Fever in Children (Part 2)

1. Fever in Children (Part 2) • In febrile infants 0-3 months old: • Recognize the risk of occult bacteremia • Investigate thoroughly • In viral infections, do not prescribe antibiotics • In those requiring antibiotics, prescribe according to likely causative organisms and local resistance patterns • Investigate patients with FUO appropriately • In febrile patients, consider life threatening causes • Aggressively and immediately treat patients with fever from serious causes • Consider non-infectious causes of hyperthermia (eg. heat stroke, drug reactions, malignant neuroleptic syndrome)

2. Fever in Children (Part 2) • Acute fever • Who is at risk? • For what germs? • Life threatening acute febrile illnesses • Non-infectious causes of acute fever • Chronic fever • Approach to PUO

3. Fever in Children (Part 2) • High Risk Populations (Clinical) • Neonates • GBS, E.coli, Listeria, HSV, Enterovirus • Hyperpyrexia (temp >40 deg. Celsius) • Meningitis, bacteremia, pneumonia, heat stroke • Fever with petechiae • N. meningitidis, also H.flu, S.pneumo.

4. Fever in Children (Part 2) • High Risk Populations (Immunocompromised) • Sickle Cell • Sepsis, pneumonia, meningitis by S.pneumo • Osteomyelitis by Salmonella and S.aureus • Asplenia • Bacteremia and meningitis • (N.meningitidis, H.flu, S.pneumo)

5. Fever in Children (Part 2) • Immunocompromised Populations • Agammaglobulinemia • Bactermia, sinoplumonary infections • AIDS • S.pneumo, H.flu, Salmonella, others • Atypicals (PCP, cryptosporidium) • Complement deficiency • N.meningitidis

6. Fever in Children (Part 2) • Immunocompromised Populations • Malignancy (+/- neutropenia) • Gram negative enterics, S.aureus, coag. neg. Staph, Candida & Aspergillus • Congenital heart disease • Endocarditis, brain abscess (R-to-L shunt) • CVL • S.aureus, coag negative Staph, Candida

7. Fever in Children (Part 2) • Life threatening causes of fever • Sepsis • Meningitis • Acute rheumatic fever • Endocarditis (separate lecture) • Kawasaki disease • Others (eg. Rocky Mountain spotted fever, etc)

8. Fever in Children (Part 2) • Acute rheumatic fever • Etiology: • Link between GAS and ARF • Peak incidence of initial attack and recurrences 5-15 • Coincides with greatest risk for GAS pharyngitis • Some serotypes more rheumatogenic than others • Epidemiology: • As high as 50 per 100,00 children in some countries • Incidence in USA • 100-200/100,000 in 1900 • As low as 0.5/100,000 in 1980 • Most common cause of acquired heart disease worldwide • Decline in industrial countries precedes antibiotic era

9. Fever in Children (Part 2) • Acute rheumatic fever • Pathogenesis: • Cytotoxic theory • GAS produces toxins that are toxic to mammalian cardiac cells (eg. Streptolysin O) • Difficult to explain latent phase between GAS infection and onset of ARF • Immune-mediated theory • Similar to other immune mediated diseases • Several GAS products and constituents are immunogenic and cross-reactive with mammalian tissue components

10. Fever in Children (Part 2) • Acute rheumatic fever • Clinical Manifestations: • No clinical or laboratory test • Jones criteria • 5 major and 4 minor criteria • MUST have evidence of recent GAS infection • Either 2 major criteria or 1 major and two minor for diagnosis • To diagnose initial attack not recurrences • Usually recurrences meet Jones criteria • Chorea can be only manifestation of ARF

11. Fever in Children (Part 2) • Jones criteria • Proof of GAS infection • Positive throat culture or rapid strep test • Elevated or increasing strep antibody titres • Major criteria • Carditis • Polyarthritis • Erythema marginatum • Subcutaneous nodules • Chorea • Minor criteria • Arthrlagia • Fever • Increased ESR or CRP • Prolonged PR interval

12. Erythemamarginatum

13. Fever in Children (Part 2) • Kawasaki disease • Etiology remains unknown • KD-associated antigen suggests viral cause • Epidemiology • 11-39/100,000 depending on population • More common in Asian/Pacific Islander populations • 80% less than 5 years old • Pathology • Medium-sized artery vasculitis

14. Fever in Children (Part 2) • Kawasaki disease • Clinical Manifestations • High fever • Unremitting, unresponsive to antibiotics • Generally 1-2 wk, up to 3-4 weeks (Min 4 days) • Irritable • Five principal clinical criteria (Need 4 of 5) • Conjuncitivits • Oropharyngeal erythema • Changes in extremities • Lymphadenopathy • Rash

15. Fever in Children (Part 2) • Kawasaki disease • Principal Clinical Criteria • Conjuncitivitis • Bilateral, non-exudative with limbal sparing • Oropharyngeal erythema • Strawberry tongue, cracked, dry lips • Extremity changes • Early: Edema and erythema of hands and feet • Late: Distal (periungual) desquamation

