History

Fact Explanation
Introduction Multiple myeloma is a malignant condition characterized by clonal proliferation of B- lymphocyte derived plasma cells. So there is an accumulation of the plasma cells in the bone marrow. In here a single clone (monoclonal) of plasma cells produce identical immunoglobulines. Incidence is around 5: 100 000 and men are slightly more affected than women. The peak age of the disease is 70 years Diagnostic criteria: 1) Monoclonal protein band in the serum or urine electrophoresis 2) Increased plasma cells found on bone marrow biopsy 3) Evidence of end organ damage from myeloma - Hypercalcaemia - Renal insufficiency - Anaemia - Bone lesions; a skeletal survey is performed after diagnosis to detect bone disease. [1][2][3].
Bone pain Patients will commonly present with intractable, continuous back pain. This is resulting from the vertibral collapse following osteolytic bone lesions. Other than that there can be long bone pains and rib pains [4][5][6].
History of sudden on set fractures/ sudden onset falls Extensive lytic lesions of the bones can finally result pathological fractures especially in long bones [4][5][6].
Features of anaemia There will be easy fatiguability, lethargy, body weakness, shortness of breath. With the infiltration of the bone marrows there will be disturbances to erythropoisis causing anaemia[7][8][9].
Recurrent infections Patient will get recurrent infectons like respiratory tract infections, diarrhoea, pyelonephritis, herpes zoster with multiple myeloma due to neutropenia, defective anti body production and alterations in cell mediated immunity[10][11][12].
Increased bleeding tendency There will be spontaneous bleeding ( eg: Gum bleeding, nasal bleeding, haematuria, PV bleeding) and excessive bleeding (eg: excessive bleeding from a small wound, menorrhagia). These are due to thrombopenia with bone marrow infiltration, defective clotting factors and interference of platelet function with the myeloma protein[13][14][15].
Features of renal failure Both acute & chronic renal failure could occur with this condition giving symptoms like reduced urine out put, generalized body swelling, haematuria and uremic features ( nausea, vomiting, loss of appetite, confusion/ drowsiness). Renal failure can occur with several reasons like the deposition of the light chains inside the renal tubules with heavy bence-Jones proteinuria, hypercalcaemia causing renal stones and recurrent urinary tract infections and amyloidosis. With the time and severity of the disease acute renal failure can finally end up in chronic renal failure [16][17][18].
Features of amyloidosis This primay amyloidosis is occur with the extracellular deposition of the abnormal protein produced in multiple myeloma. These proteins are resistant to regeneration and they deposit in an abnormal fibrillar form. patient will have multi systemic features. eg: - generalized body swelling, reduced urine out put, protein urea with renal involvement. - shortness of breath, swetting, faintisness, palpitation, chest pain with cardiac involvement ( restrictive cardiomyopathy, arrhythmia, angina) - distal muscle weakness, sensory loss, swetting, diarrhoes with peripheral nervous system involvement (periperal and autonomic neuropathy). -diarrhoes, abdominal pain, rectal bleeding with gastrointestinal involvement ( malabsorption, perforation, haemorrhages, obstruction) - Bruising, periorbital red spots with vascular involvement (purpura).[19][20][21]
Constitutional symptoms With this malignant condition patient will develop various constitutional symptoms like low grade fever, recent significant weight loss, malaise, lethargy and loss of appetite[6][30][31].
Features of hypercalcaemia Abdominal pain, vomitting, constpation, polyurea, polydipsia, depresson, anorexia, weigt loss, tiredness, weakness, confusion are some of features. Hypercalcaemia resulting from the bone lysis[5][22][23].
Features suggestive of spinal cord compression There will be progressive limb weakness, sensory loss, bladder/ bowel involvement. Spinal cord compression resulting from vertebral body involvement[24][25][26].
Features suggestive of hyper viscosity With the increase production of immunoglobuline due to multiple myeloma, there will be increased viscosity of the blood. This can affect multi systems giving symptoms like lethargy, confusion, spontaneous mucosal bleeding ( eg: haematurea, haematamesis, malena), Central nervous system disturbances (eg: confusion, body weakness, sensory loss crenial nerve involvement) and visual disturbances.[27][28][29]
References
  1. KYLE RA, RAJKUMAR SV. Multiple myeloma Blood [online] 2008 Mar 15, 111(6):2962-2972 [viewed 14 November 2014] Available from: doi:10.1182/blood-2007-10-078022
  2. ZHAN F, HUANG Y, COLLA S, STEWART JP, HANAMURA I, GUPTA S, EPSTEIN J, YACCOBY S, SAWYER J, BURINGTON B, ANAISSIE E, HOLLMIG K, PINEDA-ROMAN M, TRICOT G, VAN RHEE F, WALKER R, ZANGARI M, CROWLEY J, BARLOGIE B, SHAUGHNESSY JD JR. The molecular classification of multiple myeloma Blood [online] 2006 Sep 15, 108(6):2020-2028 [viewed 14 November 2014] Available from: doi:10.1182/blood-2005-11-013458
  3. BLADé J, ROSIñOL L. Changing paradigms in the treatment of multiple myeloma Haematologica [online] 2009 Feb, 94(2):163-166 [viewed 14 November 2014] Available from: doi:10.3324/haematol.2008.002766
  4. KRISTINSSON SY, MINTER AR, KORDE N, TAN E, LANDGREN O. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management Expert Rev Mol Diagn [online] 2011 Jul, 11(6):593-603 [viewed 14 November 2014] Available from: doi:10.1586/erm.11.44
  5. NEWMAN DB, KEARNS JJ, BECKMAN TJ. 54-Year-Old Woman With Fatigue, Back Pain, and Hypercalcemia Mayo Clin Proc [online] 2009 Dec, 84(12):e9-e12 [viewed 14 November 2014] Available from: doi:10.4065/mcp.2008.0718
  6. SOUTHERST D, DUFTON J, STERN P. Multiple Myeloma presenting as sacroiliac joint pain: a case report J Can Chiropr Assoc [online] 2012 Jun, 56(2):94-101 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364058
  7. BIRGEGåRD G, GASCóN P, LUDWIG H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY Eur J Haematol [online] 2006 Nov, 77(5):378-386 [viewed 14 November 2014] Available from: doi:10.1111/j.1600-0609.2006.00739.x
  8. TING WC, CAVILL I, JACOBS A, KAABA S, MAY A, SMITH S, WHITTAKER JA. Anaemia in patients with myelomatosis. Br J Cancer [online] 1982 Jun, 45(6):887-894 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011046
  9. BLACK J, MUSCAT-BARON J. Megaloblastic Anaemia and Multiple Myeloma Br Med J [online] 1963 Sep 14, 2(5358):682 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872801
  10. KHALAFALLAH A, MAIWALD M, COX A, BURNS D, BATES G, HANNAN T, SEATON D, FERNANDOPULLE B, MEAGHER D, BRAIN T. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation or Treated with Immunomodulatory Agents. Mediterr J Hematol Infect Dis [online] , 2(1):e2010005 [viewed 14 November 2014] Available from: doi:10.4084/MJHID.2010.005
  11. CHAPEL HM, LEE M. The use of intravenous immune globulin in multiple myeloma. Clin Exp Immunol [online] 1994 Jul, 97(Suppl 1):21-24 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550368
  12. JOLLES S, SEWELL W, MISBAH S. Clinical uses of intravenous immunoglobulin Clin Exp Immunol [online] 2005 Oct, 142(1):1-11 [viewed 14 November 2014] Available from: doi:10.1111/j.1365-2249.2005.02834.x
  13. ZHENG L, ZENG Z, LIN J, CHEN J. IgM multiple myeloma presenting with bleeding tendency: a case report with immunophenotype analysis Oncol Lett [online] 2011 Jan, 2(1):55-57 [viewed 14 November 2014] Available from: doi:10.3892/ol.2010.216
  14. LIN M, ZHU J, SHEN H, HUANG J. Gastrointestinal bleeding as an initial manifestation in asymptomatic multiple myeloma: A case report and review of the literature Oncol Lett [online] 2013 Jan, 5(1):218-220 [viewed 14 November 2014] Available from: doi:10.3892/ol.2012.945
  15. TAIWO E, WANG H, LEWIS R. Treatment of Coexisting Chronic Neutrophilic Leukemia and Light Chain Multiple Myeloma with Hydroxyurea, Bortezomib, and Dexamethasone Case Rep Hematol [online] 2014:869395 [viewed 14 November 2014] Available from: doi:10.1155/2014/869395
  16. BOOTH LJ, MINIELLY JA, SMITH EK. Acute renal failure in multiple myeloma Can Med Assoc J [online] 1974 Aug 17, 111(4):334-335 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947712
  17. MACKENZIE MR, WUEPPER KD, JORDAN G, FUDENBERG HH. Rapid renal failure in a case of multiple myeloma: the role of Bence Jones proteins Clin Exp Immunol [online] 1968 Jul, 3(6):593-601 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578955
  18. BLACKMAN SS JR, BARKER WH, BUELL MV, DAVIS BD. ON THE PATHOGENESIS OF RENAL FAILURE ASSOCIATED WITH MULTIPLE MYELOMA. ELECTROPHORETIC AND CHEMICAL ANALYSIS OF PROTEIN IN URINE AND BLOOD SERUM J Clin Invest [online] 1944 Mar, 23(2):163-166 [viewed 14 November 2014] Available from: doi:10.1172/JCI101479
  19. PRUZANSKI W, KATZ A. Clinical and laboratory findings in primary generalized and multiple-myeloma-related amyloidosis. Can Med Assoc J [online] 1976 May 22, 114(10):906-909 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1957073
  20. NAIR DR, MEHTA A, MIKHAILIDIS DP, WINDER AF. Multiple myeloma with primary amyloidosis. J R Soc Med [online] 1997 Sep, 90(9):502 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296530
  21. JACOBS P, SELLARS S, KING HS. Massive macroglossia, amyloidosis and myeloma. Postgrad Med J [online] 1988 Sep, 64(755):696-698 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428968
  22. OYAJOBI BO. Multiple myeloma/hypercalcemia Arthritis Res Ther [online] 2007, 9(Suppl 1):S4 [viewed 14 November 2014] Available from: doi:10.1186/ar2168
  23. CRAWFORD SM. Alpha-2 HS glycoprotein in the hypercalcaemia of multiple myeloma. Br J Cancer [online] 1984 Jun, 49(6):813-815 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976854
  24. HA KY, KIM YH, KIM HW. Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective J Korean Neurosurg Soc [online] 2013 Aug, 54(2):151-154 [viewed 14 November 2014] Available from: doi:10.3340/jkns.2013.54.2.151
  25. CHAKRABORTI C, MILLER KL. Multiple myeloma presenting as spinal cord compression: a case report J Med Case Reports [online] :251 [viewed 14 November 2014] Available from: doi:10.1186/1752-1947-4-251
  26. SINI V, KAMTCHUM TJ, TEGUEU CK, DJIENTCHEU VD. Multiple myeloma revealed by spinal cord compression and herpes zoster in a 36-year-old Cameroonian Pan Afr Med J [online] :21 [viewed 14 November 2014] Available from: doi:10.11604/pamj.2013.16.21.2908
  27. MACKENZIE MR, FUDENBERG HH, O'REILLY RA. The hyperviscosity syndrome: I. In IgG myeloma. The role of protein concentration and molecular shape J Clin Invest [online] 1970 Jan, 49(1):15-20 [viewed 14 November 2014] Available from: doi:10.1172/JCI106213
  28. PRUZANSKI W, CHU R, DAMJI NF, GALLER S, NORMAN CS. Anemia, splenomegaly and hyperviscosity syndrome. Can Med Assoc J [online] 1980 Oct 18, 123(8):731-737 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704856
  29. MCGRATH MA, PENNY R. Paraproteinemia: blood hyperviscosity and clinical manifestations. J Clin Invest [online] 1976 Nov, 58(5):1155-1162 [viewed 14 November 2014] Available from: doi:10.1172/JCI108568
  30. SHARMA A, KAUSHAL M, CHATURVEDI NK, YADAV R. Cytodiagnosis of multiple myeloma presenting as orbital involvement: a case report Cytojournal [online] :19 [viewed 15 November 2014] Available from: doi:10.1186/1742-6413-3-19
  31. SZETO JS, PEREZ JA JR. Multiple Myeloma Presenting as Pulmonary Renal Syndrome Methodist Debakey Cardiovasc J [online] 2013, 9(1):58-59 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600889

