What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloid Light Amyloidosis
• Immunoglobulin Light-Chain Amyloidosis
• Primary Systemic Amyloidosis

What is AL Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins). These protein aggregates are abnormally-formed and arranged into fibrils
• AL Amyloidosis occurs when plasma cells (also known as B cells) in the bone marrow produce excess amyloid (A) protein, creating wrongly-processed light (L) chains. These chains accumulate in blood and get deposited in the tissues
• AL Amyloidosis typically affects older men and women. The disorder is acquired and may evolve from pre-existing bone marrow disorders such as plasma cell dyscrasia, malignant lymphoma, and multiple myeloma
• The amyloid protein deposits may occur in major organs and tissues, including the kidney, heart, gastrointestinal system, and nerves. The symptoms of AL Amyloidosis depend on the body system(s) involved. In many, weakness, unintended weight loss, and edema, are noted
• Even though the treatment is symptomatic and supportive; typically, AL Amyloidosis is a progressive condition with no cure and the prognosis is guarded

Who gets AL Amyloidosis? (Age and Sex Distribution)

• AL Amyloidosis is reported worldwide and is the most prevalent subtype of amyloidosis
• Although amyloidosis can affect individuals of any age, most cases are noted in the age group of 50-70 years
• Men are more commonly affected than women; roughly two-thirds of the reported AL Amyloidosis cases are noted in men

What are the Risk Factors for AL Amyloidosis? (Predisposing Factors)

The risk factors for AL Amyloidosis include the following:

• Advancing age
• Male gender
• Any condition that affects the antibody-producing cells in the body, including benign monoclonal gammopathy, malignant lymphoma, and multiple myeloma

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of AL Amyloidosis? (Etiology)

• AL Amyloidosis is caused by an abnormal functioning of plasma cells in the bone marrow. The bone marrow is the location of blood generation.
• A type of blood cells known as plasma cells (also called B cells) is involved in the immune function of the body. These cells produce immunoglobulins, which are a type of proteins
• Immunoglobulins are made up of light and heavy chains. The light chain immunoglobulins are misfolded in AL Amyloidosis, and hence the name Amyloid Light Amyloidosis 
• The misfolded proteins are not recycled properly; they get accumulated in the bloodstream and are deposited in the tissues and organs

AL Amyloidosis is an acquired disorder of the plasma and is typically associated with bone marrow disorders such as dyscrasia, monoclonal gammopathy, lymphoma, multiple myeloma, and Waldenstrom’s macroglobulinemia.

What are the Signs and Symptoms of AL Amyloidosis?

The signs and symptoms of AL Amyloidosis may differ among the affected individuals in type and severity. The kidneys, heart, nervous system, and gastrointestinal system are typically affected. Some of the known general and organ-specific symptoms are as follows:

General signs and symptoms of AL Amyloidosis include:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Skin rashes, which may be purple or red spots
• Rash around the eyes; eyes that appear puffy
• Tingling sensation, numbness
• Anemia
• Clay-colored stools
• Bleeding disorders; problems with proper clotting of blood

Signs and symptoms related to kidneys include:

• Excess protein (albumin) in urine; decreased amounts of albumin protein in blood
• Low blood pressure
• Hyperlipidemia, or increased amount of fat (cholesterol) in blood 
• Edema, or swelling, is observed in hands, feet, legs and face
• Joint stiffness
• Bone cysts
• Carpal tunnel syndrome (resulting in weak grip)
• Blood clot (thrombosis) in the renal vein
• Recurrent kidney problems including kidney failure

Signs and symptoms related to the heart include:

• Shortness of breath with physical exertion or while lying down
• Irregular heartbeats
• Chest pain
• Enlargement of the heart; fluid build-up around the heart
• Excess cholesterol in blood
• Unintended weight loss
• Increased urge to urinate at night
• Edema, or swelling, of the abdomen, hands, feet, legs, and face

Signs and symptoms related to the nervous system include:

