INTRODUCTION• NORMAL BODY TEMPERATURE -36.6 to 37.2 °C• Regulated by thermosensitive neurons in the Preoptic and anterior hypothalamus• Thermoregulatory responses: Redirecting blood to or from cutaneous vascular beds Increased or decreased sweating ECF regulation Behavioral responses• Circadian rhythm or diurnal variation
• Skin temperature is 0.4 °C(0.7° F) lower than oral temperature• Rectal or eardrum temperature is 0.4 °C (0.7° F) higher than oral temperature• Oral temperature is the reference and fever is diagnosed when it exceeds (37.8° C).
DEFINITION OF FEVER• Fever is a controlled increase in body temperature above the normal hypothalamic set point• Rectal temperature >38 °C• Hyperpyrexia is > 40° C
Pel-Ebstien fever- lasting for 3-10 days followed by an afebrile period of 3-10 days,e.g.hodgkins and other lymphomas. Saddle back fever- fever lasts for 2-3 days followed by a remission for 2-3 days and reappearance after 2-3 days,e.g.Dengue fever. Biphasic fever- single illness two distinct periods of fever over one or more weeks(camel back pattern),e.g. poliomyeletis,leptospirosis,dengue fever, yellow fever,colarado tick fever,spirillary bat fever,african haemorrhagic fever.
Classification of feverFever with focus.Fever without focus.
FEVER WITHOUT A FOCUS
FEVER WITHOUT A FOCUS• Fever without a focus refers to a rectal temperature of 38 degree centigrade or higher as the sole presenting feature.• It has two subcategories :- -fever without localizing signs -fever of unknown origin.
Fever of unknown origin Best reserved for children with a fever ; lasted for 3 or more weeks with temperature >38 C for which cause could not be identified after 3 wks of evaluation as an outpatient or after 1wk of evaluation in hospital . Fever without localizing signs Patients with fever not meeting above criteria , and specifically those admitted to hospital with neither an apparent site of infection nor a noninfectious diagnosis .
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 or infants to 1 month of age .II. Infants > 1 month to 3 months of age .III. children > 3 months to 3 yrs of age .
Febrile patients at increased risk for serious bacterial infectionsRISK GROUP DIAGNOSTIC CONSIDERATIONSImmunocompetentpatientsNeonates(<28 days) Sepsis and meningitis- group B streptococcus, E. coli, listeria, HSV, enterovirusesInfants 1-3 months Serious bacterial disease 10-15% ,bacteremia 5% UTIInfants & children 3-36 months Occult bacteremia 0.5% of children immunized with Hib pneumococcal conjugate vaccine ,UTI
IMMUNOCOMPROMISEDPATIENTSSickle cell disease Sepsis, pneumonia, meningitis caused by S. pneumoniae, osteomyelitis caused by Salmonella and Staphylococcus aureusAgammaglobulinemia Bacteremia ,sinopulmonary infectionsAIDS S.pneumoniae, H.influenza ,SalmonellaCongenital heart disease Infective endocarditis ,Brain abscess with right to left shuntingMalignancy Bacteremia with gram –ve enteric bacteria , S.aureus & coagulase –ve staphylococci , fungemia with candida & aspergillus
Fever without localizing signs in NEONATES• Neonates having fever without focus display limited signs of infection making difficult to clinically distinguish between a serious bacterial infection & self limited viral illness .• SERIOUS BACTERIAL INFECTION-7% neonates , includes sepsis,meningitis,UTI,enteritis,osteomyelitis ,suppurative osteoarthritis .• Organisms responsible - group B streptococcus & Listeria(Late onset neonatal sepsis & meningitis) , community acquired pathogens (Salmonella, E.coli, Haemophillus influenza type B, Streptococcus pneumoniae, staphylococcus aureus )
• Viral causeso Viral pathogens can be identified in 40- 60%febrile infants .o Perinatally acquired HSV infectiono Respiratory syncytial virus, Influenza A virus (common during winter)o Enterovirus infection (common during summer)
Guidelines for investigations• If fever is recorded at home by reliable parent , then treat as febrile neonate .• In false cases excess covering should be removed & temp. retaken in 15-30min .• Blood ,urine ,CSF should be cultured .• CSF study includes cell counts, glucose, protein levels, gram stain & culture.• HSV & Enteroviruse polymerase chain reaction .• Stool culture ,chest radiograph .
