Toxic Shock Syndrome and Streptococcal Toxic Shock Syndrome

Dr. Batizy, D.O.

January 26, 2006

Toxic Shock Syndrome

 Severe life threatening syndrome characterized by:  High fevers  Severe hypotension  Diffuse erythroderma  Mucous membrane hyperemia  Pharyngitis  Diarrhea

Toxic Shock Syndrome

 May progress rapidly  Multisystem disfunction  Severe electrolyte disturbances  Renal failure  Shock

Toxic Shock Syndrome

 Discovered in 1978 in apparently healthy children – Staph aureus isolated  TSS epidemic – 1981 associated with increased tampon use  Incidence has dropped significantly,  Currently most cases are unrelated to menses  Case Definition of Toxic Shock Syndrome, table 142-1

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Case Definition of Toxic Shock Syndrome, Table 142-1

Fever – temp >102.0 F (>38.9 C)  Rash: diffuse macular erythroderma  Hypotension  Multisystem envolvement (three or more)  GI: vomiting or diarrhea at onset of illness  Muscular: sever myalgia or creatine phosphokinase level at least twice the upper limit of normal  Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia

   Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per highpower field) in the absence of urinary tract infection Hepatic: total bilirubin, alanine aminotransferase enzyme, or asparate aminotransferase enzyme levels at least twice the upper limit of normal for laboratory Hematologic: platelets less than 100,000/ml

 CNS: disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent  Lab criteria: negative results on the following tests, if obtained:  Blood, throat, or cerebrospinal fliud cultures (blood culture may be positive for Staphlococcus aureus  Rise in titer to Rocky Mountain Spotted fever, leptospirosis, or measles

Case Definition of TSS

 Case classification  Probable: five of six clinical findings are present  Confirmed: all six clinical findings are present, including desquamation, unless patient dies before desquamation occurs

Epidemiology

    TSS – initially a disease of young healthy menstruating women, comprised fifty percent of cases reported in 1986-87 Tampon use increased risk up to 33% In 2000, 135 reported cases, 3 were in men, and 2 fatalities were from menstrual-related TSS (MRTSS) FDA - Tampons now made of cotton and rayon, should be changed every 4-8 hrs

Epidemiology

  Non-menstrual related cases of Toxic Shock Syndrome (NMTSS)  Increasing since 1980  41% NMTSS  Men comprise one-tenth of population  Mortality rate 3.3 x that of MRTSS in women S. aureus isolated from 98% of women with TSS  Women with MRTSS most likely colonized with Staph aureus before the onset of menstruation

Epidemiology

 TSS associated with influenza or influenza-like illnesses – mortality rate (43%)  Nasal packing (nasal tampons) also associated with TSS

Pathophysiology

 Most TSS associated with S. aureus  TSST-1: toxic shock syndrome toxin, exotoxin  Induce fever via the hypothalamus or via IL-1 and TNF  T-lymphocyte “superantigenation” and overstimulation  Induce interferon production  Enhance delayed hypersensitivity  Supress neutrophil migration and IG secretion  Enhance host suseptibility to exotoxins

Pathophysiology

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

Pathophysiology

 Vaginal conditions favorable to TSST-1  Temp 39-40 C  Neutral pH  PO2 > 5%  Supplemental CO2  Menstruation – neutralizes vaginal pH  Tampon use may increase O2 and CO2  Synthetic fibers in tampon composition  Synergistic relationship between S. aureus and E. coli

Pathophysiology

  Vasodilation – rapid and massive onset Hypotension     Decreased vasomotor tone, blood pooling, decreased vascular return Nonhydrostatic leakage of fluid into the interstitium, contributing to hypotension and nonpitting edema of the head and neck Depressed cardiac function Total body water deficits from vomiting and diarrhea and fever

Pathophysiology

  IL-1  Hypoalbuminemia, hypoferrinemia, and proteolysis manifest as peripheral edema, anemia, and rhabdomyolysis seen in TSS TNF    Acidosis, shock, and multisystem organ failure Multisystem organ failure   Direct result from toxin Rapid onset of hypotension and decreased perfusion Small amts of TSST-1 and enterotoxins B and C can be detected in pts with TSS up to 1 year

Clinical Features

 TSS must be considered when  Unexplained febrile illness with erythroderma, hypotension, and diffuse organ pathology  Pts with NMTSS present 3 rd menses to 5 th days of  Postoperative NMTSS – approx 2 days

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Clinical Features

Mild TSS:  Fever         Chills myalgias Abdominal pain Sore throat Nausea Vomiting Diarrhea Self-limiting

Clinical Features

 Severe  Acute onset    Early multiorgan envolvement Prodrome   Headache, malaise, myalgias, nausea, vomiting, and diarrhea Sudden onset of fevers and chills 1-4 days prior to presentation Orthostatic lightheadedness, profuse watery diarrhea, sore throat, paresthesias, photophobia, abdominal pain, and cough

Clinical Presentation

 PE  Hypotension        Pt appears acutely ill Change in mental status Oliguria Nonpitting edema of face and extremities Watery diarrhea Pharygitis strawberry red tongue Tender erythematous external genitalia diffuse vaginal hyperemia, strawberry cervix, scant purulent cervical discharge, bilat adenexal tenderness

Clinical Features

 Rash – diffuse painless blanching erythroderma, fades in three days  Followed by full-thickness desquamation particularly of palms and soles of feet  Severely affected patients may have hair and nail loss 2-3 months later

Clinical Features

 Focal neuro findings are rare  Varying degrees of altered consciousness  Toxic encephalopathy - confusion, disorientation, agitation, hysteria, somnolence, and seizures  CT and LP will help deliniate

