AUTHOR AND EDITOR INFORMATION

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• Clinical
• Differentials
• Workup
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• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Streptococci are a large and diverse group of gram-positive cocci that grow in pairs or chains. Streptococcus pyogenes (a group A Streptococcus) is a ubiquitous organism that is known to provoke a wide variety of diseases in humans.

Group A streptococci (GAS) are gram-positive, nonmotile, non–spore-forming organisms that appear as pairs or short-to-moderate–sized chains. The individual organism is spheric or ovoid and has a diameter of 0.6-1 µm. The cultures on blood agar plates appear as white-to-gray colonies 1-2 mm in diameter surrounded by zones of complete hemolysis. Some colonies produce large amounts of hyaluronic acid, which appears mucoid on the culture plate.

Historical perspectives

S pyogenes was first described by Billroth in 1874 in patients with wound infections. In 1883, Fehleisen isolated chain-forming organisms in pure culture from perierysipelas lesions. Rosebach named the organism S pyogenes in 1884. Studies by Schottmueller in 1903 and J.H. Brown led to knowledge of different patterns of hemolysis described as alpha, beta, and gamma hemolysis. A later development in this field was the Lancefield classification of beta-hemolytic streptococci by serotyping on the basis of M-protein precipitin reactions. Lancefield established the critical role of M protein in disease causation. In the early 1900s, Dochez, George, and Dick identified that scarlet fever was caused by hemolytic streptococcal infection. The epidemiological studies of the mid 1900s helped establish a relationship of GAS infection with acute rheumatic fever (ARF) and acute glomerulonephritis.

Spectrum of diseases from group A streptococcal infections

In the preantibiotic era, streptococci frequently caused significant morbidity and mortality. However, in the postantibiotic period, diseases from streptococcal infections are well controlled and uncommonly cause death. The streptococci not only cause acute infections but are also responsible for nonsuppurative postinfectious sequelae such as rheumatic fever and glomerulonephritis. Pharyngitis and impetigo are the common streptococcal infections.

The suppurative complications of GAS tonsillopharyngitis include the following:

• Tonsillopharyngeal cellulitis or abscess
• Otitis media
• Sinusitis
• Necrotizing fasciitis
• Streptococcal bacteremia
• Meningitis or brain abscess (rare complication resulting from direct extension of an ear or sinus infection or from bacteremic spread)

The nonsuppurative complications of GAS tonsillopharyngitis include the following:

• Acute rheumatic fever
• Acute glomerulonephritis
• Streptococcal toxic shock syndrome (strep TSS)

Pathophysiology

Many strains of streptococci have a predilection for the upper respiratory tract. Multiple factors influence virulence and initiation of infection in the host. The streptococcal cell wall is resistant to degradation and may persist indefinitely in the tissues. The peptidoglycan and cell wall constituents may produce chronic inflammation by complement activation and synthesis of various mediators.

Bacterial virulence factors

In regard to antigenic structure, the cell walls of streptococci are complex structures containing many different antigenic substances. The C-polysaccharide is composed of a branched polymer of L-rhamnose and N-acetyl-D-glucosamine. GAS produce 2 major classes of protein antigens: M antigens and T antigens. T typing may be useful for epidemiologic surveillance of the isolates. Some T antigens may be restricted to a single M type, whereas others may be shared by several M antigens.

The major virulence factor of GAS is M protein. The strains containing an abundance of M protein resist phagocytosis, multiply rapidly in human tissues, and initiate disease. M protein is a macromolecule present on the cell membrane; it traverses and penetrates the bacterial cell wall. The molecule contains type-specific antiphagocytic epitopes that facilitate adherence of the organism to the cell surface. M protein is an alpha helical coiled-coil dimer, which appears as a hairlike projection on the cell wall. The M protein makes the organism resistant to phagocytosis by inhibiting activation of alternate complement pathways on the cell surface. With the development of type-specific antibodies, M protein activity is neutralized and the immunity is type-specific and long-lasting.