Treatment For ill appearing febrile infants ceftriaxone (50mg/kg every 24 hours – normal CSF finding, 80mg/kg every 24 hours – CSF pleocytosis) or cefotaxime(50 mg/kg every 6 hr) ,plus Ampicillin(50mg/kg every 6 hr) to cover L.monocytogenes & Enterococcus .Meningitis – vancomycin (15 mg/kg every 6 hr) for penicillin resistant S. pneumoniae .Acyclovir for HSV infection . For infants with fever who appear generally well & have a total WBC count of 5000-15000 cells/ml & normal urinalysis results are unlikely to have serious bacterial infection .
1 Month to 3 Months:• Majority of the cases are of viral origin• Viral diseases have a distinct seasonal pattern Eg - 1.Respiratory syncytial virus and influenza A in winter season 2.Entero virus in summer• Although viral infection are common one should suspect serious bacterial infections.• Common bacteria : Group B streptococci Salmonella enteritis Streptococcus pneumoniae H influenza etc…
• Common conditions: > Pyelonephritis >Otitis media >Pneumonia >Skin and soft tissue infections• These infants require prompt hospitalization and immediate antimicrobial therapy• Based on culture of blood ,urine ,CSF the infants are classified in to low and high risk group
Low risk criteria in 1-3months old withfever BOSTON ROCHESTER CRITERIA: CRITERIA: CBC: <20,000 CBC : 5000- Infants are at low WBC /mm3 15000 risk if they appear WBC/mm3 well , have normal physical examination and laboratory test as Urine : -ve Urine :<10 follows leucocyte WBC/HPF at esterase 40x CSF: leucocyte Stool :<5 WBC count /HPF if diarrhea <10x106/litre
PHILADELPHIA PITTSBURGH PROTOCOL: GUIDELINES: CBC :<15000 CBC:5000-15000 WBC/mm3 WBC/mm3 Urine :<10 WBC/HPF, Urine :9 WBC/mm3,no no bacteria on Gram bacteria on gram stain stain CSF:5WBC/mm3,-ve gram CSF:<8 WBC /mm3,no stain ,if bloody tap then bacteria on Gram stain WBC :RBC </= 1:500 Chest radiograph :no infiltrate Chest radiograph: no infiltrate Stool : no RBC,few to no WBC Stool :5 WBC/HPF with diarrhea
Management : Low risk : High risk: • with out antibiotic under • Intensive parenteral close observation antimicrobial therapy • Empirical antibiotic therapy • Ampicillin plus either ceftriaxone / cefotaxime • If CSF shows abnormal findings vancomycin included against penicillin resistant S.Pneumoniae
3 Month to 36 Months of Age • 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 1 to 3 months of age • S.pneumoniae, N.meningitidis and Solmonella acount for the most of occult bacteremia. • Hib was important cause in young children in the pre immunization era.
• Risk actors indicating occult bacteremia 1.temperature >39° c 2.WBC count >15000/micro litre 3.elevated a.ANC b.CRP c.ESR• Occult bacteremia caused by S. pneumoniae, Hib is the common condition• It may resolve spontaneously without sequelae or can lead to localized infection like meningitis, pneumonia, cellulitis ,pericarditis etc..
MANAGEMENT: Immunization against Hib and S.pneumoniae with conjugate vaccine. Hospitalization and prompt antimicrobial therapy Based on the blood, urine ,CSF culture antibiotics are given.
Fever of Unknown Origin• Definition : It is a term best reserved for children with a fever documented by a health care provider & fever : has lasted for 3 or more weeks . with temperature > 38 degree C on most days . & for which cause could not be identified after 3 weeks of evaluation as an outpatient or after 1 week of evaluation in hospital .
Classification :• Fever of unknown origin is classified into following 4 categories :1. Classic FUO2. Health care associated FUO3. Immune defficient FUO4. HIV –related FUO
1. CLASSIC FUO Definition: fever of > 38 degree C , lasted for > 3 wks , & cause could not be identified after 3 wks of evaluation as outpatient or after 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 : Fundi ,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 .
