Case report/Kazuistyka
Visceral varicella-zoster virus (VZV) infection as an underestimated differential diagnosis of acute
abdomen in a patient after allogeneic hematopoietic stem cell transplantation
Pó łpasiec trzewny u pacjenta po allogenicznym przeszczepie komórek hematopoetycznych szpiku – nieuwzgl ędniana przyczyna w diagnostyce ró żnicowej ostrego brzucha
Julia Rado ń-Proskura
1, Ninela Irga-Jaworska
1, Anna Malinowska
1, Jan Maciej Zaucha
2,*
1DepartmentofPediatrics, HematologyandOncology,MedicalUniversityofGdańsk,Head:Prof.dr hab.n.med.
ElżbietaAdamkiewicz-Drożyńska,Poland
2Department of Oncological Propedeutics, Medical University of Gdańsk, Head: Prof. dr hab. n. med. Janusz Kruszewski,Poland
article info
Articlehistory:
Received:24.08.2016 Accepted:20.02.2017 Availableonline:15.03.2017
Keywords:
Hematopoieticstemcell transplantation
Visceralvaricella-zostervirus
Cholecystits
Acuteabdomen
Graft-versus-hostdisease
Acyclovirprophylaxis
abstract
Wereport acaseof18-year-oldmale patientwho5.5monthsafterallogeneichemato- poieticstemcelltransplant(HSCT)developedsevereabdominalpainnotrespondingto highdoseofopioids.Thepainwasaccompaniedbygraduallyincreasingactivityofliver enzymesandbilirubinconcentration.ThepatienthadahistoryofacuteGVHDandwas onsteroidtaper.Importantly,hewasalsotemporarilyoffstandardacyclovirprophylaxis.
Provisionaldiagnosisofacutecholecystitiswasmade,however,cholecystectomydidnot improvepatient'scondition.Clinicalpictureofsevereabdominalpainwithoutclearsur- gicalcause, resistanttohighdosesofopiateswithincreasingactivityofliverenzymes was highly suspicious of visceral varicella zoster virus (VZV) reactivation. Immediate introduction of intravenous acyclovir led to full recovery and complete resolution of abdominal pain.We concludethat reactivation oflatent VZV with absent or delayed occurrenceofcharacteristicskinvesiclesmaystill poseadiagnosticchallengeresulting indelayoftheproperdiagnosisandstartoflifesavingantiviraltreatment.Severeintrac- tablepaininHSCTrecipientswithincreasingactivityofliverenzymesshouldevokehigh
*Correspondingauthorat:MedicalUniversityofGdańsk,DepartmentofOncologicalPropaedeutics,PowstaniaStyczniowego1,81-519 Gdynia,Poland.Tel.:+48587260438.
E-mailaddress:jzaucha@gumed.edu.pl(J.M.Zaucha).
ContentslistsavailableatScienceDirect
Acta Haematologica Polonica
journal homepage:www.elsevier.com/locate/achaem
http://dx.doi.org/10.1016/j.achaem.2017.02.001
0001-5814/©2017PolskieTowarzystwoHematologówiTransfuzjologów,InstytutHematologiiiTransfuzjologii.PublishedbyElsevierSp.
zo.o.Allrightsreserved.
Introduction
Primary varicella-zoster virus (VZV) infection causes vari- cella(chickenpox).VZVremainslatentindorsalrootganglia after recovery from acute illness. Zoster also known as shingles results from the reactivation of dormant VZV, which in immunocompetent individuals commonly begins with classical skin manifestation localized within a dermatomal regionwith potential subsequent cutaneous spread.VZVreactivationmightbepromotedbyaging,stress and prolonged, deep immunosuppression that occurs in hematopoietic stem cell transplant (HSCT) recipients [1].
Amongthesepatientsseveral specificfactorsfacilitate VZV reactivation such as total body irradiation (TBI) in the pretransplantconditioning [2–5] orpresence of activegraft versus host disease (GVHD) especially requiring treatment withhighdosesofcorticosteroids[3,6–13].
The most severe and life threatening complication of VZV reactivation in HSCT recipients with high morbidity and mortality rates, is an internal organs involvement which mayprecede or occur without anycutaneous erup- tions[2,14, 15].Lackoftypical skinrashwithblistersmay delaytheproperdiagnosisandthusmightbelife threaten- ing.Herewereportacaseof18-year-old malepatient,who 5.5 months after allogeneic HSCT for B-cell acute lympho- blastic leukemia developed visceralVZV reactivation with- outanyprecedingskinlesions.