The organism adheres to the mucous membranes via the lipoteichoic acid (LTA) that is present on the cell wall of streptococci. LTA is cytotoxic and is capable of several different biological activities. Once adherence has occurred, the streptococci resist phagocytosis, proliferate, and begin to invade the local tissues. In addition to M protein, the organism possesses additional virulence factors such as C5A peptidase. C5A peptidase destroys the chemotactic signals by cleaving the complement component of C5A.

GAS shows enormous and evolving molecular diversity driven by horizontal transmission among GAS strains. This is also true when GAS is compared with other streptococci. Acquisition of prophages accounts for much of the diversity, conferring both virulence through phage-associated virulence factors and increased bacterial survival against host defenses.

Extracellular products

Most strains of GAS produce 2 hemolytic toxins: streptolysin O and streptolysin S. Streptolysin is toxic to a variety of cells, including polymorphonuclear leukocytes, platelets, and tissue culture cells. Measurement of antistreptolysin O antibodies in humans is used as an indicator of recent streptococcal infection. Streptolysin S is produced by the organism in the presence of serum and is nonantigenic. Streptolysin O can be inactivated by oxygen. Streptolysin O is an immunogenic single-chain protein that induces a brisk antibody response. Streptolysin S consists of a polypeptide that has lytic effects for red and white blood cells and is responsible for the hemolysis observed on culture plates. The other extracellular products of streptococci are deoxyribonuclease A, B, C, and D and hyaluronidase, which destroys hyaluronic acid found in connective tissue.

Pyrogenic exotoxins

GAS produce 3 different types of exotoxins (ie, A, B, C). These toxins are responsible for causing fever and scarlet fever rash. Additionally, these exotoxins increase susceptibility to endotoxic shock, cause dysfunction of the reticuloendothelial system, produce cardiac and hepatic necrosis in animals, and depress antibody synthesis. These toxins serve as immunomodulators of the host defense system because they stimulate T cells to proliferate and are referred to as super antigens.

Nucleases

Four antigenically distinct nucleases (ie, A, B, C, D) assist in the liquefaction of pus and help to generate substrate for growth.

Other enzymes

GAS release a large number of proteins into the external environment. Two different types of streptokinase are released. The streptokinase forms a complex with plasminogen activator and catalyzes the conversion of plasminogen to plasmin, thus leading to digestion of fibrin. Streptococcal hyaluronidase hydrolyses hyaluronic acid found in the ground substance of connective tissues. Additionally, streptococci produce proteinase, nicotinamide adenine dinucleotidase, adenosine triphosphatase, neuraminidase, lipoproteinase, and cardiohepatic toxin.

Nonsuppurative complications

Acute rheumatic fever

ARF is a delayed nonsuppurative sequela of a pharyngeal infection with GAS. Following the initial pharyngitis, a latent period of 2-3 weeks occurs before the first signs or symptoms of ARF appear. The disease may present with a combination of clinical manifestations that may include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum.

The exact pathogenesis is unknown, although various theories have been proposed. Antigenic cross-reactivity may exist between streptococcal antigens and heart tissues. Streptococcal exotoxin may cause direct tissue toxicity, or the antigen may initiate an inflammatory process in the heart.

Poststreptococcal glomerulonephritis

Poststreptococcal glomerulonephritis is caused by infection with specific nephritogenic strains of GAS (type 12 and type 49) and may occur in sporadic cases or during an epidemic. The incidence of glomerulonephritis in children is approximately 5-10% with pharyngitis and 25% with skin infections.

This inflammatory disease probably is due to immune complex deposition within the glomerulus. With immunofluorescent staining, subepithelial deposits of immunoglobulin can be observed. The glomerulonephritis may be caused by circulating immune complexes, which may deposit in the glomerulus and initiate disease.

Streptococcal toxic shock syndrome

Severe GAS infections associated with shock and organ failure have been reported with increasing frequency, predominantly from North America and Europe. These infections have been termed strep TSS.

The M proteins of strep TSS are filamentous proteins on the cell membrane that have antiphagocytic properties. More than 80 types of M proteins are described. Types 1 and 3 are most commonly associated with strep TSS. The pathogenesis of strep TSS is associated with the streptococcal toxins (1) streptococcal pyrogenic exotoxins A, B, and C and (2) streptococcal super antigen.

