Download Brown- Clinical Conundrum

Julie Brown, MD
Midwest Pediatric Hospital
Medicine Conference
June 12, 2010
History
• 4 week old male with a 1 day history of poor feeding
and being more sleepy, fussy, sweaty, and clammy.
Infant found floppy and unresponsive with blue lips
and hands.
• Presented to outside ED with cyanosis, respiratory
distress, delayed cap refill, sat 80%.
• Two weeks prior he was hospitalized locally for
fever and RSV (late May). Septic workup negative.
Hospitalized for 7 days due to oxygen requirement
and increasing WBC that stabilized on the day of
discharge.
• The infant was seen by the PMD the day prior to
this presentation (3 days after hospital DC) and had
improved, per mom.
• Birth History: Term, vaginal delivery 7lb 12oz
No complications
• Allergies: NKDA
• Imm: Hep B given
• Medications: Xopenex
• SH: Lives with parents, maternal
grandparents and 5 year old sibling. No
daycare. All adults smoke. No reported ill
contacts. No recent travel.
• FH: no history of heart or lung disease, no
leukemia, unremarkable
ED Course
• Suctioned and oxygen applied, sat 98%, pink
• CBC and blood culture obtained
• 10 mL/kg NS bolus, 50 mg/kg IV ceftriaxone prior to
transfer via helicopter to Children’s Emergency
Department
• Upon arrival Temp 38.1 C, Pulse 185, glucose 35.
coarse breath sounds with retractions and grunting,
delayed cap refill, mottled. Septic workup
completed, LP done. Given IV cefotaxime, dextrose,
and additional 20ml/kg NS, and admitted to
inpatient unit for further care.
Laboratory
CBC: WBC 57.8, Hgb 11, Plat 624, Segs 49,
Bands 4, Lymph 38
BMP: Na 124, K 5.7, Cl 92, CO2 27, BUN 35,
Creat 0.3, Ca 9.9, Gluc 35
CSF WBC 124, RBC 89, many immature WBC
and 55% NRBC, 31% lymphs, 18%
mono/macro Glucose 37, Protein 78
UA: trace protein, otherwise negative
LFT: AST 60 (20-50), ALT 66 (20-60), Alb 3.0
(3.6-4.6), LDH 1425 (425-975), Uric Acid 2.4
Serology: ESR 1, CRP 0.6
Coags normal
CXR
• Perihilar streaking and
hyperinflation, heart size
normal
Physical Exam
Temp: 36.9 C, Resp: 32, BP 93/65, Pulse 176,
sat 95% on ½ liter NC
Wt. 4.6 kg
General: alert with spontaneous movement, no cry
HEENT: NCAT, AFSF, PERRL, no conjunctivitis or icteric sclera,
mucous membranes tacky, OP clear without erythema, TMs grey
bilaterally
Neck: supple, no lymphadenopathy
Chest: mild distress, crackles throughout, no wheeze, equal breath
sounds
CV: tachycardia, capillary refill 3 seconds
Abd: soft, non-tender, no HSM, no mass
GU: normal male, testes descended bilat
Ext: no joint swelling or limited movement
Skin: pale, no rash except neonatal acne on chin, multiple bruises
from IV attempts, no active bleeding, LP site clean
Neuro: fair tone with strong suck and grasp, no assymetry or
weakness, normal DTRs
Differential Diagnosis
ID:
Heme/Onc:
Pulm:
CV:
CC: cyanosis, floppy
HPI: 4 week old male with 1
day history of poor
feeding, decreased
activity, fever, respiratory
distress
PMH: Recent admit for
RSV, sepsis eval, report
of increasing WBC count
Physical Findings:
leukocytosis, CSF
pleocytosis, hypovolemic
shock, and hypoglycemia.
coarse lungs, dry mucous
membranes, tachycardia
Clinical Course
• On arrival to the inpatient unit he was given 40
ml/kg of NS to help correct hyponatremia and
hypovolemia. Acyclovir was added in addition to
vancomycin and ceftriaxone.
• Within the first 12 hours of hospitalization he had
worsening respiratory distress and perfusion and
was transferred to the ICU and intubated (14 days)
• Infectious Disease was consulted and supported
diagnosis of meningitis in light of CSF pleocytosis,
and were suspicious of sepsis due to shock
presentation, but most cultures were obtained after
antibiotics
Clinical Course cont.
• (ID cont.) There was also high suspicion of
viral etiology so multiple viral tests were
obtained as well as pertussis testing and
azithromycin was started pending results.
• Pathology reviewed CSF WBC and peripheral
smear: mixed granulocytic and lymphocytic
leukamoid changes. No evidence of
leukemia. did not see blasts or cells
suggestive of oncologic process
• WBC slowly returned to normal over next 7
days
Microbiology
• Blood culture (pre-antibiotic from outside
hospital) was lost in transit
• Blood culture (post-antibiotics) negative
• CSF culture (post-antibiotics) negative
• Urine culture (post-antibiotics) negative
• Viral eye, nasal, rectum negative
• CSF Enterovirus PCR negative
• CSF Herpes PCR negative
• Respiratory Viral Panel and Pertussis pending
Clinical Course cont.
