Oncology / Haematology 2 Flashcards
A 40yo male is admitted with recurrent pancreatitis. A CT scan reveals no pancreatic mass, but evidence of widespread lymphadenopathy. Liver imaging shows a stricture in the common bile duct but no stones. He also has a history of parotiditis. What is the most likely diagnosis?
IgG4 disease
Why might IgG4-related disease be described as being analogous to Sarcoidosis?
In both diseases, diverse organ manifestations are linked by similar histopathological characteristics.
What may be used to assist in diagnosing IgG4 disease?
Raised concentrations of IgG4 in tissue and serum.
*Note: this can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.
Which organ systems can be affected by IgG4-related disease?
Virtually every organ system:
- Biliary tree
- Salivary glands
- Periorbital tissues
- Kidneys
- Lungs
- Lymph nodes
- Meninges
- Aorta
- Breast
- Prostate
- Thyroid
- Pericardium
- Skin
List some examples of IgG4-related diseases.
- Riedel’s thyroiditis
- Autoimmune pancreatitis
- Mediastinal and Retroperitoneal fibrosis
- Periaortitis / periarteritis / inflammatory aortic aneurysm
- Kuttner’s tumour (submandibular glands) and Mikulicz Syndrome (salivary and lacrimal glands)
- Possibly Sjogren’s and Primary Biliary Cirrhosis
A 26yo newly qualified nurse presents as she has developed a bilateral erythematous rash on both hands. She has recently emigrated from the Philippines and has no past medical history of note. A diagnosis of Contact Dermatitis is suspected. What is the most suitable test to identify the underlying cause?
Skin patch test
- The skin patch test is useful in this situation as it may also identify irritants, not just allergens.
Describe how a Skin Prick Test is carried out.
- Drops of diluted allergen are placed on the skin, after which the skin is pierced using a needle.
- A large number of allergens can be tested in one session.
- Normally includes a histamine (positive) and water (negative) control.
- A wheal will typically develop if a patient has an allergy.
How long do you have to wait until the skin prick test can be interpreted?
15 minutes
Which allergies are the Skin Prick test useful for?
- Food allergies
- Pollen
What is the principle behind the RAST (Radioallergosorbent test) test?
Determines the amount of IgE that reacts specifically with suspected or known allergens, eg. IgE to egg protein.
Results are given in grades from 0 (negative) to 6 (strongly positive)
Why might RAST be used instead of skin prick testing?
Blood tests (RAST) may be used when skin prick tests are not suitable, eg. if there is extensive eczema or if the patient is taking antihistamines.
Which allergies is the RAST test useful for?
- Food allergies
- Inhaled allergens (eg. pollen)
- Wasp / bee venom
Which allergen test should be used to confirm a diagnosis of ?contact dermatitis?
Skin patch testing
How is Skin Patch testing carried out?
- Around 30 - 40 allergens are placed on the back.
- The patches are removed 48 hours later with the results being read by a Dermatologist after a further 48 hours.
- Irritants may also be tested for in this way.
A 25yo female presents with recurrent sinopulmonary infections. What test is most likely to confirm a Primary Immunodeficiency?
IgG level
What is the most clinically significant Primary Immunodeficiency?
Common Variable Immunodeficiency (CVID).
What is the most common Primary Immunodeficiency?
IgA deficiency (but most are asymptomatic).
Define CVID (Common Variable Immunodeficiency).
- The presence of hypogammaglobulinaemia of two or more immunoglobulin isotopes (low IgG, IgA or IgM)
- Recurrent sinopulmonary infections
- Impaired functional antibody responses.
- However, IgG is more likely to be deficient than IgM.
What is the criteria for ‘impaired functional antibody responses’?
- Absent isohaemagluttinins (eg. antibodies associated with blood transfusion reactions)
- Poor responses to protein (diptheria, tetanus) or polysaccharide vaccines (S. pneumoniae), or both.
Which cells are likely to be absent in X-linked Bruton’s agammaglobulinaemia?
Mature B-cells.
A 45yo woman is diagnosed with Non-Hodgkin’s lymphoma.
She is a recovering alcoholic and has significant alcohol-related peripheral neuropathy.
Which chemotherapy agent should be avoided if possible, given her past history?
Vincristine: can cause (reversible) peripheral neuropathy
Inhibits formation of microtubules.
A 34yo man who has Type 1 von Willebrand’s disease asks for advice. He is due to have a tooth extracted at the dentist next week. Which one of the following is the most appropriate management to reduce the risk of bleeding?
