IN THE NAME
OF GOD
• The patient is a 57 y/o man ,known
case of DM,HTN, and CKD who was
referred due to LBP and left hip pain.
• The patient is a middle aged man who
complains of bone pain in left femur
since 1 year ago .
• BMD: NL.
• Uremic symptoms :( N/V, drowsiness, anasarca
edema, and Cr=12) since 3 month ago.
hemodialysis was begune.
• A history of LBP and left hip pain begane since
3 month ago (no history of trauma).
• Bone pain worsens with activity , no
radiation.
• Other problems:
• Weight loss (30 kg) since 3 years ago,
spontaneous fracture of rib 1 year ago,
(Seldom fever and fatigue,no urine
obstruction or incontinency.
• No stool incontinency.)
Past medical
History
•
1.
2.
3.
4.
5.
6.
DM since 10 years ago
HTN since 4 years ago
CKD since 3 years ago
Coronary artery stenting 3 years ago ( after MI)
CHF since 3 years ago
Hospital admission due to uremic symptoms and
LBP
7. Hospital admission due to catheter infection 2
month ago
8. Hospital admission due to pneumonia 3 weeks ago
9. Fistula insertion 2 month ago
Drug History
• Tab ASA 80 /d
• Tab Atorvastatin 20/d
• Tab carvedilol 3.125/BD
• Caplet Renagel 800/d
• Tab Folic acid 5/d
• Tab Lasix 40 /d
• Tab Plavix 75/d
• Tab N.C 2.6/ BD
• Insulin Lantus 8 IU/qhs
Physical Examination
• GA: The patient is a middle aged man who is
pale, and complains of weakness ,bone pain
,and fatigue.
• V/S: BP=120/75, PR= 86, RR=18, T= 37 axillary,
and SO2=94% without O2
• H&N: pale conjunctivea, sclera Nl , No LAP
, No thyromegaly , Internal double lumen in
Rt Jugular vein without erythema or
discharge of the site of insertion
• Heart: Nl S1,Nl S2,II/VI early systolic
murmur in LSB
• Lung: bilateral end inspiration fine rales in
basal part.
• Abdomen: soft, no tenderness , no organomegaly
• Ext: bilateral pitting edema in pretibial without
size difference, no cyanosis, no clubbing, left
brachial fistula with thrill and bruit
• Musculosceletal: tenderness on Lumbar spine(L1),
tenderness in left SIJ, Nl ROM ,Neurology
examination: bilateral pinprick abnormality
Problem List
1. Known case of DM ,HTN ,MI, CKD
2. Bone pain
3. Weight Loss
4. Uremic symptoms
5. Fever
6. spontaneous fracture
7. Edema
8. Systolic murmur
9. Fine rales in basal part of lung
10.Tenderness on lumbar spine and SIJ
Differential diagnosis of
Bone pain
1.Injury
2.Mineral deficiency
3.Metastatic cancer
4.Bone cancer
5.Multiple myeloma
6.Infection
7.Leukemia
8.Overuse
9.Toddler fracture
10.Osteomyelitis
LAB TESTS
• CBC: WBC= 10200(Nl diff), HG= 9.6 , MCV=92 ,
Plt=293000
• Fe= 43, TIBC=387, Ferritin=107, SI=11%
• ESR=53, CRP= negative
• Na=143,K=5,Ca=9.1,P=6.6,Mg=2.8,urea=102,Cr=
9.6,uric acid=6.2
• AST=40,ALT=43,ALP=1393(Nl up to 396),Bil
T=0.7,Bil D=0.2
• GGT=220(up to 49)
• PTH=28.5(6.3-36.5)
• PSA= 0.35
• Blood culture=negative
• U/A: Pro 2+, Glu 3+, not WBC , not RBC
• U/C: negative
• Lipid Profile normal
• Alb=4.1
• Viral marker = negative
ISOLATED ELEVATION OF THE ALP
• Women in the third trimester of pregnancy
• Blood types O and B can have elevated ALP after eating
a fatty meal due to an influx of intestinal ALP
• Children and adolescents (physiological osteoblastic
activity)
• Gradually increases from age 40 to 65 years particularly
in women.
