A unique autopsy case of spontaneous necrotizing soft tissue infection of the chest-wall in healthy adult without major risk factors

(1)

1

Forensic

Pathology

2Q1

A

unique

autopsy

case

of

spontaneous

necrotizing

soft

tissue

infection

of

the

3

chest-wall

in

a

healthy

adult

without

major

risk

factors

4Q2

Fabio

SuadoniConceptualization

a

,

Sara

GioiaWriting

-

original

draft

a

,

5

Beatrice

TiriData

curation

b

,

Antonella

MencacciSupervision

c

,

Simona

VentoInvestigation

d

,

6Q3

Massimo

LanciaWriting

-

review

&

editing

a,

*

7 aLegalMedicine,UniversityofPerugia,Italy 8 bHospitalofTerni,Italy

9 cMedicalMicrobiology,UniversityofPerugia,Italy 10 dMicrobiology,HospitalofPerugia,Italy

ABSTRACT

NSTI(NecrotizingSoftTissueInfection)isaninfectionofanylayerwithinthesofttissuecompartmentthatisrapidly progressiveandoftenfatal.Theauthorsdescribeacaseofa67-year-oldmanwhodevelopedaspontaneousNSTIand diedofsepticshockapproximately36hafterhewasfirstadmittedtotheemergencyroom.Theinfectionstartedfrom thechestasaresultofaminimummusclestrain,intheabsenceofanycutaneouslesionsorimportantriskfactors suchasimmunosuppression.TheinfectionwascausedbyStreptococcuspyogenes.

Thedescribedcasehasmanypeculiaritiesthatmakeitalmostunique. ARTICLE INFO

11 Keywords: 12 NSTI

13 Necrotizingsofttissueinfection 14 Spontaneousinfection 15 Streptococcuspyogenes 16 Autopsy 17 Chest 18 Chest-wall 19 Introduction

20 Theinfectionofthesofttissuecompartmentwithnecroticchangesis

21 called necrotizingsoft tissue infection (NSTI) [1,2]. Inrecent years

22 international massmedia has defined thispathologywith alarming 23 titles such as "microbes eating meat" or "meat devours’ disease"

24 generatingalarminthepopulation.Actually,thisisnotapathologyof

25 recentonset,asevidencedbyHippocrates’sthird bookofEpidemics

26 (IVcenturyBC),reportingthefirstdefinitionofthenecrotizingfasciitis

27 [3].In adults,NSTI ismostdescribed intheextremities, perineum,

28 abdomen,neckandhead[5,6].Inneonatesorinchildreningeneral

29 NSTIismostdescribedinthetrunkasomphalitis[4].Themostcasesof

30 necrotizing infections are polymicrobial; monomicrobial NSTI is

31 common inimmunosuppressedpatients[7]. The infection mayalso

32 occur spontaneously, but this is incredibly rare [8,9]. Causative 33 organismsinNSTIare:Bacteroides,Streptococcus,Enterococcus,

Peptos-34 treptococcus, andStaphylococcusspp., Escherichiacoli,Proteusspp., or

35 otherGramnegativerods,Clostridiumspp.[10]orotheranaerobesand 36 fungi. The pathogenesis is hypothesizedtobe related with reduced

37 immuneresponseandinadequatebloodflowtothefascia,creatingan

38 environmentsuitableforpathogensproliferation[5].

39 For NSTI several risk factors have been described, such as

40 immunodeficiency, advanced age, smoking, diabetes mellitus,

41

obesity,intravenousdruguse,peripheralvasculardisease,chronic

42

renal failure, trauma, recent surgery, burns, dermal abscess,

43

perforated bowel, and insects bites [11,12]. Adverse prognostic

44

factorsincludeadvancedage,femalegender,delayindiagnosisor

45

debridement,extensivetissueinvolvement,degreeoforgansystem

46

dysfunction,andother medicalcomorbidities(suchas bacteremia

47

anddiabetesmellitus).

48

Intheearlystages,thiskindofinfectionishardtobeseparatedfrom

49

othersuperficialinfectionssuchascellulitis,leadingtohighmorbidity

50

andmortality[13,14].