Suppurative complications

Tonsillopharyngeal cellulitis or abscess

Streptococcal pharyngitis may lead to cellulitis or an abscess in the peritonsillar or retropharyngeal spaces. In these infections, GAS in association with oral flora may be the culprit organisms.

Otitis media

One of the two most common suppurative complications of streptococcal tonsillopharyngitis is caused by spread of organisms via the eustachian tube. However, GAS infections account for fewer than 5% of overall cases of otitis media.

Sinusitis

Direct spread of organisms leads to sinusitis, a common complication of streptococcal tonsillopharyngitis. Acute sinusitis presents with persistent coryza, postnasal drip, headache, and fever. Tenderness can be elicited over the affected sinus.

Necrotizing fasciitis

Rapidly invasive infections with GAS may arise following minor trauma or from hematogenous spread of GAS from the throat to the site of blunt trauma or muscle strain. Rapidly increasing unexplained pain may be the first indication of necrotizing fasciitis. Erythema may be present diffusely or locally but also may be absent. Within 24-48 hours, a reddish-purple color develops over the affected area, often evolving into a blister or bullae. Fever, malaise, myalgias, diarrhea, and anorexia also may be present. Hypotension may be present initially or may develop over time. Surgical exploration is critical for establishing the diagnosis and directing the management of necrotizing fasciitis.

Central nervous system diseases

The spectrum of poststreptococcal disease of the central nervous system (CNS) has been extended recently to include movement disorders (chorea, tics, dystonia, parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies reveal that the basal ganglia is the region primarily affected. The immunopathogenesis of the disease is unknown, although autoantibody-mediated disease remains an unproven possibility.

Frequency

United States

Infectious complications reported from the United States include head and neck infections, skin and soft tissue infections, bacteremia, strep TSS, ARF, and poststreptococcal glomerulonephritis.

International

In Denmark, the incidence of rheumatic fever decreased from 250 cases per 100,000 population to 100 cases per 100,000 population from 1862-1962. The introduction of antibiotics in 1950 led to further reduction. By 1980, the incidence ranged from 0.23-1.88 cases per 100,000 population. However, in certain populations in Hawaii and New Zealand (Maoris), the incidence of ARF continues to be 13.4 cases per 100,000 hospitalized children per year.

Mortality/Morbidity

GAS bacteremia remains a serious infection. The mortality rate is 25-48%.

CLINICAL

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History

The clinical manifestations of GAS infection vary and depend on the suppurative and nonsuppurative complications. GAS are the most common cause of acute bacterial pharyngitis. They can also cause a variety of cutaneous and invasive infections (eg, pyoderma, erysipelas, cellulitis, necrotizing fasciitis, myositis) and other complications (eg, rheumatic fever, acute glomerulonephritis).

• Head and neck infections
• • The incubation period for strep throat is 2-4 days. Sudden onset of sore throat, malaise, fever, and headache occurs. Younger patients may also develop nausea, vomiting, and abdominal pain.
  • GAS bacteremia associated with the early onset of shock and organ failure is the classic presentation of strep TSS. These patients usually develop renal failure, acute respiratory distress syndrome, hepatic dysfunction, and a diffuse capillary leak syndrome.
• Skin and soft tissue infections
• • Scarlet fever is produced by pyrogenic exotoxin released by GAS. The rash appears on the second day of illness; the rash is a diffuse red scarlatiniform rash that blanches with pressure. The rash is diffuse but spares the palms, soles, and face. The face appears flushed. The tongue may be covered with a whitish coating initially, but, at a later stage, it becomes beefy red. The skin rash fades in a week and is followed by extensive desquamation that lasts for several weeks.
  • Erysipelas is an acute infection of the skin associated with lymphatic involvement. The condition usually occurs in children or elderly people.
  • Cellulitis is inflammation of the skin and subcutaneous tissues and is associated with local pain, tenderness, swelling, and erythema. Patients also develop fever, chills, and malaise and may become bacteremic. People who abuse intravenous drugs or individuals who have abnormal lymphatic drainage are at risk of developing streptococcal cellulitis.
  • Impetigo and pyoderma, also called impetigo or impetigo contagiosa, are outbreaks of streptococcal pyoderma that may occur in children of certain population groups and in overcrowded institutions. The mode of spread is via direct contact, environmental contamination, and houseflies. The strains of streptococci causing pyoderma are different from those causing exudative tonsillitis.
  • Necrotizing fasciitis is a rapidly invasive infection with GAS that may arise following minor trauma or from hematogenous spread of GAS from the throat to the site of blunt trauma or muscle strain.
  • Varicella zoster virus infection may be associated with GAS. A retrospective review found that in 1993, 50% of new cases of invasive GAS infection were associated with varicella infection.
• Bacteremia
• • The risk factors for GAS bacteremia vary with age. Among children younger than 2 years, predisposing factors include burns, varicella virus infection, malignant neoplasm, and immunosuppression.
  • Among patients aged 40-60 years, the risk factors for GAS bacteremia include burns, cuts, surgical incisions, childbirth, intravenous drug abuse, and nonpenetrating trauma.
  • Predisposing factors for GAS bacteremia in elderly people include diabetes mellitus, peripheral vascular disease, malignancy, and corticosteroid use.
• Acute rheumatic fever
• • The Jones criteria are used to make the diagnosis of rheumatic fever.
  • The 5 major criteria include carditis, polyarthritis, chorea, erythema marginatum, and subcutaneous nodules.
  • The minor criteria include fever, arthralgia, elevated erythrocyte sedimentation rate or C-reactive protein, and prolonged PR interval on ECG findings.
• Poststreptococcal glomerulonephritis
• Pharyngitis

