What

is

new

in

pertussis

Despite

high

vaccination

coverage

over

the

last

fifteen

years

there

has

been

a

worldwide

resurgence

of

B.

pertussis

infection

While

classical

pertussis

in

the

prevaccine

era

was

primarily

a

childhood

disease

today

with

widespread

vaccination

there

has

been

a

shift

in

the

incidence

of

disease

to

adolescents

and

adults

Centers

of

Disease

Control

and

Prevention

-LRB-

CDC

-RRB-

data

from

reveal

a

nearly

increase

in

the

number

of

cases

in

individuals

years

and

a

increase

in

persons

over

years

Indeed

adolescent

and

adults

play

a

significant

role

in

the

transmission

of

pertussis

to

neonates

and

infants

who

are

vulnerable

to

substantial

morbidity

and

mortality

from

pertussis

infection

Several

explanations

have

been

proposed

to

explain

the

increasing

incidence

of

disease

with

waning

immunity

after

natural

infection

or

immunization

being

widely

cited

as

a

significant

factor

Improving

molecular

biology

diagnostic

techniques

namely

PCR

assays

also

accounts

for

the

increasing

laboratory

diagnosis

of

pertussis

Expanding

vaccination

strategies

including

universal

immunization

of

adolescents

targeted

immunization

of

adults

and

in

particular

healthcare

workers

childcare

providers

and

parents

of

newborns

will

likely

improve

pertussis

control

With

pertussis

continuing

to

pose

a

serious

threat

to

infants

and

greatly

affecting

adolescents

and

adults

there

remains

a

need

to

-LRB-

a

-RRB-

increase

the

awareness

of

physicians

as

to

the

growing

pertussis

problem

-LRB-

b

-RRB-

standardize

diagnostic

techniques

and

-LRB-

c

-RRB-

implement

various

new

vaccine

strategies

to

enhance

its

control

Introduction

Pertussis

an

acute

infectious

illness

of

the

respiratory

tract

remains

endemic

in

developed

nations

despite

high

vaccination

coverage

-LSB-

-RSB-

While

the

early

use

of

whole-cell

vaccine

was

highly

effective

in

reducing

the

incidence

of

reported

pertussis

in

the

United

States

in

the

there

has

been

a

resurgence

of

reported

pertussis

over

the

last

years

-LSB-

-RSB-

Worldwide

there

are

an

estimated

million

cases

occurring

annually

-LRB-

of

which

are

in

developing

countries

-RRB-

and

there

are

as

many

as

pertussis-related

deaths

-LSB-

-RSB-

It

is

general

consensus

moreover

that

the

reported

incidence

of

pertussis

is

considerably

lower

than

its

actual

incidence

-LSB-

-RSB-

Though

in

the

prevaccine

era

pertussis

was

regarded

as

a

childhood

disease

affecting

primarily

young

children

pertussis

epidemiology

in

the

postvaccine

era

is

different

-LSB-

-RSB-

Infants

are

the

most

vulnerable

group

with

the

highest

rates

of

complications

and

mortality

yet

adolescents

and

adults

now

comprise

a

significant

percentage

of

cases

and

a

conduit

of

infection

for

the

infants

-LSB-

-RSB-

PCR

culture

and

serology

are

the

mainstay

of

the

laboratory

diagnosis

of

pertussis

with

various

factors

affecting

the

sensitivity

and

specificity

of

each

modality

-LSB-

-RSB-

However

in

recent

years

PCR

has

become

an

increasingly

more

popular

tool

and

has

significantly

contributed

to

the

increasing

laboratory

diagnosis

of

pertussis

-LSB-

-RSB-

Advances

have

also

been

made

with

regard

to

prevention

and

disease

control

with

experts

from

countries

recently

establishing

the

Global

Pertussis

Initiative

-LRB-

GPI

-RRB-

with

the

aim

of

analyzing

the

status

of

pertussis

and

enhancing

existing

immunization

strategies

-LSB-

-RSB-

Epidemiology

of

pertussis

Before

the

introduction

of

the

whole-cell

pertussis

vaccine

in

there

were

approximately

cases

reported

annually

in

the

US

-LSB-

-RSB-

Immunizations

reduced

disease

rates

and

in

pertussis

incidence

reached

a

nadir

of

reported

cases

-LSB-

-RSB-

However

since

that

time

there

has

been

a

substantial

increase

in

the

number

of

cases

reported

-LSB-

-RSB-

Indeed

over

the

past

years

there

has

been

a

marked

increase

in

the

incidence

of

pertussis

with

reported

disease

in

the

US

reaching

a

rate

of

per

in

with

nearly

provisional

reported

cases

-LSB-

-RSB-

It

is

also

well

established

that

despite

high

vaccination

coverage

for

primary

immunization

in

infants

and

children

pertussis

continues

to

be

a

global

concern

with

increased

incidence

in

many

countries

including

Argentina

Australia

Canada

Italy

Japan

the

Netherlands

Switzerland

and

the

US

-LSB-

-RSB-

It

is

also

widely

noted

that

in

recent

years

there

is

a

general

shift

in

the

age

distribution

of

pertussis

with

adults

and

adolescents

an

underrecognized

but

significant

source

of

infection

for

neonates

and

infants

-LSB-

-RSB-

Data

from

the

EUVAC-NET

project

a

network

for

the

epidemiologic

surveillance

and

control

of

communicable

diseases

in

the

European

community

demonstrate

that

between

and

the

rate

of

disease

incidence

remained

stable

at

a

high

rate

among

children

less

than

year

old

Nevertheless

these

data

indicate

that

the

incidence

rate

among

adults

doubled

in

years

-LSB-

-RSB-

Similarly

Centers

for

Disease

Control

and

Prevention

-LRB-

CDC

-RRB-

surveillance

data

from

demonstrate

that

the

reported

incidence

of

pertussis

among

adolescents

has

substantially

increased

with

a

nearly

ten-fold

rise

-LSB-

-RSB-

Moreover

when

comparing

pertussis

disease

rates

in

recent

CDC

data

from

reveal

a

nearly

increase

in

the

number

of

cases

in

persons

aged

years

and

a

increase

in

persons

over

years

-LSB-

-RSB-

Several

factors

have

been

proposed

as

underlying

the

increasing

incidence

of

pertussis

disease

including

waning

immunity

with

subsequent

atypical

disease

manifestations

increasing

awareness

by

public

health

personnel

with

subsequent

enhanced

surveillance

and

improved

laboratory

diagnostics

-LSB-

