Toxic shock syndrome

1. Toxic Shock SyndromeToxic Shock Syndrome
Janet Zhang M.D.Janet Zhang M.D.
1/5/20121/5/2012

2. S.M.S.M.
HPI: 15 yo G0 presented to Pediatric Urgent Clinic with HPI: 15 yo G0 presented to Pediatric Urgent Clinic with
complaints of headache, fever, rash, abdominal pain and nausea/complaints of headache, fever, rash, abdominal pain and nausea/
vomiting. Pt states that it started with a headache 2 days prior, vomiting. Pt states that it started with a headache 2 days prior,
followed by fever of 102 F the night before. She then developed followed by fever of 102 F the night before. She then developed
abdominal/epigastric pain, and tender rash of the hands, feet, abdominal/epigastric pain, and tender rash of the hands, feet,
thighs and perineum. thighs and perineum.
Rash started around the perineum and spread to the rest of the Rash started around the perineum and spread to the rest of the
body. Rash is also associated with burning sensation and tingling body. Rash is also associated with burning sensation and tingling
of the extremities. of the extremities.
LMP 1 week prior to presentation. Using tampons and left 1 in LMP 1 week prior to presentation. Using tampons and left 1 in
for > 12 hours. Also accidentally dropped a tampon in the toilet for > 12 hours. Also accidentally dropped a tampon in the toilet
at school and fished out to use it.at school and fished out to use it.
OB/GYN Hx: Menarche 12, heavy periods, 8 day flow, uses OB/GYN Hx: Menarche 12, heavy periods, 8 day flow, uses
super plus tampons. Sexually active, using condoms.super plus tampons. Sexually active, using condoms.

3. S.M.S.M.
PMH: nonePMH: none
PSH: tonsillectomyPSH: tonsillectomy
Meds: noneMeds: none
Allergies: NKDAAllergies: NKDA
FHx: non contributoryFHx: non contributory
Social Hx: no smoking, occasional EtOHSocial Hx: no smoking, occasional EtOH
Vitals: 37.2 C/98.9 F (Clinic), BP 99/62, Pulse 85, Vitals: 37.2 C/98.9 F (Clinic), BP 99/62, Pulse 85,
Temp 99.5 °F (37.5 °C), Resp 16, SpO2 98% (ED)Temp 99.5 °F (37.5 °C), Resp 16, SpO2 98% (ED)

4. S.M.S.M.
Exam: Abdomen: Soft. Normal appearance. Bowel sounds are Exam: Abdomen: Soft. Normal appearance. Bowel sounds are
normal. She exhibits no distension and no mass. There is no normal. She exhibits no distension and no mass. There is no
hepatosplenomegaly. Tenderness is present in the epigastric area. hepatosplenomegaly. Tenderness is present in the epigastric area.
She has no rigidity, no rebound, no guarding and no CVA She has no rigidity, no rebound, no guarding and no CVA
tenderness. tenderness.
Genitourinary: Vulva exhibits erythema. Vulva exhibits no Genitourinary: Vulva exhibits erythema. Vulva exhibits no
exudate, no lesion, no rash and no tenderness. No discharge exudate, no lesion, no rash and no tenderness. No discharge
found. Vulva hyperemic and swollen. Tender. found. Vulva hyperemic and swollen. Tender.
Skin: Fine red scarlitini-like rash on inner thighs, hands and feet. Skin: Fine red scarlitini-like rash on inner thighs, hands and feet.
Few on abdomen. Few on abdomen.
ED Exam: “Rash on the perineum that is spreading down her ED Exam: “Rash on the perineum that is spreading down her
legs. She has another rash on her upper back and chest. The legs. She has another rash on her upper back and chest. The
rash is raised red and tender to palpation.” rash is raised red and tender to palpation.”

