Myeloma & Amyloidosis

Multiple myeloma

A cancer of plasma cells (responsible for antibody production)

Clinical features Bone involvement- Pain & fractures, due to lytic lesions, seen in X-rays of skull, ribs, spine, pelvis Can cause hypercalcemia Infection- LRTI & UTI, due to hypogammaglobulinemia Renal failure- Due to hypercalcemia, BJ proteins, amyloidosis, hyperuricemia, UTI Anemia- N/N, due to BM infiltration Neurological symptoms- Weakness, fatigue, confusion due to hypercalcemia Headache, visual changes due to hyperviscosity Radicular pain, paraplegia due to spinal cord compression Carpal tunnel syndrome due to amyloid deposition

Calcium.Renal fai lure.Anemia.Bone lesions- CRAB

Diagnosis Presence of bone pains/pathological fracture,

anemia, raised ESR & elevated creatinine raises possibility of MM

Dx- any two of three- 1- Monoclonal M-band in serum electrophoresis 2- BM with >10% plasma cells- CD56,38,138 +ve 3- C.R.A.B Asymptomatic myeloma-

1 >3 gm% &/or 2, not 3 MGUS- 1 <3 gm%, not 2 or 3

Staging Durie-Salmon staging system- I- Hb>10, Ca normal, normal/osteoporosis, serum paraprotein-

IgG<5 gm% & IgA<3gm%, urinary light chain <4 gm/24 hr II- between I & III III- Hb<8.5, Ca>12, >3 lytic lesions, serum paraprotein-

IgG>7 gm% & IgA>5 gm%, urinary light chain >12 gm/24 hr All- A- Cr<2 or B- Cr>2 International staging system- for Px- I- β2 microglobulin <3.5 mg/L- survival 62 months II- β2 microglobulin 3.5-5.5 mg/L- 45 months III- β2 microglobulin >5.5 mg/L- 29 months

Treatment Initial Rx- Melphalan + Prednisolone- preferred in elderly Thalidomide + Dexamethasone Bortezomib based regimen Curative Rx- offered to patients <65- Autologous SCT Supportive Rx- Epo-anemia, bisphosphonates-prevent fracture, dialysis-ESRD Px- ISS- β2 microglobulin

Amyloidosis Variety of conditions characterized by

deposition of amyloid Amyloid- an altered protein,

with β-pleated sheet structure Amyloid deposition leads to organ dysfunction Identified histologically by Congo red staining,

seen as apple-green birefringence under polarized light

Classification AL- immunoglobulin light chains in MM AA- amyloid associated protien in chronic

inflammatory diseases- TB, RA, SSA Transthyretin- senile systemic amyloidosis β2 microglobulin- long-term hemodialysis Aβ- brain lesions in Alzheimer disease Amylin- pancreas of T2DM patients Calcitonin- medullary carcinoma of thyroid

Manifestation AL- nephrotic syndrome, CHF,

peripheral neuropathy, hepatomegaly, carpal tunnel syndrome, macroglossia

AA- nephrotic syndrome Transthyretin- peripheral neuropathy,

cardiac & renal involvement, purpura β2 microglobulin- joint involvement

Diagnosis

Biopsy of involved organ or rectal submucosa/abdominal fat

Diagnostic ECHO, if heart involved

Treatment

Mainly supportiveRx of underlying disease

Liver/kidney transplantation