Chronic meningococcemia presenting with recurrent painful rash and poly-arthralgia without fever.

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Case

study

Chronic

meningococcemia

presenting

with

recurrent

painful

rash

and

poly-arthralgia

without

fever

C. Delwaide

a

,

P. De

Leeuw

b

,

A. François

c

,

P. Beckers

c

,

V. Hennaux

c

,

Ph.

Lefèvre

c,d,

*

a_Neurology_Service,_{IFAC-VIVALIA,}₆₉₀₀_Marche_en_Famenne,_Belgium b

InternalMedicineservice,IFAC-VIVALIA,6900MarcheenFamenne,Belgium

c

ClinicalBiologyService,IFAC-VIVALIA,6900MarcheenFamenne,Belgium

d

MicrobiologyandHygieneUnitofPharmacologicalFaculty,UniversitéLibredeBruxelles(ULB),Belgium

ARTICLE INFO

Articlehistory: Received9May2018

Receivedinrevisedform6June2018 Accepted26June2018 Keywords: Neisseriameningitidis Chronicmeningococcemia PCR ABSTRACT

Chronicmeningococcemiaisanuncommondisorder,representingadiagnosticchallenge.Classically,this

pathology wouldbe consideredin youngadults withahistory of episodesoffever, disseminated

cutaneousvasculitisandarthralgia.Exactandrapiddiagnosisisoftenfurtherchallengedbythefactthat

routine microbiological investigations frequently failed to identify incriminated micro-organism,

Neisseriameningitidis.Herewepresentthecaseofayoungmannotpresentingwiththeclassicaltriad.

license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Casereport

A 21year old patient was admitted to our emergency department with recurrent (one or two days) generalized and pruriticskinlesions,duringoneortwodays,withpolymyalgiaand polyarthralgia without fever in the third time for four weeks. Standardbiologicalanalysesperformedafterthesecondepisode showed signiﬁcant inﬂammatory syndrome (CRP: 100mg/L), hyperleukocytosis(WBC:13800/mm3_),_negativity_of_rheumatoid

factorandnegativeviralserology(Treponemapallidum,Chlamydia andMycoplasmapneumoniae,CoxsackieandEchovirus, Adenovi-rus,Parvovirus,Borreliaspp.,BartonellahenselaeandHIV).Inour emergencydepartment,clinicalexaminationrevealeda neurolog-ically conscious and well-oriented patient with generalized papularcutaneouslesionsandanerythematouspharynxwithout fever(36.8C),withoutheadache,photophobiaandneckstiffness. The vital signs showed a cardiac frequency at92/min, a blood pressureat10.5/80mmHgandthesaturationat100%.Pulmonary andcardiacexaminationswerenormal.Theabdomenwassoftand painless.Chestradiographyshowednosystematicfocusorpleural effusion.Bloodanalysisrevealedleukocytosisat18.36103_/mm3

(ReferenceValues–RV4.00–11.0)withrelativepolyneutrophiliaof 88% (RV 45.0–70.0) and a CRP at 243mg/L (RV 0–5). No abnormalities of renal and hepatic functions and coagulation

were found. All requested serologies (Treponema pallidum, ChlamydiaandMycoplasmapneumoniae,CoxsackieandEchovirus, Adenovirus, Parvovirus, Borrelia spp., Bartonella henselae) were negative. A dermatological opinion was requested and a skin biopsywasperformed.Bloodcultureswereperformedeveninthe absenceoffever.

Thepatientwashospitalizedintheinternalmedicine depart-ment.24hafterhisadmission,threepairsofbloodcultures,taken withoutfever,becamepositiveforGramnegativediplococci.APCR wasimmediatelycarriedoutusingtheE-Plex1technique (Gen-mark,California),identifyingtheorganismasN.meningitidis.An intravenous treatment was initiated with Ceftriaxone2gtwice daily. Thepatientwas transferredtotheintensive careunit for observation.Asitiswellknownthatchronicmeningococcemiacan progresstoacutemeningitis,alumbarpuncturewasperformed showing a slightly turbid cerebrospinal ﬂuid (CSF). Analysis revealed numerous leucocytes (284 leukocytes/mm3, 88% of neutrophils, 8%of lymphocytes and 4%of mono-macrophages), aproteinof0.56mg/dLandaglucoseof68mg/dL(serumglucose: 110mg/dL).The Gram staining examination did not show any bacteria. After72h, CSF culturewas still negativebut PCRwas positiveforN.meningitidisserotypeB.Aregressionofskinlesions wasobservedoverthenexttwodays.Fromtheneurologicalpoint ofview,thepatientwasalwayswellconsciousandwelloriented, from the biological point of view, leukocytosis and CRP were decreasing. The patient was transferred to a medical unit. Transesophageal ultrasound and otolaryngology examination concludednormal.Histologicexaminationoftwoadmissionskin biopsy specimen revealed dermal ectatic lymph vessels and

* Correspondingauthorat:ClinicalBiologyService,IFAC-VIVALIA,6900Marche enFamenne,Belgium.

