approach to fever

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Approach to FEVER

• Dr.Bilal Natiq Nuaman
• Lecturer at Ibn-Sina Medical College
• C.A.B.M. ,F.I.B.M.S. ,D.I.M. ,M.B.Ch.B.
• 2013-2014

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Thermoregulation

• Because Temperature affects how the enzymes work
  in your body , People should maintain a normal
  body temperature of about 37C despite wide
  variations in both their metabolic activity and
  the temperature of their environment. Enzymes are
  proteins that catalyze chemical reactions in
  living cells.
• Almost all enzymes have an "optimal" temperature.
  For example, most human derived enzymes will
  function best at around 37 C .If it gets too
  hot or cold the enzymes might denature and lose
  the shape of their active site, which means the
  substrate may no longer fit and this decreases
  the rate of the chemical reactions.
• HOMEOSTASIS

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• The body keeps its core temperature constant at
  about 37 C by physiological adjustments
  controlled by the hypothalamus (Thermostat
  Center) where there are neurons sensitive to
  changes in skin and blood temperatures. The
  temperature-regulating centers are found in the
  Preoptic Area (the anterior portion of the
  hypothalamus). This area receives input from
  temperature receptors in the skin and mucous
  membranes (Peripheral Thermoreceptors) and from
  internal structures (Central Thermoreceptors),
  which include the hypothalamus itself.

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Normal Features of Body Temperature

• 1-the mean oral temperature is 36.8 0.4C
• 2-The normal diurnal variation is typically
  0.5C
• (6 A.M. readings lt 6 P.M. readings by 0.5 C)

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Fever (Pyrexia)

• definition-
• Fever is an elevation of body temperature that
  exceeds the normal daily range and occurs in
  conjunction with an increase in the hypothalamic
  set pointfor example, from 37 C to 39 C .
• an A.M. temperature of gt37.2 C
• (98.9F ) or a P.M. temperature of gt37.7 C
  (99.9F)

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Mechanisms of fever

• (1) Exogenous pyrogens (micro-organism , toxin )
  induce host cells, such as blood leukocytes and
  tissue macrophages, to produce fever-producing
  mediators called Endogenous pyrogens (e.g.,
  interleukin-1).
• (2) resetting of hypothalamus thermostatic set
  point to a higher level through the action of
  prostaglandin E2.(prodrome)
• (3) generation of hypothalamic mediated responses
  that raise body temperature (chill)
• (4) development of fever with elevation of body
  to new thermostatic set point
• (5) production of temperature lowering responses
  (defervescence-sweating) and return of body
  temperature to a lower level.

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• Exogenous pyrogens induce host cells, such as
  blood leukocytes and tissue macrophages, to
  produce fever-producing mediators called
  endogenous pyrogens (e.g., interleukin-1).
• The endogenous pyrogens mediate a number of other
  responses. For example, interleukin-1 is an
  inflammatory mediator that produces other signs
  of inflammation, such as leukocytosis, anorexia,
  and malaise.
• The phagocytosis of bacteria and breakdown
  products of bacteria that are present in the
  blood lead to the release of endogenous pyrogens
  into the circulation.
• The endogenous pyrogens are increase the set
  point of the hypothalamic thermoregulatory center
  through the action of prostaglandin E2.
• In response to the sudden increase in set point,
  the hypothalamus initiates heat production
  behaviors (shivering and vasoconstriction) that
  increase the core body temperature to the new set
  point, and fever is established.

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• This shift of the set point from normothermic
  to febrile levels very much resembles the
  resetting of the home
• thermostat to a higher level in order to
• raise the ambient temperature in a room.

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Benefits of fever

• 1-It enhance immune function
• Increases motility and activity of the white
  blood cells (T cells and B cells ).
• Stimulates the interferon production .
• Increase phagocytic activity
• 2-Inhibits growth of some microbial agents
• Many of the microbial agents that cause infection
  grow best at normal body temperatures, and their
  growth is inhibited by temperatures in the fever
  range

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Adverse effects of fever

• Dehydration occurs because of sweating.
• Metabolic effects
• Increased need for oxygen (13 for every 1 C
  increase in body temp.).
• Increases the heart rate (10 /min. for every 1
  C increase in body temp.).
• Increases the respiration rate (4/min. for every
  1 C increase in body temp.).
• Increased use of body proteins as an energy
  source (catabolism)
• With prolonged fever, there is increased
  breakdown of endogenous fat stores .(metabolic
  acidosis)
• Precipitates febrile convulsions

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• Some Features of Fever
• Relative bradycardia(rising of HR lt5 /min. for
  each 1C rise )
• Causes Typhoid,Brucellosis,Leptospirosis,and
  Factitious fever
• Relative tachycardia (rising of HR gt15/min. for
  each 1C rise )
• Causes Myocarditis, rheumatic fever
• Reversed diurnal pattern (AM Temp. gtPM Temp.)
• Causes Typhoid , disseminated TB
• Failure to have fever
• Cause Elderly,CRF,Corticosteroid

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components of fever

• 1-Onset of fever (warming chill phase )
• Sudden rise pneumonia,malaria,meningitis
  (associated with oral herpes simplex).
• Gradual rise typhoid fever (step-ladder) .

