TOXIC SHOCK SYNDROME

1. TOXIC SHOCK SYNDROME Akmal Abbasi, M.D.

2. TOXIC SHOCK SYNDROME • Toxic shock syndrome (TSS) is an acute, febrile illness produced by a bacterial exotoxin, with a fulminating downhill course involving dysfunction of multiple organ systems. • It is not unusual for the syndrome to develop from a site of bacterial colonization rather than from an infection. • A woman with TSS may develop rapid onset of hypotension associated with multiorgan system failure.

3. Case Definition of Toxic Shock Syndrome • Fever (temperature 38.9° C, 102° F) • Rash characterized by diffuse macular erythroderma • Desquamation occurring 1-2 weeks after onset of illness (in survivors) • Hypotension (systolic blood pressure ≤90 mm Hg in adults) or orthostatic syncope

4. Case Definition of Toxic Shock Syndrome e. Hepatic (total bilirubin, SGOT, or SGPT twice normal level) f. Hematologic (platelets ≤ 100,000/mm3 ) g. Central nervous system (disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension absent)

5. Case Definition of Toxic Shock Syndrome 5. Involvement of three or more of the following organ systems: • Gastrointestinal (vomiting or diarrhea at onset of illness) • Muscular (myalgia or creatine phosphokinase level twice normal) • Mucous membrane (vaginal, oropharyngeal, or conjunctival hyperemia) • Renal (BUN or creatinine level ≥ twice normal or ≥5 WBC per HPF in absence of urinary tract infection)

6. Case Definition of Toxic Shock Syndrome h. Cardiopulmonary (adult respiratory distress syndrome, pulmonary edema, new onset of second- or third-degree heart block, myocarditis) 6. Negative throat and cerebrospinal fluid cultures (a positive blood culture for S. aureus does not exclude a case) 7. Negative serologic tests for Rocky Mountain spotted fever, leptospirosis, rubeola

7. Etiology & Pathogenesis • TSS was first described in 1978 by Todd as a sometimes fatal sequela of Staphylococcusaureus infection in children. • In the early 1980s more than 95% of the reported cases of TSS were diagnosed in previously healthy, young (<30 years), menstruating females. • S. aureus has been isolated from the vagina in more than 90% of these cases. • Presently, approximately 50% of cases of TSS are related to menses.

8. Etiology & Pathogenesis • In cases of menses-related TSS there is a history of the presence of a foreign body in the vagina, usually a tampon or diaphragm. • Nonmenstrual TSS may be a sequela of focal staphylococcal infection of the skin and subcutaneous tissue, often following a surgical procedure. • In the past few years it has been recognized that occasionally severe postoperative infections by Streptococcus pyrogenes produce a similar "streptococcal toxic shock-like syndrome."

9. Etiology & Pathogenesis • There are three requirements for the development of classical TSS: • (1) the woman must be colonized or infected with S. aureus, • (2) the bacteria must produce TSS toxin 1 (TSST-1) and/or related toxins, and • (3) the toxins must have a route of entry into the systemic circulation.

10. Etiology & Pathogenesis • The majority of strains of S. aureus are unable to produce TSS toxin 1. • Interestingly, approximately 85% of adult females have antibodies against TSST-1 • The mortality of reported cases is high—2% to 8%. • If an individual woman continues to use tampons when the vagina is colonized with S. aureus, there is a significant chance of a recurrence.

11. Etiology & Pathogenesis • The signs and symptoms of TSS are produced by the exotoxin named toxin 1. • Toxin 1 is a simple protein with a molecular weight of 22,000. • It is accepted as the underlying cause of the disease. • The current hypothesis is that toxins act as "superantigens" and facilitate the release of tumor necrosis factor, interleukins, and other cytokines, and also induce a suppression of some immune responses.

12. Etiology & Pathogenesis • Pathophysiologically, superantigens are able to bypass some of the steps of the typical immune response sequence. • The primary effects of toxin 1 are to produce increased vascular permeability and thus profuse leaking of fluid (capillary leak) from the intravascular compartment into the interstitial space and associated profound loss of vasomotor tone resulting in decreased peripheral resistance.

13. Etiology & Pathogenesis • Rarely are blood cultures positive for S. aureus in a woman with TSS. • Thus the exotoxin is believed to be absorbed directly from the vagina. • It is possible that microulcerations produced by use of tampons facilitate the toxin's entry into the systemic circulation. • The risk of nonmenstrual TSS is definitely increased in women who use barrier contraceptives such as the diaphragm, cervical cap, or a sponge containing nonoxynol 9.

