THE CLINICAL SIGNIFICANCE OF FEVER PATTERNS

Volume 10, Issue 1 (March 1996): 33-44

Infectious Disease Clinics of North America

THE CLINICAL SIGNIFICANCE OF FEVER PATTERNS

Burke A. Cunha MD
From the Infectious Disease Division, Winthrop-University Hospital, Mineola; and the State University of New York
School of Medicine, Stony Brook, New York
Address reprint requests to
Burke A. Cunha, MD
Infectious Disease Division
Winthrop-University Hospital
259 First Street
Mineola, NY 11501

Fever patterns have been appreciated for centuries by clinicians as important diagnostic
signs. When methods for diagnosing infectious diseases were primitive or nonexistent, analysis of
fever curves often provided the only way to differentiate acute febrile illnesses. Magnitude and
frequency of fever spikes, as well as the fever's characteristic fever curves, were associated with a
variety of infectious disorders. Although fever curves were helpful in only a relatively few infectious
diseases, it was noted that certain infections regularly and reproducibly were associated with a
particular fever pattern. To this day, in spite of extensive research in chemical mediators of the
febrile response (e.g., cytokines), it is not understood why certain fever patterns are characteristic of
certain infectious diseases. It is remarkable and somewhat amazing that typhoid fever still is
accompanied by a stepwise increase in temperature with a sustained fever pattern. Why this or any
other fever pattern is associated with particular infectious diseases remains a mystery. [2] [7] [10] [12]
The classical fever patterns were regarded as a key diagnostic sign by clinicians, but their
usefulness has been questioned by some in the past few decades. [9] Fever curves have limited
diagnostic usefulness in hospital-acquired infections. [4] In community-acquired infections,
characteristic fever curves are more important, but are a function of geographic location. For
example, the double quotidian fever curve seen with visceral leishmaniasis (kala-azar) is only useful
to clinicians in those parts of the world where the disease is prevalent. Reassessment of the
usefulness of fever curves for diagnostic purposes is related to the ratio of community-acquired to
hospital-acquired infections and geographically dependent epidemiology. [3]
THE CLINICAL APPROACH
Fever may indicate an infectious, inflammatory, or neoplastic disorder. Although the
absence of fever is diagnostically unhelpful, the abruptness of the onset, appearance of the patient,
fever magnitude/ pattern, and associated clinical or laboratory findings usually point to the probable
cause of the fever. Diseases behave biologically in a predictable manner even though the clinical
presentation may be quite varied, and the pattern of organ involvement and key characteristic
aspects of the fever determine the differential diagnosis. [2] [3] [4] [5]
For diagnostic purposes, fevers may be viewed as acute, subacute, or chronic, and with or
without localizing signs. [6] Febrile patients with localizing signs present few difficulties in diagnosis.
Diagnosing patients without localizing signs, however, is a diagnostic challenge. In patients with only
fever, the fever pattern may be the only way to arrive at a working diagnosis. [8] [9] [10] [11] [12] Clinically,
fever should be viewed as an important diagnostic clue as well as an essential host defense
mechanism. [4] [7]
FEVER WITHOUT LOCALIZING SIGNS
Fever can be approached from a diagnostic perspective as presenting with or without
localizing signs. Infectious diseases presenting as acute febrile illnesses without localizing signs, such

as typhoid fever, malaria, ehrlichiosis, roseola infantum, typhoidal tularemia, typhoidal Epstein-Barr
virus (EBV), mononucleosis, and miliary tuberculosis, are the most difficult diagnostic problem. The
preeruptive stages of Rocky Mountain spotted fever (RMSF), viral hepatitis, and the childhood
exanthems are further examples. If no localizing signs are present, analysis of temperature and
characteristic fever patterns are of clinical importance, and may provide the only clue to guide
further testing or suggest the diagnosis. [2] [3] [10]
FEVER PATTERNS
Fever patterns are of most help in diagnosing febrile illnesses without localizing signs, and
are of limited usefulness in nosocomial fevers. Classical fever patterns retain their usefulness/validity
in many areas of the world where traditional infectious diseases are common and retain their
importance. [8] [10] [12]
Intermittent fevers are temperature elevations that return to normal at least once during most days.
Sustained or continuing fevers do not vary more than 1F per day; remittent fevers do not return to
normal each day. Relapsing fevers are recurrent over days or weeks and may have any underlying
fever pattern (e.g., intermittent, continuous, remittent). Biphasic illnesses are not truly recurrent and
occur only once, and relapsing fevers are different from febrile diseases prone to relapse (Fig. 1) . [2]
[10] [12]