Physical

• The physical findings include erythema, edema, and swelling of the pharynx. The tonsils are enlarged, and grayish-white exudate may be present. Enlarged lymph nodes at the angles of the mandible are found commonly after palpation.
• Patients may develop chills and fever, and erythema and swelling commonly occur over the face.
• Pyoderma begins as a small papule and evolves into a vesicle surrounded by erythema. The vesicle turns into a pustule and then breaks down over 4-6 days to form a thick crust. Patients usually do not have systemic symptoms.
• Necrotizing fascitis is an extensive and rapidly spreading infection of the subcutaneous tissue and fascia that is accompanied by necrosis and gangrene of the skin and underlying structures.
• • Meleney originally described streptococcal gangrene in 1924.
  • It often begins at a site of minimal trauma.
  • Initially, the lesion appears as mild erythema, progresses rapidly to become purplish, and then develops into a bullae containing hemorrhagic fluid.
  • By the fourth or fifth day, frank gangrene is present and extensive tissue necrosis follows.

DIFFERENTIALS

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Other Problems to be Considered

Glomerulonephritis, nonstreptococcal postinfectious

WORKUP

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Lab Studies

• Throat culture
• • Because pharyngitis and tonsillitis may occur from a variety of infectious causes other than S pyogenes, confirm the diagnosis before initiating treatment.
  • Throat culture remains the most confirmatory diagnostic test for streptococcal pharyngitis.
  • Approximately 10% of the throat culture results are false negative, but these may reflect a carrier state rather than an acute infection.
  • Some throat culture results are false positive (eg, not reflecting acute infection but, rather, symptomatic carriage).
  • All patients with positive culture results are treated with antibiotics.
• Rapid antigen detection test
• • This test can be completed within minutes in the doctor's office.
  • A carbohydrate antigen is detected directly from throat swabs.
  • Presently, the test uses enzyme immunoassay, optical immunoassay, or chemiluminescent DNA probes.
  • The results from these tests are highly specific (>95%), but their sensitivity is lower than with the throat culture. Therefore, a negative antigen detection test result should prompt the submission of a throat swab for culture.
• Culture technique
• • GAS grow readily on routine media, but isolation of GAS can be achieved more easily by use of selective media that inhibit the growth of normal pharyngeal flora.
  • Most laboratories inoculate throat swabs on 5% sheep blood agar containing trimethoprim-sulfamethoxazole.
  • A bacitracin disk containing 0.04 units of bacitracin is also placed at the initial inoculation of the swab.
  • After overnight incubation at a temperature of 35-37°C, the growth of beta-hemolytic colonies that are inhibited by the antibiotic disk are presumed to be GAS.
  • The cultures that are negative after 24 hours are held for another overnight incubation and reexamined.
• In a patient with acute pharyngitis, bacterial detection is limited to a search for group A beta-hemolytic streptococci only. These are the only organisms for which specific antimicrobial treatment may prevent the development of serious nonsuppurative sequelae, such as ARF.
• Necrotizing fasciitis may be much more fulminant, usually progressing over 2-3 days, and is associated with very high mortality. These patients should be treated promptly and aggressively.

