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HPI: 15 yo G0 presented to Pediatric Urgent Clinic with complaints of headache, fever, rash, abdominal pain and nausea/vomiting. Pt states that it started with a headache 2 days prior, followed by fever of 102 F the night before. She then developed abdominal/epigastric pain, and tender rash of the hands, feet, thighs and perineum.
Rash started around the perineum and spread to the rest of the body. Rash is also associated with burning sensation and tingling of the extremities.
LMP 1 week prior to presentation. Using tampons and left 1 in for > 12 hours. Also accidentally dropped a tampon in the toilet at school and fished out to use it.
OB/GYN Hx: Menarche 12, heavy periods, 8 day flow, uses super plus tampons. Sexually active, using condoms.
Exam: Abdomen: Soft. Normal appearance. Bowel sounds are normal. She exhibits no distension and no mass. There is no hepatosplenomegaly. Tenderness is present in the epigastric area. She has no rigidity, no rebound, no guarding and no CVA tenderness.
Genitourinary: Vulva exhibits erythema. Vulva exhibits no exudate, no lesion, no rash and no tenderness. No discharge found. Vulva hyperemic and swollen. Tender.
Skin: Fine red scarlitini-like rash on inner thighs, hands and feet. Few on abdomen.
ED Exam: “Rash on the perineum that is spreading down her legs. She has another rash on her upper back and chest. The rash is raised red and tender to palpation.”
WBC'S AUTO 7.6
RBC AUTO 4.86
HCT AUTO 39.6
RDW, BLOOD 16.4 (H)
PLT'S AUTO 236
LYMPHS % AUTO 11.2 (L)
MONOS % AUTO 5.4
NEUTROPHILS % AUTO 78.8 (H)
EOS % AUTO 4.5
BASO'S % AUTO 0.1
RBC NUCLEATED, AUTO 0.0
TBILI 1.8 (H)
ALT 151 (H)
ESR WEST 23 (H)
CRP 64.0 (H)
AST 138 (H)
UA GLUC <30 (NEG)
UA KETONES <10 (NEG)
UA SP GR 1.026
UA HGB 0.50 (2+) (A)
PH UA 7.5
UA PROT 30 (1+) (A)
UA NO2 NEGATIVE
LE, UA POSITIVE (A)
UROBILINOGEN UA QL >12.0 (4+) (A)
UA BILI 1.0 (1+) (A)
RBC, UA/HPF 4-10 (A)
UA WBC'S/HPF >25 (A)
UA BACT/HPF FEW (A)
SQUAM EPITHE CELL URNS AUTO QUAL FEW (A)
TRANSIT EPITHE CELL UA AUTO QUAL FEW (A)
HIV, Hep B and syphilis negative
Blood culture negative x 2
Urine Culture negative
MRSA Culture negative
Genital Culture: +GBS
Hospital Course: Transferred from pediatric urgent clinic to ED for additional evaluation/stabilization. Started on IV Nafcillin, Gentamicin and Clindamycin in the ED. Admitted to ICU where she improved clinically and rash resolved. She was then transferred to the pediatric service where they discontinued previous antibiotics and started her on Rocephin. Pt was discharged on HD #3 with 7 day course of PO Clindamycin per Peds ID and outpatient follow up.
Toxic Shock Syndrome
Toxin mediated, acute systemic disease resulting in shock and multi-system organ failure
Staphylococcus aureus and Group A Streptococcus pyogenes are the most common organisms
Gram positive infections are responsible for > 50% of sepsis in the US.
Mortality rate higher than meningococcal septicemia
Staphylococcal TSS first reported in 1978 and increased in incidence in the early 1980s in the US
Associated with use of high absorbency tampons in women
During 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 100,000 per year
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% of healthy women and remain unchanged compared to the 1980s.
Toxic Shock Syndrome
Nonmenstrual TSS associated with Staph comprise about 50% of cases
Associated with barrier contraceptive (diaphragm, IUD), vaginal and cesarean deliveries, surgical and postpartum wound infections, mastitis, sinusitis, burns, cutaneous infections…
Streptococcal toxic shock syndrome attributed to Streptoccocus pyogenes was reported in 1987
Secondary to invasive Group A Strep soft tissue infections
Mortality of approximately 30-40%
Incidence of between 1.5 – 5.2 cases per 100,000 per year
Higher rates at extremes of age and ethnic minorities
Higher incidence in patients with underlying chronic illness, post varicella infection and NSAIDs use
Bacterial endotoxins act as superantigens
Protein toxins that have the ability to trigger excessive T-cell activation with downstream activation of other cell types and cytokine release
Conventional antigen presentation activates 0.01% of host T-cells compared to superantigen binding which activates up to 20-30% of host T-cells
Also associated with rapid increase in cytokine production from T-cells
T-cell activation leads to additional recruitment of T and B cells to the site of infection
Staphylococcal TSS-T1 (Toxic shock syndrome Toxin 1) is responsible for 95% of menstrual related TSS.