Magnitude of Fever
Although temperature elevation does not correlate with disease severity, the height of the
temperature elevation has important diagnostic significance at temperature extremes (e.g.,
hyperpyrexia or hypothermia). Temperatures more than 106F are not due to infectious diseases, and
a noninfectious origin should be the focus of the diagnostic approach (Table 1) (Table Not Available) .
Hypothermia or subnormal temperatures, if associated with bactermia, are a bad prognostic sign.
Slight hypothermia may be a normal variant in the elderly. Not infrequently, hypothermia is due to
overzealous antipyretic medications.
Most temperature elevations are encountered clinically between the extremes of
hyperpyrexia and hypothermia. Temperatures between 98F and 102F may be on an infectious basis,
but are usually due to noninfectious conditions common in hospitalized patients, especially in critical
care units. For diagnostic purposes, it is clinically useful to divide fevers into those capable of 102F or
more and those that nearly always remain below 102F. The differential diagnosis of most commonly
encountered causes of fever in the hospital/intensive care unit may be approached efficiently by
applying the "102F rule" (Table 2) (Table Not Available) . [2] [3]
TABLE 1 -- DIAGNOSTIC SIGNIFICANCE OF EXTREME HYPERPYREXIA AND HYPOTHERMIA
Adapted from Cunha BA: Clinical implications of fever. Postgrad Med 85(5): 188-200, 1989; with
permission.
(Not Available)
TABLE 2 -- DIFFERENTIAL DIAGNOSIS OF FEVER IN HOSPITALIZED PATIENTS BASED ON
TEMPERATURE--THE
102F
RULE
Adapted from Cunha BA: Clinical implications of fever. Postgrad Med 85(5): 188-200, 1989; with
permission.
(Not Available)

Figure 1. A, Intermittent (hectic/septic) fevers; B, remittent fever; C, sustained/continuous fever.

Frequency of Fever
Fevers may be described as intermittent, continuous/sustained, or remittent. Relapsing
fevers recur at various intervals after the initial febrile episode. Single isolated fever spikes are never
caused by infection and are commonly due to the transfusion of blood and blood products or the
manipulation of a colonization/infected mucosal surface.

The most specific fever pattern is the double quotidian fever because only a few diseases
are associated with two fever spikes a day (e.g., adult Still's disease, right-sided gonococcal
endocarditis, visceral leishmaniasis [kala-azar], etc). A double quotidian fever is an important clue to
the diagnosis of adult Still's disease because there are no other physical or laboratory findings to
establish the diagnosis (Fig. 2) .
Most infectious diseases have no specific fever pattern. The classic fever curves are of
limited diagnostic usefulness in hospitalized patients as most nosocomial infections are not caused
by classic infectious diseases (Table 3) (Table Not Available) . [3] [10] [12]
TABLE
3
-DIAGNOSTIC
SIGNIFICANCE
OF
FEVER
PATTERNS
Adapted from Cunha BA: Infectious Diseases. In Samiy AH, Bardoness J, Douglas RG (eds): Textbook of
Diagnostic Medicine. Philadelphia, Lea & Febiger, 1987; with permisson.
(Not Available)
Fever Duration
The magnitude of acute infectious diseases improves or worsens within 2 weeks. Not
uncommonly, many infectious diseases have persistent fever after clinical improvement that may last
2 to 4 weeks. The diagnosis of the cause of such fevers is usually straightforward, but the cause of
some remains obscure. These are best termed prolonged feversto avoid confusing them with bona
fide fevers of unknown origin (FUOs). FUOs by definition must have fever of 101F or more for at
least 3 weeks and remain undiagnosed after a week of inpatient/outpatient workup. [2] [6] [12]
Recurring Fever
Relapsing fevers may be due to a variety of infectious and noninfectious diseases.
Multisystem disease characterized by exacerbation/remission may mimic infectious relapsing fever.
Most temperature elevations occur at night as an exaggeration of our normal diurnal temperature
variation.
A biphasic fever is characterized by two fever spikes during the illness, usually over the
course of 1 or more weeks (e.g., African hemorrhagic fevers). This is in contrast to relapsing fevers
that are recurrent and not necessarily biphasic (Table 4 ; Fig. 3 ). [8] [10] [11] [12]

Figure 3. Relapsing (camelback/dromedary) fever.

