Table Of Content(cid:1)CASE REPORT
Fatal meningococcemia
John Tabacco, MPH, MD*, Elizabeth Suniega, MSIII,
Fardad Sarabchi, MD and Dimitra Mitsani, MD
Union MemorialHospital, Baltimore, MD, USA
Withinthepastsixyears,acaseofbothWaterhouse-FreidrichsenSyndromeandfulminantmeningococcemia
havepresentedtoUnionMemorialHospital.Bothcasespresentedinmarkedlydifferentfashions,differedin
microbiologic serogrouping, showed minimal histopathologic similarities; however achieved ultimately the
same outcome through two different pathological pathways. The following case reports illustrate two
mechanismsthroughwhichN.Meningitismaypathogenizeahost,bothleadingtocompletecardiovascular
collapsein lessthan12hours.
Keyword: Infectiousdisease
Received:30 October 2011; Revised:16 December 2011; Accepted:21 December 2011;Published:26January2012
‘No other infection so quickly slays.’ The truth acute adrenal apoplexy in children appeared in The
behind this quote, which was found in Lancet, authored by Langmead in 1904 (10) and
Herrick’s 1919 article entitled ‘Extramenin- Andrewes (cid:1) the first person that was able to isolate
geal meningococcalinfections,’remainsasvalidtodayas N. meningitidis from the blood of an affected patient (cid:1)
it was when he stated it more than 90 years ago, as few (11) in 1906, prior to that which was written about a
other bacterial species (besides Neisseria meningitidis) similar case report by Rupert Waterhouse in 1911 (12).
havesincebeenfoundtohavethecapacitytokillhealthy AchangeintheepidemiologyofWFS,fromapediatric
patients in less than 24 hours (1). Although the descrip- disease that was almost exclusively reported in English
tive history of meningococcal disease dates back to the childrentoaworldwidediseasethatcouldaffectpatients
16th century, the historical origin of acute adrenal ofallages,firstbegantooccuraround1914inWorldWar
apoplexy, the so-called ‘Waterhouse-Friderichsen syn- I-relatedmilitarytrainingcamps(1,3).Aftermanyearly
drome,’ (WFS) arare formofacute, rapidly-progressing, authors had theorized about the etiology of suprarenal
fulminant meningococcemiawith bilateral adrenal gland apoplexy (cid:1) most commonly with relation to an elusive
hemorrhage,liesinapre-antibioticandpre-technological toxin or infection (especially smallpox) (cid:1) McLagen and
era (2). During the late 19th century as microscopy, Cooke definitively determined N. meningitidis to be the
culturing techniques, and schemes for pathogen classifi- causative organism of this disease in 1916 (13). Carl
cation were initially being developed, medicine relied on FriderichsenpublishedanarticleintheDanishliterature
relatively fewdiagnostic tools, was largelyobservational, about two pediatric cases of acute adrenal apoplexy in
and communication between most scientists was limited 1917,andareviewarticleencompassinginformationfrom
(3).Itwasduringthistimewhenreportsof‘catastrophic 28suchcasesintheGermanliteraturein1918,andwasthe
bacterial syndromes’ were first illustrated. Time has first author to emphasize the importance of adrenal
revealed many of these observations to be early clinical cortical insufficiency in the pathogenesis of suprarenal
encounterswith Neisseria meningitidis. apoplexy (14, 15). In 1933, ‘Waterhouse-Friderichsen
ArthurVoelckerreportedthefirstdescriptionofacute syndrome’ was officially named (for currently unknown
adrenal apoplexy in a two-year-old English girl in 1894 reasons)asauniquediseaseentitybyEduardGlanzmann,
(4). Subsequently, independent case reports with analo- whilehewasgivingapresentationonthesubject(16).By
gous observationswere made between 1898 and 1901 by thetimethatFriderichsenwrotehissecondreviewarticle
Garrod and Drysdale (5), Andrewes (6), Talbot (7), about WFS in 1955 in the English literature, awealthof
Blaker and Bailey (8), and Little (who was the first information about its epidemiology, pathogenesis, diag-
author to elaborate on a hypothesis that involved acute nosis, and treatment (especially with respect to sulfona-
Addison’s disease and the action of then-unknown mides, penicillin G, chloramphenicol, and synthetic
cortisol) (9). Furthermore, two detailed articles about corticosteroids) had been discovered (17). Since the
JournalofCommunityHospitalInternalMedicinePerspectives2011.#2011JohnTabaccoetal.ThisisanOpenAccessarticledistributedundertheterms 1
of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-
commercialuse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Citation:JournalofCommunityHospitalInternalMedicinePerspectives2011,1:11584-DOI:10.3402/jchimp.v1i4.11584
(pagenumbernotforcitationpurpose)
JohnTabaccoetal.
