Toxic Shock Syndrome and Toxic Shock Syndrome and Streptococcal Toxic Shock Streptococcal Toxic Shock

SyndromeSyndrome

Dr. Batizy, D.O.Dr. Batizy, D.O.

January 26, 2006January 26, 2006

Toxic Shock SyndromeToxic Shock Syndrome

Severe life threatening syndrome Severe life threatening syndrome characterized by:characterized by: High feversHigh fevers Severe hypotensionSevere hypotension Diffuse erythrodermaDiffuse erythroderma Mucous membrane hyperemiaMucous membrane hyperemia PharyngitisPharyngitis DiarrheaDiarrhea

Toxic Shock SyndromeToxic Shock Syndrome May progress rapidlyMay progress rapidly Multisystem disfunctionMultisystem disfunction Severe electrolyte disturbancesSevere electrolyte disturbances Renal failureRenal failure ShockShock

Toxic Shock SyndromeToxic Shock Syndrome

Discovered in 1978 in apparently Discovered in 1978 in apparently healthy children – Staph aureus isolatedhealthy children – Staph aureus isolated

TSS epidemic – 1981 associated with TSS epidemic – 1981 associated with increased tampon useincreased tampon use

Incidence has dropped significantly, Incidence has dropped significantly, Currently most cases are unrelated to Currently most cases are unrelated to

mensesmenses Case Definition of Toxic Shock Case Definition of Toxic Shock

Syndrome, table 142-1Syndrome, table 142-1

Case Definition of Toxic Case Definition of Toxic Shock Syndrome, Table 142-1Shock Syndrome, Table 142-1

Fever – temp >102.0 F (>38.9 C)Fever – temp >102.0 F (>38.9 C) Rash: diffuse macular erythrodermaRash: diffuse macular erythroderma HypotensionHypotension Multisystem envolvement (three or more)Multisystem envolvement (three or more)

GI: vomiting or diarrhea at onset of illnessGI: vomiting or diarrhea at onset of illness Muscular: sever myalgia or creatine Muscular: sever myalgia or creatine

phosphokinase level at least twice the upper phosphokinase level at least twice the upper limit of normal limit of normal

Mucous membrane: vaginal, oropharyngeal, Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemiaor conjunctival hyperemia

Renal: blood urea nitrogen or creatinine at Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for least twice the upper limit of normal for laboratory or urinary sediment with pyuria laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per (greater than or equal to 5 leukocytes per highpower field) in the absence of urinary highpower field) in the absence of urinary tract infectiontract infection

Hepatic: total bilirubin, alanine Hepatic: total bilirubin, alanine aminotransferase enzyme, or asparate aminotransferase enzyme, or asparate aminotransferase enzyme levels at least aminotransferase enzyme levels at least twice the upper limit of normal for twice the upper limit of normal for laboratory laboratory

Hematologic: platelets less than Hematologic: platelets less than 100,000/ml100,000/ml

CNS: disorientation or alterations in CNS: disorientation or alterations in consciousness without focal consciousness without focal neurologic signs when fever and neurologic signs when fever and hypotension are absent hypotension are absent

Lab criteria: negative results on the Lab criteria: negative results on the following tests, if obtained:following tests, if obtained: Blood, throat, or cerebrospinal fliud Blood, throat, or cerebrospinal fliud

cultures (blood culture may be positive cultures (blood culture may be positive for for Staphlococcus aureusStaphlococcus aureus

Rise in titer to Rocky Mountain Spotted Rise in titer to Rocky Mountain Spotted fever, leptospirosis, or measlesfever, leptospirosis, or measles

Case Definition of TSSCase Definition of TSS Case classificationCase classification

Probable: five of six clinical findings are Probable: five of six clinical findings are presentpresent

Confirmed: all six clinical findings are Confirmed: all six clinical findings are present, including desquamation, unless present, including desquamation, unless patient dies before desquamation patient dies before desquamation occursoccurs

EpidemiologyEpidemiology

TSS – initially a disease of young TSS – initially a disease of young healthy menstruating women, healthy menstruating women, comprised fifty percent of cases comprised fifty percent of cases reported in 1986-87reported in 1986-87

Tampon use increased risk up to 33%Tampon use increased risk up to 33% In 2000, 135 reported cases, 3 were in In 2000, 135 reported cases, 3 were in

men, and 2 fatalities were from men, and 2 fatalities were from menstrual-related TSS (MRTSS)menstrual-related TSS (MRTSS)

FDA - Tampons now made of cotton and FDA - Tampons now made of cotton and rayon, should be changed every 4-8 hrsrayon, should be changed every 4-8 hrs