Examination

Fact Explanation
General examination Look for generalized well being and whether patient is in pain. Examine for pallor, dehydration, macroglossia and shoulder pad sign (occur with amyloidosis) and evidence of weight loss[1][2][3][4][5][6].
Examination of the skeletal system Examine the back, long bones for local tenderness and fractures ( bony deformity, redness, haematoma formation, local tenderness)[7][8][9].
Respiratory system examination look for signs of respiratory tract infections like coughing, wheezing, shortness of breath, inflammed tonsils, ear discharge and lung signs (crepitatins, effusion, fibrosis)[10][11][12].
look for evidence of increased bleeding tendency Skin examination for easy bruising marks with ecchimotic patches/patechiae/ purpura. Examine mucus membranes for spontaneous bleeding eg; gum bleeding, nasal bleeding, haematuria, per vaginal bleeding and per rectal bleeding. Examine puncture sites, cannula sites for excessive bleeding[13][14][15]. Vasculopathy with amyloidosis will give purpura, this is characterized with periorbital purpura. These two conditions need to be differentiated with examination[22][23][24].
Look for signs of renal failure With acute renal failure there will be generalized body swelling, oliguria/ anuria mainly[16][17][18]. If there is neprotic syndrome secondsry to primary amyloidosis urine examination will reveals heavy proteinuria[19]. Haematuria, lower back ache/ loin to groin pain can be associated with urinary system stone formation with hypercalcaemia[20][21].
Central and peripheral nervous system examination There can be various types of conditions. eg: With cerebral/ cerebeller hypoperfusion secondary to hyperviscosity will have body weakness, sensory loss, cranial nerve involvement and features of imbalance and incordination[25][26]. With spinal cord compression with vertibral involvement of multiple myeloma, there will be limb weakness, sensory impairement anf bladder bowel involvement[27][28][29]. Amyloidosis causing peripheral neuropathy will give specific features to the affected nerves (eg: carpal tunnel syndrome with median nerve involvement)[30][31][32].
Cardiovasular examination cardio vascular system also can affect with various reasons. eg: - irregularly irregular pulse will present with arrhythmias in amyloidoses and myocardial infarctions (due to hyperviscosity causing poor perfusion). - Right heart failure features (elevated JVP, ankle oedema,ascites, tender hepatomegaly) will present with amyloidosis causing restrictive cardiomyopathy.[33][34][35][36][37].
Abdominal examination This can reveals hepatomegaly, signs of intestinal obstruction (abdominal distension, absolute constipation, vomiting) and features of perferation (gurding, rigidity, diminsed bowel sounds) secondary to primary amyloidosis[38][39][40].
Fundoscopic examination With the hyperviscosity of the blood, there will be engorgement of retinal veins, hemorrhages, exudate and blurring of the disk[25][41][42].
References
  1. TING WC, CAVILL I, JACOBS A, KAABA S, MAY A, SMITH S, WHITTAKER JA. Anaemia in patients with myelomatosis. Br J Cancer [online] 1982 Jun, 45(6):887-894 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011046
  2. BLACK J, MUSCAT-BARON J. Megaloblastic Anaemia and Multiple Myeloma Br Med J [online] 1963 Sep 14, 2(5358):682 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872801
  3. JACOBS P, SELLARS S, KING HS. Massive macroglossia, amyloidosis and myeloma. Postgrad Med J [online] 1988 Sep, 64(755):696-698 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428968
  4. NAIR DR, MEHTA A, MIKHAILIDIS DP, WINDER AF. Multiple myeloma with primary amyloidosis. J R Soc Med [online] 1997 Sep, 90(9):502 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296530
  5. SOUTHERST D, DUFTON J, STERN P. Multiple Myeloma presenting as sacroiliac joint pain: a case report J Can Chiropr Assoc [online] 2012 Jun, 56(2):94-101 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364058
  6. MALIK A, NARANG S, HANDA U, SOOD S. Multiple myeloma presenting as bilateral orbital proptosis Indian J Ophthalmol [online] 2009, 57(5):393-395 [viewed 15 November 2014] Available from: doi:10.4103/0301-4738.55069
  7. KRISTINSSON SY, MINTER AR, KORDE N, TAN E, LANDGREN O. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management Expert Rev Mol Diagn [online] 2011 Jul, 11(6):593-603 [viewed 14 November 2014] Available from: doi:10.1586/erm.11.44
  8. NEWMAN DB, KEARNS JJ, BECKMAN TJ. 54-Year-Old Woman With Fatigue, Back Pain, and Hypercalcemia Mayo Clin Proc [online] 2009 Dec, 84(12):e9-e12 [viewed 14 November 2014] Available from: doi:10.4065/mcp.2008.0718
  9. SOUTHERST D, DUFTON J, STERN P. Multiple Myeloma presenting as sacroiliac joint pain: a case report J Can Chiropr Assoc [online] 2012 Jun, 56(2):94-101 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364058
  10. KHALAFALLAH A, MAIWALD M, COX A, BURNS D, BATES G, HANNAN T, SEATON D, FERNANDOPULLE B, MEAGHER D, BRAIN T. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation or Treated with Immunomodulatory Agents. Mediterr J Hematol Infect Dis [online] , 2(1):e2010005 [viewed 14 November 2014] Available from: doi:10.4084/MJHID.2010.005
  11. CHAPEL HM, LEE M. The use of intravenous immune globulin in multiple myeloma. Clin Exp Immunol [online] 1994 Jul, 97(Suppl 1):21-24 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550368
  12. JOLLES S, SEWELL W, MISBAH S. Clinical uses of intravenous immunoglobulin Clin Exp Immunol [online] 2005 Oct, 142(1):1-11 [viewed 14 November 2014] Available from: doi:10.1111/j.1365-2249.2005.02834.x
  13. ZHENG L, ZENG Z, LIN J, CHEN J. IgM multiple myeloma presenting with bleeding tendency: a case report with immunophenotype analysis Oncol Lett [online] 2011 Jan, 2(1):55-57 [viewed 14 November 2014] Available from: doi:10.3892/ol.2010.216
  14. LIN M, ZHU J, SHEN H, HUANG J. Gastrointestinal bleeding as an initial manifestation in asymptomatic multiple myeloma: A case report and review of the literature Oncol Lett [online] 2013 Jan, 5(1):218-220 [viewed 14 November 2014] Available from: doi:10.3892/ol.2012.945
  15. TAIWO E, WANG H, LEWIS R. Treatment of Coexisting Chronic Neutrophilic Leukemia and Light Chain Multiple Myeloma with Hydroxyurea, Bortezomib, and Dexamethasone Case Rep Hematol [online] 2014:869395 [viewed 14 November 2014] Available from: doi:10.1155/2014/869395
  16. BOOTH LJ, MINIELLY JA, SMITH EK. Acute renal failure in multiple myeloma Can Med Assoc J [online] 1974 Aug 17, 111(4):334-335 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947712
  17. MACKENZIE MR, WUEPPER KD, JORDAN G, FUDENBERG HH. Rapid renal failure in a case of multiple myeloma: the role of Bence Jones proteins Clin Exp Immunol [online] 1968 Jul, 3(6):593-601 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578955
  18. BLACKMAN SS JR, BARKER WH, BUELL MV, DAVIS BD. ON THE PATHOGENESIS OF RENAL FAILURE ASSOCIATED WITH MULTIPLE MYELOMA. ELECTROPHORETIC AND CHEMICAL ANALYSIS OF PROTEIN IN URINE AND BLOOD SERUM J Clin Invest [online] 1944 Mar, 23(2):163-166 [viewed 14 November 2014] Available from: doi:10.1172/JCI101479
  19. SHAH R, SHAH N, SHAH A, MEHTA AN. Steroid-resistant nephrotic syndrome secondary to primary focal segmental glomerulosclerosis and smoldering multiple myeloma Proc (Bayl Univ Med Cent) [online] 2014 Jan, 27(1):19-21 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862124
  20. CARROLL R, MATFIN G. Endocrine and metabolic emergencies: hypercalcaemia Ther Adv Endocrinol Metab [online] 2010 Oct, 1(5):225-234 [viewed 15 November 2014] Available from: doi:10.1177/2042018810390260
  21. LOH LC, RAO RV, NG D. Uncommon, sinister vertebral fracture: Early-onset multiple myeloma Can Fam Physician [online] 2013 Nov, 59(11):1195-1199 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828096
  22. BAKER KR, RICE L. The Amyloidoses: Clinical Features, Diagnosis and Treatment Methodist Debakey Cardiovasc J [online] 2012, 8(3):3-7 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487569
  23. LAVORATO FG, ALVES MD, MACEIRA JM, UNTERSTELL N, SERPA LA, AZULAY-ABULAFIA L. Primary systemic amyloidosis, acquired cutis laxa and cutaneous mucinosis in a patient with multiple myeloma An Bras Dermatol [online] 2013, 88(6 Suppl 1):32-35 [viewed 15 November 2014] Available from: doi:10.1590/abd1806-4841.20132531
  24. ARYASIT O, PREECHAWAI P, KAYASUT K. Clinical presentation, treatment, and prognosis of periocular and orbital amyloidosis in a university-based referral center Clin Ophthalmol [online] 2013:801-805 [viewed 15 November 2014] Available from: doi:10.2147/OPTH.S41857
  25. PARK MS, KIM BC, KIM IK, LEE SH, CHOI SM, KIM MK, LEE SS, CHO KH. Cerebral Infarction in IgG Multiple Myeloma with Hyperviscosity J Korean Med Sci [online] 2005 Aug, 20(4):699-701 [viewed 15 November 2014] Available from: doi:10.3346/jkms.2005.20.4.699
  26. MIYATA K, MIKAMI T, MIKUNI N, AISAKA W, IRIFUNE H, NARIMATSU E. Malignant Hemispheric Cerebral Infarction Associated with Idiopathic Systemic Capillary Leak Syndrome Case Rep Neurol [online] , 5(3):175-182 [viewed 15 November 2014] Available from: doi:10.1159/000355637
  27. HA KY, KIM YH, KIM HW. Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective J Korean Neurosurg Soc [online] 2013 Aug, 54(2):151-154 [viewed 14 November 2014] Available from: doi:10.3340/jkns.2013.54.2.151
  28. CHAKRABORTI C, MILLER KL. Multiple myeloma presenting as spinal cord compression: a case report J Med Case Reports [online] :251 [viewed 14 November 2014] Available from: doi:10.1186/1752-1947-4-251
  29. SINI V, KAMTCHUM TJ, TEGUEU CK, DJIENTCHEU VD. Multiple myeloma revealed by spinal cord compression and herpes zoster in a 36-year-old Cameroonian Pan Afr Med J [online] :21 [viewed 14 November 2014] Available from: doi:10.11604/pamj.2013.16.21.2908
  30. MOHTY B, EL-CHEIKH J, YAKOUB-AGHA I, MOREAU P, HAROUSSEAU JL, MOHTY M. Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations Haematologica [online] 2010 Feb, 95(2):311-319 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2009.012674
  31. TARIMAN JD, LOVE G, MCCULLAGH E, SANDIFER S, IMF NURSE LEADERSHIP BOARD. Peripheral Neuropathy Associated With Novel Therapies in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board Clin J Oncol Nurs [online] 2008 Jun, 12(3 0):29-36 [viewed 15 November 2014] Available from: doi:10.1188/08.CJON.S1.29-35
  32. JHANG Y, LEE JJ, PARK JM, KOO JS, KIM BK, KWON O. Polyneuropathy Associated with IgA Paraproteinemia and Amyloidosis: A Case Report and Literature Review J Clin Neurol [online] 2007 Jun, 3(2):116-119 [viewed 15 November 2014] Available from: doi:10.3988/jcn.2007.3.2.116
  33. CAMPANILE A, SOZZI FB, CANETTA C, DANZI GB. Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis Exp Clin Cardiol [online] 2013, 18(1):31-34 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716485
  34. GILOTRA NA, CHOW GV, CINGOLANI OH. Cardiac Amyloidosis Presenting with Prolonged QT Interval and Recurrent Polymorphic Ventricular Tachycardia Tex Heart Inst J [online] 2013, 40(2):193-195 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649786
  35. HASSAN W, AL-SERGANI H, MOURAD W, TABBAA R. Amyloid Heart Disease: New Frontiers and Insights in Pathophysiology, Diagnosis, and Management Tex Heart Inst J [online] 2005, 32(2):178-184 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163465
  36. HA CE, BHAGAVAN NV, LOSCALZO M, CHAN SK, NGUYEN HV, RIOS CN, HONDA SA. Congestive Heart Failure: A Case of Protein Misfolding Hawaii J Med Public Health [online] 2014 Jun, 73(6):172-174 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064341
  37. STUART J, KENNY MW. Blood rheology. J Clin Pathol [online] 1980 May, 33(5):417-429 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1146104
  38. BUPPAJARNTHAM S, KUE-A-PAI P. Extensive Loculated Ascites in Hepatic Amyloidosis N Am J Med Sci [online] 2014 Jul, 6(7):346-348 [viewed 15 November 2014] Available from: doi:10.4103/1947-2714.136923
  39. DESPORT E, BRIDOUX F, SIRAC C, DELBES S, BENDER S, FERNANDEZ B, QUELLARD N, LACOMBE C, GOUJON JM, LAVERGNE D, ABRAHAM J, TOUCHARD G, FERMAND JP, JACCARD A. AL Amyloidosis Orphanet J Rare Dis [online] :54 [viewed 15 November 2014] Available from: doi:10.1186/1750-1172-7-54
  40. CROSS TJ, WENDON JA, QUAGLIA A, SALISBURY JR, HENEGHAN MA, HARRISON PM. Myeloma associated amyloidosis presenting as subacute liver failure Postgrad Med J [online] 2006 Jul, 82(969):e13 [viewed 15 November 2014] Available from: doi:10.1136/pgmj.2006.044883
  41. NAUTIYAL A, AMESCUA G, JAMESON A, GRADOWSKI JF, HONG F, DOFT B. Sudden loss of vision: Purtscher retinopathy in multiple myeloma CMAJ [online] 2009 Dec 8, 181(12):E277 [viewed 15 November 2014] Available from: doi:10.1503/cmaj.081968
  42. AYANNIYI AA, EJIKEME UG, TANKO Y, MUHAMMAD RC, NNODU OE. Blinding Bilateral Hyperviscosity Retinopathy in a 43-Year-Old Nigerian Male with Lymphoplasmacytic Lymphoma: A Case Report and Management Challenges Case Rep Oncol Med [online] 2014:567632 [viewed 15 November 2014] Available from: doi:10.1155/2014/567632

