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(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 (pagenumbernotforcitationpurpose) 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). 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Science 2011; Email:[email protected] 331:778(cid:1)82. 4 Citation:JournalofCommunityHospitalInternalMedicinePerspectives2011,1:11584-DOI:10.3402/jchimp.v1i4.11584 (pagenumbernotforcitationpurpose)