March 2015

Incorporating urinalysis and paraproteinaemia screening into the assessment of multi-organ disease: lessons from AL amyloidosis

Small A, Sarween N, Cockwell P. Smith S.


Introduction:  AL amyloidosis is a rare disease with variable involvement of all major organ systems. The recent introduction of the serum light chain assay (Freelite) has been an important development in screening for AL amyloidosis and other paraprotein-related diseases. However the diagnosis of AL amyloidosis remains challenging. This case illustrates the importance of: (i) incorporating a differential diagnosis of AL amyloidosis and (ii) using the full range of relevant diagnostic tests to screen for the disease in all patients with an un-diagnosed multi-system process.

The case:  A 57 year old Afro-Caribbean gentleman with a history of previous intravenous drug use and chronic Hepatitis C (diagnosed one year previously) presented as a surgical emergency in August 2008 with a several month history of chronic diarrhoea, weight loss and peripheral oedema (including testicular oedema). He had previously been investigated as an outpatient in secondary care, by cross-sectional imaging and a flexible sigmoidoscopy; no unifying diagnosis had been identified. Previous investigations had also identified hypo-albuminaemia (24 g/l in Feb 2014).  He had a blood pressure of 80/50 on and after presentation; this was not responsive to fluid challenges. Further investigations showed a nephrotic syndrome and hypo-adrenalism. He was transferred to the QEHB renal unit for further investigations.

Diagnostic investigations:  A full soluble immunology screen showed a normal serum free light chain, but an elevated serum lambda light chain level. A 24 hour urine test showed a urinary lambda Bence Jones protein. There was no intact immunoglobulin clone by immunofixation electrophoresis. A kidney biopsy showed Amyloidosis by congo-red staining. Immunostaining showed lambda light chain deposition and electron microscopy showed fibril deposition with a classical AL amyloidosis pattern. Bone marrow showed plasma cells with aberrant phenotype ( CD117, cyclin D1 positive) accounting for 3-4% of the total nucleated cell count. A SAP scan was carried out at the National Amyloidosis Centre and this confirmed bowel, adrenal and renal involvement.

Management:  He received (i) management of the complications of the disease: fludrocortisone and hydrocortisone for hypoadrenalism; salt restriction, diuretics and ACE inhibition for nephrotic syndrome (he required a 12 litre diuresis); anti-thrombotic prophylaxis and a statin: (ii) bortezomib and dexamethasone based chemotherapy. At this early stage of treatment (first cycle chemotherapy) blood pressure has improved and oedema has resolved. In AL amyloidosis the large majority of patients respond to chemotherapy, but resorption of tissue amyloid is slow and therefore regression of organ involvement can take several years from initiation of treatment.

This case illustrates:  (i) the importance of early urinalysis in any patient with hypo-albuminaemia and/or any suggestion of a multi-system disease; (ii) that each patient with AL amyloidosis has a unique phenotype; this relates to the physico-chemical properties of the involved light chain clone; (iii) that both serum and urine light chain assays are required to maximise the sensitivity of the screening tools that are available; ultimately a tissue diagnosis is required to confirm amyloidosis.

An example of a SAP scan:  The SAP scan below demonstrates how they can be used to determine disease spread and response to treatment.  The image has been reproduced from the Patient Information Site from the   SAP scan images for the patient discussed are not available.

Sequential SAP scans from a patient with AL amyloidosis. In 2005 the scan showed significant deposits in the liver and spleen. The scan in 2009 showed considerable shrinkage of the deposits after a good response to treatment. In 2011 there was a relapse and the scan showed amyloid building up, this time in the kidneys. 
Reproduced from: Journal of Immunological Methods 384;Issues 1-2, 2012, 92-102






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