Background
Pharyngitis, or sore throat, is often caused by infection. Common respiratory viruses account for the vast majority of cases (see Pharyngitis, Viral), and these are usually self-limited. Bacteria are also important etiologic agents, and, when identified properly, may be treated with antibacterials, resulting in decreased local symptoms and prevention of serious sequelae.
The most common and important bacterial cause of pharyngitis is Streptococcus pyogenes. When suspected, bacterial pharyngitis can be confirmed with routine diagnostic tests and treated with various antibiotics. If left untreated, S pyogenes pharyngitis may lead to local and distant complications. To a lesser extent, bacteria other than S pyogenes are known to cause pharyngitis, and these are discussed in Causes.
Pathophysiology
Beta-hemolytic streptococci have the ability to cause large zones of hemolysis on blood agar, aiding in microbiological identification.[1] Lancefield antigens, carbohydrates in the cell wall, provide further differentiation of streptococci. S pyogenes, which contains group A antigens and displays beta-hemolysis, is the most common species referred to as a group A beta-hemolytic streptococci (GABHS). Streptococcus dysgalactiae subspecies equisimilis and some species from the Streptococcus anginosus group may share laboratory characteristics with S pyogenes but do not commonly cause human disease. See the image below.
Picture of Streptococcus pyogenes at 100 X magnification. Perhaps the most important virulence factor of GABHS is the M protein. This protein, located peripherally on the cell wall, is required for invasive infection. T cells exposed to this M protein are postulated to cross-react with similar epitopes on human cardiac myosin and laminin, contributing to the pathogenesis of rheumatic heart disease.[2] This protein provides a potential target for a GABHS vaccine, although successful widespread implementation of such a vaccine remains elusive.[3] More than 100 M-protein serotypes have been described. Although individuals often develop lifelong immunity to one serotype, re-infection with a different serotype may cause disease.
GABHS contains a hyaluronic acid capsule, which also plays an important role in infection.[4] Bacteria that produce large quantities of this capsule exhibit a characteristic mucoid appearance on blood agar and may be more virulent.
Certain GABHS exotoxins act as superantigens by up-regulating T cells.[5] These superantigens can prompt a release of proinflammatory cytokines and may synergize with lipopolysaccharide. It has been speculated that these superantigens evade the pharyngeal immune response, resulting in proliferation of GABHS while permitting immune-mediated elimination of commensal organisms.
Adhesins enable GABHS attachment at sites such as the pharynx. This attachment allows for colonization and competition with normal host flora.
Some strains produce erythrogenic toxins, which cause the rash of scarlet fever in susceptible hosts.
GABHS is spread from person to person through large droplet nuclei.[6] Consequently, close quarters (eg, barracks, daycares, dormitories) facilitate transmission. In temperate regions, the prevalence of GABHS infection increases in the colder months, presumably because of the tendency of people to congregate indoors. Spread within families is common. The risk of acquiring GABHS from an infected family member is 40%, and nearly one in four of infected individuals eventually exhibit symptoms. Twenty-four hours after appropriate antibiotics are initiated, the patient is no longer considered contagious.
Case reports and in vitro studies have speculated that toothbrushes, orthodontic appliances, and pets may carry and facilitate spread of GABHS,[7, 8] although these claims have not been validated by rigorous in vivo investigation.[9]
GABHS is also a common cause of erysipelas, cellulitis, and necrotizing fasciitis and has been reported as a cause of pneumonia, toxic shock syndrome, and lymphangitis. The vast majority of these manifestations do not occur in the setting of pharyngitis.
Epidemiology
Frequency
United States
Acute pharyngitis accounts for approximately 12 million annual ambulatory care visits in the United States. It ranks within the top 20 most-common primary diagnosis groups.[10]
International
An estimated 616 million cases of GABHS pharyngitis occur annually worldwide.[11] Rheumatic heart disease, which may be a consequence of GABHS pharyngitis, is estimated to cause about 6 million years of life lost annually. The burden of rheumatic heart disease disproportionately affects populations from developing countries. In terms of estimated global mortality, GABHS is one of the top 10 pathogens, behind HIV infection and malaria and ahead of tetanus and pertussis.
Mortality/Morbidity
Although GABHS pharyngitis is usually a self-limited entity, on average, a single episode in a child results in 1.9 days absence from school and a parent missing 1.8 days from work to care for the child.[12] Children with GABHS pharyngitis experience symptoms for an average of 4.5 days.