mid-1950’s, further advances in knowledge about menin-
gococcaldiseaseandWFShavebeenachieved.
Interestingly, within the past six years, a case of both
Waterhouse-Friderichsen syndrome and fulminant
meningococcemia have presented to Union Memorial
Hospital. Both cases presented in markedly different
fashions, differed in microbiologic serogrouping, and
showed minimal histopathologic similarities. However,
they ultimately achieved the same outcome through two
different pathological pathways. The following case
reports illustrate two mechanisms through which N.
Meningitidis may pathogenize a host, both leading to
Fig. 1. Myocarditis.
complete cardiovascular collapse in less than 12 hours.
with speciation later to return as Neisseria meningitides
serogroup Y.
Case reports Later autopsy revealed myocarditis (Fig. 1) Final
diagnosiswas fulminant meningococcemia.
Case1
A 46-year-old male bus driver with past medical history
of obstructive sleep apnea presented to an emergency Case2
departmentinBaltimore MarylandinearlyJuly,2011 at A 19-year-old male college student wasbrought into the
approximately 1:00 pm, complaining of sudden onset emergency department by ambulance at approximately
severe, left sided chest pain, shortness of breath, back 1:00amon26October2005.Thepatientbelievedthathe
pain, chills, and one episode of a non-witnessed seizure was having an ‘allergic reaction to Chinese food’that he
with loss ofconsciousness as hewaspreparingto depart hadconsumedanhourpriortodevelopingthepresenting
onhisbusrouteearlyinthemorning.Thepatientdenied symptoms of hot flashes, shortness of breath, light-
anyprodrometopresentingsymptoms,statinghehadfelt headedness, generalizedweakness, and myalgia.
fine the day prior. He denied sick contacts. On physical exam he was alert, pale, clammy, tachy-
His temperature on admission was 101.1, blood
cardic, normotensive, and afebrile. There was no rash.
pressure was 126/71 mmHg, and heart rate was 96
The patient was treated initially for a presumed allergic
BPM. He was an obese, well developed male who was
reaction. On subsequent re-evaluation at 7:00 am and
ill looking. He was alert and oriented with no nuchal
8:00 am, he remained tachycardic with no improvement
rigidity. Lungs were clear and no cardiac murmurs were
of symptoms. Initial laboratory workup was significant
auscultated. No abdominal or flank tenderness was
for a WBC: 2.2 k/UL, Hgb: 12.1 gr/dl, PLT: 35 K/UL,
noted. No rashes, petechiae or purpura were noted.
bandemia of 36%, non-anion gap metabolic acidosis
Neurological exam was non focal.
(CO2:16mmol/L);Urinetoxicologyscreenwasnegative.
Significant laboratory values were: WBC: 3.8 k/UL,
Approximately five hours later, the patient developed
PMN: 90.9%, troponin: 0.057 ng/ml, Hgb: 12.8 gm/dL,
restlessness, diaphoresis, and became disoriented. Blood
PLT: 198K/UL, BUN: 12, Cr: 0.68, CK: 189. ECG
cultureswere sent and broad spectrum intravenous anti-
showed non-specific Twave abnormalities.
biotics were started. He was sent to the Intensive Care
Chest radiograph revealed questionable lower lobe
Unit.At9:45amhebecamehypotensive,failedtorespond
infiltrateandpiperacillin-tazobactamwasstartedempiri-
to fluid resuscitation and went into a state of pulseless
cally. Chest CTwas negative for pulmonary embolism.
