Patient with fever

Dr Förhécz Zsolt
 Dehydration fever

Crimean-Congo hemorrhagic fever

Febrile convulsions

Fever of unknown origin (FUO)

Jaccoud's dissociated fever
Lassa fever
Jamshedpur fever
Metal fume fever ‘Q’ fever
Rat bite fever Relapsing fever
Rheumatic fever
Sennetsu fever

Tsutsugamushi fever
Valley fever
Yellow fever West Nile fever
INTRODUCTION
• FEVER(Pyrexia) Is an elevation of body temperature above the normal circadian
range (daily variation) as a result of a change in the thermoregulatory center
located in the anterior hypothalamus and pre-optic area (i.e. an increase in the
hypothalamic set point of 37 C) due to infection, metabolic derangements or
increased cell destruction.
• Hyperthermia is a state of elevated core temperature that rises rapidly above
40°C, secondary to failure of thermoregulatio, that occurs when a body produces
or absorbs more heat than it dissipates.
• Hyperpyrexia — Hyperpyrexia is the term for an extraordinarily high fever
(>41.5°C), which can be observed in patients with severe infections but most
commonly occurs in patients with central nervous system (CNS) hemorrhages.
Hyperthermia 1.
• In contradistinction to fever, the setting of the thermoregulatory center during
hyperthermia remains unchanged at normothermic levels, while body
temperature increases in an uncontrolled fashion and overrides the ability to lose
heat. Exogenous heat exposure and endogenous heat production are two
mechanisms by which hyperthermia can result in dangerously high internal
temperatures. It can be rapidly fatal, and its treatment differs from that of fever.
• The underlying cause must be removed. Antipyretics do not reduce the elevated
temperature. Rapid reduction of body temperature by physical means. Fluids.
CAUSES:
– Hypohydration is a major cause of hyperthermia.
– Overinsulating clothing can result in elevated core temperature
– Who work or exercise in hot environments –heat stroke syndromes
– Hyperthyroidism
Hyperthermia 2.
• Neuroleptic malignant syndrome (butyrophenones(haloperidol)
or phenothiazines(promethazine,chlorpromazine) are reported to be at greatest
risk, dopaminergic (levodopa), antiemetic (metoclopramide), lithium.
• Serotonin syndrome (SSRI)
• Anesthetic agents (such as halothane) or the paralytic agent succinylcholine.
• Anticholinergics
• Drugs that decouple oxidative phosphorylation may also cause hyperthermia.
From this group of drugs the most well known is 2,4-Dinitrophenol.
• Stimulant drugs, including amphetamines and cocaine, and hallucinogenic
drugs, including PCP(Angel dust), LSD, and MDMA (Ectasy)
PYROGENS — The term pyrogen is used to describe any substance that
causes fever. Pyrogens are either exogenous or endogenous. Endogenous pyrogens
belong to the class of biologically active proteins called cytokines.

• Exogenous pyrogens- mainly microbes or their products, such as toxins

– lipopolysaccharide endotoxin produced by all gram-negative bacteria
– Endotoxins belong to a classification of microbial products termed Toll-like receptor
(TLR) ligands.
– The toxic shock syndrome toxin (TSST-1) is associated with strains of Staphylococcus
aureus
– exotoxins from group A Streptococcus act both as direct toxins but also serve as
"superantigens"

