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