Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis

INTRODUCTION — Group A Streptococcus (GAS), also known as Streptococcus pyogenes, is the most common cause of bacterial pharyngitis in children and adolescents. The clinical features and diagnosis of GAS pharyngitis in children and adolescents will be discussed here. The treatment, prevention, and complications of GAS pharyngitis and the evaluation of acute pharyngitis in children and adults are discussed separately.

●(See "Treatment and prevention of streptococcal pharyngitis in adults and children".)

●(See "Complications of streptococcal tonsillopharyngitis".)

●(See "Evaluation of sore throat in children".)

●(See "Evaluation of acute pharyngitis in adults".)

MICROBIOLOGY — GAS is a facultative, gram-positive coccus that grows in chains. The only known reservoirs are the skin and mucous membranes of the human host. The pathogenic mechanisms underlying these infections are poorly understood; they are discussed separately. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms".)

EPIDEMIOLOGY — GAS is the most common cause of bacterial pharyngitis in children and adolescents. It accounts for 15 to 30 percent of all cases of pharyngitis in children between the ages of 5 and 15 years [1-4].

In temperate climates, the incidence of GAS pharyngitis peaks during the winter and early spring [5]. During these seasons, as many as 35 to 40 percent of cases of pharyngitis in children and adolescents are caused by GAS.

GAS pharyngitis is most common in school-age children but may occur in younger children, especially if they have contact with school-age children [5,6]. In a meta-analysis, the pooled prevalence of GAS among children (<18 years) who presented to an outpatient clinic or emergency department with sore throat was 37 percent (95% CI 32-43 percent) [7]. The prevalence among children <5 years was 24 percent (95% CI 21-26 percent).

CLINICAL FEATURES

Children ≥3 years — In children ≥3 years, GAS pharyngitis typically has an abrupt onset. Fever, headache, abdominal pain, nausea, and vomiting may accompany the sore throat, which can lead to poor oral intake [3,8,9]. Additional features may include exudative tonsillopharyngitis (picture 1), with enlarged erythematous tonsils, enlarged tender anterior cervical lymph nodes, palatal petechiae, inflamed uvula (uvulitis (picture 2)), and scarlatiniform rash (erythematous, finely papular rash which characteristically starts in the groin and axilla and then spreads to the trunk and extremities, followed by desquamation) (picture 3A-B) [3,8,10]. Viral features (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea) are usually absent. Symptoms usually resolve spontaneously in three to five days. (See "Complications of streptococcal tonsillopharyngitis", section on 'Scarlet fever'.)

Children <3 years — Children <3 years of age generally do not have the findings that are typical of older children [11]. Instead of a well-defined episode of pharyngitis, they may have protracted symptoms of nasal congestion and discharge, low-grade fever (eg, <38.3°C [101°F]), and tender anterior cervical adenopathy [12]. This GAS symptom complex is called "streptococcosis."

Infants <1 year of age may present with nonspecific symptoms, including fussiness, decreased appetite, and low-grade fever. They often have older siblings or day care contacts with GAS infection.

Complications — Although most cases of GAS pharyngitis resolve without complications, serious nonsuppurative and suppurative complications may occur.

●Nonsuppurative complications of GAS pharyngitis include (see "Complications of streptococcal tonsillopharyngitis", section on 'Nonsuppurative complications'):

•Acute rheumatic fever (see "Acute rheumatic fever: Clinical manifestations and diagnosis")

•Poststreptococcal glomerulonephritis (see "Poststreptococcal glomerulonephritis", section on 'Clinical manifestations')

•Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) (see "PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci", section on 'Clinical features')

●Suppurative complications of GAS pharyngitis include (see "Complications of streptococcal tonsillopharyngitis", section on 'Suppurative complications'):

•Necrotizing fasciitis (see "Necrotizing soft tissue infections", section on 'Clinical manifestations')

•Bacteremia (see "Invasive group A streptococcal infections in children")

•Peritonsillar cellulitis or abscess (see "Peritonsillar cellulitis and abscess", section on 'Evaluation')

•Otitis media (see "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical presentation')

•Sinusitis (see "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Clinical features')

IMPORTANCE OF ACCURATE DIAGNOSIS — GAS is the most common cause of bacterial pharyngitis that benefits from antimicrobial therapy. Depending upon the season, as many as 35 to 40 percent of cases of pharyngitis in children and adolescents are caused by GAS. Timely treatment of GAS in children and adolescents is necessary to:

●Prevent suppurative complications and acute rheumatic fever (ARF) (see "Complications of streptococcal tonsillopharyngitis")

●Prevent disease transmission, particularly if the patient is a contact of someone with a history of ARF [8] (see "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)')

●Reduce duration and severity of symptoms

Treatment of GAS pharyngitis is discussed separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)

Microbiologic confirmation of GAS in the pharynx before initiation of antibiotic therapy helps to prevent unnecessary prescription of antibiotics to children with viral pharyngitis (most children with pharyngitis) [13]. (See 'Differential diagnosis' below.)

