Unexplained Fever

Benedict Isaac, Serge Kernbaum, Michael J. Burke

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9781000722109
• Edition: 1
• Topic: Medicina
• Subtopic: Teoría, práctica y referencia médicas

This book covers pathophysiology of fever, the general approach to the febrile patient, and offers a systematic, in-depth discussion regarding the differential diagnosis of unexplained fever. The authors define an unexplained fever as a fever which lasts a minimum of 14 days and whose etiology is not known. This one-of-a-kind publication highlights the main causes of fever, specifically infectious diseases, cancer, connective tissue diseases, various rare disorders, plus etiologies which are often ignored. Also, laboratory and medical imaging techniques for diagnosing fevers are included. Written in a comprehensive, unrepetitious style, this "must-have" resource includes such aspects as the history of the fever, a review of published cases, the approach to the patient, and an analytical review. This up-to-date volume is an indispensable guide that should be read by physicians, surgeons, internists, microbiologists and other medical professionals.

Part I
General Aspects of Fever

Chapter 1

Introduction — Definition of Unexplained Fever, History of Fever, Statistical Data, Classification

B. Isaac, S. Kernbaum, and M. Burke

Introduction

Fever is only a symptom or sign of disease, although it is important enough to direct the clinician to find its cause in order to diagnose and treat the condition without delay. In some disorders fever is such a prominent manifestation that the condition is named in relation to certain characteristics of the fever. These may be infections, such as relapsing fever, undulant fever, and spotted fevers, or noninfectious diseases, including drug fever, and familial Mediterranean fever. The onset of fever is variable. It may occur de novo in a previously healthy individual, as a complication of a nonfebrile disorder, or be superimposed upon the compromised host. Fever may occur at all ages from the preterm neonate to the very old. Until a diagnosis is made, the physician does not know whether the cause is serious or trivial. Certain fever patterns have been described, yet none of these is entirely specific for any particular clinical entity. Although some form of standardization of approach is necessary, it must be appreciated that each febrile patient has his own particular facets which must be considered in the clinical work-up.

When evaluated initially, fever may appear to be due to a clinically obvious, known, certain, determined, or explained source, or conversely, the cause may be obscure, unknown, uncertain, undetermined, or unexplained. The latter group includes FUO^{1,2,3 and 4} (fever of unexplained, unknown, or undetermined origin), in which the fever generally lasts at least 2 or 3 weeks.² In a subgroup called prolonged FUO, the duration of fever is usually 6 months or more.⁵ However, there remains quite a considerable group of patients with potentially lethal conditions that have been largely ignored by authors because the duration of unexplained fever is less than 2 to 3 weeks. Inadvertently the impression has been created that these patients usually have “short-lived” or “self-limited” conditions and will recover without the need for carrying out an extensive work-up in order to reach a precise diagnosis. This view may lead to unfortunate consequences, which may be fatal in cases such as spotted fever without spots,^{6, 7} and systemic herpes simplex infection,^8,9 or may result in increased morbidity because of a delay in diagnosis and appropriate therapy. We feel that these patients cannot be bypassed with a “wait and see” attitude, i.e., either the patient will recover or the fever will persist so that he becomes a “true” case of FUO. We therefore have proposed to include all patients whose cause of fever is not obvious within a few days into a larger group of unexplained fever.

Definition of Unexplained Fever

The definition of unexplained fever is a febrile state with or without localizing symptoms and signs in which a definite diagnosis cannot be made following a clinical work-up that comprises a thorough history and physical examination together with initial laboratory investigations. The latter should include a complete blood count with smear, ESR, routine urine analysis, and conventional microbiologic tests (e.g., blood and urine culture), and a chest X-ray. Clearly this definition puts no time limit on the duration of the fever, but usually involves several days and up to 2 weeks. (If the fever lasts longer than this period, the patient is regarded as having FUO.)

History of Fever

Fever as a cardinal manifestation of disease has been known since antiquity. It is described in Sumerian cuneiform writings, Egyptian hieroglyphic inscriptions, and in the Bible. The greatest physician of the ancient world, Hippocrates (460—377 B.C.), considered fever to be a major feature of acute diseases. His elegant descriptions of certain febrile diseases, such as malaria, pneumonia, and enteric fever, are remarkable. He also described the supervention of tumors and articular pain in long-lasting fevers.

