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.     

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.     

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.     

Abdominal complaints and neurological symptoms as an early sign of lung cancer: a manifestation of the anti-Hu syndrome

In two patients, women aged 73 and 46 years, gastrointestinal symptoms were initially not recognised as a paraneoplastic syndrome due to small-cell lung cancer. This led to redundant diagnostics as well as a delay in final diagnosis. The anti-Hu syndrome is characterised by the presence of anti-Hu antibodies and neurological symptoms. About a quarter of the patients with the anti-Hu syndrome will develop gastrointestinal motility disorders in the course of their illness. The primary tumour is usually a small-cell lung cancer. Whereas the presence of anti-Hu antibodies appears to be beneficial for the oncological prognosis, the neurological outcome is less favourable.     

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.     

Correspondence between neurological symptoms and outcome of quantitative sensory testing in the hand-arm vibration syndrome

To evaluate neurological symptoms in the vibration syndrome, 55 patients with vascular and neurological symptoms in the hand who had been exposed to vibration were examined. Their exposure to vibration was estimated and neurological vascular symptoms were evaluated according to symptom scales. Temperature thresholds were measured on the right thenar eminence and on the distal volar aspect of the second and third fingers held together on both sides. Vibration thresholds were measured dorsally on the second and fifth metacarpal bones and on the second and fifth fingers proximal to the nail roots. Subjects with advanced neurological symptoms had higher temperature and vibration thresholds than subjects with less advanced symptoms. No such relation was found between vascular symptoms and the outcome of sensory testing. Thus neurological but not vascular symptoms are reflected by the outcome of quantitative sensory testing. In subjects with advanced neurological symptoms the tests gave a high proportion of abnormal results, indicating that these tests may be used for the diagnosis of vibration syndrome on an individual basis. Patients with advanced vascular and neurological symptoms had higher exposure dose scores than patients with less advanced symptoms, indicating a dose response relation between vibration "dose" and neurological and vascular symptoms.     

Correspondence between neurological symptoms and outcome of quantitative sensory testing in the hand-arm vibration syndrome.

To evaluate neurological symptoms in the vibration syndrome, 55 patients with vascular and neurological symptoms in the hand who had been exposed to vibration were examined. Their exposure to vibration was estimated and neurological vascular symptoms were evaluated according to symptom scales. Temperature thresholds were measured on the right thenar eminence and on the distal volar aspect of the second and third fingers held together on both sides. Vibration thresholds were measured dorsally on the second and fifth metacarpal bones and on the second and fifth fingers proximal to the nail roots. Subjects with advanced neurological symptoms had higher temperature and vibration thresholds than subjects with less advanced symptoms. No such relation was found between vascular symptoms and the outcome of sensory testing. Thus neurological but not vascular symptoms are reflected by the outcome of quantitative sensory testing. In subjects with advanced neurological symptoms the tests gave a high proportion of abnormal results, indicating that these tests may be used for the diagnosis of vibration syndrome on an individual basis. Patients with advanced vascular and neurological symptoms had higher exposure dose scores than patients with less advanced symptoms, indicating a dose response relation between vibration "dose" and neurological and vascular symptoms.     

A study of Gulf War veterans with a possible deployment-related syndrome

A previous symptom-based survey of veterans of the 1990-1991 Persian Gulf War suggested a neurological syndrome (blurred vision, loss of balance/dizziness, tremors/shaking, and speech difficulty). The authors conducted the present study to determine whether specific findings could indicate an organic basis for this possible syndrome. They completed an extensive clinical and laboratory evaluation on Gulf War veterans with all 4 symptoms, using 3 comparison groups. A single clinically based neurological syndrome could not be identified. No deployment-related exposure appeared to explain the pattern of symptoms, but this evaluation suggested comorbidities and possibly multiple vaccines as important contributors. Many of the neurological symptoms reported by the studied veterans appear to have an organic basis, but comorbidities must be excluded before researchers can conclude that a definitive syndrome exists.     

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.     

Early and definitive diagnosis of toxic shock syndrome by detection of marked expansion of T-cell-receptor VBeta2-positive T cells

We describe two cases of early toxic shock syndrome, caused by the superantigen produced from methicillin-resistant Staphylococcus aureus and diagnosed on the basis of an expansion of T-cell-receptor VBeta2-positive T cells. One case-patient showed atypical symptoms. Our results indicate that diagnostic systems incorporating laboratory techniques are essential for rapid, definitive diagnosis of toxic shock syndrome.     

From gene to disease; adrenocortical insufficiency,achalasia and disrupted tear secretion: Allgrove syndrome

Allgrove syndrome (triple A syndrome) is an autosomal recessive disorder characterised by adrenocortical insufficiency, achalasia and alacrima. Patients also suffer from diverse neurological disorders. Allgrove syndrome is caused by mutations in the AAAS gene located at chromosome 12q13, which encodes for a tryptophan-aspartic acid (WD) repeat protein (aladin). The exact function of this protein is still not known.     

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.     

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.     

Cerebral deep vein thrombosis associated with rectal cancer

The authors report a case where the patient suffered from deep cerebral venous thrombosis, which developed beside cerebral metastases of a colorectal cancer. The pathogenesis and diagnosis of this disease are also discussed. This rare location of thrombosis is mainly due to hypercoagulable state seen in the use of oral contraceptive drugs, Beh?et syndrome, nephrotic syndrome, and as paraneoplastic syndrome in malignant diseases. Literature reports less than 50 cases of deep cerebral venous thrombosis, of which less than 10 are evoked by malignant disease. The symptoms of DCVT can mimic cerebral metastases in cancer patients. The course of disease is aggressive, the prognosis is poor. Even if the patients survive considerable neurological deficits may remain. Authors emphasize the importance of current modern diagnostic imaging methods in the diagnosis. The possibility of deep cerebral venous thrombosis must be taken into account if sudden neurological symptoms develop in a cancer patient.     

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.     

Systemic capillary leak syndrome

A man aged 61 had recurrent attacks of severe shock. The episodes were preceded by symptoms such as a runny nose, epigastric discomfort with nausea, vertigo, orthostatism and sometimes light fever. During the attacks there were marked hypotension, a strong rise of the haematocrit, a decrease of the protein and albumin concentrations in the blood and prerenal kidney failure. In addition, there was a paraprotein, type IgG-kappa. The shock every time responded rapidly to intravenous administration of fluid and was followed by a period of substantial polyuria. The pattern was characteristic of systemic capillary leak syndrome, a rare but frequently fatal disease characterized by episodes of unexplained extravasation of plasma. The aetiology and pathogenesis are unknown. Attacks are suppressed by supportive therapy (administration of fluids, inotropics) and future attacks may be prevented by the intake of terbutaline and theophylline. The systemic capillary leak syndrome should be considered in the differential diagnosis of idiopathic and anaphylactic shock.