E-mailaddress:philippe.lefevre@vivalia.be(P. Lefèvre). https://doi.org/10.1016/j.idcr.2018.e00416

ContentslistsavailableatScienceDirect

IDCases

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capillaries with perivascular lymphocytic infiltration and some neutrophilgranulocytes.Giventhehistologicalappearancelargely compatiblewithasepticvasculitis,PASandGramstainingwere performed.Nomycelialandbacterialelementswerehighlighted. PCRperformedonpatient’sskinbiopsyparaffinblockconfirmed thepresenceofN.meningitidisandthechronicmeningococcemia diagnosis.Ourpatientdidn’tpresentanydeficiencyoftheclassic and alternativepathwayof hemolyticcomplement activityand lectin pathways (classical pathway of hemolytic complement activity, alternate pathway of hemolytic complement activity, mannose-bindinglectin and properdin). Althoughthe total IgG levelwasslightlylowerthannormal(6.5g/L),IgGsubclasseswere normal.Theceftriaxonetreatmentwascontinuedforatotalof7 days with a favorable evolution. In the absence of consensus regardingthe chronicform,a peroral quinolone(ciprofloxacin 500mgtwicedaily)relaywascontinuedfor7moredays. Discussion

Although chronic meningococcemia is characterized by a classic clinical triad associating prolonged fever, rash and arthralgia[2],ourpatientdidnot presentwithfeverpreceding hisadmission.Theageofourpatientwasinagreementwiththe descriptionmadebyBenoit[2].Thisdiseasecanindeedbefoundat allages,butespeciallyamongadolescentsandyoungadults.The jointsymptomsaffectingourpatientwerealsoconsistentwiththe classicpathologydescription.Thiscaninvolvealljointsexceptthe spine and temporomandibular joint. Our patient classically presentedintermittentsymptomatologybuthisstatusremained good, as described by Benoit [2]. Cutaneous involvement is classicallymaculopapular, non-purpuric and notspeciﬁc.These macularlesionsarefrequentlydescribedinchronic meningococ-cemiaandmayaffectupto86%ofpatients[2,7].Asdescribedby Dupin [4], the lesions result either from septic embolizations (acuteform)orfromimmunecomplexesandC3depositinvascular walls(chronicform).

Search for complement abnormality and immunoglobulin deficiency was performed although chronic meningococcemia occurredmorefrequentlyinimmunocompetentpatients[1,3,5].In ourpatient,thelevelsofclassicandalternativecomplement,as wellaslectinpathwaysand thecomplement-regulatingprotein properdin,werenormal.DespiteaslightlylowtotalIgGlevel,the IgGsubclasseswerenormal,excludingapredispositiontochronic meningococcemiaasdescribedbyAdams[1]andNielsen[6].We hypothesizedthattheN.meningitidisstraincouldhavebehaved with a low virulence profile, allowing to explain the chronic meningococcemia clinical form. Some strains notably show mutationsin thegene lpxL1 generating penta-acylated lipidsA withdecreased affinity for TLR4[3], producingless pro-in flam-matorycytokines favoring an easier escape to innate immune system. To exclude this hypothesis, a genomic and proteomic analysisofthestrainhasbeenconsidered.

ThediagnosiswasmadeonthebasisofN.meningitidispositive bloodcultures(group B).It isnecessarytounderscoreherethe importancetotakeandtorepeatbiologicalsamplesandespecially toobtainbloodculturesevenifthepatientdoesnotpresentfever. IndeedN.meningitidisisafragilebacteriumwhoseculturecanbe rapidlyfalselynegativebyearlierempiricalantibacterial adminis-tration. The PCR technique has been therefore proved highly

precioustoconﬁrmdiagnosisand rapidtreatment implementa-tion. Microbiological research by PCR has the advantage of maintaininggoodsensitivitydespitetheintroductionof antibac-terialtherapyandcanbeperformedondifferentmanysamples [8,9].Inthecaseofourpatient,bacteriologicalanalysesinvolved severalclinicalsamplesincludingCSF,pharynxandskinbiopsies [8,9].Asmentionedbefore,PCRconﬁrmedsecondarymeningeal involvement. Nasopharyngeal carriage has been shown to be negative,although10%ofthepopulationiscolonizedwith24–37% carriersamong15–24yearold[1,11].PCR testingofskinbiopsy specimensshouldbeusedsystematicallyinpatientswithnegative microbiologicalinvestigationforchronicmeningococcemia[10].

Earlydiagnosisofthis typeofmeningococcemiaiscrucialto avoidcomplicationsthatcanbesevere,mainlymeningitisbutalso endocarditis,glomerulonephritis and ocularsymptoms[1]. PCR carried outbyE-plex (Genmark, California)ona positiveblood cultureallowedtorapidlyinitiateanadaptedantibacterialtherapy. Inconclusion,thiscaserecallsthatchronicmeningococcemia mustbeconsideredevenintheabsenceoftheclassicprolonged fevertriad,absenthere,withcutaneousandarticularsigns.This case highlights the importance of blood cultures even in the absenceoffeveraswellastheimportantcontributionoffastPCR techniques usedonblood andskinsamples.In general, treated rapidly by beta-lactate antimicrobials, prognosis is extremely favorable.

Acknowledgments

WethankProfessorVéroniqueFontaineforthecarefulreading andcorrectionsmadetothemanuscript.

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