14. Laboratory Abnormalities in Early Toxic Shock Syndrome Present in >85% of Patients • Coagulase-positive staphylococci in cervix or vagina • Immature and mature polymorphonuclear cells >90% of WBCs • Total lymphocyte count <650/mm3 • Total serum protein level <5.6 mg/dl • Serum albumin level <3.1 g/dl • Serum calcium level <7.8 mg/dl • Serum creatinine clearance >1.0 mg/dl • Serum bilirubin value >1.5 mg/dl • Serum cholesterol level ≤120 mg/dl • Prothrombin time >12 seconds

15. Laboratory Abnormalities in Early Toxic Shock Syndrome Present in >70% of Patients • Platelet count <150,000/mm3 • Pyuria >5 WBCs per high-power field • Proteinuria ≥2 • (BUN) >20 mg/dl • Aspartate aminotransferase (formerly SGOT) > 41 U/L

16. Signs & Symptoms • Because of the severity of the disease, gynecologists should have a high index of suspicion for TSS in a woman who has an unexplained fever and a rash during or immediately following her menstrual period. • The syndrome has a wide range of symptoms. • Most women experience a prodromal flulike illness for the first 24 hours.

17. Signs & Symptoms • Between days 2 and 4 of the menstrual period, the patient experiences an abrupt onset of a high temperature associated with headache, myalgia, sore throat, vomiting, diarrhea, a generalized skin rash, and often hypotension. • It is important to consider that not all women with TSS experience the full-blown manifestations of the disease.

18. Signs & Symptoms • The most characteristic manifestations of TSS are the skin changes. • During the first 48 hours the skin rash appears similar to an intense sunburn. • During the next few days the erythema will become more macular and look like a drug-related rash. • From days 12 to 15 of the illness, there is a fine, flaky, desquamation of skin over the face and trunk with sloughing of the entire skin thickness of the palms and soles.

19. Signs & Symptoms • The vaginal mucosa is hyperemic during the initial phase of the syndrome. • During pelvic examination, patients complain of tenderness of the external genitalia and vagina. • Myalgia, vomiting, and diarrhea are experienced by more than 90% of women with TSS.

20. Differential Diagnosis • The differential diagnosis of toxic shock syndrome includes • Rocky Mountain spotted fever, • Streptococcal scarlet fever, and • Leptospirosis.

21. Management • The management of a classic case of severe TSS demands an intensive care unit and the skills of an expert in critical care medicine. • The first priority is to eliminate the hypotension produced by the exotoxin. • Copious amounts of intravenous fluids are given while pressure and volume dynamics are monitored with a pulmonary artery catheter. • Mechanical ventilation is required for women who develop adult respiratory distress syndrome.

22. Management • When the patient is initially admitted to the hospital, it is important to obtain cervical, vaginal, and blood cultures for S. aureus. • Although there is no controlled series documenting its efficacy, it is prudent to wash out the vagina with saline or dilute iodine solution to diminish the amount of exotoxin that may be absorbed into the systemic circulation. • Women with TSS should be treated with a beta-lactamase-resistant antistaphylococcal antibiotic for 10 to 14 days.

23. Management • Possible antibiotic choices include beta-lactamase-resistant penicillins (oxacillin, methicillin, or nafcillin), clindamycin and gentamicin, vancomycin, and aminoglycosides. • If the diagnosis is questionable, it is best to include the use of an aminoglycoside to obtain coverage for possible gram-negative sepsis. • Antibiotic therapy probably has little effect on the course of an individual episode of TSS.

24. Management • The reported risk of recurrence without antibiotic therapy is approximately 33%. • If the underlying etiology of toxic shock syndrome is a skin infection, the infected site should be drained and debrided. • Administration of parenteral corticosteroids is controversial.

25. Management • However, most centers no longer give corticosteroids. • Infusions of vasopressors are titrated to obtain optimal perfusion pressures. • Others have advocated naloxone (Narcan) for treatment of severe hypotension. • Recent reports suggest that intravenous immunoglobulins may be beneficial.

26. Management • It is possible to decrease the incidence of TSS by a change in use of catamenial products. • Women should be encouraged to change tampons every 4 to 6 hours. • The intermittent use of external pads is also good preventive medicine. • Women will usually accept the recommendation to wear external pads during sleep.

27. Management • The incidence of TSS has decreased dramatically with the removal of superab-sorbing tampons from the market. • A study by Tierno and Hanna reported that all-cotton tampons are the safest choice to avoid menstrual toxic shock syndrome.