Monday 18 October 2010

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.


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)

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

  • 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

    • 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.

    • 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