• Pyrogenic cytokines -Pyrogenic cytokines are specific cytokines produced upon

activation of TLR that cause fever
– IL-1, TNF, and IL-6, and each or all three cytokines trigger the hypothalamus to raise
the set-point to febrile levels
MECHANISMS OF ANTIPYRETIC AGENTS —
• The synthesis of prostaglandin E2 (PGE2) depends upon the constitutively
expressed enzyme cyclooxygenase. The substrate for cyclooxygenase is
arachidonic acid released from the cell membrane, and this release is the rate-
limiting step in the synthesis of PGE2.
• Inhibitors of cyclooxygenases (either COX-1 or COX-2) are potent antipyretics
– Aspirin
– Nonsteroidal antiinflammatory agents (NSAIDs), such as naproxen or ibuprofen, are
excellent antipyretics
– Acetaminophen is a poor cyclooxygenase inhibitor in peripheral tissue and does not
display noteworthy antiinflammatory activity; however, acetaminophen is oxidized in
the brain by the p450 cytochrome system, and the oxidized form inhibits
cyclooxygenase activity.
– Corticosteroids are also effective antipyretics, which act at two levels.
• Similar to the cyclooxygenase inhibitors, corticosteroids reduce PGE2 synthesis by inhibiting the
activity of phospholipase A2.
• Corticosteroids block the transcription of the mRNA for the pyrogenic cytokines.
 FACTITIOUS FEVER
• This is defined as fever engineered by the patient by
manipulating the thermometer and/or temperature chart
apparently to obtain medical care.
• uncommon and typically presents in young women with a
medical and nursing background.
• Examples include The dipping of thermometers into hot drinks
to fake a fever.
• The factitious disorder is usually medical but may relate to a
psychiatric illness with reports of depressive illness.
• CLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER
– A patient who looks well
– Absence of temperature-related changes in pulse rate
– Temperature > 41°C
– Absence of sweating during the period of fever
– Normal ESR and CRP despite high fever
• Useful methods for the detection of factitious fever include 1)
Supervised (observed) temperature measurement 2) Measuring
the temperature of freshly voided urine
 TYPES OF FEVER- The pattern of temperature changes may
occasionally hint at the diagnosis:
• Continuous/sustained fever: Temperature remains above normal throughout
the day and does not fluctuate more than 1 °C in 24 hours, e.g. lobar
pneumonia, typhoid fever, urinary tract infection, brucellosis

• Intermittent fever: The temperature elevation is present only for a certain

period, later cycling back to normal (i.e. Normal temp. between fever episodes),
e.g. pyaemia, or septicemia.

• Relapsing fever: temperature returns to normal for days before rising -Tertian
fever (48 hour periodicity), typical of Plasmodium vivax or Plasmodium ovale
malaria

• Remittent fever: Temperature remains above normal throughout the day and
fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis.

• Pel-Ebstein fever: A specific kind of fever associated with Hodgkins lymphoma,

being high for one week and low for the next week and so on. However, there is
some debate as to whether this pattern truly exists.
Presenting complaints of a patient with fever
• Feeling hot- A feeling of heat does not necessarily imply fever
• Rigors. profound chills accompanied by chattering of the teeth and severe
shivering, implies a rapid rise in body temperature.
– Can be produced by : 1) brucellosis and malaria 2) sepsis with abscess 3) lymphoma

• Excessive sweating. Night sweats are characteristic of tuberculosis, but sweating

from any cause is usually worse at night.
• Recurrent fever. Source is often a focus of bacterial infection such as
cholecystitis or cholangitis or urinary tract infection especially
associated with an obstruction or calculi.
• Headache. Fever from any cause may provoke headache. Severe
headache and photophobia, may suggests meningitis.
• Delirium. Mental confusion during fever is well described and
relatively more common in young children and in old age.
• Muscle pain. Myalgia is characteristic of viral infections such as
influenza, Malaria and brucellosis.
Symptom analysis for fever
• Verify presence of fever- True or factitious fever
• Duration- Acute or chronic
• Mode of onset- Abrupt or gradual
• Progression- Continuous or intermittent. If intermittent ask about frequency to
determine the pattern.
• Severity- how it affects daily work/physical activities.
• Relieving and aggravating factors
• Treatment received or/and outcome
• Associated symptoms- Localizing symptoms may indicate the source of fever.
• Respiratory tract symptoms:
– 1) Sore throat, nasal discharge, sneezing-URTI
– 2) Sinus pain and headache-suggests sinusitis
– 3) cough, sputum, wheeze or breathlessness-suggests a LRTI

