Fever without a source pediatrics
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Fever is a common reason for pediatric visits. The hypothalamus regulates body temperature and fever occurs when its set point is elevated. Fever without a source is difficult to diagnose and can be caused by infections, inflammatory disorders, or malignancies. Evaluation involves history, exam, labs including blood cultures, and imaging if indicated. Lower risk children based on criteria like Rochester may be managed as outpatients without antibiotics. Higher risk children receive empiric antibiotics targeting common pathogens until diagnosis is made. Antipyretics and antivirals are also used for symptom relief in some cases.
![The vast majority of children who present acutely with
fever without source (or fever of unclear source) have
underlying infections, typically requiring urgent
evaluation and empirical treatment (especially in young
children). In contrast, fever of unknown origin is not well
defined in children. It has been historically used to
describe a subacute presentation of a single illness of at
least 2 weeks duration during which a fever >38.3°C
(100.9°F) is present for most days and the diagnosis is
unclear after 1 week of intense investigation. [1] The
most common causes are infections,
inflammatory/vasculitic disorders, and malignancies.
These children require a more deliberate, comprehensive,
and prolonged evaluation, and frequently do not need
urgent empirical therapy.](https://image.slidesharecdn.com/feverwithoutasourcepediatrics-151101130453-lva1-app6892/85/Fever-without-a-source-pediatrics-7-320.jpg)
Fever without a source pediatrics
- 2. Fever 20% of pediatric emergency dept visits 35% of ambulatory visits 10% percent of febrile children have fever without an apparent source of infection after history and physical examination.
- 3. Physiology Hypothalamus is the thermoregulatory center for the body Fever results when a shift in the hypothalamic set point causes a controlled elevation of body temperature above the normal range Normal set point for humans has a daily circadian rhythm ranging 36C-37.8C with peak occurring in the afternoon Current Opinion in Pediatrics 2009, 21:139–144
- 4. Fever production begins when an infectious agent, toxin, immune complex, or other inflammatory agent stimulates macrophages or endothelial cells to produce endogenous pyrogens, such as interlukin-1 and tumor necrosis factor Pyrogens hypothalamus PGE2 and AA metabolites raise thermostat set point (thermoregulatory neurons) Current Opinion in Pediatrics 2009, 21:139–144 Pathophysiology
- 5. Fever without a source (FWS) Children with fever lasting one week or less without adequate explanation after a careful history and physical examination. Definitions
- 6. Fever of 38.3 or greater of at least eight days duration, with no apparent diagnosis after initial outpatient or hospital evaluation that includes a careful history and physical exam and initial laboratory assessment. (This definition is useful for clinical purposes, but there is much variability in published studies of fever of unknown origin with required duration of fever ranging between 1 to 3 weeks.) Fever of unknown origin (FUO)
- 7. The vast majority of children who present acutely with fever without source (or fever of unclear source) have underlying infections, typically requiring urgent evaluation and empirical treatment (especially in young children). In contrast, fever of unknown origin is not well defined in children. It has been historically used to describe a subacute presentation of a single illness of at least 2 weeks duration during which a fever >38.3°C (100.9°F) is present for most days and the diagnosis is unclear after 1 week of intense investigation. [1] The most common causes are infections, inflammatory/vasculitic disorders, and malignancies. These children require a more deliberate, comprehensive, and prolonged evaluation, and frequently do not need urgent empirical therapy.
- 8. Occult bacteremia is defined as the presence of bacteria in the bloodstream of a febrile child who has no apparent focus of infection and clinically does not appear to be ill. Some experts include in this definition children who have ottitis media at their initial presentation and are subsequently found to have positive blood cultures.
- 9. Etiology of occult bacteremia S. pneumoniae – 85% H. influenzae type b – 10% N. meningitidis – 3% Salmonella – 2%
- 10. Differential Diagnosis of Fever Without Focus Common 0-3 months 3-36 months Viral HSV + Enterovirus, parainflueza, adenovirus, RSV, CMV, roseola, PV, influenza Enterovirus, parainflueza, adenovirus, RSV, CMV, roseola, PV, influenza Bacterial (occult bacteremia) GBS Gram negative (E. coli, Kebsiella, Enterobacter cloacae, Salmonella) Listeria Strep pneumoniae, H.influenza, N. meningitidis, Salmonella
- 11. Differential Diagnosis of Fever Without Focus Common 0-3 months 3-36 months Bacterial (UTI) Gram negative organisms (E. coli , Klebsiella) same (other) meningitis Unlikely without signs
- 12. Differential Diagnosis of Fever Without Focus Less common 3m-36 months Connective Tissue Diseases Rheumatic fever, SLE, sarcoidosis, JRA,kawasaki Malignancies Leukemia, Lymphoma, neuroblastoma, Ewing sarcoma Poisoning Atropine, salicylates, cocaine, anticholinergics
- 13. Usually caused by common disorders which may have an atypical presentation rather than by uncommon disorders with typical presentations. Most common categories are infectious disease A diagnosis is sometimes never established.
