Questions
Case- 1
A 7-year-old boy presents
with a history of right-sided knee
pain, fever and increasing tiredness.
He had been well until 3
weeks prior to his
presentation, when he had an upper respiratory
tract infection. Since then,
his parents report that he has a
reduced appetite and has
lost weight. He has missed a significant
number of days of school and
has been unable to participate in
his usual sports activities
as he becomes short of breath.
He has a past history of
asthma, for which he uses his salbutamol
inhaler infrequently. There
is no family history of note, no
history of foreign travel
and his immunisations are all up-to-date.
His observations are as
follows:
Temperature 38.5 °C
Pulse 120 beats/minute
Respiratory rate 32
breaths/minute
Blood pressure 110/56 mmHg
Clinical examination shows
that he is pale and tired but alert.
His mucous membranes are not
dry, but pale. He is noted to
have non-tender cervical
lymph nodes bilaterally, measuring
between 1 and 2 cm, and
shotty axillary and inguinal nodes.
His throat reveals enlarged
tonsils, although they do not appear
to be inflamed. His
respiratory and cardiovascular examinations
are normal, although it is
noted that he becomes distressed
when lying supine. Abdominal
examination reveals a liver edge
that is palpable 1 cm below
the right costal margin, and a spleen
tip just below the left
costal margin. Kernig’s and Brudzinski’s
signs are negative. He does
not have any skin lesions, bruises
or petechiae. He is noted to
have a good range of movements in
both knees, with no swelling
or bony deformity.
(a) Which of the following
investigations would be most
appropriate at this stage?
(Choose THREE)
Auto-antibody screen
Electrocardiogram (ECG)
Ferritin
Fine-needle aspiration of
node
Full blood count
Haemoglobin electrophoresis
Lumbar puncture
Mantoux test
Monospot test
X-rays of his chest and knee are shown in Figure 1a and b.
His blood film is shown in Figure 1c.
(b) Which of the following is the most likely diagnosis?
(Choose ONE)
Aplastic anaemia
B-cell lymphoblastic lymphoma
Cytomegalovirus (CMV) infection
Juvenile idiopathic arthritis
T-cell acute lymphoblastic leukaemia
(c) The most important management at this stage would be:
(Choose THREE)
Abdominal ultrasound scan
Broad-spectrum intravenous antibiotics
Human leukocyte antigen (HLA) tissue-type
Lumbar puncture
Intravenous dextrose saline with potassium
Measure the serum urate level
Oral ibuprofen for management of pain and pyrexia
Send blood for CMV polymerase chain reaction
Start chemotherapy
Figure 1 a Chest x-ray of 7-year-old boy; b Knee x-ray of the same
boy; c Blood film of the same boy.0
Answers
Case-1
(a) Auto-antibody screen
Full blood count
Monospot test
(b) T-cell acute
lymphoblastic leukaemia
(c) Broad-spectrum
intravenous antibiotics
Lumbar puncture
Measure the serum urate
level
There is potentially a large
differential diagnosis for a pyrexial
child including infection,
malignancy, drug-induced and other
chronic inflammatory
conditions such as juvenile idiopathic
arthritis, inflammatory
bowel disease and Kawasaki disease.
The clinical symptoms in
this case are vague, apart from
the pyrexia, as is often seen in malignancies.
Given the
history
and
clinical findings, a full blood count, as well as
other
blood tests including blood cultures, C-reactive protein,
erythrocyte
sedimentation rate and liver function tests should
be
performed. As infectious mononucleosis often presents
with
similarly vague symptoms, a monospot test is also
appropriate.
An auto-antibody screen, although non-specific,
is
a good screening tool in autoimmune disease. Although a
lumbar
puncture should be considered in all patients with
pyrexia
of unknown cause, the patient in this case does not
appear
to have symptoms suggestive of meningism.
This
patient has T-cell leukaemia. The chest x-ray shows
mediastinal
widening, with left lower zone consolidation and
the
peripheral blood film shows blast cells. The knee x-ray
is
normal. If the blood film had been normal and lymphoma
was
suspected, a complete lymph node should be removed as
the
diagnosis is difficult to make on fine-needle aspiration.
There
are different types of childhood leukaemia, but the
most
commonly occurring in children is acute lymphoblastic
leukaemia
(ALL). Lymphomas, in general, are divided into two
broad
categories, Hodgkin lymphoma (HL) and non-Hodgkin
lymphoma
(NHL). The criteria utilised to distinguish between
lymphoma
and leukaemia has been debated for years. While
both
can be of B-cell or T-cell phenotype, the distinction is
based
on the degree of bone marrow involvement. Children
who
have greater than 25% infiltration of their marrow with
blast
cells are considered to have ALL. T-cell disease is more
likely
than B-cell to present with a mediastinal mass and a high
peripheral
white cell count. A high peripheral white cell count
indicates
bone marrow involvement and therefore leukaemia.
Except
for the high number of lymphoblasts on the peripheral
film,
none of the clinical signs and symptoms is pathognomonic
of
leukaemia. Other diagnoses to consider include
viral
infections such as Epstein–Barr virus, cytomegalovirus,
other
malignancies such as neuroblastoma, haematological
disorders
such as aplastic anaemia, histiocytosis, idiopathic
(immune)
thrombocytopenic purpura (ITP) and juvenile idiopathic
arthritis.
Prior
to instituting specific therapy, measures should be instituted
to prevent
complications, particularly in patients with a
high
white cell count or bulk disease. Serum urate, renal function,
serum
calcium, phosphate and magnesium should be measured
regularly
in these patients to monitor for tumour lysis. Tumour
lysis
can occur spontaneously or as a result of chemotherapy leading
to
serious metabolic complications such as hyperuricaemia,
hyperkalaemia
and hyperphosphataemia. This combination can
ultimately
lead to renal failure or cardiac arrest if left untreated.
Prevention
is with hyperhydration, anti-urate drugs (allopurinol
or
rasburicase) and maintenance of urine output. Fluid should
not
contain potassium, as this may exacerbate hyperkalaemia.
Pyrexia
in patients may be secondary to the disease process itself
or
due to sepsis. Given that the immune system is compromised
in
such patients, despite the high white cell count, they should
routinely
be given broad spectrum intravenous antibiotics, even
with
low grade pyrexia. Ibuprofen is not recommended in these
patients
as poor platelet function in patients with thrombocytopenia
may
lead to bleeding. Airway compromise and pleural effusions
can
be an acute problem with large mediastinal masses.
The
diagnosis of ALL must be established beyond any
doubt
and, therefore, a complete work-up is generally considered
as important as
rapidly initiated therapy in a stable child.
Bone
marrow aspiration should be performed for morphology,
immunophenotyping
and cytogenetics and a lumbar puncture
to
exclude central nervous system disease. A liver ultrasound is
unlikely
to aid diagnosis or management, as the hepatosplenomegaly
is
a reflection of disease burden. A child with leukaemia
would
not routinely need a bone marrow transplant and,
therefore, routine
HLA typing is not necessary at diagnosis.
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