Diagnosis of primary (AL) amyloidosis

INTRODUCTION

Primary (AL) amyloidosis can present with a variety of systemic symptoms or signs, including heavy proteinuria (usually in the nephrotic range), edema, hepatosplenomegaly, otherwise unexplained congestive heart failure, and the carpal tunnel syndrome [1-4]. Although virtually all patients have multisystem amyloid deposition, it is not uncommon to present with evidence of only one organ being affected. As an example, the absence of apparent extrarenal disease does not exclude AL amyloidosis as the cause of the nephrotic syndrome [5]. This is particularly true in nephrotic patients over the age of 50, up to 20 percent of whom may have primary amyloidosis [6-8]. (See "Renal amyloidosis" and "Gastrointestinal amyloidosis" and "Amyloid cardiomyopathy".)

The diagnosis and differential diagnosis of primary (AL) amyloidosis, including light chain deposition disease, will be discussed here. An overview of the amyloid disorders as well as the pathogenesis, clinical features, prognosis, and treatment of primary amyloidosis are presented separately. (See "An overview of amyloidosis" and "Pathogenesis and clinical features of AL (primary) amyloidosis and light and heavy chain deposition diseases" and "Prognosis and treatment of primary (AL) amyloidosis and light and heavy chain deposition diseases".)

RELATION TO OTHER PLASMA CELL DISORDERS

AL amyloidosis, and the related light chain deposition disease (LCDD) in which fibril formation does not occur, are due to the tissue deposition of fragments of monoclonal light chains [1,2]. The major diseases that may be linked to AL amyloidosis are multiple myeloma and Waldenstrom's macroglobulinemia (lymphoplasmacytic lymphoma), malignant disorders of plasma cells or lymphoplasmacytic cells, respectively. (See "Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenstrom macroglobulinemia", section on 'Amyloidosis'.)

Multiple myeloma — Multiple myeloma and amyloidosis can occur together, with the myeloma typically being diagnosed before or at the time of or soon after the diagnosis of amyloidosis. In a series of 1596 patients with primary amyloidosis seen at the Mayo Clinic between 1960 and 1994, only six (0.4 percent) showed delayed progression (at 10 to 81 months) to overt myeloma [9]. This usually occurred in patients without cardiac or hepatic amyloid who lived long enough to develop myeloma.

The findings of hypercalcemia, bone pain, or lytic bone lesions in a patient with a 3+ or 4+ urine dipstick for protein is suggestive of the combination of myeloma and amyloidosis (although malignancy-induced membranous nephropathy can produce a similar picture) [10]. The dipstick primarily detects albumin and will therefore be negative or trace positive when the patient has Bence Jones proteinuria alone. (See "Types of renal disease in multiple myeloma".)