Tumour-related fever

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A tumour-related fever is a paraneoplastic manifestation of cancer where a fever occurs due to the cancer rather than an infection.

Epidemiology

A paraneoplastic fever is much less common than an infection-related fever.

The most common cancers causing a neoplastic fever are:

  • Haematological malignancies
    • Lymphoma
    • Leukaemia
  • Sarcoma
  • Atrial myxomas
  • Renal cell cancer
  • Liver metastases

Pathophysiology

The biochemical abnormalities leading to a paraneoplastic fever is not understood but the mechanism probably varies between patients. Release of various cytokines such as prostaglandins (PGE), interleukins (IL) and tumour necrosis factor (TNF) are probably involved.

In lymphomas, IL-6 is associated with B symptoms and both IL-6 levels and B symptoms are connected with a worse prognosis in diffuse large B cell lymphoma.

Clinical features

In any patient with a malignancy and a fever, the initial presumption should be that there is an infectious aetiology; a paraneoplastic fever is a diagnosis of exclusion. If a number of days or weeks pass without a clear infectious aetioloy becoming apparent, then the suspicion for a paraneoplastic fever should be high. The fever is typically high and does not respond to paracetamol. Often the patient does not look toxic and there are no rigors, nor tachycardia or low blood pressure.

Management

Naproxen and NSAIDs

In a study in the 1980s 14 of 15 patients had complete resolution of fever within 24 hours of commnencing naproxen 250 mg orally twice daily. In this same study, 7 patients had a non-tumour fever (5 infection, 2 connective tissue disease) and in none of these patients did the fever respond to naproxen. A larger more recent study however showed no difference in efficacy for naproxen between tumour-related fevers and fevers of other causes.

Authors

Graham Llewellyn Grove