Toxic shock syndrome: broadening the differential diagnosis

BACKGROUND: Toxic shock syndrome is a rare but potentially fatal toxin-mediated febrile illness. Although classically associated with tampon use, it is now known that many nonmenstrual conditions are related to this syndrome. Serious morbidity and mortality can occur if this syndrome is not promptly recognized. METHODS: MEDLINE was searched from 1978 to the present using the phrase "toxic shock syndrome." Case reports and articles related to tampon-associated toxic shock syndrome were excluded from the literature review except when defining toxic shock syndrome or discussing the cause of the syndrome. A case of nonmenstrual toxic shock syndrome associated with an intrauterine device and a review of the definition, cause, diagnostic criteria, and management are reported. RESULTS AND CONCLUSIONS: Toxic shock syndrome can mimic many common diseases. Because it can be associated with a number of nonmenstrual-related conditions, patients with unexplained fever and rash and a toxic condition out of proportion to local findings should have the diagnosis of toxic shock syndrome in their differential diagnosis. Early recognition and aggressive management can decrease the overall morbidity and mortality.     

Toxic shock syndrome. I. Clinical exclusion of other syndromes by strict and screening definitions

Several clinical definitions of toxic shock syndrome have been proposed and used in extensive epidemiologic and clinical studies. Most of these definitions suggest (but usually do not require) that there be sufficient laboratory studies to exclude other potentially similar syndromes. Simplified definitions which broaden the spectrum of toxic shock syndrome illness have also been proposed but not validated. In this study, clinical findings of consecutive hospitalized patients were compared: nine with toxic shock syndrome (confirmed by a modification of the collaborative strict case definition) and 120 with potentially similar diagnoses (bacteremia with shock, meningococcemia, Staphylococcus aureus bacteremia, scarlet fever, toxic epidermal necrolysis, acute rheumatic fever, leptospirosis, Rocky Mountain spotted fever, rubeola, Kawasaki syndrome, erythema multiforme, and Stevens-Johnson syndrome). None of the 120 controls satisfied the clinical criteria of the modified strict definition of toxic shock syndrome, demonstrating its exclusionary properties even in the absence of additional laboratory data. A "simplified" screening definition was constructed which might be applied early in illness (i.e., at admission) and this definition distinguished all the patients with toxic shock syndrome from all but three (2.5%) of the 117 analyzable patients with other mucocutaneous or potential infectious shock syndromes. Applied prospectively in the state of Colorado passive/active reporting system, the screening definition identified 24 potential toxic shock syndrome cases of which 19 (76%) eventually were confirmed as toxic shock syndrome. Before being adopted and widely used, clinical syndrome definitions should be documented to exclude other potentially overlapping syndromes or should require additional mandatory exclusionary laboratory data.     

Tampon absorbency, composition and oxygen content and risk of toxic shock syndrome

Tampon use has been identified as a major risk factor for toxic shock syndrome, although the etiologic role of tampons is not clearly understood. Two epidemiologic studies conducted to date have reported an association between tampon absorbency and risk of toxic shock syndrome. This finding is not corroborated by laboratory studies, however, which have suggested that absorbency may be a marker for other characteristics that create an environment conducive to the elaboration of toxic shock syndrome toxin 1. We used data from the previously reported Tri-state study to estimate simultaneously the effects of tampon oxygen content, absorbency and chemical composition. Although the data are sparse, oxygen content was more strongly associated with risk of toxic shock syndrome than either absorbency or chemical composition. the results suggest that it may be possible to develop a highly absorbent tampon that is not associated with a high risk of toxic shock syndrome.     

Studies on staphylococci from toxic shock syndrome in France, 1981-1983

Staphylococci from 22 cases of toxic shock syndrome with onsets between 1981 and March 1983 have been studied. Another four cases were detected by abstract surveillance. Three of these patients died. The case histories show that the syndrome occurs in women during menstruation as well as in males and in children, and is associated with Staphylococcus aureus infections. The production of enterotoxins (A, B, C) and toxic shock toxin by S. aureus isolates from toxic shock syndrome was investigated. Twenty-two of the 23 isolates were found to be toxigenic: 7 produced enterotoxin A, 8 produced enterotoxin B, 3 produced enterotoxin C and 13 produced toxic shock toxin. The latter was found with enterotoxin A in five cases, and with enterotoxins A and B in only one case. Sixty-three percent of 46 S. aureus strains isolated from the vagina of patients with diseases other than toxic shock syndrome produced toxin; eight of these strains produced toxic shock toxin.     