2. 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 complication , 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 .
3. 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 disorder .
Examination emphasis : Skin folds , IV sites , lungs. Investgation emphasis : Chest radiograph , bacterial cultures , Management : Antimicrobial treatment . Time course of disease : Lasts for days .
4. 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) . Examination emphasis : Mouth , sinuses , skin , lymph nodes , eyes .
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 .
ETIOLOGY OF PUO
CAUSES OF PUO • Infectious causes • Non infectious causes
APPROACH TO PUO HISTORY PHYSICAL EXAMINATION LABORATORY INESTIGATIONS
GENERAL INFO• History should be taken from the child or reliable informant.• Significance of 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 ,pelvic infections , .• Males-allergic fever(hay fever), typhoid ,, tuberculosis. malaria.ADDRESS• ENDEMIC- e.g,mandya 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.• They give clue towards system involved eg:- fever , cough, rhinitis , sore throat -RTI fever, vomiting ,diarrhoea ,pain abdomen - GIT infection fever ,dysuria ,loin pain -UTI fever ,drowsiness ,convulsions - meningitis, encephalitis
HISTORY OF• travel?-endemic areas?,how long?any precaution?. Epidemics in resident area ?• Pets,pica-toxoplasmosis,visceral larva migrans.• Contact with animals? –leptospirosis,brucellosis.• Tick bites-relapsing fever, Q fever.• Blood transfusion-malaria,hepatitis-B virus.• Migrating joint pains-Rheumatic fever• Loss of weight-malignancies!• History of recurrent fever , oral thrush(immunocompromised)• Joint pain,rash,photosensitivity(autoimmune)
•Past history-•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 species infection• loss of appetite- malignancies ,TB, appendicitis.
• Breast feeding- Children who are not breast fed are susceptible for infection• Immunization history – vaccination induced fever.e.g,DPT,measles• Treatment history-penicillin , antihistamines.(drug induced fever)
PHYSICAL EXAMINATION A careful and complete physical examination is essential to find clue to the underlying diagnosis Repetitive examination ,preferable daily examination is important to pick up subtle or new signs
Look for the child’s general appearance , whether,sick and toxic or looks well in spite of fever. including sweating during feverContinues absence of sweat , in the presence of elevated or changing temperature because suggest Dehydration due to vomiting, diarrhea, central or nephrogenic diabetic insipidus. It also suggests exposure of child to atropine
Look for temperature pattern during hospitalization Pulse rate –relative bradycardia –typhoid, meningitis dengue,weil’s disease. Skin – look for – rashes , petechiae, splinter hemorrhages, subctaneous nodules – vasculitis , endocarditis. Built and nourishment –by anthropometric measurment .
Head to toe examinationOphthalmic examination Anemia- malaria, kala azar , ALL , SABE Icterus – infectious hepatitis, malaria, weil’s disease , liver abscess, infectious mononucleosis Proptosis –orbital tumor , thyrotoxicosis, orbital infection , wegener granulomatosis , metastasis(neuroblastoma) Petechial conjunctival hemorrhage , roth’s spots – infective endocarditis Uveitis –sarcoidosis, SLE, kawasaki disease , vasculitis
• In hypothalamic dysfunction – failure of pupillary constriction –due to absence of sphinctr constrictor muscle• Choroid tubercles in fundus – tuberculosis
