Clinical features of systemic amyloidosis: a scoping review

Area of Science:

• Hematology
• Rare Diseases
• Clinical Diagnostics

Background:

• Systemic amyloidosis is a rare, multisystem disorder with vague symptoms, often leading to delayed diagnosis and irreversible organ damage.
• Current diagnostic challenges stem from overlapping symptoms with other conditions, contributing to significant morbidity and mortality.
• A knowledge gap exists in recognizing the early clinical presentations of common amyloidosis subtypes.

Purpose of the Study:

• To identify clinical "red flags" for light chain (AL) amyloidosis and transthyretin amyloidosis (ATTRwt, ATTRv) to facilitate earlier diagnosis.
• To address the critical knowledge gap in recognizing the clinical presentation of common systemic amyloidosis subtypes.
• To enhance cross-specialty awareness and support earlier diagnosis and intervention for AL and ATTR amyloidosis.

Main Methods:

• Conducted a scoping review of 117 studies following PRISMA-ScR guidelines.
• Identified studies through a comprehensive systematic review for the American Society of Hematology (ASH) amyloidosis diagnosis guideline panel, data mining, and grey literature review.
• Extracted and synthesized data by organ system to characterize early and overlooked clinical red flags for different amyloidosis types.

Main Results:

• Early symptoms of AL amyloidosis include shortness of breath and fatigue, distinct from carpal tunnel syndrome preceding ATTRwt cardiac amyloidosis.
• Overlooked red flags for AL amyloidosis include weight loss, unexplained abdominal pain, and early satiety, contrasting with missed arrhythmias in ATTRwt evaluation.
• Sensory loss is the primary neuropathic presentation in AL amyloidosis, whereas ATTRv amyloidosis typically presents with painful, length-dependent neuropathy.

Conclusions:

• Awareness of distinct early symptoms and patterns across AL and ATTR amyloidosis subtypes is essential for timely diagnosis.
• Identifying specific clinical red flags can improve diagnostic accuracy and reduce delays in initiating treatment.
• Enhanced understanding of these presentations can improve patient outcomes by enabling earlier intervention and preventing irreversible organ damage.