Fever of Unknown Origin in Adults - Clinical Infectious Diseases
FEVER OF UNKNOWN ORIGIN-Infectious disease - PIDSPpidsphil.org/pdf/2009/09 Lec - FEVER OF...
Transcript of FEVER OF UNKNOWN ORIGIN-Infectious disease - PIDSPpidsphil.org/pdf/2009/09 Lec - FEVER OF...
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FEVER OF FEVER OF UNKNOWN UNKNOWN ORIGINORIGIN
Pinpointing the Pinpointing the CulpritCulprit
Fatima Ignacio Gimenez, MDFatima Ignacio Gimenez, MD
Pediatric Infectious DiseasePediatric Infectious Disease
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DefinitionDefinition
Presence of fever for 8 or more days in a child for whom a careful and thorough history and preliminary laboratory data fail to reveal a probable cause of fever
(Pediatric Feigin, et al. Textbook of Infectious Disease.5th edition)
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FUO in pediatrics is more likely an unusual presentation of a common disorder than by a common manifestation of a rare disorder
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Causes of FUOCauses of FUO
• Infectious diseases
• Connective tissue diseases
• Neoplasms
• Undetermined
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Prolonged Fever in a Pediatric Prolonged Fever in a Pediatric Setting(Firmalo et al.Phil J Ped,1983)Setting(Firmalo et al.Phil J Ped,1983)
• Childrens Medical Center
• January1,1977 to December 31,1981
• 256 cases
• 90% of infectious origin
• Most common were Typhoid,Primary Tuberculosis,Urinary tract infection
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Outcome of Prolonged Fever in Filipino Outcome of Prolonged Fever in Filipino Children: A Review of Thirty Four Children: A Review of Thirty Four Cases,(Cosca.Phil J of Ped ,1985 )Cases,(Cosca.Phil J of Ped ,1985 )
• UERMMC
• 1977-1982
• Infectious ( 50 %)
• Malignancy (26 % )
• Collagen Disease ( 6 % )
• Most common were Typhoid, Malaria, and Extrapulmonary tuberculosis
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FUO at the UST ( Dy,et al.Phil. J of FUO at the UST ( Dy,et al.Phil. J of Micro and Inf Diseases,1992)Micro and Inf Diseases,1992)
• UERMMC
• 1977-1982
• Infectious ( 50 %)
• Malignancy (26 % )
• Collagen Disease ( 6 % )
• Most common were Typhoid, Malaria, and Extrapulmonary tuberculosis
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FUO in Pediatric Patients: a 13 Year FUO in Pediatric Patients: a 13 Year Review at PCMC ( M.Velarde,J De Review at PCMC ( M.Velarde,J De Castro,RB Soriano,Phil J Ped 1995)Castro,RB Soriano,Phil J Ped 1995)
• 59 pediatric patients
• Age range 9 months – 18 years
• October 1,1980- October 31,1993
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Diagnostic ApproachDiagnostic Approach
Hospitalize
Advantages
Observe
Repeat history and physical examination
Analyze available data
Follow-up every potential lead
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First and Most Important First and Most Important StepStep
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A COMPLETE ,DETAILED HISTORY AND PHYSICAL EXAMINATION
A COMPLETE ,DETAILED HISTORY AND PHYSICAL EXAMINATION
A COMPLETE ,DETAILED HISTORY AND PHYSICAL EXAMINATION
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HISTORYHISTORY
• Contact with infected or otherwise ill person
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HistoryHistory
• History of travel (extend back to birth)
• Contact with persons who have visited distant countries
Possibility that rocks,soils,artifactsfrom geographically distant regions have been brought to the home
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HistoryHistory
• Prophylactic immunizations
• Malarial prophylaxis
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HistoryHistory
• If precautions were taken against ingestion of contaminated food or water
• Eating of game meat,raw meat or shellfish
• History of pica
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HistoryHistory
• Medications , topical agents.non-prescription items
• History of surgical procedure
• Genetic background
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HistoryHistory
Fever
Intermittent- pyogenic infection, tuberculosis,lymphoma, JRA
Relapsing fever- malaria,rat-bite fever,Borrelia infection,lymphoma
Recurrent episodes > 1 year duration-suggestive of metabolic defects,CNSabnormalities of temperature control,immunodeficient states
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Physical ExaminationPhysical Examination
• Lymphadenopathy and pallor were common in infections
• Splenomegaly were associated more with infections and neoplasms
( Dy, et al. Phil J of Micro and Inf Dis.,1992 )
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Physical ExaminationPhysical Examination
C - Careful
E - Extensive
R - Repeated
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Laboratory EvaluationLaboratory Evaluation
• Extent dependent on age,duration of fever,history and physical examination
• Directed towards most likely diagnostic possibility
• Tempo adjusted to severity of illness
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Laboratory EvaluationLaboratory Evaluation
Complete Blood Count
Total and differential WBC
• Leukopenia
Viral
EBV,hepatitis A and B,RSV, rubella
Bacterial
Salmonella,Staphylococcal,Mycobacterial
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• Neutropenia
(<1500/mm3 ) most often associated with viral infections
• LeukocytosisBacteria,virus,fungi,protozoa,spirochetes
(Walters.et.al. Pediatric Clinics of NA, June 1996 )
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Band Count
• Band count as a single parameter is of limited diagnostic value
• ANC is more sensitive than band count in predicting acute bacterial infection
• Morphologic changes in neutrophilsespecially toxic granulation were helpful in predicting bacterial infection
( Al-Gwaiz. et.al.Med Princ Pract 2007:16:344-347 )
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Peripheral Blood Cell Morphology
• Provide direct visualization of certain microorganisms
• Detect characteristic footprints left by various infections on morphology of blood cells,yielding diagnostic clues
