Which red flag symptoms should prompt further investigation in a patient with fatigue?

When a patient presents with fatigue, certain red flag symptoms should prompt further investigation:

• Unexplained fatigue in patients aged 40 and over with a history of smoking or asbestos exposure should lead to an urgent chest X-ray, to be completed within 2 weeks, to investigate for lung or mesothelioma ¹.
• Unexplained fatigue combined with other symptoms such as cough, shortness of breath, chest pain, unexplained weight loss, or unexplained appetite loss in patients aged 40 and over also warrants an urgent chest X-ray within 2 weeks for potential lung or mesothelioma ¹.
• Persistent fatigue in adults should prompt consideration of a very urgent full blood count, to be done within 48 hours, to investigate for leukaemia ¹.
• Unexplained fatigue in women should lead to primary care tests, including measuring serum CA125, to investigate for ovarian cancer ¹.

Additionally, for persistent fatigue, it is important to exclude alternative or contributing causes such as pain, anaemia, reduced nutritional intake, activity levels, sleep disturbance, stress, anxiety, or depression, and to manage these appropriately ². Consideration should be given to checking serum full blood count, ferritin, vitamin B12, and folate levels, as patients can develop various types of anaemia ². Referral to an appropriate secondary care specialist should be arranged if there is a suspected or confirmed underlying cause that cannot be managed in primary care ³. Specialist referral may also be considered for persistent, unexplained fatigue that does not meet the diagnostic criteria for chronic fatigue syndrome (CFS) if there is significant uncertainty regarding the presence of an underlying physical cause, or if a second opinion or thorough specialist evaluation would be beneficial ³.