Chapter 381  ◆  Acute Pharyngitis  2017

Chapter 381 
Acute Pharyngitis
Robert R. Tanz

Pharyngitis refers to inflammation of the pharynx, including ery-

thema, edema, exudates, or an enanthem (ulcers, vesicles). Pharyngeal
inflammation can be related to environmental exposures, such as
tobacco smoke, air pollutants, and allergens; from contact with caustic
substances, hot food, and liquids; and from infectious agents. The
pharynx and mouth can be involved in various inflammatory condi-
tions such as the periodic fever, aphthous stomatitis, pharyngitis,
adenitis (PFAPA) syndrome, Kawasaki disease, inflammatory bowel
disease, Stevens-Johnson syndrome, and systemic lupus erythematous.
Noninfectious etiologies are typically evident from history and physi-
cal exam, but it can be more challenging to distinguish from among
the numerous infectious causes of acute pharyngitis.
Acute infections of the upper respiratory tract account for a substan-
tial number of visits to pediatricians and many feature sore throat as a
symptom or evidence of pharyngitis on physical examination. The
usual clinical task is to distinguish important, potentially serious, and
treatable causes of acute pharyngitis from those that are self-limited
and require no specific treatment or follow-up. Specifically, identifying
patients who have group A streptococcus (GAS; Streptococcus pyo-
genes; see Chapter 183) pharyngitis and treating them with antibiotics
forms the core of the management paradigm.

INFECTIOUS ETIOLOGIES
See Table 381-1.

Viruses
In North America and most industrialized countries GAS is the most
important bacterial cause of acute pharyngitis, but viruses predominate
as acute infectious causes of pharyngitis. Viral upper respiratory tract
infections are typically spread by contact with oral or respiratory secre-
tions and occur most commonly in fall, winter, and spring, that is, the
“respiratory season.” Important viruses that cause pharyngitis include
influenza (see Chapter 258), parainfluenza (see Chapter 259), adeno-
viruses (see Chapter 262), coronaviruses (see Chapter 264), enterovi-
ruses (see Chapter 250), rhinoviruses (see Chapter 263), respiratory
2018  Part XIX  ◆  Respiratory System

F. necrophorum has been suggested to be a fairly common cause of

Table 381-1 Infectious Agents That Cause Pharyngitis pharyngitis in older adolescents and adults (15-30 yr old). Prevalence
VIRUSES BACTERIA in studies has varied from 10-48% of patients with non-GABHS phar-
yngitis, but large surveillance studies have not been performed. F.
Adenovirus Streptococcus pyogenes necrophorum pharyngitis is associated with development of Lemierre
Coronavirus (Group A streptococcus) syndrome, internal jugular vein septic thrombophlebitis. Approxi-
Cytomegalovirus Arcanobacterium haemolyticum
mately 80% of cases of Lemierre syndrome are caused by this bacterium.
Epstein-Barr virus Fusobacterium necrophorum
Enteroviruses Corynebacterium diphtheriae
Patients present initially with fever, sore throat, exudative pharyngitis,
Herpes simplex virus Neisseria gonorrhoeae and/or peritonsillar abscess. The symptoms may persist, neck pain and
Human immunodeficiency virus Group C streptococci swelling develop, and the patient appears toxic. Septic shock may ensue
Human metapneumovirus Group G streptococci along with metastatic complications from septic emboli that can involve
Influenza viruses Francisella tularensis the lungs, bones and joints, central nervous system, abdominal organs,
Measles virus Chlamydophila pneumoniae and soft tissues. The case fatality rate is 4-9%.
Parainfluenza viruses Chlamydia trachomatis Gonococcal pharyngeal infections are usually asymptomatic but can
Respiratory syncytial virus Mycoplasma pneumoniae cause acute pharyngitis with fever and cervical lymphadenitis. Young
Rhinoviruses children with proven gonococcal disease should be evaluated for sexual
abuse.
Diphtheria is extremely rare in most developed countries thanks to
extensive immunization with diphtheria toxoid. However, it remains
syncytial virus (see Chapter 260), cytomegalovirus (see Chapter 255), endemic in many areas of the world, including the former Soviet bloc
Epstein-Barr virus (see Chapter 254), herpes simplex virus (see Chapter countries, Africa, Asia, the Middle East, and Latin America. It can be
252), and human metapneumovirus (see Chapter 261). Most viral phar- considered in patients with recent travel to or from these areas and in
yngitis, except mononucleosis, is mild. Common nonspecific symp- unimmunized patients. Key physical findings are bull neck (extreme
toms such as rhinorrhea and cough develop gradually before they neck swelling) and a gray pharyngeal pseudomembrane that can cause
become prominent. However, specific findings are sometimes helpful respiratory obstruction.
in identifying the infectious viral agent. Ingestion of water, milk, or undercooked meat contaminated by
Gingivostomatitis and ulcerating vesicles throughout the anterior F. tularensis can lead to oropharyngeal tularemia. Severe throat pain,
pharynx and on the lips are seen in primary oral herpes simplex virus tonsillitis, cervical adenitis, oral ulcerations, and a pseudomembrane
infection. High fever and difficulty taking oral fluids are common. This (as in diphtheria) may be present. M. pneumoniae and C. pneumoniae
infection can last for 14 days. cause pharyngitis, but other upper and lower respiratory infections are
Discrete papulovesicular lesions or ulcerations in the posterior more important and more readily recognized. Development of a severe
oropharynx, severe throat pain, and fever are characteristic of herpan- or persistent cough subsequent to pharyngitis may be the clue to infec-
gina, caused by various enteroviruses. In hand-foot-mouth disease tion with one of these organisms.
there are vesicles or ulcers throughout the oropharynx, vesicles on the
palms and soles, and sometimes on the trunk and extremities; Cox- Group A Streptococcus
sackie A16 is the most common agent, but Enterovirus 71 and Cox- Streptococcal pharyngitis is relatively uncommon before 2-3 yr of age,
sackie A6 can also cause this syndrome. Enteroviral infections are most is quite common among children 5-15 yr old, and declines in fre-
common in the summer. quency in late adolescence and adulthood. Illness occurs throughout
Various adenoviruses cause pharyngitis. When there is concurrent the year but is most prevalent in winter and spring. It is readily spread
conjunctivitis the syndrome is called pharyngoconjunctival fever. The among siblings and schoolmates. GAS causes 15-30% of pharyngitis in
pharyngitis tends to resolve within 7 days but conjunctivitis may school-age children.
persist for up to 14 days. Pharyngoconjunctival fever can be epidemic Colonization of the pharynx by GAS can result in either asymptom-
or sporadic; outbreaks have been associated with exposure in swim- atic carriage or acute infection. After an incubation period of 2-5 days,
ming pools. pharyngeal infection with GAS classically presents as rapid onset of
Intense, diffuse pharyngeal erythema and Koplik spots, the pathog- significant sore throat and fever. The pharynx is red, the tonsils are
nomonic enanthem, occur in advance of the characteristic rash of enlarged and often covered with a white, grayish, or yellow exudate
measles. Splenomegaly or hepatomegaly may be the clue to Epstein- that may be blood-tinged. There may be petechiae or “doughnut”
Barr virus infectious mononucleosis in an adolescent with exudative lesions on the soft palate and posterior pharynx and the uvula may be
tonsillitis. Primary infection with HIV can manifest as the acute ret- red and swollen. The surface of the tongue can resemble a strawberry
roviral syndrome, with non-exudative pharyngitis, fever, maculopapu- when the papillae are inflamed and prominent (“strawberry tongue”).
lar rash, arthralgia, myalgia, adenopathy, and often a maculopapular Initially, the tongue is often coated white, and with the swollen papillae
rash. it is called a “white strawberry tongue.” When the white coating is gone
after a few days, the tongue is often quite red, and is called a “red
Bacteria Other Than Group A Streptococcus strawberry tongue.” Enlarged and tender anterior cervical lymph nodes
In addition to GAS, bacteria that cause pharyngitis include group C are frequently present. Headache, abdominal pain, and vomiting are
and group G streptococcus (see Chapter 185), Arcanobacterium hae- frequently associated with the infection, but in the absence of clinical
molyticum, Francisella tularensis (see Chapter 206), Neisseria gonor- pharyngitis, gastrointestinal signs and symptoms should not be attrib-
rhoeae (see Chapter 192), Mycoplasma pneumoniae (see Chapter 223), uted to GAS. Ear pain is a frequent complaint but the tympanic mem-
Chlamydophila (formerly Chlamydia) pneumoniae (see Chapter 225), branes are usually normal. Diarrhea, cough, coryza, ulcerations, croup/
Chlamydia trachomatis (see Chapter 226), Fusobacterium necropho- laryngitis/hoarseness, and conjunctivitis are not associated with GAS
rum, and Corynebacterium diphtheriae (see Chapter 187). Haemophilus pharyngitis and increase the likelihood of a viral etiology.
influenzae and Streptococcus pneumoniae may be cultured from the Patients infected with GAS that produce streptococcal pyrogenic
throats of children with pharyngitis, but their role in causing pharyn- exotoxin A, B, or C may demonstrate the fine red, papular (“sandpa-
gitis has not been established. per”) rash of scarlet fever. It begins on the face and then becomes
Group C and Group G streptococcus and A. haemolyticum pharyn- generalized. The cheeks are red and the area around the mouth is more
gitis have been diagnosed most commonly in adolescents and adults. pale, giving the appearance of circumoral pallor. The rash blanches with
They resemble group A β-hemolytic streptococcus (GABHS) pharyn- pressure and it may be more intense in skin creases, especially in the
gitis and a scarlet fever–like rash may be present with A. haemolyticum antecubital fossae, axillae, and inguinal creases (Pastia’s lines or Pastia’s
infections. sign). Pastia’s lines are sometimes petechial or slightly hemorrhagic.
 Chapter 381  ◆  Acute Pharyngitis  2019

