Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report

Abstract

Background Amyloidosis is a systemic disorder of abnormal protein folding and deposition resulting in a range of symptoms including neuropathy, heart failure, renal disease, and dermatologic findings. The two most common types of amyloidosis that affect the heart are transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis, which vary in clinical presentation. Skin findings such as periorbital purpura are considered more specific for AL amyloidosis. However, there are rare cases of ATTR amyloidosis causing the same dermatologic findings. Case Summary A 69-year-old female presented for evaluation of amyloidosis after cardiac imaging done at the time of a recent atrial fibrillation ablation showed signs of infiltrative disease. On examination, she had periorbital purpura which she reportedly had for years without receiving a diagnosis, as well as macroglossia with teeth indentation. These exam findings, in addition to her transthoracic echocardiogram showing apical sparing, are typically considered characteristic of light chain amyloidosis. Subsequent workup revealed the presence of hereditary transthyretin amyloidosis (hATTR) with a heterozygous pathogenic variant in the TTR gene producing the p.Thr80Ala mutation. Conclusion Spontaneous periorbital purpura is thought to be pathognomonic for light chain (AL) amyloidosis. However, we describe a case of hereditary transthyretin amyloidosis (ATTR) with the Thr80Ala TTR genetic variant presenting initially with periorbital purpura, the first case documented in the literature to our knowledge.

Coexistence of Light Chain and Transthyretin Cardiac Amyloidosis

“…Although AL and ATTR-CM can overlap regarding noncardiac manifestations of disease, macroglossia, submandibular gland enlargement, coagulopathy, and periorbital purpura more commonly associate with AL-CM, whereas bilateral carpal tunnel syndrome, spinal stenosis, hip/knee replacement, and peripheral neuropathy have been more commonly described with ATTR-CM. 1 , 5 , 6 Recognition of these unique features of AL and ATTR-CM may allow one to establish a higher pretest probability for 1 disease entity. For example, with patient 1, despite a diagnosis of MM, suspicion remained high for ATTR-CM because of the patient’s advanced age, severe aortic stenosis, bilateral carpal tunnel syndrome, and spinal stenosis.…”

Thromboembolic and Bleeding Events in Transthyretin Amyloidosis and Coagulation System Abnormalities: A Review

“…The most common dermatological findings are purpura and ecchymosis, caused by vascular fragility and wall damage possibly due to amyloid deposition and subsequent bleeding diathesis [38]. Some case reports appear to confirm these findings, such as the case of a 75-year-old man hospitalised for heart failure who presented with periorbital ecchymosis (raccoon eye) and shoulder swelling (pad sign) who was eventually diagnosed with ATTRwt-CA by cardiac biopsy [39]; and the case of a 69-year-old woman with periorbital purpura who, after echocardiography, was diagnosed with ATTRv-CA with the genetic variant Thr80Ala [40]. There have also been reports in the literature of gastrointestinal bleeding, obstruction, or perforation as a possible result of amyloid deposition in the gastrointestinal mucosa; a 79-year-old man with intra-abdominal haemorrhage underwent emergency partial resection of the transverse colon and the postoperative pathological examination of tissue samples led to the diagnosis of ATTR amyloidosis [41].…”