FEVER

 Core body temperature – 36.5˚ - 37.5˚c.

 Mean oral temperature – 36.8˚ ± 0.4˚c.
 Maximal normal oral temperature is 37.2˚ at 6am and 37.7˚c at 4pm.
 a.m temperature of >37.2˚c(>98.-˚F) or a p.m temperature of >37.7˚c.
 Elderly individuals can exhibit a reduced ability to develop fever.
 Rectal temperatures are generally 0.4˚c higher than oral readings.
 Unadjusted – mode tymphanic membrane values are 0.8˚c lower than
rectal temperature.
 In women who menstruates, the a.m temperature is generally lower in the
two weeks before ovulation.
 It then rises by -0.6˚c with ovulation and remains at that level until menses
occur.
 Body temperature can be elevated in the postprandial state.
Fever vs Hyperthermia
 Fever
1. Elevation of the body temperature that exceeds the normal
daily variations.
2. Occurs in conjugation with an increase in hypothalamic set
point (Ex. From 37˚c to 39˚c).
 Hyperpyrexia
1. A fever of >41.5˚c.
2. in patient with severe infections, CNS hemorrhages, heat stroke.
3. uncontrolled increase in body temperature that exceeds the
body’s ability to lose heat.
Hyperthermia

 Rapidly fatal.
 Does not responds antipyretics.
 Systemic sepsis can result to hyperpyrexia.
 Diagnosed on the basis of the events immediately preceding the
elevation of core temperature.
 Skin is not hot but dry.
 In fever skin can be cold due to vasoconstriction.
Pathogenesis of fever

 Pyrogens:
 Exogenous pyrogens – microbial products, microbial toxins or
whole micro organisms including viruses.
 Lipopolysaccharides(endotoxins) produced by all gram –ve
bacteria.
 Enterotoxins of staphylococcus aureus: super antigens of A and
B streptococci.
 Endotoxins – fever, leukocytosis, acute phase proteins, and
generalized symptoms of malaise.
Pyrogenic Cytokines

 Regulate immune, inflammatory and hematopoietic processes.

 Interleukin 1 and IL-6- leukocytosis seen in infections.
 IL-1, IL-6, TNF, and ciliary neurotropic factor causes fever.
 Endotoxin- fever leukocytosis, acute phase proteins and generalized
symptoms of malaise.
 Fever- prominent side effect of IFN- used in the treatment of hepatitis.
 fever- can be a manifestation of disease in the absence of microbial
infection.
 Inflammatory processes, trauma, tissue necrosis and antigen- antibody
complexes.
 PGE2- elevated in hypothalamic tissue and the third cerebral ventricle
during fever.
 First step in initiating fever- exogenous pyrogens + pyrogenic cytokines
interact with the endothelium.
 Myeloid and endothelial cells- primary cell types produce pyogenic
cytokines.
 EP3 – PGE2 receptor essential for fever.
 Cytokines produce in the brain – account for the hyperpyrexia of CNS
hemorrhage, trauma of infection.
 Viral infections of the CNS induce microglia and possibly neuronal
production of IL, TNF IL-6.
Approach to patient with fever

 Physical Examination:- Chronology of events preceding fever, exposure to other

infected individuals or to vector of disease.
 Same site should be used consistently to monitor a fibrile disease (oral, tympanic
membrane, or rectal).
 May have active infection in the absence of fever.
 Newborns
 Elderly
 Chronic liver disease
 Renal failure
 Taking glucocorticoids
 On treatment with anticytoline.
Laboratory tests:-

 CBC
 Juvenile or band forms, toxic granulation, dohle bodies – bacterial infection
 Neutropenia – viral infection.
 Levels of cytokines such as IL-1 and TNF – not advised below detection limit
of essay.
 C-reactive protein level, ESR- Markers of inflammatory process are
particularly helpful in detecting aoccult disease.
 Ciruculating IL-6- useful because it indicates C -reactive protein.
 Crohn’s disease, rheumatoid arthritis or psoriasis.
 Blocking of cytokine activity- lower the level of host defences against both
routine bacterial and opportunistic infections.
 Receiving high dose glucocorticoid therapy or anti-inflammatory agents
such as ibuprofen-blunted fever.
 Low grade fever is of considerable concern in patients receiving anti-
cytokine therapies.
Decision to treat fever