• Genitourinary symptoms:
– Frequency of micturition, dysuria, loin pain, and vaginal or urethral discharge-
suggesting a) Urinary tract infection, b) Pelvic inflammatory disease and c) Sexually
transmitted infection (STI)

• Abdominal symptoms:
– diarrhea, with or without blood, weight loss and abdominal pain -suggesting a)
Gastroenteritis, b) Intra-abdominal sepsis, c) Inflammatory bowel disease, d)
Malignancy
• Skin rash: enquire about appearance and distribution as it may provide clues to
the diagnosis-
– 1) Macular- Measles,Rubella,toxoplasmosis
– 2) Haemorrhagic- Meningococcal infections, viral haemorrhagic fever.
– 3) Vesicular- Chickenpox, Shingles, herpes simplex
– 4) Nodular- Erythema nodosum( TB and Leprosy)
– 5) Erythematous- Drug rashes, Dengue fever
 – Joint symptoms: joint pain, swelling or limitation of movement is suggestive of active
arthritis.
– A) distribution : mono , oligo or poly arthritis
– B) appearance : fleeting 1) infective arthritis- oligoarthritis 2) collagen vascular disease-
fleeting 3) reactive arthritis

• Constitutional symptoms:
– Weakness
– Fatigue
– Anorexia
– Change of weight
– Fever/chills
– Lumps
– Night sweats
 HISTORY-Past Medical /Surgical History

• Start by asking the patient if they have any medical problems

• IHD/DM/Asthma/HT/RHD, TB/Jaundice/Fits e.g. if diabetic- mention time of
diagnosis/current medication/clinic check up
• Past surgical/operation history - E.g. time/place/ what type of operation.
• Note any blood transfusion / blood grouping.
• H/O dental extractions/circumcision & any excessive bleeding during these
procedures.
• Any minor operations or procedures including endoscopies, dental
interventions, biopsies.
• History of trauma/accidents- E.g. time/place/ and what type of accident
• History of tattoo, piercing
• Clinicians should note disorders or factors that predispose to infection,
– such as immunocompromise (eg, due to disorders such as HIV infection, cancer,
diabetes, or use of immunosuppressants), structural heart disorders, urinary tract
abnormalities,operations, and insertion of devices (eg, IV lines, pacemakers, joint
prostheses).
HISTORY
• Drug and allergy History-dosage, timing &how long.
• Drug fever is uncommon and therefore easily missed-The culprits include : penicillin
and cephalosporin sulphonamide anti tuberculous agents anticonvulsants particularly
phenytoin
• Vitamins/Traditional /Herbal medicine & alternative medicine such as acupuncture.
• Blood transfusion.
• Immunization against Hepatitis A &B, Typhoid fever.
• Malaria prophylaxis
• Family History
– Any familial disease/running in families e.g. breast cancer, IHD, DM, Asthma, Arthritis
– Infections running in families as TB, Leprosy. Cholera, typhoid in case of epidemics.
 Personal and Social History
• Smoking history - amount, duration & type- strong risk factor for IHD
• Alcohol history - amount, duration & type-Unhealthy alcohol use is associated
with cardiomyopathy, CVA, liver cirrhosis, alcoholic hepatitis, hepatocellular
carcinoma.
• Occupation, social & education background, family social support& financial
situation, Social class
• Home conditions-Water supply, Sanitation status in his home & surrounding,
Geographic area of living, fresh-water swimming.
• Animals / birds in his/her house- exposure to birds (psittacosis) or animals
(toxoplasmosis, brucellosis, leptospirosis)
• Consumption of unpasteurized milk or milk products (tuberculosis, brucellosis
and Q fever).
• Sexual History- Unprotected exposure to sexual partner with STI, HIV
• Illicit drug usage- injections and sharing of needles (HIV, hepatitis B &C, infective
endocarditis), site of injection (e.g Femoral vein-septic arthritis, ilio-psoas abscess)
Travel HistoryTravel to an area known to be
endemic for certain disease
• Name of the area, duration of stay
• Onset of illness- (incubation period)
– 1 –10 Days- Malaria, Dengue, Salmonella
– 10 –21Days-Malaria,Typhoid,Brucella,HepatitisA
– Weeks-Months- Amoebiasis, HIV, Hepatitis

• Vital questions-(Always ask about foreign travel).