Differential Diagnoses

Fact Explanation
Primary tumour causing secondary bones metastesis Primary tumors from lung, thyroid gland, breast, prostate gland and Kidneys are at high risk of bone metastases compare to others. With metastatic lesions patient will have similer intractable, continuous back pain, constitutional symptoms, symptoms of other distal metastases (eg: Livers, lung and brain). There will be an evidence of primary focus of the tumour as well. Specific investigations like serum electroporesis will help to differenciate multiple myeloma.[1][2][3]
Waldenstrom Hypergammaglobulinemia This is a rare condition causing paraproteinaemia (monoclonal IgM paraprotein). It is a lymphoplasmacytoid lymphoma producing mainly constitutional symptoms (weight loss, fatiguability) and symptoms of hyperviscosity (Commonly CNS and visual complication). Monoclonal serum IgM with bone marrow/ lump node infiltration with lymphoplasmacytoid cells will confirm the diagnosis[4][5][6].
Other causes of amyloidosis Amyloidosis can be either Primary, secondary or familial.This condition is occurs with the extracellular deposition of the protein in an abnormal fibrillar form and those are resistant to regeneration. Patient will have multi systemic features. Primary amyloidosis can occur in Waldenstrom Hypergammaglobulinemia, Monoclonal Gammopathies of Uncertain Origin or lympoma other than multiple myeloma. Secondary amyloidosis can occur with chronic inflammatory conditions (eg: rheumatoid arthritis, inflammatory bowel disease) and chronic infections (eg: Tuberculosis, bronchiectasis, osteomyelitis) Familial amyloidosis is an autosomal dominant condition and patient will have family history. How ever specific investigations like serum electroporesis will help to differenciate multiple myeloma [7][8][9].
Monoclonal Gammopathies of Uncertain Origin This condition is associated with low levels of paraproteinaemia in serum with marrow plasma cell concentration less than 10%. There will be no evidence of myeloma, lymphoma or macroglobulinaemia. Aiso no associated with bone involvement and no Bence-Jones protein[10][11][12].
Malignant Lymphoma Lymphoma caused by malignant proliferation of the lympocytes. There are two types, Hodgkin's and Non-Hodgkin's lymphoma. These excessively proliferated lympocytes will accumulate in lymph nodes causing generalized lymphademnopathy and can infiltrate the other organs as well. Lymph node biopy will guide the diagnosis[13][14][15].
Presence of polycythemia causing hyperviscosity With both primary (eg; polycythemia rubra vera) and secondary polycythemia (eg: secondary to high altitude, COPD, Congenital cyanotic heart diseases, heavy smoking) there will be hyperviscosity, thrombocytosis and altered platelet membrane responses causing hypercoagulability. From full blood count polycythemia and multiple myeloma can be differenciated[16][17][18].
References
  1. COLEMAN RE, RUBENS RD. The clinical course of bone metastases from breast cancer. Br J Cancer [online] 1987 Jan, 55(1):61-66 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001575
  2. SUVA LJ, WASHAM C, NICHOLAS RW, GRIFFIN RJ. Bone metastasis: mechanisms and therapeutic opportunities Nat Rev Endocrinol [online] 2011 Apr, 7(4):208-218 [viewed 15 November 2014] Available from: doi:10.1038/nrendo.2010.227
  3. VIRK MS, LIEBERMAN JR. Tumor metastasis to bone Arthritis Res Ther [online] 2007, 9(Suppl 1):S5 [viewed 15 November 2014] Available from: doi:10.1186/ar2169
  4. HUNTER ZR, MANNING RJ, HANZIS C, CICCARELLI BT, IOAKIMIDIS L, PATTERSON CJ, LEWICKI MC, TSENG H, GONG P, LIU X, ZHOU Y, YANG G, SUN J, XU L, SHEEHY P, MORRA M, TREON SP. IgA and IgG hypogammaglobulinemia in Waldenstr?m's macroglobulinemia Haematologica [online] 2010 Mar, 95(3):470-475 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2009.010348
  5. STONE MJ, PASCUAL V. Pathophysiology of Waldenstr?m's macroglobulinemia Haematologica [online] 2010 Mar, 95(3):359-364 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2009.017251
  6. NEPARIDZE N, DHODAPKAR MV. Waldenstrom's Macroglobulinemia: Recent Advances in Biology and Therapy Clin Adv Hematol Oncol [online] 2009 Oct, 7(10):677-690 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612541
  7. HOENIG M, HALL G, FERGUSON D, JORDAN K, HENSON M, JOHNSON K, O’BRIEN T. A Feline Model of Experimentally Induced Islet Amyloidosis Am J Pathol [online] 2000 Dec, 157(6):2143-2150 [viewed 15 November 2014] Available from: doi:10.1016/S0002-9440(10)64852-3
  8. WESTERMARK P, SLETTEN K, JOHANSSON B, CORNWELL GG 3RD. Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc Natl Acad Sci U S A [online] 1990 Apr, 87(7):2843-2845 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC53787
  9. HASSAN W, AL-SERGANI H, MOURAD W, TABBAA R. Amyloid Heart Disease: New Frontiers and Insights in Pathophysiology, Diagnosis, and Management Tex Heart Inst J [online] 2005, 32(2):178-184 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163465
  10. RAJKUMAR SV, KYLE RA, BUADI FK. Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence Mayo Clin Proc [online] 2010 Oct, 85(10):945-948 [viewed 15 November 2014] Available from: doi:10.4065/mcp.2010.0520
  11. KORDE N, KRISTINSSON SY, LANDGREN O. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies Blood [online] 2011 May 26, 117(21):5573-5581 [viewed 15 November 2014] Available from: doi:10.1182/blood-2011-01-270140
  12. BIDA JP, KYLE RA, THERNEAU TM, MELTON LJ III, PLEVAK MF, LARSON DR, DISPENZIERI A, KATZMANN JA, RAJKUMAR SV. Disease Associations With Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study of 17,398 Patients Mayo Clin Proc [online] 2009 Aug, 84(8):685-693 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719521
  13. MAZZA JJ, YALE SH, ARROWOOD JR, REYNOLDS CE, GLURICH I, CHYOU PH, LINNEMAN JG, REED KD. Efficacy of the Influenza Vaccine in Patients with Malignant Lymphoma Clin Med Res [online] 2005 Nov, 3(4):214-220 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288406
  14. TALERMAN A. Clinico-Pathological Study of Malignant Lymphoma in Jamaica Br J Cancer [online] 1970 Mar, 24(1):37-47 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008523
  15. CASEY TT, COUSAR JB, MANGUM M, WILLIAMS ME, LEE JT, GREER JP, COLLINS RD. Monomorphic lymphomas arising in patients with Hodgkin's disease. Correlation of morphologic, immunophenotypic, and molecular genetic findings in 12 cases. Am J Pathol [online] 1990 Jan, 136(1):81-94 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1877457
  16. JEPSON JH. Polycythemia: diagnosis, pathophysiology and therapy. I. Can Med Assoc J [online] 1969 Feb 8, 100(6):271-277 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945593
  17. BHATT VR. Secondary Polycythemia and the Risk of Venous Thromboembolism J Clin Med Res [online] 2014 Oct, 6(5):395-397 [viewed 15 November 2014] Available from: doi:10.14740/jocmr1916w
  18. SCHAFER PW. The Etiology and Treatment of Polycythemia Rubra Vera : Observations Based upon Studies of Body Fluid Changes in Dogs Subjected to Proprioceptor Depressor Neurotomy and Extensive Sympathectomy, Including the Case Report of a Man with Polycythemia Rubra Vera Treated by Extensive Para-Vertebral Sympathectomy Ann Surg [online] 1945 Dec, 122(6):1098-1124 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618335