 Treatment of fever and it symptoms with routine antipyretics does no harm

and does not show the resolution of common viral and bacterial infections
 In bacterial infections the with holding of antipyretic therapy can be
helpful in evaluating effectiveness of a particular antibiotics.
 XXX RTC antipyretic in patient with bacterial infection.
Temperature-Pulse Dissociation

 Enteric fever
 Brucellosis
 Leptospirosis
 Drug-induced fever
 Factitious fever
 Hypothermia can develop in patient with septic shpock.
Characteristic patterns of febrile
episode
 Plasmodium vivax causes fever every 3rd day.
 Fever occur every 4th day with malariae.
 Borrelia- with days of fever followed by several day afebrile period and
then relapse into additional days of fever.
Characteristic pattern of afebrile
episode:-
 Pel- Ebstein pattern, Hodgkin’s disease, Lymphoma- fever lasting 3-10 days
followed by a afebrile periods of 3-10 days.
 Cyclic neutropenia- fever occur every 21 days and accompany the
neutropenia.
 No periodicity of fever in patient with familial mediterraneum fever, fever in
anti inflammatory diseases, recurrent fever, neutrophilia, serosal
inflammation.
 Blocking of IL-1B- reduce the fever
 Also responds to antipyretic.
Mechanism of antipyretic agents

 The reduction of fever by lowering of the elevated hypothalamic set point-

a direct function of reduction of PGE2.
 Synthesis of PGE2 depends on cyclooxygenase.
 Inhibitors of cyclooxygenase are potent antipyretics
 Aspirin, acetaminophen, NSAIDs.
Glucocorticoids:-

 Reduce PGE2 synthesis inhibiting the activity of phospholipaseA2

 Block the transcription of the mRNA for the pyrogenic cytokines
 Ibuprofen and COX2 inhibitors reduce IL-1- induce IL-6 production-
contribute to the antipyretic activity of NSAIDs.
 Regimens for the treatment of fever.
 Reduce the elevated hypothalamic setpoints.
 Facilitate heat loss.
 Reduces systemic symptoms of headache, myalgia’s and arthalgias.
 Oral aspirin and NSAIDS- reduce fever but can adversely effect platelets
and the GIT.
 ASPIRIN- increase the risk of REYES syndromein children.
 Fever increases the demand for oxygen.
 For every increase of 1˚c over 37˚c, there is a 13% increase in oxygen
consumptions.
 Aggravate preexisting impairment of cardiac, pulmonary or CNS function.
 Children with history of febrile or nonfebrile seizure should be aggressively
treated to reduce fever.
Recurrent fever

 In patient with recurrent fever, PDCs should be directed

 Fever lasting for >2 years, the fever is caused by infection or malignancy
 Diagnostic test include Scintigraphy.
 PDCs for infections, vasculities syndromes or malignancy are present or
when the patient clinical condition is deteriorating.
Scintigraphy

 Scintigraphy is a method allowing delineation of foci in all parts of the body

on the basis of functional changes in tissue.
 Plays an important role in the diagnosis of patient with FUO in clinical
practice.
 Finally CT and MRI rouitinely provide information only on part of the body,
while scintigraphy readily allows whole body imaging.
Anti biotics and Anti tuberculos
therapy
 Antibiotics or antibiotic tubercles therapy may irrevocably diminish the
ability to culture fastidious bacteria or myobacteria.
 If TST is positive or granulomatter disease is present with angery and
sarcoidosis seems unlikely atherapuetic trail for tuberculosis should be
started.
 if the fever does not respond after 6 weeks of imperical anti tuberculoais
treatment another diagnosis should be considered
Colchicine, NSAI Drugs

 Colchicine is highly effective in preventing attacks.

 If the fever persists and the source remains elusive after completion of later
stage investigations, supportive treatment with NSAI drugs can be helpful.
 NSAI drugs and glucocorticoids to mask to fever while permitting the
spread of infection or lymphoma detects that use should be avoided
unless infectious disease is and malignant lymphoma has been largely rule
out.
 Inflammatory disease is probable and is likely to be life threatening.
Anakinra

 It is recombinant form of naturally occurring IL-1 receptor antagonist.

 Monotherapy with IL-1 blockade can provide improved control without the
metabolic immunologic and gastrointestinal side effects of glucocorticoid.
 Hodgkin's lymphoma carries a high death toll.
 FUO fatality rates are very low.
 Treated with anitbiotics.
 In less affluent regions, infectious diseases are still a major cause of FUO,
and outcomes may be different