In addition to symptoms localized to the oropharynx, GABHS pharyngitis may also cause the following suppurative and nonsuppurative complications:
- Invasion of nearby structures may cause suppurative complications such as otitis media, sinusitis, peritonsillar abscess, retropharyngeal abscess, and cervical adenitis.
- Nonsuppurative complications of bacterial pharyngitis include rheumatic heart disease and poststreptococcal glomerulonephritis. These entities are discussed in Complications.
Race
GABHS pharyngitis affects all races.
Sex
GABHS pharyngitis has no sexual predilection.
Age
GABHS pharyngitis is most common in individuals aged 5-15 years, although both infants and adults may also acquire the disease.[13] (For more information on pharyngitis in children, see the article Pharyngitis in eMedicine's Pediatric: General Medicine volume.)
Spellerberg B, Brandt C. Streptococcus. In: Manual of Clinical Microbiology. 9th edition. 2007:412-29.
Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. Feb 2006;39(1):31-9. [Medline].
Dale JB. Current status of group A streptococcal vaccine development. Adv Exp Med Biol. 2008;609:53-63. [Medline].
Stollerman GH, Dale JB. The importance of the group a streptococcus capsule in the pathogenesis of human infections: a historical perspective. Clin Infect Dis. Apr 1 2008;46(7):1038-45. [Medline].
Sriskandan S, Faulkner L, Hopkins P. Streptococcus pyogenes: Insight into the function of the streptococcal superantigens. Int J Biochem Cell Biol. 2007;39(1):12-9. [Medline].
Musher DM. How contagious are common respiratory tract infections?. N Engl J Med. Mar 27 2003;348(13):1256-66. [Medline].
Brook I, Gober AE. Persistence of group A beta-hemolytic streptococci in toothbrushes and removable orthodontic appliances following treatment of pharyngotonsillitis. Arch Otolaryngol Head Neck Surg. Sep 1998;124(9):993-5. [Medline].
Roos K, Lind L, Holm SE. Beta-haemolytic streptococci group A in a cat, as a possible source of repeated tonsillitis in a family. Lancet. Nov 5 1988;2(8619):1072. [Medline].
Wilson KS, Maroney SA, Gander RM. The family pet as an unlikely source of group A beta-hemolytic streptococcal infection in humans. Pediatr Infect Dis J. May 1995;14(5):372-5. [Medline].
Schappert SM, Rechtsteiner EA. Ambulatory medical care utilization estimates for 2006. Natl Health Stat Report. Aug 6 2008;1-29. [Medline].
Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. Nov 2005;5(11):685-94. [Medline].
Pfoh E, Wessels MR, Goldmann D, Lee GM. Burden and economic cost of group A streptococcal pharyngitis. Pediatrics. Feb 2008;121(2):229-34. [Medline].
Alter SJ, Vidwan NK, Sobande PO, Omoloja A, Bennett JS. Common childhood bacterial infections. Curr Probl Pediatr Adolesc Health Care. Nov 2011;41(10):256-83. [Medline].
Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. Clin Infect Dis. Jul 15 2002;35(2):113-25. [Medline].
Centor RM, Allison JJ, Cohen SJ. Pharyngitis management: defining the controversy. J Gen Intern Med. Jan 2007;22(1):127-30. [Medline].
Shah M, Centor RM, Jennings M. Severe acute pharyngitis caused by group C streptococcus. J Gen Intern Med. Feb 2007;22(2):272-4. [Medline].
Zaoutis T, Attia M, Gross R, Klein J. The role of group C and group G streptococci in acute pharyngitis in children. Clin Microbiol Infect. Jan 2004;10(1):37-40. [Medline].
Llor C, Madurell J, Balagué-Corbella M, Gómez M, Cots JM. Impact on antibiotic prescription of rapid antigen detection testing in acute pharyngitis in adults: a randomised clinical trial. Br J Gen Pract. May 2011;61(586):e244-51. [Medline]. [Full Text].
American Academy of Pediatrics. Arcanobacterium haemolyticum Infections. In: Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatrics. 27th ed. 2006:217-8.
Holder NA. Gonococcal infections. Pediatr Rev. Jul 2008;29(7):228-34. [Medline].
Papp JR, Ahrens K, Phillips C, Kent CK, Philip S, Klausner JD. The use and performance of oral-throat rinses to detect pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections. Diagn Microbiol Infect Dis. Nov 2007;59(3):259-64. [Medline].
Centers for Disease Control and Prevention. Press Release. First-line Oral Gonorrhea Treatment Available Again in United States. April 25, 2008.
Esposito S, Blasi F, Bosis S, et al. Aetiology of acute pharyngitis: the role of atypical bacteria. J Med Microbiol. Jul 2004;53:645-51. [Medline].
Sendi P, Graber P, Lepere F, Schiller P, Zimmerli W. Mycoplasma pneumoniae infection complicated by severe mucocutaneous lesions. Lancet Infect Dis. Apr 2008;8(4):268. [Medline].
Arbaji A, Kharabsheh S, Al-Azab S, et al. A 12-case outbreak of pharyngeal plague following the consumption of camel meat, in north-eastern Jordan. Ann Trop Med Parasitol. Dec 2005;99(8):789-93. [Medline].
Gerber MA. Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am. Jun 2005;52(3):729-47, vi. [Medline].
[Best Evidence] Tanz RR, Gerber MA, Kabat W, Rippe J, Seshadri R, Shulman ST. Performance of a rapid antigen-detection test and throat culture in community pediatric offices: implications for management of pharyngitis. Pediatrics. Feb 2009;123(2):437-44. [Medline].
Gerber MA, Shulman ST. Rapid diagnosis of pharyngitis caused by group A streptococci. Clin Microbiol Rev. Jul 2004;17(3):571-80, table of contents. [Medline].
Salkind AR, Wright JM. Economic Burden of Adult Pharyngitis: The Payer's Perspective. Value Health. Dec 17 2007;[Medline].
[Best Evidence] Altamimi S, Khalil A, Khalaiwi KA, Milner R, Pusic MV, Al Othman MA. Short versus standard duration antibiotic therapy for acute streptococcal pharyngitis in children. Cochrane Database Syst Rev. Jan 21 2009;CD004872. [Medline].
Pichichero ME, Casey JR. Bacterial eradication rates with shortened courses of 2nd- and 3rd-generation cephalosporins versus 10 days of penicillin for treatment of group A streptococcal tonsillopharyngitis in adults. Diagn Microbiol Infect Dis. Oct 2007;59(2):127-30. [Medline].
Lakoš AK, Gašparic M, Kovacic D, Pangercic A, Kukuruzovic MM, Baršic B. Safety and effectiveness of azithromycin in the treatment of respiratory infections in children. Curr Med Res Opin. Dec 1 2011;[Medline].
[Best Evidence] Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child. Jun 2008;93(6):474-8. [Medline].
Clegg HW, Ryan AG, Dallas SD, et al. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial. Pediatr Infect Dis J. Sep 2006;25(9):761-7. [Medline].
Chan DS, Demers DM, Bass JW. Antimicrobial liquid formulations: a blind taste comparison of three brands of penicillin VK and three brands of amoxicillin. Ann Pharmacother. Feb 1996;30(2):130-2. [Medline].
Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. Feb 9 2006;354(6):601-9. [Medline].
Richter SS, Heilmann KP, Beekmann SE, et al. Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003. Clin Infect Dis. Sep 1 2005;41(5):599-608. [Medline].
Malhotra-Kumar S, Lammens C, Chapelle S, et al. Macrolide- and telithromycin-resistant Streptococcus pyogenes, Belgium, 1999-2003. Emerg Infect Dis. Jun 2005;11(6):939-42. [Medline].
Kaplan EL. The group A streptococcal upper respiratory tract carrier state: an enigma. J Pediatr. Sep 1980;97(3):337-45. [Medline].
Orvidas LJ, St Sauver JL, Weaver AL. Efficacy of tonsillectomy in treatment of recurrent group A beta-hemolytic streptococcal pharyngitis. Laryngoscope. Nov 2006;116(11):1946-50. [Medline].
Catanzaro FJ, Stetson CA, Morris AJ, et al. The role of the streptococcus in the pathogenesis of rheumatic fever. Am J Med. Dec 1954;17(6):749-56. [Medline].
Steer AC, Danchin MH, Carapetis JR. Group A streptococcal infections in children. J Paediatr Child Health. Apr 2007;43(4):203-13. [Medline].
Dagnelie CF, van der Graaf Y, De Melker RA. Do patients with sore throat benefit from penicillin? A randomized double-blind placebo-controlled clinical trial with penicillin V in general practice. Br J Gen Pract. Oct 1996;46(411):589-93. [Medline].
Kassutto S, Rosenberg ES. Primary HIV type 1 infection. Clin Infect Dis. May 15 2004;38(10):1447-53. [Medline].
American Academy of Pediatrics. Diphtheria. In: Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatrics. 27th ed. 2006:277-81.
Bisno AL, Peter GS, Kaplan EL. Diagnosis of strep throat in adults: are clinical criteria really good enough?. Clin Infect Dis. Jul 15 2002;35(2):126-9. [Medline].
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