5. LabsLabs
9/2/2011 9/2/2011
WBC'S AUTO 7.6 WBC'S AUTO 7.6
RBC AUTO 4.86 RBC AUTO 4.86
HGB 13.3 HGB 13.3
HCT AUTO 39.6 HCT AUTO 39.6
MCV 81.4 MCV 81.4
MCH 27.4 MCH 27.4
MCHC 33.7 MCHC 33.7
RDW, BLOOD 16.4 (H) RDW, BLOOD 16.4 (H)
PLT'S AUTO 236 PLT'S AUTO 236
MPV 8.0 MPV 8.0
LYMPHS % AUTO 11.2 (L) LYMPHS % AUTO 11.2 (L)
MONOS % AUTO 5.4 MONOS % AUTO 5.4
NEUTROPHILS % AUTO NEUTROPHILS % AUTO 78.8 (H)78.8 (H)
EOS % AUTO 4.5 EOS % AUTO 4.5
BASO'S % AUTO 0.1 BASO'S % AUTO 0.1
RBC NUCLEATED, AUTO 0.0 RBC NUCLEATED, AUTO 0.0
TBILI 1.8 (H) TBILI 1.8 (H)
ALKP 151 ALKP 151
ALT ALT 151 (H)151 (H)
ESR WEST 23 (H) ESR WEST 23 (H)
CRP 64.0 (H) CRP 64.0 (H)
AST AST 138 (H)138 (H)
Creatinine 0.8Creatinine 0.8
UA GLUC <30 (NEG) UA GLUC <30 (NEG)
UA KETONES <10 (NEG) UA KETONES <10 (NEG)
UA SP GR 1.026 UA SP GR 1.026
UA HGB 0.50 (2+) (A) UA HGB 0.50 (2+) (A)
PH UA 7.5 PH UA 7.5
UA PROT 30 (1+) (A) UA PROT 30 (1+) (A)
UA NO2 NEGATIVE UA NO2 NEGATIVE

LE, UA POSITIVE (A) LE, UA POSITIVE (A)
UROBILINOGEN UA QL >12.0 (4+) (A) UROBILINOGEN UA QL >12.0 (4+) (A)

UA BILI 1.0 (1+) (A) UA BILI 1.0 (1+) (A)
RBC, UA/HPF 4-10 (A) RBC, UA/HPF 4-10 (A)
UA WBC'S/HPF >25 (A) UA WBC'S/HPF >25 (A)
UA BACT/HPF FEW (A) UA BACT/HPF FEW (A)
SQUAM EPITHE CELL URNS AUTO QUAL SQUAM EPITHE CELL URNS AUTO QUAL
FEW (A) FEW (A)
TRANSIT EPITHE CELL UA AUTO QUAL TRANSIT EPITHE CELL UA AUTO QUAL
FEW (A) FEW (A)
GC/chlamydia negativeGC/chlamydia negative
HIV, Hep B and syphilis negativeHIV, Hep B and syphilis negative
Blood culture negative x 2Blood culture negative x 2
Urine Culture negativeUrine Culture negative
MRSA Culture negativeMRSA Culture negative
Genital Culture: +GBSGenital Culture: +GBS

6. S.M.S.M.
Hospital Course: Transferred from pediatric urgent Hospital Course: Transferred from pediatric urgent
clinic to ED for additional evaluation/stabilization. clinic to ED for additional evaluation/stabilization.
Started on IV Nafcillin, Gentamicin and Clindamycin in Started on IV Nafcillin, Gentamicin and Clindamycin in
the ED. Admitted to ICU where she improved the ED. Admitted to ICU where she improved
clinically and rash resolved. She was then transferred to clinically and rash resolved. She was then transferred to
the pediatric service where they discontinued previous the pediatric service where they discontinued previous
antibiotics and started her on Rocephin. Pt was antibiotics and started her on Rocephin. Pt was
discharged on HD #3 with 7 day course of PO discharged on HD #3 with 7 day course of PO
Clindamycin per Peds ID and outpatient follow up. Clindamycin per Peds ID and outpatient follow up.

