What is TSS?

Staphylococcal toxic shock syndrome (TSS) is a rare, life-threatening systemic bacterial intoxication.

It occurs in diverse clinical settings, often mimicking more common febrile conditions. With early treatment, the serious consequences of TSS (organ failure, limb loss, death) can often be avoided. The diagnosis rests exclusively on clinical grounds and, while often readily established, it must first be considered. Accordingly, health professionals should be familiar with the manifestations of TSS, and should vigilantly consider the diagnosis in appropriate clinical settings.

TSS is an acute, noncontagious systemic illness characterised by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period (Table 1). It is caused by any of several related staphylococcal exotoxins. The exotoxins of S. aureus are proteinaceous compounds that are secreted at certain times during bacterial growth. The most common TSS toxins are toxic shock syndrome toxin-1 (TSST-1; ~75 percent of cases) and staphylococcal enterotoxin B (SEB; 20-25 percent of cases).

How does TSS Occur?

The pathogenesis of TSS proceeds as follows: (1) human colonisation or infection by a strain of S. aureus capable of producing a TSS toxin (“toxigenic strain”), (2) toxin production, (3) toxin absorption, and (4) intoxication.

The cross-sectional carriage rate of S. aureus is 15-40 percent. The anterior nasopharynx is the principal site of carriage; others include the axillae, vagina, and perineum. Among normal postmenarcheal European women, the rate of vaginal colonisation is 5-20 percent and is greatest during the menses. Tampon use does not influence that rate, nor do tampons enhance vaginal staphylococcal growth. About 25 percent of all S. aureus strains are toxigenic. Roughly 4-10 percent of normal people harbour toxigenic strains at any given time.

Although toxigenic strains have the genetic potential to produce toxins, they actually do so only at limited times, times when toxin production serves the bacterium’s survival needs. The exact nature of the environmental signals that cue the bacterium to produce toxin in vivo are not fully understood. Even less is known about the requirements and mechanisms for toxin uptake, but circulating toxin can be demonstrated in human TSS patients.

Intoxication by the TSS toxins is a very complex process. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Antibodies directed at the TSS toxins protect against TSS, these are thought to have developed by early adolescence in the majority of people. Interestingly, TSS is often not immunising; recurrent menstrual TSS is well-described.

How common is TSS?

TSS is a very rare illness – much rarer than one would predict based only on the considerations discussed in the previous section ’How does TSS occur?’ Health Department figures likely understate the true incidence, both because of incomplete reporting and misdiagnosis. Nevertheless, only about 18 “probable” or “confirmed” cases (see Table 1 for definitions) are reported in the UK each year, from a total population of some 58 million [Source: UK Public Health Laboratory Service 1985-1995]. A similar number of cases meeting 4 or fewer criteria are also reported. The mortality rate for confirmed or probable menstrual cases has historically been about 2.5 percent. It is two- to three-fold higher for non-menstrual cases.

In what settings does TSS occur?

TSS can occur whenever a nonimmune person is exposed to a TSS toxin. Illness is said to be “menstrual” if it occurs during the menstrual period and “non-menstrual” if at other times. Each category accounts for about half of cases ( Table 2). It is thought that the risk of TSS may be greater in children and young people, and that the acquisition of protective antibodies being a function of age.

Clinical Features

What does TSS look like?

The clinical features of full-blown TSS are captured by the case definition (Table 1). A minority of patients report mild prodromal symptoms. The acute illness typically begins precipitously, with high fever, nausea, vomiting, abdominal pain, severe muscle pain and tenderness, and headache, followed shortly by profuse watery diarrhoea. One or another feature of the illness may dominate the early presentation, leading to diagnostic confusion. Orthostasis or hypotension and the characteristic macular erythroderma develop over the next 48 hours. The erythroderma is usually generalised and often intense, but may be locally distributed, and may be mild or fleeting. The site of staphylococcal colonisation and toxin production may appear entirely benign.

While not accounted for by the case definition of TSS, mild systemic intoxications by the TSS toxins probably occur. These cases lack two or more of the diagnostic criteria for TSS and should not properly be called TSS. Nevertheless, they have certain features particularly suggestive of that diagnosis. Less exuberant toxin production by some strains, partial immunity in some hosts, or prompt correction of inciting conditions in some patients may explain these mild cases.

Diagnosis

When should the diagnosis of TSS be considered?

The differential diagnosis of the patient acutely ill with fever, rash and hypotension is extensive (Table 3). A careful history with attention to past health, possible infectious exposures, travel, vocation, hobbies, vaccination status, menstrual status and medication usage often narrows the diagnostic possibilities considerably.

Consider TSS in:

1) Any patient with fever and hypotension, whether exanthem is obvious or inapparent, especially if an alternative diagnosis is not readily apparent.
Suggestive epidemiological settings include:

• Females who are either menstruating or postpartum
• Females using barrier contraceptives
• Postoperative patients
• Patients with varicella or Herpes zoster infection
• Patients with chemical or thermal burns

Laboratory findings consistent with TSS include leucocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcaemia, and pyuria. Each is present in greater than 70 percent of patients.

2) The less ill patient with suggestive symptoms who fails to meet diagnostic criteria, but who is in an epidemiological risk group. For example, consider the possibility of mild systemic staphylococcal intoxication in young women reporting substantial or recurrent perimenstrual flu-like illness, particularly if that illness is associated with erythroderma or desquamation. Of course, the great majority of women experiencing nonspecific perimenstrual symptoms have syndromes unrelated to TSS or the staphylococcal toxins.

Treatment

How should TSS be Treated?

Treatment involves several key components:

1) Identification and decontamination of the site of toxin production: Drain or debride the lesion, remove foreign material, and irrigate copiously. Recent surgical wounds should be explored and irrigated even when signs of inflammation are absent.

2) Aggressive fluid resuscitation: Loss of fluid into the extravascular compartment can be very substantial. Maintenance of cardiac filling pressures is critical in order to prevent end organ damage. Adult patients with TSS have required up to 10 L of fluid in the first 24 hr.

3) Administration of antistaphylococcal antibiotics: Semisynthetic penicillin’s have been widely used for TSS. Growing evidence, however, suggests that the protein synthesis inhibitor clindamycin is more efficacious in this illness. Accordingly, the author recommends treating suspected TSS patients with clindamycin (900 mg i.v. every 8 hours for adults; 13 mg/kg i.v. every 8 hours for children), either alone or in combination with a cell wall active agent (semisynthetic penicillin or vancomycin). If the diagnosis of TSS is initially uncertain, broader empiric coverage is appropriate.

4) General supportive care: Intensive care monitoring is often indicated. Replete calcium and magnesium; provide ventilatory, pressor, and inotropic support; manage rhabdomyolysis, renal dysfunction, and / or coagulopathy.

5) Administration of pooled human immunoglobin: This should be reserved for refractory cases or cases associated with an undrainable focus of infection. All commercial immunoglobulin preparations contain high levels of anti-TSST-1 antibody. A single infusion of 400 mg/kg i.v. will generate a protective titre in a nonimmune patient.