Amyloidosis 4/5 (12)

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Primary (AL) amyloidosis. Large tongue with bite marks. Small nodules in the skin of the chest. Kumar S, - Mediterr J Hematol Infect Dis (2013). CC BY 2.0

Amyloidosis (ICD-10 E85)

Definition

Amyloidosis is a group of diseases in which special proteins (autologous fibrillar proteins) coalesce (aggregate) in the connective tissue outside the cells (extracellular). The condition with amyloid -deposition displaces the normal tissue and eventually damages the organ functions. Amyloidosis can be seen in chronic inflammation in rheumatic diseases (type serum amyloid A (SAA) / AA amyloidosis / secondary type). The primary form (systemic light-chain, AL type) has disease features that can be misinterpreted as rheumatic disease (please see differential diagnoses below). AA amyloidosis is related to perennial systemic inflammation in familial Mediterranean feverJuvenile arthritisRheumatoid arthritisAnkylosing spondylitis,  Muckle Wells SyndromeInflammatory bowel disease and such. Localized amyloidosis is rare and is defined by the fact that amyloid is produced and deposited in an isolated part of the body. There are no monoclonal, light chains in the blood and the prognosis is excellent. Amyloidosis is investigated and followed up by a specialist in the most affected organ (s), possibly. also at a hematologist. The rheumatologist should be able to recognize the symptoms and distinguish them rheumatic connective tissue diseases, Vasculitis and arthritis diseases.

A Swedish study found that the number of new cases was 1-2 / 100.000 inhabitants. AL amyloidosis is more common than AA type. Highest incidence among 60-80 year olds (Hemminki K. 2012).

Symptoms (both AA and AL amyloidosis)

Amyloidosis with pigment changes in skin. Yang W, BMC Dermatol. (2011). CC BY 2.0

Common symptoms include heart failure with preserved pump function and kidney manifestations with egg white in the urine (proteinuria).

Heart manifestations can begin with angina, low blood pressure and arrhythmia reference: (Deshai HV, 2010). Heart failure (restrictive) of otherwise unknown cause.

Kidneys. Loss of proteins over time as by Nephrotic syndrome Painless swelling / edema is felt, especially in the ankles and calves.

Enlarged organs due to deposition of amyloid in the liver (hepatomegaly), spleen (splenomegaly), tongue (macroglossia) and salivary glands (dryness symptoms). 

Nervous System. Numbness and nerve pain in hands and feet (peripheral neuropathy, polyneuropathy (sensory)) and affected general condition with weight loss (in intestinal disorders) and fatigue are also common (reference: Al Hamed R, 2021). Carpal tunnel syndrome. Affected autonomic nervous system: Low blood pressure with dizziness when standing (orthostatic hypotension). Impotence.

Swelling over shoulder joints. Amyloid shoulder pads, shoulder pad symptom with rotator cuff thickening is seen by ultrasound or MRI and is also due to amyloid deposits (reference: Liepnieks JJ, 2008).

Hands. wax-smooth skin. Fingers with flexion contractures (palmar fascie affection), knots on the stretching side of forearms.

Skin. Minor bleeding (purpura), small nodules under the skin (papules), pigment change, pigmentation. Other symptoms are waxy thickened fingers and bleeding under the skin (ecchymosis). The brain is not attacked.

Muscles. Pseudohypertrophy (enlarged muscle volume)

Skeleton / bone substance. Bone cysts that can lead to bone fractures

Mucous membranes, mouth and gastrointestinal tract. Dryness (eyes, mouth), bleeding from mucous membranes, Enlarged tongue (macroglossia), decreased nutrient uptake, weight loss.

Lungs. Cough, heavy breathing

Thyroid gland and adrenal glands. Magnification and dysfunction

Examinations

Amyloidosis in kidney tissue. Wikimedia. Nephron / creativecommons.org / Wikimedia. CC SA 3.0

Medical history includes registration of current symptoms (see above.

Clinical examinations includes systematic assessment of mouth with tongue, skin, shoulders, hands, heart, liver and spleen.

Blood tests may include cell counts, liver and kidney function tests, albumin, as well as NTPro-BNP and troponin T. Protein electrophoresis. Laser capture microdissection and tandem mass spectrometry (LCM-MS) are used for subtyping and are more specific than anti-drug based methods / immunohistochemistry (reference: Wisniowski B, 2020).

Urine examined for protein secretion and protein / creatinine clearance. Urine electrophoresis.

Tissue samples (biopsy). The diagnosis is ensured by biopsy that can be taken from different tissues. Biopsy taking is usually uncomplicated, but one should be aware of the general increased risk of bleeding in amyloidosis. Biopsy is often selected from adipose tissue over the abdomen (sensitivity> 80%), rectum or small salivary glands in the lower lip (reference: Hallouch, RA). The samples are stained with Congo red and examined under a microscope with polarized light, but the use of electron microscopy and scintigraphy is also relevant.

ECG can reveal arrhythmias in cardiac manifestations.

Amyloidosis subgroups

Amyloidosis can be divided into more than 30 types depending on the protein that forms the amyloid. The most common are:

Amyloid A (AA) - type

Caused by another, chronic disease (secondary amyloidosis). Please see under "Definition" opposite.

Amyloidosis (AL) type)

Occurs without other disease (primary amyloidosis)

Other amyloidosis-related conditions

  • 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
  • Localized Skin-amyloidosis
  • Localized cardiac amyloidosis
  • Eye-amyloidosis
  • Urinary bladder (bleeding / blood in the urine)
  • Organ-specific amyloidosis, other organs

Diagnosis

Suspected amyloidosis by:

  • Unexplained proteinuria
  • Cardiomyopathy (large heart)

 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.

Similar diseases / differential diagnoses

Treatment

Today's treatment depends on the underlying cause of the disease, the type of amyloidosis and the patient's condition.

In AA amyloidosis is one of the attack targets is aimed at inhibiting the activity of the underlying disease to reduce risk or exacerbation. This reduces the liver's capacity to produce SAA as high serum levels of SAA increase the risk of amyloid deposition. Among immunosuppressive drugs, IL-6 inhibitors (tocilizumab) have been shown to be effective in various manifestations (Inoue D, 2010; Redondo-Pachón MD, 2013). By Family Mediterranean Fever (FMF) er Colchicine an effective drug to be used continuously. In chronic, inflammatory autoimmune disease, immunosuppressive therapy 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.

In AL amyloidosis one first considers whether autologous stem cell transplantation is relevant (selection criteria). This means that the age is not too high, that the heart, kidneys and lungs work well enough. Overall, approx. 20% such treatment (reference: Al Hamed R, 2021). Supplementary literature is also referred to for the treatment of AL amyloidosis and other types (reference: Ihne S, 2020).

Follow-up

Amyloidosis can be followed up by 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

Systemic amyloidosis is initially serious, but depends on the type of amyloidosis present, which organs are attacked and how widespread the disease is.

Literature


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