Amyloidosis is common in elderly people. Amyloidosis symptoms are usually managed through medications. However, dialysis, organ transplant, and autologous blood stem cell transplant are also part of amyloidosis treatment. Find out more about amyloidosis disease by experts at Meri Sehat.

Amyloidosis

A. JABBAR DENTAL CLINIC KARACHI

Sadia Khan

Overview

The term &lsquo;amyloid&rsquo; dates back to 1838. It was coined by Matthias Schleiden, a German botanist, to describe a normal amylaceous constituent of plants. Later in 1854, Rudolph Virchow used the term amyloid because of the exclusive reaction of the corpora amylacea (small hyaline masses found in the prostate gland, nervous system and lungs) of the nervous system with iodine.

Amyloidosis refers to a group of rare health conditions caused by an excessive quantity of an abnormal protein, called amyloid, in your organs and tissues throughout the body. This build-up of amyloid makes your organs and tissues inefficient. If the disease is left untreated, it can lead to organ failure. Amyloidosis is characteristically defined by the extracellular deposition of insoluble fibrillar proteins. Amyloid deposits are usually identified histologically by Congo red stain, which gives apple-green birefringence under the influence of polarized light. 
&nbsp;

It is not necessary for the amyloid protein to be found in the entire organ, it can be deposited in a localized area&nbsp; OR only in a single tissue of the body as well. This deposition may or may not be harmful<a href="#accordion">[1]</a>.

&nbsp;If the disease is showing a focal area, it is termed localized amyloidosis, whereas amyloidosis which affects multiple tissues of the body is called systemic amyloidosis. The systemic variant has the tendency to cause serious damage to any organ of the body, which includes your kidneys (renal amyloidosis), heart (cardiac amyloidosis), skin (cutaneous amyloidosis), and lungs (pulmonary amyloidosis). Furthermore, macular amyloidosis is the most subtle form of the cutaneous variant.

Studies prove that when symptomatic cardiac dysfunction is present, the life expectancy without any treatment is 6 months. In 2008, Primary or AL (amyloid-light chain) amyloidosis had an incidence rate of 3 and 8.3 cases per million person-years in England and Sweden, respectively<a href="#accordion">[2]</a>. Furthermore, data also proves that between 2007 and 2015, 7591 prevalent patients were diagnosed with AL amyloidosis, ranging from 368 to 1080 cases per million per year<a href="#accordion">[2]</a>. 
&nbsp;

Amyloidosis can have different types depending on the organ or its onset. Following are the subtypes of the disease: 
&nbsp;

<h5>1. AL (Primary) Amyloidosis</h5>

It is the most common form of amyloidosis. In this type, your body&#39;s immune system produces an abnormal form of antibodies termed &lsquo;light chains&rsquo;. Hence, giving the characteristic &lsquo;L&rsquo; in &lsquo;AL&rsquo; amyloidosis. Physiologically, the cells in your bone marrow i.e. &lsquo;plasma cells&rsquo; are responsible for producing protective proteins called antibodies which fight infections. If due to any reason, a plasma cell becomes cancerous, it replicates excessively and produces an extra quantity of these antibodies which we define as &lsquo;light chains&rsquo;. The light chains travel through the bloodstream, building up in your organs and leading to organ damage.

The most commonly affected organs include:

<ul>
	<li>Heart</li>
	<li>Kidneys</li>
	<li>Nerves</li>
	<li>Gut 
	&nbsp;</li>
</ul>

<h5>2.&nbsp;AA (Secondary) Amyloidosis</h5>

Secondary amyloidosis is characterized by a protein called &lsquo;serum amyloid A&rsquo;. This exclusive protein is made by the body in response to inflammation or an infection. A considerable amount of time is needed for the protein to build up and show symptoms. This is the reason that chronic states of inflammation (rheumatoid arthritis) or chronic states of infection (chronic tuberculosis) can lead to AA amyloidosis deposits over several years. AA (secondary) amyloidosis commonly affects the following organs:

<ul>
	<li>Kidneys</li>
	<li>Liver 
	&nbsp;</li>
</ul>

<h5>3. Familial ATTR Amyloidosis</h5>

It is an inherited disease, which means that it is passed on by the parents to their children. In this variant, your body makes a mutated form of a protein called &lsquo;transthyretin&rsquo; (abbreviated TTR). Hence, the name familial ATTR amyloidosis. Transthyretin production is a normal process, however, production of the mutated form can lead to the formation of amyloid fibrils. The most common form of mutation includes &lsquo;V-122-I&rsquo; and is mostly seen in individuals of African origin. Moreover, the familial ATTR variant of amyloidosis most commonly affects the heart and nerves. Even though it is a potentially serious health disease, the prognosis for familial ATTR amyloidosis is comparatively better than AL amyloidosis, because of its slow progression. 
&nbsp;

