- A 60yo DM pt presented with easy fatigability, weakness and numbness of hands and swollen feet. Exam: pedal edema, sensory neuropathy and palpable liver and spleen. Urine: proteinuria. US abdomen: enlarged kidney. Renal biopsy: amorphous homogenous substance that stained red with congo-red. What is the dx?
a. DM retinopathy
b. Sarcoidosis
c. Wilms tumor
d. Amyloidosis
e. Glycogen storage disease
answer: D
Typically, in amyloidosis there is a combination of symptoms affecting more than a single system - eg, fatigue, weight loss, easy bruising, breathlessness, peripheral oedema, sensory change, carpal tunnel syndrome, and postural hypotension.
Investigations
Amyloidosis is suspected on the basis of symptoms and signs described above, but can be diagnosed only by biopsy.
Urinalysis - proteinuria/light chain on electrophoresis.
FBC - anaemia - often mild, thrombocytopenia.
Blood film - Howell-Jolly bodies (from splenic dysfunction).
U&Es - raised creatinine.
LFTs - raised alkaline phosphatase.
Clotting - there is abnormal clotting in 50% of cases - raised INR, factor X deficiency.
Inflammatory markers - raised ESR, normal CRP.
Bone marrow - colonial dominance of plasma cells (gamma greater than kappa).
ECG - characteristic low-voltage pattern with poor R-wave progression across the limb leads.
Echocardiography - ventricular thickening with reduced ventricle size.
Serum amyloid P (SAP) scintigraphy - this shows the distribution and amount of amyloid within the body's organs without the need for biopsies
Biopsy of an affected organ, or simple subcutaneous aspiration of abdominal fat - stains red with Congo red stain giving red-green birefringence under polarised light. Diagnosis is established in 80% of cases.
Immunofixation electrophoresis to establish the form of amyloidosis.
Signs
Unexplained renal disease may be observed, especially with nephrotic syndrome or restrictive cardiomyopathy (especially if both together):
Massive proteinuria with normal or only slightly enlarged kidneys.
Cardiac amyloidosis causes an infiltrative restrictive cardiomyopathy leading to progressive heart failure.
Marked hepatomegaly with kidney disease:
Hepatic amyloid disease produces hepatomegaly, but rarely jaundice.
Massive hepatomegaly has been reported.
LFT results usually are normal, but elevated alkaline phosphatase may be observed.
Occasionally, portal hypertension may occur with oesophageal varices and ascites.
Mainly right-sided, rapidly progressive heart failure can be seen:
This often occurs without chest pain.
There is a characteristic low-voltage pattern ECG.
In the elderly there may be an infiltrative cardiomyopathy.
Sensory glove- and stocking-type polyneuropathy:
Especially carpal tunnel syndrome, which may significantly predate the diagnosis.
20% of cases have a peripheral neuropathy.
Vitreous opacities or involvement of other major organs suggest hereditary amyloidosis.
Subtle signs of autonomic disturbance:
Postural hypotension or early satiety.
Gastrointestinal amyloid may cause:
Oesophageal motility abnormalities, gastric atony, motility abnormalities of the small and large intestine and pseudo-obstruction.
Malabsorption.
Bleeding.
Macroglossia, which is common in primary and myeloma-related amyloidoses.
Skin lesions:
Spontaneous periorbital purpura - racoon eye sign.
A firm, symmetrical, non-tender goitre resembling Hashimoto's thyroiditis may result from amyloidosis of the thyroid gland.