cases

                                                                                                                                                 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.