<h5>4. Wild-type (senile) ATTR Amyloidosis</h5>

It is similar to familial ATTR amyloidosis, other than the presence of mutated transthyretin protein. As discussed earlier, the normal transthyretin protein is less likely to form amyloid deposits compared to the mutated variant. Hence, patients only develop this type of amyloidosis in their older age, most commonly at 65 years of age or older. This type holds a better prognosis than AL (primary) amyloidosis and familial ATTR amyloidosis as the amyloid deposits accumulate very slowly over a long period of time. 
&nbsp;

<h5>5. Beta-2 ̶ Microglobulin (beta-2m) Amyloidosis</h5>

This disabling type of amyloidosis affects patients who are undergoing long-term hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). It usually does not present in individuals with normal or mildly reduced kidney functions, or in patients with an efficiently working kidney post transplant. However, it develops slowly and is rare in the first few years of HD.

Beta-2m is considered a major component of amyloid fibrils. Because of the accumulation, it penetrates the synovial membranes and osteoarticular sites causing destructive osteoarthropathy, such as carpal tunnel syndrome, flexor tenosynovitis, subchondral bone cysts, and erosions, along with pathologic fractures. Moreover, it can also be found in sites such as the gastrointestinal (GI) tract, heart, and tongue. The most feared complication is the beta-2m amyloid deposits obliterating the paravertebral ligaments and intervertebral discs, leading to paraplegia. This is an inability to voluntarily move the lower parts of the body. 
&nbsp;

Signs and Symptoms

You may not experience symptoms of amyloidosis until the disease has progressed to a specific stage. Moreover, symptoms can vary and are dependent upon the organ involved. 
&nbsp;

Signs and symptoms of the disease may include<a href="#accordion">[3]</a>:

<ul>
	<li>Severe fatigue and weakness</li>
	<li>Shortness of breath</li>
	<li>Numbness, tingling, or pain in the hands or feet</li>
	<li>Swelling of the ankles and legs</li>
	<li>Diarrhea, that may contain blood</li>
	<li><a href="https://merisehat.pk/disease/constipation">Constipation</a></li>
	<li>Enlarged tongue, which may look rippled around the edge</li>
	<li>Thickening of your skin</li>
	<li>Easy bruising of skin</li>
	<li>Purplish patches around the eyes 
	&nbsp;</li>
</ul>

Causes

As discussed earlier, AL amyloidosis is caused by an abnormality in the plasma cells present in the bone marrow. These abnormally functioning plasma cells are responsible for producing improper light chain proteins, which enter your bloodstream and can lead to amyloid deposition. Physiologically, light chain proteins help in fighting infections. However, an abnormal light chain, found in patients with AL amyloidosis, clumps together to form a thread-like string (amyloid fibrils) that the body can not clear easily. As time progresses, amyloid fibrils build up in your tissues and organs. Disease progression alters the functionality of your organs, exhibiting the classical symptoms of AL amyloidosis<a href="#accordion">[4]</a>. 
&nbsp;

A detailed history and examination may help your healthcare provider evaluate you for amyloidosis. 
&nbsp;

Diagnosis

A biopsy analyzes tissue samples for signs of amyloidosis. Samples may be taken from the fat under your abdominal skin (subcutaneous), or from your bone marrow. However, some people might need a biopsy of an affected organ, for example, the liver or kidney. This is to ensure the type of amyloid involved.

Following are the imaging diagnostic modalities that can be used as well<a href="#accordion">[5]</a>: 
&nbsp;

<h5>1.&nbsp;Echocardiogram</h5>

Echocardiogram uses sound waves to create moving images to give information about the heart&rsquo;s functionality and structure. Hence, it can help in identifying heart damage which can be exclusive to particular forms of amyloidosis. 
&nbsp;

<h5>2.&nbsp;Magnetic Resonance Imaging (MRI)</h5>

MRI uses radio waves and a strong magnetic field to form highly detailed images of your organs and tissues. An MRI is used to check the structure and function of the heart. 
&nbsp;

<h5>3.&nbsp;Nuclear&nbsp;Imaging</h5>

Tiny amounts of radioactive material, called tracers are injected into a vein. This helps in distinguishing between different forms of amyloidosis, on which the treatment plan is dependent. 
&nbsp;