Imaging Studies

• The physician is aided further in the diagnosis of necrotizing fasciitis by obtaining radiographs of the affected area and performing a CT scan or MRI scan of the deep tissue structures.

TREATMENT

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Medical Care

• Therapy for streptococcal pharyngitis primarily is aimed at prevention of nonsuppurative and suppurative complications. The infecting streptococci must be eradicated from the pharynx in order to prevent ARF. A 10-day course of treatment is associated with minimal treatment failure. Penicillin can be administered by a single intramuscular injection of 1.2 million units of penicillin G benzathine or penicillin V orally for 10 days. Amoxicillin is equally effective and may be better tolerated in children.
• Meta-analysis compared bacterial and clinical cure rates in patients with GAS tonsillopharyngitis treated with oral beta-lactam or macrolide antibiotics for 4-5 days versus 10-day comparators. Twenty-two trials that involved 7470 patients were included in 4 separate analyses. Short-course cephalosporin treatment was superior for bacterial cure rate compared with 10 days of penicillin, short-course penicillin therapy was inferior to 10 days of penicillin, and clinical cure rates were similar to bacteriologic cure rates.¹
• In patients who are allergic to penicillin, erythromycin or the newer macrolides (eg, azithromycin, clarithromycin) appear to be effective. Oral cephalosporins are also highly effective in the treatment of streptococcal pharyngitis. Although eradication rates with cephalosporins may be better than those with penicillin, penicillin is the recommended drug of choice by the American Heart Association and the Infectious Diseases Society of America.
• Treatment failures are few, but they may occur. If the symptoms recur, the throat should be recultured and another course of treatment should be prescribed, preferably with an oral cephalosporin. An asymptomatic carrier state, as evidenced by positive throat culture results obtained on a weekly basis, is not treated with antibiotics.
• Streptococcal pyoderma is treated with oral antibiotics, such as penicillin or erythromycin, for 10 days. However, because concomitant infection with Staphylococcus aureus may occur, therapy with cloxacillin, cephalexin, or cefaclor is suggested. Treatment of pyoderma may not prevent occurrence of nephritis if the patient is infected with a nephritogenic strain.
• Treatment of necrotizing fasciitis consists of administering antibiotics and supportive therapy for associated shock. GAS remain susceptible to beta-lactam antibiotics; clinical failures of penicillin therapy for streptococcal infections may occur. Higher failure rates occur in patients with invasive infections because of the larger number of organisms. Clindamycin may be more effective in invasive infections. Unlike penicillin, the efficacy of clindamycin is not affected by the size of the inoculum or the stage of bacterial growth. In addition, clindamycin inhibits the production of toxin by streptococci.
• Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by GAS. GAS can also cause necrotizing fasciitis, for which an early and extensive surgical intervention is currently advocated. The use of a medical regimen including IVIG in patients may allow an initial nonoperative or minimally invasive approach, thus limiting the need for extensive debridements and amputations.

Surgical Care

A plastic surgeon should be consulted early to assess the need for debridement in patients with necrotizing fasciitis.

MEDICATION

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The goals of pharmacotherapy are to eradicate the microorganism, to reduce morbidity, and to prevent complications.

To date, S pyogenes has remained universally susceptible to the first-line treatment of choice, penicillin. European surveillance in Italy identified that 32% of GAS isolates exhibited resistance to macrolides. France has reported a steady escalation of erythromycin resistance that has reached 23%. Portugal identified 11% of GAS isolates as resistant to macrolides. Resistance in other European countries during the 1990s fell between 1% and 7%.

Invasive GAS isolates were tested for fluoroquinolone susceptibility from 1992-1993 and in 2003 in Ontario, Canada. All isolates were susceptible to levofloxacin. Two of 153 (1.3%) in 1992-1993 and 7 of 160 (4.4%) in 2003 had a levofloxacin minimal inhibitory concentration (MIC) of 2 mcg/mL; all 9 had parC mutations, and 8 were serotype M6.

