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CASE 65: A RASH ON THE THIGHS
A 34-year-old woman presents to her GP with a rash on her thighs, which appeared this
morning. She started noticing it following 2 days of coryzal symptoms.
Following a quick assessment, the GP suspects meningitis and administers intramuscular
benzylpenicillin and refers the patient to the local emergency department. Upon arrival, the
doctors take a more detailed history. She has no photophobia or neck stiness, and apart
from being worried about the rash, she is otherwise well. She also remembers some gum
bleeding from the night before while she was brushing her teeth. Her family history reveals
several relatives with autoimmune disease.
Examination
She is not febrile, and cardiovascular and respiratory examinations are normal. She has no
palpable spleen, liver, or lymph nodes. The rash is purpuric and does not blanch on stretch-
ing the skin. Joint examination is unremarkable.
INVESTIGATIONS
Haemoglobin 125
White cell count 12.0
Neutrophils 1.0
Lymphocytes 7.0
Platelets 8
Mean corpuscular volume 80
C-reactive protein 23
Blood film is shown in
Figure 65.1.
QUESTIONS
1. What are the two most likely differential diagnoses?
2. How would you describe the findings in her blood film? What abnormal cells are
you looking for?
3. Does this patient need platelet transfusion?
4. What is your management plan?
DOI: 10.1201/9781003242697-68
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ANSWERS
Blood results show thrombocytopenia and mild neutropenia with lymphocytosis. The top
two dierential diagnoses are leukaemia, which aects normal haemopoiesis and causes
cytopenia by the rapid division of abnormal leukaemia cells in the bone marrow. The other
main dierential diagnosis is primary immune thrombocytopenia (ITP), previously known
as idiopathic thrombocytopenic purpura, which typically causes low platelets and sometimes
neutropenia if there is a concurrent viral illness or autoimmune disease.
To exclude leukaemia, a blood film is usually examined for blast cells, which are cells with
abnormal maturation. This blood film (
Figure 65.1) does not show blast cells. Instead it con-
firms thrombocytopenia, neutropenia, and giant platelets at the centre of the film.
This patient has ITP, which is an autoimmune condition characterised by low platelets and
tendency to bleed. It was initially thought to be a condition caused purely by autoantibodies
against platelets leading to opsonisation and premature destruction in the reticuloendothelial
system. However, recently a deeper understanding of the pathophysiology has shown that in
fact other mechanisms are involved.
Autoantibodies opsonise megakaryocytes, which are the cells of the bone marrow that syn-
thesise platelets. This has an inhibitory eect of their growth and platelet release and induces
apoptosis. Relatively low levels of free thrombopoietin (TPO), the hormone that drives plate-
let production, might also be contributing to low levels of platelets, as may T-cell–directed
lysis of platelets.
Figure 65.1 Blood film showing thrombocytopenia, neutropenia and giant platelets at the
centre of the film.
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Case 65: A Rash on the Thighs
181
As ITP is an autoimmune condition, giving a transfusion of platelets will not correct the
abnormality. Platelet transfusion is reserved for emergencies, where there is serious bleeding,
or when an urgent procedure needs to be done and cannot be delayed.
Patients with ITP have low levels of platelets. With a platelet count of less than 30 × 10
9
/L
most patients will not bleed. Younger patients who are otherwise well might even tolerate
platelets of less than 20 × 10
9
/L with no symptoms at all.
The main treatment is immunosuppression, and the first-line therapy is usually steroids,
or intravenous immunoglobulins (IVIGs). Other treatment options include anti-D immu-
noglobulin, rituximab or TPO agonists. Steroids are given either orally or intravenously
depending on severity of bleeding. The patient is usually started on a high dose of 1 mg per
kg oral prednisolone or 1 g methylprednisolone intravenously.
The dose is gradually weaned o over several weeks. The patient may be kept in hospital
overnight for observations, but if she is well, she can be sent home and return the next day for
a review and a blood test to ensure appropriate rise in platelet count following steroids. She
must be referred to a haematologist who will ensure appropriate follow-up.
ITP can be associated with infections, usually viral, and can relapse with future infections.
HIV, hepatitis B, and hepatitis C should be screened for. It can also be associated with auto-
immune diseases; hence some physicians send an autoimmune screen at presentation.
KEY POINTS
•
ITP is an autoimmune bleeding disorder caused by increased platelet destruction
and impaired production.
•
Acute leukaemia needs to be excluded with any presentation with
thrombocytopenia.
•
Platelet transfusion is rarely needed, unless in emergency or to cover a procedure.
•
In the short term, steroids work very well, and the platelet level rises appropriately,
but long-term follow-up is needed with the haematology team.
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CASE 66: FATIGUE AND WEIGHT LOSS
A previously healthy 55-year-old man presents to his GP with concerns regarding his energy
levels; it has gotten so bad lately that he feels very tired while doing simple gardening. He has
lost 10 kg of weight over the last 6 weeks. He has no previous history of heart or lung disease,
and the only medication he takes is allopurinol for recurrent gout. His only other symptom is
slight abdominal discomfort, which he is attributing to his medication.
Examination
The patient appeared breathless, but with normal examination of cardiology and the respi-
ratory system. His abdominal examination is also normal apart from an enlarged spleen.
Temperature is 37.2°C. Blood pressure is 135/75.