51

Astheinfectionprogresses,systemicsignsoccur,withhighfever,

52

tachycardia,skinblistering,andwounddischarge[1].Rapiddiagnostic

53

procedureincludingCTscan,plainradiographs,MRIand

ultrasonogra-54

phymaybehelpfulforthediagnosisofNSTI[15],butthetissuebiopsy,

55

tissueandbloodculturemayberequiredtoconfirmthediagnosisand

56

isolatethepathogens.

57

BecauseNSTIcanrapidlyleadtodeathinaffectedpatientswhoare

58

otherwise apparently healthy, and because of the rising number of

59

medicolegalcasesthatarerelatedtohealthcare,casesofdeathassociated

60

withNSTIareincreasinglyenteringtherealmofforensicmedicineand

61

pathology.ThedescribedcasepresentssomeparticularaspectsofNSTI

62

that will help toremind forensicpathologists of this disease entity,

63

whethertheyaremanagingcasesrelatedtopotentialmedicalmalpractice

E-mailaddress:massimo.lancia@unipg.it(M.Lancia).

http://doi.org/10.1016/j.fsir.2020.100113

Received18May2020;Receivedinrevisedform28May2020;Accepted28May2020 Availableonlinexxx

ForensicScienceInternational:Reportsxxx(xxxx)xxx–xxx

FSIR1001131–4

ContentslistsavailableatScienceDirect

Forensic

Science

International:

Reports

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64 orsimplyhavetodeterminethecauseofanunexpecteddeathinapatient

65 [16,17].

66 This typeof infectionis rarely described in thegeneral forensic

67 literature,thereforeforensicpathologistsshouldconsider thistypeof

68 infectionwhentheyperformautopsiesinsimilarcases.

69 WhethertheyencounterNSTIsinthecourseofcaseworks,forensic

70 pathologistsneedtobeawareofpathogenesis,grossautopsyfindings,and

71 appropriateculturingtechniquesoftheseinfections.

72 Casereport

73 A67-year-oldmanwithoutanyknowncomorbidityexceptdiabetes

74 mellitus,wasadmittedtotheemergencyroom(ER)foramoderateback

75 painradiatingfromribs3–4ontherightside.Thepainhadfirstbegun

76 afteronlyasimplemovementofthechestwhenthepatientstretched.

77 The patientwas notfebrile andhe hadnormal vitalsigns. Clinical

78 examinationrevealedabackhematomabetweenthe3rdand4thribs.

79 Heunderwentaradiographicexaminationofthechest,thatrevealed 80 thepresenceofacompoundfractureofrib3ontherightside.The

81 patientwasdischarged.

82 Thenextday, thepatientwas hospitalizedagain forpersisting

83 painoftherighthemithorax.Clinicalexaminationfoundedemaof

84 the right chest and of the right abdominal wall. High-resolution

85 computerized tomography (CT) scan showed numerous enlarged

86 lymphnodesintherightaxillarychain.Therewasalsoimbibitionof

87 thesoft tissuecompartment oftheright hemithorax,but without

88 evidenceofaccumulationoffluid,suchasintheformofhematoma

89 or abscess, and without lung or pleural involvement (Fig. 1).

90 Moreover, the CT scan excludedthepresenceof theribfracture.

91 Laboratory investigation revealed increased levels of glucose

92 (308mg/dl;normalreferenceranges60 110mg/dl)andcreatinine

93 (2.24mg/dl;normalreferenceranges0.81–1.43mg/dl).Attheend

94 oftheERinvestigations,hewasadmittedtothemedicalwardfor

95 therapy-resistant-pain.

96 During theevaluationthepatient’sclinical conditiondeteriorated

97 withworseningofthestateofconsciousness,dyspneaandmarblingtothe

98 lower limbs. He also developed a new onset atrial fibrillation. A

99 cardiologicassessmentwasperformedanddiscoveredacollapsedinferior

100 vena cava and anejection fraction strongly reduced (35 %;normal

101 reference ranges 55–70 %). Therapy with amiodarone and saline

102 solution/glucosewasstarted.ThepatienthadaGlasgowComa Scale 103 (GCS)of12.Healsohadtachypnea22beatsperminute(normalreference

104

ranges60–100bpm)andmetabolicacidosis,sohewasmovedtothe

105

intensivecareunit(ICU).Physicalexaminationshowedadecreaseofthe

106

bloodpressure(90/50mmHg;normalreferenceranges80/120mmHg).

