In the immunology laboratory, we can detect if there is an excessive amount of immunoglobulin in the blood and if so, how much. We can also detect the amount of immunoglobulin light chains in the blood and whether they are present in the urine. To do this, we use protein migration techniques using an electrical field (electrophoresis) and ‘immunological’ techniques: immunofixation, immunonephelometry. These further examinations help the diagnostic process and the treatment which then follows. For treatment to be successful, the amount of immunoglobulin and/or free light chains must be reduced.
Senile or ‘wild type’ Amyloidosis
Diagnosing senile amyloidosis is often a process of elimination for patients who suffer from heart failure and concentrated cardiac hypertrophy and it can only be confirmed once the possibility of other amyloidosis types has been eliminated.
Giving a definite diagnosis of senile amyloidosis is only possible using a myocardial biopsy to locate the transthyretin amyloid deposits. However, performing a biopsy on elderly patients has ethichal implications as it can lead to complications (myocardial perforation, lesions on the tricuspid valve).
Histological evidence of amyloid deposits in systemic senile amyloidosis can be obtained through biopsies of non-cardiac tissues (salivary glands, carpal tunnels, the rectum, abdominal fats) or subcutaneous fats. However, non-cardiac biopsies for systemic senile amyloidosis are less reliable than for other types of amyloidosis and so a negative result does not always mean that this can be ruled out as a possibility.
Senile amyloidosis can also be found in the aforementioned tissues without there being any damage to the heart. However, this does not mean that cardiac problems will not occur later on. Patients whose synovial biopsies show no cardiopathy at the time of surgical treatment for their carpal tunnel treatment but do show TTR amyloidosis, can develop cardiopathies several years later. Moreover, patients who have been treated for carpal tunnel syndrome are often found to have systemic senile amyloidosis four or five years later.
Below is the diagnostic approach for a patient suspected of having amyloidosis.
This is the diagnostic strategy for suspected cardiac amyloidosis. The MRI can be carried out if the patient has a pacemaker, but an arrhythmia specialist will have to either switch it off or regulate it and then check it after the examination. Implanting patients with pacemakers which are compatible with MRIs makes it easier to evaluate a cardiopathy in this way.
Hereditary TTR Amyloidosis
Hereditary Amyloidosis can appear in many different clinical forms. A family history of the disease really helps diagnosis, but this has not been present in around half of the cases found in French families. Before there are signs of a developing axonal neuropathy, the diagnosis must be confirmed by evidence of amyloid deposits from a simple tissue biopsy (the salivary glands, subcutaneous fat) and by evidence of a pathological mutation found in an ATTR gene sequencing test. Genetic and histological confirmation is necessary, especially because heavy treatments like liver transplants might be necessary. If there is no family history of the disease, then diagnosis is difficult. This is the situation faced by half of the French families found to have the disease, particularly in cases where the disease is late-onset, i.e. after the age of 50. This type of amyloidosis often has a mix of symptoms (cardiological and neurological) but it can be the case that just the heart is affected. In cases like this, the biopsy is necessary to detect amyloid deposits and confirm the diagnosis. If histological tests confirm that it is amyloidosis, the diagnosis must then be further refined by an ATTR gene sequencing test and further blood and urine tests. The objective is to identify the type of amyloidosis (AL, TTR, AA) and guide treatment because this can differ greatly from case to case.