-RSB-

Waning

of

both

vaccine-induced

immunity

and

infection-acquired

immunity

is

widely

cited

as

an

important

reason

for

recent

epidemiologic

trends

-LSB-

-RSB-

While

the

assessment

of

the

duration

of

immunity

afforded

after

either

natural

infection

or

vaccination

is

complex

individuals

are

clearly

susceptible

to

initial

infection/reinfection

after

vaccination

or

previous

pertussis

illness

respectively

Studies

vary

in

their

estimation

of

protection

against

disease

with

protective

immunity

after

natural

infection

waning

years

after

illness

and

duration

of

immunity

after

vaccination

waning

at

approximately

years

in

children

-LSB-

-RSB-

Yet

regardless

of

the

precise

interval

when

individuals

do

contract

pertussis

after

the

waning

of

their

immunity

their

disease

manifestations

are

frequently

atypical

-LSB-

-RSB-

As

such

their

illness

is

often

underdiagnosed

Such

underdiagnosis

poses

a

potentially

serious

public-health

concern

in

that

those

untreated

persons

with

protracted

cough

continue

to

unknowingly

transmit

the

disease

to

others

Finally

it

has

been

proposed

that

the

increased

incidence

rates

may

also

be

a

function

of

enhanced

surveillance

as

well

as

improved

and

more

sensitive

diagnostic

lab

techniques

-LRB-

e.g.

PCR

-RRB-

in

that

such

techniques

allow

for

the

diagnosis

of

cases

that

would

probably

have

been

missed

in

the

past

-LSB-

-RSB-

Nevertheless

it

is

important

to

note

that

the

current

estimates

are

likely

to

be

if

anything

an

underrepresentation

of

the

true

incidence

of

disease

-LSB-

-RSB-

First

the

clinical

diagnosis

of

pertussis

is

complicated

by

underconsulting

particularly

among

adolescents

and

adults

-LSB-

-RSB-

Second

with

prolonged

cough

often

being

their

only

clinical

feature

by

the

time

these

adolescents

and

adults

finally

do

seek

medical

attention

it

is

often

too

late

to

culture

or

detect

the

organism

by

PCR

thus

potentially

resulting

in

a

missed

diagnosis

-LSB-

-RSB-

Moreover

the

wide

heterogeneity

in

disease

expression

modification

of

disease

by

immunization

mixed

infection

inconsistent

definition

and

insensitive

nonstandardized

poorly

performed

or

lack

of

available

laboratory

tests

further

complicate

physician

diagnosis

-LSB-

-RSB-

While

the

classic

or

typical

pertussis

may

be

easily

recognized

it

is

seen

less

often

since

general

immunization

began

Instead

atypical

pertussis

usually

characterized

by

the

absence

of

whoop

and

often

a

somewhat

shorter

duration

of

cough

is

more

common

than

classical

pertussis

among

adolescents

and

adults

-LSB-

-RSB-

And

finally

it

should

be

noted

that

immunized

young

children

that

are

PCR

positive

for

B

pertussis

can

be

asymptomatic

-LSB-

-RSB-

Regardless

of

whether

an

individual

displays

classical

pertussis

signs

and

symptoms

or

a

more

protracted

atypical

cough

pertussis

may

not

be

suspected

because

of

the

misconception

among

many

physicians

that

pertussis

is

a

childhood

disease

-LSB-

-RSB-

Co-occurrence

of

other

infections

like

Influenza

A

or

B

adenovirus

and

RSV

may

also

complicate

the

clinical

diagnosis

-LSB-

-RSB-

And

finally

even

when

diagnosed

pertussis

is

often

underreported

-LSB-

-RSB-

Indeed

Sutter

and

Cochi

report

that

in

the

US

only

an

estimated

of

pertussis

cases

were

actually

reported

-LSB-

-RSB-

Thus

multiple

institutional

clinical

and

laboratory

factors

diminish

the

true

assessment

of

pertussis

incidence

and

the

current

data

clearly

are

an

underestimation

of

the

true

burden

of

disease

Laboratory

diagnosis

of

pertussis

Because

accurate

diagnosis

of

pertussis

can

not

be

made

by

clinical

signs

and

symptoms

alone

there

is

a

need

for

improved

laboratory

diagnosis

of

pertussis

-LSB-

-RSB-

While

several

laboratory

techniques

exist

for

the

identification

of

B.

pertussis

namely

culture

serology

and

PCR

overall

several

practical

factors

may

adversely

affect

the

sensitivity

of

its

laboratory

diagnosis

Delayed

specimen

collection

poor

specimen

collection

techniques

specimen

transport

problems

and

lab

media

contamination

are

but

a

few

of

the

practical

constraints

often

influencing

the

outcomes

of

the

laboratory

diagnosis

of

pertussis

Moreover

previous

exposure

to

the

organism

patient

's

age

stage

of

disease

previous

antibiotic

administration

and

immunization

are

other

factors

that

may

have

a

substantial

impact

on

the

sensitivity

of

the

tests

Finally

limited

access

to

diagnostic

or

laboratory

methods

in

both

developed

and

developing

countries

undoubtedly

affects

B.

pertussis

laboratory

confirmation

-LSB-

-RSB-

Culture

B.

pertussis

is

a

fastidious

gram-negative

cocobacillus

and

its

isolation

from

nasopharyngeal

secretions

remains

the

gold

standard

for

diagnosis

Culture

requires

collection

of

a

posterior

nasopharyngeal

specimen

with

a

dacron

or

calcium

alginate

swab

To

increase

the

yield

of

positive

cultures

specimens

should

be

immediately

plated

onto

selective

Regan

Lowe

agar

or

Bordet

Gengou

medium

selective

media

that

are

seldom

readily

available

in

physician

's

offices

because

of

their

cost

and

short

shelf-life

-LSB-

-RSB-

The

main

reasons

for

failure

of

bacterial

growth

in

culture

from

correctly

collected

and

transported

specimens

stem

from

bacterial

and

fungal

contamination

and

the

lack

of

fresh

media

-LSB-

-RSB-

Generally

days

are

required

to

grow

isolate

and

identify

the

organism

an

obvious

limitation

of

the

culture

method.The

timing

of

obtaining

specimens

for

culture

is

also

of

paramount

importance

and

greatly

affects

its

yield

The

proportion

of

patients

testing

positive

for

pertussis

by

culture

is

highest

when

the

initial

specimens

are

obtained

early

in

the

course

of

illness

i.e.

during

the

early

catarrhal

phase

of

the

illness

when

the

organism

is

present

in

the

nasopharynx

in

sufficient

quantity

However

adults

and

adolescents

often

present

late

in

the

course

of

their

illness

thereby

greatly

reducing

the

likelihood

of

culturing

the

organism

-LSB-

-RSB-

Studies

also

demonstrate

that

proportions

of

positive

cultures

decline

in

patients

who

have

been

previously

immunized

and

undoubtedly

in

those

in

whom

antibiotics

have

been

started

Thus

given

the

limited

window

of

opportunity

for

positive

culture

it

is

important

to

stress

that

a

negative

culture

does

not

exclude

pertussis

-LSB-

-RSB-

Finally

it

is

important

to

emphasize

that

despite

its

low

yield

culture

should

be

attempted

as

the

bacterial

isolates

are

needed

for

genotypic

and

phenotypic

analysis

PCR

The

use

of

PCR

for

the

diagnosis

of

pertussis

is

rapidly

evolving

as

it

provides

a

sensitive

rapid

means

for

laboratory

diagnosis

in

circumstances

in

which

the

probability

of

a

positive

culture

is

low

-LSB-

-RSB-

Notably

the

CDC

and

World

Health

Organization

-LRB-

WHO

-RRB-

now

include

a

positive

PCR

in

their

lab

definition

of

pertussis

-LSB-

-RSB-

While

the

sensitivity

of

PCR

also

decreases

somewhat

with

the

duration

of

cough

and

among

previously

immunized

individuals

it

is

nevertheless

a

significantly

more

robust

tool

for

diagnosis

for

those

in

the

later

stages

of

the

disease

or

for

those

who

have

already

received

antibiotics

-LSB-

-RSB-

Specifically

in

their

consensus

paper

the

European

Research

Programme

for

Improved

Pertussis

Strain

Characterization

and

Surveillance

-LRB-

EUpertstrain

-RRB-

state

that

the

real-time

PCR

is

more

sensitive

than

culture

for

the

detection

of

B.

pertussis

especially

after

the

first

weeks

of

coughing

and

after

antibiotic

therapy

has

been

initiated

-LSB-

-RSB-

In

a

prospective

study

in

which

nasopharyngeal

samples

were

obtained

simultaneously

for

both

PCR

and

culture

the

identification

of

B.

pertussis

infections

was

nearly

four-fold

higher

with

PCR

-LSB-

-RSB-

Finally

PCR

is

an

invaluable

tool

for

the

diagnosis

of

pertussis

among

young

infants

since

the

yield

of

culture

is

low

and

serology

is

problematic

in

this

age

group

-LSB-

-RSB-

As

with

culture

important

factors

for

the

successful

application

of

PCR

in

the

diagnosis

of

infection

by

Bordetella

species

include

proper

sample

collection

and

preparation

For

example

a

Dacron

swab

with

a

fine

flexible

wire

shaft

and

not

calcium

alginate

is

the

recommended

swab

After

obtaining

the

nasopharyngeal

sample

the

swab

should

be

shaken

vigorously

in

saline

solution

the

swab

discarded

and

the

vial

sealed

for

further

processing

-LSB-

-RSB-

Appropriate

primer

selection

amplification

conditions

and

controls

are

also

essential

for

effective

PCR

testing

Primers

have

been

derived

from

four

chromosomal

regions

and

common

primers

employed

in

PCR

detection

systems

include

and

-LSB-

-RSB-

Inherent

with

the

high

sensitivity

false

positive

results

are

a

well-recognized

problem

associated

with

the

PCR

diagnosis

of

pertussis

and

other

respiratory

illnesses

While

at

the

present

time

PCR

is

not

routinely

available

and

its

methods

need

more

standardization

optimization

and

quality

control

in

the

future

an

internationally

accepted

standardized

kit

might

be

available

which

would

facilitate

the

expanded

use

of

PCR

for

pertussis

diagnosis

-LSB-

-RSB-

Serology

Natural

infection

with

B.

pertussis

is

followed

by

an

increase

in

serum

levels

of

IgA

IgM

and

IgG

antibodies

to

specific

pertussis

antigen

whereas

the

primary

immunization

of

children

induces

mainly

IgM

and

IgG

antibodies

During

the

past

years

ELISAs

have

constituted

the

mainstay

of

serologic

diagnosis

using

specific

B.

pertussis

protein

as

antigens

and

the

serologic

diagnosis

of

pertussis

is

suspected

with

increases

in

IgA

or

IgG

antibody

titers

to

pertussis

toxin

-LRB-

PT

-RRB-

filamentous

hemmaglutinin

-LRB-

FHA

-RRB-

pertactin

fimbriae

or

sonicated

whole

organisms

in

two

serum

samples

collected

weeks

apart

-LSB-

-RSB-

Notably

these

antibody

responses

to

FHA

are

not

specific

to

B.

pertussis

but

also

occur

following

other

Bordetella

species

moreover

these

antibodies

may

be

cross-reacting

epitopes

to

other

bacteria

including

H.

influenzae

and

M.

pneumoniae

Thus

the

greatest

sensitivity

and

specificity

for

the

serological

diagnosis

of

B.

pertussis

infection

is

by

ELISA

measurement

of

IgG

and

IgA

antibodies

to

PT

demonstrating

at

least

a

two-fold

rise

in

titer

between

acute

and

convalescent-phase

sera

-LSB-

-RSB-

Still

the

main

problem

in

the

serologic

diagnosis

of

B.

pertussis

by

ELISA

is

the

frequent

delay

in

obtaining

the

acute-phase

specimen

In

individuals

with

re-infections

there

is

a

rapid

increase

in

titer

such

that

if

a

delayed

acute-phase

sample

is

obtained

the

titer

is

likely

to

have

already

peaked

thereby

hampering

the

detection

of

the

significant

titer

increase

between

the

acute

and

convalescent-phase

serum

samples

-LSB-

-RSB-

Notably

for

those

individuals

not

recently

immunized

a

single-serum

sample

ELISA

may

circumvent

the

problem

as

ill

patients

will

have

significantly

higher

ELISA

titers

than

the

geometric

mean

titers

-LRB-

GMT

-RRB-

of

healthy

controls

-LSB-

-RSB-

With

this

in

mind

although

a

rise

in

PT

IgA

is

more

suggestive

of

a

recent

antibody

response

it

is

less

consistent

than

a

PT

IgG

rise

hence

in

adolescents

and

adults

a

single

high

value

of

IgG

or

IgA

antibodies

to

PT

suggests

pertussis

infection

-LSB-

-RSB-

Indeed

de

Melker

et

al.

demonstrated

that

an

IgG

concentration

to

PT

of

at

least

units/mL

in

a

single

serum

sample

was

diagnostic

of

either

a

recent

or

active

pertussis

infection

-LSB-

-RSB-

The

serological

diagnosis

of

pertussis

among

infants

also

has

notable

limitations

Some

culture-positive

patients

particularly

infants

younger

than

months

do

not

develop

measurable

antibodies

a

finding

that

calls

into

question

the

utility

of

even

obtaining

a

serum

specimen

for

serology

in

young

infants

-LSB-

-RSB-

In

summary

despite

the

shortcomings

of

serology

a

single-sample

serology

test

can

be

a

useful

tool

particularly

among

older

patients

presenting

late

in

the

course

of

their

illness

when

culture

and

PCR

testing

are

negative

Use

of

antibiotics

in

the

treatment

and

prevention

of

pertussis

Antimicrobial

agents

administered

early

in

the

course

of

disease

i.e.

during

the

catarrhal

stage

may

ameliorate

the

disease

although

after

the

cough

is

established

antibiotics

do

not

have

a

discernable

effect

on

the

course

of

the

illness

but

rather

are

recommended

to

limit

the

spread

of

organisms

to

other

individuals

-LSB-

-RSB-

Erythromycin

clarithromycin

or

azithromycin

are

now

considered

first-line

agents

for

treatment

-LRB-

and

prophylaxis

-RRB-

of

pertussis

in

individuals

months

of

age

or

older

-LRB-

Table

-RRB-

The

antibiotic

choice

for

infants

younger

than

months

of

age

however

requires

special

attention

The

FDA

has

not

yet

approved

azithromycin

or

clarithromycin

for

use

in

infants

younger

than

months

however

the

AAP

endorsed

Red

Book

lists

azithromycin

as

the

preferred

macrolide

for

this

age

group

because

of

the

risk

of

idiopathic

hypertrophic

pyloric

stenosis

associated

with

erythromycin

-LSB-

-RSB-

Notably

however

there

was

a

recent

report

of

infantile

hypertrophic

pyloric

stenosis

among

two

young

infants

treated

with

azithromycin

for

pertussis

-LSB-

-RSB-

Table

antimicrobial

therapy

and

postexposure

prophylaxis

for

pertussis

in

infants

children

adolescents

and

adults

-LSB-

-RSB-

AgeRecommended

drugsAlternativeAzithromycinErythromycinClarithromycinTMP-SMX

mg/kg

per

day

as

a

single

dose

for

mg/kg

per

day

in

divided

doses

for

daysNot

recommendedContraindicated

at

mo

of

moSee

aboveSee

mg/kg

per

day

in

divided

doses

for

days

mo

of

age

TMP

mg/kg

per

day

SMX

mg/kg

per

day

in

doses

for

days

mo

and

mg/kg

as

a

single

dose

on

day

-LRB-

maximum

mg

-RRB-

then

mg/kg

per

day

as

a

single

dose

on

days

-LRB-

maximum

mg/day

-RRB-

See

above

-LRB-

maximum

g/day

-RRB-

See

above

-LRB-

maximum

g/day

-RRB-

See

aboveAdolescents

and

mg

as

a

single

dose

on

day

then

mg

as

a

single

dose

on

days

g/day

in

divided

doses

for

g/day

in

divided

doses

for

daysTMP

mg/day

SMX

mg/day

in

divided

doses

for

daysUsed

with

permission

of

the

American

Academy

of

Pediatrics

Red

Book

Report

of

the

Committee

on

Infectious

Diseases

Book

American

Academy

of

Pediatrics

trimethoprim

SMX

sulfamethoxazoleaPreferred

macrolide

for

this

age

because

of

risk

of

idiopathic

hypertrophic

pyloric

stenosis

associated

with

erythromycin

Postexposure

prophylaxis

The

American

Academy

of

Pediatrics

Red

Book

recommends

that

chemoprophylaxis

be

administered

to

all

household

contacts

and

other

close

contacts

regardless

of

age

and

immunization

status

The

rationale

behind

this

recommendation

is

that

administration

of

chemoprophylaxis

to

asymptomatic

contacts

within

days

of

onset

of

cough

in

the

index

patient

can

limit

secondary

transmission

-LSB-

-RSB-

Other

countries

like

the

United

Kingdom

limit

the

use

of

prophylaxis

for

the

protection

of

only

those

with

the

greatest

risk

from

pertussis

namely

young

infants

-LSB-

-RSB-

Notably

an

evidence-based

review

of

literature

on

the

use

of

erythromycin

in

preventing

secondary

transmission

of

pertussis

to

close

contacts

concluded

that

in

countries

where

effective

pertussis

vaccines

are

in

use

chemoprophyalxis

should

be

limited

to

those

most

susceptible

to

the

complications

of

pertussis

-LRB-

i.e.

unimmunized

or

partially

immunized

infants

-RRB-

and

to

those

individuals

who

come

in

close

contact

with

the

latter

-LSB-

-RSB-

Regardless

of

the

policy

the

agents

dose

and

duration

of

prophylaxis

are

the

same

as

for

treatment

of

pertussis

Prevention

of

pertussis

vaccination

strategies

Pertussis

vaccines

licensed

for

use

in

infants

children

and

adults

vary

across

countries

These

vaccines

differ

both

in

terms

of

their

active

ingredients

and

in

terms

of

the

other

diseases

for

which

coverage

is

provided

-LRB-

e.g.

polio

diptheria

-RRB-

For

example

Repevax

-LRB-

Sanofi

Pasteur

-RRB-

contains

diptheria

tetanus

pertussis

-LRB-

acellular

component

-RRB-

as

well

as

inactivated

polio

whereas

ADACEL

contains

only

tetanus

toxoid

reduced

diphtheria

toxoid

and

acellular

pertussis

Vaccination

strategies

similarly

vary

from

country

to

country

Over

the

last

several

years

many

potential

immunization

strategies

have

been

proposed

to

improve

pertussis

control

-LRB-

Table

-RRB-

Universal

immunization

of

adolescents

and

adults

selective

perinatal

immunization

of

women

who

recently

gave

birth

and

close

contacts

of

newborns

are

but

a

few

of

the

strategies

that

were

discussed

by

the

Global

Pertussis

Initiative

-LRB-

GPI

-RRB-

which

first

convened

in

Specified

immunization

goals

also

included

improvement

of

current

infant

and

toddler

vaccination

programs

-LSB-

-RSB-

The

second

GPI

convened

in

and

reiterated

several

intervention

strategies

to

address

the

ongoing

severe

pertussis

disease

among

neonates

and

infants

-LSB-

-RSB-

Table

strategies

assessed

by

GPI

participantsa

-LRB-

see

-LSB-

-RSB-

Table

pg

-RRB-

StrategyPrimary

objectivesSecondary

Universal

adult

immunizationReduce

morbidity

in

adultsReduce

transmission

to

young

infantsDevelop

herd

immunityReduce

morbidity

in

older

Selective

immunization

of

new

mothers

family

and

close

contacts

of

newbornsReduce

transmission

to

infantsReduce

morbidity

in

adults

particularly

young

Selective

immunization

of

health

care

workersReduce

transmission

to

patientsReduce

morbidity

in

health

care

Selective

immunization

of

child

care

workersReduce

transmission

to

infantsReduce

morbidity

in

child

care

Universal

adolescent

immunizationReduce

morbidity

in

adolescents

and

young

adultsReduce

transmission

to

infantsDevelop

herd

Preschool

booster

at

years

of

ageReduce

morbidity

in

to

oldsReduce

transmission

to

infantsDevelop

herd

Reinforce

and/or

improve

the

current

infant

and

toddler

immunization

strategyReduce

morbidity

and

mortality

in

infants

toddlers

and

childrenReduce

overall

circulation

of

pertussisUsed

with

permission

from

Lippincott

Williams

WilkinsaEntries

represent

the

consensus

of

opinion

of

the

GPI

participants

Immunization

of

adolescents

As

previously

noted

the

incidence

of

pertussis

among

adolescents

is

increasing

and

these

individuals

then

serve

as

a

reservoir

of

infection

to

unvaccinated

or

incompletely

vaccinated

infants

-LSB-

-RSB-

Two

Tdap

vaccines

-LRB-

Boostrix

and

ADACEL

-RRB-

are

licensed

for

use

in

the

US

Recently

the

CDCs

Advisory

Committee

on

Immunization

Practices

-LRB-

ACIP

-RRB-

has

recommended

routine

Tdap

for

adolescents

from

years

-LSB-

-RSB-

Several

other

countries

including

Canada

Austria

Australia

France

and

Germany

have

also

introduced

the

universal

immunization

of

adolescents

-LSB-

-RSB-

In

Germany

for

example

the

current

immunization

schedule

recommends

DTaP

at

and

months

and

dTaP

at

years

and

at

years

-LSB-

-RSB-

For

a

complete

overview

of

the

pertussis

vaccination

in

other

European

countries

please

access

the

EUVAC.NET

website

-LSB-

-RSB-

Future

studies

will

be

needed

to

evaluate

the

duration

of

protection

afforded

and

the

potential

need

for

an

adult

booster

Immunization

of

adults

The

Adult

Pertussis

Trial

-LRB-

APERT

-RRB-

a

study

sponsored

by

the

United

States

National

Institute

of

Health

-LRB-

NIH

-RRB-

has

recently

demonstrated

the

efficacy

of

acellular

pertussis

vaccines

in

preventing

pertussis

disease

in

adults

-LRB-

and

adolescents

-RRB-

-LSB-

-RSB-

To

date

only

ADACEL

is

licensed

for

use

in

adults

and

the

recommended

adult

immunization

schedule

in

the

US

-LRB-

October

September

-RRB-

now

recommends

that

Tdap

replace

a

single

dose

of

Td

for

adults

years

who

have

not

previously

received

a

dose

of

Tdap

-LRB-

either

in

the

primary

series

booster

or

for

wound

management

-RRB-

-LSB-

-RSB-

Given

the

increased

public

awareness

of

adolescent

and

adult

pertussis

in

conjunction

with

perhaps

an

increased

awareness

about

vaccines

in

general

-LRB-

e.g.

HPV

and

influenza

-RRB-

the

general

public

may

be

more

receptive

to

a

universal

adult

vaccination

against

pertussis

-LSB-

-RSB-

The

expected

benefits

of

such

programs

would

be

to

build

up

herd

immunity

and

reduce

disease

Alternatively

the

selective

vaccination

of

only

those

adults

at

highest

risk

of

transmitting

B.

pertussis

to

vulnerable

infants

is

likely

to

decrease

both

the

incidence

and

the

impact

of

pertussis

on

young

infants

Regardless

of

the

approach

used

successful

adult

vaccination

programs

must

include

education

and

public

awareness

Cocoon

strategy

The

vaccination

of

household

members

including

parents

and

siblings

of

newborn

infants

has

been

recently

coined

the

cocoon

strategy

-LSB-

-RSB-

Recent

studies

have

demonstrated

that

parents

are

frequently

the

source

of

pertussis

infection

to

their

infants

-LSB-

-RSB-

While

implementation

of

this

strategy

is

expected

to

lead

to

only

modest

reductions

in

typical

adult

cases

there

is

a

strong

indirect

effect

on

infants

and

young

children

In

countries

where

universal

immunization

of

adults

is

not

yet

feasible

many

experts

consider

such

targeted

immunization

as

worthy

of

implementation

-LSB-

-RSB-

Presently

the

cocoon

strategy

is

recommended

in

several

European

countries

including

Australia

France

Germany

and

Austria

-LSB-

-RSB-

Maternal

vaccination

Although

there

is

efficient

placental

transfer

of

pertussis

antibodies

low

maternal

levels

and

rapid

decay

in

newborns

render

the

infants

vulnerable

to

life-threatening

pertussis

-LSB-

-RSB-

Maternal

immunization

during

pregnancy

might

afford

some

degree

of

protection

to

mother

and

infant

during

a

vulnerable

period

and

the

use

of

Tdap

during

pregnancy

is

currently

under

consideration

Neonatal

vaccination

Given

the

resurgence

of

reported

pertussis

in

infant

populations

noted

in

multiple

countries

and

the

high

morbidity

and

mortality

in

this

age

group

newborn

pertussis

immunization

is

a

potentially

attractive

strategy

-LSB-

-RSB-

It

is

still

unclear

however

if

such

a

strategy

will

induce

sufficient

and

timely

immunity

for

this

targeted

immunization

Future

trials

are

needed

to

address

these

concerns

Conclusion

Despite

the

increasing

awareness

of

B.

pertussis

it

continues

to

affect

millions

of

people

worldwide

While

classical

pertussis

was

once

regarded

as

a

child

's

disease

today

pertussis

poses

a

serious

threat

to

infants

and

greatly

affects

adolescents

adults

now

functioning

as

reservoirs

of

infection

While

advances

in

molecular

biology

have

undoubtedly

increased

the

capacity

to

diagnose

pertussis

work

is

still

needed

to

standardize

laboratory

techniques

The

increased

awareness

of

the

pertussis

problem

among

experts

and

the

lay

public

will

hopefully

pave

the

way

for

the

implementation

of

various

vaccine

strategies

to

enhance

its

control

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

bordetella pertussis
polymerase chain reaction (pcr)


Epithelioid sarcoma in the thoracic spine Epithelioid sarcoma is a rare and highly malignant soft tissue tumor that is commonly found in the extremities and rarely in the trunk area . This malignant tumor often mimics granuloma or nodular fasciitis , which causes a delay in establishing the diagnosis . This type of cancer has a high recurrence rate . Surgical treatment requires wide radical resection . The objective of this case report is to highlight the unique location of a rare neoplasm and to illustrate the relentless course of epithelioid sarcoma despite initial radical resection . A 14-year-old boy was admitted to our facility with a soft tissue mass on the right lower thoracic spine . The large tumor mass had deeply penetrated into the muscles , infiltrated the neuroforamen of T9 -- T10 level , and compressed the dural sac . Immunohistological study of the biopsy was highly consistent with an epithelioid sarcoma . Wide excision of the mass , laminectomy and spine fusion with instrumentation was performed . The patient received chemotherapy and irradiation . The first recurrence of the neoplasm was seen as a contralateral metastasis 21 months after the resection . On the last follow-up , 3 years postoperatively , the patient was in a good general condition . However , further progression of the sarcoma had to be recognized . Our case encompasses multiple features that represent negative prognostic factors . Initial wide excision of the neoplasm and adjuvant therapy including chemotherapy and irradiation seem to slow down the relentless course of epithelioid sarcoma in the trunk . Introduction Epithelioid sarcoma is a rare type of a fibrohistiocytic tumor , which is not extensively documented in the literature . It is common at the extremities , and rare at the trunk area . The incidence of epithelioid sarcoma in the trunk is 4 % with a range from 0 to 44 % -LSB- 2 , 12 , 14 -RSB- . It affects mainly adolescent males -LSB- 1 -- 3 , 11 , 13 , 14 , 17 -RSB- . To our knowledge there are only two cases reported of localization in the spine -LRB- lumbosacral junction and sacrum -RRB- -LSB- 7 , 14 -RSB- , and there are no reports on epithelioid sarcoma at the thoracic spinal level . Laskowski -LSB- 9 -RSB- has first described the unique histological appearance in 1961 . It resembles a chronic inflammatory process , necrotizing granuloma , squamous cell carcinoma or other fibrohistiocytic tumors . Electron microscopic appearance suggests origin from synovial structures -LSB- 6 , 10 -RSB- . There is 85 % local recurrence rate and 30 -- 50 % likelihood for metastases predominately lymphatic or in the lungs -LSB- 2 , 4 , 11 -RSB- . The 5-year survival rate varies from 65 to 100 % -LSB- 1 , 12 , 13 -RSB- . Factors adversely affecting the survival rate are -LSB- 2 , 12 -RSB- : Size of the tumor ; Infiltration of the tumor into muscular , neural or vascular structures ; Primary location in the trunk ; Pulmonary metastasis.Wide surgical resection is indicated , since epithelioid sarcoma frequently follows a relentless course with multiple recurrences -LSB- 4 , 17 -RSB- . Chemotherapy and irradiation are recommended to decrease recurrence rate -LSB- 2 , 8 -RSB- . Case report A 14-year-old overweight boy presented at an orthopaedist 's private practice with a painless , bulging mass on his back that was incidentally discovered by his grandmother . He was 183 cm tall and weighted 107 kg . Besides obesity no other medical problems were reported . There was no family history of a soft tissue mass . On the physical examination the tumor had a soft consistence and could not be shifted from the underlying tissue . Neurological examination did not reveal any deficit . Magnetic resonance imaging -LRB- MRI -RRB- with gadolinium of his thoracolumbar spine revealed a right paravertebral cystic mass . The soft tissue tumor extended from T7 to T11 level and measured 9.5 × 3 × 3 cm . The mass infiltrated via the neuroforamen at T9 -- T10 levels compressing one quarter of the spinal cord -LRB- Fig. 1 -RRB- . There was no osseous involvement . Open biopsy of the mass showed necrobiotic granuloma including epithelioid and fusiform cells . Immunohistochemical studies revealed a co-expression of vimentin and cytokeratin , with pathological diagnosis of epithelioid sarcoma grade III . During the tumor staging a craniolateral metastasis was depicted on the PET scan -LRB- Fig. 2 -RRB- . Consecutive MRI confirmed a soft tissue mass of 1 cm diameter , located about 10 cm distant from the main mass . Wide mass resection , including the locoregional metastasis , led to a sacrifice of large parts of the paravertebral thoracic muscles . In addition a hemilaminectomy of T9 -- T10 vertebra with resection of the adjacent pedicles and careful dissection from the dural sac was performed . There was no sparing of right ninth nerve root . The tumor resection was intralesional . Posterior transpedicular instrumentation from T6 to L1 was carried out . After surgery no new motor or sensory deficits were noted . Chemotherapy was initiated on the 6th postoperative week and irradiation on 10th postoperative week . The patient received nine courses of chemotherapy within 25 weeks -LRB- Table 1 -RRB- and a total dose of 3-Gy irradiation over 4 weeks . He developed a wound dehiscence 2 