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Toxic shock syndrome
Diseases & Conditions A-Z

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Clinical Symptoms

Dennis L. Stevens, Ph.D., M.D

Pain the most common initial symptom of streptococcal TSS is abrupt in onset and severe, and usually precedes tenderness or physical findings. The pain usually involves an extremity but may also mimic peritonitis,pelvic inflammatory disease, pneumonia, acute myocardial infarction, or pericarditis. Twenty percent of patients have an influenza-like syndrome characterized by fever, chills, myalgia, nausea, vomiting, and diarrhea (8). Fever is the most common early sign, although hypothermia may be present in patients with shock. Confusion is present in 55% of patients, and in some, coma or combativeness is manifest (8). Eighty percent of patients have clinical signs of soft tissue infection, such as localized swelling and erythema, which in 70% of patients progressed to necrotizing fasciitis or myositis and required surgical debridement, fasciotomy or amputation (8). An ominous sign is the progression of soft tissue swelling to the formation of vesicles, then bullae, which appear violaceous or bluish. In such patients, emergent surgical exploration should be performed to establish the diagnosis and distinguish GAS infection from other necrotizing soft tissue infections. Among the 20% of patients without soft tissue findings, clinical symptoms include endophthalmitis, myositis, perihepatitis, peritonitis, myocarditis, and overwhelming sepsis. A diffuse, scarlatina-like erythema occurs in only 10% of patients. Nearly 50% of patients may have normal blood pressure (systolic pressure >110 mm Hg) on admission but develop hypotension within the subsequent 4 hours (8).

Laboratory Evaluation of Patients

On admission, renal involvement is indicated by the presence of hemoglobinuria and by serum creatinine values that are, on average, >2.5 times normal. Renal impairment precedes hypotension in 40% to 50% of patients (8). Hypoalbuminemia is associated with hypocalcemia on admission and throughout the hospital course. The serum creatinine kinase level is useful in detecting deeper soft-tissue infections; when the level is elevated or rising, there is a good correlation with necrotizing fasciitis or myositis. Though the initial laboratory studies demonstrate only mild leukocytosis, the mean percentage of immature neutrophils (including band forms, metamyelocytes, and myelocytes) is striking, reaching 40% to 50%. Blood cultures are positive in 60% of cases (8).

Clinical Course

Shock is apparent at the time of admission or within 4 to 8 hours in virtually all patients (Table 2). In only 10% of patients does systolic blood pressure become normal 4 to 8 hours after administration of antibiotics, albumin, and electrolyte solutions containing salts or dopamine; in all other patients, shock persists. Similarly, renal dysfunction progresses or persists in all patients for 48 to 72 hours in spite of treatment, and many patients may require dialysis (8). In patients who survive, serum creatinine values return to normal within 4 to 6 weeks. Renal dysfunction precedes shock in many patients and is apparent early in the course of shock in all others. Acute respiratory distress syndrome occurs in 55% of patients and generally develops after the onset of hypotension (8). Supplemental oxygen, intubation, and mechanical ventilation are necessary in 90% of the patients in whom this syndrome develops. Mortality rates vary from 30% to 70% (1,8,24-26). Morbidity is also high; 13 of 20 patients in one series underwent major surgical procedures, which included fasciotomy, surgical debridement, exploratory laparotomy, intraocular aspiration, amputation, or hysterectomy (8).

Clinical Isolates

M types 1, 3, 12, and 28 have been the most common isolates from patients with shock and multiorgan failure (8,29). Recently, 80% of strains in Sweden from all types of GAS infection have been M type 1 (S. Holm, pers. comm.). Pyrogenic exotoxin A and/or B was found in most cases of severe infection. In the United States, pyrogenic exotoxin A is most frequently associated with these infections (8,23,29-33), while in Sweden and the United Kingdom, exotoxin B has been most common (12,25). Recently, streptococcal superantigen (SSA), a novel pyrogenic exotoxin, was isolated from an M 3 strain, albeit in small concentrations (34). In addition, mitogenic factor (MF) has been demonstrated in many different M types of GAS (35,36).