Case report
An 18-year-old male after unrelated allogeneic HSCT (day +172) with late onset GVHD involving skin and liver was admitted in March 2008 to the Department of Pediatrics, Hematology and Oncology at University Medical Center in Gdansk (not a transplant center) with a sudden 1-day history of severe progressive abdominal pain. The day beforeadmissionpatient underwent regular controlcheck- up andwas dischargedwithout anyremarkable symptoms or complaints. Upon admission, patient was afebrile anic- teric, had normal vital signs and complained of severe crampy pain in the epigastric/right hypochondriac region withapositiveMurphy sign.Thepainwas localized,with- out any radiation, periodically excruciating and no stimuli exacerbatednoralleviatedthepain.Onpalpationtherewas no rigidity or rebound tenderness, vivid peristalsis was audible, stools were normal, no hepatosplenomegaly was noted. Additionally characteristic GVHD skin and mucosa
lesions (stage 1) were present, however, without any skin eruptions. Laboratory testsrevealed mild lymphocytopenia (0.81G/l), with normal neutrophil (4.29G/l) and monocytes (0.21G/l)counts,thrombocytopenia(40G/l)andmildanemia (hemoglobin of 114g/l) with increased activity (200IU/l) of gamma-glutamyltranspeptidase(GGTP;normalranges(NR):
8–61IU/l)andalanineaminotransferase(83IU/l)(ALT,NR:0–
55IU/l). Aspartate aminotransferase (AST), alkaline phos- phatase (ALP), lactate dehydrogenase (LDH) activity were normal. Serum and urine amylase levels, serum bilirubin, creatinine, electrolytes, glucose and clotting screen remainedwithinnormalranges.MildelevationofC-reactive protein (CRP) 7.9mg/l was noted. Early cytomegalovirus (CMV) antigen was absent; serology viral investigations for hepatitis B and C were negative. The results of directly performed abdominalultrasoundand plainfilm wereunre- markableaswellascomputedtomographyoftheabdomen.
Gastroscopy revealed mild mucosal inflammation without ulceration.
The patient was transplanted from matched unrelated donorforrelapsedacuteB-celllymphoblasticleukemia.The patientVZVserostatuswaspositive–varicellaattheageof 4. Conditioning regimen included total body irradiation combined with etoposide, anti-thymocyte globulin with standardmethotrexateandcyclosporineGVHDprophylaxis.
Posttransplant course was complicatedbymild cutaneous GVHD(stage1,day+43)andlatehepatic(stage2,day+133) GVHD that required oral methylprednisolone (1mg/kg/d).
The patient responded to high dose of steroids – gradual decrease of bilirubin concentration and activity of hepatic enzymes was observed that allowed start of standard steroids taper. Standard prophylactic post-transplant oral acyclovir wassuspendedtemporarilyat thattime(approxi- mately6weeksbeforeacuteonsetofabdominalsymptoms) duetosuspectedrenalandhepatictoxicitiesofconcomitant medications.
The clinical picture was unclear therefore conservative palliative therapy with broad-spectrum antibiotics, intrave- nous fluids and intensive pain relief medications (opioids) was initiated.The patient did not improve. Repeated ultra- sound of theabdomen onthe fourthday of hospitalization showedbroadencommonbileductof7–10mmdiameterand hyperechogenic gallstone of 6–7mmdiameterat theborder ofthegallbladderneckandcysticductwithenhancementof intrahepatic bile ducts. Ultrasoundfindings were indicative for calculus cholecystitis. Therefore endoscopic retrograde cholangiopancreatographywasperformedandrevealedmild distension of the cystic duct without visible gallstones.
Subsequent abdominal ultrasound of the abdomen was Słowakluczowe:
przeszczep komórek hematopoe- tycznychszpiku
półpasiectrzewny
zapaleniepęcherzykażółciowego
ostrybrzuch
choroba przeszczep-przeciwko- gospodarzowi
profilaktykaacyklowirem
indexofsuspicionofthepossibledisseminatedVZVandimposestartofempiricaltreat- mentwithhighdoseacyclovir.