weeks after initiation of the irradiation therapy . Under daily dressing no infection was observed . The wound was finally closed with a pedicle musculocutaneous flap using the Latissimus dorsi muscle 4 weeks after the completing the course of irradiation . Routine follow-up consisted of a physical examination , plain radiograms of the thoracic spine plus MRI Scans every 3 month -LRB- Fig. 3 -RRB- . Fig. 1Preoperative antero-posterior -LRB- a -RRB- and lateral -LRB- b -RRB- plain X-rays of the middle thoracic spine . On the ap view no irregular formation of the pedicles can be depicted -- the lateral view of the thoracic spine show apophyseal endplate changes as a feature of Scheuermans disease . No signs of osteolytic lesion can be detected . Preoperative transverse -LRB- c -RRB- and sagittal -LRB- d -RRB- MRI scan -LRB- T2 sequences : TR = 3,070 , TE = 120 -RRB- demonstrating the tumor mass in the region of the paravertebral muscles , reaching and compressing the dural sac via the right neuroforamen Th9/10Fig . 2On the PET scan a craniolateral metastasis was detected -LRB- a -RRB- and the paravertebral tumor mass was confirmed -LRB- b -RRB- . No further satellite lesions were foundTable 1Agents and dosage of the quadruple chemotherapyAgent -LRB- trade name -RRB- Total dose -LRB- mg -RRB- Ifosfamid -LRB- Holoxan ® -RRB- 100,440 Vincristin -LRB- Onkocristin ® -RRB- 20Actinomycin D -LRB- Lyovac ® -RRB- 12Doxorubicin -LRB- Ribodoxo ® -RRB- 494Fig . 3Postoperative antero-posterior -LRB- a -RRB- and lateral -LRB- b -RRB- plain radiograph of the thoracic spine at final follow-up . Postoperative transverse -LRB- c -RRB- and sagittal -LRB- d -RRB- MRI scan -LRB- T2 sequences : TR = 3,682 , TE = 120 -RRB- at 1.5 year showing no sign of recurrence A metastasis at the fifth intercostal space of the chest contralateral to the initial tumor location was observed at 21 months follow-up . At this stage the patient denied further intervention . Two years postoperatively pulmonary metastases were detected on CT scans in addition to a local recurrence on the right thoracic spine . There was no significant progression of the tumor growth at the last follow-up 37 month after surgical treatment . The young male was in good general condition fully participating in social life . Discussion Epithelioid sarcoma is a rare soft tissue neoplasm with a high local recurrence rate . Epithelioid sarcoma presents histologic characteristics similar to inflammatory processes and other benign soft tissue tumors , which frequently delays the diagnosis and adequate treatment . Typical for this soft tissue sarcoma is an immunohistochemical co-expression of cytokeratin and/or epithelial membrane antigen -LRB- EMA -RRB- and vimentin , and in half of the cases an immunoreactivity for CD34 , an occasional reactivity for smooth muscle actin -LRB- SMA -RRB- , desmin , neuron specific enolase and S100 protein -LSB- 2 , 5 -RSB- . In our specimen a strong positive immunoreaction with antibodies to cytokeratin , vimentin and EMA was registered -LRB- Fig. 4 -RRB- . Histomorphology and immunohistochemical pattern are typical and separates this tumor entity from other sarcomas . To differentiate from osteogenic sarcoma , which may also co-express cytokeratin and vimentin , and may demonstrate a immunoreactivity with SMA and CD99 , epithelioid sarcoma , however , does not produce tumor osteoid , which is the key finding in osteogenic sarcoma . Fig. 4a Histomorphologic aspect of epithelioid sarcoma with solid and nodular growth pattern , H&E -LRB- 10 × -RRB- . b The tumor cells are roundish , admixed with spindle shaped cells and are featuring an eosinophilic cytoplasm with vesicular , irregular nuclei -LRB- 20 × -RRB- . c Immunohistochemical investigation with antibodies against cytokeratin shows a strong positive immunoreaction -LRB- 20 × -RRB- . d The immunoreaction against epithelial membrane antigen -LRB- EMA -RRB- demonstrates a comparable picture -LRB- 20 × -RRB- . e The immunoreactivity against smooth muscle actin -LRB- SMA -RRB- features a weak staining -LRB- 20 × -RRB- . f The immunoreaction against CD 99 is negative -LRB- 20 × -RRB- Wide local resection is the recommended treatment of epithelioid sarcoma -LSB- 1 , 8 , 11 , 14 -RSB- . In the spine however , total eradication of the sarcoma by an enbloc excision is compromised by the presence of neural structures -LSB- 16 -RSB- . Thus the concept of intralesional resection was followed both for the main tumor mass and the metastasis . Nerve sheaths may serve as a pathway for the spread of the sarcoma -LSB- 1 , 2 , 8 , 11 , 17 -RSB- . Enzinger -LSB- 4 -RSB- reported six cases with a mass infiltration along nerve sheaths or vascular structures . In our case there was involvement of the right ninth nerve root . The mass expansion into the right T9 -- T10 neuroforamen with compression of the dural sac necessitated a wide hemilaminectomy with resection of the facet joints and the adjacent pedicles . The wide paraspinal muscle resection required six levels segmental instrumentation and fusion to avoid scoliotic deformity due to muscular imbalance -LSB- 15 -RSB- . Pulmonary metastasis and local recurrence of the sarcoma were first diagnosed 24 month after the resection . In comparison , a survival period of 22 month after the initial surgery was described in a case report of epithelioid sarcoma in the lumbosacral spine -LSB- 14 -RSB- . Moreover , on first diagnosis , our case embodied many factors that promote recurrence of this neoplasm : large size , localization in the trunk and infiltration in both muscle and neural structures . Recurrence as the typical feature of epithelioid sarcoma can not be prevented even in extremities , where a radical surgical regimen can be pursued -LSB- 8 -RSB- . In conclusion , epithelioid sarcoma of the spine is an extremely rare entity , which differs from other sarcoma subtypes in propensity for local recurrence and spread along the lymphatic pathways . Initial radical resection followed by adjuvant chemotherapy and irradiation can retard the relentless course of this malignancy .