electricalactivity.Cardiopulmonaryresuscitationcontin-
At 7:45 pm, while in the ER, the patient began to
uedfor45minandpatientwaspronounceddeadat10:30
hemodynamically decompensate as blood pressure
dropped to 80/60 mmHg. The patient was given two am,lessthanninehoursfromtimeofpresentation.
liters of normal saline and was moved to the Intensive The following day, blood cultures grew gram negative
CareUnit.Cardiopulmonaryarrestoccurredatapproxi- diplococci later speciated as Neisseria meningitidis ser-
mately 8:45 pm. Cardiopulmonary resuscitation was ogroup B. Reviewof school records showed that he had
started and intubation was attempted but failed and beenvaccinatedwith the meningococcal vaccine.
pulse was unable to be established. Approximately eight On autopsy, there were macroscopic bilateral areas
hours after presenting to the Emergency Room the of adrenal hemorrhage consistent with Waterhouse-
patient was pronounced dead. Friderichsensyndrome(Fig.2) aswellasfloridconjunc-
At 8:00 am on the following morning, morphologyof tival petechiae and bilateral subconjuntival hemorrhage.
blood cultures returned as Gram negative diplococci, Myocarditiswasnoted.
2
Citation:JournalofCommunityHospitalInternalMedicinePerspectives2011,1:11584-DOI:10.3402/jchimp.v1i4.11584
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Fatalmeningococcemia
OnehundredyearsagoWaterhousereportedadisease
that was humbling in its ferocity. A century has passed
and our understanding is at a rewardable depth. We are
equally impressed and humbled today.
Conflicts of interest and funding
The authors have not received any funding or benefits
from industryor elsewhere to conduct this study.
Fig. 2. Adenalcortexhemorrhage.
Discussion
References
Neisseia meningitides is a gram negative aerobic diplo-
coccus that colonizes human nasopharynx in up to 10% 1. Herrick W. Extrameningeal meningococcus infections. Arch
ofthepopulation(18).Humansarethesolereservoirfor InterMed1919;23:409(cid:1)18.
2. Manchanda V, Gupta S, Bhalla P. Meningococcal disease:
this pathogen which is spread by physical contact or by
History, epidemiology, pathogenesis, clinical manifestations,
inhalation of respiratory droplets (18). Infections in
diagnosis, antimicrobial susceptibility and prevention. Indi
industrialized countries occur sporadically or in out- MedMicrobiol2006;24:7(cid:1)19.
breaks, tend to exhibit seasonality (late winter (cid:1) early 3. Cartwright K. Handbook of Meningococcal Disease:
spring)andareobservedmainlyincrowdedsettingssuch infection iiology, vaccination, clinical management. Weinheim
(Germany):Wiley;2006.
asschoolsormilitarycampswheretransmissionisreadily
4. Voelcker A. (Abstract of post-mortem report, no title). Mid-
facilitated. Thereare 13 antigenicallydistinct serogroups
dlesexHospitalRepMedSurgPathRegistrars.1894;278.
ofN.meningitides.SerogroupsB,CandYaccountforthe 5. Archibald G, Drysdale J. Transactions of the pathological
majority of disease in the United States whose annual society.London1898;49:257.
6. Andrewes F. Transactions of the pathological society. London
incidence amounts to 1,000 cases (19).
1898;49:259.
Neisseria meningitis is the second most common
7. Talbot E. Cases of hemorrhage into suprarenal capsules. St.
pathogen of community acquired meningitis (19) but Bartholomew’sHosp.Rep.1900;36:207.
meningococcaldiseasecanpresentwithextremelyrapidly 8. BlakerP,BaileyB.Onsomecasesofhaemorrhageintotheskin
developingfataloutcomesintheabsenceofmeningitisas andsuprarenalcapsules.BritMedJ1901;2(2115):75(cid:1)7.
