A 83-year-old woman was admitted to hospital with chest pain, fever, dry cough and palpitations. Chest X-ray revealed a pleural effusion, assumed to be caused by cardiac failure and respiratory infection. Despite treatment with antibiotics and diuretics, the pleural effusion increased on chest X-ray and there were signs of pleural and pericardial effusion on computed tomography (CT) scan. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was not successful. Meanwhile patients' long-term use of ergotamine for migraine was revealed, which is associated with pleuropulmonary and cardiac fibrotic reactions. Tentative treatment with colchicine was successful, with complete resolution of pleural fluid, fever, cough and inflammatory parameters. This case highlights the importance of establishing an ergot alkaloid use registry in unexplained pleuropericardial effusions and supports the use of colchicine as a potential therapeutic approach.