- 14. Diagnostic Approach A careful history and physical is the first step in evaluating a patient with fever of unknown origin.
- 15. History Fever : Duration, height and pattern, measurement technique Whether or not the fever responds to antipyretic drugs Lack of response to NSAIDs may indicate a non-inflammatory condition as the cause of the fever Fever pattern?!
- 16. Associated symptoms and behaviors Medications Environmental exposures Similar symptoms in siblings Birth and nursery history (STD, TORCH, GBS, ROM) in infants Date of last immunizations (MMR-fever and rash 7-10 days afterwards)
- 17. Physical Examination Toxic appearance (irritability, poor perfusion, lethargy) SpO2 – better predictor of pulmonary infection Signs of infection (omphalitis, arthritis, cellulitis, herpes lesions) Meningitis – change in sleep pattern, decreased feeding ,paradoxical irritability, bulging fontanelle (late sign).
- 18. Laboratory Data And Interpretation WBC Neutrophils / Bands Acute-phase reactants Antigen testing Blood cultures Lumbar puncture UA/Urine culture CXR Stool Analysis and Culture Other tests (KFT , LFT, etc) as indicated
- 19. WBC There is direct relationship between the WBC count and the prevalence of bacteremia Temperature curve – not useful Combination of temperature curve and WBC curve offered no advantage over the WBC curve alone Jaffe et al. Pediatrics 1991; 87:670
- 20. WBC Limitations Up to 50% of children with Hib bacteremia will have WBC 5,000-15,000 Children with Neisseria meningitidis may be leukopenic Not predictive of bacteremia in infants < 8 weeks of age Jaffe et al. Pediatrics 1991; 87:670
- 21. Neutrophils, Bands, ESR Have value in identifying children at risk for serious illness Higher the values, the greater the risk of bacteremia
- 22. C – Reactive Protein Acute phase reactant released by the liver following inflammation or tissue damage. High sensitivity but low specificity Increase until 12 hours after the onset of fever and can rise in both viral and bacterial infections. Pulliam PN. Pediatrics. 2001 Dec; 108(6):1275-9.
- 23. Procalcitonin cutoff value 0.12 ng/mL to detect SBI Sensitivity 95-96% (95% CI 83-99 percent) Specificity 23-26% (95% CI 20-32 percent) NPV 96% (95% CI 85-99 percent) Maniaci, et al. Pediatrics. 2008 Oct;122(4):701-10. Dauber, et al. Pediatrics. 2008 No5;122(4):e1119-22.
- 24. Antigen Testing Strep pneumoniae H. influenzae type b PCR methods (VZV, enterovirus)
- 25. Blood cultures Gold standard False negatives Prior treatment with antibiotics Missing an episode of bacteremia Inoculation of too little blood (<1ml) into the media; too much blood may yield false negative due to ongoing killing of bacteria by neutrophils False positives Improperly cleaning the skin, resulting in contamination with skin flora
- 26. LP Indicated if the diagnosis of sepsis or meningitis is considered
- 27. UA/Urine culture Best method if not toilet trained are bladder catheterization or supra-pubic aspiration NOT BAG COLLECTION OBTAIN IN ALL CHILDREN ON EMPIRIC ANTIBIOTICS
- 28. CXR Children > 3 months Oxygen Saturation <95% Respiratory distress Tachypnea Rales on lung auscultation Fever 39.5 C (103.1 F) or higher Asymptomatic with WBC >20,000
- 29. Stool Analysis and Culture Important if diarrhea present Can be considered a focus of infection
- 30. Criteria Rochester - Jaskiewicz JA, et al. Febrile infants at low risk for serious bacterial infection - an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 1994 Sep;94(3):390-6 Philadelphia - Baker MD, et al. Outpatient management without antibiotics of fever in selected infants. N Engl J Med 1993 Nov 11;329(20):1437-41. Boston - Baskin MN, et al. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr 1992 Jan; 120(1): 22-7.