Investigations - for Diagnosis

Fact Explanation
Full blood count This is to identify the abnormalities of the blood counts (eg: anaemia, netropenia, thrombocytopenia) with infiltration of the disease to bone marrows[1]-[7].
Blood film There will be large number of plasma cells with many abnormal forms. There will be normocytic normochromic or macrocytic anemia. netropenia and thrombocytopenia. Rouleaux formation can also be seen in blood picture[8][9][10].
ESR and CRP These are persistently high in multiple myeloma[11][12][13].
Immunoglobuline electrophoresis Using this presence of paraprotein in serum and urine can be identified with the abnormal rise. majority of cases the paraprotein is IgG and the rest it is IgA. Very few will gave IgD and IgE. Hypogammaglobinaemia can be identified[14][15][16].
Free light chain level in the serum As all plasma cella are producing free light chains tis test in useful in diagnosis as well and monitoring the patient following traeatment. In multiple myeloma κ: λ (2:1) normal free light chain ratio is disturb with with the excess production of both[17][18][19].
Bence- Jones protein in urine As serum free light chains are filtered to the urine via kidnys, they can be detected in urine(Bence- Jones protein) in majority[20][21][22].
Bone marrow biopsy It will show increase plasma cells often with abnormal forms. Staining with monoclonal antibodies (IgG kappa monoclonal antibody) will confirm the diagnosis further. plasm cells will be >10%[23][24][25].
Radiological investigations for skeletal system (X ray, CT and MRI) Investigations can be started according to the patients complain and continue to screen the whole skeletal system. There will be osteolytic, punched out lesions (eg; pepper pot skull) without evidence of surrounding osteoblastic reaction/ sclerosis, generalized reduction in bone density, pathological fractures and vertebral collapse[26][27][28]. CT and MRI of the spine will be useful in the presence of symptoms with spinal cord compression[29][30][31].
Serum levels of RNAKL (Receptor Activator of Nucler factor kB ligand) This is produced by plasma cells and bone marrow. It activate the osteoclasts resulting lysis of the bone. So the levels of RNAKL will be high[28][32][33].
Serum calcium level and serum alkaline posphatase level With the bone destruction, there will be hypercalcaemia. Usually serum alkaline posphatase level is normal but will be high with pathological fractures[9][28][34][35][36][37].
Renal function tests including UFR, serum creatinine, blood urea and serum electrolytes UFR will give evidence of proteinuria, haematuria (renal stones), pus cells (In UTI). Serun creatinine and blood uria will be high with the renal involvement and there can be alterations in serum electrolytes like hypernatraemia and hyperkalaemia[20][41][42].
polarized light microscopic look for biopsy of affected tissue (amyloidosis) and Cango Red staining Histological changes and positive Congo Red staining with red- green birefringence will confirm the diagnosis of amyloidosis in suspected cases[38][39][40].
Liver function tests AST, ALT and serum albumin As Amyloidosis can affect the liver function there tests are useful. AST, ALT will be high and serum albumin level will be low[43][44][45].
ECG/ Echocardiogram This is useful in assessing the cardiac function as it can disturb with amyloidosis and hyperviscosity of the blood[46]-[50].
CT/ MRI brain This is important in the presence of neurological symptoms[51][52].
Nerve conduction studies This is important is assessing the presence of peripheral neuropathy either secondary to amyloidosis or following chemotherapy[53][54][55].
lactate dehydrogenase measurement lactate dehydrogenase levels will be high in multiple myeloma[56][57][58].
References
  1. BIRGEGåRD G, GASCóN P, LUDWIG H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY Eur J Haematol [online] 2006 Nov, 77(5):378-386 [viewed 14 November 2014] Available from: doi:10.1111/j.1600-0609.2006.00739.x
  2. TING WC, CAVILL I, JACOBS A, KAABA S, MAY A, SMITH S, WHITTAKER JA. Anaemia in patients with myelomatosis. Br J Cancer [online] 1982 Jun, 45(6):887-894 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011046
  3. BLACK J, MUSCAT-BARON J. Megaloblastic Anaemia and Multiple Myeloma Br Med J [online] 1963 Sep 14, 2(5358):682 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872801
  4. ZHENG L, ZENG Z, LIN J, CHEN J. IgM multiple myeloma presenting with bleeding tendency: a case report with immunophenotype analysis Oncol Lett [online] 2011 Jan, 2(1):55-57 [viewed 14 November 2014] Available from: doi:10.3892/ol.2010.216
  5. LIN M, ZHU J, SHEN H, HUANG J. Gastrointestinal bleeding as an initial manifestation in asymptomatic multiple myeloma: A case report and review of the literature Oncol Lett [online] 2013 Jan, 5(1):218-220 [viewed 14 November 2014] Available from: doi:10.3892/ol.2012.945
  6. FIELD-SMITH A, MORGAN GJ, DAVIES FE. Bortezomib (Velcade(TM)) in the Treatment of Multiple Myeloma Ther Clin Risk Manag [online] 2006 Sep, 2(3):271-279 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936263
  7. LONIAL S, WALLER EK, RICHARDSON PG, JAGANNATH S, ORLOWSKI RZ, GIVER CR, JAYE DL, FRANCIS D, GIUSTI S, TORRE C, BARLOGIE B, BERENSON JR, SINGHAL S, SCHENKEIN DP, ESSELTINE DL, ANDERSON J, XIAO H, HEFFNER LT, ANDERSON KC, FOR THE SUMMIT/CREST INVESTIGATORS. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma Blood [online] 2005 Dec 1, 106(12):3777-3784 [viewed 15 November 2014] Available from: doi:10.1182/blood-2005-03-1173
  8. KYLE RA, RAJKUMAR SV. Multiple myeloma Blood [online] 2008 Mar 15, 111(6):2962-2972 [viewed 15 November 2014] Available from: doi:10.1182/blood-2007-10-078022
  9. NEWMAN DB, KEARNS JJ, BECKMAN TJ. 54-Year-Old Woman With Fatigue, Back Pain, and Hypercalcemia Mayo Clin Proc [online] 2009 Dec, 84(12):e9-e12 [viewed 15 November 2014] Available from: doi:10.4065/mcp.2008.0718
  10. KYLE R, RAJKUMAR S. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma Leukemia [online] 2009 Jan, 23(1):3-9 [viewed 15 November 2014] Available from: doi:10.1038/leu.2008.291
  11. VERMEIRE S, VAN ASSCHE G, RUTGEERTS P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut [online] 2006 Mar, 55(3):426-431 [viewed 15 November 2014] Available from: doi:10.1136/gut.2005.069476
  12. CASTRO C, GOURLEY M. Diagnostic Testing and Interpretation of Tests for Autoimmunity J Allergy Clin Immunol [online] 2010 Feb, 125(2 Suppl 2):S238-S247 [viewed 15 November 2014] Available from: doi:10.1016/j.jaci.2009.09.041
  13. HEIKKILä K, EBRAHIM S, LAWLOR DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer J Epidemiol Community Health [online] 2007 Sep, 61(9):824-833 [viewed 15 November 2014] Available from: doi:10.1136/jech.2006.051292
  14. DASH NR, MOHANTY B. Multiple Myeloma: A Case of Atypical Presentation on Protein Electrophoresis Indian J Clin Biochem [online] 2012 Jan, 27(1):100-102 [viewed 15 November 2014] Available from: doi:10.1007/s12291-011-0178-3
  15. SINCLAIR D, KUMARARATNE DS, STOTT D. Detection and identification of serum monoclonal immunoglobulin by immunoisoelectric focusing. Limits of sensitivity and use during relapse of multiple myeloma. J Clin Pathol [online] 1984 Mar, 37(3):255-262 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC498695
  16. MARGARIDA R. Modification of the Starch Block Electrophoresis Method for the Preparation of Immunoglobulin A from Multiple Myeloma Sera on a Large Scale Appl Microbiol [online] 1973 Sep, 26(3):419-420 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC379804
  17. TOSI P, TOMASSETTI S, MERLI A, POLLI V. Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions Ther Adv Hematol [online] 2013 Feb, 4(1):37-41 [viewed 15 November 2014] Available from: doi:10.1177/2040620712466863
  18. VAN RHEE F, BOLEJACK V, HOLLMIG K, PINEDA-ROMAN M, ANAISSIE E, EPSTEIN J, SHAUGHNESSY JD JR, ZANGARI M, TRICOT G, MOHIUDDIN A, ALSAYED Y, WOODS G, CROWLEY J, BARLOGIE B. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis Blood [online] 2007 Aug 1, 110(3):827-832 [viewed 15 November 2014] Available from: doi:10.1182/blood-2007-01-067728
  19. HUTCHISON CA, PLANT T, DRAYSON M, COCKWELL P, KOUNTOURI M, BASNAYAKE K, HARDING S, BRADWELL AR, MEAD G. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure BMC Nephrol [online] :11 [viewed 15 November 2014] Available from: doi:10.1186/1471-2369-9-11
  20. BLACKMAN SS JR, BARKER WH, BUELL MV, DAVIS BD. ON THE PATHOGENESIS OF RENAL FAILURE ASSOCIATED WITH MULTIPLE MYELOMA. ELECTROPHORETIC AND CHEMICAL ANALYSIS OF PROTEIN IN URINE AND BLOOD SERUM J Clin Invest [online] 1944 Mar, 23(2):163-166 [viewed 15 November 2014] Available from: doi:10.1172/JCI101479
  21. DENT CE, ROSE GA. The Bence-Jones protein of multiple myelomatosis: its methionine content and its possible significance in relation to the aetiology of the disease Biochem J [online] 1949, 44(5):610-618 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1274920
  22. ASKONAS BA, FAHEY JL. Formation of Bence-Jones protein and myeloma protein in vitro by the plasma-cell tumour MPC-2 Biochem J [online] 1961 Aug, 80(2):261-268 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243992
