CASE REPORT Open Access
Immunoglobulin-induced asep ic
meningi is: a case epo
Luísa G aça
1,2,3*
, Joana Al es
1,2,3
, João Nuak
1,2,3
and An ónio Sa men o
1,2,3
Abs ac
Backg ound: Immunoglobulin associa ed meningi is is a a e disease ha mimics in ec ious meningi is. This is, o
ou knowledge, he i s case o Immunoglobulin-associa ed meningi is desc ibed in a pa ien wi h Sys emic Lupus
E y hema osus and hypogammaglobulinemia seconda y o Ri uximab.
Case p esen a ion: A 46-yea -old emale wi h a pas medical his o y o Sys emic Lupus E y hema osus, p esen ed
wi h meningismus 36 h a e i s in usion o in a enous immunoglobulin. The ce eb ospinal luid analysis showed
neu ophilic pleocy osis and hype p o eino achia. All mic obiological es s we e nega i e. The pa ien eco e ed
ema kably as wi hou sequela a e jus i e days o an ibio ic he apy.
Conclusion: Sys emic Lupus E y hema osus is a well-documen ed isk ac o o asep ic meningi is associa ed wi h
o he d ugs. Possibly, i is also a isk ac o o Immunoglobulin associa ed meningi is. This diagnosis, al hough a e,
should be conside ed in pa ien s ecei ing Immunoglobulin since i is a sel -limi ed condi ion and ea men is suppo i e.
Keywo ds: Asep ic meningi is, Hypogammaglobulinemia, In a enous immunoglobulin, Sys emic lupus e y hema ous
Backg ound
D ug associa ed asep ic meningi is is a a e complica ion
o many d ugs. I usually esembles in ec ious meningi is,
he e o e p esen ing a diagnos ic challenge [1].
Es ablishing a causal ela ionship be ween he use o a
d ug and he onse o symp oms is he hallma k o
diagnosis and i is suppo ed by bo h nega i e es s o
in ec ious causes and quick esolu ion o symp oms
a e d ug discon inua ion [2].
The medicines mos commonly associa ed wi h asep ic
meningi is a e non-s e oidal an i-in lamma o y d ugs
(NSAIDs), an ibio ics, in a enous immunoglobulin
(IVIG) and OKT3 an ibodies [3]. The equency o IVIG
associa ed meningi is a ies widely, om 0 o 11% wi h a
ecen s udy sugges ing an o e all incidence o 0.60% [1].
Al hough Mo is and colleagues epo ed a highe
incidence o d ug associa ed meningi is in pa ien s wi h
Sys emic Lupus E y hema osus (SLE) (29 ou o 194
cases), he culp i d ug was ne e IVIG [3,4]. This is,
o ou knowledge, he i s case o IVIG-associa ed
meningi is desc ibed in a pa ien wi h SLE and
hypogammaglobulinemia seconda y o Ri uximab.
Case p esen a ion
A 46-yea -old emale wi h a pas medical his o y o SLE
and associa ed Sjög en synd ome, usual in e s i ial
pneumonia and mig aine, medica ed wi h p ednisolone
5 mg and hyd oxiclo oquine 400 mg, wi h a ecen ly
wo sened asymp oma ic hypogammaglobulinemia (IgG o
297 mg/dL and IgA < 8 mg/dL) seconda y o i uximab
( aken 4 yea s ea lie ), was p oposed o eplacemen
he apy wi h IVIG. She had no p e ious his o y o he apy
wi h IVIG. She was s a ed on IVIG 10%, 2 g/Kg o e 5
consecu i e days. She was gi en wo doses o IVIG in wo
consecu i e days wi hou any immedia e eac ion.
The pa ien p esen ed o he eme gency depa men ,
36 h a e he i s in usion, wi h headache, pho ophobia,
nausea, omi ing and e e . On examina ion, she was
p os a ed and had neck s i ness wi hou ocal neu ological
signs. Blood wo k showed low in lamma o y pa ame e s.
The b ain CT was no mal. The CSF analysis showed
neu ophilic pleocy osis wi h 1547 cells/mm
3
(87.5%
neu ophils), hype p o eino achia (15.3 mg/dL) and mildly
educed glucose (50 mg/dL in CSF and 113 mg/dL in
* Co espondence: [email p o ec ed]
1
In ec ious Diseases Depa men , Cen o Hospi ala de São João, Alameda
P o . He nâni Mon ei o, 4202-451 Po o, Po ugal
2
Ins i u o Nacional de Engenha ia Biomédica (INEB), Ins i u o de Ino ação e
In es igação em Saúde (I3S), G upo de I&D em Ne ologia e Doenças
In ecciosas, Po o, Po ugal
Full lis o au ho in o ma ion is a ailable a he end o he a icle
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G aça e al. BMC Neu ology (2018) 18:97
h ps://doi.o g/10.1186/s12883-018-1102-8
plasma). The pa ien was admi ed o he In ec ious
Diseases Depa men wi h he diagnosis o meningi is
and gi en ce iaxone 2 g e e y 12 h and ampicillin
2ge e y4h.
Blood cul u es we e nega i e as well as G am s ain,
India ink smea , CSF cul u e o bac e ia and ungus and
Nucleic Acid Ampli ica ion Tes (NAAT) o Lis e ia
monocy ogenes in he CSF. The u ina y pneumococcal
an igen was also nega i e.