Capillary fragility can cause petechiae distal to a tourniquet or constric- rapid test with a throat culture is recommended. RADTs and throat
tion from clothing, a positive tourniquet test or Rumpel-Leeds phe- culture exhibit spectrum bias: They are more sensitive when the pretest
nomenon. Erythema fades in a few days and when the rash resolves it probability of GAS is high (signs and symptoms are typical of GAS
typically peels like a mild sunburn. Sometimes there is sheet-like des- infection) and less sensitive when the pretest probability is low. Avoid-
quamation around the free margins of the finger nails. Streptococcal ance of testing when patients have signs and symptoms more sugges-
pyrogenic exotoxin A, encoded by the gene spe A, is the exotoxin most tive of a viral infection is recommended.
commonly associated with scarlet fever. Testing for bacteria other than GAS is performed infrequently, and
The M protein is an important GAS virulence factor that facilitates should be reserved for patients with persistent symptoms and symp-
resistance to phagocytosis. The M protein is encoded by the emm gene toms suggestive of a specific non-GAS bacterial pharyngitis, for
and determines the M type (or emm type). Molecular methods have example, when there is concern for gonococcal infection or sexual
identified more than 200 emm genes (emm types). The M protein is abuse. Special culture media and a prolonged incubation are required
immunogenic; an individual can experience multiple episodes of GAS to detect A. haemolyticum. Viral cultures are often unavailable and are
pharyngitis in a lifetime because natural immunity is M type-specific. generally too expensive and slow to be clinically useful. Polymerase
Numerous GAS M types can circulate in a community simultaneously chain reaction is more rapid and multiplex polymerase chain reaction
and they enter and leave communities unpredictably and for unknown testing for respiratory pathogens can identify a variety of viral and
reasons. bacterial agents within a few hours. This may be useful in determining
the isolation needs of hospitalized patients, assisting in patient prog-
DIAGNOSIS nosis, and epidemiology, but in the absence of specific treatment for
The clinical presentations of streptococcal and viral pharyngitis often most viral infections such testing is usually not necessary. A complete
overlap. In particular, the pharyngitis of mononucleosis can be difficult blood cell count showing many atypical lymphocytes and a positive
to distinguish from GAS pharyngitis. Physicians relying solely on clini- mononucleosis slide agglutination test can help to confirm a clinical
cal judgment often overestimate the likelihood of a streptococcal etiol- diagnosis of Epstein-Barr virus infectious mononucleosis.
ogy. Various clinical scoring systems have been described to assist in
identifying patients who are likely to have GAS pharyngitis. Criteria TREATMENT
developed for adults and modified for children by McIsaac give 1 Specific therapy is unavailable for most viral pharyngitis. However,
point for each of the following criteria: history of temperature >38°C nonspecific, symptomatic therapy can be an important part of the
(100.4°F); absence of cough; tender anterior cervical adenopathy; ton- overall treatment plan. An oral antipyretic/analgesic agent (acetamino-
sillar swelling or exudates; and age 3-14 yr. It subtracts a point for age phen or ibuprofen) can relieve fever and sore throat pain. Anesthetic
≥45 yr. At best, a McIsaac score ≥4 is associated with a positive labora- sprays and lozenges (often containing benzocaine, phenol, or menthol)
tory test for GAS in less than 70% of children with pharyngitis (Table can provide local relief in children who are developmentally appropri-
381-2), so it, too, overestimates the likelihood of GAS. Consequently, ate to use them. Systemic corticosteroids are sometimes used in
laboratory testing is essential for accurate diagnosis. Clinical findings children who have evidence of upper airway compromise due to
and/or scoring systems can best be used to assist the clinician in iden- mononucleosis. Although corticosteroids are used fairly commonly in
tifying patients in need of testing. Streptococcal antibody tests are not adults with pharyngitis, large scale studies capable of providing safety
useful in assessing patients with acute pharyngitis. and efficacy data are lacking in children. Corticosteroids cannot be
Throat culture and rapid antigen-detection tests (RADTs) are the recommended for treatment of most pediatric pharyngitis.
diagnostic tests for GAS available in routine clinical care. Throat Antibiotic therapy of bacterial pharyngitis depends on the organism
culture remains the “gold standard” for diagnosing streptococcal phar- identified. On the basis of in vitro susceptibility data, oral penicillin is
yngitis. There are both false-negative cultures as a consequence of often suggested for patients with group C streptococcal isolates and
sampling errors or prior antibiotic treatment and false-positive cul- oral erythromycin is recommended for patients with A. haemolyticum,
tures as a consequence of misidentification of other bacteria as GAS. but the clinical benefit of such treatment is uncertain.
Some laboratories prefer nucleic acid testing that is specific for GAS Most untreated episodes of GAS pharyngitis resolve uneventfully
and no longer use culture to confirm the diagnosis. A child who is within 5 days, but early antibiotic therapy hastens clinical recovery by
chronically colonized with GAS (streptococcal carrier) can have a posi- 12-24 hr. The primary benefit and intent of antibiotic treatment is the
tive culture if it is obtained when the child is evaluated for pharyngitis prevention of acute rheumatic fever (ARF); it is highly effective when
that is actually caused by a viral infection. started within 9 days of onset of illness. Antibiotic therapy does not
Streptococcal RADTs detect the group A carbohydrate of GAS. They prevent acute poststreptococcal glomerulonephritis (APSGN). Antibi-
are used by the vast majority of office-based pediatricians. All RADTs otic therapy should not be delayed for children with symptomatic
have very high specificity, generally ≥95%, so when a RADT is positive pharyngitis and a positive GAS RADT or throat culture. Presumptive
it is assumed to be accurate and throat culture is unnecessary. Because antibiotic treatment can be started when there is a clinical diagnosis of
RADTs are generally less sensitive than culture, confirming a negative scarlet fever, a symptomatic child has a household contact with

