Pitfalls in the Diagnosis of Primary Amyloidosis

In This Article

Abstract and Introduction

Abstract

Primary (AL) amyloidosis is the most prevalent type of systemic amyloidosis, and management of this disease has evolved through the years from supportive care to aggressive treatments that include immunomodulatory agents and high-dose chemotherapy with hematopoietic stem cell transplantation. However, other types of amyloidosis are increasingly recognized, such as familial amyloidosis and senile cardiac amyloidosis, and management of these conditions is different from that of AL amyloidosis. Congo red staining with exhibition of an apple-green birefringence is diagnostic of amyloid. Immunohistochemistry can detect amyloid deposits but has limitations, and newer molecular techniques such as mass spectrometry show promise in determining types of amyloidosis. Physicians need to be aware of clinical scenarios that can mimic AL amyloidosis to avoid misdiagnosis and harm to the patient.

Introduction

Amyloidosis constitutes the deposition of extracellular fibrils in a configuration of β-pleated sheets in various tissues. The structure of the β-pleated sheet allows binding of Congo red stain, which emits a characteristic apple-green birefringence under polarized light.^[1] There are distinct types of amyloidosis, which are classified according to the protein composition of the amyloid deposits.^[2] Immunoglobulin light chain (AL) amyloidosis (also known as primary amyloidosis) is the most common form of systemic amyloidosis and is associated with an underlying monoclonal plasma cell disorder that produces immunoglobulin light chains as constituents of the deposits.^[1] In secondary (AA) amyloidosis, the amyloidogenic precursor is a normal acute-phase reactant called serum amyloid A (SAA), which is produced as the result of chronic infection or inflammation.^[1] Hereditary amyloidosis consists of amyloid fibrils that are usually derived from genetic variants of mutant proteins, with the most common type being transthyretin (TTR). In elderly patients, the wild-type TTR might cause senile cardiac amyloidosis.^[3]

As described above, there are different forms of amyloidosis, each associated with different disease outcomes and treatment options. This review uses a case-based approach to highlight the importance of an accurate diagnosis of the type of amyloidosis to provide identifies the common pitfalls that a physician might encounter when evaluating a patient for amyloidosis (Table 1).

Cite this: Pitfalls in the Diagnosis of Primary Amyloidosis - Medscape - Jun 01, 2010.

Table 1. Diagnostic Pathway of Primary Amyloidosis
1. Consider primary amyloidosis in: Nondiabetic nephrotic syndrome Nonischemic cardiomyopathy with an echocardiogram showing "hypertrophy" Hepatomegaly or alkaline phosphatase elevation without imaging abnormality Peripheral neuropathy with MGUS or CIDP with autonomic features Atypical myeloma with monoclonal light chains and modest marrow Plasmacytosis
2. Screen patients with suspicious symptoms with serum and urine immunofixation and serum FLC assay. If assay is negative: It is not amyloidosis It is localized amyloidosis and not systemic If it is systemic, it could be senile or familial
3. Perform a biopsy in patients with a monoclonal protein; fat and bone marrow should be sampled first. Consider mass spectrometry on biopsy specimens.
4. Assess prognosis with echocardiography, including Doppler and strain, serum troponin, and NT-proBNP.
5. Refer for antiplasma cell therapy.

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