• ALP was increased due to previous fracture healing.
• The first step in the elevation of an elevation ALP is
to identify its source.
• Either a GGT level or serum 5’-nucleotidase level
should be obtained.
• These tests are usually elevated in parallel with the
ALP in liver disorders but are not increased in bone
disorders.
ELEVATED GGT
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DM
COPD
Alcohol abuse
ESRD
Pancreas disease
Biliary disease
NASH
Chronic Hepatitis(B,C)
Alpha1- antitrypsin deficiency
Medication(phenytoin , barbiturats)
• An elevated GGT with otherwise normal liver
biochemical tests should not lead to an
exhaustive work-up for liver disease.
• Serum Protein Electrophoresis:
Alb= 56.4(54-66)
Alpha 1= 4.9(1.4-2.8)
Alpha 2= 18(9.1-13.8)
Beta= 14.3(8.7-14.4)
Gamma= 11.7(10.6-19.2)
• Serum Immuno Electrophoresis
IgG= 725(700-1600)
IgM= 77(40-230)
IgA= 61(70-400)
IgE= 38(<182)
• 20% of MM produce only light chains
• In nephrotic syndrome(decreased all of the IG)
• Non-secretory multiple myeloma
NON-SECRETORY MULTIPLE MYELOMA
• 3% of patients with MM have no M-protein in the serum
or urine on immunofixation at the time of diagnosis.
• Free light chain (FLC) assays can be used to detect
monoclonal protein in the absence of M protein with the
above studies.
• 60% of patients with MM who have a normal serum and
urine immunofixation, monoclonal free light chain can be
detected in the serum using FLC assays.
• The FLC assay measures serum Kappa and Lambda light chain
levels.
• Patients with myeloma who have normal serum and urine
immunofixation and normal serum FLC assay are considered
to have nonsecretory myeloma.
• 85% will have M-protein that be detected in the cytoplasm of
the neoplastic plasma cells by immunochemistry, but have
impaired secretion of this protein,
• 15% do not have immunoglobulin detectable in the plasma
cells( non-producer myeloma)
•
• Patients with nonsecretory MM are not at risk for meloma
kidney as long as light chains cannot be detected in the
urine, but they are at risk for other complication of MM.
• BMA and BMB were done for his which
were diagnostic for MM.(16% plasma
cells)
• PBS: rouleaux formation
Paraclinic finding
• Chest CT Scan: sign of heart is enlarged
with significant prominanting venus
marking. No Lymphadenopathy
• ECG: LBBB
• Echocardiography: EF=35-40% ,
PAP=50, Mild AI, Mild TR, Global LV
H.K.Moderate to severe LV disfunction.
And RA enlargement.
NEUROSURGERY CONSULT
• EMG & NCV : polyradiculopathy
• Candidate for surgery
Abdominopelvic sonography:
• Liver normal in size and echogenicity ,
Gallblodder and biliary ducts were normal
without dilatation. Diameter hepatic and
portal veins were normal. Spleen was
normal in size and echogenicity. Pancrease
is normal. Kidney was normal in size and
echogenicity. Prostat normal in size and
echogenicity.
CKD WITH NORMAL SIZE OF KIDNEY
• Diabetes
• Polycystic kidneys
• AIDS
• Multiple Myeloma
• Amyloidosis
WHOLE BODY BONE SCAN
• Area of abnormal bone activity are noted in
skeleton especially: prominent hypo-active
(lytic) lesion with peripheral increased
osseous activity in left iliac wing superior to
acetabulum.
• Poorly defined but hyper-vascular lesion in
left trochanteric region and suspected one
in right proximal femur.
• Area of increased activity in about L1.
• Several foci of increased uptake in some ribs
bilaterally.
• Suspected lesion on left side of skull.
• Finding are more suggestive of malignant
process (MM, Lymphoma,….metastases).More
evaluation to exclude hyperparathyroidism/Brown tumor may also be
considered.
• Radiographic survey is also recommended; some
lesion may be undetectable or poorly defined by
bone scan.
