Pyrexia or fever is a pathologic increase in body temperature above the normal range occurring in a wide variety of pathogenic conditions. Hyperpyrexia is a fever greater than 105°F. An intermittent fever is one in which the temperature becomes normal but then rises again each day. A remittent fever is characterized by marked variation in temperature level each day with the lowest temperature level still remaining above normal. A relapsing fever has periods of increased temperature distributed among periods of one or more days of normal temperature. A septic fever has large daily oscillations in body temperature (Lorenz 2006).

Body temperature is controlled by balancing heat production against heat loss. If loss is greater than production, then the body temperature will decrease and vice versa. Heat production is a principal end product of metabolism, and the rate of heat production is determined by the metabolic rate of the body. The most important factors determining rate of heat production are (1) the basal rate of metabolism of all cells in the body; (2) an extra rate of metabolism caused by muscle activity during exercise or while shivering; (3) extra metabolism caused by the effect of thyroxine on all cells; (4) extra metabolism caused by the catecholamines and sympathetic stimulation on cells; (5) extra metabolism caused by increased chemical activity in the cells, especially when the temperature is elevated; and (6) extra metabolism needed for food processing referred to as the thermogenic effect of food.

Heat loss from the body occurs in three basic methods: radiation, conduction/convection, and evaporation. Heat loss by radiation refers to loss in the form of infrared heat rays that radiate from the body. Conductive heat loss refers to loss from the body as heat is conducted to the surrounding air and objects in contact with the body. Heat conducted to the air can then be carried away by convection air currents referred to as heat loss by convection. When water evaporates from the body surface, heat is also lost (Guyton and Hall 2006). In dogs and cats, the primary mechanisms for heat loss are radiation and evaporation. Panting is the primary means of dissipating excessive heat via evaporation because heat is not rapidly dissipated through the skin due to hair and lack of sweat glands.

Body temperature is regulated almost exclusively by nervous feedback mechanisms, with the majority of these operating through temperature-regulating centers in the hypothalamus. Sensory cold and warmth receptors are found in the skin for peripheral detection of temperature. Deep body temperature receptors are found mainly in the spinal cord, abdominal viscera, and in or around the great veins in the upper abdomen and thorax. These receptors detect the body’s core temperature. The majority of these receptors, both peripheral and deep, mainly detect cold rather than warmth; therefore, they are concerned more with preventing hypothermia (Guyton and Hall 2006).

The central thermostat is set at 101–102°F, and all temperature control mechanisms continually attempt to return the body temperature to this set-point value. When the body is too cold, temperature-increasing mechanisms are instituted, such as peripheral vasoconstriction, piloerection, and increased muscle activity (shivering). When the body becomes too hot, opposite mechanisms are instituted and include peripheral vasodilation, panting, and decreased muscle activity. In general, sympathetic stimulation controls temperature-increasing mechanisms, while parasympathetic stimulation controls temperature-decreasing mechanisms (Guyton and Hall 2006).

Fever-inducing (pyrogenic) diseases or substances affect the hypothalamic sensory and/or integrating centers by resetting the set point to a higher temperature than normal. This causes all the temperature-raising mechanisms to be activated, leading to heat conservation and increased heat production. The body temperature can approach the new set point within only a few hours.

Activators of Fever

Many proteins, protein breakdown products, and other substances, especially lipopolysac-charide toxins released from bacterial cell membranes, can cause fevers and are called pyrogens or fever-inducing substances. When these pyrogens are present in the tissues or blood, they are phagocytized by blood leukocytes, tissue macrophages, and large granular killer lymphocytes. These cells digest the pyrogens and release interleukin-1 (IL-1), also called leukocyte pyrogen or endogenous pyrogens (Guyton and Hall 2006). Other cytokines released and acting as endogenous pyrogens include IL-6, β–and γ–interferon, and tumor necrosis factor-α. The endogenous pyrogens are thought to induce local release of prostaglandins in the hypothalamus, causing elevation of the set point (Lunn 2001).

