Diagnosis and treatment of gastrointestinal dysfunction in hereditary TTR amyloidosis

Abstract

Purpose To review the management of gastrointestinal symptoms in patients with hereditary transthyretin amyloidosis, discussing diagnostic evaluations, assessment of disease progression and therapeutic strategies that could be implemented in routine practice. Methods Literature review. Key search terms included "gastrointestinal symptoms", "autonomic neuropathy", "hereditary transthyretin amyloidosis" and "familial amyloid polyneuropathy". Results Gastrointestinal disturbances are a common and serious manifestation of hereditary transthyretin amyloidosis, with significant effects on patients' quality of life and demonstrating a strong association with mortality. Gastrointestinal involvement is more often subclinical in the early stages of the disease, although in some patients gastric and/or bowel abnormalities may be the inaugural symptoms. In both cases, under-recognition, delayed investigation and suboptimal treatment frequently occur. A clear understanding of the mechanisms underlying gastrointestinal dysfunction in hereditary transthyretin amyloidosis is still lacking, but similar to diabetic enteropathy, multiple pathophysiological alterations seem to play a role. Conclusions Early detection and treatment of gastrointestinal disturbances is key to the successful treatment of this devastating disease. Gastroenterologists play a valuable role in both the diagnosis and the timely management of gastrointestinal symptoms in hereditary transthyretin amyloidosis and should, therefore, be part of a multidisciplinary and comprehensive approach to this disorder.

Gastrointestinal amyloidosis: A focused review

“…In patients with symptoms of dysmotility (stasis syndrome), dietary modifications, adequate hydration, and the use of pro-kinetic and anti-emetic agents is advised. Dietary modification consists of frequent, small-volume liquid or homogenized foods with low soluble fibre and fat content along with additional nutritional supplementation when necessary[ 48 ]. Prokinetic agents such as metoclopramide, erythromycin or domperidone (if indicated) are the mainstay of therapy for dysmotility[ 48 ].…”

“…Dietary modification consists of frequent, small-volume liquid or homogenized foods with low soluble fibre and fat content along with additional nutritional supplementation when necessary[ 48 ]. Prokinetic agents such as metoclopramide, erythromycin or domperidone (if indicated) are the mainstay of therapy for dysmotility[ 48 ]. Parenteral nutrition is indicated in severe cases of chronic GI dysmotility.…”

Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

“…Early recognition of GI dysfunction is important to enable prompt treatment to relieve symptoms, preserve quality of life, and prevent malnutrition [16]. Diagnostic tools for GI abnormalities are still limited, so currently self-reported symptoms are widely accepted measures for monitoring GI involvement in hereditary ATTRv amyloidosis [7,8,16].…”

“…Gastrointestinal manifestations are commonly reported in patients with hereditary ATTRv amyloidosis [7,8] representing a frequent cause for a poor quality of life [9]. Gastrointestinal symptoms can anticipate the onset of the polyneuropathy, and the most commonly reported initial symptoms are often diarrhea, unintentional weight loss, constipation or nausea [7].…”

JCS 2020 Guideline on Diagnosis and Treatment of Cardiac Amyloidosis

“…78 Examples of digestive symptoms that may occur include gastrointestinal symptoms such as severe alternating diarrhea and constipation and nausea due to dysautonomia. 79 Although severity differs from case to case, the patient's daily lifestyle may be impaired drastically if symptoms are severe. In particular, persistent watery diarrhea might occur during the endstage of juvenile-onset ATTRv amyloidosis in areas of high disease concentration, leading to malabsorption and protein leakage.…”