16. Fever in Children (Part 2) • Kawasaki disease • Principal Clinical Criteria • Lymphadenopathy • Non-suppurative cervical lymphadenopathyUsually unilateral • Greater than 1.5cm • Rash • Various forms (EM, maculopapular, scarletiniform) • Accentuation in groin area • NOT vesicular

17. Kawasaki disease Conjunctivitis

18. Fever in Children (Part 2) • Kawasaki disease • Associated symptoms • GI symptoms • Hydrops of gall bladder • Hepatitis • Sterile urethritis/pyuria • Arthritis • Cardiac aneurysms • 25% of untreated patients

19. Fever in Children (Part 2) • Kawasaki disease • Treatment • Referral to centre with experience treating • Intravenous Immunoglobulin (2g/kg) • Sometimes requires second dose • Aspirin • Initially high dose (80-100mg/kg/d divided q6h) • Later antithrombotic dose (3-5mg/kg/d) • After afebrile for 48hr • Continue 6-8 weeks • Influenza vaccine (prevent Reye syndrome)

20. Fever in Children (Part 2) • Non-infectious causes • Heat injuries (cramps, exhaustion, stroke) • Children more vulnerable than adults • Heat cramps • Mild dehydration/salt depletion • Calf/hamstring muscles • Heat syncope • Heat edema • Heat tetany • Respond to oral hydration and cool environment

21. Fever in Children (Part 2) • Non-infectious causes • Heat exhaustion • Symptoms • Elevated core temperature • Headache, Nx, Vx, dizziness • Orthostasis/syncope, weakness, piloerection • Treatment • Move to cool environment, remove excess clothing • Active cooling (ice packs to groin/axillae) • Fluids (po if tolerated, otherwise IV) • Temperature monitoring • Transfer to emergency facility if not responding

22. Fever in Children (Part 2) • Non-infectious causes • Heat stroke • Sports related • Profuse sweating, intense exertion • “Classic” • Dry, hot skin • Slower onset • Elderly or chronically ill persons

23. Fever in Children (Part 2) • Non-infectious causes • Heat stroke • Core temperature >40 degrees • CNS disturbance • Potential tissue damage • Treatment • Constant monitoring of ABC/GCS • Rapid cooling via cold water immersion • Can discontinue once temp under 39 degrees • IV fluids • NS or RL: 800ml/m2 in first hour

24. Fever in Children (Part 2) • Non-infectious causes • Drug reactions • Hypersensitivity reactions • Altered thermoregulation • Idiosyncratic reaction

25. Fever in Children (Part 2) • Non-infectious causes • Malignant neuroleptic syndrome • Few days after starting neuroleptic agent • After withdrawl of dopaminergic agent • Mortality up to 20-30% • Symptoms: • Fever greater then 38 degrees • Encephalopathy (Delerium) • Vital signs unstable – tachycardia, diaphoresis • Elevated CPK • Rigidity of muscles (Dystonia)

26. Fever in Children (Part 2) • Fever of Unknown origin • Definition • Fever documented by health care provider • No cause identified after 3 weeks • Or after 1 week observation in hospital • Etiology • Neoplastic • Infectious • Atypical organisms • Atypical presentation of common organism • Rheumatologic • Drug fevers

27. Fever in Children (Part 2) • Fever of Unknown origin (History) • Age • Children: Resp&GU infection, localized infection, JIA, rarely leukemia • Adolescents: TB, IBD, autoimmune disease, lymphoma • Travel history • malaria • Zoonotic exposures • Leptospirosis, tularemia, lyme disease • Pica/atypical diet • Toxacara canis, toxoplasmosis • Genetic background • Periodic fever syndromes (FMF, PFAPA, TRAPS) • Medication history

28. Fever in Children (Part 2) • Fever of Unknown origin (Assessment) • Pattern of fever • Eg. Quotidien with am hypothermia vs constant with variable spikes • Physical examination • Eye findings (Conjunctivitis, uveitis, chorioretinitis) • Sinus tenderness, dental problems, thyroiditis • Hepatosplenomegaly, lymphadenopathy, masses • Murmur (endocarditis) • Skin (petechiae, splinter hemorrhages, nodules, etc)

29. Fever in Children (Part 2) • Fever of Unknown origin (Labs) • Directed by history and physical • Consider: • CBC with differential • Blood culture • Aerobic – specials (eg. leptospirosis, etc) based on clinical assessment • May need multiple cultures • Urinalysis • ESR/CRP • >30 consistent with infectious, autoimmune, malignancy • >100 consistent with TB, KD, autoimmune, malignancy • TB Skin test • Radiographs (based on clinical assessment) • Serology (CMV, EBV, Bartonella, Toxoplasma, Borrelia, Salmonella, etc) • Other tests (BMA, bone scan, Echo) as appropriate

30. Fever in Children (Part 2) • Fever of Unknown origin • Treatment • Based on underlying diagnosis • Trial of antimicrobial generally avoided • Exception: Critically ill children • Prognosis • Based on underlying diagnosis • Generally better prognosis in children than adults • Often resolves spontaneously without diagnosis • As many as 25% of cases remain elusive