Immunoglobulin-related Amyloidosis - Types, Causes, and Treatment

What Is Immunoglobulin-Related Amyloidosis?

Immunoglobulin-related amyloidosis is a disorder of the monoclonal plasma cells characterized by the deposition of monoclonal secretory immunoglobulin proteins in the body's different tissues leading to organ involvement and dysfunction. The organs commonly involved are the kidneys, heart, stomach, liver, small and large intestines, and brain.

What Are the Types of Immunoglobulin-Related Amyloidosis?

There are two types of immunoglobulin-related amyloidosis reported in the literature:

1. AL- amyloidosis (Amyloid Light-chain Amyloidosis) - AL-amyloidosis is the most common form of systemic immunoglobulin-related amyloidosis where the amyloid fibril deposits are composed of the immunoglobulin lambda light chains.

2. AH- amyloidosis (Amyloid Heavy-chain Amyloidosis) - AH-amyloidosis is a very rare disorder characterized by the deposition of amyloid fibril protein deposition in the organs that consist of mainly immunoglobulin heavy chain fragments.

Older individuals are frequently involved in both diseases. Both types are associated with the mutation in the plasma cells or B cells, affecting the lymphoproliferative process.

What Is the Pathophysiology of Immunoglobulin-Related Amyloidosis?

The immunoglobulin-related amyloidosis occurs when the monoclonal bone marrow plasma cells undergo mutation, and there is clonal expansion of these mutated plasma cells. These plasma cells are responsible for synthesizing antibodies that are primarily light and heavy protein chain fragments. However, the antibodies with too many lambda light protein chain fragments are produced because of the mutation of these plasma cells. These light chain proteins are misfolded and clumped together, leading to the immunoglobulin amyloid fibril protein deposition in various tissues and organs.

What Is the Epidemiology of Immunoglobulin-Related Amyloidosis?

Immunoglobulin-related amyloidosis shows male predilection. Usually, the disorder is manifested in older individuals. Amyloid light-chain amyloidosis is more common as compared to amyloid heavy-chain amyloidosis.

What Are the Symptoms of Immunoglobulin-Related Amyloidosis?

The clinical features of immunoglobulin-related amyloidosis can be described as follows:

Symptoms Affecting the Head and Neck:

• Lightheadedness.

• Purple-colored rash around the eyes.

• The tongue becomes larger.

Symptoms Affecting the Arms and Legs:

• There may be feelings of pain, numbness, and burning sensation suggestive of peripheral neuropathy.

• There may be tingling and numbness in the fingers suggesting carpal tunnel syndrome.

• Swelling in the legs.

• Lethargy and weakness.

• The patient may bleed or bruise very easily.

Symptoms When the Heart and Lungs Are Involved:

• Palpitations in the heart (the heart is pounding faster).

• Shortness of breath with tightness in the chest.

• Sharp or dull aching chest pain.

• Extreme tiredness.

Symptoms Affecting the Gastrointestinal Tract:

• Loss of appetite.

• Gas buildup in the stomach or bloating.

• Constipation (poop less than two times a week).

• Diarrhea (watery loose stools).

• Nausea and vomiting.

Symptoms Affecting the Kidneys or Urinary Bladder:

• Frothy or foamy urine.

• The frequency of urination is decreased.

What Are the Diagnostic Tests for Immunoglobulin-Related Amyloidosis?

Several tests may be performed to establish the diagnosis of the condition in the affected individual. The following tests can be performed:

• Biopsy of the Bone Marrow - The healthcare professional might advise the biopsy of a small sample of bone marrow from the affected bone.

• Biopsy of the Kidneys - If the kidneys are involved, a biopsy of the renal tissue can also be performed. Light microscopic examination of the sections stained in Congo red is the chief mode of diagnosis.

• Biopsy of the Heart - In case of heart involvement, a sample of the heart muscle can be taken to perform a biopsy.

• Fat-Pad Biopsy - In case of abdomen involvement, a small sample of the fat tissue from the abdomen can be taken to perform a biopsy.

• Hematological Tests - Blood tests can be done to detect the number of light chain immunoglobulins in the blood and the presence of protein deposits in the heart, kidneys, liver, and brain.

• Urine Test - This is performed to check the presence of amyloidosis in the kidneys.

• Cardiac MRI - To visualize a detailed picture of the heart.

What Is the Treatment for Immunoglobulin-Related Amyloidosis?

There is no definite cure for the disease. Healthcare practitioners may adopt ways to control the progression of the disease and provide symptomatic relief to the patients.

• Drug Therapy - The doctors may use chemotherapeutic drugs along with immuno- modulatory drugs and corticosteroids to treat the condition. These drugs will act to destroy the monoclonal plasma cells that produce the defective light chain proteins. However, these drugs do not eliminate the amyloid fibril deposits from the organs.

• Novel Therapeutic Modality - New monoclonal antibodies are being developed and evaluated by researchers that may be used to target the amyloid fibrils deposited in the tissues and organs.

• Bone Marrow Transplantation - The doctor can also advise for stem cell transplant in advanced cases.

How Can Immunoglobulin-Related Amyloidosis Be Prevented?

It is not possible to prevent the occurrence of the disease. It is caused due to the monoclonal expansion of the mutated plasma cells. The plasma cells begin to form uncontrolled deposits of immunoglobulin-secreted amyloid fibril proteins.

What Is the Life Expectancy of Immunoglobulin-Related Amyloidosis?

Healthcare practitioners are trying their best to improve the life expectancy of the affected individuals. They are helping the patients to lead normal lives for a longer period of time. Immunoglobulin-related amyloidosis is a chronic disease that is difficult to cure. However, proper drug therapy can be administered to provide symptomatic relief to the patients. However, it is a serious disease with severe implications leading to organ failure and life-threatening conditions. If a patient is suffering from this condition, immediately contact the healthcare provider, who will provide accurate information about the condition.

How to Take Care of Oneself?

If one is suffering from the disease, immediately seek the doctor’s advice. The healthcare provider will prescribe medicines to provide symptomatic relief and aim to slow down the disease's severity and progression. However, along with medical treatment, one must also take care of themselves to improve overall health. Some of the suggestions are:

• Adopt healthy eating habits. Incorporate a diet rich in vitamins, proteins, and minerals to provide overall nutrition. This will improve the stamina to fight the disease.

• Get proper rest and ensure a proper night's sleep to show improvement in the treatment.

• Physical exercises can be done as the doctor recommends to improve health and maintain the body's weight. But do not put extra strain on the body.

• Join or connect through social groups with people suffering from the same condition. Since immunoglobulin-related amyloidosis is an emotionally draining disorder, try to get involved in constructive activities.

• Connect with family and friends.

Conclusion

Immunoglobulin-related amyloidosis is a complex, debilitating disease characterized by the misfolding and deposition of the amyloid protein. It usually has a poor prognosis, making the early diagnosis very difficult. It is a challenging disease from the diagnostic and treatment point of view. Due to delayed diagnosis, the condition can lead to devastating outcomes resulting in organ failure. It is, therefore, important to identify the type of amyloid protein involved to provide a specific treatment. Researchers are developing and testing many novel agents to target the amyloid fibrils in the organs to cure the disease. Patients should also take care of themselves to improve their overall health.