About multiple
myeloma
• When a doctor is investigating symptoms that
suggest multiple myeloma, such as bone pain,
anemia, fatigue, unexplained fractures, or recurrent
infections, to look for the presence of a
characteristic band (monoclonal immunoglobulin) in
the beta or gamma region; if a sharp band is seen,
its identity as a monoclonal immunoglobulin is
typically confirmed by immunofixation
electrophoresis.
• To monitor treatment of multiple myeloma to see if
the monoclonal band is reduced in quantity or
disappears completely with treatment
• Multiple myeloma (myelo + oma, "marrow"
+ "tumor"), also known as plasma cell
myeloma, myelomatosis, or Kahler's
disease (after Otto Kahler), is a cancer of
plasma cells, a type of white blood cell
normally responsible for producing
antibodies.
• Multiple Myeloma is a type of blood cancer that affects
the plasma cells. Plasma cells are immune cells that
normally make special proteins, called antibodies, to fight
off disease. These antibodies are part of the body’s
defense system to neutralize infections that invade the
blood stream. Patients who have multiple myeloma make
plasma cells that are abnormal. These plasma cells do not
make normal antibodies anymore, but instead make too
much of one kind of protein. When this happens, the
levels of these proteins in the blood become higher than
normal.
•
In multiple myeloma, collections of abnormal
plasma cells accumulate in the bone marrow, where
they interfere with the production of normal blood
cells. Most cases of multiple myeloma also feature
the production of a paraprotein —an abnormal
antibody which can cause kidney problems. Bone
lesions and hypercalcemia (high blood calcium
levels) are also often encountered
• Multiple myeloma is diagnosed with blood
tests (serum protein electrophoresis, serum
free kappa/lambda light chain assay), bone
marrow examination, urine protein
electrophoresis, and X-rays of commonly
involved bones.
• Multiple myeloma is considered to be incurable
but treatable. Remissions may be induced with
steroids, chemotherapy, proteasome inhibitors,
immunomodulatory drugs such as thalidomide
or lenalidomide, and stem cell transplants.
• Radiation therapy is sometimes used to reduce
pain from bone lesions
• Multiple myeloma develops in 6.1 per 100,000
people per year. It is more common in men and,
for unknown reasons, is twice as common in
African-Americans as it is in EuropeanAmericans. With conventional treatment,
median survival is 3–4 years, which may be
extended to 5–7 years or longer with advanced
treatments. Multiple myeloma is the second
most common hematological malignancy in the
U.S. (after non-Hodgkin lymphoma), and
constitutes 1% of all cancers. The five year
survival rate is 45%
• Because many organs can be affected by
myeloma, the symptoms and signs vary greatly. A
mnemonic sometimes used to remember some
of the common symptoms of multiple myeloma
is CRAB: C = Calcium (elevated), R = Renal failure,
A = Anemia, B = Bone lesions.
• Myeloma has many other possible symptoms,
including opportunistic infections (e.g.,
pneumonia). CRAB symptoms and proliferation
of monoclonal plasma cells in the bone marrow
are part of the diagnostic criteria of multiple
myeloma.
• Illustration showing the most common site of bone lesions
in vertebrae
• Bone pain affects almost 70% of patients and is the most
common symptom
• Myeloma bone pain usually involves the spine and ribs,
and worsens with activity and does not occur at night
except with change of position. Persistent localized pain
may indicate a pathological bone fracture. Involvement of
the vertebrae may lead to spinal cord compression.
• The patient’s height may be reduced because of
vertebral collaps.
• Plasmacytomas of the ribs occur and can present
with costal lesion or soft tissue mass.
Clinical Manifestation
• Hypercalcemia: The breakdown of bone also
leads to release of calcium into the blood,
leading to hypercalcemia and its associated
symptoms.
• Anemia: The anemia found in myeloma is usually
normocytic and normochromic. It results from
the replacement of normal bone marrow by
infiltrating tumor cells , kidney damage , and
hemolysis . Macrocytosis can presented with
unknown reason,investigation must be done to
rule out pernicious anemia.
HYPERVISCOSITY
• Increased serum viscosity is occasionally noted in patients
with multiple myeloma. It is more frequently noted in
patients with heavy chain immunoglobulin(IgM) .
