Atypical Presentation of Systemic Amyloid Light Chain (AL) Amyloidosis

Abstract

Light chain (AL) amyloidosis is caused by a plasma cell clone that produces a dysfunctional, monoclonal light chain. This light chain misfolds and aggregates, resulting in catastrophic organ damage and eventual death. Due to the multiple organs affected by the disease, symptoms can be vague, such as lethargy, fatigue, weight loss, and peripheral edema. This case presentation follows a 66-year-old female patient who presented to our emergency department complaining of progressive shortness of breath (SOB). The patient denied any other associated symptoms and denied any past significant medical history. The lack of other associated symptoms or past diagnoses was a part of this atypical presentation, as the patient frequently complained of a multitude of symptoms affecting more than one organ system, as the pathogenesis of the disease is systemic in nature. Additionally, individuals with undiagnosed amyloidosis have often been diagnosed with other disease processes based on their symptomatology, due to their sometimes nonspecific nature. Upon further evaluation, bilateral pleural effusions were noted on imaging, which was treated with a pigtail pleural catheter. Atrial fibrillation was noted on ECG and was treated with both rate- and rhythm-controlled amiodarone. AL amyloidosis was suspected on transthoracic cardiac ultrasound, which was described as a "grainy" appearance of the myocardium, along with heart failure and left ventricular hypertrophy, supported by serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) results. This was confirmed by abdominal fat pad and bone marrow biopsies. While the use of cardiac ultrasound in the preliminary workup of amyloidosis is supported by evidence-based practice, there is a need for confirmatory diagnostic testing. This led to the decision to utilize fat pad biopsy as the primary definitive diagnostic tool, as it was readily available within the hospital system and was technically easier than many of the alternatives. However, this is neither supported nor refuted as the gold standard by the available literature. The patient was transferred to a higher level of care at a center specifically focused on the treatment of amyloidosis to receive the current gold standard of treatment, which was unavailable at our facility due to a lack of these specialized medications, as well as a provider comfortable with the use of these treatments.

Keywords: amyloidosis al; cardiac amyloidosis; cardiac amyloidosis with reduced ejection fraction; daratumumab; delayed diagnosis cardiac amyloidosis; light chain amyloidosis.

Figure 1. Electrocardiogram at presentation within the ED (A) and then upon admission to the progressive care unit (PCU; B)

The findings of low voltage QRS along with non-specific T and R wave abnormalities are both classic, though non-specific findings for amyloidosis. The progression to A-fib with rapid ventricular response (RVR) along with worsening symptomatology further supports cardiac involvement in this patient, even in the absence of confirmatory cardiac muscle biopsy.

Figure 2. Chest X-ray at time of presentation demonstrating a large left and a smaller right pleural effusion, as denoted by the arrows

While this finding did not necessarily raise clinical suspicion for amyloidosis, it did provide a rationale for the presenting shortness of breath and also led to the further workup that eventually led to the confirmatory diagnosis.

Figure 3. Transthoracic echocardiogram demonstrating a grainy appearance to the myocardium, as denoted by the white arrow

This interpretation by the cardiologist first raised the clinical suspicion for amyloidosis. This finding, along with the increased left atrial enlargement (demarcated by the dotted line) and the corresponding left ventricular hypertrophy (also denoted by the arrow), showed a pattern typically seen in amyloidosis.

Figure 4. Congo Red staining of the patient's abdominal fat pad biopsy

The presence of the areas of apple green birefringence under polarized light (denoted by the arrows) is significant, as the Congo Red staining reagent preferentially binds to misfolded protein chains, characteristically seen in amyloidosis. Therefore, this finding helped confirm the diagnosis, which was previously only suspected based on serum markers and imaging.