Pulse/Temperature Relationships
The relationship of the pulse to the temperature is often more useful than the fever pattern.
If the pulse is elevated out of proportion to the temperature, the relationship is termed relative
tachycardia. Relative tachycardia is associated with noninfectious conditions and toxin-mediated
infections, such as gas gangrene. When the pulse is not elevated proportionately to the temperature
elevation, a pulse-temperature deficit exists (e.g., relative bradycardia). The finding of relative
bradycardia has important diagnostic significance. For example, if a hospitalized patient presents
with fevers and relative bradycardia, the differential diagnosis is limited to legionnaires' disease or
drug fever. If the chest radiograph is negative, the workup should be focused toward drug fever.
Drug fever is usually accompanied by relative bradycardia; associated findings include negative blood

cultures (excluding contaminants), slightly elevated serum transaminases, elevated erythrocyte

sedimentation rate (ESR), and eosinophils in the peripheral smear without eosinophilia, which is
uncommon (Fig. 4) (Figure Not Available) . [2] [3] [12]
Figure 4. (Figure Not Available) Temperature
chart showing relative bradycardia in a patient with Legionn
aire's disease prior to initiation of doxycycline treatment on day 5. Solid line represents temperature;
dotted line represents pulse. ( Adapted from Cotton LM, Strampfer MJ, Cunha BA: Legionella and mycoplasma
pneumonia: A community hospital experience. Clin Chest Med 8:441-453, 1987.)

Figure 2. Double quotidian fever.

Fever Defervescence Patterns

Viral illnesses have a slow temperature defervescence, usually over a week. Febrile,
noninfectious diseases will not decrease without specific therapy. Steroids and antipyretics decrease
temperatures nonspecifically; this needs to be taken into account in assessing therapeutic
responses. Clinicians may be misled into thinking an antibiotic is being effective as evidenced by a
decrease in temperature only to learn later the patient was concomitantly receiving an antipyretic
medication. For this and other reasons, fevers should not be eliminated without reason.
Bacterial infections usually manifest a prompt drop in temperature with appropriate
treatment. Infections respond at different rates, however, and this may be useful clinically. For
example, enterococcal subacute bacterial endocarditis (SBE) defervesces slowly over a week in
contrast to viridans streptococcal SBE. Similarly, temperature from Haemophilus influenzaeor
Klebsiella pneumoniaecomes down more slowly than if the patient had pneumococcal pneumonia.
Pneumococcal and H. influenzaemeningitis, in contrast, have a slower rate of temperature decrease
than does meningococcal meningitis. Even the febrile response to antibiotic therapy may vary, as is
the case with pneumococcal pneumonia, which has three patterns of febrile defervescences. The
usual pattern of proven pneumonia is rapidly decreasing temperature during the first 24 to 36 hours
of antibiotic therapy. The second pattern is a more gradual decrease over 3 to 4 days, usually seen in
compromised hosts (e.g., alcoholics). Lastly, after initial defervescence, a small group of patients will
have another temperature spike on day 3 or 4 (Fig. 5) .
After an initial response to antimicrobial therapy, patients usually continue with low-grade
to no fever until discharge. Reappearance of fever during treatment suggests an infectious
complication (i.e., septic emboli in a patient with subacute bacterial endocarditis) or drug fever. The
reappearance of fever after an initial response is virtually never because of resistant organisms, but
may be due to superinfection. The diagnostic approach should be directed accordingly, and

antibiotic therapy should not be changed because of the possibility of resistant organisms.
Immunocompromised hosts, in general, respond more slowly to antibiotic therapy.
CONCLUSION
The clinical validity of fever curves remains intact. Clinicians of old were not wrong in their
astute observations. The diagnostic usefulness of fever curves is best applied to difficult-to-diagnose
infectious diseases where present day investigations are relatively unhelpful (i.e., adult Still's disease
[adult juvenile rheumatoid arthritis]). Fever patterns are particularly useful in eliminating diagnoses
from consideration and suggesting otherwise unsuspected disorders that may be diagnosed by
further procedures.

TABLE 4 -- FEVERS PRONE TO RELAPSE

Infectious Causes
Relapsing fever (Borrelia recurrrentis)

Colorado tick fever

Trench fever (Rochalimaea quintana)

Dengue fever

Q Fever

Leptospirosis

Typhoid fever

Brucellosis

Vibrio fetus

Bartonellosis (Oroyo fever)

Syphilis

Acute rheumatic fever

Tuberculosis

Rat-bite fever (Spirillum minus)

Histoplasmosis

Visceral leishmaniasis

Coccidioidomycosis

Lyme disease

Blastomycosis

Malaria

Pseudomonas pseudomallei (meliodosis)

Babesiosis

LCM

Noninfluenzal respiratory viruses

Dengue fever

Epstein-Barr virus

Yellow fever

Cytomegalovirus

Chronic meningococcemia
Noninfectious Causes
Bechet's disease

Familial Mediterranean fever

Crohn's disease

Fever, Adenitis, Pharyngitis,

Weber-Christian disease (panniculitis)

Aphthous Ulcer syndrome

Leukoclastic angiitis

Systemic lupus erythematosus

Sweet's syndrome

Hyper IgD syndrome

Figure 5. Pneumococcal pneumonia fever defervescence patterns. A, common pattern; B, uncommon pattern;
C, pattern in compromised hosts.

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