Case 47 – summary

Thank you for all your help with this weeks case! We have had some very helpful renal input this week!
This week we looked at the case of a normally fit 60year old gentleman who presented with peripheral oedema and was found to have proteinuria. Further in investigation revealed that this was due to nephrotic syndrome as a result of renal AL amyloidosis with associated myeloma.
Our patient had base line investigations including a skeletal survey and echo which were normal. 
He was referred down to the national amyloidosis centre for advice on assessment and management of his amyloidosis.
The patient was treated with VCD chemotherapy and his symptoms, as well as his light chains and para protein improved. A bone marrow after 6 cycles of treatment did not reveal any excess of plasma cells and he had an insect able paraprotein. And he went on to have an autologous stem cell transplant.
Systemic AL amyloidosis is a disorder caused by deposition of abnormally proteins which are associated with deposition of monoclonal light chains. These can lead to organ dysfunction/failure and can affect the kidneys/liver/heart/nerves.
Presentation can vary significantly from patient to patient and will depend on site or amyloid deposition, severity of symptoms. A high index of suspicion is needed to ensure a prompt diagnosis.
When AL amyloid is suspected histological assessment is needed to confirm this. This would normal done from sites which are suspected of being involved, however where this is not possible a bone marrow and subcutaneous abdominal fat biopsy should be done. However it should be noted that if amyloid is not seen on these it can not be fully excluded. Staining of specimens with Congo red, which should show an apple green birefringence under polarised light where amyloid is present, should be done on specimens. 
Base line investigations for all patients with suspected amyloid should include urine and serum free light chain analysis. Patients should also have a bone marrow aspirate and trephine, not only to look for amyloid, but to investigate for underlying plasma cell dyscrasia or low grade lymphoma. 
Patients can also get an acquired factor X deficiency and it is important to check a coag and enquire regarding bleeding symptoms.
Extent of organ involvement/dysfunction should be established at diagnosis. This should include a serum amyloid P component scan where possible and should also include cardiac assessment. 
Cardiac assessment is usually via means on an transthoracic echo, which can show organ dysfuction and the myocardium can show a granular sparkling appearance in amyloid deposition is present. It is important to ensure that the person performing the echo is aware of the potential diagnosis as the likely hood of indentification of amyloid is increased. Cardiac MRI can also be used to asses cardiac involvement. BNP and trop T can be used as part of a staging system aimed at guiding prognosis. eg. Dispenzieri et al (2004) 
If there is evidence of neuropathy assessment of autonomic function and nerve conduction should be performed.
All patients should be referred to the national amyloidosis centre (NAC) who are able to provide expertise in diagnosis, management and assessment of patients.
In terms of treatment where available patients should be offered clinical trials. Treatment first line is usually a proteasome inhibitor based treatment. However treatment should take into account age/comorbidities/patient choice. In very poor prognosis patient treatment can be offered, however some patients may not benefit and may decide best treatment would be supportive care/symptom control. IF the patient has underlying lymphoplasmocytic lymphoma rather than myeloma other treatments eg rituximab/bensamustine have been used. It is alway important to ensure treatment has been discussed with the NAC if the patient is too unwell to be seen there at diagnosis.
Where bortezimib is used this is usually given SC, however in patient with severe oedema where there are concerns regarding absorption this can be given IV
Monitoring of treatment should be with serum free light chains/paraprotein monitoring and should be done with each cycle of treatment. If response in not achieved/lost then alternative treatment should be used. 
Thalidomide, lenalidomide and pomalidomide have all been shown to be useful in treatment.
Autologous stem cell transplant with high dose melphalan can be considered following first line treatment in certain patients. This is usually recommended in patient under 70, with egfr >50ml/min, low BNP and trop and low plasma cell % at time of transplant. It is not usually recommended in patients with a poor performance status, those with advanced renal failure, severe neuropathy or significant bleeds due to GI amyloid.
Very rarely patients can get localised amyloid and in certain patients this can be treated with resection/radiotherapy.
In certain young patients with severe renal/cardiac involvement with minimal extra organ involvement. This would need to be discussed with local and national experts.
Thomboprophylaxis should be considered for all patients and this is usually either aspirin or prophylactic LMWH depending upon risk. In some patients with cardiac involvement or severe nephrotic syndrome there can be significant thrombotic risk and anticoagulation may need to be considered. Patients with nephrotic syndrome can develop anti thrombin deficiency, if they are being anticoagulated with LMWH anti Xa need to be monitored. If there is difficulty in achieving therapeutic levels, anti thrombin levels will need to be checked.
The are also experimental treatments currently being investigated that are aimed at targeting the precursor protein in amyloid.
We have have some excellent input in this weeks case, does anyone have any questions, or knowledge they would like to share!!
Remember to use #teamhaem on all your posts to help us follow the case! Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality. TeamHaem are not a position of authority. It is an educational platform to allow discussion and learning.

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