Drug Category: Antibiotics

Therapy should cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

FOLLOW-UP

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Further Outpatient Care

• Pharyngitis and scarlet fever result in complications of streptococcal infection but are rare in asymptomatic carriers. Antibiotics have been shown to reduce the severity of acute symptoms and to shorten the duration of the illness by about one day. Another important reason for treating uncomplicated streptococcal pharyngitis is to markedly reduce the incidence of subsequent rheumatic fever or its recurrence. Whether antibiotic treatment reduces the risk of poststreptococcal glomerulonephritis is unknown, but one recent review noted a trend that showed some protection.²

Deterrence/Prevention

• Uncertainty remains about the risk of secondary cases of invasive disease developing among close contacts of an index case of GAS infection. The currently available evidence does not justify the routine administration of chemoprophylaxis to close contacts. All household contacts of a patient with invasive GAS disease should be informed of the clinical manifestations of invasive disease and to seek immediate medical attention if they develop such symptoms.

Complications

• The suppurative complications of GAS tonsillopharyngitis include the following:
• • Tonsillopharyngeal cellulitis or abscess
  • Otitis media
  • Sinusitis
  • Necrotizing fasciitis
  • Streptococcal bacteremia
  • Meningitis or brain abscess (rare complication resulting from direct extension of an ear or sinus infection or from bacteremic spread)
• The nonsuppurative complications of GAS tonsillopharyngitis include the following:
• • Acute rheumatic fever
  • Streptococcal toxic shock syndrome
  • Acute glomerulonephritis
• Other streptococcal infections may occur, described as follows:
• • Puerperal sepsis follows abortion or delivery when streptococci colonize the patient and invade the endometrium and then the blood stream. Pelvic cellulitis, septic pelvic thrombophlebitis, pelvic abscess, and septicemia may occur.
  • Meningitis may occur following upper respiratory tract infection with S pyogenes, but this is rare.
  • S pyogenes is an uncommon cause of pneumonia, but pneumonia may occur secondary to influenza, measles, or varicella or in patients with chronic obstructive lung disease. The onset is sudden. Chills, fever, dyspnea, productive cough, hemoptysis, and chest pain are associated.
• Empyema may develop in 30-40% of cases. Complications include mediastinitis, pericarditis, pneumothorax, and bronchiectasis.

Prognosis

• The prognosis in poststreptococcal acute proliferative glomerulonephritis is good, as more than 95% of patients recover spontaneously within 3-4 weeks with no long-term sequelae.

Patient Education

• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center; Women's Health Center; and Ear, Nose, and Throat Center. Also, see eMedicine's patient education articles Sore Throat, Toxic Shock Syndrome, and Strep Throat.

MISCELLANEOUS

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Medical/Legal Pitfalls

• GAS are some of the most important human pathogens. GAS are the most frequent bacterial cause of acute pharyngitis and produce a variety of skin infections including impetigo, cellulitis, erysipelas, wound infection, and gangrene.
• GAS are causative organisms for 2 nonsuppurative sequelae: ARF and poststreptococcal acute glomerulonephritis.
• GAS are important organisms that cause necrotizing fasciitis and strep TSS. Both of these conditions are associated with high mortality rates unless treated promptly and aggressively.

Special Concerns

• Acute rheumatic fever
• • General description: ARF is a delayed nonsuppurative sequela of GAS tonsillopharyngitis. Following the pharyngitis, a latent period of 2-3 weeks passes before the signs or symptoms of ARF appear. The disease presents with various clinical manifestations, including arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum.
  • Epidemiology: A streptococcal strain capable of causing bacterial pharyngitis is capable of causing rheumatic fever, although some exceptions have been noted.
  • Pathogenesis: The pathogenic mechanisms that lead to the development of ARF remain incompletely understood. Streptococcal pharyngeal infection clearly is a prerequisite, but genetic susceptibility may exist. The evidence that toxins produced by the streptococci are important in pathogenesis is insufficient.
  • Genetic susceptibility: Rheumatic fever might be the result of host genetic predisposition. The disease gene may be transmitted either in an autosomal dominant fashion or in an autosomal recessive fashion with limited penetrance. The disease gene has not yet been identified.