  23. AL-QURAN SZ, YANG L, MAGILL JM, BRAYLAN RC, DOUGLAS-NIKITIN VK. Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry Hum Pathol [online] 2007 Dec, 38(12):1779-1787 [viewed 15 November 2014] Available from: doi:10.1016/j.humpath.2007.04.010
  24. ALEXANDRAKIS MG, PASSAM FH, DAMBAKI C, PAPPA CA, STATHOPOULOS EN. The relation between bone marrow angiogenesis and the proliferation index Ki-67 in multiple myeloma J Clin Pathol [online] 2004 Aug, 57(8):856-860 [viewed 15 November 2014] Available from: doi:10.1136/jcp.2003.013110
  25. RICCARDI A, UCCI G, LUONI R, CASTELLO A, COCI A, MAGRINI U, ASCARI E. Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma. J Clin Pathol [online] 1990 Jun, 43(6):469-475 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC502499
  26. GHOSH S, WADHWA P, KUMAR A, PAI K, SESHADRI S, MANOHAR C. Abnormal radiological features in a multiple myeloma patient: a case report and radiological review of myelomas Dentomaxillofac Radiol [online] 2011 Dec, 40(8):513-518 [viewed 15 November 2014] Available from: doi:10.1259/dmfr/74265829
  27. KRISTINSSON SY, MINTER AR, KORDE N, TAN E, LANDGREN O. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management Expert Rev Mol Diagn [online] 2011 Jul, 11(6):593-603 [viewed 15 November 2014] Available from: doi:10.1586/erm.11.44
  28. OYAJOBI BO. Multiple myeloma/hypercalcemia Arthritis Res Ther [online] 2007, 9(Suppl 1):S4 [viewed 15 November 2014] Available from: doi:10.1186/ar2168
  29. HA KY, KIM YH, KIM HW. Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective J Korean Neurosurg Soc [online] 2013 Aug, 54(2):151-154 [viewed 14 November 2014] Available from: doi:10.3340/jkns.2013.54.2.151
  30. CHAKRABORTI C, MILLER KL. Multiple myeloma presenting as spinal cord compression: a case report J Med Case Reports [online] :251 [viewed 14 November 2014] Available from: doi:10.1186/1752-1947-4-251
  31. SINI V, KAMTCHUM TJ, TEGUEU CK, DJIENTCHEU VD. Multiple myeloma revealed by spinal cord compression and herpes zoster in a 36-year-old Cameroonian Pan Afr Med J [online] :21 [viewed 14 November 2014] Available from: doi:10.11604/pamj.2013.16.21.2908
  32. GRIMAUD E, SOUBIGOU L, COUILLAUD S, COIPEAU P, MOREAU A, PASSUTI N, GOUIN F, REDINI F, HEYMANN D. Receptor Activator of Nuclear Factor ?B Ligand (RANKL)/Osteoprotegerin (OPG) Ratio Is Increased in Severe Osteolysis Am J Pathol [online] 2003 Nov, 163(5):2021-2031 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892410
  33. SFIRIDAKI K, PAPPA CA, TSIRAKIS G, KANELLOU P, KAPAROU M, STRATINAKI M, SAKELLARIS G, KONTAKIS G, ALEXANDRAKIS MG. Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment Mediators Inflamm [online] 2011:867576 [viewed 15 November 2014] Available from: doi:10.1155/2011/867576
  34. JACOBS P, SELLARS S, KING HS. Massive macroglossia, amyloidosis and myeloma. Postgrad Med J [online] 1988 Sep, 64(755):696-698 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428968
  35. ZOPPOLI G, BALLEARI E, GHIO R. Soluble molecules and bone metabolism in multiple myeloma: a review Clin Cases Miner Bone Metab [online] 2008, 5(1):67-70 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781188
  36. SINGH AP, MAHAJAN S, SINGH AP. Spontaneous bilateral fracture of the proximal humerus: an unusual presentation of multiple myeloma Can J Surg [online] 2008 Aug, 51(4):E95-E96 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552934
  37. LEE J, VASIKARAN S. Current Recommendations for Laboratory Testing and Use of Bone Turnover Markers in Management of Osteoporosis Ann Lab Med [online] 2012 Mar, 32(2):105-112 [viewed 15 November 2014] Available from: doi:10.3343/alm.2012.32.2.105
  38. SHATNAWEI A, DASARI V, DUMOT J, KIRBY DF. Two Cases of Gastric and Esophageal Amyloidosis Gastroenterol Hepatol (N Y) [online] 2009 Aug, 5(8):571-574 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886404
  39. BOWEN K, SHAH N, LEWIN M. AL-Amyloidosis Presenting with Negative Congo Red Staining in the Setting of High Clinical Suspicion: A Case Report Case Rep Nephrol [online] 2012:593460 [viewed 15 November 2014] Available from: doi:10.1155/2012/593460
  40. DEVATA S, HARI P, MARKELOVA N, LI R, KOMOROWSKI R, SHIDHAM VB. Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: Role of electron microscopy and Congo red stained cell block sections Cytojournal [online] :11 [viewed 15 November 2014] Available from: doi:10.4103/1742-6413.82278
  41. BOOTH LJ, MINIELLY JA, SMITH EK. Acute renal failure in multiple myeloma Can Med Assoc J [online] 1974 Aug 17, 111(4):334-335 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947712
  42. MACKENZIE MR, WUEPPER KD, JORDAN G, FUDENBERG HH. Rapid renal failure in a case of multiple myeloma: the role of Bence Jones proteins Clin Exp Immunol [online] 1968 Jul, 3(6):593-601 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578955
  43. BUPPAJARNTHAM S, KUE-A-PAI P. Extensive Loculated Ascites in Hepatic Amyloidosis N Am J Med Sci [online] 2014 Jul, 6(7):346-348 [viewed 15 November 2014] Available from: doi:10.4103/1947-2714.136923
  44. DESPORT E, BRIDOUX F, SIRAC C, DELBES S, BENDER S, FERNANDEZ B, QUELLARD N, LACOMBE C, GOUJON JM, LAVERGNE D, ABRAHAM J, TOUCHARD G, FERMAND JP, JACCARD A. AL Amyloidosis Orphanet J Rare Dis [online] :54 [viewed 15 November 2014] Available from: doi:10.1186/1750-1172-7-54
  45. CROSS TJ, WENDON JA, QUAGLIA A, SALISBURY JR, HENEGHAN MA, HARRISON PM. Myeloma associated amyloidosis presenting as subacute liver failure Postgrad Med J [online] 2006 Jul, 82(969):e13 [viewed 15 November 2014] Available from: doi:10.1136/pgmj.2006.044883
  46. CAMPANILE A, SOZZI FB, CANETTA C, DANZI GB. Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis Exp Clin Cardiol [online] 2013, 18(1):31-34 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716485
  47. GILOTRA NA, CHOW GV, CINGOLANI OH. Cardiac Amyloidosis Presenting with Prolonged QT Interval and Recurrent Polymorphic Ventricular Tachycardia Tex Heart Inst J [online] 2013, 40(2):193-195 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649786
  48. HASSAN W, AL-SERGANI H, MOURAD W, TABBAA R. Amyloid Heart Disease: New Frontiers and Insights in Pathophysiology, Diagnosis, and Management Tex Heart Inst J [online] 2005, 32(2):178-184 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163465
  49. HA CE, BHAGAVAN NV, LOSCALZO M, CHAN SK, NGUYEN HV, RIOS CN, HONDA SA. Congestive Heart Failure: A Case of Protein Misfolding Hawaii J Med Public Health [online] 2014 Jun, 73(6):172-174 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064341
  50. STUART J, KENNY MW. Blood rheology. J Clin Pathol [online] 1980 May, 33(5):417-429 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1146104
  51. PARK MS, KIM BC, KIM IK, LEE SH, CHOI SM, KIM MK, LEE SS, CHO KH. Cerebral Infarction in IgG Multiple Myeloma with Hyperviscosity J Korean Med Sci [online] 2005 Aug, 20(4):699-701 [viewed 15 November 2014] Available from: doi:10.3346/jkms.2005.20.4.699
  52. MIYATA K, MIKAMI T, MIKUNI N, AISAKA W, IRIFUNE H, NARIMATSU E. Malignant Hemispheric Cerebral Infarction Associated with Idiopathic Systemic Capillary Leak Syndrome Case Rep Neurol [online] , 5(3):175-182 [viewed 15 November 2014] Available from: doi:10.1159/000355637
  53. MOHTY B, EL-CHEIKH J, YAKOUB-AGHA I, MOREAU P, HAROUSSEAU JL, MOHTY M. Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations Haematologica [online] 2010 Feb, 95(2):311-319 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2009.012674
  54. TARIMAN JD, LOVE G, MCCULLAGH E, SANDIFER S, IMF NURSE LEADERSHIP BOARD. Peripheral Neuropathy Associated With Novel Therapies in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board Clin J Oncol Nurs [online] 2008 Jun, 12(3 0):29-36 [viewed 15 November 2014] Available from: doi:10.1188/08.CJON.S1.29-35
  55. HANG Y, LEE JJ, PARK JM, KOO JS, KIM BK, KWON O. Polyneuropathy Associated with IgA Paraproteinemia and Amyloidosis: A Case Report and Literature Review J Clin Neurol [online] 2007 Jun, 3(2):116-119 [viewed 15 November 2014] Available from: doi:10.3988/jcn.2007.3.2.116
  56. KIBA T, ITO T, NAKASHIMA T, OKIKAWA Y, KIDO M, KIMURA A, KAMEDA K, MIYAMAE F, TANAKA S, ATSUMI M, SUMITANI Y, SHITAKUBO Y, NIIMI H. Bortezomib and dexamethasone for multiple myeloma: higher AST and LDH levels associated with a worse prognosis on overall survival BMC Cancer [online] :462 [viewed 15 November 2014] Available from: doi:10.1186/1471-2407-14-462
  57. TEKE HÜ, BAşAK M, TEKE D, KANBAY M. Serum Level of Lactate Dehydrogenase is a Useful Clinical Marker to Monitor Progressive Multiple Myeloma Diseases: A Case Report Turk J Haematol [online] 2014 Mar, 31(1):84-87 [viewed 15 November 2014] Available from: doi:10.4274/Tjh.2013.0044
  58. KUBICZKOVA L, KRYUKOV F, SLABY O, DEMENTYEVA E, JARKOVSKY J, NEKVINDOVA J, RADOVA L, GRESLIKOVA H, KUGLIK P, VETESNIKOVA E, POUR L, ADAM Z, SEVCIKOVA S, HAJEK R. Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance Haematologica [online] 2014 Mar, 99(3):511-518 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2013.093500