EpidemiologyEpidemiology Non-menstrual related cases of Toxic Non-menstrual related cases of Toxic

Shock Syndrome (NMTSS)Shock Syndrome (NMTSS) Increasing since 1980Increasing since 1980 41% NMTSS41% NMTSS Men comprise one-tenth of populationMen comprise one-tenth of population

Mortality rate 3.3 x that of MRTSS in womenMortality rate 3.3 x that of MRTSS in women

S. aureus isolated from 98% of women S. aureus isolated from 98% of women with TSSwith TSS

Women with MRTSS most likely Women with MRTSS most likely colonized with Staph aureus before the colonized with Staph aureus before the onset of menstruationonset of menstruation

EpidemiologyEpidemiology TSS associated with influenza or TSS associated with influenza or

influenza-like illnesses – mortality influenza-like illnesses – mortality rate (43%)rate (43%)

Nasal packing (nasal tampons) also Nasal packing (nasal tampons) also associated with TSSassociated with TSS

PathophysiologyPathophysiology Most TSS associated with Most TSS associated with S. aureusS. aureus TSST-1: toxic shock syndrome toxin, TSST-1: toxic shock syndrome toxin,

exotoxinexotoxin Induce fever via the hypothalamus or via IL-1 Induce fever via the hypothalamus or via IL-1

and TNFand TNF T-lymphocyte “superantigenation” and T-lymphocyte “superantigenation” and

overstimulationoverstimulation Induce interferon productionInduce interferon production Enhance delayed hypersensitivityEnhance delayed hypersensitivity Supress neutrophil migration and IG Supress neutrophil migration and IG

secretionsecretion Enhance host suseptibility to exotoxinsEnhance host suseptibility to exotoxins

PathophysiologyPathophysiology

Enterotoxins B and C Enterotoxins B and C Similar chemical structure to TSST-1Similar chemical structure to TSST-1 Seen primarily in NMTSS Seen primarily in NMTSS Elicit similar clinical manifestations as Elicit similar clinical manifestations as

TSST-1TSST-1

PathophysiologyPathophysiology

Vaginal conditions favorable to TSST-1Vaginal conditions favorable to TSST-1 Temp 39-40 CTemp 39-40 C Neutral pHNeutral pH PO2 > 5%PO2 > 5% Supplemental CO2Supplemental CO2 Menstruation – neutralizes vaginal pHMenstruation – neutralizes vaginal pH Tampon use may increase O2 and CO2Tampon use may increase O2 and CO2 Synthetic fibers in tampon compositionSynthetic fibers in tampon composition Synergistic relationship between Synergistic relationship between S. S.

aureusaureus and and E. coliE. coli

PathophysiologyPathophysiology Vasodilation – rapid and massive onsetVasodilation – rapid and massive onset HypotensionHypotension

Decreased vasomotor tone, blood pooling, Decreased vasomotor tone, blood pooling, decreased vascular returndecreased vascular return

Nonhydrostatic leakage of fluid into the Nonhydrostatic leakage of fluid into the interstitium, contributing to hypotension interstitium, contributing to hypotension and nonpitting edema of the head and and nonpitting edema of the head and neckneck

Depressed cardiac functionDepressed cardiac function Total body water deficits from vomiting Total body water deficits from vomiting

and diarrhea and feverand diarrhea and fever

PathophysiologyPathophysiology IL-1IL-1

Hypoalbuminemia, hypoferrinemia, and Hypoalbuminemia, hypoferrinemia, and proteolysis manifest as peripheral edema, proteolysis manifest as peripheral edema, anemia, and rhabdomyolysis seen in TSSanemia, and rhabdomyolysis seen in TSS

TNFTNF Acidosis, shock, and multisystem organ failureAcidosis, shock, and multisystem organ failure Multisystem organ failure Multisystem organ failure

Direct result from toxinDirect result from toxin Rapid onset of hypotension and decreased perfusionRapid onset of hypotension and decreased perfusion

Small amts of TSST-1 and enterotoxins B and C Small amts of TSST-1 and enterotoxins B and C can be detected in pts with TSS up to 1 yearcan be detected in pts with TSS up to 1 year

Clinical FeaturesClinical Features TSS must be considered whenTSS must be considered when

Unexplained febrile illness with Unexplained febrile illness with erythroderma, hypotension, and diffuse erythroderma, hypotension, and diffuse organ pathologyorgan pathology

Pts with NMTSS present 3Pts with NMTSS present 3rdrd to 5 to 5thth days of mensesdays of menses

Postoperative NMTSS – approx 2 Postoperative NMTSS – approx 2 daysdays

Clinical FeaturesClinical Features Mild TSS: Mild TSS:

FeverFever ChillsChills myalgiasmyalgias Abdominal painAbdominal pain Sore throatSore throat NauseaNausea Vomiting Vomiting DiarrheaDiarrhea Self-limitingSelf-limiting

Clinical FeaturesClinical Features SevereSevere

Acute onset Acute onset Early multiorgan envolvementEarly multiorgan envolvement ProdromeProdrome

Headache, malaise, myalgias, nausea, Headache, malaise, myalgias, nausea, vomiting, and diarrheavomiting, and diarrhea

Sudden onset of fevers and chills 1-4 days Sudden onset of fevers and chills 1-4 days prior to presentationprior to presentation

Orthostatic lightheadedness, profuse Orthostatic lightheadedness, profuse watery diarrhea, sore throat, watery diarrhea, sore throat, paresthesias, photophobia, abdominal paresthesias, photophobia, abdominal pain, and coughpain, and cough

Clinical PresentationClinical Presentation PEPE

HypotensionHypotension Pt appears acutely illPt appears acutely ill Change in mental statusChange in mental status OliguriaOliguria Nonpitting edema of face and extremitiesNonpitting edema of face and extremities Watery diarrheaWatery diarrhea Pharygitis strawberry red tonguePharygitis strawberry red tongue Tender erythematous external genitalia Tender erythematous external genitalia

diffuse vaginal hyperemia, strawberry diffuse vaginal hyperemia, strawberry cervix, scant purulent cervical discharge, cervix, scant purulent cervical discharge, bilat adenexal tendernessbilat adenexal tenderness

Clinical FeaturesClinical Features Rash – diffuse painless blanching Rash – diffuse painless blanching

erythroderma, fades in three days erythroderma, fades in three days Followed by full-thickness Followed by full-thickness

desquamation particularly of palms desquamation particularly of palms and soles of feetand soles of feet

Severely affected patients may have Severely affected patients may have hair and nail loss 2-3 months laterhair and nail loss 2-3 months later

Clinical FeaturesClinical Features Focal neuro findings are rareFocal neuro findings are rare Varying degrees of altered Varying degrees of altered

consciousnessconsciousness Toxic encephalopathy - confusion, Toxic encephalopathy - confusion,

disorientation, agitation, hysteria, disorientation, agitation, hysteria, somnolence, and seizuressomnolence, and seizures

CT and LP will help deliniateCT and LP will help deliniate

Clinical FeaturesClinical Features

Lab findingsLab findings LeukocytosisLeukocytosis lymphocytopenialymphocytopenia AnemiaAnemia ARF: azotemia, myoglobinuria, sterile pyuria, ARF: azotemia, myoglobinuria, sterile pyuria,

RBC castsRBC casts Liver abnormalitiesLiver abnormalities Metabolic acidosis 2Metabolic acidosis 2ndnd to hypotension to hypotension Electrolyte abnormalitiesElectrolyte abnormalities ArrhythmiasArrhythmias ARDSARDS

Differential DiagnosisDifferential Diagnosis

Acute pyelonephritisAcute pyelonephritis Septic shockSeptic shock Acute rheumatic feverAcute rheumatic fever Scarlet fever: strep or staph Scarlet fever: strep or staph

etiologiesetiologies Leigionare’s diseaseLeigionare’s disease PIDPID HUSHUS

Differential DiagnosisDifferential Diagnosis Acute viral syndromeAcute viral syndrome LeptospirosisLeptospirosis SLESLE Rocky Mountain Spotted feverRocky Mountain Spotted fever Tick typhusTick typhus GastroenteritisGastroenteritis Kawasaki diseaseKawasaki disease Reye syndromeReye syndrome Toxic epidermal necrolysisToxic epidermal necrolysis Erythema multiformeErythema multiforme

TreatmentTreatment Aggressive shock managementAggressive shock management Continuous monitoring: centralContinuous monitoring: central Aggressive fluid replacement – 4-20 L of Aggressive fluid replacement – 4-20 L of

crystalloid and FFPcrystalloid and FFP Ventilatory management if ARDS developsVentilatory management if ARDS develops Complete blood work and culturesComplete blood work and cultures Removal of foreign bodies, i.e. tampon or Removal of foreign bodies, i.e. tampon or

nasal packingnasal packing Antistaphlococcal penicillin or Antistaphlococcal penicillin or

cephalosporincephalosporin

TreatmentTreatment Antistaphlococcal penicillin or Antistaphlococcal penicillin or

cephalosporincephalosporin Nafcillin or oxacillin 2g IV every Nafcillin or oxacillin 2g IV every