MULTIMEDIA

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Media file 1:  Streptococcus group A infections. Necrotizing fasciitis rapidly progresses from erythema to bullae formation and necrosis of skin and subcutaneous tissue.
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Media file 2:  Streptococcus group A infections. Beta hemolysis is demonstrated on blood agar media.
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Media file 3:  Streptococcus group A infections. M protein.
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Media file 4:  Streptococcus group A infections. Erysipelas is a group A streptococcal infection of skin and subcutaneous tissue.
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Media file 5:  Streptococcus group A infections. White strawberry tongue observed in streptococcal pharyngitis. Image courtesy of J. Bashera, eMedicine, Inc.
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Media file 6:  Streptococcus group A infections. Streptococcal rash. Image courtesy of J. Bashera, eMedicine, Inc.
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Media file 7:  Group A Streptococcus on Gram stain of blood isolated from a patient who developed toxic shock syndrome.
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Media file 8:  Streptococcus group A infections. Necrotizing fasciitis of the left hand in a patient who had severe pain in the affected area.
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Media file 9:  Streptococcus group A infections. Patient who had had necrotizing fasciitis of the left hand and severe pain in the affected area (from Image 8). This photo was taken at a later date, and the wound is healing. The patient required skin grafting.
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Media file 10:  Streptococcus group A infections. Gangrenous streptococcal cellulitis in a patient with diabetes.
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Media file 11:  Erythema secondary to group A streptococcal cellulitis.
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REFERENCES