Treatment

Currently, there is no cure for amyloidosis. However, management to control the presenting signs and symptoms, along with limiting further production of amyloid protein is possible. For example, if amyloidosis has been triggered due to a primary condition, such as rheumatoid arthritis or tuberculosis, treating it may help the existing condition. 
&nbsp;

Following are the treatment modalities which can be used for amyloidosis<a href="#accordion">[5]</a>: 
&nbsp;

<h5>1.&nbsp;Medications</h5>

<ul>
	<li>Chemotherapy:&nbsp;Some cancer drugs, called chemotherapeutic agents, may be used in AL or Primary amyloidosis to limit the growth of abnormal cells responsible for producing the protein that forms amyloid.</li>
	<li>Heart Medications:&nbsp;If amyloidosis manages to affect your heart, you might need to routinely take blood thinners to reduce the risk of blood clots. Moreover, you may also require medications to control your heart rate. Drugs that increase urination can be considered, as it reduces the strain on your heart and kidneys.</li>
	<li>Targeted Therapy: For certain types of amyloidosis, drugs such as patisiran and inotersen can help by running interference with the commands sent by abnormal genes responsible for producing amyloid. Other drugs, such as tafamidis and diflunisal, can help by preventing bits of protein in the bloodstream from getting transformed into amyloid deposits. 
	&nbsp;</li>
</ul>

<h5>2.&nbsp;Surgical Procedures</h5>

<ul>
	<li>Autologous Blood Stem Cell Transplant: The procedure involves the collection of your own stem cells from the blood through a vein and storing them for a brief period while you undergo high-dose chemotherapy. After the session, your stem cells are then restored in your body through a vein. This treatment helps people whose disease isn&#39;t advanced and whose heart isn&#39;t immensely compromised.</li>
	<li>Dialysis: If amyloidosis has affected your kidneys greatly, you may need to be started on dialysis. The procedure includes a machine to filter out the waste products, salts and fluid from your blood on a set schedule.</li>
	<li>Organ Transplant: If the damage done is great by the disease, you might need surgery to replace the affected organs such as kidneys. For example, some types of amyloid are formed in your liver; hence, a liver transplant can help stop the production of the protein. 
	&nbsp;</li>
</ul>

If amyloidosis is allowed to progress, it can have the following consequences<a href="#accordion">[6]</a>: 
&nbsp;

<ul>
	<li>Kidneys become overwhelmed with amyloid. This in turn leads to scarring of the tissues, renal problems, bone diseases, <a href="https://merisehat.pk/disease/anemia">anemia</a>, and <a href="https://merisehat.pk/disease/hypertension-57">high blood pressure</a>. Due to renal insufficiency, you may also develop swelling in the body, especially on the ankles and legs.</li>
	<li>Amyloidosis has the tendency to decrease your heart&rsquo;s function as well. This happens because amyloid builds up throughout your body, including the blood vessels and muscle tissue.Thus, making it hard for your heart to pump efficiently. This can result in abnormal heart rhythms and shortness of breath.</li>
	<li>People with amyloidosis may also develop high blood pressure or hypertension.</li>
	<li>Amyloid can also cause disruption of your nerves. When there&rsquo;s a considerable buildup of amyloid proteins in your body, your nervous system becomes inefficient and you experience numbness and tingling sensations, especially in your hands and feet. 
	&nbsp;</li>
</ul>

Risk factors are independent reasons that may put you at an increased risk for the disease than the other population. Risk factors for amyloidosis consist of<a href="#accordion">[7]</a>: 
&nbsp;

<ul>
	<li>Age</li>
</ul>

The risk of amyloidosis is directly proportional to age. Studies show that in AL amyloidosis, most people were diagnosed when they were older than 40 years. 
&nbsp;

<ul>
	<li>Gender</li>
</ul>

Amyloidosis has shown a predilection for the male gender. 
&nbsp;

<ul>
	<li>Other Diseases</li>
</ul>

Amyloidosis can sometimes be associated with another disease. Studies show that 12% to 15% of people with multiple myeloma are at a higher risk to develop AL amyloidosis<a href="#accordion">[7]</a>. 
&nbsp;

<ul>
	<li>Family History</li>
</ul>

Our genes play a crucial role in developing diseases and amyloidosis is no different. Hereditary variants of amyloidosis run in families. This is because of a genetic change, also called a mutation, which is passed down from one generation to another. 
&nbsp;

There is no definite prevention for amyloidosis. However, if the developed disease is a secondary form of amyloidosis, it can be prevented by managing the primary condition that is linked with the inflammation. 
&nbsp;