– a) Where have you been? …Endemic area or not ?
– b) What have you done?
– c) How long were you there?
– d) Did you have insect bites or contact with animals?
– e) Did you take precautions/prophylaxis against malaria?

• If the patient has been in an endemic area The most common diagnoses :Malaria,
Typhoid fever, Viral hepatitis, Dengue fever Malaria must be excluded whatever the
presenting symptoms
Vital signs – Schock DD, SEPSIS!!!

CAUSE of relativ bradycardia

• Infectious Causes
• Intracellular organisms
– Gram-negative bacteria :Salmonella typhi, Francisella tularensis, Brucella spp., Coxiella
burnetii (Q fever), Leptospira interrogans, Legionella pneumophila, Mycoplasma
pneumoniae
– Tick-borne organisms Rickettsia spp., Orientia tsutsugamushi (scrub typhus), Babesia
spp.,
– Other Corynebacterium diphtheriae, Plasmodium spp. (malaria)

• Viruses/viral infections Yellow fever virus, Dengue virus, Viral hemorrhagic

feversa, Viral myocarditis
• Noninfectious Causes
– Drug fever, Beta blocker use, Central nervous system lesions, Malignant lymphoma,
Factitious fever
Diagnostic tests
• All of these tests should be viewed as adjuncts to the
history and physical examination—not a replacement for
them. The selection of initial tests should be based directly
on the patient’s history and physical exam findings
• White Blood Cell (WBCare often associated with
infection,) –
– though many viral infections are associated with
leukopenia.
– bacteria are associated with an increase in
polymorphonuclear neutrophils, often with
elevated levels of earlier developmental forms
such as bands;
– viruses are associated with an increase in
lymphocytes;
– and certain parasites are associated with an
increase in eosinophils
 Causes of an Extremely Elevated Erythrocyte
Sedimentati on Rate (>100 mm/h)
Inflammatory Markers
• The erythrocyte sedimentation rate (ESR)
and the C-reactive protein (CRP) level are
indirect and direct measures of the acute-
phase response, respectively, that can be
used to assess a patient’s general level of
inflammation
• ESR changes relatively slowly, and its
measurement more often than weekly
usually is not useful; in contrast, CRP
concentrations change rapidly, and daily
measurements can be useful in the
appropriate context.
• Although these markers are sensitive
indicators of inflammation, neither is very
specific.
Cultures
• The mainstays of infectious disease diagnosis include the culture of infected
tissue (e.g., surgical specimens) or fluid (e.g., blood, urine, sputum, purulence
from a wound).
• Samples can be sent for culture of bacteria (aerobic or anaerobic), fungi, or vir
• Ideally, specimens are collected before the administration of antimicrobial
therapy uses.

Pathogen-Specific Testing
• Numerous pathogen-specific tests (e.g., serology, antigen testing, PCR testing)
Analysis of Cerebrospinal Fluid (CSF
• Assessment of CSF is critical for patients with suspected meningitis or encephalitis.

• An opening pressure should always be recorded, and fluid should routinely be sent for cell
counts, Gram’s stain and culture, and determination of glucose and protein levels. A CSF Gram’s
stain typically requires >105 bacteria/mL for reliable positivity; its specificity approaches 100%