Table 381-2 Positive Predictive Value of McIsaac Score in Children in Clinical Studies*
McISAAC, 2004 EDMONSON, 2005 TANZ, 2009 FINE, 2012
SCORE (N = 454) (N = 1184) (N = 1848) (N = 64,789)
0 — — 7% 17%
1 — 0.5% 19% 23%
2 20.5% 8.9% 20% 34%
3 27.5% 42.4% 29% 50%
≥4 67.8% 48.2% 49% 68%
GAS prevalence 34% 38% 30% 37%
*One point is given for each of the following criteria: history of temperature >38°C (100.4°F); absence of cough; tender anterior cervical adenopathy; tonsillar swelling
or exudates; and age 3-14 yr. Note that the Centor score lacks only the age criterion. Positive predictive value refers to the proportion of patients with documented
GAS by rapid antigen-detection test and/or throat culture.
2020  Part XIX  ◆  Respiratory System

Table 381-3 Recommended Treatment for Acute Streptococcal Pharyngitis

MOST PATIENTS
WEIGHT <27 kg WEIGHT ≥27 kg ROUTE DURATION
Amoxicillin 50 mg/kg once daily (maximum 1000 mg) Oral 10 days
Penicillin V 250 mg bid 500 mg bid Oral 10 days
Benzathine penicillin G 600,000 units 1.2 million units IM Once
Benzathine penicillin G + procaine penicillin G 900,000 units + 300,000 units 900,000 units + 300,000 units IM Once
PENICILLIN-ALLERGIC PATIENTS
ORAL DOSE FREQUENCY DURATION
Cephalosporins* Varies with agent chosen 10 days
Erythromycin
Ethylsuccinate 40 mg/kg/day up to 1000 mg/day bid 10 days
Estolate 20-40 mg/kg/day up to 1000 mg/day bid 10 days
Clarithromycin 15 mg/kg/day up to 500 mg/day bid 10 days
†
Azithromycin 12 mg/kg day 1; 6 mg/kg days 2-5 qd 5 days
Clindamycin 20 mg/kg/day up to 1.8 g/day tid 10 days
*First-generation cephalosporins are preferred; dosage and frequency vary among agents. Do not use in patients with history of immediate (anaphylactic)
hypersensitivity to penicillin or other β-lactam antibiotics.
†
Maximum dose is 500 mg the 1st day, 250 mg subsequent days.