Clinical Features

 Lab findings          Leukocytosis lymphocytopenia Anemia ARF: azotemia, myoglobinuria, sterile pyuria, RBC casts Liver abnormalities Metabolic acidosis 2 nd to hypotension Electrolyte abnormalities Arrhythmias ARDS

Differential Diagnosis

 Acute pyelonephritis  Septic shock  Acute rheumatic fever  Scarlet fever: strep or staph etiologies  Leigionare’s disease  PID  HUS

Differential Diagnosis

          Acute viral syndrome Leptospirosis SLE Rocky Mountain Spotted fever Tick typhus Gastroenteritis Kawasaki disease Reye syndrome Toxic epidermal necrolysis Erythema multiforme

Treatment

 Aggressive shock management  Continuous monitoring: central  Aggressive fluid replacement – 4-20 L of crystalloid and FFP  Ventilatory management if ARDS develops  Complete blood work and cultures  Removal of foreign bodies, i.e. tampon or nasal packing  Antistaphlococcal penicillin or cephalosporin

Treatment

 Antistaphlococcal penicillin or cephalosporin  Nafcillin or oxacillin 2g IV every 4hrs  Cefazolin 2g IV every 6hrs  Oral anti-staphlococcal ABx for the next 10 -14 days

Treatment

 Pt not treated with β-lactamase-stable abx can have recurrence  MRTSS – recurrence occurs in second month after the initial disease, recurring on the same day of the menstrual cycle  Initial episode is the most severe

Streptococcocal Toxic Shock Syndrome

 Group A Strep  Soft tissue infection, early shock, multisystem organ failure, higher mortality than TSS, “Flesh eating bacteria”  Most serious – Strep necrotizing fasciitis and myositis  STSS  Most commonly affects 20 – 50 yr olds without prior illness

STSS

 Risk factors  Extremes of age  Diabetes  EtOH  Drug abuse  NSAIDS  Immunodeficiency  Rarely develops from symptomatic pharyngitis

STSS

 2000-3000 cases annually; with 500 to 1500 cases of necrotizing fasciitis  Mortality rate of 30 – 80%  70% of cases progress to necrotizing fasciitis  Surgical intervention  Mortality   Strep fasciitis – 60% Strep Myositis – 85-100%

Case Definition of Streptococcocal Toxic Shock Syndrome

 An illness with   Hypotension Multiorgan involvement with two or more of the following:  Renal impairment      Coagulopathy Liver involvement ARDS Generalized erythematous macular rash that may desquamate Soft tissue necrosis

Case Definition of Streptococcal Toxic Shock Syndrome

 Laboratory Criteria  Isolation of group A streptococcus  Case Classification  Probable – clinical case definition in the absence of another identified etiology with isolation of group A strep from a nonsterile site  Confirmed – clinical case definition with isolation of group A streptococcus from an otherwise sterile site

STSS

 Epidemiology  Incidence – 1-5 per 100,000  STSS associated Necrotizing Fasciitis 13-46%  Pathophysiology  GAS invasive infections – more virulent exotoxins than TSS  SPE – Streptococcal pyogenic exotoxins   SPE A – Scarlet fever toxin – most potent and commonly isolated SPE in STSS cases SPE A and B – pyrogenicity, superactivation of T-cells, synthesis of TNF, IL-1 and IL-6, leading to acidosis, shock, organ failure

STSS

 Patients without immunity to M-type SPE A and B producing strains of GAS are most susceptible to STSS  Portal of entry  Vagina, pharynx, mucosa, and skin, most are unidentifiable  Commonly begins at site of minor skin trauma

STSS

 Clinical Features   Pain most common with preceding local tenderness May present as  Peritonitis         PID Pneumonia Pericarditis Fever Severe pain Swelling Redness Compartment syndrome

STSS

 PE  Fever  Shock on admission or within 4-8hrs  Vesicles and/or bullae at infection site  ARDS  Less commonly erythematous rash  Labs  Mild increase in WBC  LFT 2x normal

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STSS

Labs  Decreased platelets  Disseminated intravascular coagulopathy  Renal dysfunction – requiring dyalysis  Blood cultures - +GAS 60%  Tissue cultures – 90%

STSS

 Diagnosis  Differential is the same as for TSS with the addition of invasive and noninvasive GAS infections, necrotizing fasciitis, myositis, serious infections caused by C. perforingens and C. septicum, and mixed aneorbic and aerobic organisms  Treatment  Aggressive shock management with early use of vasopressors

STSS

 IV ABx should be started in the ED once cultures have been taken. Inability to obtain Cx should not delay administration of IV ABx  Pen G 24 million U/d divided  Clindamycin 900mg IV q 8hr  Erythromycin 1g IV q 6 hr in PCN allergic pts  Ceftriaxone 2g IV q 24 hr with Clindamycin 900mg IV q 8hr  IVIG 2g/kg q 48 hr in patients without IGA deficiency improve 30 day mortality

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STSS

Surgery  Prompt consultation in addition to IV ABx  Exploration  Debridement  70% of cases require debridement, fasciotomy, or amputation

TSS and STSS

 1.) Toxic Shock Syndrome is only a disease of young healthy menstruating women. T/F  2.) The rash of TSS is a diffuse, blanching, erythroderma, classically described as a “painless sunburn”, that fades within 3-4 days of its appearance and is followed by full-thickness desquamation of the palms and soles during convalescence. T/F

TSS and STSS

 3.) STSS is defined as any group A streptococcocal (GAS) infection with invasive soft tissue infection, early onset of shock, and organ failure. T/F   4.) STSS associated with GAS invasive infections most commonly affects individual between the ages of 20 – 50 with a predisposing illness. T/F Answers: 1.) F, 2.) T, 3.) T, 4.) F

TSS and STSS

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