• PCR analysis of CSF is increasingly being used for the diagnosis of bacterial (e.g., N.
meningitidis, S. pneumoniae, mycobacteria) and viral (e.g., herpes simplex virus, enterovirus)
infections;
 Radiology
• Imaging provides an important adjunct to the physical examination, allowing
evaluation for lymphadenopathy in regions that are not externally accessible
(e.g., mediastinum, intraabdominal sites), assessment of internal organs for
evidence of infection, and facilitation of image-guided percutaneous sampling of
deep spaces.
– X-ray, CT, MRI, ultrasound, nuclear medicine, use of contra
 TREATMENT
• Physicians often must balance the need for empirical
antibiotic treatment with the patient’s clinical
condition.
• When clinically feasible, it is best to obtain relevant
samples (e.g., blood, CSF, tissue, purulent exudate)
for culture prior to the administration of antibiotics,
as antibiotic treatment often makes subsequent
diagnosis more difficult.
• Although a general maxim for antibiotic treatment is
to use a regimen with as narrow a spectrum as
possible, empirical regimens are necessarily
somewhat broad, given that a specific diagnosis has
not yet been made.
• These regimens should be narrowed as appropriate
once a specific diagnosis is made
WHEN TO OBTAIN AN INFECTIOUS DISEASE
CONSULT?
• Multiple studies have demonstrated that an infectious disease consult is
associated with positive outcomes for patients with various diseases.
• Specific situations that might prompt a consult include
– (1) difficult-to diagnose patients with presumed infections,
– (2) patients who are not responding to treatment as expected,
– (3) patients with a complicated medical history (e.g., organ transplant recipients,
patients immunosuppressed due to autoimmune or inflammatory conditions), and
– (4) patients with “exotic” diseases (i.e., diseases that are not typically seen within the
region).
Fever of unknown origin (FUO)
• is defined as fever higher than 38.3ºC on several occasions lasting for at least
three (some use two) weeks without an established etiology despite intensive
evaluation and diagnostic testing.
• Three general categories of illness account for the majority of "classic" FUO cases
and have been consistent through the decades. These categories are:
– Infections (25 to 50%)
– Connective tissue disorders (10 to 20%)
– Neoplasms (5 to 35%)
– Miscellaneous (15 to 25%)

• The most important aspects of the evaluation of a patient with FUO are:
– to take a careful history,
– perform a detailed physical examination,
– and to reassess the patient frequently.
 FUO is currently classified into 4 distinct categories
• Classic FUO: Fever for > 3 wk with no identified cause after 3 days of hospital
evaluation or ≥ 3 outpatient visits
• Health care–associated FUO: Fever in hospitalized patients receiving acute care and
with no infection present or incubating at admission if the diagnosis remains uncertain
after 3 days of appropriate evaluation
• Immune-deficient FUO: Fever in patients with immunodeficiencies if the diagnosis
remains uncertain after 3 days of appropriate evaluation, including negative cultures
after 48 h
• HIV-related FUO: Fever for > 3 wk in outpatients with confirmed HIV infection or > 3
days in inpatients with confirmed HIV infection if the diagnosis remains uncertain after
appropriate evaluatio
• Infections are the most common cause of FUO.

• In patients with HIV infection, opportunistic infections (eg, TB; infection by atypical mycobacteria,
disseminated fungi, or cytomegalovirus) should be sought.

• Common connective tissue disorders include SLE, RA, giant cell arteritis, vasculitis, and juvenile RA of
adults (adult Still disease).

• The most common neoplastic causes are lymphoma, leukemia, renal cell carcinoma, hepatocellular
carcinoma, and metastatic carcinomas. However, the incidence of neoplastic causes of FUO has been
decreasing, probably because they are being detected by ultrasonography and CT, which are now widely
used during initial evaluation.

• Important miscellaneous causes include drug reactions, deep venous thrombosis, recurrent pulmonary
emboli, sarcoidosis, inflammatory bowel disease, and factitious fever.

• No cause of FUO is identified in about 10% of adults.

Physical examination
• The skin is thoroughly inspected for focal erythema (suggesting a site of
infection) and rash(eg, malar rash of SLE). Clinicians should also check for
cutaneous findings of endocarditis, including painful erythematous
subcutaneous nodules on the tips of digits (Osler nodes),nontender
hemorrhagic macules on the palms or soles (Janeway lesions), petechiae, and
splinter hemorrhages under the nails.