©2017PolskieTowarzystwoHematologówiTransfuzjologów,InstytutHematologiii Transfuzjologii.PublishedbyElsevierSp.zo.o.Allrightsreserved.
performedthatshowedbroadencommonbileductof9mm, gallbladderwithirregularthickeningofthewallupto13mm and2gallstonesof9and6.5mmdiameterprobablyincystic orcommonhepaticduct.AtthesametimeCRPincreasedup to102mg/l,GGTP643IU/l,ALP155IU/l,totalbilirubin1.8mg/
dl (direct 1.2mg/dl), ALT 358IU/l, AST 286IU/l, serum and urineamylaselevelsremainedwithinnormalranges. Dueto thedeteriorationofpatientgeneralconditionandincreasing severityof abdominalpainthatrequiredcontinuousopiates infusion,emergencyopencholecystectomywasperformedin suspicion of cholecystitis. At the surgical examination macroscopically acalculous, inflamed gallbladder wasfound with infiltration of hepatoduodenal ligament and dilatation ofcysticductupto8mmwithout gallstones.Histopatologi- cal examination was consistent with cholecystitis chronica activafibrosa;noviralinclusionswerefound.
Thefollowingdayaftersurgery –8daysafteradmission, skin rashappeared at the trunkand epigastric regionwith gradualgeneralizedspreadover theupperpartofthebody.
Consultedby telephone primary pediatrictransplant center suggested flare of GVHD and recommended to increase methyloprednisolonedoseupto2mg/kg/d.Sincetheclinical picturewasnot completelyconsistentwith GVHDexacerba- tion(intractable,excruciatingwithfastonsetabdominalpain without any other concomitant GVHD symptoms is not acharacteristicfeatureat thestartof GVHDflare)asecond opinionwasaskedfromalocaladulttransplantspecialistfor whomthesequelofclinicalsymptomswasrathercharacter- istic for visceral VZV reactivation than GVHD flare. Hence, immediateintravenousacyclovirtherapywasadded:500mg/
m2every8halongwithhumanvaricella-zosterimmunoglo- bulin administration. Next day after the start of antiviral therapy typical herpetic cutaneous vesicles appeared that indirectlyconfirmedVZVreactivationwithprecedingvisceral involvement. Before acyclovir treatment hepatic enzymes reached the highest activity: GGTP 2184IU/l, ALT 686IU/l, AST 670IU/l, while bilirubin level increased to 5.2mg/dl;
serum and urine amylase levels remained within normal ranges.Overthenextdaysof acyclovirtreatmentactivityof hepatic enzymes started to decline. However, the patient developed bilateral pneumonia with hypoxemia that was probably VZV related. Early CMV antigen was repeatedly absent although PCR testing for CMV was not available at our center at that time. In addition the patient was on continuous trimethoprim/sulfamethoxazole prophylaxis therefore P. Jiroveci pneumonia was less likely. Fortunately within four next days of acyclovir treatment and after the patient's general condition improved, hypoxemia and abdominalpain resolved,skin lesionsstarted toheal. After morethantwoweekspatientwasswitchedtooralacyclovir and continued it without VZV relapse for the next twelve months. The patient is alive and in good condition, off immunosuppressionatthetimeofmanuscriptpreparation.
Discussion
Before introduction of routine antiviral prophylaxis post HSCT, VZVreinfectionoccurred inalmost50% of seroposi- tive adult recipients[7, 16, 17]. Similarly, the incidence of
herpes zoster in VZV seropositive children following allo- and auto-HSCT was reported within the range of 23–67%
[18–23]. In the era of posttransplant antiviral prophylaxis, VZV reactivation still occurs although at the significantly lowerrates between2.6%and 30%inthefirst yearand 5%
thereafter; VZV visceral reactivation without skin involve- mentinHSCTrecipientsisevenlesscommon[10,24,25].
VZV reactivation can present as localized zoster (shin- gles), or may cause end organ disease such as hepatic failure thatmightbefulminantand fatal[26],pneumonitis [27, 28]and pancreatitis [29, 30]. It may alsocause gastric ulcers [31], intestinenecrosis[32],paralytic ileus–Olgivie's syndrome[33], ulcerativeoesophagitis,gastritis andduode- nitis [34], acute glomerulonephritis [11, 12], disseminated intravascular coagulation [12, 26], urinary retention from sacralnervesVZV[35],meningoencephalitis[28,36,37].VZV reactivation maystartwithvisceralpresentation, asinour casewithoutprecedingcharacteristicvesicularskinchanges whichcausesconsiderablediagnosticdifficulties[3,6,12,15, 20,26,30,38–41].Inimmunocompromisedpatientsitcanbe fulminantandfatalandtheproperdiagnosismightbemade postmortem[6,12,26,38–41].
Theclinicalpictureof visceralVZVreactivationisrather characteristic. It usually presents as gradually but shortly developing severe abdominally localized pain in the upper right hypochondriac region indicating a need for surgical intervention and requiringopioids for treatment. Thepain ismainlyofneuropathicnatureduetoVZV-neuritis.There- fore may be responsive toantineuropathic agents but less likely to opioid therapy. If response to antineuropathic treatment isobserved it might behelpfuldiagnostically as suggestedbysomereports[34,38,40,42,43].
Other less specificsymptoms such as vomiting,nausea and diarrhea oftenaccompany abdominaltenderness[3,6, 27, 39].Inagroupof 600immunocompromisedchildren,31 developed varicella and almost 50% (15/31) of them had visceral involvement (hepatitis, pneumonitis), 11/15 had severe abdominal pain requiring opioids [44]. Our patient also developedbilateral pneumonia that was likelycaused by VZV spread. Skin lesions may never appear or appear delayed.Thedelay from thefirst visceralsymptomstothe vesicular rashoccurrencemaytake1–10daysinabout50%
ofpatients[6,14,28–30,34,39].Inourpatientittook8days.
Spanishauthorsconcludetheirreportof4casesofdissemi- nated VZV that an abdominal severe pain of unknown origin in HSCT recipients should always be regarded as apossibleprodromalphaseofadisseminatedVZVinfection [39].
In additiontothepainthe secondcharacteristic feature of visceral VZV reactivation is increasing activity of liver enzymes: transaminases (ALT, AST) and GGTP that is accompanied by gradual rise in concentration of bilirubin.
Other laboratory findings include increase of pancreatic enzymes activity.In our case the laboratory abnormalities inliverenzymes,althoughmild,concernedinitiallyALTand GGTP and later also AST and ALP activity. Pancreatic enzymesinourpatientremainedwithinnormalranges.
According toDokiet al. [6] visceralVZVinfection could beestablished through histologicalexamination of internal organ or viral culture made from it. At present, definite
diagnosis of visceral VZV reactivation in HSCT recipients couldbemadeusing PCRtodetectVZV DNAinperipheral blood[15, 38,45].Unfortunately, atthe timeofhospitaliza- tion of ourpatient it was notavailable at ourcenter (year 2008).
DifficultiesinaproperdiagnosisofvisceralVZVreactiva- tion without skin lesions may, as in our case, lead to unnecessary surgical interventions [29, 38, 40, 46]. In the absenceof cutaneous manifestations, occasionally,laparot- omy may help to establish correct diagnosis by revealing hemorrhagic spots on the internal organs [32, 38] or viral herpesinclusionsatmicroscopicassessmentoftheaffected tissues[40]. Unfortunatelyin ourpatient,the histopatholo- gical examination of inflamed gallbladder did not find pathognomonicviralinclusions.
In our patient cholecystitis was an initial provisional diagnosis.Thereare fewsimilar reportsofHSCT recipients with such provisional diagnosis who underwent surgical interventionand werefinally diagnosed with visceral VZV [14, 26, 27, 40]. Severe abdominalpain with unsatisfactory responseto opioids was a dominant clinical featurein all cases.Acute cholecystitis among adult HSCT recipientsup to 100 days after transplantation, despite the etiology is arareevent–ithasbeenreportedinabout1–5%ofpatients [47,48].Interestingly,cholelithiasiswasrecognized through ultrasound examination in8.5% (20) of 235 pediatricHSCT patients,inwhichthreehad symptomsofacutecholecysti- tis[49].Davidet al.[27]inthe groupof10 HSCTrecipients with visceral VZV reported 6 patients in whom abdomen ultrasound disclosed biliary sludge inaround 70%, solitary gallstone in 20% and 20% had biliary tract dilatation, no surgicalinterventions wereundertaken. Additionally, com- putedtomography of theabdomen wasdone in6of these 10 patients which results wereirrelevant as it was in our case.
Difficultiesinthediagnosticsledalsotothesuspicionof hepatic GVHD exacerbation inour patient.Theincrease in activityof liverenzymes andriseof bilirubinconcentration could be consistent with this diagnosis, however, severe acutepainthatoccurredfromtheverybeginningrathernot.
The decision to increase the dose of methyloprednisolone could have fatal outcome in a patient with active VZV replication,asitisemphasizedbyotherauthors[27,50].
Themost important factor contributingto the reactiva- tion of VZV in our case was discontinuation of acyclovir
prophylaxis at the time of the diagnosis of hepatic GVHD (day +133 post HSCT). This emphasizes the importance of current guidelines thatrecommend acyclovir (orvalacyclo- vir) prophylaxis for the period of 1year or evenlonger in thepresenceofimmunosuppressive therapyandGVHD[10, 24, 51, 52]. Still, despite oral acyclovir prophylaxis, in a recent 2-year multicenter nationwide study within all recordedviralinfectionsinallo-HSCTpediatricpatientsVZV stands for 2.6% [25]. The reactivation of VZV most com- monly occurs 3–12 months after transplantation, but may reactivate considerablylaterwhich hasto bekeptinmind especiallywhenacyclovirprophylaxisisstopped[2].
VZV IgG statusdocumentationbefore transplantationis recommended for all HSCT recipients, since recommenda- tion on the length of acyclovir treatment post transplant dependsontheVZVserostatusoftherecipient(TableI)[10, 24]. VZV seronegative patients are at high riskfor serious complications resultingfrom primaryinfectionaswell,and thus exposure should be prevented if at all possible.
Althoughafter bonemarrowtransplantationVZVinfections are commonly reactivation of latent virus, primary infec- tions occur as well and there have been reports of newly acquired varicella infections in VZV seropositive patients [53,54].Thereforeeliminatingorlimitingtheexposureofall HSCT recipientsto varicella is recommended. Forinstance any child without a history of chickenpox who willbe in direct contact with HSCT recipients should be vaccinated againstVZV.Ifitdevelopsvaricellainfection(chickenpox),it isrecommendedtotreatthechildwithantiviralstoreduce the period of contagion and the severity of potential exposure tothe HSCTpatient. Thelessonfrom ourcaseis thateventemporarysuspensionofacyclovirmayhavefatal consequences for the patientand careful adherence tothe anti-infective prophylaxis guidelines post HSCT should be kept.Itisalsonecessarytocontinuouslyreevaluateindica- tions for anti-infective prophylaxis in HSCT recipients and reintroduce beyond recommended time if needed in selectedcases.
In summary,HSCT recipientswithundeterminedsevere abdominal pain posesignificant diagnosticand therapeutic challenge. Visceral VZV must be included as possible diagnosis, irrespective of acyclovir prophylaxis. Abdominal painwithoutclearsurgicalcause,resistanttohighdosesof opioids together with increasing activity of liver enzymes should alert physicians taking care of HSCT recipients of
TableI–VZVprophylaxisdependsontheVZVserostatusofHSCTrecipient
VZVrecipientserostatus Startofprophylaxis Discontinuationofprophylaxis Allogeneicrecipients
Positive,notvaccineinduced Startofconditioning Day+365or6monthsafterimmunosuppressionends
Positive,vaccineinduced Startofconditioning Day+100
Negative None N/A
Autologousrecipients
Positive,notvaccineinduced Startofconditioning Day+365
Positive,vaccineinduced Startofconditioning Day+100
Negative None N/A
N/A,notapplicable.
rare but fatal, if not diagnosed on time, visceral VZV reactivation.
Authors’ contributions/Wkład autorów
Accordingtoorder.
Conflict of interest/Konflikt interesu
Nonedeclared.
Financial support/Finansowanie
Nonedeclared.
Ethics/Etyka
Theworkdescribedinthis articlehavebeencarriedout in accordance with The Code of Ethics of the World Medical Association(Declaration of Helsinki)for experimentsinvol- ving humans; EU Directive 2010/63/EU for animal experi- ments;UniformRequirementsformanuscriptssubmittedto Biomedicaljournals.
references/pi smiennictwo
[1] HeiningerU,SewardJF.Varicella.Lancet2006;368:1365–
1376.
