From the Guidelines
Amyloidosis is not primarily classified as an autoinflammatory disorder, though it can share some features with these conditions. Amyloidosis is a group of diseases characterized by the abnormal deposition of misfolded proteins called amyloid fibrils in various tissues and organs, leading to organ dysfunction, as described in a comprehensive review of AL amyloidosis 1. While inflammation may play a role in some types of amyloidosis, particularly AA amyloidosis which can develop secondary to chronic inflammatory conditions, the fundamental pathology involves protein misfolding and deposition rather than dysregulated inflammatory pathways.
Key Characteristics of Amyloidosis
- Abnormal deposition of misfolded proteins in various organs
- Organ dysfunction and failure due to protein deposition
- Usually a plasma cell disorder, with a small, slowly proliferating, bone-marrow-residing PC clone secreting unstable immunoglobulin light chains, as seen in AL amyloidosis 1
Treatment Approaches
- Reducing the production of amyloid precursor proteins
- Eliminating existing deposits
- Autologous stem cell transplantation (ASCT) remains the standard of care and first-line treatment in a small proportion of patients, with new first-line agents like bortezomib improving outcomes for ASCT-ineligible patients 1 In contrast, true autoinflammatory disorders like Familial Mediterranean Fever or TRAPS are characterized by inappropriate activation of the innate immune system leading to recurrent episodes of inflammation without evidence of infection, autoantibodies, or antigen-specific T cells. Some amyloidosis types have genetic components similar to hereditary autoinflammatory diseases, but the primary disease mechanism differs.
Distinction from Autoinflammatory Disorders
- Autoinflammatory disorders involve dysregulated inflammatory pathways
- Amyloidosis involves protein misfolding and deposition
- Treatment approaches differ, with amyloidosis focusing on reducing protein production or eliminating deposits, rather than directly targeting inflammatory pathways 1
From the Research
Definition and Classification of Amyloidosis
- Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues 2.
- There are several types of amyloidosis, including AA amyloidosis, AL amyloidosis, and transthyretin (ATTR) amyloidosis 3, 4, 2.
Relationship between Amyloidosis and Autoinflammatory Disorders
- AA amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders, including autoinflammatory syndromes such as familial Mediterranean fever 5, 3.
- Autoinflammatory syndromes are a group of diseases characterized by intermittent bouts of clinical inflammation with focal organ involvement, and can increase the risk of developing AA amyloidosis 5.
- The development of AA amyloidosis is thought to be related to a permanent acute phase response, which can be triggered by chronic inflammation or autoinflammatory disorders 5.
Diagnosis and Management of Amyloidosis
- The diagnosis of amyloidosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, as well as clinical and laboratory evaluations to determine the type and extent of organ involvement 4, 2, 6.
- Treatment of amyloidosis depends on the type and severity of the disease, and may include anti-inflammatory biologic agents, chemotherapy, and supportive care to manage organ failure 3, 4, 6.
- Early diagnosis and treatment are critical to improving patient outcomes and reducing the risk of complications, including organ failure and death 2, 6.