• (ex Dohle bodies,haemophagocytosis)
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Laboratory EvaluationLaboratory Evaluation
Peripheral Blood Cell Morphology
• Disclose certain infection predisposing conditions
• Reveal infection-related hematologic and systemic complications
( Potasman.et.al.Postgrad Med J 2008;84;586-589)
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Laboratory EvaluationLaboratory Evaluation
ESR
• No specific diagnostic value
• General marker of inflammation
• Help determine need for further evaluation
• Monitor progress of disease
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Laboratory EvaluationLaboratory Evaluation
• ESR and A/G ratio were helpful screening tests in 75 % of patients with serious illness (collagen and malignancy)
• Increased sedimentation rates or reversal of A/G ratio
( Pizzo,et al.,Pediatrics,1975;55 ( 4);468)
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Laboratory EvaluationLaboratory EvaluationBlood cultures
• Aerobic and anaerobic
• Media appropriate ( isolation of Francisella,Leptospira,Spirillum )
• Appropriate volumes in children
1 to 2 ml in neonates
2-3 ml in infants
3-5 ml in children
10-20 ml in adolescents
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Laboratory EvaluationLaboratory Evaluation
• Single sampling may be sufficient
• Multiple samples may be appropriate in certain circumstances (suspected endocarditis, 2-3 samples are desirable to obtain a sensitivity of 96% especially if patient received antibiotics )
• Indwelling intravascular devices - two sets of cultures from different sites are helpful
( Long et. al., Pediatric Infectious Disease. Third edition )
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Laboratory EvaluationLaboratory Evaluation
Blood cultures were most useful when done serially and correlated clinically especially in conditions as septicemia,enteric fever and endocarditis
( Dy, et al. Phil J of Micro and Inf Dis.,1992 )
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Urine analysis and Urine culture
• Failure to perform and investigate pyuria were the most common laboratory errors
( Mclung,Amer J.Dis Child, 1972, Vol 124 )
• Radiographic study of urinary tract - only when indicated
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Diagnostic ImagingDiagnostic Imaging
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Laboratory EvaluationLaboratory Evaluation
Intradermal tuberculin skin test
• Negative tuberculin test result still does not rule out tuberculosis
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Laboratory EvaluationLaboratory Evaluation
Malarial Smear
• Thin and thick smears diagnostic
• Of little diagnostic value, history of exposure and physical examination necessitated therapeutic trial
( Dy, et al. Phil J of Micro and Inf Dis.,1992 )
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Laboratory EvaluationLaboratory Evaluation
Serum tests
• Human immunodeficiency virus
• Salmonellosis
• Brucellosis
• Tularemia
• EBV
• Cytomegalic Inclusion virus
• Other viral infections ( Hepatitis antigens)
• Toxoplasmosis
• Fungal infections
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Laboratory EvaluationLaboratory Evaluation
Bone Marrow
• Recommended as an important tool for detection of occult infection and malignancy
• In immunocompetent children-occasionally useful for diagnosis of selected infectious diseases especially brucellosis and typhoid fever
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• 383 pediatric patients who underwent 414 marrow examinations
• Concomitant blood and urine cultures
• 15 (3.6 % ) of 414
• Isolates :
Salmonella
Mycobacterium avium intracellulare
Histoplasma capsulatum
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Yield of marrow microbial culture in immunocompetent host with prolonged fever was very low( 1.9%) but a somewhat better yield was seen in immunocompromised hosts (8.7 %) especially in patients with AIDS
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• Helpful in establishing or supporting the diagnosis of opportunistic infection in the febrile immunocompromised host
• Not warranted in a child with prolonged fever with no suggestions of malignancy or immunodeficiency to detect occult infection
(Hayani et.al. J of Ped, June 1990 )
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Laboratory EvaluationLaboratory Evaluation
Biopsy
• If with evidence of organ involvement
• Most definitive approach to investigation of neoplastic cause in FU0
• Helpful in diagnosis of tuberculosis
( Dy, et al. Phil J of Micro and Inf Dis.,1992 )
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Other tests
• Hepatic enzymes
• Serum chemistries
• Electrolytes
• BUN, creatinine
• ANA > 5 years of age
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Laboratory EvaluationLaboratory Evaluation
• Echocardiography,electroencephalography,stool culture, examination for ova and parasites generally should be performed in selected cases
• CT, gallium scan, ,radioisotope scan
• Ultrasonography
• CSF examination
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GuidelinesGuidelines
• Antibiotics or other medications should not be administered empirically as a diagnostic measure
• Empirical trials of broad spectrum antibiotics generally do more to obscure than illuminate and may mask or delay diagnosis of infection such as meningitis,parameningealinfection,enocarditis or osteomyelitis
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GuidelinesGuidelines
Exceptions
• Use of non-steroidal agents in children with presumed JRA
• Use of antituberculosis drugs in critically ill children thought to have
disseminated TB (Pediatric Feigin, et al. Textbook of Infectious Disease.5th edition)
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GuidelinesGuidelines• Children with strongly suspected bacteremia and with deteriorating condition
• Children with a chronic illness( HIV ) ,severe malnutrition or haemoglobinopathy,which increases risk of serious bacterial infection
( Akpede.et.al. Paediatr Drugs 2001 ,3( 4):247-262 )