Before the thermometer was invented, physicians used three main procedures for determining temperature: the patient’s perception of his own body warmth, his appearance, and the use of the “educated hand” on various parts of the body. Hand thermometry as a clinical method was taught to physicians as an art.

Galen (131—201) designated neutral heat as being neither hot nor cold and achieved it by mixing equal quantities of ice and boiling water. A person with hot hands would regard this mixture as chilly and one with cold hands would perceive it as warm. However, it was not for nearly another millennium and a half that measurement of temperature came into effect.

The forerunner of the thermometer was first constructed by Galileo in about 1593. This device was actually an air-thermoscope, which consisted of a glass bulb attached to a long, narrow, open-mouthed neck. When the neck was inverted and dipped in water and the bulb was heated, air was expelled from the neck into the water. On cooling, water again rose in the neck. On re warming, the air in the bulb expanded and the water level in the neck dropped. Sanctorius, a colleague of Galileo, was the first physician to employ instruments of precision in the practice of medicine. In 1625, he converted this elementary, uncalibrated air-thermoscope into a true thermometer by adding a scale, which was determined by the application of snow or a candle flame for the low and high points, respectively, and subdividing the intervening distance into 110 equal parts. The bulb of the thermometer was either grasped by the patients in their hands or inserted into the mouth.

Rey, a French physician, devised the first liquid-in-glass thermometer in 1632. This device consisted of a flask with a long, narrow neck down which water was poured. When the flask was heated the water would ascend in the neck.

Florentine thermometers were introduced around the year 1641 and became very popular all over Europe. Wine spirits were placed in the bulb and the stem was closed. The spirit, when heated, would rise in the stem, and on cooling, fell back into the bulb. Glass beads fused onto the stem marked high and low values. However, standardization was not yet perfected.

In 1694, Renaldini, a member of the Academia del Cimento, proposed using the freezing and boiling points of water as a temperature range. The following year, his colleague, Bouilliau, suggested the substitution of mercury for alcohol in the bulb.

In 1701, Newton proposed a scale in which the freezing point of salted ice was set at zero and the temperature of the human body was set at 12°. Fahrenheit, in 1717, multiplied this scale by 8, using a value of zero for the lowest temperature that could be attained by freezing salt water and 96° for body temperature. He noted a value of 100° for the temperature of a febrile patient. His thermometer employed mercury, possibly due to the suggestion of the physician Boerhaave, and the bulb was modified into an oval shape.

Boerhaave (1668—1738), who was Professor of Medicine, Botany, and Chemistry at Leyden, was one of the greatest consultants of the time. Together with his pupils, van Swieten and de Haen, he noted the potential utility of the Fahrenheit thermometer in medicine. The instrument was first used on a healthy man and calibrated accordingly. The thermometer was then used to measure the temperature of a febrile patient by placing it in the hand or mouth, on the bare chest, or in the axilla.

Reaumur, in 1730, established a thermometer calling the freezing point of water 0, and boiling point 80 units. Celsius, in 1742, employed a scale using 100 units with ice at 100° and boiling water at 0°. The next year Christin reversed these points to establish the centigrade scale which has been in use since.

The first systematic record of temperature was carried out in 1852 by Traube, who probably influenced Wunderlich to make a systematic study of the subject. At about this time the German surgeon Billroth produced fever in cats by injecting filtrates of pus, although it would take another century until the mechanism was elucidated.

Thermometry was introduced into clinical practice by Wunderlich in 1868, when he published his classic treatise “Das Verhalten der Eigenwarme in Krankheiten”;¹⁰ 3 years later an English version was released.¹¹ He originally applied a 30-cm long weather thermometer to the axilla for 20 min. He considered the mouth and the closed fist to be unreliable, and the rectum and vagina indecent for measurement. Together with his colleagues and students, he made observations on temperature changes in 25,000 patients, and he wrote his classic treatise on fever patterns. The instrument was later modified to resemble the modern clinical thermometer which required pl...

Table of contents

• Cover
• Title Page
• Copyright Page
• Preface
• The Editors
• Acknowledgment
• Dedication
• Contributors
• Table of Contents
• Part I General Aspects of Fever
• Part II Unexplained Fever Associated With Diseases of Organ Systems
• Part III Environmental and Biologic Causes of Unexplained Fever
• Part IV Unexplained Fever in Surgery
• Part V Unexplained Fever at Different Ages
• Part VI Diagnostic Procedures and Management of Unexplained Fever
• Index