Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Amyloidosis

What is Amyloidosis?

• Amyloidosis is a group of disease in which amyloid fibrils, a type of abnormal protein, accumulate in various tissues
  • These abnormal proteins are the result of a normal protein becoming misfolded
• The disease causes a variety of vague and non-specific symptoms
• There are 36 different types of amyloidosis, which are distinguished by which protein is affected
  • Some forms are localized, while others are considered systemic
• Amyloidosis has been known since at least 1639
• This group of illnesses has an estimated combined prevalence of 30 per 100,000 people affected

How Do You Get It?

• ​Amyloidosis can have a genetic cause or can be acquired. Potential causes may include:
  • Long-term treatment with dialysis
  • Inflammatory diseases, such as rheumatoid arthritis
    • Amyloid serum protein A (AA) amyloidosis is often cause by inflammatory illness
  • Multiple myeloma, a rare blood cancer
  • Inherited DNA mutations
    • This is most often associated with transthyretin amyloidosis
• Ultimately, different forms of the disease tend to have varied causes

What Are the Symptoms?

• Symptoms of amyloidosis vary broadly and can vary depending on which form of the disease is present, where the disease is located, and other factors
• Kidneys
  • Amyloid protein can be deposited in the kidneys, leading to dysfunction
  • Common symptoms include proteinuria and nephrotic syndrome. These symptoms are often associated with AL and AA type amyloidosis
• Heart
  • If amyloid protein is deposited in the heart, it can trigger heart failure. ATTR amyloidosis is often associated with heart issues, particularly in men
• Nervous System
  • Amyloidosis can lead to peripheral neuropathy and dysfunction of the autonomic nervous system
  • Symptoms may include erectile dysfunction, incontinence, and sensory loss
  • If the central nervous system is affected, potentially lethal complications can occur
• Digestive System
  • Bleeding, weight loss, abdominal pain, and heartburn are possible symptoms impacting the digestive tract in amyloidosis
• Musculoskeletal System
  • Amyloid deposits can cause joint pain, tissue inflammation, and carpal tunnel syndrome
• Other symptoms include:
  • Amyloid purpura, or bleeding around the eyes, sometimes called “raccoon eyes”
  • Enlarged tongue, common in AL amyloidosis
    • This can lead to obstructive sleep apnea, changes to taste, and swallowing issues

How Is It Treated?

• Without treatment, amyloidosis can be lethal in as little six months, though this varies depending on the type
• AL amyloidosis can be treated with stem cell transplant followed by chemotherapy with melphalan; however, only about a quarter of patients are eligible for transplant.
  • Others may receive treatment with a chemo regimen of cyclophosphamide-bortezomib-dexamethasone
• AA amyloidosis can improve if the underlying condition is effectively treated.
  • TNF-alpha inhibitors and interleukin-1 inhibitors may be used
• Wild-type and variant ATTR amyloidosis can be treated with tafamidis, a drug that prevents correctly folded proteins from losing stability
  • A number of new drugs have been introduced for genetic ATTR amyloidosis; previously, a liver transplant was the only option
• a clinical trial testing CRISPR gene editing showed some potential for ATTR amyloidosis in 2021.
• Outcomes vary depending on the form of amyloidosis and the age of the patient. Some patients can survive for around a decade or more with proper treatment.

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more from the Amyloidosis Foundation.