7. Toxic Shock SyndromeToxic Shock Syndrome
Toxin mediated, acute systemic disease resulting in shock and multi-system Toxin mediated, acute systemic disease resulting in shock and multi-system
organ failureorgan failure
Staphylococcus aureus and Group A Streptococcus pyogenes are the most Staphylococcus aureus and Group A Streptococcus pyogenes are the most
common organismscommon organisms
Gram positive infections are responsible for > 50% of sepsis in the US.Gram positive infections are responsible for > 50% of sepsis in the US.
Mortality rate higher than meningococcal septicemiaMortality rate higher than meningococcal septicemia
Staphylococcal TSS first reported in 1978 and increased in incidence in the Staphylococcal TSS first reported in 1978 and increased in incidence in the
early 1980s in the USearly 1980s in the US
Associated with use of high absorbency tampons in womenAssociated with use of high absorbency tampons in women
During this time, peak incidence was 6.2 – 12.3 cases per 100,000 per yearDuring this time, peak incidence was 6.2 – 12.3 cases per 100,000 per year
With changes in tampon manufacture and usage, incidence fell to 1 case per With changes in tampon manufacture and usage, incidence fell to 1 case per
100,000 per year100,000 per year
133 cases of toxic shock syndrome in United States reported to CDC in 2003 133 cases of toxic shock syndrome in United States reported to CDC in 2003
The rate of vaginal colonization by Staph aureus remains approximately 1-5% The rate of vaginal colonization by Staph aureus remains approximately 1-5%
of healthy women and remain unchanged compared to the 1980s.of healthy women and remain unchanged compared to the 1980s.

8. Toxic Shock SyndromeToxic Shock Syndrome
Nonmenstrual TSS associated with Staph comprise about 50% Nonmenstrual TSS associated with Staph comprise about 50%
of casesof cases
Associated with barrier contraceptive (diaphragm, IUD), vaginal and Associated with barrier contraceptive (diaphragm, IUD), vaginal and
cesarean deliveries, surgical and postpartum wound infections, mastitis, cesarean deliveries, surgical and postpartum wound infections, mastitis,
sinusitis, burns, cutaneous infections…sinusitis, burns, cutaneous infections…
Streptococcal toxic shock syndrome attributed to Streptoccocus Streptococcal toxic shock syndrome attributed to Streptoccocus
pyogenes was reported in 1987pyogenes was reported in 1987
Secondary to invasive Group A Strep soft tissue infectionsSecondary to invasive Group A Strep soft tissue infections
Mortality of approximately 30-40%Mortality of approximately 30-40%
Incidence of between 1.5 – 5.2 cases per 100,000 per yearIncidence of between 1.5 – 5.2 cases per 100,000 per year
Higher rates at extremes of age and ethnic minoritiesHigher rates at extremes of age and ethnic minorities
Higher incidence in patients with underlying chronic illness, post varicella Higher incidence in patients with underlying chronic illness, post varicella
infection and NSAIDs useinfection and NSAIDs use

9. PathophysiologyPathophysiology
Bacterial endotoxins act as superantigensBacterial endotoxins act as superantigens
Protein toxins that have the ability to trigger excessive T-cell Protein toxins that have the ability to trigger excessive T-cell
activation with downstream activation of other cell types and activation with downstream activation of other cell types and
cytokine releasecytokine release
Conventional antigen presentation activates 0.01% of Conventional antigen presentation activates 0.01% of
host T-cells compared to superantigen binding which host T-cells compared to superantigen binding which
activates up to 20-30% of host T-cellsactivates up to 20-30% of host T-cells
Also associated with rapid increase in cytokine Also associated with rapid increase in cytokine
production from T-cellsproduction from T-cells
T-cell activation leads to additional recruitment of T T-cell activation leads to additional recruitment of T
and B cells to the site of infectionand B cells to the site of infection

10. PathophysiologyPathophysiology
Staphylococcal Staphylococcal TSS-T1 TSS-T1 (Toxic shock syndrome Toxin 1) is responsible for (Toxic shock syndrome Toxin 1) is responsible for
95% of menstrual related TSS. 95% of menstrual related TSS.
TSS-T1 able to cross mucosal barriersTSS-T1 able to cross mucosal barriers
Also detectable in 50% of non menstrual TSSAlso detectable in 50% of non menstrual TSS
Not all patients colonized with Staph aureus or strep pyogenes develop TSS Not all patients colonized with Staph aureus or strep pyogenes develop TSS
and interaction between host immune system and pathogen play an important and interaction between host immune system and pathogen play an important
rolerole
Absence of antibodies against superantigens is a major risk factor to Absence of antibodies against superantigens is a major risk factor to
developing TSSdeveloping TSS
> 85% of women aged 13-40 have TSS-T1 antibodies that are thought to > 85% of women aged 13-40 have TSS-T1 antibodies that are thought to
be protectivebe protective
Low or negative antibody titers are found in 90.5% of patients with Low or negative antibody titers are found in 90.5% of patients with
menstrual TSSmenstrual TSS
More than 50% of these patients fail to seroconvert within 2 months of More than 50% of these patients fail to seroconvert within 2 months of
their illnesstheir illness