4hrs4hrs Cefazolin 2g IV every 6hrsCefazolin 2g IV every 6hrs Oral anti-staphlococcal ABx for the Oral anti-staphlococcal ABx for the

next 10 -14 daysnext 10 -14 days

TreatmentTreatment

Pt not treated with Pt not treated with ββ-lactamase--lactamase-stable abx can have recurrencestable abx can have recurrence

MRTSS – recurrence occurs in MRTSS – recurrence occurs in second month after the initial second month after the initial disease, recurring on the same day disease, recurring on the same day of the menstrual cycleof the menstrual cycle

Initial episode is the most severeInitial episode is the most severe

Streptococcocal Toxic Shock Streptococcocal Toxic Shock SyndromeSyndrome

Group A StrepGroup A Strep Soft tissue infection, early shock, Soft tissue infection, early shock,

multisystem organ failure, higher multisystem organ failure, higher mortality than TSS, “Flesh eating mortality than TSS, “Flesh eating bacteria”bacteria”

Most serious – Strep necrotizing Most serious – Strep necrotizing fasciitis and myositisfasciitis and myositis

STSSSTSS Most commonly affects 20 – 50 yr olds Most commonly affects 20 – 50 yr olds

without prior illnesswithout prior illness

STSSSTSS Risk factorsRisk factors

Extremes of ageExtremes of age DiabetesDiabetes EtOHEtOH Drug abuseDrug abuse NSAIDSNSAIDS ImmunodeficiencyImmunodeficiency Rarely develops from symptomatic Rarely develops from symptomatic

pharyngitispharyngitis

STSSSTSS

2000-3000 cases annually; with 500 2000-3000 cases annually; with 500 to 1500 cases of necrotizing fasciitisto 1500 cases of necrotizing fasciitis Mortality rate of 30 – 80%Mortality rate of 30 – 80% 70% of cases progress to necrotizing 70% of cases progress to necrotizing

fasciitisfasciitis Surgical interventionSurgical intervention MortalityMortality

Strep fasciitis – 60%Strep fasciitis – 60% Strep Myositis – 85-100%Strep Myositis – 85-100%

Case Definition of Case Definition of Streptococcocal Toxic Shock Streptococcocal Toxic Shock

Syndrome Syndrome An illness with An illness with

HypotensionHypotension Multiorgan involvement with two or more of Multiorgan involvement with two or more of

the following:the following: Renal impairment Renal impairment CoagulopathyCoagulopathy Liver involvementLiver involvement ARDSARDS Generalized erythematous macular rash that may Generalized erythematous macular rash that may

desquamatedesquamate Soft tissue necrosisSoft tissue necrosis

Case Definition of Streptococcal Case Definition of Streptococcal Toxic Shock SyndromeToxic Shock Syndrome

Laboratory CriteriaLaboratory Criteria Isolation of group A streptococcusIsolation of group A streptococcus

Case ClassificationCase Classification Probable – clinical case definition in the Probable – clinical case definition in the

absence of another identified etiology absence of another identified etiology with isolation of group A strep from a with isolation of group A strep from a nonsterile sitenonsterile site

Confirmed – clinical case definition with Confirmed – clinical case definition with isolation of group A streptococcus from isolation of group A streptococcus from an otherwise sterile sitean otherwise sterile site

STSSSTSS EpidemiologyEpidemiology

Incidence – 1-5 per 100,000Incidence – 1-5 per 100,000 STSS associated Necrotizing Fasciitis 13-STSS associated Necrotizing Fasciitis 13-

46%46% PathophysiologyPathophysiology

GAS invasive infections – more virulent GAS invasive infections – more virulent exotoxins than TSSexotoxins than TSS SPE – Streptococcal pyogenic exotoxinsSPE – Streptococcal pyogenic exotoxins

SPE A – Scarlet fever toxin – most potent and SPE A – Scarlet fever toxin – most potent and commonly isolated SPE in STSS casescommonly isolated SPE in STSS cases

SPE A and B – pyrogenicity, superactivation of T-cells, SPE A and B – pyrogenicity, superactivation of T-cells, synthesis of TNF, IL-1 and IL-6, leading to acidosis, synthesis of TNF, IL-1 and IL-6, leading to acidosis, shock, organ failureshock, organ failure

STSSSTSS

Patients without immunity to M-type Patients without immunity to M-type SPE A and B producing strains of SPE A and B producing strains of GAS are most susceptible to STSSGAS are most susceptible to STSS

