Transcript Neisseria Meningitidis

USC Case # 16
Pediatric Febrile Rash
Greg Vigesaa OMSIII
Wythe County Community Hospital
Preceptors: Albert Aymer, DO
Belle Jones, MD
Chief Complaint and HPI
CC: Fever with a rash
 HPI: K.C. is a 10 year-old white female
who presented to the ER on 3/5/06 with a
one day history of fever, vomiting,
diarrhea, joint pain, and painful rash. She
also complained of intermittent abdominal
pain over the past day and a frontal
headache.

HPI Cont.

HPI: K.C. did eat hamburger at a fast
food restaurant two days prior to the
onset of her symptoms. She has not been
hiking or done any foreign travel. She
does have multiple animals at home
including a ferret, finches, and a cockateil
bird.
Past Medical/Surgical History

PMH: History of multiple urinary tract
infections since she was three years old.
She has never been hospitalized.

PSH: None
Allergies and Medications

Allergies: penicillin and ciprofloxacin

Medications: Urised- medication used as a
bladder antispasmodic and antiseptic. It
contains atropine, benzoic acid,
hyoscyamine, methenamine, methylene
blue, and phenyl salicylate.
Family/Social History
FH: Significant for kidney disease.
Multiple family members have either a
single kidney or a history of vesicoureteral
reflux.
 SH: C.K. lives at home with her father,
mother, 18 year-old brother, and 14
month old sister.

Review of Systems






General: +fever, +fatigue, no chills, change in
weight, appetite.
HEENT: +HA, no pharyngitis, rhinorrhea,
tinnitus, epistaxis, hearing or visual changes.
CV: No CP, palpitations, orthopnea, syncope.
Resp: No SOB, dyspnea, cough, hemoptysis.
GI: +intermittent abdominal pain, +vomiting,
+diarrhea, no melena or hematochezia.
GU: No dysuria, hematuria, increased
frequency, hesitancy.
Review of Systems
MS: +arthralgias, no myalgias, weakness,
swelling.
 Neuro: No change in sensation, strength,
LOC, dizziness, seizures or parathesias.
 Skin: +painful rash, no puritis.
 Psych: No depression, anxiety.

Physical Exam






Vitals: T 100.9 P 136 BP 94/46 R 20 O2 100%
General: overweight, alert, pink, NAD.
HEENT: NC/AT, PERRLA, EOMI, TMs clear
bilaterally, mucous membranes moist.
Neck: supple with full range of motion.
Lungs: CTAB.
Heart: RRR without murmur, gallop, rub.
Physical Exam
Abdomen: soft, NT/ND, normoactive BS, no
masses, oragnomegally, guarding, rebound or
CVA tenderness.
 Extremities: no C/C/E, brick capillary refill.
 Skin: petechial, purpuric rash with some
maculopapular areas throughout her body,
sparing her face.
 Neruo: CN II-XII grossly intact, normal tone,
moving all extremities well. Symmetrical
sensation and strength. Negative Kernig and
Brudzinski sign.

Review of Kernig and Brudzinski

Kernig- upon flexion of
the thigh to 90 degrees,
there will be resistance to
extension at the knee if
meningeal irritation is
present.

Brudzinski- involuntary
flexion of the thighs and
knees upon flexion of the
neck when meningeal
irritation is present.
ER Management
Seeing that her blood pressure was only 94/46
and pulse was 136, it was determined that K.C.
needed immediate fluid resuscitation to increase
her intravascular volume and cardiac output.
 She received a bolus of NS 20 ml/kg x 2. After
the fluids her blood pressure increased to
116/68.
 STAT labs and blood cultures were obtained.
 Following labs K.C. received Rocephin 1 gram IV
x 1.

Consultation
After interviewing and examining K.C., Dr.
Turski consulted Dr. Belle Jones who was
the pediatrician on call.
 She agreed with the initial assessment
and management and agreed to admit her
to the hospital.
 It was decided that a lumber puncture
was not indicated do to lack of meningeal
signs.

