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FEVER OF UNKNOWN ORIGIN
- Dr.Apoorva.E
PG,DCMS
NORMAL BODY TEMPERATURE• The hypothalamus is the heat-regulating center of
the body
• The normal body temperature ranges from 37.0 degree C and 37.5 degree C
• Evening temperatures being 0.5 degree C higher than in the morning.
• Rectal temperature>oral temperature (0.4 degree C)
>axillary temperature (1 degree C)
• A rectal temperature with a glass- mercury or digital-electronic thermometer is considered the gold standard for taking temperatures
• Liebermeisters rule -The pulse rate rises about 15 beats/min for each degree centigrade rise of fever
FEVER
• Fever is a controlled increase in body temperature above the normal hypothalamic set point
• A rectal temperature of 38 degree C or more (100.4 degree F)
• A temperature of 40 degree C or more is termed as hyperpyrexia
PATHOGENESIS OF FEVER
PATTERNS OF FEVER
Intermittent fever - Fever that touches the baseline for a few hours during the day.
• Seen in malaria, acute pyelonephritis, local boils,furuncles,kala azar,sepsis
• Types of intermittent fever :
- Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium falciparum
- Tertian fever,with a 48 hour periodicity,typicalof Plasmodium vivax or Plasmodium ovale
-Quartan fever,with a 72 hour periodicity,typicalof Plasmodium malariae
Remittent fever - Fever that fluctuates by more than 1.5 degree F but never touches the baseline in 24 hours
• Seen in infective endocarditis
Continuous fever - Fever that never touches the baseline in 24 hours and fluctuates by less than 1.5 degree F in a day.
• Seen in enteric fever,lobarpneumonia,brucellosis,typhus.
Pel-ebstein fever - Fever lasting for 3-10 days followed by an afebrile period of 3-10 days
• Seen in hodgkins lymphoma
CLASSIFICATION OF FEVER
Fever with focus Fever without focus
Fever without localizing signs
Fever of unknown origin
( refers to a rectal temperature of 38 degree C or higher as the sole presenting feature)
FEVER OF UNKNOWN ORIGIN
• Children with fever,documented by a health care provider,for which cause could not be identified even after 3 weeks of evaluation as an outpatient or after 1 week of evaluation in the hospital
CLASSIFICATION
• 4 categories :
1. Classic FUO
2. Health care associated FUO
3. Immune deficient FUO
4. HIV – related FUO
CLASSIC FUO
• Definition: fever of > 38 degree C ,lasted for > 3 wks, >2 visits or 1 wk in hospital
• Patient location : community , clinic or hospital
• Leading causes : cancer , infections , inflammatory conditions, undiagnosed , habitual hyperthermia
• History emphasis : H/O travel , contacts , animal & insect exposure , medications , immunization , family history , cardiac valve disorder
• Examination emphasis : oropharynx , temporal artery , abdomen , lymph nodes , spleen , joints , skin , nails , genitalia , lower limb deep veins .
• Investigation emphasis : Imaging , biopsies , erythrocyte sedimentation rate , skin test
• Management : Observation , outpatient temperature chart , investigations , avoidance of empirical drug treatment
• Time course of disease : For months
HEALTH CARE ASSOCIATED FUO• Definition : Fever of > 38 degree C ,lasted for > 1
week , not present or incubating on admission
• Patient location : Acute care hospital
• Leading causes : Hospital acquired infections , post- operative complications , drug fever
• History emphasis : Operation & procedures , devices used , anatomic considerations , drug treatment
• Examination emphasis : Wounds , drains , devices , sinuses , urine
• Investigation emphasis : Imaging , bacterial cultures & other microbiological investigations
• Management : Depends upon situation
• Time course of disease : Lasts for weeks .
IMMUNE DEFICIENT FUO
• Definition : Fever of > 38 degree C , lasted for > 1 wk & negative culture after 48 hrs
• Patient location : Hospital or clinic
• Leading causes : Majority are due to infections but cause has been documented in only 40-60%
• History emphasis : Stage of chemotherapy , drugs administered , underlying immunosuppressive disorders
• Examination emphasis : Skin folds , IV sites , lungs, perianal area
• Investigation emphasis : Chest radiograph , bacterial cultures
• Management : Antimicrobial treatment
• Time course of disease : Lasts for days .
HIV – RELATED FUO
• Definition : Fever of >38 degree C , >3 wks for outpatients , >1 wk for inpatients & HIV infection confirmed
• Patient location : Community , clinic or hospital
• Leading causes : HIV (primary infection) , typical & atypical mycobacteria , CMV , toxoplasmosis , cryptococcosis , lymphomas , immune reconstitution inflammatory syndrome (IRIS)
• History emphasis : drugs,exposures,riskfactors,travel,contacts,stage of hiv infection
• Examination emphasis : Mouth , sinuses , skin , lymph nodes , eyes , lungs,perianal area.