Once the set point is elevated, the body temperature is perceived as too low by the hypothalamus, which sets the temperature-raising mechanisms into action. Heat is conserved by vasoconstriction, and heat production increases by shivering or chills. Once the fever stimulus is removed, the set point is returned to normal, but now the hypothalamus perceives the body temperature as too high; therefore, temperature-lowering mechanisms are initiated and seen as flushing or peripheral vasodilation, sweating, and panting.

The benefit of fever to the patient is uncertain. It is presumed to be beneficial because it has persisted as a response to infections and other diseases. Most microorganisms grow within a certain temperature range, and an increase in temperature can inhibit their growth. Also, antibody production is increased when body temperature is elevated. Hyperthermia can also slow the growth of some tumors (Ganong 2001).

However, once a critical temperature is reached, permanent intracellular changes and cell membrane instability can lead to multiple tissue and organ dysfunction. Multiorgan dysfunction or failure can involve the coagulation, hematologic, renal, gastrointestinal, cardiopulmonary, and central nervous systems. A temperature of 105.8°F for prolonged periods can lead to permanent brain damage (Flournoy et al. 2003). Temperatures above this threshold should be suppressed to prevent permanent damage to the patient.

The cause of a fever resulting from an acute inflammatory process can usually be found from a thorough physical examination. On the other hand, fevers of unknown origin (FUOs) or obscure, unexplained fevers, are usually caused by a chronic inflammatory process not easily identified on physical examination or with routine laboratory procedures. FUOs have three characteristics: (1) at least a 2-week duration, (2) temperature exceeding normal by 1.5° Fon multiple occasions, and (3) an obscure etiology. In humans, 30–40% of cases of FUOs are caused by infection, 20–30% by neoplasia, 10–20% by rheumatologic diseases, 15–20% by miscellaneous causes, and 5–15% remain undiagnosed. A similar distribution is seen in veterinary patients, and, overall, infection, immune-mediated disease, and neoplasia are the most important causes of FUO in small animals (Lunn 2001). Certain medications can also induce fevers, and a complete, detailed history should be obtained in all FUO patients.

The majority of small animals with FUO probably have an infection, but the prevalence of the causative infectious agents varies depending on the geographic area and the previous travel history of the patient. In some areas, systemic fungal disease or rickettsial infections may be more common in dogs than bacterial infections. Other infectious causes of FUO in dogs include endocarditis, pyelonephritis, prostatitis, closed pyometra, pyothorax, and other abscesses. In the cat, viral diseases are a more common cause of FUO than bacterial infections, and the most common viral infections include feline leukemia virus (FeLV), feline infectious peritonitis (FIP), and feline immunodeficiency virus (FIV).

The second most common cause of FUO in small animals is immune-mediated disease. Immune complexes are potent stimulators for release of endogenous pyrogens and can lead to temperatures above 105°F. Immune-mediated polyarthritis is an often forgotten cause of FUO in dogs. Finally, neoplasia is not as common as immune-mediated disease in causing FUO but should be considered, especially in older patients (Miller 2005).

The diagnostic plan should include testing for each of the most common causes of FUO. Four factors should be considered when developing a diagnostic plan for FUO: (1) the plan should begin with tests that are safe, simple, inexpensive, and easy to interpret; (2) the plan should minimize the chance of overlooking any rule-outs; (3) the plan should evolve as results from tests become available; and (4) the plan should allow for repeating simple and basic diagnostic tests. The initial database should include a thorough history, complete physical examination, complete blood count, serum chemistry profile, urinalysis, urine culture and sensitivity, fundic examination, neurologic examination, thoracic and abdominal radiographs, and FeLV and FIV tests (in cats). Further testing will depend on the clinical signs and physical examination findings in each individual patient. For example, echocardiography is recommended if a murmur is present, and arthrocentesis is recommended if joint swelling is present. Titers for infectious diseases prevalent in certain geographical areas should also be submitted. Other testing could also include blood cultures, abdominal ultrasound, lymph node aspirates, fecal culture, antinuclear antibody and rheumatoid factor, and bone marrow aspirate, as indicated.

The problems identified in BoBo were as follows: