n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
Re is a
de
la
Sociedad
Española
de
Ne ología
w
w
w. e is ane ologia.com
Case
epo
Anaemia
and
e e
in
kidney
ansplan .
The
ole
o
human
pa o i us
B19夽
Yane
Pa odis
Lópeza,
Raquel
San ana
Es upi ˜
nána,
Sil ia
Ma e o
Robaynaa,
Robe o
Gallego
Sampe a,
Fe nando
Hen íquez
Palopa,
José
Ca los
Ri e o
Ve a b,
Ra ael
Camacho
Galánb,
Ma ía
José
Pena
Lópezc,
Ne y
Sablón
Gonzáleza,
Fayna
González
Cab e aa,
Elena
Oli a
Dámasoa,
Nicano
Vega
Díaza,
José
Ca los
Rod íguez
Pé eza,∗
aSe icio
de
Ne ología,
Hospi al
Uni e si a io
de
G an
Cana ia
D .
Neg ín,
Uni e sidad
de
Las
Palmas
de
G an
Cana ia,
Las
Palmas
de
G an
Cana ia,
Spain
bSe icio
de
Ana omía
Pa ológica,
Hospi al
Uni e si a io
de
G an
Cana ia
D .
Neg ín,
Uni e sidad
de
Las
Palmas
de
G an
Cana ia,
Las
Palmas
de
G an
Cana ia,
Spain
cSe icio
de
Mic obiología,
Hospi al
Uni e si a io
de
G an
Cana ia
D .
Neg ín,
Uni e sidad
de
Las
Palmas
de
G an
Cana ia,
Las
Palmas
de
G an
Cana ia,
Spain
a
i
c
l
e
i
n
o
A icle
his o y:
Recei ed
26
Decembe
2015
Accep ed
25
Augus
2016
A ailable
online
24
Ap il
2017
Keywo ds:
Renal
ansplan
Human
pa o i us
B19
Pos - ansplan
anaemia
a
b
s
a
c
In ec ions
emain
an
issue
o
pa icula
ele ance
in
enal
ansplan
pa ien s,
pa icula ly
i al
in ec ions.
Human
pa o i us
B19
in ec ion
causes
se e e
e ac o y
anaemia,
pancy openia
and
h ombo ic
mic oangiopa hy.
I s
p esence
is
ecognised
by
analysing
blood
polyme ase
chain
eac ion
(PCR)
and
by
he
disco e y
o
ypical
gian
p oe y h oblas s
in
he
bone
ma ow.
We
epo
he
case
o
a
65
yea -old
man
wi h
a
his o y
o
deceased
dono
enal
ansplan
in
Sep embe
2014.
A
38
days
a e
he
ansplan ,
he
pa ien
p esen ed
p og essi e
anaemia
ha
was
esis an
o
e y h opoiesis-s imula ing
agen s.
A
64
days
a e
ansplan ,
hype -
he mia
occu ed
wi h
p og essi e
de e io a ion
o
he
pa ien ’s
gene al
condi ion.
The
i al
se ology
and
he
fi s
blood
PCR
o
human
pa o i us
B19
we e
bo h
nega i e.
A
4
mon hs
and
19
days
a e ,
a
bone
ma ow
biopsy
was
conduc ed,
showing
gian
e y h oblas s
wi h
nuclea
i al
inclusions
ha
we e
compa ible
wi h
pa o i us;
a
PCR
in
he
issue
confi med
夽Please
ci e
his
a icle
as:
Pa odis
López
Y,
San ana
Es upi˜
nán
R,
Ma e o
Robayna
S,
Gallego
Sampe
R,
Hen íquez
Palop
F,
Ri e o
Ve a
JC,
e
al.
Anemia
y
fieb e
en
el
pos asplan e
enal:
su
elación
con
el
pa o i us
humano
B19.
Ne ologia.
2017;37:206–212.
∗Co esponding
au ho .
E-mail
add ess:
j odpe [email p o ec ed]
(J.C.
Rod íguez
Pé ez).
2013-2514/©
2016
Sociedad
Espa˜
nola
de
Ne olog´
ıa.
Published
by
Else ie
Espa˜
na,
S.L.U.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
207
he
diagnosis.
A
second
blood
PCR
was
posi i e
o
pa o i us.
A e
ea men
wi h
in a-
enous
immunoglobulin
and
he
empo a y
discon inua ion
o
mycophenola e
mo e il,
a
comple e
emission
o
he
disease
occu ed,
al hough
he
blood
PCR
o
pa o i us
B19
emained
posi i e,
so
moni o ing
is
necessa y
o
u u e
likely
ecu ence.
©
2016
Sociedad
Espa˜
nola
de
Ne olog´
ıa.
Published
by
Else ie
Espa˜
na,
S.L.U.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/
by-nc-nd/4.0/).
Anemia
y
fieb e
en
el
pos asplan e
enal:
su
elación
con
el
pa o i us
humano
B19
Palab as
cla e:
T asplan e
enal
Pa o i us
B19
humano
Anemia
pos asplan e
e
s
u
m
e
n
Las
in ecciones
con inúan
siendo
un
p oblema
ele an e
en
el
pacien e
asplan ado
enal,
en
especial
las
in ecciones
i ales.
La
in ección
po
el
pa o i us
humano
B19
causa
anemia
e ac a ia
g a e,
panci openia
y
mic oangiopa ía
ombó ica.
Dicha
in ección
se
diagnos ica
median e
el
análisis
de
la
eacción
en
cadena
de
la
polime asa
(PCR)
en
sang e
y
po
la
p esencia
de
p oe i oblas os
gigan es
ípicos
en
la
médula
ósea.
P esen amos
el
caso
clínico
de
un
a ón
de
65
a˜
nos
con
asplan e
enal
de
donan e
cadá e
en
sep iemb e
de
2014.
A
los
38
días
del
asplan e
comienza
con
anemia
p og esi a
y
esis en e
a
los
agen es
es imulan es
de
la
e i opoyesis.
A
los
64
días
se
p oduce
hipe e -
mia,
con
de e io o
p og esi o
de
su
es ado
gene al.
La
se ología
í ica
esul ó
nega i a,
al
igual
que
la
PCR
inicial
en
sang e
del
pa o i us
humano
B19.
A
los
4
meses
y
19
días
se
eal-
iza
una
biopsia
de
médula
ósea
en
la
que
se
obse an
e i oblas os
gigan es
con
inclusiones
í icas
nuclea es
compa ibles
con
pa o i us,
po
lo
que
se
ealiza
una
PCR
en
dicho
ejido
que
confi ma
el
diagnós ico.
Una
segunda
PCR
en
sang e
esul ó
posi i a.
T as
el
a amien o
con
inmunoglobulinas
in a enosas
(IGIV)
y
la
suspensión
empo al
del
mico enola o
de
mo e ilo,
se
p oduce
una
emisión
comple a
de
la
en e medad,
aunque
pe sis ía
posi i a
la
PCR
pa a
el
pa o i us
B19
en
sang e,
lo
que
hace
necesa io
igila
p obables
ecidi as.
©
2016
Sociedad
Espa˜
nola
de
Ne olog´
ıa.
Publicado
po
Else ie
Espa˜
na,
S.L.U.
Es e
es
un
a ´
ıculo
Open
Access
bajo
la
licencia
CC
BY-NC-ND
(h p://c ea i ecommons.o g/licenses/
by-nc-nd/4.0/).
In oduc ion
Fac o s
in ol ed
in
he
de elopmen
o
pos - ansplan
anaemia
a e:
blood
loss,
i on
and
ola e
deficiency,
low
e y h opoie in,
and
also
hype pa a hy oidism,
neoplasms,
angio ensin-con e ing
enzyme
inhibi o s,
and
angio ensin
II
ecep o
blocke s,
immunosupp essi e
d ugs,
alganciclo i ,
co- imoxazole,
and
ch onic
g a
dys unc ion1in ec ions
caused
by
cy omegalo i us
(CMV),
Eps ein–Ba
i us
(EBV)
and
pa o i us
B19,
which
can
p oduce
bone
ma ow
aplasia.1,2
Pa o i us
B19
in ec ion
a ec s
40–60%
o
he
gene al
pop-
ula ion,
and
i s
highes
incidence
is
in
school
age
child en
(“fi h
disease”).
In
kidney
ansplan s,
pa o i us
B19
in ec ion
is
a
a e
complica ion.
Molecula
biology
echniques
ha e
shown
i al
DNA
in
he
blood
o
20–30%
o
ansplan
pa ien s.3Se e al
au ho s
ha e
epo ed
ha
he
incidence
o
his
i us
in
solid
o gan
ansplan s
is
2%.4Howe e ,
he
exac
incidence
o
in ec ion
in
kidney
ansplan s
is
no
known,
al hough
i
has
been
epo ed
up
o
12%.5
In
heal hy
subjec s
wi h
no
ansplan ,
pa o i us
B19
is
ansmi ed
h ough
espi a o y
sec e ions,
blood
and
u ine,6
and
ac oss
he
placen a
o
he
oe us.5In
kidney
ansplan
pa ien s,
o he
possibili ies
a e
seconda y
i al
eac i a ion
due
o
se e e
immunosupp ession,
ansmission
h ough
blood
ans usions,
o
e en
dono -de i ed
pa hways.5,7
The
symp oms
o
pa o i us
B19
in ec ion
include
e e ,
a h algia
and
ash.
O he
clinical
changes
include
a h opa-
hy,
ansien
aplas ic
c isis,
hyd ops
e alis,
abo ion
and
oe al
dea h;
i
has
also
been
associa ed
wi h
asculi is,
pe iphe al
neu opa hy,
myoca di is,
ulminan
li e
ailu e
and
Nezelo
synd ome.8In
kidney
ansplan
pa ien s,
he
main
sign
is
he
p esence
o
acu e
o
ch onic
aplas ic
anaemia.1
He e
we
p esen
a
sho
e iew
accompanied
by
a
case
epo
o
a
kidney
ansplan
pa ien
who
had
anaemia
e ac-
o y
o
e y h opoiesis-s imula ing
agen s
gi en
du ing
he
fi s
ew
mon hs
a e
ansplan a ion.
Fe e
and
gene al
malaise
subsequen ly
appea ed,
and
bo h
he
se ological
and
poly-
me ase
chain
eac ion
(PCR)
es s
o
pa o i us
B19
we e
nega i e.
Case
epo
We
p esen
he
case
o
a
65-yea -old
man
wi h
a
his o y
o
hype ension
due
o
p ima y
hype aldos e onism
and
ch onic
kidney
disease
since
1999,
wi h
neph o ic- ange
p o einu ia
208
n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
due
o
ch onic
glome uloneph i is
(no
kidney
biopsy).
He
was
on
haemodialysis
since
May
2012
un il
30/09/2014,
when
a
cada e ic
kidney
ansplan
wi h
6
incompa ibili ies
was
pe -
o med.
The
dono
biopsy,
wi h
41
glome uli,
showed
ha
7.3%
we e
scle o ic
glome uli,
sligh
hyaline
hickening,
less
han
25%
ubula
a ophy
and
less
han
5%
in e s i ial
fib o-
sis.
Induc ion
immunosupp essi e
ea men
was
gi en
wi h
basiliximab,
ac olimus,
mycophenola e
mo e il
(MMF)
and
s e oids.
In
he
immedia e
pos - ansplan
pe iod,
he
pa ien
had
e ec i e
diu esis
wi h
no
need
o
dialysis.
In
e ms
o
complica ions,
he
de eloped
pos - ansplan
diabe es
melli us
and
haema oma
om
he
su gical
bed
wi h
de el-
opmen
o
anaemia
equi ing
ans usion
o
5
packed
ed
blood
cells.
A
discha ge,
he
ollowing
alues
we e
obse ed:
plasma
c ea inine
(pC ):
1.56
mg/dl;
haemoglobin
(Hb):
8.2
g/dl;
haema oc i :
25.5%;
leukocy es:
11,300/␮l;
pla ele s:
291,000/␮l.
His
immunosupp essi e
ea men
consis ed
o
p ednisone
25
mg/day,
ac olimus
5.5
mg/day
and
MMF
2
g/day.
He
was
also
p esc ibed
alganciclo i
and
ime hop im-sul ame hoxazole
as
p ophylaxis.
The
pa ien
p og essed
wi hou
symp oms,
wi h
a
educ ion
in
pC
o
1.2
mg/dl
in
he
fi s
15
days
a e
he
ansplan .
His
Hb
was
a ound
8–9
g/dl,
wi h
a
p og essi e
inc ease
in
e y h opoie in
equi emen s
and
fluc ua ing
lymphopenia,
bu
wi h
no
o he
haema ological
abno mali ies.
Due
o
p o einu ia
o
up
o
1.2
g/day,
wi h
no
impai men
in
enal
unc ion,
a
g a
biopsy
was
pe o med,
his
was
fi y
six
days
a e
he
ansplan
(No /2014),.
The
findings
we e
compa ible
wi h
mild
ubula
oxici y
caused
by
an ical-
cineu inics,
segmen al
scle osis
o
one
glome ulus,
in e s i ial
fib osis
wi h
mild
ubula
a ophy
wi hou
inflamma ion,
as
well
as
he
p esence
o
isola ed
lymphocy es
in
he
a e ial
in ima.
Immunofluo escence
e ealed
mild-mode a e
IgM
and
C3
posi i i y
and
he
C4d
s aining
was
nega i e.
The
pa ien
was
asymp oma ic
wi hou
impai men
o
enal
unc ion
(pC :
1–1.2
mg/dl),
wi h
op imal
immunosupp ession
le els,
0%
an i-HLA
class
I
and
II
an ibodies,
wi h
no
changes
on
he
ul asound
and
nega i e
i ological
es s
(CMV/BK).
I
was
decided
o
main ain
close
moni o ing,
and
a
p og essi e
educ ion
in
u ine
p o ein
was
obse ed.
Six y
ou
days
a e
he
ansplan
(Decembe
2014),
he
pa ien
had
hype he mia,
no
ocal
defici
and
a
poo
gene al
condi ion,
wi h
as henia,
hypo exia,weigh
loss,
wi h
a
educ-
ion
o
haemoglobin
o
7.1
g/dl
and
a
haema oc i
o
20.6%,
o
which
he
was
hospi alised.
The
addi ional
es s
showed
no
leukopenia
o
h ombocy openia;
no mal
p ocalci onin
le -
els
(0.15
ng/ml)
and
ele a ed
LDH
(321–397
U/l)
and
C- eac i e
p o ein
(7.17
mg/l);
o al
p o eins:
5.7
g/dl;
ele a ed
o al
bili u-
bin
(1.62
mg/dl)
wi h
indi ec
bili ubin
o
0.98
mg/dl;
ele a ed
e i in
(1528.60
ng/ml);
Na
130
mEq/l,
Mg
1.02
mg/dl
and
K
3.4
mEq/l,
in
he
con ex
o
his
p ima y
hype aldos e onism.
As
a
as
enal
unc ion,
plasma
c ea inine
did
no
exceed
1.05
mg/dl.
Du ing
his
fi s
admission,
he
comple e
se ology
o
he
ollowing
pa hogens
was
nega i e:
EBV,
CMV,
he pes i us,
hepa o opic
i us,
ubella,
a icella-zos e ,
pa o i us
B19,
Mycoplasma
pneumoniae,
Coxiella
bu ne ii,
Ricke sia
yphi,
Ba -
onella
henselae,
Toxoplasma
gondii,
leishmania,
mycobac e ia
and
ungi;
as
well
as
he
blood
PCR
o
pa o i us
B19
and
CMV.
He
had
e e
only
he
fi s
day
o
admission,
and
he ea e
he
pa ien
emained
a eb ile.
He
was
ea ed
wi h
quinolones
and
hi d-gene a ion
cephalospo ins,
which
we e
discon inued
a
discha ge.
No mocy ic,
no moch omic
and
hypo egene a i e
anaemia
wi h
i on
o e load
was
a ibu ed
o
he
blood
ans usions
and
d ug
oxici y
( alganciclo i
and
ime hop im-sul ame hoxazole),
which
was
decided
o
be
discon inued.
A
discha ge,
a
se ology
sugges ed
acu e
Q
e e
wi h
pos-
i i e
IgM
an ibodies
on
he
indi ec
immunofluo escence
(IIF)
es
o
Coxiella
bu ne ii,
o
which
ea men
wi h
doxycycline
was
s a ed
o
10
days.
As
he
e e
and
anaemia
las ed
4
mon hs
a e
he
ansplan ,
i
was
decided
o
admi
him
o
hospi al
in
o de
o
ule
ou
ch onic
Q
e e .
Du ing
his
second
admission,
ches
X- ay,
abdominal
ul asound,
abdominal
CT,
PET-CT,
echoca diog am,
gas-
oscopy
and
colonoscopy
we e
no mal.
The
umou al
ma ke s
and
se ology
es s
(including
new
an ibody
assay
[IIF]
o
pa o i us
B19
and
Coxiella
bu ne ii),
as
well
as
cul u es
o
ube culosis
and
i uses
(HSV-1,
HSV-2,
VZV,
CMV,
EBV,
VHH-
6,
VHH-7,
VHH-8
and
en e o i us
RNA),
we e
nega i e
in
all
cases.
The e o e,
he
diagnosis
o
Q
e e
as
he
o igin
o
he
clinical
symp oms
was
uled
ou .
I
was
conside ed
a
alse
pos-
i i e,
as
he e
was
no
se ocon e sion
in
he
second
sample
and
he
e e
pe sis ed
despi e
ea men .
8.48.0
9.08.5
7.78.09.2
11.5
14.3
16.5
5
7.5
10
12.5
15
17.5
20/02
23/02
26/02
28/02
02/03
06/03
09/03
16/03
31/03
05/05
Flebogamma
Fig.
1
–
Changes
in
haemoglobin
alues
(g/dl).
n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
209
0.7
0,7
0.9861
0.4
0.6
1.01.3
1.6
1.4
1.3
0
1
2
3
20/02
23/02
26/02
28/02
02/03
06/03
09/03
16/03
31/03
05/05
Flebogamma
Fig.
2
–
Changes
in
lymphocy e
alues
(10×3/␮l).
2.1
3.6
2.5
3.9
5.1
2.9
6.6
6.3
6.9
6.66.7
0
2.5
5
7.5
18/02
20/02
23/02
26/02
28/02
02/03
06/03
09/03
16/03
31/03
05/05
Flebogamma
Fig.
3
–
Changes
in
leukocy es
(10×3/␮l).
The
pa ien
emained
wi h
e e
wi h
a
ma ked
de e i-
o a ion
in
his
gene al
condi ion,
anaemia
and
lymphopenia
(Figs.
1–3);
i
was
he e o e
decided
o
pe o m
a
bone
ma ow
biopsy
on
Feb ua y/2015,
in
which
hypocellula
bone
ma ow
was
obse ed
wi h
a
ma ked
dec ease
o
he
e y h oid
se ies
and
wi h
gian
e y h oblas s,
wi h
sca ce
eosinophilic
nuclea
inclusions
ha
de e mined
an
inc ease
in
cell
size.
All
o
his
was
sugges i e
o
pa o i us
B19
in ec ion
(Figs.
4
and
5),
which
was
confi med
by
PCR
wi h
a
posi i e
esul
in
he
is-
sue
specimen
o
he
biopsy.
Simul aneously,
i
was
decided
o
pe o m
a
new
blood
PCR
es
o
pa o i us
B19,
which
his
ime
was
posi i e.
A e
he
confi ma ion
o
pa o i us
B19
in ec ion,
he
MMF
was
discon inued,
and
ea men
wi h
a
daily
IV
immunoglob-
ulin
0.5
g/kg/dose
(10
doses)
was
s a ed,
wi h
adequa e
ole ance,
disappea ance
o
e e ,
and
no malisa ion
o
Hb
and
WBC
se ies,
a e
which
he
was
discha ged
in
Ma ch
2015.
A
he
end
o
he
ea men ,
wi h
s able
Hb
and
a eb ile,
i
was
decided
o
esume
he
MMF
a
low
doses.
Howe e ,
6
mon hs
a e
discha ge,
he e
was
a
sligh
impai men
o
enal
unc ion:
pC
up
o
1.55
mg/dl
and
u ine
p o ein
o
2.1
g/24
h
(p e ious
0.6–0.8
g/24
h).
In
conside ing
ha
i
could
be
due
o
he
educed
immunosupp ession
a
second
kid-
ney
biopsy
was
pe o med
in
No embe
2015,
which
e ealed
mild
enal
ubuli is
indica i e
o
bo de line
acu e
ejec ion,
in e s i ial
fib osis,
mode a e
ubula
a ophy,
and
a eas
o
isome ic
acuola ion.
The e
we e
inflamma o y
cells
in
he
a e y
wall
he e
we e,
mos
o
which
we e
in apa ie al
and
a
ew,
subendo helial.
C4d
s aining
and
immunofluo escence
we e
nega i e.
Fig.
4
–
Image
o
bone
ma ow
showing
imma u e
e y h oid
cells
wi h
signs
o
pa o i us
B19
in ec ion
(haema oxylin
and
eosin;
100x).
210
n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
Fig.
5
–
Image
o
bone
ma ow
showing
p oe y h oblas
wi h
nuclea
i al
inclusion
cha ac e is ic
o
pa o i us
B19
in ec ion
(haema oxylin
and
eosin;
400x).
The
pa o i us
i al
load
was
s abilised,
so
he
immuno-
supp ession
was
op imised
by
inc easing
he
MMF
dose
om
500
o
750
mg/24
h
and
wi h
a
ac olimus
dose
able
o
main ain
le els
a ound
7–8
ng/dl,
a e
which
he e
was
a
educ ion
in
u ine
p o ein
and
a
s abilisa ion
o
enal
unc ion,
wi h
plasma
C
o
1.48–1.55
mg/dl.
The
possibili y
o
adminis e ing
an i-
ejec ion
he apy
was
no
conside ed
since
i
could
lead
o
an
inc ease
in
he
eplica ion
o
pa o i us
B19.9
A
yea
a e
he
end
o
ea men ,
he
pa ien
emained
a eb ile,
wi h
inc eased
appe i e
and
weigh
gain.
Wi h
ega d
o
he
lab
esul s,
he
pa ien
had
Hb
le els
o
15.2
g/dl,
wi h
no
need
o
e y h opoie in,
s able
enal
unc ion,
and
wi h
u ine
p o ein
o
less
han
1
g/day
(con olled
wi h
dual
RAAS
blockade).
An i-HLA
class
I
and
II
an ibodies
emained
nega i e.
As
o
plasma
PCR
o
pa o i us
B19,
ou
hospi al’s
labo a-
o y
alida ed
he
quan i a i e
me hod
o
pa o i us
B19.
We
did
no
ha e
he
i al
load
a ailable
a
he
ime
o
diagnosis,
and
he
fi s
quan i a i e
measu emen
was
done
in
Sep em-
be
2015
(app oxima ely
7
mon hs
a e
he
end
o
ea men ),
wi h
<50
copies/ml.
We
in e ed
ha ,
al hough
we
we e
no
able
o
comple ely
elimina e
he
i us,
he
p e- ea men
i al
load
was
p obably
much
la ge ,
gi en
he
clinical
and
lab- alue
imp o emen
obse ed.
The
cu en
i al
load
emains
below
100
copies/ml,
and
clinical
and
lab
pa ame e s
a e
being
mon-
i o ed,
including
pe iodic
PCR
measu emen s
so
a
elapse
can
be
de ec ed.
Discussion
Vi al
in ec ions
p edomina e
in
he
fi s
yea
a e
ansplan ,
when
immunosupp ession
is
a
maximum.10 Pa o i us
in ec-
ion
in
he
ansplan ed
popula ion
is
a e,
and
he
symp oms
may
be
sub le:
anaemia
is
he
main
mani es a ion.11
Ou
pa ien
was
diagnosed
wi h
pa o i us
B19
in ec-
ion
142
days
a e
ansplan a ion.
Anaemia
was
he
ini ial
finding,
which
subsequen ly
wo sened;
he e
was
also
hype -
he mia,
wi h
a
p og essi e
de e io a ion
in
his
gene al
s a e,
as henia,
hypo exia
and
weigh
loss.
The
pa o i us
in ec ion
could
ha e
been
ansmi ed
om
he
dono ,
bu
he e
was
no
se ology
o
i al
load
a ail-
able;
he e o e
we
canno
confi m
ansmission
by
his
ou e.
Ano he
possible
sou ce
o
in ec ion
migh
ha e
been
blood
ans usions
du ing
he
immedia e
pos - ansplan
pe iod.
I
could
be
a
eac i a ion
o
he
i us
in
he
ecep o
caused
by
immunosupp ession,
since
we
did
no
ha e
he
ecipien ’s
p e-
ansplan
se ology.
Conside ing
ha
a
he
ime
o
diagnosis
he e
was
an
epidemic
o
pa o i us
B19
in
he
popula ion,
we
suspec
ha
ou
pa ien
may
ha e
acqui ed
he
in ec ion
du ing
his
epidemiological
ou b eak.
The
eason
o
anaemia
Pa o i us
B19
p oduces
lysis
o
p oe y h oblas
(e y h oid
p ogeni o
cell).8,9 The
in ec ion
o
his
cell
occu s
h ough
he
P
an igen
(globoside
Gb4),
a
ecep o
p esen
in
e y h oid
cells
and
in
o he s,
including
endo helial
cells,
pla ele s,
syn-
o iocy es,
smoo h
muscle
cells
and
oe al
myocy es.
The
i us
need
he
P
an igen
o
bind
o
he
cell
bu
i
is
also
equi ed
he
p esence
o
a
co- ecep o
(␣5␤1)
o
he
in ec ion
o
be
suc-
cess ul
and
o
ac
as
an
in eg in.
E y h oid
cells
con ain
la ge
amoun
o
bo h
molecules
on
hei
su ace.9
Anaemia
may
be
no mocy ic,
se e e
no moch omic,
o
wi h
poo
e iculocy e
esponse
which
does
no
espond
o
blood
ans usions
o
e y h opoiesis-s imula ing
agen s.4
Leukopenia,
h ombocy openia,
and
eac i e
haemophago-
cy ic
synd ome
ha e
also
been
associa ed
o
pa o i us
B19
in ec ion.12
In
ou
pa ien ,
no mocy ic
and
no moch omic
anaemia
was
he
main
mani es a ion
du ing
he
clinical
cou se,
wi h
Hb
alues
as
low
as
o
6.7
g/dl,
wi h
no
esponse
o
e y h opoiesis-s imula ing
agen s,
so
he
had
o
ecei e
se e al
ans usions.
Diagnosis
The
diagnosis
o
pa o i us
B19
in ec ion
is
made
based
on
he
p esence
o
pe sis en
anaemia,
usually
e iculocy openia,
wi h
gian
p oe y h oblas s
wi h
p ominen
eosinophilic
i al
inclusions
in
he
bone
ma ow,
an i-pa o i us
se um
IgM/IgG
and
an i-DNA
posi i e
pa o i us
PCR.13
In
kidney
ansplan
pa ien s,
he
main
sign
is
he
p esence
o
acu e
o
ch onic
aplas ic
anaemia.1In
a
s udy
o
98
pa ien s,
he
main
clinical
mani es a ions
associa ed
wi h
pa o i us
B19
in ec ion
we e
anaemia
wi h
associa ed
dyspnoea
and
as henia
in
98%
o
cases,
and
e e
in
54.9%.14 The
li e a u e
on
he
ela ionship
be ween
ch onic
g a
dys unc ion
and
ac i e
pa o i us
B19
in ec ion
is
no
consis en .
Some
au ho s7,15
confi m
his
ela ionship,
whe eas
o he s
do
no .5
The
se ological
es ing
needed
o
make
he
diagnosis
o
acu e
pa o i us
B19
in ec ion
(IgM)
has
a
sensi i i y
and
specifici y
o
89%
and
99%,
espec i ely,
in
immuno-
compe en
pa ien s.
This
ac
has
no
been
confi med
in
ansplan
pa ien s
because
o
hei
immunosupp ession;
in
hese
pa ien s
he
mos
eliable
me hod
is
pe iphe al
blood
o
bone
ma ow
PCR.
The
choice
o
diagnos ic
es
o
PCR
o
pa o i us
B19
is
impo an
so
alse
nega i es
a e
a oided.
Some
me hods
a e
sensi i e
o
geno ype
1,
bu
no
sui able
o
de ec ing

n
e
o
l
o
g
i
a.
2
0
1
7;3
7(2):206–212
211
geno ypes
2
o
3.
The e o e
i
is
necessa y
o
ha e
me hods
able
o
de ec
he
3
geno ypes.
Inhibi o s
in
blood
samples
may
also
cause
alse
nega-
i es.
Tes ing
o
in e nal
inhibi o s
should
be
included
when
analysing
he
samples,
o
be
ce ain
ha
he
nega i e
esul
is
no
due
o
inhibi o s
in
he
sample.
In
ou
pa ien ,
blood
PCR
o
pa o i us
B19
was
fi s
pos-
i i e
o
4
mon hs
and
19
days
a e
he
ansplan ,
wi h
a
p e ious
nega i e
esul
a
73
days.
The
PCR
me hod
used
in
ou
hospi al
is
he
Ligh Mix®pa o i us
B19
ki ,
which
is
able
o
de ec
all
3
ypes
o
pa o i us.
The
ac
ha
he
fi s
esul
was
nega i e
could
be
jus ified
by
he
possibili y
o
in e mi -
en
i aemia
o
a
low
le el
o
i aemia
a
he
ime
o
he
measu emen .
In
pa ien s
whose
blood
PCR
is
nega i e
bu
in
whom
clin-
ical
suspicion
pe sis s,
as
in
ou
case
he e,
he
defini i e
diagnosis
o
pa o i us
B19
in ec ion
is
pe o med
by
bone
ma ow
aspi a ion.16 I
shows
no
only
a
pu e
ed
cell
apla-
sia
wi h
he
cha ac e is ic
medulla y
“shu down”
in
he
gian
p oe y h oblas
phase,
bu
also,
h ough
molecula
biology
echniques,
he
i us
in
he
ma ow.3
T ea men
The e
a e
cu en ly
no
an i i al
d ugs
ha
a e
e ec i e
agains
pa o i us
B19.
