How do I differentiate between infectious and non-infectious causes of PUO in a primary care setting?

In a primary care setting, differentiating between infectious and non-infectious causes of pyrexia of unknown origin (PUO) involves a thorough clinical assessment focusing on identifying symptoms and signs of serious infection or specific diseases. Key steps include:

• Clinical assessment: Look for features suggestive of infection such as non-blanching rash, neck stiffness, bulging fontanelle, focal neurological signs, respiratory distress signs (tachypnoea, crackles, nasal flaring), urinary symptoms, or localized signs like joint swelling or limb non-use. These point towards infectious causes like meningitis, pneumonia, urinary tract infection, septic arthritis, or herpes simplex encephalitis ¹.
• Vital signs and observation: Measure temperature, heart rate, respiratory rate, and assess for signs of shock or dehydration (prolonged capillary refill, weak pulse, cool extremities). Abnormal vital signs increase suspicion of infection ¹.
• Basic investigations: In children under 5, especially under 3 months, perform full blood count, C-reactive protein, blood cultures, and urine testing to detect bacterial infections. Chest X-ray is indicated if respiratory signs are present. Lumbar puncture is considered in infants under 3 months or if meningitis is suspected ¹.
• Consider non-infectious causes: If no signs of infection are found and investigations are negative, consider non-infectious causes such as autoimmune diseases (e.g., Kawasaki disease in prolonged fever), malignancy, or drug fever. Persistent fever without infection signs warrants specialist referral ¹.
• Use of response to antipyretics: Do not rely on temperature response to antipyretics to differentiate infectious from non-infectious causes ¹.

Overall, the differentiation relies on careful clinical evaluation, targeted investigations, and consideration of the clinical context to identify infectious causes or raise suspicion for non-infectious etiologies requiring further specialist assessment ¹.