Investigations - Fitness for Management

Fact Explanation
FBC This can be use to assess the level of anaemia(Hb), WBC counts to detect coexisting infections and also useful before an invasive procedure like bone narrow biopsy to assess the platelet levels [1][2][3].
Clotting profile including PT/INR, APTT This is useful in excluding the presence of clotting factor defect in the presence of spontaneous bleeding and will useful before invasive procedures[4][5][6].
Urine/ seru B HCG level This is to excude pregnence in a patient (in fertile age) before deciding the treatment options (eg: thlidomide is a teratogenic immunomodulator)[7][8][9].
Tests to assess the fitness of the patient prior to surgery ( eg; chest X ray, ECG/ecocardiogram, renal function tests, liver function tests) These will perform pre operatively to assess the fitness of the patient for surgery[4][5][6].
References
  1. ZHENG L, ZENG Z, LIN J, CHEN J. IgM multiple myeloma presenting with bleeding tendency: a case report with immunophenotype analysis Oncol Lett [online] 2011 Jan, 2(1):55-57 [viewed 14 November 2014] Available from: doi:10.3892/ol.2010.216
  2. LIN M, ZHU J, SHEN H, HUANG J. Gastrointestinal bleeding as an initial manifestation in asymptomatic multiple myeloma: A case report and review of the literature Oncol Lett [online] 2013 Jan, 5(1):218-220 [viewed 14 November 2014] Available from: doi:10.3892/ol.2012.945
  3. TAIWO E, WANG H, LEWIS R. Treatment of Coexisting Chronic Neutrophilic Leukemia and Light Chain Multiple Myeloma with Hydroxyurea, Bortezomib, and Dexamethasone Case Rep Hematol [online] 2014:869395 [viewed 14 November 2014] Available from: doi:10.1155/2014/869395
  4. LIUMBRUNO GM, BENNARDELLO F, LATTANZIO A, PICCOLI P, ROSSETTI G, ITALIAN SOCIETY OF TRANSFUSION MEDICINE AND IMMUNOHAEMATOLOGY (SIMTI) WORKING PARTY. Recommendations for the transfusion management of patients in the peri-operative period. I. The pre-operative period Blood Transfus [online] 2011 Jan, 9(1):19-40 [viewed 15 November 2014] Available from: doi:10.2450/2010.0074-10
  5. AKHTAR A, MACFARLANE RJ, WASEEM M. Pre-Operative Assessment and Post-Operative Care in Elective Shoulder Surgery Open Orthop J [online] :316-322 [viewed 15 November 2014] Available from: doi:10.2174/1874325001307010316
  6. BENARROCH-GAMPEL J, SHEFFIELD KM, DUNCAN CB, BROWN KM, HAN Y, TOWNSEND CM JR, RIALL TS. Preoperative Laboratory Testing in Patients Undergoing Elective, Low-Risk Ambulatory Surgery Ann Surg [online] 2012 Sep, 256(3):518-528 [viewed 15 November 2014] Available from: doi:10.1097/SLA.0b013e318265bcdb
  7. D'AMATO RJ, LOUGHNAN MS, FLYNN E, FOLKMAN J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A [online] 1994 Apr 26, 91(9):4082-4085 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43727
  8. CAVALLO F, BOCCADORO M, PALUMBO A. Review of thalidomide in the treatment of newly diagnosed multiple myeloma Ther Clin Risk Manag [online] 2007 Aug, 3(4):543-552 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374936
  9. YANG G, CHEN W, WU Y. Bortezomib, dexamethasone plus thalidomide for treatment of newly diagnosed multiple myeloma patients with or without renal impairment Chin J Cancer Res [online] 2013 Apr, 25(2):155-160 [viewed 15 November 2014] Available from: doi:10.3978/j.issn.1000-9604.2013.03.07

Investigations - Followup

Fact Explanation
FBC, blood/ urine culture and ABST and ESR/ CRP These are important in patients receiving chemotherapy to assess any drug induced pancytopeni. (lowest count occur around 6-14 days after chemotherapy) other than secondary to multiple myeloma. In the presence of Neutropenic sepsis (neutrophil count less than 1.0x 109/L), IV broad spectrum antibiotics need to start quickly after taking blood/ urine for culture and ABST. CRP can also use as a prognostic marker. [1][2][3].
Skeletal survey including, X ray of the chest, cervical, thoracic, lumbar spine, skull and pelvis If the patient is not presented with a bone pain, this is usually done after diagnosis of the multiple myeloma to detect the presence of any bone lesions[4][5][6].
Serum beta2 microglobuline Serum beta2 microglobuline is often raise and this is useful in assessing the prognosis [7][8][9].
FSH/ LH levels As chemotherapy can induce ovarion failure, theses teats need to be done in women in their fertile age[10][11][12].
References
  1. MUNSHI HG, MONTGOMERY RB. Severe neutropenia: a diagnostic approach West J Med [online] 2000 Apr, 172(4):248-252 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070837
  2. MACHADO NO. Neutropenic enterocolitis: A continuing medical and surgical challenge N Am J Med Sci [online] 2010 Jul, 2(7):293-300 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341635
  3. DALE DC. Advances in the Treatment of Neutropenia Curr Opin Support Palliat Care [online] 2009 Sep, 3(3):207-212 [viewed 15 November 2014] Available from: doi:10.1097/SPC.0b013e32832ea6ae
  4. KRISTINSSON SY, MINTER AR, KORDE N, TAN E, LANDGREN O. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management Expert Rev Mol Diagn [online] 2011 Jul, 11(6):593-603 [viewed 15 November 2014] Available from: doi:10.1586/erm.11.44
  5. LüTJE S, DE ROOY JW, CROOCKEWIT S, KOEDAM E, OYEN WJ, RAYMAKERS RA. Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical evaluation of patients with multiple myeloma Ann Hematol [online] 2009 Dec, 88(12):1161-1168 [viewed 15 November 2014] Available from: doi:10.1007/s00277-009-0829-0
  6. SEXTON C, CRICHLOW C. Multiple myeloma: imaging evaluation of skeletal disease J Community Hosp Intern Med Perspect [online] , 3(2):10.3402/jchimp.v3i2.21419 [viewed 15 November 2014] Available from: doi:10.3402/jchimp.v3i2.21419
  7. CUZICK J, COOPER EH, MACLENNAN IC. The prognostic value of serum beta 2 microglobulin compared with other presentation features in myelomatosis. Br J Cancer [online] 1985 Jul, 52(1):1-6 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977159
  8. VINCENT C, REVILLARD JP, BATAILLE R. Characterization of polyclonal autoantibodies specific for beta 2-microglobulin in multiple myeloma sera. Clin Exp Immunol [online] 1983 Dec, 54(3):689-696 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1536147
  9. CHILD JA, CRAWFORD SM, NORFOLK DR, O'QUIGLEY J, SCARFFE JH, STRUTHERS LP. Evaluation of serum beta 2-microglobulin as a prognostic indicator in myelomatosis. Br J Cancer [online] 1983 Jan, 47(1):111-114 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011252
  10. LIPTON A, UZZO R, AMATO RJ, ELLIS GK, HAKIMIAN B, ROODMAN GD, SMITH MR. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors J Natl Compr Canc Netw [online] 2009 Oct, 7(Suppl 7):S1-S30 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047391
  11. GRALOW JR, BIERMANN JS, FAROOKI A, FORNIER MN, GAGEL RF, KUMAR RN, SHAPIRO CL, SHIELDS A, SMITH MR, SRINIVAS S, VAN POZNAK CH. NCCN Task Force Report: Bone Health in Cancer Care J Natl Compr Canc Netw [online] 2009 Jun, 7(Suppl 3):S1-S35 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047404
  12. STEGER GG, BARTSCH R. Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion Ther Adv Med Oncol [online] 2011 Sep, 3(5):233-243 [viewed 15 November 2014] Available from: doi:10.1177/1758834011412656

Investigations - Screening/Staging

Fact Explanation
The International Staging System (ISS) for myeloma by the International Myeloma Working Group (2005) This is applicableiIn a patient who fulfill the diagnostic criteria for the multiple myeloma. Stage I: β2 microglobulin (β2M) < 3.5 mg/L, albumin ≥ 3.5 g/dL Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5–5.5 mg/L irrespective of the serum albumin Stage III: β2M ≥ 5.5 mg/L [1][2][3]
Durie-Salmon staging system (1975) Stage I: all of -Hb > 10g/dL -normal calcium -Skeletal survey: normal or single plasmacytoma or osteoporosis -Serum paraprotein level < 5 g/dL if IgG, < 3 g/dL if IgA -Urinary light chain excretion < 4 g/24h Stage II: fulfilling the criteria of neither I nor III Stage III: one or more of -Hb < 8.5g/dL -high calcium > 12 mg/dL -Skeletal survey: Three or more lytic bone lesions -Serum paraprotein > 7g/dL if IgG, > 5 g/dL if IgA -Urinary light chain excretion > 12g/24h Stages I, II, and III of the Durie-Salmon staging system divided into A or B depending on serum creatinine: A: serum creatinine < 2 mg/dL (< 177 μmol/L) B: serum creatinine > 2 mg/dL (> 177 μmol/L) [2][3][4]
References
  1. HARI PN, ZHANG MJ, ROY V, PéREZ WS, BASHEY A, TO LB, ELFENBEIN G, FREYTES CO, GALE RP, GIBSON J, KYLE RA, LAZARUS HM, MCCARTHY PL, MILONE GA, PAVLOVSKY S, REECE DE, SCHILLER G, VELA-OJEDA J, WEISDORF D, VESOLE D. IS THE INTERNATIONAL STAGING SYSTEM SUPERIOR TO THE DURIE SALMON STAGING SYSTEM? A COMPARISON IN MULTIPLE MYELOMA PATIENTS UNDERGOING AUTOLOGOUS TRANSPLANT Leukemia [online] 2009 Aug, 23(8):1528-1534 [viewed 15 November 2014] Available from: doi:10.1038/leu.2009.61
  2. KYLE R, RAJKUMAR S. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma Leukemia [online] 2009 Jan, 23(1):3-9 [viewed 15 November 2014] Available from: doi:10.1038/leu.2008.291
  3. SHIM H, HA JH, LEE H, SOHN JY, KIM HJ, EOM HS, KONG SY. Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma Biomed Res Int [online] 2014:893243 [viewed 15 November 2014] Available from: doi:10.1155/2014/893243
  4. LAURIA F, FOA R, CAVO M, GOBBI M, RASPADORI D, GIUBELLINO MC, TAZZARI PL, TURA S. Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease. Clin Exp Immunol [online] 1984 Jun, 56(3):653-658 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535996

Management - General Measures

Fact Explanation
Health education The patient should be educated regarding the disease, progression, complications associated with, prognosis, investigation and treatment options available[1][2][3].
Pain management As majory of patient suffer from bony pain, analgesics should be added according to the analgesics ladder. eg: 1) Paracetamol : widely used over the counter drugs and simple pain could be managed. They decreases the the nociception in central and peripheral nervous system. 2) Antidepressants : mainly tricyclic anti depressants such as amitriptyllin are widely used. Side effects of them mainly the drowsiness will be beneficial in managing pain at nigh causing sleep deprivation. Other anti depressants would be serotonin-norepinephrine re-uptake inhibitors such as duloxetine. 3) Anti-convulsants : Anti-convulsants such as gabapentin and lamotrigine is beneficial in managing neuropathic pains. 4) Opioid and tramadol also has evidence in managing pain. NSAIDs should be avoided as it can cause renal impairement. [4][5][6][7]
Supportive management in renal failure Rehydration with maintaing adequate input and out put and dialysis can be use[8][9][10].
Supportive management for bone disease ans hypercalcaemia Bisphosphonate (eg: clodronate, zolendronate, pamidronate) give to all patients as it reduces the pathological fracture risk and bone pain. So it improve the over all mobility of the patient. In acute hypercalaemia, patient can manage with rehydrate with IV 0.9% saline, diuretics like frusemide, steroids (eg: prednisolone) and bisphosphonate[11][12][13][14].
Treat infections If patient developing recurrent infections and neutropenia is present Iv broad spectrum antibiotics should be given after taking blood/urine/sputum for culture and ABST. Prevention also very important vaccination, avoiding exposure to infected people and avoiding crowded places will helpful. If the frequency of recurrent infections are high, IV immunoglabuline infusion need to be given[15][16][17].
Treat anaemia According to the severity of the anaemia and symptoms, patient can be treated with blood transfusion and erythropoietin treatment[18][19][20].
Supportive management for compression symptoms Orthopaedic procedures such as vertebroplasty, kyphoplasty and decompression laminectomy will be useful[21][22][23].
Management of increased bleeding tendency Minimize trauma eg: avoid contact sports), minimize/ prevent puncturing (eg; avoid spinal anaesthesia) the body as much as possible, carefully look for spontaneous bleeding. If the patient is having life threatening acute bleeding platelet transfusion can be consider[24][25].
Management of hyperviscosity Repeated plasmapheresis will be useful according to the symptoms presenting with[26][27][28].
References
  1. KYLE RA, RAJKUMAR SV. Multiple myeloma Blood [online] 2008 Mar 15, 111(6):2962-2972 [viewed 14 November 2014] Available from: doi:10.1182/blood-2007-10-078022
  2. ZHAN F, HUANG Y, COLLA S, STEWART JP, HANAMURA I, GUPTA S, EPSTEIN J, YACCOBY S, SAWYER J, BURINGTON B, ANAISSIE E, HOLLMIG K, PINEDA-ROMAN M, TRICOT G, VAN RHEE F, WALKER R, ZANGARI M, CROWLEY J, BARLOGIE B, SHAUGHNESSY JD JR. The molecular classification of multiple myeloma Blood [online] 2006 Sep 15, 108(6):2020-2028 [viewed 14 November 2014] Available from: doi:10.1182/blood-2005-11-013458
  3. BLADé J, ROSIñOL L. Changing paradigms in the treatment of multiple myeloma Haematologica [online] 2009 Feb, 94(2):163-166 [viewed 14 November 2014] Available from: doi:10.3324/haematol.2008.002766
  4. KRISTINSSON SY, MINTER AR, KORDE N, TAN E, LANDGREN O. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management Expert Rev Mol Diagn [online] 2011 Jul, 11(6):593-603 [viewed 15 November 2014] Available from: doi:10.1586/erm.11.44
  5. CöMERT M, GüNEş AE, ŞAHIN F, SAYDAM G. Quality of Life and Supportive Care in Multiple Myeloma Turk J Haematol [online] 2013 Sep, 30(3):234-246 [viewed 15 November 2014] Available from: doi:10.4274/Tjh.2012.0192
  6. SOUTHERST D, DUFTON J, STERN P. Multiple Myeloma presenting as sacroiliac joint pain: a case report J Can Chiropr Assoc [online] 2012 Jun, 56(2):94-101 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364058
  7. O'CALLAGHAN CA. Acute renal failure associated with NSAIDS. BMJ [online] 1994 Mar 26, 308(6932):857-858 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540015
  8. BOOTH LJ, MINIELLY JA, SMITH EK. Acute renal failure in multiple myeloma Can Med Assoc J [online] 1974 Aug 17, 111(4):334-335 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947712
  9. MACKENZIE MR, WUEPPER KD, JORDAN G, FUDENBERG HH. Rapid renal failure in a case of multiple myeloma: the role of Bence Jones proteins Clin Exp Immunol [online] 1968 Jul, 3(6):593-601 [viewed 14 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578955
  10. BLACKMAN SS JR, BARKER WH, BUELL MV, DAVIS BD. ON THE PATHOGENESIS OF RENAL FAILURE ASSOCIATED WITH MULTIPLE MYELOMA. ELECTROPHORETIC AND CHEMICAL ANALYSIS OF PROTEIN IN URINE AND BLOOD SERUM J Clin Invest [online] 1944 Mar, 23(2):163-166 [viewed 14 November 2014] Available from: doi:10.1172/JCI101479
  11. POZZI S, RAJE N. The Role of Bisphosphonates in Multiple Myeloma: Mechanisms, Side Effects, and the Future Oncologist [online] 2011 May, 16(5):651-662 [viewed 15 November 2014] Available from: doi:10.1634/theoncologist.2010-0225
  12. TONOGAI I, GOTO T, HAMADA D, IWAME T, YOSHIOKA S, TSUTSUI T, GODA Y, EGAWA H, SAIRYO K. Bilateral Atypical Femoral Fractures in a Patient with Multiple Myeloma Treated with Intravenous Bisphosphonate Therapy Case Rep Orthop [online] 2014:452418 [viewed 15 November 2014] Available from: doi:10.1155/2014/452418
  13. MELEA PI, MELAKOPOULOS I, KASTRITIS E, TESSEROMATIS C, MARGARITIS V, DIMOPOULOS MA, TERPOS E. Conservative Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients Int J Dent [online] 2014:427273 [viewed 15 November 2014] Available from: doi:10.1155/2014/427273
  14. DRAKE MT, CLARKE BL, KHOSLA S. Bisphosphonates: Mechanism of Action and Role in Clinical Practice Mayo Clin Proc [online] 2008 Sep, 83(9):1032-1045 [viewed 15 November 2014] Available from: doi:10.4065/83.9.1032
  15. KHALAFALLAH A, MAIWALD M, COX A, BURNS D, BATES G, HANNAN T, SEATON D, FERNANDOPULLE B, MEAGHER D, BRAIN T. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation or Treated with Immunomodulatory Agents. Mediterr J Hematol Infect Dis [online] , 2(1):e2010005 [viewed 15 November 2014] Available from: doi:10.4084/MJHID.2010.005
  16. JOLLES S, SEWELL W, MISBAH S. Clinical uses of intravenous immunoglobulin Clin Exp Immunol [online] 2005 Oct, 142(1):1-11 [viewed 15 November 2014] Available from: doi:10.1111/j.1365-2249.2005.02834.x
  17. CHAPEL HM, LEE M. The use of intravenous immune globulin in multiple myeloma. Clin Exp Immunol [online] 1994 Jul, 97(Suppl 1):21-24 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550368
  18. BIRGEGåRD G, GASCóN P, LUDWIG H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY Eur J Haematol [online] 2006 Nov, 77(5):378-386 [viewed 15 November 2014] Available from: doi:10.1111/j.1600-0609.2006.00739.x
  19. OLUJOHUNGBE A, HANDA S, HOLMES J. Does erythropoietin accelerate malignant transformation in multiple myeloma? Postgrad Med J [online] 1997 Mar, 73(857):163-164 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431253
  20. BIRGEGåRD G. Managing anemia in lymphoma and multiple myeloma Ther Clin Risk Manag [online] 2008 Apr, 4(2):527-539 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504072
  21. OMIDI-KASHANI F, HASANKHANI EG, AKHLAGHI S, GOLHASANI-KESHTAN F, TOOSI KZ. Percutaneous vertebroplasty in symptomatic hemangioma versus osteoporotic compression fracture Indian J Orthop [online] 2013, 47(3):234-237 [viewed 15 November 2014] Available from: doi:10.4103/0019-5413.111498
  22. ZHANG GQ, GAO YZ, ZHENG J, LUO JP, TANG C, CHEN SL, WANG HQ, LIU K, XIE RG. Posterior decompression and short segmental pedicle screw fixation combined with vertebroplasty for K?mmell's disease with neurological deficits Exp Ther Med [online] 2013 Feb, 5(2):517-522 [viewed 15 November 2014] Available from: doi:10.3892/etm.2012.833
  23. PAN J, QIAN ZL, SUN ZY, YANG HL. Open kyphoplasty in the treatment of a painful vertebral lytic lesion with spinal cord compression caused by multiple myeloma: A case report Oncol Lett [online] 2013 May, 5(5):1621-1624 [viewed 15 November 2014] Available from: doi:10.3892/ol.2013.1222
  24. TAIWO E, WANG H, LEWIS R. Treatment of Coexisting Chronic Neutrophilic Leukemia and Light Chain Multiple Myeloma with Hydroxyurea, Bortezomib, and Dexamethasone Case Rep Hematol [online] 2014:869395 [viewed 15 November 2014] Available from: doi:10.1155/2014/869395
  25. FIELD-SMITH A, MORGAN GJ, DAVIES FE. Bortezomib (Velcade(TM)) in the Treatment of Multiple Myeloma Ther Clin Risk Manag [online] 2006 Sep, 2(3):271-279 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936263
  26. PARK MS, KIM BC, KIM IK, LEE SH, CHOI SM, KIM MK, LEE SS, CHO KH. Cerebral Infarction in IgG Multiple Myeloma with Hyperviscosity J Korean Med Sci [online] 2005 Aug, 20(4):699-701 [viewed 15 November 2014] Available from: doi:10.3346/jkms.2005.20.4.699
  27. PRUZANSKI W, CHU R, DAMJI NF, GALLER S, NORMAN CS. Anemia, splenomegaly and hyperviscosity syndrome. Can Med Assoc J [online] 1980 Oct 18, 123(8):731-737 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704856
  28. MCGRATH MA, PENNY R. Paraproteinemia: blood hyperviscosity and clinical manifestations. J Clin Invest [online] 1976 Nov, 58(5):1155-1162 [viewed 15 November 2014] Available from: doi:10.1172/JCI108568