UC San Diego Health is one of those rare centers in California which utilize a much targeted approach towards the treatment of amyloidosis. The institute came up with a class of drugs called the &lsquo;silencers&rsquo; which essentially decrease the production of the protein that creates amyloid<a href="#accordion">[8]</a>. After receiving the medication in clinical trials, amyloidosis-related polyneuropathy or pain developed at a much slower rate, and in fact, symptoms improved in some patients. They recently obtained FDA approval for their silencer drug called Amvuttra<a href="#accordion">[8]</a>. 
&nbsp;

Key Points

<ul>
	<li>Amyloidosis refers to a group of rare health conditions which are caused by an excessive quantity of an abnormal protein called amyloid in your organs and tissues</li>
	<li>Amyloidosis is characteristically defined by the extracellular deposition of insoluble fibrillar proteins</li>
	<li>If the disease is showing a focal area, it is termed localized amyloidosis, whereas amyloidosis which affects multiple tissues of the body is called systemic amyloidosis.</li>
	<li>Studies prove that when symptomatic cardiac dysfunction is present, the life expectancy without any treatment is 6 months</li>
	<li>Primary or AL amyloidosis had an incidence rate of 3 and 8.3 cases per million person-years in 2008 in England and Sweden, respectively</li>
	<li>Between 2007 and 2015, 7591 prevalent patients were diagnosed with AL amyloidosis, ranging from 368 to 1080 cases per million per year.</li>
	<li>AL amyloidosis is the most common form of amyloidosis, in which your body&#39;s immune system produces an abnormal form of antibodies termed &lsquo;light chains&rsquo;.</li>
	<li>Secondary amyloidosis is characterized by a protein called &lsquo;serum amyloid A&rsquo;. This exclusive protein is made by the body in response to inflammation or an infection.</li>
	<li>Familial ATTR amyloidosis is an inherited disease, which means that it is passed on by the parents to their children. In this variant, your body makes a mutated form of a protein called &lsquo;transthyretin&rsquo;.</li>
	<li>Senile amyloidosis is similar to familial ATTR amyloidosis, other than the abundance of mutated transthyretin protein.</li>
	<li>Beta 2 amyloidosis is a type of amyloidosis that disables and affects patients who are undergoing long-term hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).</li>
	<li>Signs and symptoms of the disease may include severe fatigue and weakness, shortness of breath, numbness, tingling or pain in the hands or feet, swelling of the ankles and legs along with diarrhea that may present with blood.</li>
	<li>AL amyloidosis is caused by an abnormality in the plasma cells which is found in the bone marrow. As time progresses, amyloid fibrils build up because AL amyloid builds up in your tissues and organs.</li>
	<li>A detailed history and examination may help your healthcare provider to evaluate you for amyloidosis.</li>
	<li>A tissue sample can be checked for signs of amyloidosis, called a biopsy. Samples may be taken from the fat under your skin (subcutaneous) on the abdomen or from your bone marrow</li>
	<li>Imaging tests such as an echocardiogram, MRI and Nuclear Imaging might be used for diagnosing amyloidosis.</li>
	<li>Currently, there is no cure for amyloidosis. However, management to control the presenting signs and symptoms along with limiting further production of amyloid protein is possible.</li>
	<li>Chemotherapeutic agents, cardiac medications, and targeted therapy is used in medical management. Whereas surgical intervention includes stem cell transplant, organ transplant, and dialysis.</li>
	<li>Due to renal insufficiency caused by amyloidosis, you may also develop swelling in the body, especially on the ankles and legs.</li>
	<li>Amyloidosis has the tendency to decrease your heart&rsquo;s function as well. This happens because amyloid builds up throughout your body, including your blood vessels and muscle tissues, making it hard for your heart to pump efficiently.</li>
	<li>Amyloid can also cause disruption of your nerves.</li>
	<li>Studies show that 12% to 15% of people with multiple myeloma are at a higher risk to develop AL amyloidosis</li>
	<li>There is no definite prevention for amyloidosis.</li>
	<li>UC San Diego Health is one of those rare centers in California which utilize a much targeted approach towards the treatment of amyloidosis. After receiving the medication in clinical trials, amyloidosis-related polyneuropathy or pain developed at a much slower rate, and in fact, symptoms improved in some patients. 
	&nbsp;</li>
</ul>

[1] Kyle RA. Amyloidosis: A convoluted story. British Journal of Haematology. 2001;114(3):529-538. doi:10.1046/j.1365-2141.2001.02999.x

[2] Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of al amyloidosis: A real-world study using US claims data. Blood Advances. 2018;2(10):1046-1053. doi:10.1182/bloodadvances.2018016402