AB0901 TWO TYPES OF SYSTEMIC AMYLOIDOSIS IN A SINGLE PATIENT

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Background The systemic amyloidoses are a group of rare diseases, in which extracellular deposition of a variety of proteins in an abnormal fibrillar confirmation results in life-threatening organ dysfunction. Acquired and hereditary amyloidoses differ in their precursor proteins and predilection for specific organ involvement. Objectives To describe the history of two types of amyloidosis developing consecutively in a single individual. Methods Targeted biopsies were used to confirm the presence of amyloid by Congo red staining viewed under polarized light, while immunohistochemistry and mass spectrometry were used to characterize the amyloid fibril type. I123labeled serum amyloid P component (SAP) scintigraphy was performed to map the distribution of amyloid deposits. Results We report a woman of Sudanese origin who presented aged 31 with dysuria and haematuria. She was found to have an estimated Glomerular Filtration Rate of 38 ml/min and no proteinuria, and a renal biopsy demonstrated AA amyloid deposition. An I-123 labelled SAP scan demonstrated a small amount of amyloid confined to the kidneys. She had no overt underlying inflammatory disease, an infectious diseases work up, including blood borne viruses, was negative and serial measurement of serum amyloid A protein showed no significant elevation with a median of 5 mg/L. Management was blood pressure control only, and her inflammatory markers and renal function remained stable until she was lost to follow up 3 years later. Thirteen years after her renal biopsy she represented in end stage renal failure with a history of weight loss, deranged liver function tests and marked easy bleeding. Further investigation demonstrated well controlled C reactive and serum amyloid A proteins, and an IgG lambda M-band with no serum free light chain bias. A bone marrow demonstrated 7% neoplastic plasma cells and was complicated by a retroperitoneal bleed. An SAP scan now showed a large amyloid load with amyloid deposition in the liver and spleen obscuring the kidneys. Review of the bone marrow and a duodenal biopsy demonstrated amyloid deposition which was AL (lambda) type by both immunohistochemistry and proteomic analysis after laser dissection and mass spectroscopy. Review of the original biopsy confirmed AA type amyloid by both immunohistochemistry and proteomics. Six-cycle chemotherapy for AL amyloidosis was administered with complete clonal response. She remained on dialysis and died four years later of a cerebrovascular accident. Conclusion This is the first reported case of two types of amyloidosis in a single patient. The underlying inflammatory driver of her AA amyloidosis was never identified and given that she had migrated some years earlier from Africa, previous chronic infection that has resolved or responded to non-disclosed prior treatment was thought to be the most likely cause. Whether the subsequent development of AL amyloidosis was pure chance remains unclear. Theoretically chronic inflammation/infection may drive generation of oligoclonal bands with the potential for monoclonal breakthrough. Whether her AA amyloid deposits played a role by providing a template for deposition of subsequent AL amyloidosis derived from an entirely separate precursor protein is also unknown although this theoretically possible and has been shown in reverse in mice models.