Studies on staphylococci from toxic shock syndrome in France, 1981-1983.

Staphylococci from 22 cases of toxic shock syndrome with onsets between 1981 and March 1983 have been studied. Another four cases were detected by abstract surveillance. Three of these patients died. The case histories show that the syndrome occurs in women during menstruation as well as in males and in children, and is associated with Staphylococcus aureus infections. The production of enterotoxins (A, B, C) and toxic shock toxin by S. aureus isolates from toxic shock syndrome was investigated. Twenty-two of the 23 isolates were found to be toxigenic: 7 produced enterotoxin A, 8 produced enterotoxin B, 3 produced enterotoxin C and 13 produced toxic shock toxin. The latter was found with enterotoxin A in five cases, and with enterotoxins A and B in only one case. Sixty-three percent of 46 S. aureus strains isolated from the vagina of patients with diseases other than toxic shock syndrome produced toxin; eight of these strains produced toxic shock toxin.     

A hospital discharge code review of toxic shock syndrome in Wisconsin

The Wisconsin Division of Health conducted a review of discharge coding for 142 (97%) of the state's general care hospitals for the period 1980-1983 to evaluate the use of International Classification of Diseases codes for toxic shock syndrome and to estimate completeness of reporting of recognized hospitalized cases of the syndrome to the Division of Health. Hospital use of code 040.89 (other bacterial diseases-other) recommended for toxic shock syndrome by the National Center for Health Statistics in January 1981 increased from 23% of Wisconsin hospitals in 1980 to 92% in 1983. The sensitivity of this code for toxic shock syndrome increased from 54% to 85% from 1981 to 1983; study population specificity was stable at approximately 95%, and the predictive value was 65% in 1981 and 70% in 1983. The use of codes 785.50 (shock, unspecified) and 785.59 (nontraumatic shock-other) frequently assigned to toxic shock syndrome was also assessed; all measures of their utility decreased in proportion to the increasing use of 040.89. The coding review identified 20 previously unreported cases of toxic shock syndrome; the 10 confirmed and 10 probable cases represent 4% and 21% of the state's 223 confirmed and 47 probable cases with onsets in 1980-1983. Results indicate that a National Center for Health Statistics coding recommendation for a disease of emerging significance can result in relatively uniform coding of the illness, which can provide a tool for case finding and surveillance evaluation for hospitalized cases.     

A patient with toxic shock syndrome following correction of the nasal septum

A male aged 30 suffered from toxic shock syndrome after septorhinoplasty with positioning of a tampon. Initial treatment consisted of removing the tampon and supportive care, as a result of which the patient recovered. The patient was a carrier of Staphylococcus aureus which produced toxic shock syndrome toxin-I (TSST-I). Anti-TSST-I antibodies were already found in the serum in the initial phase of the disease.     

Toxic shock syndrome. II. Estimated occurrence in Colorado as influenced by case ascertainment methods

Medical records for hospitalized patients between 30 days and 30 years of age at two hospitals, one in each of two Colorado counties, were reviewed for possible cases of toxic shock syndrome conforming to one or both of two clinical case definitions. Patients with toxic shock syndrome were detected in each year from 1970 through 1982. Fifty patients with possible toxic shock syndrome were identified; 14 were males, five were premenarchal females, and the remaining 31 were females of menstrual age of whom 21 (42% overall) were menstruating at the time of illness. The combined annual toxic shock syndrome incidence rate ranged between 0.8/100,000 population less than or equal to 30 years of age (1974) and 9.1/100,000 (1980) with a maximum of 15.8/100,000 (1980) in females between the ages of 10 and 30. Incidence curves for males, females less than or equal to 30 years of age, and females of menstrual age (10-30 years) fluctuated in a statistically (p less than 0.02) nonrandom fashion, each peaking in 1979-1980 and declining in 1981. In a separate statewide voluntary case reporting system, 103 cases of toxic shock syndrome of all ages were reported by health care providers with onset from 1970-1982. A minimum estimate of 26 (26%) of these were not menstrually-associated, occurring in five females prior to menarche, three following menopause, three postpartum, and 15 males. Total cases reached an annual peak in 1980, declined somewhat in 1981, and increased during 1982 to levels comparable to 1980. Less than half (46%) of the strictly defined cases actively ascertained in the retrospective hospitalized population study had been reported voluntarily to the statewide system. Jurisdictions depending primarily on passive toxic shock syndrome case ascertainment techniques, even with periodic active solicitations, may not be reliably detecting the majority of cases, and those cases which are so reported may be limited by physician perception of syndrome spectrum.     