• Generalized pain in the body (including muscle spasm)
• Bone abnormalities
• Changes in the skin, nails, and hair
• Numbness and tingling sensation in the limbs
• Unusual sensations (parasthesia) that may be painful
• Insensitivity to extreme temperatures
• Sweating
• Extreme drop in blood pressure while standing up from a seated position
• Lightheadedness
• Loss of voluntary muscle control
• Carpal tunnel syndrome (resulting in weak grip)
• Involuntary urination; inability to empty urinary bladder
• Lack of appetite; feeling of fullness after eating a little food
• Constipation
• Loss of sensation (such as in the hands and feet)
• Loss of coordination and balance
• Inability to respond to emotional inputs
• Having trouble with sleep 
• Problems with sexual performance (erectile dysfunction in men)
• Heart-related abnormalities that may lead to a heart attack
• Stomach-related signs and symptoms that include vomiting and diarrhea
• Headache (in some specific areas)
• Confusion
• Double vision
• Abnormal position of eyelids; drooping eyelids
• Change in the position of eyeballs
• Drowsiness
• Seizures
• Paralysis 

Signs and symptoms related to gastrointestinal system include:

• Thickening of tongue (macroglossia)
• Difficulty in swallowing
• Acid reflux (gastroesophageal reflux disease or GERD)
• Sluggish peristaltic movement (process that moves food in the GI tract by involuntary muscle contractions)
• Nausea
• Loss of appetite; feeling of fullness after eating a small amount of food
• Gastric polyps (nodules on the stomach wall)
• Slowing of stomach emptying (gastrointestinal atony) 
• Pseudo-obstruction of intestines; a sense of blocked intestines without any actual physical blockage
• Abdominal bloating and distension; abdominal pain
• Constipation or diarrhea that may even contain blood
• Clay-colored stools; or, fatty and foul-smelling stools (steatorrhea)

In addition to the above, the following organs and systems may be affected as well, with accompanying symptoms that include:

Signs and symptoms related to skin:

• Small, red blood spots on skin
• Round or irregularly shaped flat spots that may be red, purple, or blue in color
• Raised spots (papules) or plaques near eyelids, neck and genital area
• Dark skin patches, which may be distributed symmetrically on the body
• Skin rashes; nodules on skin
• Itching 
• Brittle nails
• Loss of hair in patches across the skin

Signs and symptoms related to the adrenal glands (in rare cases):

• Fever, headache
• Loss of appetite and weight loss
• Low blood pressure that worsens when the individual stands from a sitting or lying position; this results in lightheadedness
• Muscle weakness and muscle spasms
• Behavioral changes, irritability, anxiety, or depression
• Darkening of the skin, especially in pressure areas such as belt regions, nail, gums, and nipples
• Decreased body hair
• Nausea and vomiting
• Anorexia
• Abdominal pain, chest pain
• Joint pain and neck pain
• Problems with gait
• Problems with intellect
• Decrease in sex drive

Signs and symptoms related to respiratory tract:

• Hoarseness in voice
• Cough, which may contain blood
• Wheezing
• Grating noise while breathing (stridor)
• Labored breathing, which may mimic asthma symptoms
• Shortness of breath
• Repetitive infections in the respiratory tract, which may mead to pneumonia
• Night sweats

When the thyroid gland is affected, the signs and symptoms may include decreased hormone synthesis (hypothyroidism) and increased hormone synthesis (hyperthyroidism), as well as inflammation and swelling of the gland.

General signs and symptoms of thyroid gland amyloidosis: 

• Sore throat, hoarseness
• Swallowing difficulty
• Signs and symptoms of hypothyroidism:
  • Weight gain
  • Feeling cold
  • Dry skin
  • Constipation
  • Weakness
• Signs and symptoms of hyperthyroidism:
  • Rapid heartbeat
  • Sweating
  • Weight loss
  • Mood swings, irritability
• Signs and symptoms of thyroiditis:
  • Swollen thyroid gland
  • Fever
  • Rapid heartbeat
  • Weakness
  • Trembling
  • Changes in menstruation
  • Reduced sex drive
• Signs and symptoms of goiter:
  • Visible swelling in throat
  • Cough
  • Difficulty breathing
  • Feeling of tightness in throat

Signs and symptoms related to the lymphatic system:

• Swelling of lymph nodes, which may or may not be painful
• Obstruction of lymph nodes, causing lymphedema, leading to
  • Fluid accumulation in the body, causing generalized swelling
  • Ascites or fluid accumulation in the peritoneal cavity, which causes swelling of the abdomen
  • Pleural effusion, which is the accumulation of fluid in the lining between the lungs and chest. This can lead to chest pain, cough, and difficulty breathing

Signs and symptoms related to liver:

• Enlarged liver (hepatomegaly)
• Enlarged spleen (splenomegaly)
• Upper abdominal pain; abdominal swelling
• Possible changes in the levels and function of liver enzymes

Signs and symptoms related to spleen:

• Enlarged spleen (splenomegaly)
• Abdominal swelling
• Left abdominal and left shoulder pain

How is AL Amyloidosis Diagnosed?