documented streptococcal pharyngitis, or a history of ARF in the episodes of sore throat. Patients with repeated test-positive pharyngitis
patient or a family member, but a diagnostic test should be performed create anxiety among their families and physicians. It is usually unnec-
to confirm the presence of GAS. essary to attempt to eliminate chronic carriage. Instead, evaluation and
A variety of antimicrobial agents are effective for GAS pharyngitis treatment of pharyngitis should be undertaken without regard for
(Table 381-3). Group A streptococci are universally susceptible to peni- chronic carriage, treating test-positive patients in routine fashion and
cillin and all other β-lactam antibiotics. Penicillin is inexpensive, has avoiding antibiotics in patients who have negative tests. Expert opinion
a narrow spectrum of activity, and few adverse effects. Amoxicillin is suggests that eradication might be attempted in select circumstances:
preferred for children because of taste, availability as chewable tablets a community outbreak of ARF or APSGN; personal or family history
and liquid, and convenience of once-daily dosing. The duration of oral of ARF; an outbreak of GAS pharyngitis in a closed or semiclosed
penicillin and amoxicillin therapy is 10 days. A single intramuscular community, nursing home or healthcare facility; repeated episodes of
dose of benzathine penicillin or a benzathine-procaine penicillin G symptomatic GAS pharyngitis in a family with “ping pong” spread
combination is effective and ensures compliance. Follow-up testing for among family members despite adequate therapy; when tonsillectomy
GAS is unnecessary after completion of therapy and is not recom- is being considered because of chronic carriage or recurrent strepto-
mended unless symptoms recur. coccal pharyngitis; and extreme, unmanageable anxiety related to GAS
Patients allergic to penicillin can be treated with a 10-day course of carriage (“streptophobia”) among family members. Clindamycin given
a narrow-spectrum (first-generation) cephalosporin (cephalexin or by mouth for 10 days is effective therapy (20 mg/kg/day divided in 3
cefadroxil) if the previous reaction to penicillin was not an immediate, doses; adult dose 150-450 mg tid). Amoxicillin-clavulanate (40 mg
type I hypersensitivity reaction. Most often, penicillin-allergic patients amoxicillin/kg/day up to 2000 mg amoxicillin/day divided tid for
are treated for 10 days with erythromycin, clarithromycin, or clinda- 10 days) and 4 days of oral rifampin plus either intramuscular benza-
mycin, or for 5 days with azithromycin. thine penicillin given once or oral penicillin given for 10 days have also
The increased use of macrolides and related antibiotics for a variety been used.
of infections, especially the azalide, azithromycin, is associated with
increased rates of resistance to these drugs among GAS in many coun- RECURRENT PHARYNGITIS
tries. Approximately 5% of GAS in the United States and more than True recurrent GAS pharyngitis can occur for several reasons: reinfec-
10% in Canada are macrolide-resistant (macrolide resistance includes tion with the same M type if type-specific antibody has not developed;
azalide resistance), but there is considerable local variation in both poor compliance with oral antibiotic therapy; macrolide resistance if a
countries. Some macrolide-resistant GAS isolates are also resistant to macrolide was used for treatment; and infection with a new M type.
clindamycin. Although not a major hindrance for treatment of phar- Unfortunately, determining the GAS M type in an acute infection is
yngitis, clindamycin resistance may be important in management of not available to the clinician. Treatment with intramuscular benzathine
invasive GAS infections. Use of these antibiotics should be restricted penicillin eliminates nonadherence to therapy. Apparent recurrences
to patients who cannot safely receive a β–lactam drug for GAS phar- can represent pharyngitis of another cause in the presence of strepto-
yngitis. Tetracyclines, fluoroquinolones, or sulfonamides should not be coccal carriage. Chronic GAS carriage is particularly likely if the
used to treat GAS pharyngitis. illnesses are mild and otherwise atypical for GAS pharyngitis.
Undocumented histories of recurrent pharyngitis are an inadequate basis
CHRONIC GROUP for recommending tonsillectomy.
A STREPTOCOCCUS CARRIERS Tonsillectomy may lower the incidence of pharyngitis for 1-2 yr
Patients who continue to harbor GAS in the pharynx despite appropri- among children with frequent episodes of documented pharyngitis (≥7
ate antibiotic therapy are streptococcal carriers. They have little or no episodes in the previous year or ≥5 in each of the preceding 2 yr, or ≥3
evidence of an immune response to the organism. The pathogenesis of in each of the previous 3 yr). However, the frequency of pharyngitis
chronic carriage is not known. Carriage generally poses little risk to (GAS and non-GAS) generally declines over time. By 2 yr posttonsil-
patients and their contacts, but it can confound testing in subsequent lectomy the incidence of pharyngitis in severely affected children is
similar among those who have tonsillectomy and those who do not.
Few children are so severely affected and the limited clinical benefit of
tonsillectomy for most must be balanced against the risks of anesthesia
and surgery.
Recurrent GAS pharyngitis is rarely, if ever, a sign of an immune
disorder. However, recurrent pharyngitis can be part of a recurrent
fever or autoinflammatory syndrome such as PFAPA syndrome. Pro-
longed pharyngitis (>1 wk) can occur in infectious mononucleosis and
Lemierre syndrome, but it also suggests the possibility of another dis-
order such as neutropenia, a recurrent fever syndrome, or an autoim-
mune disease such as systemic lupus or inflammatory bowel disease.
In such instances, pharyngitis would be one of a number of clinical
findings that together should suggest the underlying diagnosis.

COMPLICATIONS AND PROGNOSIS

Viral respiratory tract infections can predispose to bacterial middle ear
infections and bacterial sinusitis. The complications of GAS pharyngi-
tis include local suppurative complications, such as parapharyngeal
abscess, and subsequent nonsuppurative illnesses, such as ARF,
APSGN, poststreptococcal reactive arthritis, and possibly PANDAS
(pediatric autoimmune neuropsychiatric disorders associated with S.
pyogenes) or CANS (childhood acute neuropsychiatric symptoms).

PREVENTION
A variety of GAS vaccines are being developed. A recombinant multi-
valent M-type vaccine uses the terminal portions of various M proteins
to take advantage of their immunogenicity. Other vaccines are based
on more conserved GAS epitopes in order to avoid the necessity of
matching the vaccine with the M types prevalent in a community or
target population. None of the investigational GAS vaccines are near
licensing for use. Antimicrobial prophylaxis with daily oral penicillin
prevents recurrent GAS infections but is recommended only to prevent
recurrences of ARF.

Bibliography is available at Expert Consult.

 Chapter 381  ◆  Acute Pharyngitis  2021.e1

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