The pyrexial periods are not usually associated with any clinically demonstrable exacerbation of the joint trouble, nor indeed is it possible to usually find any definite cause of the fever.
In our case, it was just the opposite; Monique’s destructive hip monoarthritis along with her fever implied infection.
A fever in a rheumatology patient can have a chilling effect on the treating clinician. On the one hand, we are compelled to assume the likelihood of an underlying infection. Although an exhaustive series of tests may fail to yield a culprit, confirming a negative result can be a daunting task.
Defining a Fever
Until the dawn of the golden age of microbiology, the era of Koch and Pasteur, clinicians usually considered fever to be a final diagnosis rather than a symptom of a disease. Documenting a fever was challenging enough due to the lack of instruments, such as thermometers that could measure body temperature. Carl Wunderlich, MD, of Leipzig University in Germany is credited as being among the first clinicians to quantify fever in patients. During the mid-19th century, using a cumbersome device that measured 1 foot long and took 20 minutes to measure a temperature, he painstakingly recorded more than 1 million readings by pressing this device into the axillae of 25,000 patients. He concluded that temperatures above 38.0°C (100.4°F) should be considered a fever.5
A Fever in The Brain
Now that body temperature could be measured accurately, investigators began to focus on the pathophysiology of fever. This puzzle was not easily unraveled; in fact, there still remain several unanswered questions. What is known suggests that the generation of a fever requires the coordinated activities of several key components of our immune system.
Circulating pyrogenic cytokines, such as interleukin (IL) 1, tumor necrosis factor (TNF) alpha and IL-6, alert the hypothalamus to danger in the periphery. Receptors for these cytokines that are present on the surfaces of brain microglial cells activate the arachidonic acid pathways, causing the release of prostaglandin E2 (PGE2). The PGE2 then acts on neurons in the preoptic area of the hypothalamus, which respond by regulating temperature. These neurons are also connected to neural pathways that regulate sleep and eating. This helps to explain, in part, why fever is associated with somnolence and loss of appetite.6 Recently, using a murine model, researchers identified RANKL/RANK as a critical element in the mediation of gender-specific, physiological thermoregulation.7 The authors speculate this pathway may be critical for the generation of menopause-associated hot flashes in some women.
