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Pallor and Limb pain

Sam is a 13 year-old boy with a four week history of fatigue and lethargy. When he gets home from school, he lies on the sofa and watches the TV. He used to go out on his bike with his friends, but now says he does not want to. Sam has also noticed that his legs have been achy, particularly his right leg. In the last 3 weeks he has been waking up at night with his legs aching. He was previously very active, cycling and playing football, but is now struggling to take part in sport and physical education classes at school due to tiredness and feeling cold. He has been struggling to recover from repeated viral infections over the last few months. His mother noticed that he has lost weight.

On examination, Sam was thin and looked pale. He had some bruising around his shins and calves. His chest was clear and heart sounds were normal. He had no joint abnormalities on pGALS examination. Abdominal examination showed hepatosplenomegaly.

Sam's GP checked some urgent blood tests and arranged an early follow-up appointment.

What are the red flags in the history?

Lethargy, malaise, possible weight loss, night pain.

What is your differential based on the history?

Leukaemia, primary bone tumour, post-viral fatigue and streptococcal infection should all be considered. 

Would the differential diagnosis change if Sam was found to have a knee effusion ?

You may consider arthritis, e.g., Juvenile Idiopathic Arthritis (JIA), or a reactive arthritis secondary to a recent infection, as well as considering malignancy.

In endemic areas or with a relevant travel history, acute rheumatic fever or Lyme disease should be considered. 

If there has been risk factors for HIV infection or Tuberculosis, these must also be considered.


The blood test results were as follows: haemoglobin 90 g/L, platelets 12 x106/L, white cell count 42 x 106/L (neutrophils 20% and lymphocytes 80%). Peripheral blood smear showed blast cells. A bone marrow aspiration and biopsy confirmed blast cells indicating Acute Leukaemia.