A 73 y.o. male presents with a problem with his tongue
What could be wrong?
Our patient had amyloidosis with infiltration of the tongue causing enlargement and indentation of the upper teeth on the enlarged tongue. Amyloid is a clinical puzzle; often presenting in different systems and with sensory neuropathy, autonomic neuropathy or gastrointestinal manifestations.
There are many types of amyloidosis. The word comes from the Greek word for starch because of the way it stains in pathologic specimens, but it is actually formed from misfolded proteins. The nomenclature consists of A for amyloid followed by the protein that is misfolded as in ATTR (transthyrethin) or AL(light chain). More than 30 proteins are known to form amyloid which leads to human disease with over 72 gene mutations found to date. Mutations can be hereditary or acquired.
The most common form of amyloidosis worldwide is AA; related to chronic infection and acute phase reactants circulating in the blood. Rheumatoid arthritis and tuberculosis cause this type of amyloid. The least common type of amyloidosis is localized amyloidosis; occurring in only one organ, for example the larynx or eye.
Localized amyloidosis is thought to be due to a localized mutation in organ specific plasma cells.
The two types seen most frequently in the ED are AL amyloid which is made from abnormal light chains produced by plasma cells in the bone marrow and ATTR made by a transthyretin protein mostly produced in the liver. This protein in its monomer form carries thyroid hormone and Vit A however if it becomes misfolded through a genetic mutation it deposits amyloid plaques in multiple organs including the heart. This form can be hereditary and may be responsible for unrecognized heart failure in older individuals. It is not necessary to do a cardiac biopsy to make the diagnosis since LV thickening and a positive technetium test are considered diagnostic if no light chains are present in the serum or urine.
cardiac scan positive for ATTR
The new treatment for ATTR with monoclonal antibodies results in decreased serum vitamin A levels since it blocks the protein which carries Vit A .These antibodies: tafamidis and acoramidis both led to a reduction in all cause mortality in recent trials.
TO REVIEW
It is confusing. Amyloid is known to be produced after a mutation in a protein; but finding the mutation does not necessarily mean that amyloid will develop. This is true in amyloid beta protein which can be present in the brain without producing Alzheimer’s or islet beta polypeptide mutations which can produce age-related diabetes. Once an organ has been infiltrated; a biopsy will be positive for green birefringence under polarized light or Congo red staining confirming the diagnosis.
Our patient had AL which has a worse prognosis than ATTR. 40% of patients with AL amyloid have tongue involvement. His disease affected multiple organs and he expired within a year. Bone marrow transplantation is recommended but he declined.
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Palladini G , Kastritis E, Maurer, M, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020 136(1): 71-80.