This document discusses various types of para-proteinemias, which are immunoglobulins produced in excess by abnormal B-lymphocytes or plasma cells. It describes conditions like monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, Waldenstrom's macroglobulinemia, and others. For each condition, it covers causes, risk factors, symptoms, complications, diagnostic tests, and common treatments.

1. Para-Proteinemias

2. Para-Proteins are immunoglobulins that are produced
in excess by abnormal clonal proliferation of B-
lymphocytes or plasma cells.
They exist as heavy chain ( Ig-G, Ig-A ,Ig-E,& Ig-D) and
light chain ( Kappa or lambda)

3. Types
Mono-clonal gammapathy of undetermined
significance ( MGUS)
Multiple myeloma
Waldenstrom’s Macroglobulinemia
Alpha – heavy chain disease
Amyloidosis

4. Light chain 1) Multiple myeloma
2) AL-Amyloidosis
 Heavy chain  Heavy chain disease
Whole immunoglobulins  Cryoglobulinemia

5. Causes
Leukemias
Lymphomas NH-L
Myelomas
Plasmocytomos
Idiopathic
AL- Amyloidosis

6. MGUS
Presents of M-proteins in serum and urine without the
evidence of the multiple myeloma , Waldenstrom’s
Macroglobulinemia, AL- Amyloidosis .

7. Etiology Unknown
Risk factors 1) Old age.
2) Males
3) Blacks
4) Family history

8. Other Risk factors Inflammatory Disorder.
2) Auto-immune disorders
3) Smoking
4) Pesticides
5) Infection
6) Obesity

9. Age group 50 to 85
Median age 70years
A/w chromosomal translocation 14q32

10. Symptoms
Generalized weakness
Infection
Weightloss
Bleeding manifestation

11. Complications
Venousthrombo-embolism
Osteoporosis
Infections
Neuropathy
Nephropathy
Skin

12. Investigations
CBC
Serum and urine protein electrophoresis
Quantitative immunoglobulin measurements
Bone marrow study
Skeletal survey

13. Multiple myeloma
Etiology
Genetic Cmyc , Kras and Nras
Environmental✓ Pesticides
✓Industries
✓ Radiation
✓ Infections

14. Age group-50 to 70 years
Median age 65 years

15. Symptoms
Bone pain
Pathological fracture
Weakness
Infections
Spinal cord compression
Neurological symptoms
Hepato-splenomegaly
Cardiomegaly

16. Complications
Renal failure
Haematological ✓ Anemia
✓ Neutropenia
✓ Thrombocytopenia
Hyperviscocity  Thrombosis

17. Diagnosis
 CBC
 Urine analysis  Bence jones proteinuria
 SPEP Finding out M-Proteins
 UPEP
 Quantitative immunoglobulin measurements
 Beta 2 microglubulins surrogate marker of tumor burden
 CRP  Surrogate marker of IL-6

18. Radilogical
X-Ray Skull- punched out lesion
MRI
PET scan
Bone marrow aspiration

19. Treatment
Immunomodulator Lenalidomide
Proteosome inhibitor  Bortezomib
Steroids Dexamethasone
High dose melphalan
Stem cell transplantation

20. Waldenstrom’s Macroglobulinemia
Etiology  Mutation in MyD88L265p
Hepatitis C/G
HHV-8
Median age-65 years

21. Clinical manifestations
 weakness
Anorexia
Peripheral neuropathy
Weight loss
Fever
Raynaud’s phenomenon

22. Complications
Hyperviscocity syndrome
Bleeding tendency
Hepato-splenomegaly
Lymphadenopathy
Purpura

23. Investigations
CBC
LDH-Increased
Uric acid –increased
ESR – Increased
Beta 2 microglubulins and CRP  not specific.

24. SPEP M component with beta to gamma mobility is
specific.
Imaging  CT , MRI
Bone marrow aspiration
Flow cytometry

25. Treatment
Rituximab
Ibrutinib
Fludarabine
Cladriabine
Bortezomib

26. Thank you