In vitro amplification of toxic shock syndrome toxin-1 by intravaginal devices

Super-absorbent tampons and an exotoxin of Staphylococcus aureus have been associated with the recent emergence of toxic shock syndrome (TSS). In the majority of cases, when a TSS strain of S. aureus was cultivated in the presence of various tampons and a contraceptive sponge, increased amounts of toxic shock syndrome toxin-1 (TSST-1) were observed to be produced into the blood medium by the bacterium. The amplification of toxin by these products adds support to the epidemiologic data in establishing the causal link between tampons and TSS.     

Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001-2005

On July 19, 2005, the Food and Drug Administration (FDA) issued a public health advisory regarding the deaths of four women in the United States after medical abortions with Mifeprex (mifepristone, formerly RU-486; Danco Laboratories, New York, New York) and intravaginal misoprostol. Two of these deaths occurred in 2003, one in 2004, and one in 2005. Two of these U.S. cases had clinical illness consistent with toxic shock and had evidence of endometrial infection with Clostridium sordellii, a gram-positive, toxin-forming anaerobic bacteria. In addition, a fatal case of C. sordellii toxic shock syndrome after medical abortion with mifepristone and misoprostol was reported in 2001, in Canada. All three cases of C. sordellii infection were notable for lack of fever, and all had refractory hypotension, multiple effusions, hemoconcentration, and a profound leukocytosis. C. sordellii previously has been described as a cause of pregnancy-associated toxic shock syndrome.     

Knowledge of Toxic Shock Syndrome Among Adolescent Females: A Need for Education

Toxic shock syndrome (TSS) has been identified as a potentially fatal but preventable illness that causes disease, disability, and premature death, especially among adolescent females using high absorbency tampons. In 1983 the authors surveyed 129 high school girls in three midwestern senior high schools to determine the relationship between choice of a menstrual product and knowledge about toxic shock syndrome. The study found that the knowledge level of adolescent females about TSS was fragmented and inaccurate. No significant relationship was found between choice of a menstrual product and knowledge about TSS; very little variation existed between the scores for napkin users, regular tampon users, and high absorbency tampon users. Results of the study are discussed in terms of the implications for the health of adolescent females. Recommendations are offered for utilizing health professionals, parents, and the news media in the development of toxic shock education programs.     

Periodically leaking capillaries

The systemic capillary leak syndrome (Clarkson's syndrome) is a rare idiopathic disorder, characterized by recurrent episodes of hypovolaemic shock, haemoconcentration and hypoalbuminaemia due to a sudden shift of fluid and macromolecules from the intravascular to the interstitial space. A young man is presented in whom recurrent attacks of hypotension and diffuse swelling were initially attributed to staphylococcal toxic shock syndrome. With the additional finding of a monoclonal gammopathy, the diagnosis of systemic capillary leak syndrome was made. Recognition of this syndrome is important, as prophylactic treatment with terbutaline and theophylline may be beneficial in this life threatening syndrome.     

Toxic shock syndrome and diaphragm use

A case of toxic shock syndrome (TSS) associated with diaphragm use is presented. Adolescents who use a diaphragm should be informed of the symptoms of TSS, and those with the syndrome should be questioned about diaphragm use.     

Toxic shock syndrome (TSS) in children

Toxic shock syndrome is uncommon in the prepubertal age group. Two children presented with pyrexia, macular erythroderma, vomiting, hypotension and rapid deterioration of consciousness. One child had severe neurological involvement. The diagnosis of toxic shock syndrome was established in both cases by the exclusion of other causes and by culturing staphylococcus aureus. We postulate that the neurological manifestations were caused by a direct neurotoxic action of the staphylococcal-produced toxin. Both children made a complete recovery.     

