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

• Amyloidosis of Spleen

What is Splenic 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 (slender fibers). An amyloid build-up can occur locally in only one organ or may occur throughout the body. The deposition of amyloid proteins in the spleen leads to Splenic Amyloidosis, which may result in enlarged spleen and abdominal discomfort
• There are 5 major types of amyloidosis which can lead to Splenic Amyloidosis:
  • AL amyloidosis that occurs when bone marrow produces too much amyloid protein, creating light (L) chains
  • AA amyloidosis, when amyloid proteins build up secondary to a chronic disease
  • Hereditary amyloidosis: It is an inherited form of the disease; the amyloid build-up primarily affects the kidneys and nerves
  • Wild-type ATTR amyloidosis: This form leads to amyloid protein deposits in elderly adults, particularly in the heart and tendons
  • Dialysis-related amyloidosis: This occurs in individuals who have undergone dialysis for a long time. The amyloid protein tends to get deposited in the tendons and joints
• Splenic Amyloidosis may be observed in AA, AL, and hereditary subtypes of Amyloidosis. Splenic Amyloidosis occurs in older adults, and men are more susceptible to the condition than women
• The treatment involves effectively managing amyloidosis and the underlying condition causing it. The outcome of Splenic Amyloidosis depends on the underlying condition causing it, the severity of symptoms, and the response of the affected individual to treatment(s)

Who gets Splenic Amyloidosis? (Age and Sex Distribution)

• The exact overall prevalence of Splenic Amyloidosis is not known; however, the condition is extremely rare
• It is reported in AA, AL, and hereditary subtypes of Amyloidosis. In AL Amyloidosis, 4-13% of affected individuals are said to be affected by Splenic Amyloidosis
• The condition is more frequent in older adults and may occur worldwide. Typically, men are more susceptible to the condition than women

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

The following are some known risk factors for developing Splenic Amyloidosis:

• Advancing age
• Male gender
• A family history of Amyloidosis
• Any condition that affects the antibody-producing cells in the body, including benign monoclonal gammopathy, malignant lymphoma, and multiple myeloma
• Chronic infections or inflammatory disease, including rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, and tuberculosis
• Chronic inflammatory conditions such as:
  • Arthritis, including rheumatoid arthritis, juvenile inflammatory arthritis, psoriatic arthritis, and ankylosing spondylitis
  • Inflammatory bowel disease (IBD) such as ulcerative colitis
  • Chronic infections, including:
  • Tuberculosis
  • Leprosy
  • Bronchiectasis
  • Osteomyelitis
  • Skin infections (in drug abusers who use needles to inject themselves)
  • Chronic infection in skin with burns
  • Chronic kidney infections (pyelonephritis)
  • Whipple’s disease
• Poorly-controlled diabetes
• Infectious diseases such as HIV/AIDS
• Cystic fibrosis; individuals with this condition are prone to repeat infections
• Certain cancers, such as Hodgkin’s lymphoma and renal cell carcinoma
• Family history of certain hereditary disorders that may include:
  • Familial Mediterranean fever (FMF)
  • Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
  • Hyper immunoglobulin D syndrome and periodic fever syndrome (HIDS)
  • Cryopyrin associated periodic syndrome (CAPS)
  • Majeed syndrome

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 Splenic Amyloidosis? (Etiology)

• Splenic Amyloidosis develops consequent to AA-, AL-, and hereditary subtypes of Amyloidosis
• Regardless of the subtype of Amyloidosis, abnormal proteins are generated, which undergo misfolding to form amyloid proteins. The amyloid protein fibrils circulate in the bloodstream and get deposited in the spleen
• However, clinically significant manifestation of symptoms is rare in Splenic Amyloidosis

What are the Signs and Symptoms of Splenic Amyloidosis?

The signs and symptoms of Splenic Amyloidosis may vary among affected individuals in severity. The symptoms may include:

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

Since Splenic Amyloidosis rarely occurs in isolation but coexists with symptoms involving other major organs and tissues, additional signs and symptoms that may be present include:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Skin rashes, which may be purple or red spots
• Rash around eyes
• Eyes that appear puffy
• Tingling sensation
• Numbness
• Anemia
• Clay-colored stools
• Carpal tunnel syndrome (resulting in weak grip)
• Bleeding disorders
• Problems with proper clotting of blood

How is Splenic Amyloidosis Diagnosed?

The diagnosis of Splenic Amyloidosis may include general tests to ascertain the subtype of amyloidosis (and its underlying cause), as well as specific tests to assess damage to the structure and function of the spleen.

The following methods may be used to diagnose Amyloidosis of Spleen:

• A thorough physical examination
• An evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests to assess:
  • Complete blood count (CBC)
  • Perform “Freelite assay”, a measurement of light chain immunoglobulins
  • Measure immunoglobulin by immunofixation electrophoresis
  • Assess liver function by measuring liver enzymes
  • To assess abnormal antibodies
  • To check heart function (cardiac biomarkers for stress on the heart)
  • For measuring levels of an enzyme known as alkaline phosphatase to assess liver function
• Urine tests to:
  • Check for excess protein (a 24-hour urine test is usually done)
  • Measure immunoglobulin by “immunofixation electrophoresis”
• Electrocardiography and echocardiography for checking heart functions
• Imaging tests to assess amyloid deposits in and damage to organs, tissues, and bones
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • 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 (in this case, the liver) 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 microscope findings, the pathologist arrives at a definitive diagnosis. Examining the biopsy sample under a microscope by a pathologist is considered the gold standard in arriving at a conclusive diagnosis. In Splenic Amyloidosis,
  • Immunohistochemical analysis of tissue samples using anti-AA serum may be performed to identify the type of amyloidosis an individual has
  • 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 genetic testing to check for mutation(s) in genes known to cause various types of amyloidosis
• Molecular testing to check the type of proteins in amyloid deposits through mass spectrophotometry

What are the possible Complications of Splenic Amyloidosis?

The potential complications of Splenic Amyloidosis may include:

• Spontaneous rupture of the spleen, which can result in
• Confusion
• Dizziness
• Bleeding in the abdominal cavity

How is Splenic Amyloidosis Treated?

The following are some treatment options for Splenic Amyloidosis:

• Chemotherapy with high-dose intravenous Malphalan
• Autologous peripheral blood 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
  • Healthy ones replace the damaged stem cells after chemotherapy
• Surgical removal of spleen

Splenic Amyloidosis generally does not occur in isolation and is associated with the involvement of many other organs in systemic AA, AL, and hereditary subtypes of amyloidosis. Therefore, additional treatments pertaining to these subtypes and their underlying cause are often necessary.

How can Splenic Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Splenic Amyloidosis
• Seeking prompt medical attention for pre-existing conditions that can lead to amyloidosis, which consequently causes Splenic Amyloidosis, is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

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

What is the Prognosis of Splenic Amyloidosis (Outcomes/Resolutions)

• The prognosis for Splenic Amyloidosis may be determined by many factors, such as the extent of the disease, the overall health of the affected individual, and his/her response to treatment
• Even though Splenic Amyloidosis is rare, it results in an increased risk of splenic rupture. The rupture of the spleen can cause abdominal bleeding and can be life-threatening

Additional and Relevant Useful Information for Splenic 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 many reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum