Amyloid A Amyloidosis - Causes, Symptoms, Diagnosis and Management

Introduction

Amyloidosis is a rare health condition that is marked by the collection of specific proteins over a lot of organs. This protein settling (deposition) can happen either in single or multiple organs. Amyloid A amyloidosis is a health condition that can negatively impact the functioning of vital organs in the human body.

What Is Amyloidosis?

Amyloidosis is a specific group of disorders characterized by atypical protein deposits in organs. Though other proteins can also form deposits, amyloid proteins are the ones that result in serious health issues. When proteins build up in the tissues and organs, it greatly influences the normal functioning of the organs. Amyloidosis can be of different types:

• Immunoglobulin light chain amyloidosis.

• Amyloid A amyloidosis.

• Dialysis-related amyloidosis.

• Familial amyloidosis.

• Age-related amyloidosis.

• Organ-specific amyloidosis.

What Is Amyloid A Amyloidosis?

Amyloid A amyloidosis (AA amyloidosis) is a specific class of amyloidosis that develops due to an underlying long-standing infection or inflammation (immune response). Secondary amyloidosis is the synonym for AA amyloidosis as it develops secondarily to other health conditions. In AA amyloidosis, a specific protein called serum amyloid A (SAA) is gathered in the tissues and organs.

What Is Serum Amyloid A?

Serum amyloid A (SAA) is a typical protein produced chiefly by the liver cells (hepatocytes). SAA exhibits certain key roles during various inflammatory and infectious conditions. Inflammatory conditions are accompanied by a sudden hike in the SAA level in the circulatory blood. In addition, it has some immunomodulatory functions.

What Causes Amyloid A Amyloidosis?

The clear mechanism leading to this rare condition's development is still unknown. However, it develops secondary to various conditions accompanied by lingering inflammation. When there is a long-standing inflammatory (immune response) condition, a higher concentration of SAA circulates in the bloodstream over a longer period, eventually precipitating in the tissues and organs in the form of insoluble fibrils. Amyloid protein collection may completely disrupt the structure and function of organs and potentiate the complications of chronic (long-standing) conditions. In most instances, AA amyloidosis is seen in connection with conditions like:

• Rheumatoid arthritis (inflammation of joints and surrounding tissues).

• Crohn’s disease (inflammation of the digestive tract).

• Ulcerative colitis (chronic inflammation and ulcers in the colon).

• Ankylosing spondylitis (inflammation of joints and ligaments of the spine).

• Familial periodic fever syndrome (a hereditary disorder that causes recurrent fever and other symptoms).

• Bronchiectasis (a long-term lung disease).

• Cystic fibrosis (a genetic disorder that causes the accumulation of sticky, thick mucus).

• Chronic osteomyelitis (infection of the bone).

• Tuberculosis (bacterial infection of the lungs).

• Hairy cell leukemia (a rare type of blood cancer).

• Multiple myeloma (blood cancer that affects plasma cells).

• Hodgkin lymphoma (blood cancer of the lymphatic system).

• Vasculitis (inflammation and damage of the blood vessels).

What Are the Risk Factors for Amyloidosis?

Some of the risk factors of amyloidosis include:

• Amyloidosis is mostly seen in males between 60 and 70 years of age.

• Individuals with a family history of amyloidosis.

• Patients with a history of inflammatory diseases or chronic infections are more prone to develop AA amyloidosis.

• Patients undergoing dialysis procedures.

Which Organs Are More Frequently Affected by AA Amyloidosis?

Though SAA proteins can accumulate anywhere in the body, they routinely affect the kidney and significantly impair kidney functions. In addition, the liver, intestine, spleen, and stomach are also affected occasionally. It affects the heart less frequently, but it is potentially dangerous.

What Are the Signs and Symptoms Associated With Amyloid A Amyloidosis?

• The affected organs largely influence the symptoms exhibited in AA amyloidosis and vary accordingly.

• Kidney involvement gets reflected in the ballooning of legs and arms. Apart from that, proteinuria (protein in urine) can also be detected as the kidney is improperly functioning.

• When the stomach and intestines are affected, symptoms like diarrhea (loose and watery stools) and bloating occur. Sometimes, the tongue enlarges, obstructing the swallowing of food. Occasionally, constipation is also reported with gastrointestinal tract association.