• Tenderness to tapping over sinus – sinusitis• Oral cavity• Hyperemia of pharynx – with or with out exudate – infectious mononucleosis , CMV infection ,• Tender tooth – periapical abscess• Ulceration – disseminated histoplasmosis• Recurrent oral candidiasis – disorder of immune system• Smooth tongue with absence of fungiform papillae – familial dysautonomia
• Fever blister – seen in - pneumococcal , streptococcal ,malaria, rickettsial infection• Neck• Enlargment or tenderness of thyroid gland – thyroiditis• Heart- Murmur – infective endocarditis• Abdomen –splenomegaly – infective endocarditis, malaria, kala azar , CML,• abdominal tenderness-pelvic abccess.• Loin tenderness-pyelonephritis.• Hepatomegaly- liver abscess , primary or metastatic malignancy
• Muscle and bone should be palpated• Point tenderness- occult osteomyelitis or bone marrow invasion from neoplasm• Painful and swollen joints – arthritis – rheumatic fever , SABE , leukemia,• Tenderness over trapezius muscle –clue to - subdiaphragmatic abscess• Generalised muscle tenderness – arboviral infection, dermatomyositis , trichinosis ,
CASE BY CASE BASIS CASE 1 LABORATORY INVESTIGATIONS CASE CASE 2 3
HOW TO GO ABOUT LABORATORYINVESTIGATIONS DETAILED HISTORY LABORATORY PRESENTATIONINVESTIGATIONS OF ILLNESS CLINICAL EXAMINATION
HOW TO GO ABOUT LABORATORYINVESTIGATIONS HISTORY SUDDEN IN CHRONIC ONSET PRESENTATION OUT PATIENT BASISHOSPITALIZATION INVESTIGATIONS REGULAR CHECK UP
WHAT IF HISTORY & PHYSICALEXAMINATIONS ARE NOT SIGNIFICANT…!!! NO CLUES CONTINUED SURVEILLANCE RE-EVALUATION NEW CLINICAL FINDINGS
LIST OF INVESTIGATIONS WHICH HELPUS ARRIVE AT THE DIAGNOSIS• Blood cell count• Urine analysis• Blood smear• Erythrocyte sedimentation rate• Blood and urine culture• Radiological diagnosis• Bone marrow examination• Serologic tests• Radionuclide scans• CT and MRI
BLOOD CELL COUNTDifferential WBC count is a must…. ABSOLUTE <5000/MICRO LITER INDOLENT BACTERIALNEUTROPHIL COUNT INFECTION PMN >10000/MICRO LITER SEVERE BACTERIAL INFECTIONS NON >500/MICROLITRE SEGMENTED PMN
ERYTHROCYTE SEDIMENTATION RATE FURTHER >30mm/hr INFLAMATION EVALUATION ESR TUBERCULOSIS >100mm/hr MALIGNANCY AUTO IMMUNE
BLOOD CULTURESNormally 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 EXAMINATIONS RADIOLOGICAL EXAMINATION PHYSICAL HISTORY FINDINGS SINUSES & CHEST GI TRACT MASTOID
BONE MARROW EXAMINATION BONE MARROW EXAMINATION BIOPSY ASPIRATIONMETASTATIC LEUKEMIANEOPLASM CULTURE FUNGI FUNGAL &PARASITIC INFECTIONS BACTERIAL
SEROLOGIC TESTS• SPECIFICITY & SENSITIVITY are the two important aspects which should be checked before ordering serologic examinations. INFECTIVE CMV MONONUCLEOSIS SEROLOGY BRUCELLOSIS TOXOPLASMOSIS
RADIONUCLEIDE SCANS • These are mainly helpful in detecting abdominal abscess & osteomyelitis, especially in multifocal disease. • GALLIUM CITRATE- mainly localizes in inflammatory tissues. • IODINATED IgG- helpful in detecting localized pyogenic abscess.
ECHOCARDIOGRAPHY&ULTRASONOGRAPHY• ECHOCARDIOGRAMS detect vegetations on valve leaflets in INFECTIVE ENDOCARDITIS.• ULTRASONOGRAPHY detects intra- abdominal abscesses of LIVER & SPLEEN.
CT SCAN AND MRI• These permit detection of neoplasms with out the use of surgical exploration.• CT scan guided aspiration & biopsy has reduced the need for surgical exploration.• MRI is mainly useful in detecting osteomyelitis .
SUMMARY ETIOLOGY SHOULD BE KEPT IN MIND COMPLETE HISTORY IS TAKENCOMPLETE PHYSICAL EXAMINATION DONE REQUIRED INVESTIGATIONS DONE WE ARRIVE AT THE DIAGNOSIS
REFERENCES.Nelson text book of paediatrics 19th edition( pg-839-846)IAP text book of paediatrics(pg-295-302)O.P Ghai textbook of paediatrics(pg)Meharban singh textbook of paediatrics