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• 2-Main (pattern-plateau phase)
• Continuous fever does not fluctuate more than
  1C during 24hrs, but at no time touches the
  normal.e.g.pneumonia, typhoid fever, urinary
  tract infection, brucellosis
• Remitent daily fluctuations exceed 2C but at
  no time touches the normal.
• It is associated with viral upper respiratory
  tract, legionella, and mycoplasma infections
• Intermittent fever reaches normal level
• Quotidian wn. Paroxysms of fever occur
  daily(P.Falciparum)
• Tertian wn. Paroxysms of fever on alternate
  days(P.Vivax ,Ovale)
• Quartan every 72 hrs (P.Malaiae)

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• 3-End of fever
• Crisis (sudden reduction )associated with
  sweating
• e.g. pneumonia
• Lysis ( gradual reduction)
• e.g. Typhoid

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Approach to patient with fever

• 1- History taking
• 1)Onset (sudden vs. gradual)2) grade (High
  vs. low grade)
• Low grade temp.lt38.5 , not associated with
  rigor (but chills ) , relieved by antipyretics or
  sponging , not interfere with usual activity .
• High grade temp.gt38.5 , associated with rigor
  and sweating , not relieved by antipyretics or
  sponging , interfere with usual activity.
• 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 , malaria , pyelonephritis ,
  Pneumonia
• 2) abscess ,cholangitis , septic arthritis
• 3) lymphoma

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• 3)Duration of the fever
• 4)Fever pattern (Remittent fever, Intermittent,
  continuous fever)
• 5)Timing (through out the day, at night, day
  time)
• 6)Severityinterfere with sleep , interfere with
  usual activity
• 7)Relieving and aggravating factors
• 8)Treatment received or/and outcome

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• 9)Associated symptoms
• Complete review of systems a) Upper respiratory
  tract infection (sore throat, coryza)b) Lower
  respiratory tract infection (cough, chest pain,
  shortness of breath)c) GIT symptoms (diarrhea
  watery or mucous, abdominal pain,
  constipation)d) GUT (Pain on micturation,
  hesitancy, urgency)e) Skin lesion (rash,
  infection), night sweat.
• f) Musculoskeletal pain,
• Excessive sweating.
• Night sweats are characteristic of
  tuberculosis, brucellosis , endocarditis
  ,lymphoma

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• Drug and allergy History
• Drug fever is a disorder characterized by a
  febrile response coinciding temporally with the
  administration of a drug in the absence of
  underlying conditions that can be responsible for
  the fever. A key feature that differentiates drug
  fever from fever of other causes is that it
  disappears once the offending drug is
  discontinued. Drug fever tends to be a diagnosis
  of exclusion, often suspected in patients with
  otherwise unexplained fevers. causes
• antibiotics (penicillin) ,anticonvulsants(phe
  nytoin) , and some cardiac drugs
• Blood transfusion.
• Immunization and vaccinations .

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Personal and Social History

• Smoking history - amount, duration type
• Alcohol history - amount, duration type
• 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 (,avian flu ,
  toxoplasmosis, brucellosis, rabies.)
• Consumption of unpasteurized milk or milk
  products (tuberculosis, brucellosis and Q fever).

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• Sexual History- Unprotected exposure to sexual
  partner with STD, HIV,syphilis
• 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 History
• Travel to an area known to be endemic for certain
  disease
• Name of the area, duration of stay
• Onset of illness- (incubation period)
• If the patient has been in an endemic area
• The most common diagnoses
• Malaria, Typhoid fever, Viral hepatitis .

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2-Complete Physical Examination
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FEVER AND SKIN RASH (EXANTHEM)

• DAY1 Chicken pox
• DAY2 Scarlet fever
• DAY3 Rubella
• DAY4 Measles
• DAY5 Typhus
• DAY6 Typhoid
• (rose spot)

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FEVER AND MUCUS MEMBRANE RASH (ENANTHEM)

• Koplik's spots in measles
• Forchheimer spots in rubella

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• FEVER AND LYMPHADENOPATHY
• Brucellosis
•  Cytomegalovirus
• Epstein-Barr virus
• Human immunodeficiency virus(AIDS)
• Lymphoma
• Syphilis (secondary) 
• Toxoplasmosis