• Investigation emphasis : Blood & lymphocyte count , serologic tests , chest X-ray , stool examination, biopsies of lung , bone marrow & liver for cultures and cytologic tests , brain imaging
• Management : Antiviral & antimicrobial protocols , vaccines , revision of treatment regimen , good nutrition
• Time course of disease : Lasts for weeks to months
CAUSES OF PUO•Infectious causes • Non infectious causes
Infectious causes-> Bacterial –
salmonella,brucellosis,meningococcal,mycoplasmapneumonia,TB,actinomycosis
-> Sphirochaetal -B burgdorferi ,leptospirosis ,relapsing fever,syphillis
-> Parasitic-amoebiasis,giardiasis,toxoplasmosis,babesiosis,malaria
-> Fungal-blastomycosis,histoplasmosis,coccidiodomycosis
-> Chlamydial -lym venereum,psittacosis
-> Rickettsial -Q fever,tick borne typhus,rockymountain spotted fever
-> Viruses –CMV,HIV,hepatitis
-> Local septic infection -dental abscess,subphrenicabscess,sinusitis,tonsillitis,hepaticabscess,bronchiectasis,mastoiditis
-> Local infection without pus formation -UTI,ulcerative colitis ,diverticulitis,phlebitis,regionalenteritis
Non infectious causes-> Collagen vascular disorders -JRA ,SLE ,behcets
disease,juvenile dermatomyosis
-> Neoplastic -leukaemia ,lymphoma,neuroblastoma,wilmstumour
-> Metabolic - gout,porphyria
-> Endocrine - thyrotoxicosis ,addisons disease
-> HS reactions - serum sickness
-> Misc - liver cirrhosis ,familial mediterannean fever ,poisoning ,sarcoidosis ,whipples disease ,factitious fever
HISTORY
History should be taken from the child or reliable informant
• AGE
-> 1-5 yrs - common causes are RTI,UTI,diarrhoea and osteomyelitis
->5-10 yrs-measles,mumps,chicken pox,typhoid
->10yrs- TB, typhoid ,rheumatic fever
• GENDER -> Females-urinary tract infections,pelvicinfections
-> Males-allergic fever(hay fever), typhoid , tuberculosis,malaria
• ADDRESS -> endemic regions for malaria and japanese encephalitis,epidemics,out breaks in that area
• CHIEF COMPLAINTS -> History of fever and other symptoms should be taken in chronological order,give clue towards system involved
eg:-
fever,dysuria ,loin pain –UTI
fever ,drowsiness ,convulsions - meningitis, encephalitis
HOPI
• ONSET
• GRADE
• DURATION
fever
• PROGRESSION -> Viral fever peaks in 2 days and declines-> Bacterial fever worsens day by day without treatment-> Parasite fever like malaria shows cyclical cold,hot and
sweating stages.
• TYPE -> Continuous-Pneumonia ,uti-> Remittent-Viral, collagen vascular diseases-> Intermittent - Malaria , Brucellosis-> Step ladder fever-Typhoid.
• Associated with ->Chills and rigors- Malaria,brucellosis ,otitis mediaMyalgia- brucellosis,dengue,bartonellosisSweating-Meningitis , TB ,Bacteraemia ,Malaria
• History of travel to endemic areas,how long,anyprecautions.
• Epidemics in resident area • Pets - toxoplasmosis,visceral larva migrans• Contact with animals – leptospirosis,brucellosis• Tick bites-relapsing fever, Q fever• Blood transfusion - malaria,hepatitis-B • Migrating joint pains - Rheumatic fever• Loss of weight-malignancies• History of recurrent fever,oral thrush -
immunocompromised• Joint pains,rash,photosensitivity - autoimmune
• Past history - of surgeries(occult infection)
• Family history - similar complaints suggest infectious disease,genetic background-familial dysautonomia(recurrent hyperpyrexia)
• Personal history - diet -> unpasteurized milk(brucellosis,TB),raw egg (salmonella)
• Loss of appetite - malignancies ,TB
• Immunization history - vaccination induced fever. e.g,DPT,measles
• Treatment history - drug induced fever
PHYSICAL EXAMINATION
• Careful and complete examination
• Repetitive examination to pick up subtle or new signs
• Look for the child’s general appearance, built and nourishment,
for temperature pattern ,
pulse rate –relative bradycardia in typhoid, meningitis dengue,
Skin – look for rashes , petechiae, splinter hemorrhages, subctaneous nodules
Eye
-> Anemia- malaria, kala azar ,ALL , SABE
-> Icterus – infectious hepatitis, malaria, weil’sdisease,liver abscess
-> Proptosis – orbital tumor , thyrotoxicosis, orbital infection , wegener granulomatosis , metastases(neuroblastoma)
-> Roth’s spots – infective endocarditis
-> Uveitis – sarcoidosis, SLE, kawasakidisease,vasculitis
-> Chorioretinitis – CMV, toxoplasmosis , syphilis
Tenderness to tapping over sinus – sinusitis
Oral cavity - Hyperemia of pharynxTender tooth –> periapical abscessRecurrent oral candidiasis –> disorder of immune system
Neck - Enlargment or tenderness of thyroid gland –> thyroiditis
Heart- Murmur –> infective endocarditisAbdomen –Splenomegaly –> malaria, kala azar , CMLAbdominal tenderness -> pelvic abccessLoin tenderness -> pyelonephritisHepatomegaly- > liver abscess , primary or metastatic malignancy
Muscle and bone –
Point tenderness- occult osteomyelitis or bone marrow invasion from neoplasms
Painful and swollen joints – arthritis –> rheumatic fever
Rectal examination – pelvic abscess,adenitis
INVESTIGATIONS• On IP or OP basis,determined on a case by case basis,OP if chronic• CBC,DC• Urine analysis• Blood smear• ESR• Serologic tests• Tuberculin test• Blood and urine culture• Bone marrow examination( aspiration and biopsy)• Xray ,2D ECHO,USG,CT , MRI , Radionuclide scans
NO INDOLENT BACTERIAL INFECTION
SEVERE BACTERIAL INFECTION
BLOOD SMEAR -> WITH GIEMSA OR WRIGHT STAIN
MALARIA
TRYPANOSOMIASIS RELAPSING FEVER
BABESIOSIS
ESR >30 mm ->
inflammation -> further evaluation
ESR >100 mm -> TB/malignancy/autoimmune/ kawasaki disease
• BLOOD CULTURES –
- Normally aerobic culture is done as anaerobic culture gives low yield
- Repeated culture done in case of infective endocarditis and osteomyelitis
- Poly microbial infection suggests GI infection.
