Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review

Area of Science:

• Medical Research
• Rare Diseases
• Diagnostic Medicine

Background:

• Systemic amyloidosis, encompassing immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) amyloidosis, is often diagnosed late, leading to severe organ damage and poor prognosis.
• A significant percentage of patients with AL and ATTR amyloidosis die within months of diagnosis, highlighting the need for earlier detection.

Purpose of the Study:

• To establish evidence-based recommendations for earlier diagnosis and accurate staging of systemic amyloidosis.
• To guide clinicians in patient counseling regarding prognosis and treatment options for this rare group of diseases.

Main Methods:

• A comprehensive literature search was performed for studies published between January 1, 2000, and December 31, 2019.
• Key search terms included "amyloid," "amyloidosis," "nephrotic syndrome," "heart failure preserved ejection fraction," and "peripheral neuropathy."
• Exclusion criteria involved case reports, non-English articles, and case series with fewer than 10 patients; authors independently selected and appraised the literature.

Main Results:

• The review included 81 articles from 1769 initially identified studies, comprising 12 randomized clinical trials, 9 case series, and 3 cohort studies.
• Incidence and prevalence rates were detailed for AL amyloidosis (approx. 12 cases/million/year, 30,000-45,000 US/EU cases), variant ATTR amyloidosis (0.3 cases/million/year, 5.2 cases/million prevalence), and wild-type ATTR amyloidosis (155-191 cases/million prevalence).
• Amyloidosis should be considered in differential diagnoses for unexplained nephrotic syndrome, heart failure with preserved ejection fraction, hepatomegaly, peripheral neuropathy, and monoclonal gammopathy of undetermined significance; staging is possible via blood tests; specific therapies exist for AL and ATTR amyloidosis.

Conclusions:

• All forms of amyloidosis remain underdiagnosed, underscoring the need for increased clinical suspicion.
• Approved therapies are available for all amyloidosis types, demonstrating improvements in survival, disability, and quality of life.
• Consideration of amyloidosis in patients with multisystem disorders affecting the heart, kidney, liver, or nervous system is essential for timely diagnosis and management.