Pyrexia of unknown origin 90 years on: a paradigm of modern clinical medicine.

In 1925, Sir Thomas Horder, a leading physician of his day, gave a lecture, published in this journal, entitled 'Some cases of pyrexia without physical signs'. The paper highlighted what was already a familiar clinical presentation "which taxes our resources to the utmost". Fast-forward through 90 years of careful clinical description, technological innovation in diagnosis and treatment, emergent infections, novel diagnoses, demographic shifts, and radical changes in the health economy. Sir Thomas would find certain aspects familiar, and others revolutionary, in the differential diagnosis and management of the 21st century patient with pyrexia of unknown origin (PUO). Within high-income settings, the proportion of cases due to infection has declined, albeit unevenly. The era of untreated HIV, and the consequences of iatrogenic intervention and immunosuppression, led to Durack and Street's subclassification of the condition in the early 1990 s into classic, nosocomial, neutropenic and HIV-associated PUO. Shifts towards ambulatory care have driven a change in the definition of many diseases. An era of observant clinicians, who lent their names to eponymous syndromes, followed by meticulous serological, genetic and clinicopathological correlation, generated a battery of diagnoses that, along with malignancy, form a large proportion of diagnoses in more recent clinical care. In the current era, universal access to cross-sectional imaging and an infinite array of laboratory tests has undermined the attention paid to history and examination. In some areas of the clinical assessment, such as assessing the fever pattern, this shift is supported by research evidence. The issues that need to be addressed in the next 90 years of technological innovation, information sharing and health service transformation are likely to include: transcriptomic approaches to diagnosis; the place of positron emission tomography (PET) in the diagnostic pathway; the optimal management of high ferritin states; and the most cost-effective diagnostic environment, in the face of this era of specialisation and fragmentation of care. In the meantime, this review covers some important early 21st century lessons to be shared in avoiding diagnostic pitfalls and choosing empirical therapy.

Prolonged and perplexing fevers in antiquity: malaria and typhoid fever.

Fever of unknown origin is a topic that has enduring interest to physicians. Prolonged fevers of infectious etiology were of particular concern to the ancient physician. This overview of prolonged fevers in antiquity focuses on malaria and typhoid fever as the primary infectious causes. By studying texts from Mesopotamian, Greek, and Roman physicians and observers of disease, it is possible to determine the likely etiology of many of these ancient plagues. The historical import of these diseases should not be overlooked, and it is for this reason that the prolonged fevers of antiquity have profound significance and enduring interest.

[Fever--a millenarian subject]. / Fieber--Thema seit Jahrtausenden.

Since the antiquity up to the 19th century fever goes for an illness of its own rights. About 1900 temperature measurement has become clinical routine and fever synonymous with elevated body heat. In the time before accelerated pulse rate was the pathognomic sign. The detection of specific pathogen organisms leads to a new understanding of nosology and to the dissolution of the fever entity. However the antipyretic therapy remains essentially the same until the appearance of antibiotics.

Revisiting the death of Eleanor Roosevelt: was the diagnosis of tuberculosis missed?

Controversy has surrounded the death of Eleanor Roosevelt in 1962. There has been a persistent sense that doctors missed the diagnosis of miliary tuberculosis, thereby jeopardizing her life. This article, using Roosevelt's medical chart and other previously unreviewed documents, revisits her illness and death. What disease actually killed Eleanor Roosevelt? Did her physicians miss the diagnosis? These questions are of particular importance in light of the recent Institute of Medicine report estimating that almost 100,000 Americans die each year from medical mistakes. Why has the possibility of error clouded the care of Roosevelt for almost 40 years? What can Roosevelt's case reveal about ongoing efforts to reduce mistakes in clinical practice?