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1778 Part XI: Malignant Lymphoid Diseases Chapter 108: Immunoglobulin Light-Chain Amyloidosis 1779

TABLE 108–3. Suggested Testing of a Known Amyloid confirm cardiac involvement by amyloidosis, but also help differentiate
one type versus another.
Patient
If mass spectroscopy identifies light-chain amyloid: Liver
Consider localized amyloidosis (bladder, larynx, skin, bronchi) Liver infiltration from amyloid can be seen in up to one-quarter
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If systemic (visceral involvement) perform the following tests: of patients with AL amyloidosis. These patients will present with
• Alkaline phosphatase hepatomegaly, elevation of the serum alkaline phosphatase with normal
• Aspartate aminotransferase or near-normal transaminases and bilirubin. Half of the patients with
hepatic amyloidosis have renal amyloidosis, which dominates the clini-
• β -Microglobulin
2 cal syndrome. When a patient presents with hepatomegaly and imaging
• Bilirubin shows no filling defects, the presence of proteinuria, a monoclonal pro-
• Calcium tein, or the presence of Howell–Jolly bodies in a blood film indicative of
• Creatinine hyposplenism are highly suggestive of amyloidosis. Most patients have
• Glucose symptoms consistent with chronic liver disease, early satiety, anorexia,
• Complete blood count and unexplained weight loss. It is common to find spider telangiecta-
sias on the upper chest. Portal hypertension and ascites are uncommon,
• Immunoglobulin free light chains however. Rare instances of both hepatic and splenic rupture have been
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• Immunofixation and electrophoresis reported. The diagnosis can usually be established with fat aspiration
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• Serum and 24-hour urine and marrow biopsy, but a liver biopsy is safe and does not have a higher
• Quantitative immunoglobulins risk of bleeding complications than in other patients with liver disease.
• N-terminal probrain natriuretic peptide
• Troponin T Nervous System
• Factor X level Amyloid, by virtue of its deposition in the vasa nervorum, causes a
• Chest x-ray mixed axonal and demyelinating peripheral neuropathy. The neuropa-
thy is symmetric, tends to ascend beginning in the toes, and eventually
• Electrocardiogram involves the upper extremities. It causes paresthesias, often painful dys-
• Echocardiogram esthesias, and eventually causes motor loss. Approximately half of the
• Doppler and strain imaging patients have an associated carpal tunnel syndrome, and approximately
• Creatinine clearance one-quarter have associated autonomic features including orthos-
tatic hypotension, autonomic dysmotility of the gastrointestinal tract,
If mass spectroscopy identifies transthyretin (TTR) amyloid, including vomiting because of pseudoobstruction and alternating con-
perform these tests: stipation with diarrhea, often intractable, and bladder abnormalities,
• Echocardiogram including overflow incontinence and incomplete emptying. 59,60 The pro-
• Doppler and strain imaging gression of amyloid neuropathy is slow, and it is common to have delays
• Familial amyloidosis genetic testing (mass spectroscopy of of 2 to 3 years before a diagnosis is established. Electromyography is not
serum TTR; if abnormal, TTR gene sequencing) particularly useful in the early diagnosis because amyloid preferentially
affects the small unmyelinated fibers of the extremities, which are not
well assessed with standard electrodiagnostic studies. Patients with an
unexplained peripheral neuropathy who are not diabetic should have
immunofixation of serum and urine and a free light-chain assay per-
to therapeutic interventions. 49–51 All patients who present with amyloi-
dosis, whether or not cardiac disease is suspected, should have cardiac formed. A positive finding requires the consideration of amyloidosis in
biomarkers performed. Table 108–3 lists the suggested diagnostic tests the differential; although, for patients who have an immunoglobulin (Ig)
to perform when a patient with amyloidosis is seen. M monoclonal protein, the possibility that the IgM is directly responsi-
Contrast-enhanced cardiac MRI is increasingly being used in the ble for neuropathy in the absence of amyloid is significant. Sural nerve
assessment of cardiac amyloid. Cardiac MRI (Fig. 108–6) can measure biopsies can usually detect the amyloid deposits, but there are reports
the thickness of the myocardium accurately and, after gadolinium injec- in the literature of sural nerve biopsies having missed proven amyloido-
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tion, can demonstrate delayed subendocardial enhancement that can sis. Mass spectroscopic analysis of the amyloid deposits is particularly
be quite specific for cardiac amyloidosis. 52,53 Phase-contrast MRI pro- important because of the high prevalence of neuropathy in patients with
vides information on flow dynamics, diastolic filling parameters, and non-AL amyloidosis.
mitral peak in-flow velocity. By providing a functional assessment, this
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technique can help establish an early diagnosis and has the potential THERAPY
to assess response to therapy. MRI cannot be used in the presence of
a pacemaker or defibrillator or if there is renal insufficiency, because Treatment of amyloidosis has improved significantly with the intro-
gadolinium is contraindicated. Radionuclide scanning is being explored duction of novel agents and refinements in autologous stem cell trans-
for amyloidosis. Technetium pyrophosphate is a sensitive marker for the plantation. For years, the regimen of melphalan and prednisone was the
presence of ATTR amyloidosis, both wild-type and mutant, whereas standard of therapy, but the response rate never exceeded 25 percent,
uptake is not seen in AL amyloidosis. A recent small study assessing and the impact on survival was unimpressive. Melphalan and predni-
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11
11 C-labeled Pittsburgh Compound-B ( C-PiB)–based positron emis- sone therapy has now been supplanted by the use of melphalan and
sion tomography (PET) imaging identified cardiac amyloid deposits in dexamethasone, which has a very low therapy-related mortality and
all patients with light chain amyloidosis and ATTR and was negative in can be administered to patients with cardiac and renal failure as well
controls. Therefore, nuclear imaging in the future may not only help as frail patients. The 5-year actuarial survival in patients treated with
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