Amyloidosis is a group of diseases that generally affect the elder segment of the population. There are over 30 different types of the disease, and the symptoms are often distinct for each type. Even though amyloidosis in most cases has no cure, early detection has become a challenge that scientists are facing by utilizing new research technologies that have substantially improved disease treatment therapy.
Types Of Amyloidosis
The group of diseases that is amyloidosis are the result of abnormal extracellular protein deposits in various tissues of the body. These proteins are known as amyloids and occur in the same way as cancerous cells; they can accumulate in one tissue or be widespread, affecting different organs (1).
It has been determined that amyloidosis is caused by changes in the structure of some proteins, mostly due to mutations that affect gene expression (2). As a result, some proteins misfold and become insoluble, forming fibrils that can float in plasma or accumulate in the spaces between cells (2). The formation of these fibrils is known as fibrillogenesis (3).
Subsequently, disease occurs due to the deposition of amyloids in specific areas that affect a single tissue. This is known as localized amyloidosis and results in diseases like Alzheimer’s disease, the most clinically relevant and widely known type of localized amyloidosis (2).
The systemic form of amyloidosis is more frequent than localized amyloidosis. It affects many tissues and can cause severe damage in any organ such as heart, kidney, or lungs (4). Systemic amyloidosis and can be classified into three types:
– Primary (AL) amyloidosis: occurs as its own entity and is caused by a plasma cell dyscrasia that is characterized by the expansion of the number of monoclonal bone marrow plasma cells, which are responsible for the production of monoclonal immunoglobulins. This type of systemic amyloidosis is often more prevalent in developed countries (3).
– Secondary (AA) amyloidosis: occurs as a byproduct or a complication of another illness, including chronic infections, such as tuberculosis, or chronic inflammatory diseases, such as rheumatoid arthritis. This type of systemic amyloidosis generally affects the kidneys and occurs more frequently in developing countries, as a likely result of a higher burden of chronic infectious diseases such as leprosy and tuberculosis (3).
– Hereditary amyloidosis: Genetics are responsible for the formation of many types of amyloidosis, and several forms involve heritable factors such as mutant genes or disorders or polymorphisms of cofactors (3).
Clinical manifestations and progression of the type of disease depend on the affected organ and the amount of protein deposition.
Treatment of Amyloidosis
Amyloidosis is a complex disease and tissue biopsy still remains the most utilized method of detection. However, non-invasive techniques such as imaging, SAP scanning, and more effective protein analysis methods have also become very useful elements of diagnosis.
The selection of treatment for the different types of amyloidosis differs based on the cause of fibrillogenesis and the age of the patient, which is a major risk factor for potential acquisition of the disorder. In primary amyloidosis, the therapy is aimed at the the underlying plasma cell dyscrasia, while in secondary amyloidosis, treatment is aimed at the underlying infectious disorder (3). Chemotherapy and hematopoietic cell transplantation are often utilized in patients with AL. In particular, transplantation is sometimes employed in patients with an affected kidney or liver (5).
Evidence shows that the stage of the illness is of great relevance, as several treatments rely on early detection of amyloidosis (6). For example, intravenous infusion, various treatment drugs, and antibodies and other biologic agents are often times only effective treatment options if administered in early stages of the disease. Undoubtedly scientists will continue to develop and employ the most accurate methods of detection to improve life expectancy in patients with this group of disorders (7).
- Merlini G, Seldin D, Gertz M. (2011) Amyloidosis: Pathogenesis and New Therapeutic Options. J Clinical Oncology. 2011 May 10; 29(14): 1924–1933. Published online 2011 Apr 11. doi: 10.1200/JCO.2010.32.2271
- Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. (2014). Update on treatment of light chain amyloidosis. Haematologica. 2014 Feb; 99(2): 209–221. doi: 10.3324/haematol.2013.087619
- Pinney J, et al. (2013) Systemic Amyloidosis in England: an epidemiological study. Br J Haematol. 2013 May; 161(4): 525–532. Published online 2013 Mar 11. doi: 10.1111/bjh.12286
- Ando Y. (2013) Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013; 8: 31. Published online 2013 Feb 20. doi: 10.1186/1750-1172-8-31
- Hawkins P, et al. (2015) Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015 Nov 17; 47(8): 625–638. Published online 2015 Nov 27. doi: 10.3109/07853890.2015.1068949
- Merlini G, et al. (2016) Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis. Leukemia. 2016 Oct; 30(10): 1979–1986. Published online 2016 Aug 2. Prepublished online 2016 Jul 15. doi: 10.1038/leu.2016.191