MRCP revision battle 33.1: Myeloma

So today is going to be a galavant through the world of paraproteinaemias, taking in 4 of the top 6 causes (myeloma, Waldenstrom's, MGUS and amyloid; lymphoma/leukaemia related are not discussed, nor is heavy chain disease)

While on the topic of paraproteinaemia is seems appropriate to cover hyperviscosity syndrome, which lends itself to a quick forray into polycythaemia and then on to two completely random topics to round off the day.

Enjoy!


MRCP revision battle 33.1: Myeloma
MRCP revision battle 33.2: Hyperviscosity syndrome

MRCP revision battle 33.3: Waldenstrom's macroglobulinaemia
MRCP revision battle 33.4: MGUS
MRCP revision battle 33.5: Amyloidosis
MRCP revision battle 33.6: Polycythaemia
MRCP revision battle 33.7: Levels of evidence
MRCP revision battle 33.8: Holmes Adie pupil



MRCP revision battle 33.1: Myeloma


Myeloma is a malignant monoclonal proliferation of plasma cells.
The commonest subclass is IgG (IgG>IgA>IgM)



Symptoms:

• osteolytic bone lesions --> backache/pathological fractures
• symptoms of hypercalcaemia
• bacterial infections due to immunoparesis
• renal impairment due to light chains

Investigations:

• Bloods:
• normocytic normochromic anaemia
• rouleaux on blood film
• raised calcium (40%)
• raised urea and creatinine
• raised ESR
• Urine
• Bence Jones proteins (=free serum light chains) in urine (66%)
• XR
• ?pepper pot skull, vertebral collapse

The diagnostic criteria for myeloma is:

1. monoclonal protein band in serum or urine electrophoresis
2. increased plasma cells on BM biopsy
3. evidence of end organ damage from myeloma

Treatment:

• supportive
• chemo
• younger patients: aggressive (VAD - vincristine, adriamycin, dexamethasone)
• older patients: less aggressive (CDT - cyclophosphamide, dexamethasone, thalidomide)

Complications of myeloma include:

• Hyperviscosity syndrome
• Hyperviscosity syndrome occurs most commonly in IgM myeloma (IgM>IgA>IgG)
• Transfusions should be avoided in hyperviscosity syndrome.
• hypercalcaemia
• spinal cord compression
• acute renal failure
• AL amyloidosis (15%)

Survival with myeloma tends to be 3-4 yrs. 
Higher beta 2 microglobulin implies a worse prognosis.



Onwards for a bit more about hyperviscosity syndrome....

MRCP revision battle 33.2: Hyperviscosity syndrome

Hyperviscosity syndrome is a condition in which the viscosity (='stickiness') of the blood has increased to a degree which prevents easy flow through the microcirculation.



This causes symptoms such as:

• lethargy
• confusion
• headache
• visual disturbances
• spontaneous bleeding

The visual disturbance is described as 'looking through a watery car windscreen'
The optic disc may occur blurred.



Normal plasma viscosity is 1.4-1.8.  Hyperviscosity syndrome develops above around 4.



Causes of hyperviscosity syndrome include:

• myeloma
• Waldenstroms macroglobulinaemia
• leukaemias
• polycythaemia

Treatment depends on the cause; in myeloma/waldenstroms the patient needs plasmaphersis whereas in polycythaemia the treatment is venesection.



So now seems a good time to battle Waldenstrom's macroglobulinaemia...

MRCP revision battle 33.3: Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia, AKA lymphoplasmacytoid lymphoma, is a condition in which monoclonal proliferation of terminally differentiated lymphocytes results in a monoclonal IgM paraprotein.

The significance of this is that IgM carries a high risk of hyperviscosity syndrome.



Treatment for Waldenstom's:

• none if asymptomatic
• plasmapheresis if hyperviscosity
• ? chemo

On to another paraproteinaemia, MGUS...

MRCP revision battle 33.4: MGUS

MGUS stands for monoclonal gammopathy of undetermined significance.
As the name suggests, it is a low-level paraproteinaemia of unknown relevance.

It is common, affecting around 3% of those over 70 yrs of age.


For MGUS to be diagnosed the following diagnostic criteria must be met:

1. low level paraprotein (<30g/l)
2. less than 10% plasma cells on BM
3. no clinical evidence of myeloma.

Around 10% have myeloma at 5yrs so management tends to be yearly observation.


On to amyloidosis...

MRCP revision battle 33.5: Amyloidosis

coming soon....


for now skip on to polycythaemia..

MRCP revision battle 33.6: Polycythaemia

Polycythaemia is a raised red cell count and haemocrit, defined as >0.52 in males or >0.48 in females.


The first thing to establish is if the polycythaemis is 'true/absolute' or 'relative/pseudo'.



Relative/pseudo polycythaemia occurs due to decreased plasma volume.  This may occur due to dehydration (eg vomiting, diarrhoea, diuretics)

A special form of relative polycythaemia is Gaisbocks.  This tends to affect middle-aged men and is attributed to stress (hypertension, smoking, mild obesity) causing a chronically reduced plasma volume.




True/absolute polycythaemis is due to raised red cell mass.
It can be further divided into primary true polycythaemia and secondary true polycythaemia.





Primary true polycythaemia = polycythaemia rubra vera


Polycythaemia rubra vera is associated with JAK2 mutation in 95% of cases.

It peaks in the 6th decade.


Features include:

• hyperviscosity-syndrome symptoms
• pruritis, especially after a hot bath
• splenomegaly
• plethoric features
• hypertension in 1/3
• haemorrhage secondary to abnormal platelets
• DVTs/arterial thrombosis
• peptic ulceration
• gout

WCC/platelets/neutrophil alkaline phosphatase are raised; this helps distinguish primary from secondary polycythaemia.




Secondary polycythaemia 


Secondary polycythaemia is due to raised erythropoietin.

Causes:

• physiological - neonates, high altitude
• congenital cyanotic heart disease
• smoking/COPD
• HbM
• renal cysts
• post renal transplant
• fibroids
• hepatoma

Management of true polycthaemia is:

• venesection
• hydroxyurea to supress erythropoesis
• aspirin

Now for something completely different - levels of evidence...

MRCP revision battle 33.7: Levels of evidence

In this age of evidence-based medicine there is a scale to judge how "good" the evidence is:






Ia: metaanalysis of RCT
Ib: RCT


IIa: controlled trial
IIb: experimental trial


III: case series, case-control studies


IV: 'expert' opinions



Remember these because the odd MRCP question asks you what level of evidence a particular study is providing.


To the final MRCP revision battle of the day...

MRCP revision battle 33.8: Holmes Adie pupil

Holmes-Adie pupil is a dilated (myotonic) pupil.


It is a benign condition.

Females (70%) > males (20%)
Unilateral in 80% of cases


A Holmes-Adie pupil is sluggish to accomodate and reacts poorly, if at all, to light.



If a Holmes-Adie pupil is associated with absent leg reflexes it is known as Holmes-Adie Syndrome.





Since that was such a short battle lets just throw in a quick recap of the diferentials for a dilated pupil:

• third nerve palsy
• drugs
• antidepressants
• amphetamines
• atropine
• tropicamide
• Holmes-Adie
• trauma - sphincter pupillae rupture