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•     Fever and Jaundice
• Cholangitis ,  Hepatic abscesses,  Malaria
  ,  Viral hepatitis  , Yellow fever
• Fever and pulmonary involvement
• Influenza
• Pneumonia
• Severe acute respiratory syndrome (SARS)

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3-Full Investigations

• Lab.
• A-Bld.film
• 1-DÖhle bodeis , toxic granulation , band form
  bacterial inf.
• 2-neutropenia viral inf.,SLE ,typhoid ,
  brucellosis , and b.marrow infiltration(lymphoma,T
  B,leukemia
• 3-lymphocytosis typhoid , brucellosis , TB
  ,viral inf.
• 4-Atypical lymphocyte viral inf.
• 5-monocytosis typhoid , brucellosis , TB
  ,lymphoma
• 6-eosinophilia drug reactions ,hodgkin s
  dis.,adrenal insufficiency
• 7-thich and thin bld film for malaria

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• B-Biochemical
• urea and electrolytes, liver function tests
  (LFTs), blood glucose , GUE, GSE,
• Sputum for routine microscopy and culture, and
  microscopy and culture for mycobacteria ,
• Culture of blood , urine .
• inflammatory markers, erythrocyte sedimentation
  rate (ESR) and C-reactive protein (CRP)
• autoantibodies, including antinuclear antibodies
  (ANA)
• C- Radiology
• CXR, Abdominal US , Echocardiogram , CT/MRI of
  thorax and abdomen

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Treatment of fever

• Fever must be reduced in some groups of patients
  
• 1- Patients with preexisting cardiac disease
  (IHD)
• 2- Patients with cerebrovascular disease
• 3- patient with preexisting pulmonary disease
• 4-Children with a history of seizure
• 5-Pregnants
• 6-Elderly.
• 7-Temp.gt39
• Oral aspirin and NSAIDS (paracetamol, ibuprufen
  ) effectively reduces fever.
• Also reduce systemic symptoms of headache,
  myalgias, arthralgias due to reduction of PGE2
  production.
• It is better to avoid aspirin in children to
  prevent Reye syndrome.

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HYPERPYREXIA
A fever of gt41.5C (gt106.7F) is called
hyperpyrexia. This extraordinarily high fever can
develop in patients with severe infections but
most commonly occurs in patients with central
nervous system (CNS) hemorrhages.
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HYPERTHERMIA

• Hyperthermia is characterized by an unchanged
  (normothermic) setting of the thermoregulatory
  center in conjunction with an uncontrolled
  increase in body temperature that exceeds the
  bodys ability to lose heat.
• Causes of Hyperthermia Syndromes
• HEAT STROKE
• Exercise in higher-than-normal heat and/or
  humidity
• DRUG-INDUCED HYPERTHERMIA
• Anticholinergics, including antihistamines
  antiparkinsonian drugs diuretics antipsychotics
  , anesthetics
• ENDOCRINOPATHY
• Thyrotoxicosis, pheochromocytoma

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Hyperthermia Vs Fever

• 1-Daily temperature swings do not occur in
  patients with hyperthermia
• 2-hyperthermia can be rapidly fatal
• 3-characteristically does not respond to
  antipyretics
• 4-Hyperthermia is characterized by an unchanged
  setting of the thermoregulatory center
• 5-Hyperthermia is often diagnosed on the basis of
  the events immediately preceding the elevation of
  core temperaturee.g ., heat exposure or
  treatment with drugs
• that interfere with thermoregulation.
• 6-In patients with heat stroke syndromes and in
  those taking drugs that block sweating , the skin
  is hot but dry.

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Treating Hyperthermia

• Physical cooling with sponging, fans, cooling
  blankets, and even ice baths should be initiated
  immediately in conjunction with the
  administration of intravenous fluids and
  appropriate pharmacologic agents ,if insufficient
  cooling is achieved by external means , internal
  cooling can be achieved by gastric or peritoneal
  lavage with iced saline. .
• In extreme circumstances, hemodialysis or even
  cardiopulmonary bypass with cooling of blood be
  performed.

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Pyrexia of unknown origin (PUO) Fever of
Unknown origin (FUO)

• PUO (FUO) is defined as a temperature
  persistently above 38.0 C for more than 3 weeks,
  without diagnosis despite initial investigation
  during 3 days of inpatient care or after 3
  outpatient visits or more . (rule of 3 )

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• Three major Infectous causes
• Abscess .. especially occult ..
• Intracellular organisms. (salmonella
  mycobacterium, brucella)
• Intravascular Endocarditis

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• Tuberculosis
• The single most common infection in most PUO
  series
• Tuberculosis (TB) is an infection, primarily in
  the lungs (a pneumonia), caused by bacteria
  called
• tuberculosis. Mycobacterium
• It is spread usually from person to person by
  breathing infected air during close contact.
• TB can become active and cause infection in the
  lungs or other parts of the body (Caseating
  Granuloma).
• The most common symptoms and signs of TB are
  fatigue, fever, weight loss, coughing, and night
  sweats.