• The entire body (particularly over the spine, bones, joints, abdomen, and
thyroid) is palpated for areas of tenderness, swelling, or organomegaly; digital
rectal examination and pelvic examination are included. The teeth are
percussed for tenderness (suggesting apical abscess).

• During palpation, any regional or systemic adenopathy is noted.

• The heart is auscultated for murmurs (suggesting bacterial endocarditis) and

rubs (suggesting pericarditis due to a rheumatologic or infectious disorder).
Red flags
• The following are of particular concern:
• • Immunocompromise
• • Heart murmur
• • Presence of inserted devices (eg, IV lines, pacemakers, joint prostheses)
• • Recent travel to endemic areas
Minimum diagnostic evaluation:
• blood cultures
• erythrocyte sedimentation rate or C-reactive protein,
• serum lactate dehydrogenase,
• HIV antibody test and viral load,
• rheumatoid factor, heterophile antibody test, creatine phosphokinase, antinuclear
antibodies,
• tuberculin skin test or interferon-gamma release assay,
• serum protein electrophoresis,
• and computed tomography scan of abdomen and chest
Imaging tests are guided by symptoms and signs.
• Typically, areas of discomfort should be imaged—
– eg, in patients with back pain, MRI of the spine (to check for infection or tumor);
– In patients with abdominal pain, CT of the abdomen.
– However, CT of the chest, abdomen, and pelvis should be considered to check for adenopathy and occult
abscesses even when patients do not have localizing symptoms or signs.

• If blood cultures are positive or heart murmurs or peripheral signs suggest endocarditis,
echocardiography is done.
• In general, CT is useful for delineating abnormalities localized to the abdomen or chest.
• MRI is more sensitive than CT for detecting most causes of FUO involving the CNS and should be
done if a CNS cause is being considered.
• Venous duplex imaging may be useful for identifying cases of deep venous thrombosis.
• Radionuclide scanning with indium-111–labeled granulocytes may help localize some infectious or
inflammatory processes. This technique has generally fallen out of favor because it is thought to
contribute very little to diagnosis, but some reports suggest that it provides a higher diagnostic yield
than CT.
• PET may also be useful in detecting the focus of fever.
• Biopsy may be required if an abnormality is
suspected in tissue that can be biopsied (eg,
liver(possible miliary tuberculosis, granulomatous
hepatitis, or other granulomatous diseases such as
sarcoidosis), bone marrow, skin, pleura, lymph
nodes(malignancy, especially lymphoma, or
infections such as cat-scratch disease), intestine,
muscle). Biopsy specimens should be
• evaluated by histopathologic examination and
cultured for bacteria, fungi, viruses, and
mycobacteria or sent for molecular (PCR) diagnostic
testing.
• Muscle biopsy or skin biopsy of rashes may confirm
vasculitis.
• Bilateral temporal artery biopsy may confirm giant
cell arteritis in elderly patients with unexplained
ESR elevation.
• Patients with FUO should not have empiric antibiotics started solely to treat fever.
• A therapeutic trial of glucocorticoids for an inflammatory process should not replace
relevant biopsies for steroid-responsive disease such as sarcoidosis, other granulomatous
diseases, or vasculitis.
• The rapid and marked decrease in temperature following a therapeutic trial of naproxen is
said to distinguish the fever of malignancy, and especially lymphomas, from infectious
causes.
• Antipyretics improve patients' comfort, reducing headache, myalgias, arthralgias, and
fatigue. In addition, they may also prevent delirium, particularly in older adults, and
reduce exacerbations of chronic lung and heart disease. However, drugs with antipyretic
effects may delay or obscure early symptoms and signs of specific diseases. Thus, we try to
avoid prescribing acetaminophen, nonsteroidal antiinflammatory drugs, or
glucocorticoids.
The most important aspects of the evaluation of a
patient with FUO are

• to take a careful history,

• perform a detailed physical examination,
• and to reassess the patient frequently.