- 31. The purpose of these criteria is to reduce the number of infants hospitalized unnecessarily and to identify infants who may be managed as outpatients by using clinical and laboratory criteria.
- 32. Philadelphia Rochester Boston Age 29-60d <60days 28-89d Temp >38.2C >38C >38C History Not specified Term infant No perinatal Abx No underlying disease Not hospitalized longer than the mother No immunizations < 48h No antimicrobial < 48h Not dehydrated Physical Exam Well-appearing Unremarkable exam Well-appearing No ear, soft tissue or bone infection Well-appearing No ear, soft tissue, or bone infection Labs (define Lower risk) WBC<15,000 Band-neutrophil ratio<0.2 UA <10wbc/hpf Urine gm stain: negative CSF<8wbc CSF gm stain: negative CXR: no infiltrate Stool: no RBC, no WBC WBC 5,000-15,000 Absolute band <1500/mm3 UA<10wbc/hpf Stool smeal <5WBC/hpf WBC <20,000 CSF<10/mm3 UA<10wbc/hpf CXR: no infiltrate
- 33. Three Most Common Strategies for Managing Febrile Infants Philadelphia Rochester Boston Higher Risk patients Hospitalize + Empiric antibiotics Hospitalize+ Empiric antibiotics Hospitalize+ Empiric antibiotics Lower risk patients Home No antibiotics Follow-up required Home No antibiotics Follow-up required Home Empiric antibiotics Follow-up required Reported Stats Sensitivity 98% Specificity 42% PPV 14% NPV 99.7% Sensitivity 92% Specificity 50% PPV 12.3% NPV 98.9% Sensitivity-not available Specificity 94.6% PPV-not available NPV-not available
- 34. Criteria In the first 2 strategies, the lower risk patients are selected for outpatient therapy without antibiotics, whereas the Boston strategy treats all patients with empiric antibiotics but selects a smaller high-risk population for hospitalization.
- 35. Criteria Philadelphia protocol and Rochester criteria: High NPV - 99.7% and 98.9%, respectively. Low PPV - 14% and 12% - large numbers of patients considered higher risk and therefore hospitalized for antibiotics. Boston criteria - more cost-effective strategy Treating all with antibiotics Fewer patients require admission.
- 36. Rochester Criteria Indications Assessment of febrile child ages 60-90 days Reassures against serious infection Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
- 37. Rochester Criteria Reassuring if all criteria are present Well appearing infant No skeletal, soft tissue, skin or ear infections Full term birth No prior illness No prior hospitalizations Not hospitalized longer than mother after delivery No prior antibiotics No Hyperbilirubinemia No chronic or underlying illness CBC normal WBC normal (5000 to 15,000/mm3) Band Neutrophils < 1,500/mm3 Other Lab Findings If Diarrhea is present, Fecal WBC <5 per hpf Urine WBC <10 per hpf Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
- 38. Rochester Criteria Occult bacteremia risk Well-appearing febrile infant risk: 7-9% All Rochester criteria present: <1% Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
- 39. Management: 0 months to 3 months
- 40. Management: 3m to 36m
- 41. Empiric Treatment Generally avoid empiric treatment with anti-inflammatory medications or antibiotics as an effort to diagnose the patient’s condition. Empiric antibiotics can mask or delay diagnosis of infections . Exceptions: Nonsteroidal agents in children with presumed JIA Patients who are clinically deteriorating in whom bacteremia or sepsis is strongly suspected Patients who are immunocompromised
- 42. Antibiotics 0-1 month: Ampicillin Gentamicin or Cefotaxime 1-2 months: Ampicillin and Cefotaxime Ceftriaxone (100mg/kg/day) 2m-36 months: Ceftriaxone
- 43. Antivirals Acyclovir In patients 0-1 month 20 mg/kg/dose three times daily Ill appearing Mucocutaneous vesicles Seizures Elevated LFT (disseminated infection) Send HSV antigen DFA (vesicles) HSV DNA PCR (CSF).
- 44. Antipyretics Acetaminophen 15mg/kg/dose q4hours prn temperature > 39oC (102.2 F) Ibuprofen 10mg/kg/dose q6hours prn temperature > 39oC (102.2 F) Use in children 6 months or older
- 45. Antipyretics In children with baseline temperatures < 102.2°F - both ibuprofen doses and acetaminophen are equally effective. In those children with temperatures > 102.2°F, the ibuprofen 10 mg/kg dose is more effective. It is superior in efficacy and length of anti-pyretic effect that 5 mg/kg dose. Infants: Safety and efficacy of ibuprofen in < 6 months has not been established