11. Clinical ManifestationClinical Manifestation
Hallmark symptoms include fever, shock and multi-system Hallmark symptoms include fever, shock and multi-system
failurefailure
Staphylococcal TSS: starts with flu like prodromal illness Staphylococcal TSS: starts with flu like prodromal illness
including fever, GI distress and severe myalgia. Desquamation is including fever, GI distress and severe myalgia. Desquamation is
a late feature and happens 10-21 days after initial onset of a late feature and happens 10-21 days after initial onset of
symptoms.symptoms.
Blood cultures are positive in < 5% of Staph TSSBlood cultures are positive in < 5% of Staph TSS
Menstrual and non menstrual TSS are identical clinicallyMenstrual and non menstrual TSS are identical clinically
Up to 95% of patients diagnosed with menstrual TSS have onset of illness Up to 95% of patients diagnosed with menstrual TSS have onset of illness
during mensesduring menses
Fever and rash more prevalent in early diseaseFever and rash more prevalent in early disease
Recurrence of menstrual TSS well documented but rare in non menstrual Recurrence of menstrual TSS well documented but rare in non menstrual
TSSTSS

12. Clinical ManifestationClinical Manifestation
Postoperative nonmenstrual TSS usually occurs within Postoperative nonmenstrual TSS usually occurs within
48 hours of surgery48 hours of surgery
Nonmenstrual TSS patient are more likely to acquire Nonmenstrual TSS patient are more likely to acquire
infection nosocomially and to have had prior antibiotic infection nosocomially and to have had prior antibiotic
treatment.treatment.
Nonmenstrual TSS are more commonly associated with Nonmenstrual TSS are more commonly associated with
CNS and renal complicationsCNS and renal complications
Streptococcal TSS typically arise from deep seated Streptococcal TSS typically arise from deep seated
invasive soft tissue infections such as necrotising invasive soft tissue infections such as necrotising
fasciitis, cellulitis and myositis which are extremely fasciitis, cellulitis and myositis which are extremely
painful. painful.

14. Derm manifestationsDerm manifestations
Diffuse macular Diffuse macular
erythroderma followed erythroderma followed
by desquamation in 1-2 by desquamation in 1-2
weeksweeks
Conjunctival injectionConjunctival injection

15. Mucosal (oral and Mucosal (oral and
genital) hyperemiagenital) hyperemia
Strawberry tongueStrawberry tongue

17. TreatmentTreatment
Aim to decrease bacterial load and endotoxin productionAim to decrease bacterial load and endotoxin production
Penicillinase resistant penicillin, cephalosporin for suspected Penicillinase resistant penicillin, cephalosporin for suspected
Staphylococcus aureus TSSStaphylococcus aureus TSS
Vancomycin for suspected MRSAVancomycin for suspected MRSA
Group A Streptococcus very sensitive to B-lactam agents Group A Streptococcus very sensitive to B-lactam agents
including Penicillin G (first line treatment)including Penicillin G (first line treatment)
Although PCN is bactericidal, it is less effective against high organism Although PCN is bactericidal, it is less effective against high organism
load (ineffective if treatment delayed by > 2 hours)load (ineffective if treatment delayed by > 2 hours)
Given with Clindamycin which is inhibitory of protein synthesis Given with Clindamycin which is inhibitory of protein synthesis
of superantigen productionof superantigen production
Inhibitory of endotoxin production in both Staph and Group A StrepInhibitory of endotoxin production in both Staph and Group A Strep

