From the Guidelines
Amyloidosis presents with a variety of clinical signs and symptoms that depend on which organs are affected by the abnormal protein deposits, including heart failure, nephrotic range proteinuria, organomegaly, peripheral neuropathy, and constitutional symptoms such as weight loss and fatigue, as reported in a 2021 study 1.
Clinical Manifestations
The symptoms and presentation of amyloidosis depend on the organs involved in the disease, and patients can present with a myriad of unspecific symptoms that could be easily misinterpreted, thus clouding the diagnosis of amyloidosis and delaying treatment initiation.
- Common symptom constellations include:
- Heart failure with preserved ejection fraction (HFpEF)
- Nephrotic range proteinuria
- Organomegaly due to amyloid deposition (hepatomegaly, macroglossia, enlarged salivary glands etc.)
- Peripheral neuropathy
- Constitutional symptoms (weight loss, fatigue)
Organ Involvement
The heart and the kidneys are the 2 most frequently affected organs in systemic AL amyloidosis, by restrictive CM and proteinuria, respectively, as noted in a 2023 study 1.
- Other organs that can be involved include:
- Soft tissues
- Liver
- Gastrointestinal (GI) tract
- Autonomic and peripheral nervous systems
- Lymph nodes
Diagnosis and Treatment
Early recognition and initiation of treatment before the occurrence of irreversible organ damage is crucial, as stated in a 2021 study 1.
- Diagnosis requires tissue biopsy and typing, followed by risk stratification and disease staging.
- Treatment options include autologous stem cell transplantation (ASCT) and novel agents, such as bortezomib.
Prognosis
The prognosis of amyloidosis depends on the extent of organ involvement and the effectiveness of treatment, with cardiac involvement being the main driver of disease prognosis and mortality, as reported in a 2021 study 1.
- The median survival for patients with AL amyloidosis is around 13 months, with a range of 4 months if heart failure is present, as noted in a 2016 study 1.
From the Research
Clinical Signs and Symptoms of Amyloidosis
The clinical signs and symptoms of amyloidosis vary depending on the organ system affected by the disease. Some common signs and symptoms include:
- Nonspecific symptoms such as weight loss, chronic diarrhea, abdominal pain, intestinal bleeding, or pseudo-obstruction 2
- Macroglossia and periorbital purpura, which are highly specific signs of light chain (AL) amyloidosis, but are insensitive 3
- Musculoskeletal and articular symptoms, which can be associated with chronic rheumatic diseases 4
- Neuromuscular symptoms, such as motor, painful sensory and severe autonomic dysfunction, profound weight loss, and systemic features 5
- Cardiac symptoms, which can be the major determinant of survival, and early detection is crucial for better survival 3
Organ-Specific Symptoms
Different organs can be affected by amyloidosis, leading to various symptoms, including:
- Liver involvement, which is often seen, but symptoms are usually mild and nonspecific in isolated hepatic amyloidosis 6
- Intestinal involvement, which can cause a heterogeneous clinical picture, with weight loss, chronic diarrhea, abdominal pain, intestinal bleeding, or pseudo-obstruction 2
- Cardiac involvement, which is the most common cause of death in amyloidosis 6
- Neuromuscular involvement, which can cause amyloid neuropathy and amyloid myopathy, with distinct characteristics such as relentlessly progressive nature with motor, painful sensory and severe autonomic dysfunction 5
Diagnostic Challenges
Amyloidosis can be difficult to diagnose due to its nonspecific symptoms and the need for tissue biopsy for definitive diagnosis 6, 4, 3, 5, 2. Therefore, clinicians need to be aware of the signs and symptoms that raise suspicion for amyloidosis and include it in their diagnostic work-up, especially in patients with neuropathy or myopathy 5 or gastrointestinal symptoms 2.