Assessment and Plan







10 year-old female with petechial, purpuric rash,
fever, gastroenteritis, arthralgias, leukocytosis,
mild dehydration, metabolic acidosis.
Admit to hospital.
CBC with diff., PT/PTT/FDP, BMP, UA/UC, blood
cultures, stool cultures, rapid strep (TC),
influenza A and B.
Rocephin 50 mg/Kg q24h pending BC/UC.
Bolus of NS at 20 ml/kg x 2 in ER.
D5 1/2 NS IV with 20 mEq of KCL at 100ml/h.
NPO.
Differential Diagnosis









Rocky Mountain Spotted Fever
Ehrlichiosis
Hemolytic-Uremic Syndrome
Toxic Shock Syndrome
Henoch-Schonlein Purpura
Serum Sickness
Meningococcemia
Meningitis
Coxsackie Virus (hand-foot-and-mouth)
Working Through the Differential

RMSF is caused by Rickettsia rickettsii and can cause fever, cough,
headache, macular and petechial rash. It is transmitted by the
ixodid ticks in the Atlantic states mainly from May to September. A
history of a tick bite can be elicited in about 70% of patients. K.C.
has no history of cough, playing outside, or being bitten by a tick.
Being that it is March it is unlikely that she has RMSF.

Ehrlichiosis is caused by Ehrlichia species and causes fever, chills,
headache, malaise, macular or petechial rash involving the trunk
and extremities. It can also cause abdominal pain, vomiting, and
diarrhea, DIC. It is an obligate intracellular bacteria that invades
lymphocytes and neutrophils. It is also transferred by ticks,
sometimes carried on canines. We are unsure if she has contact
with doges. This scenario matches the signs and symptoms of K.C.;
therefore, we cannot rule this out without further investigation.
Working Through the Differential

HUS is most commonly caused by Escherichia coli 0157. It is causes
fever, petechial/purpuric rash, micoangiopathic hemolytic anemia,
thrombocytopenia, diarrhea with bloody stool, and abdominal pain.
It is also one of the main causes of acute renal failure in children.
E. coli is transmitted through contaminated food such as beef that is
undercooked. She does not complain of hematochezia or melena,
but the fact that she ate a hamburger at a fast food restaurant
raises the suspicion that she may have HUS.

TSS is caused by the exotoxin of Staphylococcus aureus it causes
fever, vomiting, diarrhea, hypotension, and a skin rash. It occurs
most commonly in menstruating women who use tampons. The
fact the K.C. has hypotension and other symptoms support the
diagnosis. But fact that she has not started menses and dose not
uses tampons argues against TSS being the cause of her illness.
We can put this farther down on the list of differential diagnosis.
Working Through the Differential

HSP is an acute or chronic vasculitis that affects small blood vessels
of the skin, joints, GI tract, and kidneys. The disease causes a
purpuric rash of the extensor surfaces feet, legs, arms which is
often preceded by an acute respiratory illness. Patients also often
complain of fever, arthralgias, abdominal pain, and edema of the
hands and feet. Being that K.C. has no history of previous episodes,
URI, or edema of the hands or feet we can put this lower in the
differential diagnosis. We cannot; however, rule this out without
further workup.

Serum sickness is a type III immune reaction which causes
antibody-antigen immune complexes to deposit in various tissues.
These complexes initiate inflammation by causing complement
activation and recruitment of phagocytic cells. The signs and
symptoms include fever, arthralgias, skin rash. It is usually
preceded by administration of vaccinations, new medications to
which the patient develops an allergy to. K.C. has not received and
new vaccinations or medications so this can be put lower in the
differential diagnosis.
Working Through the Differential

Meningococcemia and meningitis are caused by the bacteria
Neisseria meningitidis. It can cause fever, vomiting, headache,
nuchal rigidity, arthralgias, myalgias, petechial or purpuric rash. In
meningitis the CNS is involved and may cause confusion, stupor, or
coma. A patient with meningitis will often have a positive Kernig or
Brudzinski sign. K.C. does not have nuchal rigidity, confusion, or a
positive Kernig or Brudzinski sign, this argues against meningitis.
But her symptoms are consistent with meningococcemia. Because
this is a potentially fatal disease we will put this possible diagnosis
at the top of the differential diagnosis and possibly begin empiric
antibiotics.