• RADIOLOGICAL EXAMINATION –of sinuses,mastoid,GIT,chest
• SEROLOGIC TESTS – widal test,ANA,RF, for inf mononucleosis,cmv,brucellosis,toxoplasmosis
• RADIONUCLEIDE SCANS - These are mainly helpful in detecting abdominal abscess & osteomyelitis and in multifocal disease.
• ECHOCARDIOGRAPHY - detects vegetations on valve leaflets in infective endocarditis
• ULTRASONOGRAPHY detects intra- abdominal abscesses of liver and spleen
• CT SCAN AND MRI - detection of neoplasms,CTscan guided aspiration and biopsy,MRI for detecting osteomyelitis
FEVER WITHOUT LOCALIZING SIGNS
• Fever of acute onset,with duration of <1 wk and without localizing signs is a common diagnostic dilemma in children < 36 months of age .
• Etiology and evaluation of this type depends upon age of the child
• 3 age groups are considered :
I. Neonates
II. Infants > 1 month to 3 months of age .
III. Children > 3 months to 3 yrs of age .
NEONATES
• Neonates having fever without focus show limited signs of infection -> difficult to clinically distinguish between a serious bacterial infection & self limited viral illness
• Every febrile neonate has to be hospitalized
• 7% risk of having serious bacterial infection (sepsis,meningitis,UTI,enteritis,osteomyelitis, pneumonia,septic arthritis)
• Organisms responsible - Group B streptococcus & Listeria(Late onset sepsis & meningitis) ,
Ecoli,HSV,Enterovirus
• Blood ,urine ,CSF should be cultured
• CSF study should include cell counts, glucose, protein levels,gram stain & culture
• HSV & Enterovirus polymerase chain reaction
• Stool culture,chest radiograph
• Combination antibiotics- ampicillin and cefotaxime is recommended, acyclovir if HSV is suspected.
1 MONTH TO 3 MONTHS
• Majority of the cases are of viral origin
• Respiratory syncytial virus and influenza A in winter season
• Entero virus in summer
• Also suspect serious bacterial infections
• Common bacteria : Group B streptococci,listeria,salmonellaenteritis,ecoli,pneumococus,meningococcus, hiB,staph aureus
• Common conditions : Pyelonephritis > Otitis media > Pneumonia > Skin and soft tissue infections
• Based on blood ,urine ,CSF cultures,these infants are classified in to low and high risk groups
•With out antibiotics under close observation • Empirical antibiotic therapy
• Ampicillin plus either ceftriaxone/ cefotaxime• If CSF shows abnormal findings, vancomycinincluded against penicillin resistant S.Pneumoniae
LOW RISK HIGH RISK
3 MONTHS TO 36 MONTHS
• 30% of these infants with fever have no localizing signs of infection
• Majority are viral but serious bacterial infection do occur
• Pathogens are same as in 1 to 3 months of age
• S.pneumoniae,meningococcus,salmonella,hiBaccount for most of occult bacteremia
• Risk factors indicating occult bacteremia1.temperature >39° c
2.WBC count >15000/micro litre
3.elevated ANC,band count
4.elevated CRP
5.elevated ESR
• It may resolve spontaneously without sequelaeor can lead to localized infections like meningitis, pneumonia etc
• Management :
Child 3-36 mo and temperature38-39 ° C
Reassurance that diagnosis is likely self-limiting viral infection, but advise return if fever persists,temperatures > 39 ° C andnew signs / symptoms
Child 3-36 mo and temperature> 39 ° C
-Hospitalization and prompt antimicrobial therapy based on the blood, urine ,CSF cultures
• Immunize against Hib and S.pneumoniae with conjugate vaccine
THANK YOU