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1. Casey JR, Pichichero ME. Metaanalysis of short course antibiotic treatment for group a streptococcal tonsillopharyngitis. Pediatr Infect Dis J. Oct 2005;24(10):909-17. [Medline].
2. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2004;CD000023. [Medline].
3. Albert DA, Harel L, Karrison T. The treatment of rheumatic carditis: a review and meta-analysis. Medicine (Baltimore). Jan 1995;74(1):1-12. [Medline].
4. Aviles RJ, Ramakrishna G, Mohr DN, Michet CJ Jr. Poststreptococcal reactive arthritis in adults: a case series. Mayo Clin Proc. Feb 2000;75(2):144-7. [Medline].
5. Barg NL, Kish MA, Kauffman CA, Supena RB. Group A streptococcal bacteremia in intravenous drug abusers. Am J Med. Apr 1985;78(4):569-74. [Medline].
6. Brusch JL. Streptoccocal Pharyngitis. In: Rakel RE, Bope ET, eds. Conn's Current Therapy 2001. ed. Philadelphia, Pa: WB Saunders; 2001:246-9.
7. Currie BJ. Group A streptococcal infections of the skin: molecular advances but limited therapeutic progress. Curr Opin Infect Dis. Apr 2006;19(2):132-138. [Medline].
8. Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American. Pediatrics. Oct 1995;96(4 Pt 1):758-64. [Medline].
9. Dale RC. Post-streptococcal autoimmune disorders of the central nervous system. Dev Med Child Neurol. Nov 2005;47(11):785-91. [Medline].
10. Doctor A, Harper MB, Fleisher GR. Group A beta-hemolytic streptococcal bacteremia: historical overview, changing incidence, and recent association with varicella. Pediatrics. Sep 1995;96(3 Pt 1):428-33. [Medline].
11. Feder HM, Gerber MA, Randolph MF, et al. Once-daily therapy for streptococcal pharyngitis with amoxicillin. Pediatrics. Jan 1999;103(1):47-51. [Medline].
12. Feinstein AR, Spagnuolo M. The clinical patterns of acute rheumatic fever: a reappraisal. 1962. Medicine (Baltimore). Jul 1993;72(4):272-83, 262-3. [Medline].
13. Gagliotti C, Nobilio L, Milandri M. Macrolide prescriptions and erythromycin resistance of Streptococcus pyogenes. Clin Infect Dis. Apr 15 2006;42(8):1153-6. [Medline].
14. Gastanaduy AS, Kaplan EL, Huwe BB, et al. Failure of penicillin to eradicate group A streptococci during an outbreak of pharyngitis. Lancet. Sep 6 1980;2(8193):498-502. [Medline].
15. Gibofsky A, Zabriskie JB. Rheumatic fever: new insights into an old disease. Bull Rheum Dis. Nov 1993;42(7):5-7. [Medline].
16. Henkel JS, Armstrong D, Blevins A, Moody MD. Group A beta-hemolytic Streptococcus bacteremia in a cancer hospital. JAMA. Feb 9 1970;211(6):983-6. [Medline].
17. Holm SE, Norrby A, Bergholm AM, Norgren M. Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989. J Infect Dis. Jul 1992;166(1):31-7. [Medline].
18. Horn DL, Zabriskie JB, Austrian R, et al. Why have group A streptococci remained susceptible to penicillin? Report on a symposium. Clin Infect Dis. Jun 1998;26(6):1341-5. [Medline].
19. Horstkotte D, Niehues R, Strauer BE. Pathomorphological aspects, aetiology and natural history of acquired mitral valve stenosis. Eur Heart J. Jul 1991;12 Suppl B:55-60. [Medline].
20. Kaplan EL, Johnson DR. Eradication of group A streptococci from the upper respiratory tract by amoxicillin with clavulanate after oral penicillin V treatment failure. J Pediatr. Aug 1988;113(2):400-3. [Medline].
21. Krober MS, Bass JW, Michels GN. Streptococcal pharyngitis. Placebo-controlled double-blind evaluation of clinical response to penicillin therapy. JAMA. Mar 1 1985;253(9):1271-4. [Medline].
22. Lamagni T, Efstratiou A, Vuopio-Varkila J. The epidemiology of severe Streptococcus pyogenes associated disease in Europe. Euro Surveill. Sep 1 2005;10(9):[Medline].
23. Marcus RH, Sareli P, Pocock WA, Barlow JB. The spectrum of severe rheumatic mitral valve disease in a developing country. Correlations among clinical presentation, surgical pathologic findings, and hemodynamic sequelae. Ann Intern Med. Feb 1 1994;120(3):177-83. [Medline].
24. Norrby-Teglund A, Muller MP, Mcgeer A. Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach. Scand J Infect Dis. 2005;37(3):166-72. [Medline].
25. Pichichero ME. Group A streptococcal tonsillopharyngitis: cost-effective diagnosis and treatment. Ann Emerg Med. Mar 1995;25(3):390-403. [Medline].
26. Pichichero ME, Disney FA, Talpey WB, et al. Adverse and beneficial effects of immediate treatment of Group A beta- hemolytic streptococcal pharyngitis with penicillin. Pediatr Infect Dis J. Jul 1987;6(7):635-43. [Medline].
27. Powis J, McGeer A, Duncan C. Prevalence and characterization of invasive isolates of Streptococcus pyogenes with reduced susceptibility to fluoroquinolones. Antimicrob Agents Chemother. May 2005;49(5):2130-2. [Medline].
28. Randolph MF, Gerber MA, DeMeo KK, Wright L. Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. J Pediatr. Jun 1985;106(6):870-5. [Medline].
29. Smith A, Lamagni TL, Oliver I. Invasive group A streptococcal disease: should close contacts routinely receive antibiotic prophylaxis?. Lancet Infect Dis. Aug 2005;5(8):494-500. [Medline].
30. Stevens DL. Invasive group A streptococcus infections. Clin Infect Dis. Jan 1992;14(1):2-11. [Medline].
31. Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic shock- like syndrome and scarlet fever toxin A. N Engl J Med. Jul 6 1989;321(1):1-7. [Medline].
32. Tamayo J, Perez-Trallero E, Gomez-Garces JL. Resistance to macrolides, clindamycin and telithromycin in Streptococcus pyogenes isolated in Spain during 2004. J Antimicrob Chemother. Oct 2005;56(4):780-2. [Medline].
33. Wilson P, Tierney L. Lemierre syndrome caused by Streptococcus pyogenes. Clin Infect Dis. Oct 15 2005;41(8):1208-9. [Medline].

Article Last Updated: May 5, 2006