- Mefanamic acid
- Vitamin K
- Desmopressin
- Factor VIII concentrate
- Factor VII concentrate
Desmopressin: raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells.
Which disease is the most common inherited bleeding disorder?
Von Willebrand’s disease
How are the majority of cases of von Willebrand disease inherited?
Autosomal Dominant
List 2 symptoms which are commonly seen in von Willebrand disease, and 2 symptoms which are rare.
Common: Epistaxis, Menorrhagia
Rare: Haemarthroses, Muscle haematomas.
What is the role of von Willebrand factor in normal physiology?
- Promotes platelet adhesion to damaged endothelium
- Carrier molecule for Factor VIII
- vWF is a large glycoprotein which forms massive multimers up to 1,000,000 Da in size
What is the difference between Types 1, 2 and 3 von Willebrand disease?
Type 1: partial reduction in vWF (80% of patients)
Type 2: abnormal form of vWF
Type 3: total lack of vWF (Autosomal Recessive)
What might investigations yield if a patient has von Willebrand’s disease?
- Prolonged bleeding time
- APTT may be prolonged
- Factor VIII levels may be moderately reduced
- Defective platelet aggregation with ristocetin.
Describe the management of a patient with von Willebrand’s disease.
- Tranexamic acid for mild bleeding
- Desmopressin (DDAVP) raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- Factor VIII concentrate.
What is Type 2A von Willebrand’s disease caused by?
Type 2A: Caused by defective platelet adhesion due to decreased high molecular weight vWF multimers (i.e. the vWF protein is too small).
What is Type 2B von Willebrand’s disease characterised by?
Type 2B: Characterised by an pathological increase of vWF-platelet interaction.
What is Type 2M von Willebrand’s disease caused by?
Type 2M: caused by a decrease in vWF-plately interaction (not related to loss of high molecular weight multimers).
What is Type 2N von Willebrand’s disease caused by?
Type 2N: Caused by abnormal binding of the vWF to Factor VIII.
What is the correlation between symptomatic presentation and type of von Willebrand’s disease?
- No clear correlation
- Common themes amongst patients include:
> Excessive mucocutaneous bleeding
> Bruising in the absence of trauma
> Menorrhagia in females
Which is the most severe form of von Willebrand’s disease?
Type 3 = most severe form
Inherited as an Autosomal Recessive trait.
Which of the following is least likely to cause a warm autoimmune haemolytic anaemia?
- Mycoplasma infection
- Methyldopa
- Chronic lymphocytic leukaemia
- Lymphoma
- Systemic Lupus Erythematous
Mycoplasma infection
-> Mycoplasma infection causes a COLD autoimmune haemolytic anaemia.
SLE can rarely be associated with a mixed-type autoimmune haemolytic anaemia.
How is Autoimmune haemolytic anaemia (AIHA) divided into ‘warm’ and ‘cold’ types?
AIHA can be divided into warm and cold types, according to at what temperature the antibodies best cause haemolysis.
What causes AIHA (Autoimmune Haemolytic Anaemia)?
- Idiopathic (most common)
- Secondary to:
> Lymphoproliferative disorder
> Infection
> Drugs
How is AIHA (autoimmune haemolytic anaemia) identified?
Positive direct antiglobulin test (Coombs’ test)
In Warm AIHA, which antibody is usually implicated?
Usually IgG
In Warm AIHA, what temperature does haemolysis occur ‘best’ at?
Body temperature
In Warm AIHA, where does haemolysis tend to occur?
In the extravascular sites eg, the spleen.
What are the management options for Warm AIHA?
- Steroids
- Immunosuppression
- Splenectomy
What are the causes of Warm AIHA?
- Autoimmune disease eg. SLE
- Neoplasia eg. Lymphoma, CLL
- Drugs eg. Methyldopa
Which antibody is usually implicated in Cold AIHA?
Usually IgM
In Cold AIHA, what temperature does haemolysis occur ‘best’ at?
4 degrees centigrade
Describe the haemolysis seen in Cold AIHA.
Haemolysis is:
- Mediated by complement
- More commonly intravascular (as opposed to Warm AIHA, where haemolysis is extravascular).
List 2 symptoms seen in a patient with Cold AIHA.
- Raynauds
- Acrocyanosis (blue/purple colouring of the feet, caused by slow circulation)
What are the causes of Cold AIHA?
- Neoplasia eg. Lymphoma
- Infections eg. Mycoplasma, EBV
Which disease can (rarely) be associated with a mixed-type Autoimmune Haemolytic Anaemia?
Systemic Lupus Erythematous