107

Bloodtestsshowedanormalwhitebloodcellcountandtherewasno

108

evidenceofacutekidneyinjury.However,thelevelsofotherindiceswere

109

consistentwithnon-specificinflammation.Adiagnosisofsepticshock

110

wasreached.Bloodcultureswerecollectedandbroadspectrumantibiotic

111

therapywasinitiatedwithintravenousvancomycin(2ginsalinesolution

112

250/mL/h) and piperacilline/tazobactam 4.5g every 6h). Fluid

113

resuscitationtherapywasalsoinitiated,withnorepinephrineinfusion

114

duetothefluid-resuscitationresistanthypovolemia.Withinafewhours,

115

theclinicalconditionofthepatienthadfurtherdeteriorated,andhedied

116

ofsepticshockandmulti-organfailureonly36hafterbeingfirstadmitted

117

to the ER. Blood cultures were negative for aerobic and anaerobic

118

pathogenicorganisms.

119

Theforensicautopsy

120

Aforensicautopsy wasperformed 48hlater,toruleout medical

121

malpractice.Theautopsyrevealedthepresenceoflargeandmultiple

122

reddishareasontheskinoftherighthemithoraxthatextendedtotheright

123

sideandtotherightgluteus,with4de-epithelializedareas(Fig.2).Atthe

124

internalexamination,themusclesunderlyingtheseareasofskinweresoft

125

andblackish-brownincolor.

126

Organandbodyfluidsamplesweretakenforfurtheranalysis.For

127

post-mortemmicrobiologicalanalyses,bloodsampleswerecollected

128

fromaortaandinoculatedontovariousagarplates(chocolate,blood

Fig.1.High-resolutioncomputedtomographyshowingimbibitionofthesoft tissuecompartmentoftherighthemithorax(indicatedbywhitedottedcircle) withoutevidenceofaccumulationoffluid,suchashematomaorabscess,and withoutlungorpleuralinvolvement.

Fig.2.Externalanalysisshowingthepresenceoflargeandmultiplereddishareas ontherighthemithoraxthatextendtotherightsideandtotherightgluteuswith de-epithelializedareas.

F.Suadoni,S.Gioia,B.Tirietal. FSIRxxx(xxxx)xxx–xxx

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129 supplemented with colistin and nalidixic acid (CAN); McConkey,

130 mannitol salt; Sabouraud; Schaedler; and Schaedler

kanamycin-131 vancomycin(allmediafromBectonDickinson).Plateswereincubated

132 at 352C in ambient air, 5% carbon dioxide, or anaerobic

133 conditions, aspreviously described [18].Blood samples were also

134 inoculatedin BACTECPlusaerobic andanaerobic bottles

(Becton-135 Dickinson,Erem-bodegem,Belgium).Afterover-nightincubation,a

136 Streptococcuspyogenesisolatewasisolatedinpureculturefromboth 137 solidmediaandbroths.TheorganismwasidentifiedusingtheBruker

138 MALDI Biotyper instrument (Bruker Daltonik GmbH, Bremen,

139 Germany),asdescribedelsewhere[19].Antimicrobialsusceptibility 140 testingshowedthattheisolatewassensitiveto

b

-lactamantibiotics

141 includingpenicillin, amoxicillin,andcephalosporins,andto

glyco-142 peptidesandtetracycline,whileitwasresistanttomacrolides.Blood

143 was also tested using the multiplex PCR-based FilmArray blood

144 cultureID(BCID)panel(bioMérieux,Marcyl’Etoile,France),andwas

145 positiveforS.pyogenesDNA.

146 Histological analysis of the organs was also performed, revealing 147 widespread necrosis of the soft tissues and muscle fibers of the right

148 hemithorax,thebuttocks,therightflankandthepectoralregion,withan

149 associated inflammatory infiltrate comprising. Other histologic findings 150 included:lymphocyteinfiltrationwithrareneutrophilsintheleftepicardium;

151 pulmonaryinterstitialhemorrhage;mildcerebellarlymphocyteinfiltration;

152 pancreaticsteatonecrosis;rarelymphocyteinfiltratesinthekidneys. 153 Thecauseofdeathinthispatientwasdeterminedtobesepticshock

154 duetoS.pyogenes-associatedNSTI.Theinfectionhadoriginatedinthe

155 rightchestwallandextendedtotherightabdomen.