B I O O B I B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

epithelioid sarcoma
thoracic spine
survival


Pure cervical radiculopathy due to spontaneous spinal epidural haematoma -LRB- SSEH -RRB- : report of a case solved conservatively Introduction : Spontaneous spinal epidural haematoma -LRB- SSEH -RRB- is widely recognised throughout the literature as a cause of myelopathy , radicular compression being very rarely reported . Surgical management is almost always recommended , especially in the cases of spinal cord compression . Conservative treatment is reported as a curiosity and only in the case of spontaneous improvement . This report presents the particular case of a 64-year-old patient undergoing anticoagulant therapy that had a cervical radiculopathy due to a SSEH confirmed by MRI . The patient improved spontaneously and symptoms were solved with unconventional conservative treatment and without stopping the anticoagulant therapy . Conclusions : Spontaneous epidural haematoma must be kept in mind when patients undergoing anticoagulant therapy have a sudden onset of cervicobrachialgia . Even though most spinal surgeons advocate surgical treatment , a conservative approach may lead to a complete recovery and may be considered as a good option in the case of radicular involvement . Discontinuation of the anticoagulant therapy may not always be needed , especially when the clinical syndrome improves spontaneously . Introduction Although spontaneous spinal epidural haematoma -LRB- SSEH -RRB- is a low incidence condition , it is widely recognised throughout the literature as a cause of myelopathy -LSB- 5 , 15 -RSB- . The relationship between SSEH and anticoagulant therapy is well known and the probable cause of bleeding is thought to be the rupture of the venous epidural plexus during a sudden elevation of thoracic or abdominal pressure -LSB- 4 , 6 , 8 , 10 , 11 , 13 , 15 -RSB- . The most common symptoms are cervical or thoracic pain followed by cord compression signs . Radicular involvement is very rare and , when it appears , it mostly affects the lumbar spine , producing ciatalgia -LSB- 1 , 3 , 11 -RSB- . Although the currently suggested approach is an urgent surgical decompression -LSB- 9 , 10 -RSB- , conservative treatment is recommended when there is an objective improvement of the neurological status -LSB- 2 , 11 , 12 -RSB- . In general , anticoagulation treatment must be suspended or adjusted before surgery . The originality of this report arises in three points : The case involved the cervical spine producing simple radiculopathy.It was solved spontaneously.Anticoagulation therapy was not discontinued . Case report A 64-year-old white man undergoing anticoagulant therapy because of cardiac valve prosthesis arrived at the emergency room of our Hospital suffering from a sudden onset of cervical pain and a left C5 brachial pain and weakness . The physical exam revealed a 4/5 deltoid weakness and abolition of the bicipital reflex . The patient showed no signs or symptoms of cord compression . Standard radiographs of the cervical spine were normal . Based on the suspicion that it was a case of disc herniation with left C5 root involvement , symptomatic treatment by means of non-steroid anti-inflammatory drugs and painkillers was indicated . A cervical MRI was scheduled and the patient was invited to undergo further examination at the Spinal Surgery Unit . Owing to the fact that the first physician was not a spinal surgeon and therefore not aware of the relationship between anticoagulation and SSEH , discontinuation of anticoagulant therapy was not indicated . Two days later , when the patient was examined by the Spinal Surgery Unit , the pain had been completely relieved and the weakness had also decreased . The MRI revealed a left posterolateral ovoid mass compatible with a haematoma extending from C4 to C5 -LRB- Fig. 1 -RRB- . Symptomatic medical treatment was interrupted . Once the specialist knew the real cause of the radicular syndrome , the haematologist was consulted and they preferred not to suspend the anticoagulant therapy -LRB- despite an adequate level of anticoagulation , INR 2,7 -RRB- in order to prevent thromboembolism . Fig. 1MRI 2 days after the onset of symptoms . Posterolateral placement of the haematoma at C4 -- C5 level . a , c Isointense appearance of the haematoma on the MRI T1-weighted sagittal and axial images . b , d Hyperintense appearance of the haematoma on the MRI T2-weighted sagittal and axial images Seven days later , the patient was free of weakness and the MRI showed a decrease in the haematoma size -LRB- Fig. 2 -RRB- . Successive MRI results were obtained 1 month -LRB- Fig. 3 -RRB- and 1 year later on -LRB- Fig. 4 -RRB- to document the resolution of the haematoma . One year on , the patient remains asymptomatic.Fig . 2MRI performed 7 days later . The haematoma is smaller nevertheless it is located at the same C4 -- C5 levelFig . 3MRI 1 month later : disappearance of the haematomaFig . 4MRI 1 year later : normal MRI Discussion Radicular compression due to SSEH is far less frequent than myelopathy . Groen and Van Alphen -LSB- 6 -RSB- reported that 4.5 % of a series of 320 SSEH cases treated surgically presented radiculopathy ; all cases affecting the lumbar spine . Recently , Groen -LSB- 7 -RSB- reported that 9 % of a series of 64 SSEH cases treated conservatively presented an isolated radicular compromise ; only one of his cases was located on the cervico -- thoracic spine . Our case adds little in terms of number but the fact that it may be the only report of its kind on purely cervical radiculopathy due to SSEH , which may be considered anecdotic , as well as interesting . Although the spreading of the haematoma throughout the epidural space is the most likely hypothesis proposed for spontaneous recovery in case of neurological impairment -LSB- 7 , 14 -RSB- , our case does not support that theory because the haematoma did not spread throughout the epidural space . -LRB- Figs. 1 , 2 -RRB- Conservative management is currently indicated in uncommon situations or when neurological symptoms improve before medical evaluation . Geographic isolation , initial inaccurate diagnosis , neurological improvement pending an adequate coagulation level prior to surgery , high surgical risks and several other reasons had been referred to as the likely causes that led to the opportunity for spontaneous recovery -LSB- 4 , 7 , 9 , 11 , 16 -RSB- . Our case can be categorised as wrong diagnosis initially , but we have to admit that the first non-specialised consultation spared our patient from the operation . If the patient had first consulted a more skilled specialist , following the state of the art , he would have probably been operated on , thus obtaining a good result and a proud surgeon . Finally , the main interest of our case would be focused on the controlled maintenance of the anticoagulant therapy in patients with mild neurological compromise such as radiculopathy due to SSEH in order to avoid thromboembolic risk .

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O O O O O O O O B I O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O

cervicobrachialgia
anticoagulant therapy
conservative treatment