DRG Category: 546
Mean LOS: 4.4 days
Description: Medical: Connective Tissue Disorders With Complication or Comorbidity
Amyloidosis is a rare, chronic metabolic disorder characterized by the extracellular deposition of amyloid, a fibrous protein, in one or more locations of the body. Technically, amyloidosis is a constellation of disorders. Primary amyloidosis is a monoclonal plasma cell disorder, and the abnormal protein is an immunoglobulin; it is not associated with other clinical conditions and is considered idiopathic because it arises spontaneously. Secondary amyloidosis occurs as a result of chronic infection, inflammation, or malignancy and is caused by the degradation of the acute-phase reactant serum amyloid; familial amyloidosis results from accumulation of a mutated version of a plasma protein. Because normally soluble proteins are folded or pleated, they become deposited as insoluble fibrils that progressively disrupt tissue structure and function. The modern classification of amyloidosis is based on the chemistry of the protein. The disease is referred to with an A followed by an abbreviation of the fibril protein. Most people with primary amyloidosis have a fibril protein that is a light chain, abbreviated L. Therefore, most people with primary amyloidosis have light chain amyloidosis (AL). Eight out of 1 million people develop amyloidosis, and the average age of diagnosis is 65 years. The Amyloidosis Foundation estimates that approximately 4,500 people are diagnosed with AL each year in the United States. AL is caused by a disorder of the bone marrow, which produces plasma cells that make an abnormal immunoglobin (antibody) that is deposited in organs and other tissues. Organ dysfunction results from accumulation and infiltration of amyloid into tissues, which ultimately puts pressure on surrounding tissues and causes atrophy of cells. Some forms of amyloidosis cause reticuloendothelial cell dysfunction and abnormal immunoglobulin synthesis.
The associated disease states may be inflammatory, hereditary, or neoplastic; deposition can be localized or systemic. Secondary amyloidosis is associated with such chronic diseases as tuberculosis, syphilis, HIV, Hodgkin disease, and rheumatoid arthritis and with extensive tissue destruction. Amyloidosis occurs in about 5% to 10% of patients who have multiple myeloma, the second-most common malignant tumor of bone. The spleen, liver, kidneys, and adrenal cortex are the organs most frequently involved. For a patient with generalized amyloidosis, the average survival rate is 1 to 4 years. Some patients have lived longer, but amyloidosis can result in permanent or life-threatening organ damage. The major causes of death are renal failure and cardiac failure. When heart failure is associated with amyloidosis, the average survival rate is less than a year.
The precise causes of amyloidosis are unknown, although some experts suspect an immunobiological basis for the disease. The disease has complex causes, with both immune and genetic factors involved. It may be due to an enzyme defect or an altered immune response. Some forms of amyloidosis appear to have a genetic cause. Another form of amyloidosis appears to be related to Alzheimer disease.
While not specifically a genetic disease, several genes have been associated with amyloidosis. These include the apolipoprotein A1 gene (APOA1), the fibrinogen alpha-chain gene (FGA), and the lysozyme gene (LYZ). Amyloidosis can also occur as a feature of heritable diseases, such as familial Mediterranean fever (FMF), which is an autosomal recessive disease more common among persons of Mediterranean origin; autosomal dominant cases have also been reported. FMF causes fever and pain in the joints, chest, and abdomen. Amyloid aggregation has also been linked to familial amyloid neuropathies, which are usually caused by mutations in transthyretin (TTR), apolipoprotein A1 (APOA1), or gelsolin (GSN).
Amyloidosis is seen more in adult populations than in children and adolescents. Older individuals, especially those with Alzheimer disease and rheumatoid arthritis, are at risk. In the United States, because of higher rates of rheumatoid arthritis in women, inflammatory (secondary) amyloidosis is more common in women than in men. Considering all forms of amyloidosis, the male-to-female ratio is 2:1 because males have higher incidence of primary amyloidosis than females.
Some studies show that Black persons have a higher risk for cardiac-related amyloidosis leading to cardiomyopathy and a more aggressive form of the disease than do other groups. Sexual and gender minority status has no known effect on the risk for amyloidosis.
