Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner

Abstract

Background Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. Methods These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. Results The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. Conclusions A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.

Cardiac amyloidosis‐A review of current literature for the practicing physician

“…Furthermore, Carpal Tunnel Syndrome, tendon rupture, and lumbar spinal stenosis are all associated with hATTR 13 . Occasionally, patients have ophthalmological involvement in the form of vitreous deposition 14 . Unlike in AL amyloidosis, macroglossia does not occur in hATTR, and renal involvement is less common 11…”

“…(Figure 2). A finding of increased ventricular wall mass in the setting of a low voltage ECG should raise suspicion of cardiac amyloidosis, as the thickening is due to amyloid infiltration and not true cardiomyocyte hypertrophy 14 . Despite wtATTR causing statistically significant greater ventricular wall thickening on a population level, this cannot be used to differentiate it from hATTR or AL on an individual level 19 …”

Unusual Pain Disorders – What Can Be Learned from Them?

“…88 The most common porphyria, porphyria cutanea tarda (PCT), has a prevalence of 1:10,000 according to European studies. 51 It is of utmost importance to consider porphyrias when related symptoms and findings appear-not least due to the fact that the wrong medication can lead to a dramatic exacerbation of the disease. Clinical features are dependent on the type of porphyria.…”

“…50 In order to facilitate early diagnosis of the disease, red flags were defined by Conceicao et al ( Figure 2) 49 and more recently Gertz et al recommended an algorithm for general practitioners. 51 In contrast to the hereditary form, the wild type ATTR amyloidosis presents predominantly with cardiomyopathy, although data from the THAOS (Transthyretin-Associated Amyloidosis Outcome Survey) registry show that about 20% of the patients complain about accompanying or solely polyneuropathic symptoms. 52 Affected patients are most frequently males of older age.…”

Echocardiographic diagnosis of cardiac amyloidosis: Does the masquerader require only a "cherry on top"?

“…The authors of this editorial would like to propose that larger multicenter studies are probably necessary to form a universal consensus, based on all the available published data, including the Umea and Kumamoto criteria. This would make clinical assessment and management of cardiac amyloidosis simpler and cost‐effective and avoid misdiagnosis of this life‐threatening disease 14 …”