9. Little E. Cases of purpura, ending fatally, associated with
in our two cases. Our second case is an example of
hemorrhage into the suprarenal capsules. Brit J Dermatol
Waterhouse-Friderichsen syndrome with extensive adre-
1901;13:445(cid:1)67.
nal hemorrhages; a catastrophic development in a septic 10. LangmeadF.Onthreecasesofsuprarenalapoplexyinchildren.
patient. Our first case had a similar clinical course but Lancet1904;163:1496(cid:1)8.
without the adrenal hemorrhage. This autopsy result 11. AndrewesF.Acaseofacutemeningococcalsepticaemia.Lancet
1906;1:1172.
surprisedus,butservestopointouttheuniquevirulence
12. WaterhouseR.Acaseofsuprarenalapoplexy.Lancet1911;177:
of this organism, as well as illustrating the important 577(cid:1)8.
point that myocarditis during N. Meningococcus infec- 13. McLagen P, Cooke W. The fulminating type of cerebrospinal
tionsincreasesthemortalityofthisdestructivepathogen. fever:pathologyandcauseofdeath.Lancet1916;2:1054(cid:1)5.
14. Friderichsen C. Binyreaopoleski hos Smaaborn. Ugeskrift for
Meningococcus possesses an array of characteristics
Laeger1917;79:1817(cid:1)26.
that serve to evade the host immune response, rendering
15. Friderichsen C. Nebennierenapoplexie bei kleinen Kindern.
havoc in individual cases (20). First, structural compo- JahrbuchfurKinderhilkunde1918;87:109(cid:1)25.
nentsofitsservicedisplaymolecularmimicryofhostcells 16. Clansman E. Beitrag zur Klinik, Hamatologie und Pathologie
(20). Second, the organism employs genetic transforma- des Syndroms von Waterhouse-Friderichsen. Jahrbuch fur
Kinderheilkunde1933;139:49(cid:1)63.
tion- reuptake of DNA from other bacteria in the
17. Friderichsen C. Waterhouse-Friderichsen syndrome. Acta
environment along with iron scavenging and chelation
Endocronologica1955;18:482(cid:1)92.
to a binding human lactoferrin that selects for survival 18. Rosenstein M, Perkins B, StephensS, Popovic T, Hughes JM.
and commensal state and allows for rapid multiplication NEnglJMed.2001;344:1378(cid:1)88.
19. CDC. Active Bacterial Core Surveillance Report, Emerging
andoutermembraneproteinswhichpromoteattachment
InfectionsProgramNetwork,NeisseriaMeningitides,1997(cid:1)2009.
andhostinvasion(21).Theuniquestructureoftheouter
Available from: http://www.cdc.gov/abcs/reports-findings/
membrane liposaccharide leads to bleb formation and survreports/mening09.html
release of potent endotoxin that quickly achieves high 20. Brown-ElliottBA,WallaceRJ.Jr.Infectionsduetonontuber-
blood stream levels readily culminating in clinical sepsis culous mycobacteria other than Mycobacterium avium-intra-
cellulare. In: Mandell, DOuglas and Bennett’s Principles and
(21).Finally,theinnerbacterialcapsuleiswellknownto
Practice of Infectious Diseases, Seventh Edition, Mandell,
display resistance to complement phagocyte mediated
Bennett,Dolin,eds.ElsevierChurchhillLivingstonInc.,2010;
lysis (22). 2(253)3191(cid:1)3198.
3
Citation:JournalofCommunityHospitalInternalMedicinePerspectives2011,1:11584-DOI:10.3402/jchimp.v1i4.11584
(pagenumbernotforcitationpurpose)
JohnTabaccoetal.
21. HelenaLo,TangC,ExleyR.Mechanismsofavoidanceofhost
*JohnPatrickTabacco
immunity by Neisseria meningitides and its effect on vaccine
1201W.Mt.RoyalAve
development.LancetInfectDis2009;9(7):418(cid:1)27.
Baltimore,MD
22. Chamot-RookeJ,MikatyG,MalosseC,SoyerM,DumontA,
USA21217
GaultJ,etal.PostTranslationalmodificationofpiliuponcell
Tel:(240)4988282
contact triggers N. Meningitidis Dissemination. Science 2011;
Email:[email protected]
331:778(cid:1)82.
4
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