Hand-foot-and-mouth disease is caused by the Coxsackievirus A16.
It often causes a fever, vesicular rash that affects the oral mucosa,
hands, and feet. K.C. has no oral lesions and her rash is not
vesicular, but petechial and purpuric. Hand-foot-and-mouth disease
is self-limiting and the treatment is symptomatic; therefore, we will
put this at the bottom of the differential diagnosis.
Labs/Workup
CBC w/differential
 PT/PTT/FDP
 BMP
 UA/UC
 Blood cultures
 Stool cultures
 Rapid strep
 Influenza swab

Labs/Workup

CBC w/diff:
BMP:
WBC- 18,000
Na- 134
Hgb- 13.4
K- 3.2
Hct- 38
Cl- 103
Plts- 291,000
CO2- 18
Neut%- 93.4
BUN- 16
Lymp%- 5.0
Cr- 0.8
Bands- 6
Glu- 120
Neut- 80
Ca- 8.4
Lymp- 11
AG-16
Toxic granulations: moderate
UA:
Color- yellow
App- clear
WBC- 1-5
RBC- 1-5
Sp. Gravity- 1.030
Mucous- large
Bacteria- many
Squamous- many
Protein- 30
Labs/Workup
PT: 13.3
9.4-11.0
 PTT: 35.2
24.3-30.2
 FDP: 5
<5
 Rapid strep- Negative.
 Influenza- Negative.

Labs/Cultures
UC: >100,000 col/ml gram- rods (E.coli).
 TC: Normal flora.
 SC: Normal flora.
 BC: Gram- cocci predominately in pairs.

 Probable Neisseria meningitidis.
 Sent to state lab for serotyping.
 Final ID: Neisseria meningitidis serogroup Y.
Diagnosis
Septic meningococcemia
 Urinary tract infection

Hospital Course

Throughout her admission K.C. continued
to receive Rocephin 1 g IV q24h and D5
½ NS with 20 mEq of KCL at 100 ml/h.
Routine labs included: CBC with
differential and BMP. Her CBC, BMP, and
vital signs improved throughout her nine
day admission and were normal on the
day of her discharge.
Hospital Course
Blood Pressure
Temperature
102
Systolic
130
98
110
90
Diastolic
Temp F
100
96
94
Admission
Day3
Day5
Day7
70
50
D/C
Admission
Day5
Day7
D/C
Resp and O2 Sat
Heart Rate
140
02 sat
110
120
100
Resp
Pulse
Day3
80
60
Admission
Day3
Day5
Day7
D/C
90
70
50
30
10
Admission
Day3
Day5
Day7
D/C
Labs on 3/10/06

CBC w/diff:
WBC- 6.2
Hgb- 11.6
Hct- 32.9
Plts- 261,000
Neut %- 56.1
Lymph %- 32.5
BMP:
UA: (3/7/06)
Na- 136
K- 3.7
Cl- 105
CO2- 24
BUN- 4
Cr- 0.5
Glu- 98
Ca- 8.8
AG-11
Color- yellow
App- clear
WBC- none
RBC- 5-10
Sp. Gravity- 1.020
Mucous- none
Bacteria- none
Squamous- few
Protein- negative
Discharge Instructions

K.C. was discharged on 3/13/06, nine
days after admission in good condition.
She was to follow up with Dr. Belle Jones
two days after discharge at Wythe Bland
Pediatrics. Prophylactic antibiotics were
given to her family and healthcare
providers who were in close contact with
her.
Etiology

Neisseria meningitidis.

Gram-negative diplococcus.
Polysaccharide capsule with lipid A
lipooligosaccharide (endotoxin).
13 serogroups- A, B, C, Y, W-135 cause
majority of clinical disease.
Grows on Thayer-Martin chocolate agar.
Ferments glucose and maltose.




Epidemiology






Causes outbreaks of bacterial meningitis, acute
and chronic meningococcemica.
5-10% of the population are nasopharyngeal
carriers, higher in daycare centers.
Incidence: 0.8-1.3 / 100,000 persons
Mortality: 8-13%
50% of cases occur in children < 2yo
Risk factors: day care centers, military recruit
camps, college freshman living in dorms (2-8
fold increased risk), viral illness, smoking,
chromic disease, low socioeconomic status,
complement deficiency (c5-c9)
Pathogenesis