[2] BermanJN,WangM,BerryW,NeubergDS,GuinanEC.
Herpeszosterinfectioninthepost-hematopoieticstemcell transplantpediatricpopulationmaybeprecededby transaminitis:aninstitutionalexperience.BoneMarrow Transplant2006;37:73–80.
[3] LocksleyRM,FlournoyN,SullivanKM,MeyersJD.Infection withvaricella-zostervirusaftermarrowtransplantation.J InfectDis1985;152:1172–1181.
[4] HanCS,MillerW,HaakeR,WeisdorfD.Varicellazoster infectionafterbonemarrowtransplantation:incidence, riskfactorsandcomplications.BoneMarrowTransplant 1994;13:277–283.
[5] ErardV,GuthrieK,VarleyC,etal.One-yearacyclovir prophylaxisforpreventingvaricella-zostervirusdisease afterhematopoieticcelltransplantation:noevidenceof reboundvaricella-zostervirusdiseaseafterdrug discontinuation.Blood2007;110:3071–3077.
[6] DokiN,MiyawakiS,TanakaM,etal.Visceralvaricella zostervirusinfectionafterallogeneicstemcell transplantation.TransplInfectDis2013;15:314–318.
[7] SteerCB,SzerJ,SasadeuszJ,etal.Varicella-zosterinfection afterallogeneicbonemarrowtransplantation:incidence, riskfactorsandpreventionwithlow-doseaciclovirand ganciclovir.BoneMarrowTransplant2000;25:657–664.
[8] HillG,ChauvenetAR,LovatoJ,McLeanTW.Recentsteroid therapyincreasesseverityofvaricellainfectionsinchildren withacutelymphoblasticleukemia.Pediatrics
2005;116:525–529.
[9] DowellSF,BreseeJS.Severevaricellaassociatedwith steroiduse.Pediatrics1993;92:223–228.
[10] StyczynskiJ,ReusserP,EinseleH,etal.Managementof HSV,VZVandEBVinfectionsinpatientswith
hematologicalmalignanciesandafterSCT:guidelinesfrom theSecondEuropeanConferenceonInfectionsin
Leukemia.BoneMarrowTransplant2009;43:757–770.
[11] OsI,StrömEH,StenehjemA,etal.Varicellainfectionina renaltransplantrecipientassociatedwithabdominalpain, hepatitis,andglomerulonephritis.ScandJUrolNephrol 2001;35:330–333.
[12] GrantRM,WeitzmanSS,ShermanCh.G..etal.Fulminant disseminatedvaricellazostervirusinfectionwithoutskin involvement.JClinVirol2002;24:7–12.
[13] PishvaianAC,BahrainM,LewisJH.Fatalvaricella-zoster hepatitispresentingwithsevereabdominalpain:acase reportandreviewoftheliterature.DigDisSci2006;51:
1221–1225.
[14] StratmanE.Visceralzosterasthepresentingfeatureof disseminatedherpeszoster.JAmAcadDermatol 2002;46:771–774.
[15] deJongMD,WeelJF,SchuurmanT,Wertheim-vanDillen PM,BoomR.Quantitationofvaricella-zostervirusDNAin wholeblood,plasma,andserumbyPCRand
electrochemiluminescence.JClinMicrobiol2000;38:
2568–2573.
[16] AtkinsonK,MeyersJD,StorbR,PrenticeRL,ThomasED.
Varicella-zostervirusinfectionaftermarrow transplantationforaplasticanemiaorleukemia.
Transplantation1980;29:47–50.
[17] KocY,MillerKB,SchenkeinDP,etal.Varicellazostervirus infectionsfollowingallogeneicbonemarrow
transplantation:frequency,riskfactors,andclinical outcome.BiolBloodMarrowTransplant2000;6:44–49.
[18] KawasakiH,TakayamaJ,OhiraM.Herpeszosterinfection afterbonemarrowtransplantationinchildren.JPediatr 1996;128:353–356.
[19] LeungTF,ChikKW,LiCK,etal.Incidence,riskfactorsand outcomeofvaricella-zostervirusinfectioninchildrenafter haematopoieticstemcelltransplantation.BoneMarrow Transplant2000;25:167–172.
