Amyloidosis (ICD-10 E85)

Definition

Amyloidosis is a group of diseases in which special proteins (autologous fibrillary proteins) accumulate (aggregate) in the connective tissue outside the cells (extracellularly). The proteins form three-dimensional depots of low molecular weight fibrils (amyloid). Amylodose suppresses the normal tissue and eventually damages the organ functions. Amyloidosis can be divided into more than 30 types depending on the amyloid-forming protein. The most common are:

Amyloid A (AA) amyloidosis

• Caused by another, chronic disease (secondary amyloidosis). Please see more below

Amyloidosis (AL)

• Occurs without any other disease (primary amyloidosis), more below

Other groups

• Family amyloidosis
• Beta-2-microglobulin-related amyloidosis (by prolonged dialysis)
• Age-related (senile) amyloidosis (often with heart failure)
  • Alzheimer's disease with amyloid degeneration in blood vessels in the brain
  • Skin
  • Heart
  • Eye
  • Urinary bladder (bleeding / blood in the urine)
  • Organ specific amyloidosis

Symptoms (both AA and AL amyloidosis)

Kidneys

• Asymptomatic proteinuria, Nephrotic syndrome or progressive renal failure with little proteinuria

Skin

• Purpura, bleeding, papules, skin tumors, pigmentation

Hands

• wax-smooth skin.
• Fingers with bending contractures (palmar fascia affection), knots on the stretch side of forearms

Mucous membranes and gastrointestinal tract

• Bleeding
• Reduced nutrition (weight loss)

Nerves

• Polyneuropathy (Sensory).
• Carpal tunnel syndrome.
• The autonomic nervous system: Orthostatic hypotension. impotence

Heart

• Cardiac failure (restrictive) of unknown cause
• Cardiac arrhythmias (heart block)
• Coronary heart disease

Liver and spleen

• Increased Size (Hepato Splenomegaly)

Oral

• Dryness
• Enlarged tongue (macroglossi)
• Mucosa that easily bleeds

Muscles

• Pseudohypertrophy (enlarged muscle volume)
• Shoulder cushion symptom (Rotator cuff thickened, seen by ultrasound or MR)

Lungs

• Coughing, heavy breathing

Thyroid (metabolism) and adrenal glands

• Enlargement and dysfunction

Skeletal

• Bone cysts that can lead to bone fractures

Diagnosis

Suspected amyloidosis

• Unexplained proteinuria
• Cardiomyopathy (large heart) when echocardiography shows concentric hypertrophy with thickened heart muscle and Pro-BNP in blood test is increasing without known coronary heart disease

Biopsy (tissue test)

• "Gold standard" is tissue sample (biopsy) from affected organ, fatty tissue (sensitivity 90%, Reference: Hallouch, RA), small salivary glands (lip biopsy, sensitivity 50%), bone marrow or rectum (sensitivity 75-85%).
• The samples are stained with Congo red and examined under the microscope with polarized light, but also the use of electron microscopy and scintigraphy is relevant

 AA ("secondary")

The amyloid consists of serum amyloid-A which is an inflammatory component. AA-Amyloidosis has become less frequent with time because the underlying chronic rheumatic inflammation is better treated now. However, in the case of AA amyloidosis, the kidneys are infested with 80%. Some chronic diseases that can cause AA amyloidosis are:

• Familiar Mediterranean Fever (FMF)
• Juvenile Arthritis (Childhood Arthritis)
• Ankylosing spondylitis (Bekhterev's disease)
• Rheumatoid arthritis (RA, arthritis)
• Crohn's Disease and Ulcerative Colitis (IBD)
• Tuberkulosis (Tbc)

 AL "(primary") amyloidosis

Suspected when serum (blood test) or urine electrophoresis shows light chain monoclonal component (λ, κ> 95%) (Myeloma. Mb. Waldenstrøm) and proteinuria or other suspicious symptoms and findings are identified (see above). Amyloid tissue consists of light chains. Nephrotic syndrome with high protein excretion in urine is often detected. Bone marrow biopsy is often done as part of the investigation.

Treatment

AA amyloidosis can be prevented by the use of effective drugs against the underlying disease over time. If AA amyloidosis is detected, intensifying treatment of the underlying disease may still have an effect. Attempts are made to achieve a serum SAA level (in blood) <10 mg / liter. CRP can be used as a surrogate marker.

• By Family Mediterranean Fever (FMF) er Colchicine an effective drug that will be used continuously
• In case of chronic inflammatory autoimmune disease, immunosuppressive treatment is important. Methotrexate and biological drugs such as TNF inhibitors, rituximab and especially tocilizumab (RoActemra) has been shown to be effective in removing serum amyoid A and can be considered as more specific therapy for amyloid potency.

Follow-up

Amyloidosis can be followed up ^{med 123}I - scintigraphy examinations. Regular checks of blood and urine are also done. The follow-up should reveal active inflammation and show that internal organs are functioning normally.

Prognosis

Amyloidosis is basically severe, but depends on what type of amyloidosis is present, which organs are attacked and how widespread the disease is in the body.

Incorrect diagnosis? (Similar diseases / differential diagnoses)

• Glomerulonephritis (Renal insufficiency of another cause)
• Diabetes mellitus (diabetes)
• Hypothyroidism (low metabolism with soft edema)
• Macroglossia for another reason (genetic, hypothyroidism and more)
• Restrictive cardiomyopathy (a form of heart failure)
• Systemic Sclerosis (Scleroderma)
• Scleroderma (scleredema)
• Sjögren's syndrome

Literature

• Merlini G, 2011
• Wikipedia, English
• Grans Compendium in Rheumatology

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