Periorbital Ecchymoses Are Not Pathognomonic of the Light-chain Type of Amyloidosis

Abstract

CASE REPORT A 52-year-old man presented with a progressive 16month course of severe sensorimotor polyneuropathy. He had no personal or familial medical past history. Clinical manifestations appeared in July 2003 and were characterized by decreased sensation and painful paraesthesia of the upper extremities, followed 4 months later by distal weakness. Then, decreased sensation, painful paraesthesia and distal weakness of the lower limbs progressively appeared. Alternating diarrhoea and constipation, Raynaud’s syndrome and erectile dysfunction were noted at the same time. The patient also complained of effort dyspnoea and orthopnoea. Electromyography demonstrated a severe axonal sensorimotor polyneuropathy involving all 4 limbs. Investigations revealed a normal blood count and serum glucose, creatinine, and urea, electrolytes and liver function test. There were no inflammatory biological markers. Classical causes of axonal polyneuropathy, such as alcoholism, vitamin deficiency, diabetes melli tus, dysthyroidea and auto-immune diseases, were ruled out. The suspected dysautonomia was confirmed by an abnormal heart-rate variability on electrophysiological tests. Echocardiography showed thickened ventricular walls with a granular sparkling appearance and impaired diastolic dysfunction. The patient developed periorbital and scleral ecchymoses after vomiting (Fig. 1). Since periorbital ecchymoses are classically considered as pathognomonic of AL amyloidosis, we performed a salivary gland biopsy and a sural nerve biopsy. Amyloid deposits were observed in both figures, but immunofluorescence with anti-light-chain (lambda or kappa) antibodies did not reveal any immunoreactivity. There was no evidence of monoclonal gammopathy in spite of an exhaustive work-up comprising blood and urinary immunoelectrophoresis, nephelometric assay of light chain in serum and an osteomedullar biopsy. Since the AL type of amyloidosis was not confirmed, a molecular analysis of the TTR gene was performed and revealed a heterozygous Ser77Tyr mutation, resulting in a diagnosis of familial TTR type amyloid polyneuropathy. Immunohistochemistry confirmed the transthyretin nature of the amyloid deposits (Fig. 2).