Amyloidosis occurs around the world, but no prevalence data are available. International rates depend on the prevalence of associated diseases in the country of origin. Patients whose origins are Portuguese, Japanese, Swedish, Greek, and Italian may be more susceptible.
PLANNING AND IMPLEMENTATION
Collaborative
Therapy is targeted to support care that manages symptoms of the underlying organ dysfunction through pharmacologic therapy, but there is no known cure. Autologous blood stem cell transplant is a treatment option for people whose disease is not advanced with good cardiac function, but only a minority of patients with AL are eligible for this procedure. Chemotherapy and immunomodulator therapy may also be administered. Surgical procedures may be used to treat severe symptoms. The patient may develop a complication of the tongue called macroglossia. If this occurs, a tracheotomy may be necessary to maintain oxygenation. Patients with severe renal amyloidosis and azotemia may undergo bilateral nephrectomy and renal transplantation followed by immune therapy, although the donor kidney may be susceptible to amyloidosis as well. Strict control of blood glucose levels and treatment of hypertension are important for people with renal amyloidosis.
Other Management
A dietary consultation can provide the patient with a plan to supplement needed nutrients and bulk-forming foods based on the patient's symptoms. Unless the patient requires fluid restriction, they need to drink at least 2 L of fluid per day. A referral to a speech therapist may be necessary if the patient's tongue prevents clear communication.
| Medication or Drug Class | Dosage | Description | Rationale |
|---|
| Melphalan and prednisone combined therapy | Varies with drug protocol | Antineoplastic alkylating agent and corticosteroid | Interrupts the growth of the abnormal cells that produce amyloid protein; decreases amyloid deposits; no known effective therapy to reverse amyloidosis |
Other Therapies: Drug combinations are tailored to individual patients to enable the best course of treatment. New and experimental combinations include cyclophosphamide, proteasome inhibitors, and immunomodulators such as thalidomide. Dimethylsulfoxide (DMSO) and colchicine have been used at times to decrease amyloid deposits. Doxycycline may be used to reduce joint pain and increase range of motion. To prevent serious cardiac complications in patients with cardiac amyloidosis, antidysrhythmic agents are prescribed. Digitalis is avoided because patients are susceptible to toxicity. Vitamin K is used to treat coagulation problems, and analgesics are prescribed for pain. As the disease progresses and malabsorption develops secondary to GI involvement, parenteral nutrition is used to meet nutritional needs.
Independent
Maintain a patent airway when the patient's tongue is involved. Prevent respiratory tract complications by gentle and adequate suctioning when necessary. Keep a tracheotomy tray at the patient's bedside in case of airway obstruction. When the patient is placed on bedrest, institute measures to prevent atrophy of the muscles, development of contractures, and formation of pressure ulcers.
Provide a pleasant environment to stimulate the patient's appetite. Give oral hygiene before and after meals and assist the patient as needed with feeding. Note that the disease puts tremendous stressors on the family and patient as they cope with a chronic disease without hope of recovery. Encourage the patient to verbalize their feelings. Involve loved ones in the care of the patient, and involve the patient in all discussions surrounding their care. Present a realistic picture of the prognosis of the illness, but do not remove the patient's hope. This illness tends to be progressive and debilitating with significant dysfunction of the involved organs. Long-term health planning is essential. Refer the patient and family to the chaplain or a clinical nurse specialist for counseling if appropriate.
Evidence-Based Practice and Health Policy
Rubin, J., & Maurer, M. (2020). Cardiac amyloidosis: Overlooked, underappreciated, and treatable. Annual Review of Medicine, 71, 203–219.
- The authors proposed to review the literature that explains cardiac amyloidosis, a disease that leads to infiltrative and restrictive cardiomyopathy and ultimately to heart failure. Cardiac amyloidosis is often underdiagnosed. Diagnostic testing such as nuclear scintigraphy has reduced the need for patients to undergo a biopsy to make the diagnosis. In nuclear scintigraphy, radioisotopes are attached to drugs that are injected, travel to the heart, and allow for capture of two-dimensional images.
- In addition to sodium restrictions and diuretic use, advanced chemotherapies are being targeted to different stages of the disease process depending on the pathophysiology of the disease.