The pa ien was asymp oma ic a e 2 days o he apy.
The lumba punc u e was epea ed a e 5 days o
he apy. The CSF analysis showed 0 cells, no mal
glucose (67 mg/dL in CSF and 91 mg/dL in plasma) and
no mal p o eins (3.5 mg/dL). Acco dingly, he an ibio ics
we e wi hd awn and he pa ien was discha ged.
D ug-induced asep ic meningi is usually mani es s as
meningismus wi hin 48 h a e d ug exposu e. Typically,
CSF examina ion e eals neu ophilic pleocy osis
(median 147, ange 8–19,000 cells/mm
3
), p o ein
ele a ion (median 1.20, ange 0.04–3.90 g/L) and
no mal le els o glucose (median 61.64 mg/dL, ange
43.45–157.45 mg/dL). Eosinophilic pleocy osis has been
epo ed in some pa ien s. CSF cul u e is necessa ily
nega i e.
In ou case, he diagnosis was based on he p esence o
isk ac o s o IVIG associa ed meningi is (mig aine, SLE,
i s in usion and high dose IVIG), he s ong empo al
ela ionship be ween adminis a ion o IVIG and onse o
symp oms, he ypical CSF cha ac e is ics, he exclusion o
al e na i e causes and he quick imp o emen wi hin a
ew days.
Discussion and conclusions
This sho pape epo s, o ou knowledge, he i s case
o immunoglobulin induced asep ic meningi is, a a e
complica ion o IVIG, in a pa ien wi h SLE and hypo-
gammaglobulinemia seconda y o Ri uximab.
The i s associa ion o asep ic meningi is wi h IVIG
was epo ed in 1988, and mo e han 30 such epo s
ha e ollowed. I has been epo ed in many indica ions
including Idiopa hic Th ombocy openic Pu pu a [5],
Myas henia G a is [6], In lamma o y Demyelina ing
Neu opa hy [7] and Guillain-Ba é synd ome [8], bu
no e e in a pa ien wi h SLE and hypogammaglobuli-
nemia seconda y o Ri uximab.
Pa ien s appea o be a highes isk a e he i s
adminis a ion, especially i ecei ing apid, high-dose
in usion o IVIG [1,7]. A p e ious his o y o mig aine
seems o be an impo an p edisposing condi ion [7].
SLE is a well-documen ed isk ac o o asep ic
meningi is associa ed wi h NSAIDs and o he d ugs [4].
Al hough he cause o his associa ion is unknown, SLE
may, as well, be a isk ac o o IVIG-associa ed asep ic
meningi is. Ne e heless, mo e s udies a e needed o
con i m his hypo hesis.
The pa hophysiology o IVIG-associa ed meningi is is
unclea . The e a e nume ous possible mechanisms,
including lep omeningeal hype sensi i i y eac ion,
complemen di ec meningeal i i a ion igge ed by
IgG, o in e ac ions be ween IgG and meningeal essel
an igens causing in lamma o y cy okine elease [1,5].
The neu ologic symp oms pa allel he concen a ion o
IgG in he CSF [9].
IVIG is a a e bu clinically ele an cause o asep ic
meningi is ha is o en unde ecognized. Unlike in ec ious
meningi is, i is sel -limi ed and ea men is suppo i e.
This case epo highligh s he impo ance o his
diagnosis in o de o a oid unnecessa y p ocedu es and
he apies.
Abb e ia ions
CSF: Ce eb ospinal luid; CT: Compu ed omog aphy; IVIG: In a enous
immunoglobulin; NAAT: Nucleic acid ampli ica ion es ; NSAIDs: Nons e oidal
an i-in lamma o y d ugs; SLE: Sys emic lupus e y hema osus
Acknowledgmen s
We hank D . Rica do Soa es-dos-Reis, MD (Cen o Hospi ala de São João)
o c i ical e iew o his manusc ip o non-in ellec ual con en and
D . Miguel Be na des, MD (Cen o Hospi ala de São João) o help ul discussion
ega ding his pa ien ’s pas heuma ological his o y.
Au ho s’con ibu ions
LG d a ed he manusc ip and e iewed he li e a u e. JA, JN and AS e ised
he manusc ip . All au ho s con ibu ed o ob aining and in e p e ing he
clinical in o ma ion. All au ho s ead and app o ed he inal e sion o he
manusc ip .
E hics app o al and consen o pa icipa e
No applicable.
Consen o publica ion
W i en in o med consen was ob ained om he pa ien o publica ion o
his Case epo . A copy o he w i en consen is a ailable o e iew by he
Edi o o his jou nal.
Compe ing in e es s
The au ho s decla e ha hey ha e no compe ing in e es s.
Publishe ’sNo e
Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in published
maps and ins i u ional a ilia ions.
Au ho de ails
1
In ec ious Diseases Depa men , Cen o Hospi ala de São João, Alameda
P o . He nâni Mon ei o, 4202-451 Po o, Po ugal.
2
Ins i u o Nacional de
Engenha ia Biomédica (INEB), Ins i u o de Ino ação e In es igação em Saúde
(I3S), G upo de I&D em Ne ologia e Doenças In ecciosas, Po o, Po ugal.
3
Depa men o Medicine, Facul y o Medicine, Uni e si y o Po o, Po o,
Po ugal.
Recei ed: 1 Sep embe 2017 Accep ed: 11 July 2018
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