• On HD #5 respiratory viral testing returned
positive rhinovirus/enterovirus. ID felt this was
likely etiology of CSF WBC but infant
completed 7 days of antibiotics due to pretreatment.
• On HD #7, final day of azithromycin treatment,
pertussis PCR returned positive which was
likely explanation for leukocytosis and
respiratory symptoms.
• He had issues with hypoxia, feeding difficulties
and abstinence syndrome but was finally
discharged after a month in the hospital
Pertussis
• In prevaccination era, pertussis was a leading cause
of infant death.
• Recent increase in number of cases by 2300%
between 1976 and 2005
• significant cause of morbidity and mortality in infants
younger than 2 years.
• Differential diagnosis of protracted cough with
cyanosis or vomiting, persistent rhinorrhea, and
marked lymphocytosis
Pathophysiology
• Bordetella pertussis: aerobic, nonmotile, gramnegative coccobacillus attaches to/multiplies on
respiratory epithelium
• Transmission is only human to human by aerosol
• highly contagious. 80-90% of susceptible individuals
who are exposed develop the disease.
• late summer and early fall.
Mortality/Morbidity
• Overall infant mortality rate is 2.4 per 1 million live
births.
• CDC reported 39 deaths from pertussis in 2005; 32
(82%) occurred in infants <3 months.
• World Health Organization (WHO) estimates that
294,000 children died from pertussis worldwide in
2002.
• Risk factors include the following:
– Nonvaccination in children
– Contact with an infected person
– Epidemic exposure
– Pregnancy
Age
• occurs predominantly in ages 3 months to 5 years,
>70% of cases reported in children <5 years.
• lack of maternal immunity transfer
• 10-15% of all cases occur in infants <6 months, with
>90% of all death in same age group.
• growing majority of cases are now in 10 years and
older, leading to increased booster recommendations.
• Natural disease does not provide lifelong immunity as
earlier thought.
• 3 injections of cellular/acellular vaccine provides up to
12 years of protection.
Clinical History
• 3 stages: incubation, catarrhal, and paroxysmal.
• asymptomatic incubation period lasts 7-10 days.
• catarrhal stage, lasts 2-7 days.
– Minimal or no fever, Rhinorrhea, Anorexia, Mild but
increasing cough
• paroxysmal stage, lasts 1-8 weeks.
– paroxysms of coughing, provoked by feeding (in infants)
and exertion.
– The inspiratory gasp or whoop eventually develops,
especially in those aged 6 months to 5 years.
Clinical History cont.
• Infants younger than 6 months often with cyanosis
and apneic spells.
• Vaccinated adults usually develop only prolonged
bronchitis without a whoop, whereas unvaccinated
adults are most likely to have whooping and
posttussive emesis.
• About 12-32% of adults with persistent cough (>2
wk) have pertussis. On average, they wait a median
of 3 weeks before seeking treatment.
Laboratory Findings
• Blood work
– Lymphocytosis is often profound (>70% of the total WBC
count), especially in children.
– The WBC count often increases to 20-40,000 or even
100,000 cells/mm2.
– In adults, especially those that had been vaccinated,
lymphocytosis is rare.
• Cultures
– A definitive culture diagnosis is not always possible.
Laboratory Findings
• Direct fluorescent antibody (DFA) studies
– results within minutes, its use is not recommended
because of both low sensitivity and low specificity.
– Results are positive in 40-80% of patients so is
commonly used to confirm cases.
• Polymerase chain reaction (PCR) testing to detect
DNA
– PCR testing may reveal <10 organisms per swab
sample.
– high sensitivity
– PCR or positive culture is the case definition for
reporting pertussis to the CDC or WHO
Treatment
• Infants should be observed for apnea, cyanosis, or
hypoxia.
• Try to isolate patients from others (especially
infants) for 4 weeks, especially until 5-7 days of
antibiotic therapy is completed when transmission is
considerably decreased.
• considerations for admission:
– Age younger than 1 year
– Pneumonia
– Apneic or cyanotic spells or hypoxia
– Moderate-to-severe dehydration
Treatment
• prophylaxis for household and close contacts is
recommended.
– Erythromycin 50 mg/kg/d divided 4 times a day (qid) for
14 days
– Alternative: Azithromycin 10 mg/kg on day 1 then 5
mg/kg on days 2 through 5.
• If the patient is allergic to erythromycin/azithromycin,
use trimethoprim sulfamethoxazole (TMP-SMZ).
Vaccination
• prevention of pertussis through immunization is
vital.
• Herd immunity does not completely protect
unvaccinated children.
• Measurable antibody wanes after 3-5 years and is
not measurable after 12 years
• Vaccination is recommended with DTaP at the ages of 2,
4, 6, and 15-18 months, and 4-6 years of age. A booster
with Tdap is recommended in adolescents or adults
requiring tetanus immunization who did not have an
adolescent booster.
• Exploring means of preventing disease transmission
to infants including maternal vaccination to provide
passive antibody and vaccinating at birth
Questions??
Enjoy your Summer!