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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.