156 Discussion

157 Thecaseunderdiscussionhasmanypeculiaritiesthatmakeitalmost 158 unique.Infact,inadults,NSTIisusuallydescribedintheextremities,

159 perineum(Fourniergangrene),abdomen,andhead/neck[4–6].

Occur-160 renceinthechestwallisrareandprimarychestwallNSTI,astheone 161 described,isincrediblyrare[9]:thefewcasesreportedintheliterature

162 aresubsequenttolungsurgery,thepresenceofathoracicchest-tubeor

163 esophagealresection[20].

164 Moreover, in this case under discussion, the infection started in

165 association withonly a minortrauma of thechest due toa simple

166 movement(stretching).Nocutaneouslesionwasidentified,despitethe

167 causativeorganismbeingS.pyogenes,abacteriumthatmoreusually

168 colonizesskinormucousmembranes.

169 NSTIcanbeclassifiedinfourcategoriesbasedonthetypeoforganism

170 involved:

171 NSTItypeI(polymicrobial/synergistic,70–80%);

172 NSTItypeII(monomicrobial,20%);

173 NSTItypeIII(Gram-monomicrobial);

174 NSTItypeIV(fungal)[18,19].

175 Mostcasesofnecrotizinginfectionsarepolymicrobial(TypeI),while

176 monomicrobial NSTIs (Type II) are common in immunosuppressed

177 patients[21].

178 InthepresentcasethepatienthadamonomicrobialNSTI,buthewas

179 notimmunosuppressed:heonlyhadtype2diabetesmellitusasarisk

180 factor. This particular casecan thus be categorizedas typeII NSTI.

181 Infectionsinthiscategory,especiallyinthepresenceofgroupA

beta-182 haemolitic streptococci,show anextremely rapidevolution toseptic

183 shockanddeath(almost70%),despiteundergoinganymedical/surgical

184 treatmentorintensivesupportivecare[22].

185 Inconclusionthecasedescribedisalmostuniquebecausetheinfection

186 developed in a man without major risk factors, after a minor trauma

187 (stretching)ofthechestduringasimplemovement;furthermore,theinfection

188 wasmonomicrobial,anotherrarefindinginanon-immunosuppressedpatient,

189 and was caused without any cutaneous lesion by a bacteriumusually colonizing 190 theskinormucousmembranes(S.pyogenes).

191

This type of infection is rarely described in the general forensic

192

literature,thereforeforensicpathologistsshouldneverthelessbeopen

193

mindedandconsiderthistypeofinfectionwhentheyperformautopsiesin

194

similarcases.

195

WhethertheyencounterNSTIsinthecourseofmedicalmalpractice

196

casesorinsuddenunexpecteddeaths,forensicpathologistsespecially

197

need to be aware of key points of these infections, such as their

198

pathogenesis,grossautopsyfindings,andappropriateculturing

techni-199

ques.Itisespeciallyimportantforforensicpathologiststobeableto

200

recognizethegrosslesionsassociatedwithNSTIs,becausetheycanoften

201

mimicpostmortemchangessuchaslivormortis.Overall,thisincreased

202

awarenesswillimprovetheforensicpathologist'sabilitytopromptlyand

203

accurately diagnose NSTIs, provide a comprehensive and accurate

204

evaluationtobestassistinpotentialmalpracticecases, andpromptly

205

informat-riskpeoplewhomayhavebeeninclosecontactwiththepatient

206

beforedeath.

207

DeclarationofCompetingInterest

208

Allauthorsdenyanyfinancialandpersonalrelationshipswithother

209

peopleororganizationsthatcouldinappropriatelyinfluencetheirwork.

210

Inparticularthey denyemployment,consultancies, stockownership,

211

honoraria,paidexperttestimony,patentapplications/registrations,and

212

grantsorotherfunding.

213

CRediTauthorshipcontributionstatement

214

FabioSuadoni:Conceptualization.SaraGioia:Writing -original

215

draft.BeatriceTiri:Datacuration.AntonellaMencacci:Supervision.

216

Simona Vento: Investigation. Massimo Lancia: Writing - review&

217

editing. Q4

218

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* Correspondingauthorat:SectionofLegalMedicine,UniversityofPerugia,P.zzaLucioSeveri,1,06129,Perugia,Italy. E-mailaddress:massimo.lancia@unipg.it(M.Lancia).

FSIR1001131–4