Infectious exanthems and unusual infections

Invasive disease due to group A beta-hemolytic streptococci (GABHS) can be divided into 3 categories of disease: streptococcal toxic shock syndrome (strepTSS), necrotizing fasciitis, and other invasive GABHS disease. Patients with strepTSS may have multiorgan failure within hours of presentation. Clindamycin and penicillin G should be used in combination for treatment of invasive GABHS disease. The mortality rate for menstrual staphylococcal toxic shock syndrome has decreased with early recognition and treatment, and removal of hyperabsorbent tampons from the market. Kawasaki syndrome (KS) is the most common cause of acquired heart disease in children in the U. S., and atypical forms have a higher mortality rate than typical KS. Hantavirus pulmonary syndrome is a zoonosis with an 80% mortality rate if the diagnosis is not made on first presentation and patients return to the hospital in shock. Children and adolescents with Lyme disease have an excellent prognosis and respond well to antimicrobial therapy. Cat scratch disease (CSD) is caused by Bartonella henselae and is transmitted by flea-infested kittens. CSD lymphadenopathy typically resolves spontaneously in 2?3 months; however, there is a 50% likelihood of resolution in 1 month if patients receive a 5-day treatment course with azithromycin.     

Infectious Shock and Toxic Shock Syndrome Diagnoses in Hospitals,Colorado, USA

In Colorado, USA, diagnoses coded as toxic shock syndrome (TSS) constituted 27.3% of infectious shock cases during 1993–2006. The incidence of staphylococcal TSS did not change significantly overall or in female patients 10–49 years of age but increased for streptococcal TSS. TSS may be underrecognized among all ages and both sexes.     

Enterotoxins and toxic-shock syndrome toxin-1 in non-enteric staphylococcal disease.

Over the 7 years 1985-91, 997 strains of Staphylococcus aureus from 962 patients with diseases other than food poisoning have been tested for the production of enterotoxins and toxic shock syndrome toxin-1 (TSST-1) and phage typed. In all, 128 cases could be classified as confirmed or probable toxic shock syndrome (TSS) but a further 199 cases were classified as possible or unconfirmed TSS. In 219 cases, an alternative diagnosis could be supported and 45 cases were classified as sudden infant death syndrome. In 371 cases, insufficient information for classification was available. Strains of phage group I producing TSST-1 were associated with menstrual TSS. Many menstrual TSS cases were aged less than 20 and were using non-introducer tampons. When all strains were reviewed, strong associations were observed between TSST-1 production and phage group I strains, enterotoxin B production and group V strains, enterotoxin C and phage-type 95 strains and between enterotoxin A without TSST-1 and phage group III strains.     

Toxic shock syndrome in the United States: surveillance update, 1979 1996

Menstrual toxic shock syndrome (TSS) emerged as a public health threat to women of reproductive age in 1979 80. We reviewed surveillance data for the period 1979 to 1996, when 5,296 cases were reported, and discuss changes in the epidemiologic features of TSS.     

Tampon disease, still not past tense]

On the basis of three case histories we discuss the menstrual toxic shock syndrome (TSS), characterised by multi-organ involvement, fever, exanthema and shock. The symptoms are provoked by a toxin (TSST-1), a product of certain St. aureus strains. Rapid recognition is important in order to prevent complications such as the adult respiratory distress syndrome, disseminated intravascular coagulation or ventricular fibrillation. It appears that a tampon can lower the magnesium concentration in the vagina by a process of ion exchange, thus creating an environment that favours the production of TSST-1 by St. aureus. This knowledge may lead to preventive measures in the production of tampons in the future.     

Toxic shock syndrome in three adolescent males

Toxic shock syndrome (TSS) is associated with a spectrum of Staphylococcus aureus infections and is not just a disease of menstruating females. We report three cases of TSS in adolescent males. In one case the origin of infection was a cauterized wart that did not appear clinically infected. Two cases were associated with bacteremia and had demonstrable acute phase antibody to toxic shock syndrome toxin-1 (TSST-1). One of these patients died. The S. aureus strain from this patient did not produce TSST-1 but did produce enterotoxin D. The historical and clinical features of TSS are reviewed.