Necrotizing Fasciitis

Necrotizing fasciitis, a deep-seated infection of the subcutaneous tissue that progressively destroys fascia and fat but may spare the skin and muscle, can be caused by GAS, Clostridium perfringens, or C. septicum. Necrotizing fasciitis caused by mixed organisms such as aerobic gram-negative bacteria, anaerobes, and microaerophilic streptococci may develop in diabetic patients or patients with open wounds contaminated with bowel contents. Though Meleney called infections caused by hemolytic streptococci "streptococcal gangrene" (37), the process has been renamed necrotizing fasciitis. His patients' infections began at the site of trivial or inapparent trauma. Within 24 hours of the initial lesion which frequently was only mild erythema swelling, heat, erythema, and tenderness rapidly developed. During the next 24 to 48 hours, the erythema changed from red to purple and then to blue, and blisters and bullae, which contained clear yellow fluid, appeared. On days 4 and 5, the purple areas became gangrenous. From day 7 to day 10, the line of demarcation became sharply defined, and the dead skin began to separate at the margins or breaks in the center, revealing an extensive necrosis of the subcutaneous tissue. In more severe cases, the process advance d rapidly until several large areas of skin became gangrenous, and the intoxication rendered the patient dull,unresponsive, mentally cloudy, or even delirious. Meleney was the first to advocate aggressive "bear scratch" fasciotomy and debridement. With this treatment, together with irrigation with Dakains solution, the mortality rate dropped to 20% (37).

These older reports of necrotizing fasciitis (6) differ from reports of current necrotizing fasciitis cases associated with streptococcal TSS (8). First, recent cases have mainly occurred in young healthy persons who had no underlying disease but sustained minor trauma to an extremity. Earlier series describe older patients with multiple medical problems (6). Meleney's cases (reported from China) were probably among young healthy persons who sustained minor trauma, though the major difference between them and present cases is the low mortality rate (20% vs 20% to 60% in streptococcal TSS) (6,37) before antibiotics were available (37). Analysis of Meleney's reports also suggests that most of his patients did not have shock or organ failure, nor did they require amputation. In contrast, present cases of necrotizing fasciitis caused by GAS are invariably associated with severe manifestations of systemic illness and high morbidity despite the absence of underlying disease and the use of antibiotics, dialysis, ventilators, intravenous fluids, and improved surgical techniques. In summary, the high mortality rate among current cases of streptococcal necrotizing fasciitis could be due to the emergence of more virulent streptococci (8).

Streptococcal Myositis

Streptococcal myositis is an extremely uncommon GAS infection. Adams et al. (38) documented only 21 reported cases from 1900 to 1985, and Svane (39) found only four cases in more 20,000 autopsies. Severe pain may be the only early symptom, and swelling and erythema may be the only early physical findings, though muscle compartment syndromes may develop rapidly (8-10,38-41). Distinguishing streptococcal myositis from spontaneous gas gangrene caused by C. perfringens or C. septicum (42) may be difficult, though crepitus or demonstration of gas in the tissue favors clostridial infection (40). Patients with streptococcal TSS may have both necrotizing fasciitis and myositis (8,38). In published series, the case-fatality rate for necrotizing fasciitis is 20% to 50%, whereas GAS myositis has a fatality rate of 80% to 100% (6). Aggressive surgical debridement is extremely important for establishing a diagnosis and removing devitalized tissue.


Streptococcal bacteremia has occurred most commonly in the very young and in the elderly (5). Among children, predisposing factors (other than scarlet fever) include burns,varicella, malignant neoplasm,immunosuppression, and age less than 2 years (5). In patients with scarlet fever, the pharynx is the most common source of GAS. Frequently such patients have complications, such as extension of infection into the sinuses, peritonsillar tissue, or mastoids (septic scarlet fever or scarlet fever anginose); yet documented bacteremia occurs in only 0.3% of febrile patients (43). Among the children with varicella studied by Bullowa and Wischik (43), GAS bacteremia occurred in only approximately 0.5% of patients. In elderly patients the source of GAS infection is invariably the skin and is associated with cellulitis or erysipelas (5). GAS sepsis in the elderly (mean age, 50 to 60 years) has also been associated with diabetes, peripheral vascular disease, malignancy, and corticosteroid use. Not surprising, mortality rates of 35% to 80% have been described in this patient population. In the past, GAS bacteremia was rare among persons 14 to 40 years of age; puerperal sepsis accounted for most bacteremia in this age group. Recently, intravenous drug abuse has emerged as a leading cause of GAS bacteremia in this age group (5). Martin and Hoiby have comprehensively demonstrated that the prevalence of GAS bacteremia in Norway in the late 1980s increased in all age groups, but the greatest increase (600% to 800%) was in adolescents and young adults (10). Thus, the demographics of invasive streptococcal infection have changed dramatically in the past 4 to 6 years.

Toxic shock syndrome > 1 > 2 > 3 > 4

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