TSS-T1 able to cross mucosal barriers
Also detectable in 50% of non menstrual TSS
Not all patients colonized with Staph aureus or strep pyogenes develop TSS and interaction between host immune system and pathogen play an important role
Absence of antibodies against superantigens is a major risk factor to developing TSS
> 85% of women aged 13-40 have TSS-T1 antibodies that are thought to be protective
Low or negative antibody titers are found in 90.5% of patients with menstrual TSS
More than 50% of these patients fail to seroconvert within 2 months of their illness
Hallmark symptoms include fever, shock and multi-system failure
Staphylococcal TSS: starts with flu like prodromal illness including fever, GI distress and severe myalgia. Desquamation is a late feature and happens 10-21 days after initial onset of symptoms.
Blood cultures are positive in < 5% of Staph TSS
Menstrual and non menstrual TSS are identical clinically
Up to 95% of patients diagnosed with menstrual TSS have onset of illness during menses
Fever and rash more prevalent in early disease
Recurrence of menstrual TSS well documented but rare in non menstrual TSS
Postoperative nonmenstrual TSS usually occurs within 48 hours of surgery
Nonmenstrual TSS patient are more likely to acquire infection nosocomially and to have had prior antibiotic treatment.
Nonmenstrual TSS are more commonly associated with CNS and renal complications
Streptococcal TSS typically arise from deep seated invasive soft tissue infections such as necrotising fasciitis, cellulitis and myositis which are extremely painful.
Diffuse macular erythroderma followed by desquamation in 1-2 weeks
Mucosal (oral and genital) hyperemia
Aim to decrease bacterial load and endotoxin production
Penicillinase resistant penicillin, cephalosporin for suspected Staphylococcus aureus TSS
Vancomycin for suspected MRSA
Group A Streptococcus very sensitive to B-lactam agents including Penicillin G (first line treatment)
Although PCN is bactericidal, it is less effective against high organism load (ineffective if treatment delayed by > 2 hours)
Given with Clindamycin which is inhibitory of protein synthesis of superantigen production
Inhibitory of endotoxin production in both Staph and Group A Strep
Possible consideration of starting IV immunoglobulins if no clinical response within the first 6 hours of IV antibiotics
IV immunoglobulin G (IVIG) may reduce mortality.
High dose corticosteroid may also improve outcome as shown in isolated case reports
Remove tampon or other infectious sources
Supportive measures for shock with fluid resuscitation and pressors
Possible vaginal irrigation with betadine solution
Avoidance of tampons, barrier contraceptives (e.g. diaphragm, IUDs) in patients who do not seroconvert to prevent recurrence
Staphylococcal toxic shock has an associated 5% mortality in menstrual related cases.
Nonmenstrual related Staph TSS has 2-3x higher mortality rate
Streptococcal toxic shock is very virulent with up to 70% mortality
Patients with deficient antibody response against TSS-T1 are at increased risk of primary and recurrent TSS
Recurrence rate is up to 40% in individuals who do not generate appropriate titers of antibodies against TSS-T1
Magnitude of inflammatory response may be governed by host genetic factors such as MHC class II haplotype
90-95% of middle aged women have detectable antibody titers against TSST-1.
Patients with TSS have poor antibody production against TSST-1 with titers < 1:5, whereas healthy patients have titers > 1:100
Possible variable effects on immune system based on estradiol levels
Low concentration augmenting immune response by release of IL-6 and TNF
High levels inhibiting release
Lappin E, Ferguson A. Gram-positive toxic shock syndromes. Lancet Infect Dis 2009; 9: 281-90.
Drage L. Life-threatening rashes: Dermatologic signs of four infectious diseases. Mayo Clinic Proceedings 74.1 Jan 1999: 68-72.
Herzer C. Toxic Shock Syndrome: Broadening the Differential Diagnosis. J Am Board Family Practice Mar-Apr 2001: 14(2): 131.
Andrews J, Shamshirsaz A, Diekema D. Nonmentrual toxic shock syndrome due to methicillin resistant Staphlococcus aureus. Obstetrics and Gynecology Vol. 112, No. 4, October 2008