amyloidosis may have raised serum transaminase levels due to liver infiltration by amyloid. The patient should have a renal biopsy to delineate the cause of the nephrotic syndrome. The principal causes of nephrotic syndrome are listed below. Adults presenting with nephrotic syndrome should have a renal biopsy. The exception is the patient with long-standing diabetes mellitus, with concomitant retinopathy and neuropathy, who almost certainly has diabetic nephropathy.
• Diabetes mellitus • Minimal change disease • Focal and segmental glomerulosclerosis • Membranous nephropathy • Systemic lupus erythematosus • HIV infection • Amyloidosis/myeloma Causes of nephrotic syndrome!
In this case renal biopsy confirmed the diagnosis of amyloidosis, and staining was positive for lambda light chains. Immunofixation confirmed the presence of a IgG paraprotein in the blood. A bone marrow aspirate showed the presence of an excessive number of plasma cells, consistent with an underlying plasma cell dyscrasia. Patients with amyloidosis should have an echocardiogram to screen for cardiac infiltration, and if the facilities are available a serum amyloid P scan should be arranged which assesses the distribution and total body burden of amyloid.
The initial treatment of this patient involves fluid and salt restriction, and diuretics to reduce the oedema. He should be anticoagulated to reduce the risk of deep vein thrombosis or pulmonary embolus. His hyperlipidaemia should be treated with a statin. Definitive treatment is by chemotherapy supervised by the haematologists to suppress the amyloidogenic plasma cell clone. In younger patients, bone marrow transplantation may be considered. Patients with nephrotic syndrome secondary to amyloidosis usually progress to end-stage renal failure relatively quickly. Death is most commonly due to cardiac involvement.