Spread through respiratory droplets.
Incubation: 1-10 days.
Adheres to non-ciliated epithelial cells via
a pili (capsule prevents phagocytosis).
Induces host to rearrange microvilli
production which causes endocytosis.
Traverses the cell in membrane bound
vacuoles, possesses porins that assist in
escaping complement (c3b, c4b).
Pathogenesis
 Enters the circulation:
 If abs present- blocks dissemination via complementmediated bacterial lysis.
 If abs not present- meningococcemia with potential to
cause meningitis.
 Lipid A of the LOS activates inflammatory
cytokines TNF-a, IL-1, IL-6, IL-8, also the
intrinsic and extrinsic coagulation cascade.
 The amount of inflammatory response is directly
proportional to the concentration of lipid A in the
circulation.
 The inflammatory response can lead to
progressive capillary leakage and DIC leading to
multi-organ system failure, septic shock, and
circulatory collapse.
Pathogenesis
Pathogenesis
Clinical Manifestations









Fever
Pharyngitis
Headache
Nausea and vomiting
Myalgias
Arthralgias
Altered mental status (stupor)
Nuchal rigidity
Petechial or purpuric rash
Petechial/Purpuric Rash
Purpuric Rash/Necrosis
Diagnosis
Isolation of N. meningitidis from a sterile
body fluid (Blood cultures, CSF, synovial
or pleural fluid).
 Culture and gram stain of petechial or
purpuric scrapings.
 Latex agglutination test of CSF.
 PCR used in the United Kingdom.

Gram-negative Diplococcus
Complications
Waterhouse-Friderichsen Syndrome.
 Gangrene
 Endocarditis, myocarditis, pericarditis.
 Renal infarcts.
 Avascular necrosis of epiphyseal plates.

Waterhouse-Friderichsen Syndrome
Bilateral adrenal hemorrhagic necrosis.
 Caused by DIC- adrenal glands become
“sacs of clotted blood”.
 Decreased adrenocortical steroids
(aldosterone and cortisol) leads to
hyponatremia and hyperkalemia.
 Tx the underlying cause with antibiotics,
may require supplemental corticosteriods.

Waterhouse-Friderichsen Syndrome
Hemorrhagic necrosis
of adrenal gland.
 Loss of normal
architecture:

– Fasiculata
– Glomerulosa
– Reticularis
Treatment

Neisseria Meningitidis is very sensitive to
antibiotics.
 Penicillin G 250,000 U/kg/d IV x 5-7 d.
 Cefotaxime 200 mg/kg/d IV x 5-7 d.
 Ceftriaxone 100 mg/kg/d IV x 5-7 d.
 Isolation (droplet precautions) for 24 hrs
after initiation of antibiotics.
Immunization
There is a quadrivalent meningococcal vaccine
against serogroups A, C, Y, and W-135.
 It is available to patients older than two years
of age. Routine immunization is not
recommended because the infection rate in the
general population is low.
 However, immunization is recommended for
persons in high-risk groups with risk factors.

Prophylaxis for Contacts
Ciprofloxacin 500 mg PO, single dose if
>18 years old.
 Ceftriaxone 250 mg IM, single dose if >12
years old.
 Ceftriaxone 125 mg IM, single dose if <12
years old.

Osteopathic Considerations





Very little literature about OMM and sepsis.
OMM seems contraindicated in a child with septic
meningiococcemia.
Would not want to facilitate further dissemination of the
bacteria.
Also given the potential for DIC, manipulation could
cause hemorrhage because of decreased platelets and
clotting factors.
Osteopathic principles apply to all patients:
–
–
–
–
Body is a unit.
Body has self-regulating mechanisms.
Structure and function are reciprocally interrelated.
Rational treatment is based on these principles.
References





Behrman, Kliegman, Jensen. Nelson’s Textbook of
Pediatrics. 17th ed. Pgs. 896-899. 2004. Saunders.
Cohen & Powderly: Infectious Diseases. 2nd ed. Pgs.
2173-2187. 2004. Mosby.
Long. Principles and Practice of Pediatric Infectious
Diseases. 2nd ed. Pgs 748-756. 2003. Churchill
Livingstone.
Kumar, Abbas, Fausto. Robbins and Cotran Pathologic
Basis of Disease. 7th ed. Pgs. 377-378, 1214-1215. 2005.
Saunders.
The Red Book Report on the Committee of Infectious
Disease. American Academy of Pediatrics. Pgs. 430-436.