Which red flag symptoms in a patient with chronic fatigue should promp

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

In a patient with chronic fatigue, the following red flag symptoms should prompt immediate referral to secondary care:

Fatigue unexplained in adults aged 40 and over who have ever smoked or have been exposed to asbestos, as this may indicate lung cancer or mesothelioma; an urgent chest X-ray should be offered within 2 weeks .
Fatigue accompanied by cough, shortness of breath, chest pain, weight loss, or appetite loss (unexplained) in adults aged 40 and over, which also suggests possible lung cancer or mesothelioma and requires an urgent chest X-ray within 2 weeks .
Persistent fatigue in adults may indicate leukaemia; a very urgent full blood count should be performed within 48 hours .
Fatigue unexplained in women should prompt primary care tests including serum CA125 to assess for ovarian cancer, with referral as appropriate .
Fever (unexplained) or fever with unexplained splenomegaly or lymphadenopathy in adults may indicate haematological malignancies such as leukaemia or lymphoma and requires urgent full blood count and suspected cancer pathway referral .
Night sweats with unexplained splenomegaly or lymphadenopathy in adults also warrant urgent referral for suspected lymphoma .
Pallor or pruritus with unexplained splenomegaly or lymphadenopathy may indicate leukaemia or lymphoma and require urgent investigation and referral .

Which red flag symptoms in a patient with chronic fatigue should prompt immediate referral to secondary care?