How should I manage a patient with lymphadenopathy and systemic symptoms such as fever or weight loss?

When managing a patient presenting with lymphadenopathy accompanied by systemic symptoms such as fever or weight loss, it is critical to promptly assess for potential serious underlying causes including haematological malignancies like lymphoma or leukaemia. Initial investigations should include a very urgent full blood count within 48 hours to evaluate for leukaemia, especially if lymphadenopathy is generalized or unexplained. Consider urgent referral via a suspected cancer pathway (2-week referral) for adults presenting with unexplained lymphadenopathy and systemic symptoms such as fever, night sweats, pruritus, or weight loss, as these may indicate Hodgkin's or non-Hodgkin's lymphoma. For children and young people (up to 24 years), a very urgent referral for specialist assessment within 48 hours is recommended under similar clinical circumstances. Clinical judgement should also guide the need for additional investigations such as chest X-ray in adults aged 40 and over with supraclavicular or persistent cervical lymphadenopathy to exclude lung cancer, tuberculosis, or sarcoidosis.

In cases where infection is suspected, management should be tailored accordingly: if viral, monitor and arrange review if systemic illness develops or lymphadenopathy persists beyond 7 days; if bacterial, assess the need for antibiotics based on clinical signs. If lymphadenopathy does not resolve after 2–4 weeks or worsens, urgent referral to an ENT specialist is advised for further evaluation including imaging and biopsy. Emergency hospital admission is warranted if there are signs of airway obstruction or superior vena cava obstruction.

This approach integrates NICE guideline recommendations with expert clinical practice and literature emphasizing the importance of early identification and referral of potential malignancies, while also considering infectious causes and the need for timely specialist input. (Gaddey and Riegel, 2016) highlight that systemic symptoms with lymphadenopathy increase the likelihood of malignancy, supporting the guideline emphasis on urgent investigation and referral.