[20] PeritzDC,DuncanC,KurekK,Perez-AtaydeAR,Lehmann LE.Visceralvaricellazostervirus(VZV)afterallogeneic hematopoieticstemcelltransplant(HSCT)inpediatric patientswithchronicgraft-versus-hostdisease(cGVHD).J PediatrHematolOffJAmSocPediatrHematol2008;30:
931–934.
[21] NakayamaH,OkamuraJ,OhgaS,etal.Herpeszosterin childrenwithbonemarrowtransplantation:reportfroma singleinstitution.ActaPaediatrJpn1995;37:302–307.
[22] SauerbreiA,PragerJ,HengstU,ZintlF,WutzlerP.Varicella vaccinationinchildrenafterbonemarrowtransplantation.
BoneMarrowTransplant1997;20:381–383.
[23] WackerP,HartmannO,BenhamouE,SalloumE,LemerleJ.
Varicella-zostervirusinfectionsafterautologousbone marrowtransplantationinchildren.BoneMarrow Transplant1989;4:191–194.
[24] DukkipatiSS,VelezAP,YacoubAT,GreeneJ.Prophylaxis forinfectionsfollowingallogeneichematopoieticstemcell transplantation.InfectDisClinPract(BaltimMd)2015;23:
7–12.
[25] StyczynskiJ,CzyzewskiK,WysockiM,etal.Increasedrisk ofinfectionsandinfection-relatedmortalityinchildren undergoinghaematopoieticstemcelltransplantationin comparisontoconventionalanticancertherapy:a multicentrenationwidestudy.ClinMicrobiolInfect2016;22:
179.e1–179.e10.
[26] RogersSY,IrvingW,HarrisA,RussellNH.Visceralvaricella zosterinfectionafterbonemarrowtransplantationwithout skininvolvementandtheuseofPCRfordiagnosis.Bone MarrowTransplant1995;15:805–807.
[27] DavidDS,TegtmeierBR,O’DonnellMR,PazIB,McCartyTM.
Visceralvaricella-zosterafterbonemarrow
transplantation:reportofacaseseriesandreviewofthe literature.AMJGastroenterol1998;93:810–813.
[28] BalkisMM,GhosnS,ShararaAI,AtwehSF,KanjSS.
Disseminatedvaricellapresentingasacuteabdominalpain ninedaysbeforetheappearanceoftherash.IntJInfectDis 2009;13:93–95.
[29] SchillerGJ,NimerSD,GajewskiJL,GoldeDW.Abdominal presentationofvaricella-zosterinfectioninrecipientsof allogeneicbonemarrowtransplantation.BoneMarrow Transplant1991;7:489–491.
[30] KimSH,HaycoxC.Primarydisseminatedvaricella presentingasanacuteabdomen.PediatrDermatol 1999;16:208–210.
[31] MilliganKL,JainAK,GarrettJS,KnutsenAP.Gastriculcers duetovaricella-zosterreactivation.Pediatrics
2012;130:1377–1381.
[32] SanzMorenoJ,López-RubioM,Calero-GarcíaMA,Ratia- JiménezT,Arranz-CasoA,Martínez-MartínezJ.Acute abdomenandintestinalnecrosisproducedbyvaricella- zostervirusinanimmunocompromisedhost.ClinInfect Dis1996;22:857–858.
[33] NomdedéuJF,NomdedéuJ,MartinoR,etal.Ogilvie's syndromefromdisseminatedvaricella-zosterinfectionand infarctedceliacganglia.JClinGastroenterol1995;20:157–159.
[34]LeenaM,VilleV,Veli-JukkaA.Visceralvaricellazostervirus infectionafterstemcelltransplantation:apossiblecauseof severeabdominalpain.ScandJGastroenterol2006;41:242–244.
[35] SchuchterLM,WingardJR,PiantadosiS,BurnsWH,Santos GW,SaralR.Herpeszosterinfectionafterautologousbone marrowtransplantation.Blood1989;74:1424–1427.
[36] LévêqueN,GalambrunC,NajioullahF,BleyzacN,PagesMP, BertrandY.Twocasesofvaricellazostervirusmeningitis foundinpediatricpatientsafterbonemarrow
transplantationdespitevalaciclovirprophylaxisand withoutskinlesions.JMedVirol2006;78:514–516.
