Amyloidosis

It is a rare but life-threatening disease characterized by the accumulation of a substance called amyloid, a glycoprotein resistant to protein-degrading enzymes, containing fibrils.

Types of amyloidosis:

Amyloidosis can be grouped into different types. The most common grouping method is grouping according to the number of organs involved. According to this:

• Local amyloidosis: Amyloid accumulates in a region and causes damage to this region, causing loss of function. The reason is not known exactly. Local amyloid deposition can be seen in different organs such as lungs, tongue, bladder, eyes, skin, upper respiratory tract, gastrointestinal tract. There is no risk of developing into systemic amyloidosis. Generally, except for AL amyloid type, accumulation is very, very rare. It does not show genetic transmission. For the most part, the prognosis is very good, requiring no special follow-up or treatment. Diagnosis is made by biopsy.
• Systemic amyloidosis: Amyloid accumulates in more than one region, organ, and tissue. It can damage vital organs such as the heart, lungs, kidneys and cause loss of function. Systemic amyloidosis is seen in 3 different types according to the type of amyloid deposited:
• Primary Amyloidosis (AL Amyloidosis): It is the most common type of amyloidosis. It occurs when the bone marrow produces abnormal antibodies due to plasma cell anomaly. Plasma cells produce abnormal light chain proteins with the property of amyloid deposition. It is especially seen in bone marrow related diseases such as Multiple Myeloma. It is more common in men over the age of 40. Amyloid accumulates in the lungs, heart, skin, tongue, thyroid, liver, kidney, blood vessels, etc. There is no familial inheritance feature.
• Secondary Amyloidosis (AA Amyloidosis) : It is more common in chronic inflammatory diseases and rheumatic diseases such as tuberculosis, rheumatoid arthritis, FMF (familial Mediterranean fever), osteomyelitis, empyema, ulcerative colitis, Crohn’s disease, and hemodialysis patients. It is more common in men over the age of 40. The basic protein is amyloid A (AA). Amyloid accumulation occurs in the spleen, liver, kidney, lymph nodes, etc.
• Hereditary Amyloidosis (ATTR amyloid, beta amyloid, TTR (transthyretin), beta2 microglobulin vs amyloidosis): It is a very rare and familial amyloidosis that occurs due to amyloid gene mutation. It is common in FMF (familial Mediterranean fever). Amyloid builds up in nerves, heart, blood vessels, kidneys, etc. Beta amyloid accumulation is observed in Alzheimer’s disease or brain lesions, TTR in the elderly (senile) and beta2 microglobulin accumulation in hemodialysis patients.

Symptoms of amyloidosis:



Amyloidosis usually does not give early signs and symptoms. However, signs and symptoms can be seen in advanced cases. Signs and symptoms may differ according to the organ or tissue involved. Fatigue, weight loss, liver spleen enlargement, heart failure are often seen.

Common signs and symptoms include:

• Oral involvement: Enlargement of the tongue (macroglossia) may be seen. This may cause difficulty in swallowing, breathing problems, and speech difficulties. Rarely, toothache, aphtha-like lesions, numbness, tingling, sicca syndrome due to salivary gland involvement can be seen.
• Involvement of the esophagus: Due to gastroesophageal reflux, there may be bitter water in the mouth and a burning sensation in the chest.
• Stomach involvement: Stomach ulcers, gastric bleeding, prolonged gastric emptying time, indigestion, nausea, and vomiting may occur.
• Small bowel involvement : Increase in the amount of fat in the stool, diarrhea, intestinal infections may be encountered.
• Involvement of the large intestine : It may present with diarrhea, constipation, rectal bleeding, abdominal pain, ulcers, intestinal obstruction.
• Liver involvement: It is characterized by liver enlargement. It is a sign of poor prognosis.
• Cardiac involvement: Heart failure is seen. Respiratory problems, chest pain, palpitations, rhythm disorders, edema in the legs, fainting may occur. The prognosis is bad.
• Renal involvement: The disease manifests itself with loss of protein in the urine. Renal dysfunction and renal failure may occur in the future.
• Skin involvement: Rapid injury, rash, color change, skin thickening, bruises in the eye area are seen.
• Nerve involvement: Tingling sensation in hands and feet, numbness, weakness, swelling in the wrist (Carpal Tunnel Syndrome) and dementia can be seen.
• Joint pains,
• Anemia,
• Sudden weight loss may occur.

Diagnosis of amyloidosis:

Diagnosis is made by biopsy. Amyloid deposition can be seen in biopsy samples taken from areas such as kidney, rectum, and gingiva.



In addition, tests for suspected organs can be performed. These:

• Blood tests (Liver, kidney tests etc.),
• genetic testing (for hereditary amyloidosis),
• Urine tests: (Proteinuria for kidneys etc.),
• EKG (heart involvement),
• ECO (heart involvement),
• Endoscopy (esophagus, stomach, intestinal involvement) may be required.

Treatment of amyloidosis:

There is no definitive treatment for the disease. Treatment is primarily based on treating or correcting the underlying disease.

• Chemotherapy: Chemotherapy directed to plasma cells can be applied, especially in AL amyloidosis. In this way, amyloid accumulation is tried to be stopped. Melphalan and dexamethasone can be used for this purpose. In AA amyloidosis, it is aimed to treat the underlying disease.
• Stem cell therapy: The basis of treatment is stem cells are placed in place of sick cells.
• Organ transplantation: Kidney transplantation can be tried if kidney functions are irreversibly affected, especially in patients with kidney involvement.
• Splenectomy: Splenectomy can be used to stop amyloid production in spleen involvement.
• Dialysis: May be required if kidney failure has developed.
• Diuretics reduce edema due to amyloid accumulation,
• Steroids can reduce amyloid production, increase the effectiveness of chemotherapy drugs,
• dietary regulations,
• Supportive treatment with painkillers can be given.

In hereditary amyloidosis, patisiran and inotersen can stop the progression of the disease and improve the quality of life.