Portal of entryPortal of entry Vagina, pharynx, mucosa, and skin, Vagina, pharynx, mucosa, and skin,

most are unidentifiablemost are unidentifiable Commonly begins at site of minor skin Commonly begins at site of minor skin

traumatrauma

STSSSTSS Clinical FeaturesClinical Features

Pain most common with preceding local Pain most common with preceding local tendernesstenderness

May present as May present as PeritonitisPeritonitis PIDPID PneumoniaPneumonia PericarditisPericarditis FeverFever Severe painSevere pain SwellingSwelling RednessRedness Compartment syndromeCompartment syndrome

STSSSTSS PEPE

FeverFever Shock on admission or within 4-8hrsShock on admission or within 4-8hrs Vesicles and/or bullae at infection siteVesicles and/or bullae at infection site ARDSARDS Less commonly erythematous rashLess commonly erythematous rash

LabsLabs Mild increase in WBCMild increase in WBC LFT 2x normalLFT 2x normal

STSSSTSS LabsLabs

Decreased plateletsDecreased platelets Disseminated intravascular Disseminated intravascular

coagulopathycoagulopathy Renal dysfunction – requiring dyalysisRenal dysfunction – requiring dyalysis Blood cultures - +GAS 60%Blood cultures - +GAS 60% Tissue cultures – 90% Tissue cultures – 90%

STSSSTSS DiagnosisDiagnosis

Differential is the same as for TSS with Differential is the same as for TSS with the addition of invasive and noninvasive the addition of invasive and noninvasive GAS infections, necrotizing fasciitis, GAS infections, necrotizing fasciitis, myositis, serious infections caused by myositis, serious infections caused by C. C. perforingensperforingens and and C. septicumC. septicum, and , and mixed aneorbic and aerobic organismsmixed aneorbic and aerobic organisms

TreatmentTreatment Aggressive shock management with Aggressive shock management with

early use of vasopressorsearly use of vasopressors

STSSSTSS IV ABx should be started in the ED once IV ABx should be started in the ED once

cultures have been taken. Inability to cultures have been taken. Inability to obtain Cx should not delay administration obtain Cx should not delay administration of IV ABxof IV ABx Pen G 24 million U/d dividedPen G 24 million U/d divided Clindamycin 900mg IV q 8hrClindamycin 900mg IV q 8hr Erythromycin 1g IV q 6 hr in PCN allergic ptsErythromycin 1g IV q 6 hr in PCN allergic pts Ceftriaxone 2g IV q 24 hr with Clindamycin Ceftriaxone 2g IV q 24 hr with Clindamycin

900mg IV q 8hr900mg IV q 8hr IVIG 2g/kg q 48 hr in patients without IGA IVIG 2g/kg q 48 hr in patients without IGA

deficiency improve 30 day mortalitydeficiency improve 30 day mortality

STSSSTSS SurgerySurgery

Prompt consultation in addition to IV Prompt consultation in addition to IV ABxABx Exploration Exploration Debridement Debridement 70% of cases require debridement, 70% of cases require debridement,

fasciotomy, or amputation fasciotomy, or amputation

TSS and STSSTSS and STSS 1.) Toxic Shock Syndrome is only a 1.) Toxic Shock Syndrome is only a

disease of young healthy menstruating disease of young healthy menstruating women. T/Fwomen. T/F

2.) The rash of TSS is a diffuse, 2.) The rash of TSS is a diffuse, blanching, erythroderma, classically blanching, erythroderma, classically described as a “painless sunburn”, that described as a “painless sunburn”, that fades within 3-4 days of its appearance fades within 3-4 days of its appearance and is followed by full-thickness and is followed by full-thickness desquamation of the palms and soles desquamation of the palms and soles during convalescence. T/Fduring convalescence. T/F

TSS and STSSTSS and STSS 3.) STSS is defined as any group A 3.) STSS is defined as any group A

streptococcocal (GAS) infection with streptococcocal (GAS) infection with invasive soft tissue infection, early invasive soft tissue infection, early onset of shock, and organ failure. T/Fonset of shock, and organ failure. T/F

4.) STSS associated with GAS invasive 4.) STSS associated with GAS invasive infections most commonly affects infections most commonly affects individual between the ages of 20 – 50 individual between the ages of 20 – 50 withwith a predisposing illness. T/F a predisposing illness. T/F

Answers: 1.) F, 2.) T, 3.) T, 4.) F Answers: 1.) F, 2.) T, 3.) T, 4.) F

TSS and STSSTSS and STSS

Tintinalli et al; Tintinalli et al; Emergency MedicineEmergency Medicine: : A Comprehensive Study Guide. A Comprehensive Study Guide. Chap. 142, pg. 913-918.Chap. 142, pg. 913-918.