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Unusual clinical manifestations of primary systemic AL amyloidosis: are myasthenic symptoms and dilated cardiomyopathy caused by muscular or myocardial amyloid angiopathy?

AL amyloidosis is the most common form of systemic amyloidoses and is caused by deposition of amyloid fibrils, the precursor of which is the N-terminal portion of immunoglobulin light chain. This abnormal protein (M-protein) is produced by plasma cells with a monoclonal proliferative process and thus, AL systemic amyloidosis can be classified into two forms:primary with plasma cell dyscrasia and myeloma-associated amyloidosis (1). Marked amyloid deposition on the myocardium which is referred to as “cardiac amyloidosis” or “amyloid heart disease” frequently occurs in this disease, showing intractable heart failure with or without serious types of conduction block. This cardiac disorder is usually characterized by marked symmetrical thickening of ventricular walls and the ventricular septum with hyperrefractile myocardial echoes, normal or decreased left ventricular internal dimentions and reduced left ventricular diastolic function on echocardiogram. This cardiac involvement is, therefore, hemodynamically defined as restrictive cardiomyopathy (2). On the other hand, skeletal muscular manifestations due to amyloid deposition are rare in systemic amyloidosis and they develop mainly in the patients with AL systemic amyloidosis:histopathologically, vascular or perimysial/endomysial amyloid deposition is extensively seen but this amyloid myopathy produces a few different phenotypes (3). Muscular pseudohypertrophy or palpable nodules within the muscle is the predominant clinical picture usually accompanied with macroglossia (4), and a less frequent manifestion is progressive proximal limb weakness. However, if the latter develops as a sole presentation, it might be very difficult to make a correct diagnosis of amyloid myopathy (3). In this issue Yoshita et al reported an AL systemic amyloidosis case with unusual clinical manifestations of myasthenic symptoms and dilated cardiomyopathy, and these symptoms were considered to be caused by severe amyloid deposits on small vessels, that is, “AL amyloid angiopathy” (5). Amyloid deposition on small vascular walls is a consistent histopathological finding in systemic amyloidoses including AL, reactive AA and familial ATTR types (1), but the relationship between the clinical manifestations and this vascular involvement by amyloid has not been clarified in detail. In the reported case exercise induced easy fatigability of both the upper and lower limbs and this symptom improved by the use of prostaglandin E1 (PGE1) derivatives with an action of strong vasodilator. Disturbed microcirculation was demonstrated by toe pulse waves and direct angiography in the lower limbs. Dilated cardiomyopathy without thickness of ventricular walls seen in the reported patient is an infrequent finding in cardiac amyloidosis (2) and myocardial ischemia due to heavy occlusive amyloid deposits on the intramural small vessels seems to play an important role in the pathogenesis of this amyloid heart disease. Smith and Hutchins first described the presence of ischemic heart disease secondary to amyloidosis of intramyocardial arteries on the basis of pathological findings of a large series of cardiac amyloidosis (6) and this pattern of myocardial amyloid disease may contribute to the appearance of some cardiac symptoms in the patients with clinically apparent amyloid heart diseas.