Fever, a History

A normal temperature is 98.6°F, so they say. This dogmatic fact persisted for 150 years, ever since a single physician derived this fact from compulsively prodding thousands of patients with primitive thermometers. He was close (the average temperature is actually 98.2). But it is variation in temperature, both normal and pathologic, that is more interesting.

Fever, as it is understood today, can result from external ‘pyrogens’, like lipopolysaccharides (LPS) from bacteria and/or from the effect of intrinsic molecules like Prostaglandin E (PGE), a pyrogenic cytokine produced by the immune system (amongst others, like interleukins and interferons). In any case, fever is one of a number of physiologic alterations that occur during the ‘acute phase response’ to illness.

The historical understanding of fever was less complicated:

“Those die, whom the fever does not leave ...” Hippocrates (5th Century BCE).

Merck

The Greeks gave it the term ‘pyrexia’ (fire) and the Romans built a temple to the goddess Febris on the Palatine Hill. Recognition of fever as an ominous sign motivated physicians for centuries to better understand and treat it. The earliest notions attributed fever to ‘heating of the blood’ as a proximal cause. In the words of Palladius (?650 CE), fever is “a preternatural heat, which begins in the heart, and is diffused by the arteries over the whole body, sensibly injuring the actions of the body.” This general concept was preserved up to and after the 17th century wherein Shakespeare wrote, in Venus and Adonis, of “The marrow-eating sickness, whose attaint disorder breeds by heating of the blood”  

Palatine Hill, where the Romans built a temple to the goddess Febris

Palatine Hill, where the Romans built a temple to the goddess Febris

Understanding grew slowly. By the 3rd century BCE Herophilus used a water clock to associate fever with rapid pulse. Around this time Erasistratus put forth a theory of inflammation as the cause of fever. These phenomena we now know to be at least correlated, but the idea was dismissed by the great Galen some 500 years later, in favor of ‘putrefaction of the humors’—(semantics?).  Celsius in the 1st century CE warned that postpartum fever was life-threatening.

Fever patterns were known since the time of Hippocrates. The earliest descriptions were in fevers due to malaria where the release of merozoites caused spikes of fever at predictable intervals: every two days for tertian, and every three days for quartan fever patterns. By Galen’s era it was de rigueur to link everything medicinal to the four humors, thus quotidian (daily) fever was linked to phlegm, tertian to yellow bile and quartan to black bile. Identifying such patterns reached a fever–pitch: semi-tertian, double tertian and double quartan were described and debated. Ephemeral (less than a day) and non-periodic fevers (like hyperthermia) were also recognized.

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With the collapse of the Roman Empire the accumulated medical knowledge was conveyed to the East. By the 7th century CE Arabs had conquered Persia. They encouraged the continued translations of Greek and Roman texts into the Syriac language. The medical texts were handled mostly by Persians. Amongst the pantheon of great Persian physicians, were Rhazes, Avicenna, and Akhawayni. Avicenna took Galen to task on the role of putrefaction and pondered the relative contributions of infection and inflammation in the etiology of fever. 

It was during this time, the 10th century CE, that Akhawayni, famous in his own time as “Physician to the Insane”, gave much thought to fever and made the distinction between primary fever, a disease untoitself, and secondary fever, due to inflammation. His treatment of fever patterns was, not surprisingly for a Persian, a work of mathematical beauty. He determined that there were up to 4 components to each fever pattern, each component having 4 subtypes and 2 modes (intermittent or continuous). This leads to 84 possible combinations (4,096). He simplifies this for the bewildered reader of his medical handbook (the first to be written in Persian instead of Arabic). He used lines and dots to plot fever patterns. “… I will do a trick so that it will become apparent to you. I will draw lines corresponding to the number of days, and I will connect the tops together … so it will be apparent what I am saying.” His work was never translated into European languages, as was Avicenna’s Canon, and thus lapsed into obscurity.

fever.jpg

Ancient insights about periodic fevers is all the more remarkable given that the clinical thermometer was not available until well after Galileo’s experiments. Others added a scale (Santorio), changed from water to alcohol to mercury (Fahrenheit).  Fahrenheit’s scale was registered in 1724, but Celsius revived the centigrade scale in 1742.

The device found favor with the famous medical educator Herman Boerhaave (b 1668), who at the Dutch University of Leiden was the “first great clinical, or ‘bedside,’ teacher.” He was a major influence on the great medical centers to come in Edinburgh, Vienna and Germany. But medical thermometry didn’t catch on. It was very cumbersome.

Boerhaave

Boerhaave

Wunderlich

Wunderlich

Then about the time of the American Civil War, between 1866-1867, Sir Thomas Clifford Allbutt shrunk the clinical thermometer from 1 foot long to six inches and reduced the set up time from 20 mins. to 5 mins. Now of course we have infrared sensors and semiconductor transducers that permit instant, accurate and non-invasive measurements. But Albutt’s ingenuity allowed the German physician, Carl Reinhold August Wunderlich to take over one million readings from twenty-five thousand patients. 

One foot thermometer from the Wunderlich era

One foot thermometer from the Wunderlich era

As Medical Director at the University of Leipzig he introduced fever curves to bedside medicine and reminded students that fever is a symptom, not a disease. He said of his studies that, “From many quarters, and repeatedly too, I have been urged to collect them together in a complete and connected form.”

Curves from Wunderlich's Textbook

Curves from Wunderlich's Textbook

His 500 page tome, published in 1863 in English translation by the New Sydenham Society was titled “On the Temperature in Diseases, a Manual of Medical Thermometry.” It contained 40 woodcuts and seven lithographs. In the preface he lauds the practicality of clinical thermometry, giving seventeen reasons why it is “highly important to the medical practitioner.” He starts with “all the phenomenon of the sick are deserving of study” and ends with “because it furnishes a certain proof of the reality of death, when this is otherwise uncertain.”—echos of Hippocrates (see above). He opined, even then, on a preference for the centigrade scale, as used in Europe. And yet, in the British Empire and the United States, the Fahrenheit scale still rules.

There is a fever pattern named after Wunderlich, associated with typhoid . But, by a curious accident of history, Wunderlich, like that other fever investigator before him, Akhawayni, was also renowned in his own time for treatment of the mentally ill.

In modern times quotidian, tertian and quartan fevers are considered pathognomonic of malaria, each corresponding to specific forms of the infectious agent, Plasmodium.

While there are several other documented fever patterns, only two enjoy the attention of the savvy physician. Pel-Ebstein fever is associated with Hodgkin’s Disease. Here the temperature is high one week and low the next. Saddleback (or quintan) fever (after the shape of the 5 day temperature alterations) is characteristic of infection by Bartonella quintana, from lice. It was prevalent amongst soldiers in WWI. 

Fever Patterns

Fever Patterns

Papers by Dr. Philip Mackowiak, an infectious disease specialist and Professor of History of Medicine at the University of Maryland, were especially informative on this topic and are referenced above. His other writings on history of medicine are worth a look.

Post-Mortem: Solving History's Great Medical Mysteries

4.5 Stars. "Their lives changed history. Their deaths were mysteries, until now! Post-Mortem: Solving History's Great Medical Mysteries by Philip A. Mackowiak, MD, FACP, examines the controversial lives and deaths of 12 famous men and women."

Leave a comment, or email me at info@medicalhistorytour.com.

And FYI: Here's how to use a thermometer from the Wunderlich era.

From Wunderlich's Textbook

From Wunderlich's Textbook

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