• . Hyperviscosity is more frequently noted in patients with
Waldenström's macroglobulinemia.
• High viscosity interferes with efficient blood circulation of
the brain, kidneys, and extremities. Symptoms of
hyperviscosity include headache, dizziness, vertigo, and
severe ischemia
RENAL FAILURE
• Renal failure may develop both acutely and
chronically.
• Kidney failure is a common complication of multiple
myeloma. When first diagnosed, as many as 20-40%
of patients with multiple myeloma will have some
amount of kidney failure. Multiple myeloma can
affect the kidney in several ways. It can affect the
filter (glomerulus), the tubules (pipes), or the tissue
of the kidney itself (interstitium).
• The most common cause of renal failure in multiple
myeloma is due to proteins secreted by the malignant
cells. Myeloma cells produce monoclonal proteins of
varying types, most commonly immunoglobulins
(antibodies) and free light chains, resulting in abnormally
high levels of these proteins in the blood.(myeloma
kidney)
• Depending on the size of these proteins, they
may be excreted through the kidneys. Kidneys
can be damaged by the tubulopathic effects of
proteins or light chains. Increased bone
resorption leads to hypercalcemia and causes
nephrocalcinosis thereby contributing to the
renal failure.
• Amyloidosis is a distant third in the causation.
Patients with Amyloidosis have high levels of
Amyloid protein that can be excreted through
the kidneys and cause damage to the kidneys
and other organs.
• Light chains produce myriad effects which can
manifest as the Fanconi syndrome (type II renal
tubular acidosis).
• Other causes include hyperuricemia, recurrent
infections (pyelonephritis), and local infiltration
of tumor cells.
• Medication (NSAIDs,Bisphosphonats)
• Contrast exposure
INFECTION
• The most common infections are pneumonias and
pyelonephritis.
• Common pneumonia pathogens include S. pneumoniae,
S. aureus, and K. pneumoniae, while common
pathogens causing pyelonephritis include E. coli and
other gram-negative organisms.
• The greatest risk period for the occurrence of infection
is in the initial few months after the start of
chemotherapy. The increased risk of infection is due to
immune deficiency.
• Although the total immunoglobulin level is
typically elevated in multiple myeloma, the
majority of the antibodies are ineffective
monoclonal antibodies from the clonal plasma
cell. A selected group of patients with
documented hypogammaglobulinemia may
benefit from replacement immunoglobulin
therapy to reduce the risk of infection.
NEUROLOGICAL SYMPTOMS
• Some problems (e.g., weakness, confusion and
fatigue) may be due to anemia or hypercalcemia.
Headache, visual changes and retinopathy may
be the result of hyperviscosity of the blood
depending on the properties of the paraprotein.
• Finally, there may be radicular pain, loss of bowel or
bladder control (due to involvement of spinal cord leading
to cord compression) or carpal tunnel syndrome and other
neuropathies (due to infiltration of peripheral nerves by
amyloid). It may give rise to paraplegia in late presenting
cases.
• When the disease is well-controlled, there may
be neurological symptoms resulting from current
treatments, some of which may cause peripheral
neuropathy, manifesting itself as numbness or
pain in the hands, feet, and lower legs.
Diagnostic criteria for MM
and related disorders
MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANT(MGUS)
• Serum monoclonal protein<3g/dl
• Bona marrow plasma cells<10%
• No end organ damage to plasma dyscrasia
• Often does not need to be treated right away
SMOLDERING (ASYMPTOMATIC) MM
• Serum monoclonal protein>3g/dl
• Bona marrow plasma cells>10%
• No end organ damage to plasma dyscrasia
• Often does not need to be treated right away
MULTIPLE MYELOMA
• Serum or urinary monoclonal protein
• Clonal plasma cells in the BM or a plasmacytoma
• End organ damage
1. Increased Ca
2. Lytic bone lesions
3. Anemia
4. Renal failure
ISS( INTERNATIONAL STAGING SYSTEM)
• I ( B2M < 3.5 , Alb> 3.5)
• II ( neither stage 1 nor stage 3)
• III( B2M > 5.5)
29 month
62 month
44 month
Thanks for your
attention