FEVER IN A PATIENT ON CHEMOTHERAPY
History
The parents of 6-year-old Lucy, who has B-cell lymphoma, have brought her to the children’s ward of their local hospital as they have recorded a temperature at home of 38.7C. They have since given her a dose of paracetamol. Lucy completed her second course of chemotherapy 6 days previously. They know that her last blood count 2 days ago showed that she was neutropenic (neutrophils 1.0 109 /L). The whole family, including the patient, have had symptoms of a viral illness with a sore throat, a runny nose and a bit of a cough, but she has also had three bouts of diarrhoea in the preceding 24 hours and some lower abdominal pain. There are four other children at home, ranging in age from 6 months to 9 years. The mother works part-time in the evenings serving behind a bar, while the father is a self-employed painter and decorator. Their daughter was very sick at presentation and spent 5 weeks in the regional paediatric oncology centre 40 miles away. She has only been home since the end of the recent course of chemotherapy.
Examination
Lucy is playing in a side-room with her dolls. She is reluctant to be examined. Her temperature is 37.4C. Her pulse is 130 beats/min and her blood pressure 95/60 mmHg. Oxygen saturation is 97 per cent in air. The indwelling central-line exit site is slightly erythematous and tender. There are no murmurs and examination of the respiratory and abdominal systems is unremarkable. Her ears, nose and throat are normal.
INVESTIGATIONS
Normal
Haemoglobin 7.4 g/dL 11.5–15.5 g/dL
White cell count 0.6 109/L 6.0–17.5 109/L
Neutrophils 0.1 109/L 3.0–5.8 109/L
Platelets 24 109/L 150–400 109/L
Sodium 134 mmol/L 138–146 mmol/L
Potassium 3.8 mmol/L 3.5–5.0 mmol/L
Urea 6.2 mmol/L 1.8–6.4 mmol/L
Creatinine 64 mol/L 27–62 mol/L
C-reactive protein 67 mg/L 6 mg/L
Questions • What factors increase the risk of infection in children with cancer? • What is the management?
Medicine
Once a child with cancer undergoing treatment is in remission, the commonest cause of death is infection. Families have written instructions about temperature monitoring and when to seek advice. All admitting hospitals have protocols for treatment based on the degree of fever (e.g. 38.5C) and the neutrophil count (e.g. 0.75 109 /L).
Contributing factors to infection in children with cancer
• Neutropenia – the more severe (0.5 109/L) and prolonged, the greater the risk. There may be loss of the inflammatory response, e.g. insufficient white blood cells to form an abscess
• Mucositis – following radiotherapy or chemotherapy. Can affect the whole gastrointestinal tract. There is a risk that intestinal bacteria will breach the gut wall and enter the bloodstream
• Indwelling central lines – crucial for giving chemotherapy and blood sampling, but significant source of infection, both blood-borne and at exit site • Frequent hospital admissions
• Poor nutrition
• Generalized immunosuppression, inhibiting the usual host defences – viruses that rarely cause severe illness in immunocompetent children can be lifethreatening in oncology patients, e.g. varicella, measles and cytomegalovirus. Chemotherapy also predisposes children to ‘opportunistic infections’ – organisms that only infect an immunocompromised host. Prophylaxis against Pneumocystis carinii is included in protocols for cancers where the chemotherapy regimen is particularly immunosuppressive
The reduction in temperature is irrelevant – the protocols are initiated on the recorded temperature at home. That she is playing is also irrelevant – she has worrying symptoms and signs. Abdominal pain and diarrhoea suggest mucositis and she is tachycardic. Although a visible source of sepsis is her central line site, this rarely causes significant systemic features. Gram-negative sepsis is the real threat and she requires admission and the immediate administration of intravenous broad-spectrum antibiotics that include cover for Gram-negative bacteria (e.g. Pseudomonas aeruginosa, Klebsiella), as well as Gram-positive bacteria that may be causing a line infection. Blood cultures and swabs (e.g. throat and line site) must be taken first and preferably urine and stool samples. However, collecting these should never delay antibiotics. A chest X-ray is needed if there are respiratory symptoms or signs. Careful monitoring and frequent re-evaluation are required, changing the regimen according to response and culture results, e.g. coagulase-negative staphylococci frequently cause infections in central lines. If Lucy is still febrile and significantly neutropenic after about 5 days, antifungal agents may be added. Haemopoietic growth factors, e.g. granulocyte colonystimulating factor, are sometimes given. She will almost certainly need blood and/or platelet transfusions. Again, protocols vary but an example would be a haemoglobin 7 g/dL and platelets 10 109/L or active bleeding. Once afebrile and recovering, she can be discharged home where, if necessary, the parents or community nurses can continue antibiotics. Life for such families is inevitably disrupted socially and financially – the main breadwinner here is self-employed. They will be supported by specific staff and charities.
KEY POINTS
• Once in remission, infection is the commonest cause of death in children receiving treatment for cancer.
• Febrile neutropenia in an immunocompromised child is a medical emergency.
• Common viral illnesses can kill immunocompromised children.
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