[37] FukunoK,TomonariA,TakahashiS,etal.Varicella-zoster virusencephalitisinapatientundergoingunrelatedcord bloodtransplantationformyelodysplasticsyndrome-overt leukemia.IntJHematol2006;84:79–82.
[38] YagiT,KarasunoT,HasegawaT,etal.Acuteabdomen withoutcutaneoussignsofvaricellazostervirusinfection asalatecomplicationofallogeneicbonemarrow transplantation:importanceofempirictherapywith acyclovir.BoneMarrowTransplant2000;25:1003–1005.
[39] MuñozL,BalmañaJ,MartinoR,SuredaA,RabellaN,Brunet S.Dolorabdominalcomoformadepresentaciónde infecciónvisceralporelvirusvaricelazosterenreceptores detrasplantedeprogenitoreshematopoyéticos.MedClin (Barc)1998;111:19–22.
[40] StemmerSM,KinsmanK,TellschowS,JonesRB.Fatal noncutaneousvisceralinfectionwithvaricella-zostervirus inapatientwithlymphomaafterautologousbonemarrow transplantation.ClinInfectDis1993;16:497–499.
[41] RowlandBP,WaldER,MirroJR,etal.Progressivevaricella presentingwithpainandminimalskininvolvementin childrenwithacutelymphoblasticleukemia.JClinOncol 1995;13:1697–1703.
[42] HylandJM,ButterworthJ.Severeacutevisceralpainfrom varicellazostervirus.AnesthAnalg2003;97(4):1117–1118.
[43] ZawilinskaB.Zosterinimmunodeficiencypatients (Półpasiecupacjentówwstanieimmunosupresji).
Zakażenia2007;1:97–100.
[44] MorganER,SmalleyLA.Varicellainimmunocompromised children.Incidenceofabdominalpainandorgan
involvement.AmJDisChild1983;137:883–885.
[45] RauR,FitzhughCD,BairdK,etal.Triadofsevereabdominal pain,inappropriateantidiuretichormonesecretion,and disseminatedvaricella-zostervirusinfectionpreceding cutaneousmanifestationsafterhematopoieticstemcell transplantation:utilityofPCRforearlyrecognitionand therapy.PediatrInfectDisJ2008;27:265–268.
[46] O’LoughlinCJ,KarnamUS,BarkinJS.Visceralvaricella zosterafterbonemarrowtransplantation:anobscurecause ofan‘acuteabdomen’.DigDisSci2002;47:1962–1964.
[47] BagleySJ,SehgalAR,GillS,etal.Acutecholecystitisisa commoncomplicationafterallogeneicstemcell transplantationandisassociatedwiththeuseoftotal parenteralnutrition.BiolBloodMarrowTransplant 2015;21:768–771.
[48] JardinesLA,O’DonnellMR,JohnsonDL,TerzJJ,FormanSJ.
Acalculouscholecystitisinbonemarrowtransplant patients.Cancer1993;71:354–358.
[49] SaffordSD,SaffordKM,MartinP,RiceH,KurtzbergJ, SkinnerMA.Managementofcholelithiasisinpediatric patientswhoundergobonemarrowtransplantation.
JPediatrSurg2001;36:86–90.
[50] Perez-OteyzaJ,PascualC,Garcia-LaranaJ,OdriozolaJ, RocamoraA,NavarroJL.Abdominalpresentationof varicellazosterinfectionafterbonemarrow transplantation.BoneMarrowTransplant1992;9(3):
217–220.
[51]MeyersJD,WadeJC,SheppDH,NewtonB.Acyclovir treatmentofvaricella-zostervirusinfectioninthe compromisedhost.Transplantation1984;37:571–574.
[52] UllmannAJ,Schmidt-HieberM,BertzH,etal.Infectious diseasesinallogeneichaematopoieticstemcell transplantation:preventionandprophylaxisstrategy guidelines2016.AnnHematol2016;95:1435–1455.
[53] WeinstockDM,BoeckhM,BouladF,etal.Postexposure prophylaxisagainstvaricella-zostervirusinfectionamong recipientsofhematopoieticstemcelltransplant:
unresolvedissues.InfectControlHospEpidemiol 2004;25:603–608.
[54] FeldmanS,CroutJD,AndrewME.Incidenceandnatural historyofchemicallydefinedvaricella-zostervirus hepatitisinchildrenandadolescents.ScandJInfectDis 1997;29:33–36.