• Amyloid buildup in the nerve endings causes tingling and numbness, especially in the hands and feet.

• Protein collection in the skin makes it weak and delicate, thus increasing the tendency to bleed (bruising) through the skin.

• Amyloid fibrils in the heart muscle significantly impair the rhythm of the heartbeat. In addition, it reflects short, shallow breaths and a dramatic reduction in blood pressure.

Other routinely encountered symptoms include the following:

• Frothy feces (pee).

• Weight loss.

• Weakness.

• Rash.

• Weak grip.

• Abdominal pain.

How Is Amyloid A Amyloidosis Diagnosed?

Certain tests and procedures, along with medical history and clinical findings, are advised to confirm the diagnosis of AA amyloidosis.

• Blood Tests: To assess urea, nitrogen, and creatinine levels in the blood.

• Urine Analysis: To detect the presence of protein in the urine.

• Biopsy: Biopsy specimens are collected from the involved organ to detect amyloidosis changes.

• Aspiration Cytology: To assess the fat under the skin layer.

• Ultrasound: Ultrasound of the abdomen reveals structural changes in the organs like the liver.

• Nerve Conduction Velocity: To assess the transmission of impulses through the nerves.

• Echocardiogram: To assess the heart's functioning and detect damaged areas.

• Electrocardiogram: To detect irregularities in the heart's electrical conduction.

• Nuclear Imaging: To identify damage in heart muscle using radioactive agents as tracers.

• Magnetic Resonance Imaging (MRI): The magnetic field provides a clear picture of the organ.

• Computed Tomography: To visualize the organ structure.

What Are the Available Treatment Methodologies?

AA amyloidosis is not a completely curable condition. However, symptomatic management effectively controls the disease by checking protein accumulation. As an underlying disease precipitates the disorder, treating the primary condition is vital in managing AA amyloidosis.

• The involved organs and the underlying disease tend to guide treatment strategies.

• Occasionally, immunosuppressive medicines are suggested to control the immune response, thereby, SAA protein deposition.

• Dialysis is considered if the kidney function is severely affected.

• Cardiac medicines are prescribed to maintain the rate and rhythm of the heartbeat. Blood thinners are recommended to minimize the risk of clot formation. Certain drugs may be prescribed to increase urination and reduce the strain on the heart and kidneys.

• Targeted therapies using certain medications, such as Inotersen, Diflunisal, Tafamidis, etc., can stabilize blood protein from transforming into amyloid deposits.

• If the organs are damaged to the extent that further corrective treatments do not seem fruitful, it is better to consider organ transplantation as an effective treatment intervention. However, organ transplantation is a complex surgical procedure; hence, it is initiated only if all the patient factors are favorable for the surgery.

• Autologous blood stem cell transplant can be performed in individuals whose condition is not much advanced, and the heart is not affected by amyloidosis.

What Are the Potential Complications That Could Arise From AA Amyloidosis?

• Kidney failure.

• Respiratory failure.

• Heart failure.

• Internal bleeding.

• Perforation in the bowel.

• Endocrine failure.

• End-stage renal disease.

• Multiple organ failure.

• Amyloidosis can cause pain, numbness in the hands and feet, and nerve damage.

What Is the Prognosis for AA Amyloidosis?

The prognosis of AA amyloidosis revolves around certain factors like:

• Affected organs.

• Severity and nature of the underlying disease.

Can Amyloid A Amyloidosis Be Prevented?

Amyloid A amyloidosis cannot be prevented, but specialists may prescribe different medications to slow its development and protect the organs. However, appropriate treatment for any underlying persistent inflammatory diseases can decrease protein in the blood. Also, managing kidney diseases under proper medical care can prevent kidney damage, which in turn reduces the risk of developing AA amyloidosis.

Conclusion

AA amyloidosis is a serious condition that originates due to a long-standing infectious condition expressed as an accumulation of amyloid fibrils. Protein deposits in tissues and organs lead to disrupted functioning over time. So, it needs to be treated at the right time; otherwise, it can potentially cause multiple organ failures and death. However, it can be prevented by properly managing and treating other systemic conditions.