Management - Specific Treatments

Fact Explanation
Allogenic stem cell transplantation This is use in young patients and it can cure the disease. But there is increased risk of mortality in 30%[1][2][3].
Intensive treatment This is usually given to the patients less than 70 years of age.In here, amount of the tumour will reduce with several course of chemotherapy (eg: cyclophospamide, vincristine). This reduces the paraprotein level and bony lesions.In elderly patients these drugs can be given combine with steroids (eg: dexamethasone). With the reduction of tumour bulk, chemotherapy usually followed by stem cell collection and autologus stem cell transplantation[4]-[9].
Non- intensive treatment In elderly patients this treatment option is use to control the disease progression and improve the morbidity of the patient. Oral alkylating agent melpalan is use nearly for a month. this can be combine with prednisolone[10][11][12]. Thalidomide is proven to have marked improvement in survival. This can vbe use in elderly population and better to avoid in fertile age as it is having a teratogenic effect. If it is indicated in young patients proper contraseptive method need to be used[13][14][15].
Treatment in relapses Thalidomide, lenalidomide and bortezomib like drugs can be use in relapsing[16][17][18].
Radiotherapy This is effective in symptomatic management of multiple myeloma especially when intractable bone pain and spinal cord compression is presen[19]20][21].
Surgical management This will include the management of existing fractures (orthopedic management will depend on the site of the fracture, extend of it and the age of the patient), prophylactic measures in impending pathological fractures ( health education, calcium treatment and life style modifications to prevent injuries) & decompression of spinal cord injuries (eg:vertebroplasty, kyphoplasty and decompression laminectomy) [22][23][24].
References
  1. BENSINGER WI. Is there still a role for allogeneic stem-cell transplantation in multiple myeloma? Best Pract Res Clin Haematol [online] 2007 Dec, 20(4):783-795 [viewed 15 November 2014] Available from: doi:10.1016/j.beha.2007.09.007
  2. KUMAR S. Stem cell transplantation for multiple myeloma Curr Opin Oncol [online] 2009 Mar, 21(2):162-170 [viewed 15 November 2014] Available from: doi:10.1097/CCO.0b013e328324bc04
  3. SUMRALL B, DIETHELM L, BROWN A JR. Multiple Myeloma Relapse Following Autologous Stem Cell Transplant Presenting With Diffuse Pulmonary Nodules Ochsner J [online] 2013, 13(4):553-557 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865837
  4. ANDERSON H, SCARFFE JH, RANSON M, YOUNG R, WIERINGA GS, MORGENSTERN GR, FITZSIMMONS L, RYDER D. VAD chemotherapy as remission induction for multiple myeloma. Br J Cancer [online] 1995 Feb, 71(2):326-330 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033610
  5. FIELD-SMITH A, MORGAN GJ, DAVIES FE. Bortezomib (Velcade(TM)) in the Treatment of Multiple Myeloma Ther Clin Risk Manag [online] 2006 Sep, 2(3):271-279 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936263
  6. RICCARDI A, MORA O, BRUGNATELLI S, TINELLI C, SPANEDDA R, DE PAOLI A, BARBARANO L, DI STASI M, BERGONZI C, GIORDANO M, DELFINI C, NICOLETTI G, RINALDI E, PICCININI L, VALENTINI D, ASCARI E. Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma. Br J Cancer [online] 1998, 77(3):485-491 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151281
  7. KYLE RA. Role of Maintenance Therapy After Autologous Stem Cell Transplant for Multiple Myeloma: Lessons for Cancer Therapy Mayo Clin Proc [online] 2011 May, 86(5):419-420 [viewed 15 November 2014] Available from: doi:10.4065/mcp.2011.0171
  8. MOHTY M, HAROUSSEAU JL. Treatment of autologous stem cell transplant-eligible multiple myeloma patients: ten questions and answers Haematologica [online] 2014 Mar, 99(3):408-416 [viewed 15 November 2014] Available from: doi:10.3324/haematol.2013.096149
  9. GERTZ MA, DINGLI D. How we manage autologous stem cell transplantation for patients with multiple myeloma Blood [online] 2014 Aug 7, 124(6):882-890 [viewed 15 November 2014] Available from: doi:10.1182/blood-2014-03-544759
  10. KYLE RA, RAJKUMAR SV. Multiple myeloma Blood [online] 2008 Mar 15, 111(6):2962-2972 [viewed 15 November 2014] Available from: doi:10.1182/blood-2007-10-078022
  11. JOHNSON PW, SELBY PJ. The treatment of multiple myeloma--an important MRC trial. Br J Cancer [online] 1994 Nov, 70(5):781-785 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033545
  12. MANSI JL, CUNNINGHAM D, VINER C, ELLIS E, MELDRUM M, MILAN S, GORE M. Repeat administration of high dose melphalan in relapsed myeloma. Br J Cancer [online] 1993 Nov, 68(5):983-987 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968739
  13. D'AMATO RJ, LOUGHNAN MS, FLYNN E, FOLKMAN J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A [online] 1994 Apr 26, 91(9):4082-4085 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43727
  14. CAVALLO F, BOCCADORO M, PALUMBO A. Review of thalidomide in the treatment of newly diagnosed multiple myeloma Ther Clin Risk Manag [online] 2007 Aug, 3(4):543-552 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374936
  15. YANG G, CHEN W, WU Y. Bortezomib, dexamethasone plus thalidomide for treatment of newly diagnosed multiple myeloma patients with or without renal impairment Chin J Cancer Res [online] 2013 Apr, 25(2):155-160 [viewed 15 November 2014] Available from: doi:10.3978/j.issn.1000-9604.2013.03.07
  16. SHAH N, LONIAL S. Treatment options for patients with relapsed/refractory myeloma who have previously been treated with novel agents and high-dose chemotherapy/autologous stem cell transplant Hematology Am Soc Hematol Educ Program [online] 2010:310-313 [viewed 15 November 2014] Available from: doi:10.1182/asheducation-2010.1.310
  17. MATEOS MV, SAN MIGUEL JF. Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma Ther Adv Hematol [online] 2012 Apr, 3(2):117-124 [viewed 15 November 2014] Available from: doi:10.1177/2040620711432020
  18. VAN DE DONK NW, GöRGüN G, GROEN RW, JAKUBIKOVA J, MITSIADES CS, HIDESHIMA T, LAUBACH J, NIJHOF IS, RAYMAKERS RA, LOKHORST HM, RICHARDSON PG, ANDERSON KC. Lenalidomide for the treatment of relapsed and refractory multiple myeloma Cancer Manag Res [online] :253-268 [viewed 15 November 2014] Available from: doi:10.2147/CMAR.S27087
  19. NGUYEN SK, DAGNAULT A. Radiotherapy for multiple myeloma with skin involvement Curr Oncol [online] 2010 Oct, 17(5):74-77 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949377
  20. MAYER MN, KERR ME, GRIER CK, MACDONALD VS. Immunoglobulin A multiple myeloma with cutaneous involvement in a dog Can Vet J [online] 2008 Jul, 49(7):694-702 [viewed 15 November 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430402
  21. LIU J, BAKST R, PHELPS R, JAGANNATH S, BLACKSBURG S. Radiation Therapy for Secondary Cutaneous Plasmacytomas Case Rep Hematol [online] 2013:739230 [viewed 15 November 2014] Available from: doi:10.1155/2013/739230
  22. SARAHRUDI K, HORA K, HEINZ T, MILLINGTON S, VéCSEI V. Treatment results of pathological fractures of the long bones: a retrospective analysis of 88 patients Int Orthop [online] 2006 Dec, 30(6):519-524 [viewed 28 November 2014] Available from: doi:10.1007/s00264-006-0205-9
  23. OFLUOGLU O, EROL B, OZGEN Z, YILDIZ M. Minimally invasive treatment of pathological fractures of the humeral shaft Int Orthop [online] 2009 Jun, 33(3):707-712 [viewed 28 November 2014] Available from: doi:10.1007/s00264-008-0540-0
  24. LI Y, WALKER CL, ZHANG YP, SHIELDS CB, XU XM. Surgical decompression in acute spinal cord injury: A review of clinical evidence, animal model studies, and potential future directions of investigation Front Biol (Beijing) [online] 2014 Feb 1, 9(2):127-136 [viewed 28 November 2014] Available from: doi:10.1007/s11515-014-1297-z