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• The diagnosis of TB involves
• PPD (Skin Tuberculin Test),
• sputum analysis (smear for AFB and culture),
• Chest-X-ray (Apical cavitation , pleural effusion
  )
• PCR(polemerase chain reaction) tests to detect
  the genetic material of the causative bacteria.
• Diagnosis sometimes requires Biopsy of Lymph
  nodes , Bone marrow, Liver .
• Active TB is treated W multiple AntiTB Drugs for
  6 months

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• Abscess
• An abscess is a collection of pus (neutrophils)
  that has accumulated within a tissue because of
  an inflammatory process in response to an
  infectious process (usually caused by bacteria)
• Usually located in abdomen or pelvis.
• Secondary to appendicitis or diverticulitis.
• Pyogenic liver abscess usually follow biliary
  tract dis./abd. Suppuration.
• Splenic abscess is usually secondary to
  hematogenous seeding.
• Perinephric or renal abscess is usually secondary
  to UTI.
• Intracranial abscess, lung abscess

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• Bacterial Endocarditis
• Endocarditis is an inflammation of the valves of
  the heart caused by the growth of bacteria on one
  of the heart valves, leading to a mass known as a
  vegetation.
• Symptoms can be nonspecific and include fever,
  shortness of breath, and weakness , and it
  carries a high complications and mortality rates
  .
• People with existing diseases of the heart valves
  are at an increased risk of developing
  endocarditis.
• Diagnosis of Endocarditis depend on Duke Criteria
  ( ve blood cultures and presence of vegetation
  on Echo )

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The most accurate method of detecting the valve
vegetations of endocarditis is with a procedure
called transesophageal echocardiography (TEE) but
transthoracic echocardiography (TTE) may benefit
. The treatment for endocarditis consists of
aggressive (multiple) antibiotics, generally
given intravenously, usually for 4 to 6 weeks.
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• Malignancy
• Cancer is the uncontrolled growth of abnormal
  cells anywhere in a body. The abnormal cells are
  termed cancer cells, malignant cells, or tumor
  cells. a mass of cancer cells develop
• Many cancers and the abnormal cells that compose
  the cancer tissue are further identified by the
  name of the tissue that the abnormal cells
  originated from (for example, breast cancer, lung
  cancer, colon cancer).
• Frequently, cancer cells can break away from this
  original mass of cells, travel through the blood
  and lymph systems, and lodge in other organs
  where they can again repeat the uncontrolled
  growth cycle.
• This process of cancer cells leaving an area and
  growing in another body area is termed metastatic
  spread or metastatic disease.

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• Malignant causes of fever
• Renal cell carcinoma
• Hepatocellular carcinoma
• Hepatic metastases from any primary
• Leukemia
• Lymphoma
• Fever is a well-recognized manifestation in
  Lymphoma .
• A Pel-Ebstein phenomenon is one type of
  Intermittent Fever
• noted in patients with Hodgkin's lymphoma in
  which the patient experiences fevers which
  cyclicly increase then decrease over an average
  period of one or two weeks.(2weeks fever then
  2weeks normal)

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• Family History
• Search for possible infectious or hereditary
  disorders
• Tuberculosis
• FMF
• Periodic Fever (Familial Mediterranean fever-FMF)
• An inherited disorder featuring short recurring
  crises of severe abdominal pain and bouts of
  fever. Other symptoms include arthritis, chest
  pain from inflammation of the lung cavity, and
  skin rashes. Between attacks, the patient seems
  healthy.
• Amyloidosis (the abnormal deposition of a
  particular protein, called amyloid, in various
  tissues of the body) is a potentially serious
  complication
• Treatment W Colchicin

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for PUO Invasive Investigations

• 1-Aspiration of fluid for analysis (pleural ,
  ascitic, joint, CSF)
• 2- Lymph node Biopsy
• When there is LAP( lymphadenopathy) to diagnose
  Lymphoma , TB , Malignancy
• 3-bone marrow biopsy
• A biopsy is most useful in revealing
  haematological malignancy, and tuberculosis. It
  may also lead to a diagnosis of brucellosis,
  enteric fever or visceral leishmaniasis.

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• 4-Liver biopsy
• The procedure may be required to diagnose
  tuberculosis,
• It is unlikely to be helpful in patients with
  normal LFTs and normal liver parenchyma on
  imaging.
• 5-Temporal artery biopsy
• Temporal artery biopsy should be considered in
  patients over the age of 50 to diagnose giant
  cell arteritis

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• Questions??

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Thank you