AL Amyloidosis is diagnosed based on the following tests and exams:

• A thorough physical examination
• Evaluation personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests:
  • Complete blood count (CBC)
  • To assess abnormal antibodies 
  • To check heart function (cardiac biomarkers for stress on the heart)
  • To perform “Freelite assay”, a measurement of light chain immunoglobulins
  • For measuring immunoglobulin, by immunofixation electrophoresis
  • For measuring levels of an enzyme known as alkaline phosphatase
• Urine tests:
  • To check for excess protein (a 24-hour urine test is usually undertaken)
  • For measuring immunoglobulin, by immunofixation electrophoresis
• Electrocardiography and echocardiography for checking heart functions 
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging scans
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Tissue biopsy: A biopsy of an affected organ or tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In case of amyloidosis,
  • Immunohistochemical analysis of tissue samples using anti-AA serum may be performed, to identify the type of Amyloidosis an individual has
  • Biopsy of affected tissue, such as organ tissue, bone, muscle, or fat, may be necessary
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
• Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains 
• Molecular testing to check the type of proteins in amyloid deposits (AL or AA chains) through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of AL Amyloidosis?

AL Amyloidosis may lead to complications such as:

• Kidney failure, resulting in end-stage kidney disease (ERSD)
• Heart failure
• Increased susceptibility to infections
• Stiffness and pain in joints leading to difficulty with movement
• Dizziness and risk of fall, if one stands up too quickly from a seated position

How is AL Amyloidosis Treated?

Currently, there are no treatment options to cure AL Amyloidosis. However, treatment of pre-existing conditions and supportive therapy may aid in improving the quality of the affected individual’s life. The treatment measures are also unique to each individual and depend on the organs affected.

The treatment measures for AL Amyloidosis may include:

• Medications for restoring normal heart function including:
  • Beta blockers
  • Angiotensin converting enzyme (ACE) inhibitors 
  • Angiotensin receptor blockers 
  • Calcium channel blockers
  • Digoxin
• Chemotherapy may be used to destroy cells producing abnormal amyloid proteins. The following chemotherapeutic drugs may be combined with dexamethasone or prednisone 
  • Cyclophosphamide
  • Melphalan
• Targeted therapy such as the following:
  • Specific monoclonal antibodies that recognize faulty protein and destroy cells containing such proteins. Examples include elotuzumab and daratumumab
  • Immune modulating medication such as thalidomide, lenalidomide and pomalidomide
  • Proteasome inhibitors target the proteasome enzyme. This enzyme is responsible for removing defective proteins from cells
• Bone marrow transplantation
• Autologous stem cell transplantation
  • Autologous refers to cells obtained from the affected individual himself/herself
  • This type of transplantation may be required when one undergoes chemotherapy for an underlying condition
  • The stem cells from an individual are collected and stored before high-dose chemotherapy is administered
  • After chemotherapy, the damaged stem cells are replaced by healthy ones
• Blood transfusions for anemia
• Dialysis, in case of kidney failure
• Kidney transplantation for kidney failure
• Pacemaker implantation to improve heart function
• Heart transplantation for severe dysfunction of heart
• Diet: Having frequent and small meals through the day, with reduced fat content

How can AL Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent AL Amyloidosis
• Seeking medical attention for pre-existing conditions that can lead to AL Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of such disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of AL Amyloidosis? (Outcomes/Resolutions)

The prognosis for AL Amyloidosis may be determined by a number of factors, such as the extent of the disorder at diagnosis, underlying bone marrow condition, organs affected, overall health of the affected individual, and his/her response to treatment.

• The outcome is generally favorable, if underlying bone marrow disease as well as amyloidosis, are diagnosed and treated promptly
• Nevertheless, a majority of those with AL Amyloidosis succumb within two years of being diagnosed with the disorder. Approximately, 20% of those affected survive for over 5 years
• The most common causes of death are heart disease and uremia (excess of waste products in blood caused by kidney failure)

Additional and Relevant Useful Information for AL Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum
• In the USA, about 4,000 new cases of AL Amyloidosis are reported each year