19. TreatmentTreatment
Possible consideration of starting IV Possible consideration of starting IV
immunoglobulins if no clinical response within immunoglobulins if no clinical response within
the first 6 hours of IV antibiotics the first 6 hours of IV antibiotics
IV immunoglobulin G (IVIG) may reduce IV immunoglobulin G (IVIG) may reduce
mortality.mortality.
High dose corticosteroid may also improve High dose corticosteroid may also improve
outcome as shown in isolated case reportsoutcome as shown in isolated case reports

20. Additional Additional
Treatments/ConsiderationsTreatments/Considerations
Remove tampon or other infectious sourcesRemove tampon or other infectious sources
Supportive measures for shock with fluid Supportive measures for shock with fluid
resuscitation and pressorsresuscitation and pressors
Possible vaginal irrigation with betadine solutionPossible vaginal irrigation with betadine solution
Avoidance of tampons, barrier contraceptives Avoidance of tampons, barrier contraceptives
(e.g. diaphragm, IUDs) in patients who do not (e.g. diaphragm, IUDs) in patients who do not
seroconvert to prevent recurrenceseroconvert to prevent recurrence

21. PrognosisPrognosis
Staphylococcal toxic shock has an associated 5% Staphylococcal toxic shock has an associated 5%
mortality in menstrual related cases.mortality in menstrual related cases.
Nonmenstrual related Staph TSS has 2-3x higher Nonmenstrual related Staph TSS has 2-3x higher
mortality ratemortality rate
Streptococcal toxic shock is very virulent with up to Streptococcal toxic shock is very virulent with up to
70% mortality70% mortality
Patients with deficient antibody response against TSS-Patients with deficient antibody response against TSS-
T1 are at increased risk of primary and recurrent TSST1 are at increased risk of primary and recurrent TSS
Recurrence rate is up to 40% in individuals who do not Recurrence rate is up to 40% in individuals who do not
generate appropriate titers of antibodies against TSS-T1generate appropriate titers of antibodies against TSS-T1

22. Disparity Disparity
Magnitude of inflammatory response may be governed Magnitude of inflammatory response may be governed
by host genetic factors such as MHC class II haplotypeby host genetic factors such as MHC class II haplotype
90-95% of middle aged women have detectable 90-95% of middle aged women have detectable
antibody titers against TSST-1. antibody titers against TSST-1.
Patients with TSS have poor antibody production Patients with TSS have poor antibody production
against TSST-1 with titers < 1:5, whereas healthy against TSST-1 with titers < 1:5, whereas healthy
patients have titers > 1:100patients have titers > 1:100
Possible variable effects on immune system based on Possible variable effects on immune system based on
estradiol levelsestradiol levels
Low concentration augmenting immune response by release Low concentration augmenting immune response by release
of IL-6 and TNFof IL-6 and TNF
High levels inhibiting release High levels inhibiting release

23. ReferencesReferences
Lappin E, Ferguson A. Gram-positive toxic shock Lappin E, Ferguson A. Gram-positive toxic shock
syndromes. Lancet Infect Dis 2009; 9: 281-90.syndromes. Lancet Infect Dis 2009; 9: 281-90.
Drage L. Life-threatening rashes: Dermatologic signs of Drage L. Life-threatening rashes: Dermatologic signs of
four infectious diseases.four infectious diseases. Mayo Clinic Proceedings 74.1 Mayo Clinic Proceedings 74.1
Jan 1999: 68-72.Jan 1999: 68-72.
  Herzer C. Toxic Shock Syndrome: Broadening the Herzer C. Toxic Shock Syndrome: Broadening the
Differential Diagnosis. J Am Board Family Practice Differential Diagnosis. J Am Board Family Practice
Mar-Apr 2001: 14(2): 131.Mar-Apr 2001: 14(2): 131.
Andrews J, Shamshirsaz A, Diekema D. Nonmentrual Andrews J, Shamshirsaz A, Diekema D. Nonmentrual
toxic shock syndrome due to methicillin resistant toxic shock syndrome due to methicillin resistant
Staphlococcus aureus. Obstetrics and Gynecology Vol. Staphlococcus aureus. Obstetrics and Gynecology Vol.
112, No. 4, October 2008 112, No. 4, October 2008