Immunoglobulin-induced aseptic meningitis: A case report

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 © The Au ho (s). 2018 Open Access This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion 4.0 In e na ional License (h p://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed. 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 Re e ences 1. Bha a h V, Ecke K, Kang M, Chin-Yee IH, Hsia CC. Incidence and na u al his o y o in a enous immunoglobulin-induced asep ic meningi is: a e ospec i e e iew a a single e ia y ca e cen e . T ans usion. 2015;55(11): 2597–605. G aça e al. BMC Neu ology (2018) 18:97 Page 2 o 3 2. Cascella C, Nausheen S, Cunha BA. A di e en ial diagnosis o d ug-induced asep ic meningi is. In ec Med. 2008;25:331–4. 3. Mo is G, Ga cia-Monco JC. The challenge o d ug-induced asep ic meningi is. A ch In e n Med. 1999;159(11):1185–94. 4. Mo is G, Ga cia-Monco JC. The challenge o d ug-induced asep ic meningi is e isi ed. JAMA In e n Med. 2014;174(9):1511–2. 5. Chaabane A, Hamzaoui A, Aouam K, Klai R, F edj NB, Bougha as NA, e al. Human in a enous immunoglobulin-induced asep ic meningi is: a case epo . J Clin Pha macol. 2012;52(2):279–81. 6. Ellis RJ, Swenson MR, Bajo ek J. Asep ic meningi is as a complica ion o in a enous immunoglobulin he apy o myas henia g a is. Muscle Ne e. 1994;17(6):683–4. 7. Sekul EA, Cuple EJ, Dalakas MC. Asep ic meningi is associa ed wi h high-dose in a enous immunoglobulin he apy: equency and isk ac o s. Ann In e n Med. 1994;121(4):259–62. 8. Jain RS, Kuma S, Agga wal R, Kookna JC. Acu e asep ic meningi is due o in a enous immunoglobulin he apy in Guillain-Ba e synd ome. Ox Med Case Repo s. 2014;2014(7):132–4. 9. Wada A, Yoshida R, Oda K, Fukuba E, Uchida N, Ki agaki H. Acu e encephalopa hy associa ed wi h in a enous immunoglobulin he apy. AJNR Am J Neu o adiol. 2005;26(9):2311–5. G aça e al. BMC Neu ology (2018) 18:97 Page 3 o 3