INVESTIGATIONS
The GP arranges an urgent blood test:
Haemoglobin 125
White cell count 65.0
Neutrophils 50.0
Lymphocytes 4.0
Platelets 430
Mean corpuscular volume 82
C-reactive protein 6
Blood film is shown in
Figure 66.1.
The patient is referred to the local haematology clinic and is seen under the 2-week wait
referral pathway.
QUESTIONS
1. What is the most likely diagnosis?
2. What specific test would you request to confirm the diagnosis?
3. What is the management plan of this patient?
DOI: 10.1201/9781003242697-69
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ANSWERS
The blood test shows high white cell count (with a significant neutrophilia) and a normal
C-reactive protein level. So this is not an inflammatory response, especially given that the
patient is apyrexial and has no signs of infection.
The blood film (Figure 66.1) shows neutrophilia, myelocytes (cells in the maturation stage
previous to neutrophils) and some blast cells. This is likely to be chronic myeloid leukae-
mia (CML), which is a myeloproliferative disorder characterised by clonal expansion of the
myeloid mass in the bone marrow, which eventually displaces normal haemopoiesis. Many
cases are diagnosed incidentally on a routine blood test that shows typical features shown
in
Figure 66.1. However, it can also present with the symptoms typical of those in this case.
The disease has several phases: the ‘chronic’ phase is when the most cases are diagnosed, and
it represents the initial stage of the disease, which could last 2–7 years. It can then transform
into the ‘accelerated’ phase, which can take months to years, before the final phase, which is
known as ‘blast transformation’. At this final phase, the overwhelming majority of cells are
blast cells, either myeloid or lymphoid, which are non-functioning cells that occupy the bone
marrow and have the potential to invade other tissues.
Note that the dierence between the presentation of acute and chronic leukaemia is that in
chronic leukaemia, all of the stages of maturation of blood cells are expanded in numbers,
namely blast cells, promyelocytes, myelocytes, band cells and neutrophils. In acute leukae-
mia, or blast transformation of CML, most cells are blast cells, and hence the bone marrow
produces no eective blood cells, leading to bone marrow failure.
Figure 66.1 Blood film showing neutrophilia, myelocytes and some blast cells.
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Case 66: Fatigue and Weight Loss
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To confirm the diagnosis, a bone marrow biopsy to detect the BCR-ABL1 fusion gene is
needed. Some 90–95% of patients with CML have this gene, which is the result of transloca-
tion (9;22), also known as the Philadelphia chromosome.
The ABL gene is a proto-oncogene coding for a non-receptor tyrosine kinase. However, with
the translocation of this gene onto chromosome 22, its fusion with the BCR produces a new
oncoprotein which has a greater activity than the normal product of the ABL gene. The
mechanism by which this new gene product aects the cell kinetics is still not fully understood.
The treatment that has changed the course of this condition is tyrosine kinase inhibitors, the
first line being imatinib. This family of drugs is thought to act by binding to the oncoprotein
product of the BCR-ABL1 gene and inactivating it. Other generations of this family are avail-
able now, such as dasatinib and nilotinib.
The response to the drugs is assessed by testing three modalities: peripheral blood to ensure
normalisation of blood count, cytogenetics to ensure elimination of Philadelphia-positive
cells from the bone marrow and finally molecular studies to confirm the elimination of BCR-
ABL1 transcript product in the circulation.
KEY POINTS
•
CML is a myeloproliferative disorder in which there is an expansion of numbers of
cells at all stages of maturation.
•
The condition should be suspected in any patient with persistent unexplained
neutrophilia, as this might represent CML at the chronic phase.
•
Tyrosine kinase inhibitors are an example of targeted therapy, in which the onco-
protein product of the BCR-ABL1 gene is bound to and inactivated by the drug.
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CASE 67: PNEUMONIA WITH ABNORMAL LIVER
FUNCTION
A 32-year-old man presents to his GP with symptoms of productive cough and fever. He is not
a smoker, and he does not have any past medical history. He works as a civil engineer, and he
does not drink any alcohol. There is no history of any recent travel.
Examination
The patient looks unwell, his temperature is 37.9°C, and auscultation of his chest reveals
crepitations in the right base. Examination of the cardiovascular and abdominal systems
is unremarkable. The GP makes a diagnosis of community-acquired pneumonia and pre-
scribes a course of amoxicillin.
The patient returns in 1 week with no improvement. The GP sends a routine blood test and
a screen for atypical pneumonia, which comes back positive. He adds clarithromycin to the
treatment, and the patient eventually improves.
Concerned about extrapulmonary complications of an atypical pneumonia, the GP performs
a full liver screen 6 weeks later.
INVESTIGATIONS
Blood tests at the time of the pneumonia:
Haemoglobin 138
White cell count 20.0
Neutrophils 15.0
Lymphocytes 4.0
Platelets 500
Mean corpuscular volume 88
Bilirubin 20
Aspartate aminotransferase 100
Alkaline phosphatase 190
C-reactive protein 40
Atypical pneumonia screen: Serology for Legionella pneumonia is positive.
Liver screen 6 weeks after the pneumonia:
Bilirubin 18
Aspartate aminotransferase 114
Alkaline phosphatase 196
Ferritin 1100
Negative for HIV; CMB; EBV; hepatitis A, B and C.
Iron studies:
Serum iron 30
Transferrin saturation 70%
Total iron binding capacity 40
DOI: 10.1201/9781003242697-70
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