In
anaemia
associa ed
wi h
pa o i us
B19
in ec ion,
di e en
he apeu ic
op ions
can
be
consid-
e ed:
dec easing
immunosupp ession
( educ ion/wi hd awal
o
d ugs),
changing
he
immunosupp essan
(subs i u ing
ac olimus
o
cyclospo in
–
some
au ho s
ha e
desc ibed
he
de ec i e
clea ance
o
he
i us
in
pa ien s
ea ed
wi h
ac olimus17 o ,
in
o de
o
p o ide
i us-neu alising
an ibodies,18 adminis e ing
IVIG
a
doses
o
0.4–0.5
g/kg,
om
2
o
10
days13 wi h
a
cumula i e
dose
ha
usually
anges
be ween
2
and
5
g/kg).3Anaemia
is
co ec ed
in
mo e
han
90%
o
cases
wi h
only
one
cou se
o
ea men ,
bu
he
isk
o
elapse
anges
om
23%
o
33%.19
Ou
pa ien
was
ea ed
by
a
change
in
immunosupp es-
sion,
empo a ily
suspending
MMF
oge he
wi h
in a enous
immunoglobulin
(IVIg;
Flebogamma)
daily
o
10
days,
wi h
a
good
clinical
and
lab- alue
ou come,
helping
Hb,
lymphocy e
and
leucocy e
alues
o
eco e
g adually,
and
discon inuing
e y h opoie in
(EPO)
(Figs.
1–3).
Al hough
ad e se
eac ions
o
IVIg20 ha e
been
desc ibed,
ou
pa ien
did
no
ha e
any
o
hese
diso de s,
and
ole a ed
he
d ug
e y
well.
Al hough
he
had
a
good
ini ial
he apeu ic
esponse,
i
is
ecommended
o
closely
moni o
pa ien s
whe e
elapse
and
eappea ance
o
he
anaemia
is
possible;
his
would
equi e
hem
o
be
ea ed
wi h
a
new
immunoglobulin
cycle
e e y
3
mon hs
o
p e en
hem.21
The
possibili y
o
ea ing
hese
pa ien s
wi h
mTOR
inhibi o s
could
be
a
p omising
op ion,
bu
he e
a e
no
cu -
en
publica ions
ha
suppo
hei
use.
In
ou
case,
we
did
no
use
i
due
o
he
pos - ansplan
p o einu ia
obse ed,
which
eached
2
g/24
h.
We
did
no
know
he
specific
diagnosis
o
kidney
disease
ha
led
o
haemodialysis,
so
he
possibili y
o
ocal
segmen al
glome uloscle osis
could
no
be
uled
ou .
In
addi ion,
he
his ological
epo
on
he
fi s
g a
biopsy
e eals
he
p esence
o
a
glome ulus
wi h
segmen al
scle o-
sis
and
mild-mode a e
IgM
and
C3
posi i i y
in
7
glome uli.
This
was
a
eason
o
no
using
mTOR
inhibi o s,
since
ocal
segmen al
glome uloscle osis
associa ed
wi h
mTOR
use
has
been
desc ibed
in
ansplan
pa ien s.
The
impac
o
his
in ec ion
on
he
pa ien ’s
su i al
o
long- e m
mo bidi y
is
no
known.22 No
specific
s a egies
ha e
p o ed
use ul
in
p e en ing
pa o i us
B19
in ec ion.20
The
ela i ely
low
incidence
o
his
in ec ion
and
he
ad e se
e ec s
o
he
he apeu ic
measu es
make
dono / ecipien
sc eening
o
his
i us
non- iable,
and
he
de elopmen
o
accines
o
pa o i us
B19
is
s ill
unde
in es iga ion.20
Conclusion
He e
i
is
desc ibed
a
kidney
ansplan
pa ien
wi h
anaemia
e ac o y
o
EPO
and
subsequen
hype he mia,
wi h
he
diagnosis
o
pa o i us
B19
in ec ion.
Due
o
he
pa ien ’s
immunosupp ession,
he
se ological
an i-pa o i us
IgM/IgG
es s
pe o med
we e
always
nega i e.
Suspec ed
acu e
Q
e e
in ec ion
delayed
an
accu a e
diagnosis,
bu
gi en
ha
he e
was
no
clinical
imp o emen
wi h
he
ea men
and
no
se o-
con e sion
occu ed,
he
diagnosis
o
Q
e e
in ec ion
was
uled
ou .
Then
bone
ma ow
aspi a ion
was
pe o med
ha
e ealed
pa o i us
B19
in ec ion,
so
he
diagnosis
was
finally
made
since
he
fi s
blood
PCR
did
no
show
posi i e
esul s.
Ou
pa ien
was
s udied
ho oughly,
and
cance
and
o he
in ec ions
we e
also
uled
ou ;
he
symp oms
disappea ed
a e
adjus ing
he
immunosupp essi e
ea men
and
s a -
ing
IV
Ig.
Conflic s
o
in e es
The
au ho s
decla e
ha
hey
ha e
no
po en ial
conflic s
o
in e es
ela ed
o
he
con en
o
his
manusc ip .
e
e
e
n
c
e
s
1.
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