DIAGNOSIS

Diagnostic criteria — The diagnosis of GAS pharyngitis is supported by a positive microbiologic test (throat culture, rapid antigen detection test [RADT], or molecular point-of-care test [POC] for GAS) in a patient with symptoms of GAS pharyngitis and absence of signs and symptoms of viral infections (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea). However, the presence of isolated viral features (eg, cough, rhinorrhea) does not preclude a diagnosis of GAS pharyngitis. (See 'Clinical features' above and 'Microbiologic tests' below.)

Although a positive test supports the diagnosis of GAS, between 5 and 21 percent of children between 3 and 15 years of age are pharyngeal carriers of GAS [7,14,15]. Neither throat culture, RADT, nor molecular POC test for GAS can differentiate patients with acute GAS pharyngitis from GAS carriage with intercurrent viral illness [3]. Such patients may fail to respond to appropriate therapy for GAS infection. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Chronic GAS carriers'.)

Identification of GAS carriage is discussed separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Persistent or recurrent symptoms'.)

Approach to testing — Our approach to testing for GAS pharyngitis is generally consistent with that of the Infectious Diseases Society of America, the American Heart Association, American Academy of Pediatrics, and other professional groups [3,8,16,17].

Whom to test — We suggest microbiologic testing for GAS [3,8,16]:

●In children ≥3 years of age and adolescents with evidence of acute tonsillopharyngitis (erythema, edema, and/or exudates) or scarlatiniform rash (picture 3A-B) on physical examination. The likelihood of identifying a GAS infection is lower in the presence of characteristic signs and symptoms of viral infections (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea). (See 'Viral infections' below.)

●In children <3 years of age with prolonged nasal discharge, tender anterior cervical adenopathy, and low-grade fever (eg, <38.3°C [101°F]), particularly if they have exposure to contacts with GAS infection [6,11,12].

●In children with the suspected diagnosis of acute rheumatic fever (ARF) or acute poststreptococcal glomerulonephritis. (See "Acute rheumatic fever: Clinical manifestations and diagnosis" and "Poststreptococcal glomerulonephritis".)

●In children with a previous diagnosis of ARF when there is a household contact with GAS.

No single sign or symptom reliably identifies GAS pharyngitis in children with sore throats [3,8,10]. In a meta-analysis, although individual findings (eg, scarlatiniform rash, palatal petechiae, tonsillar enlargement, tender cervical lymphadenopathy) increased the probability of GAS pharyngitis to >50 percent, they could not be used for definitive diagnosis [10].

Similarly, clinical scoring systems for GAS that consist of various constellations of clinical findings and epidemiologic features [18-21] are insufficiently sensitive or specific to eliminate the need for microbiologic testing in children and adolescents with suspected GAS [3,10,22-24].

To prevent identification of GAS carriers with viral respiratory infection, we avoid microbiologic testing for GAS in children and adolescents with multiple manifestations strongly suggestive of viral illness (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea) [3,16,25,26]. Nonetheless, in a child with fever, exudative pharyngitis, and isolated rhinorrhea or cough, microbiologic testing may be warranted. Although viral features are usually absent in children with GAS pharyngitis, the presence of isolated viral features does not preclude a diagnosis of GAS pharyngitis. In a retrospective study of >60,000 children and adolescents (age 3 to 21 years) who were tested for GAS in a national network of retail clinics, the prevalence of GAS positivity was 28 percent among those with ≥1 feature of viral illness [27]. The prevalence of GAS positivity decreased with increasing numbers of viral features. Among children with viral features, the prevalence of GAS positivity was greater than the prevalence of GAS carriage (ie, the prevalence of GAS positivity in asymptomatic children), which ranged from 5 to 21 percent in a systematic review [7], suggesting that some of the children with viral features had acute GAS pharyngitis.

Choice of test — The diagnosis of GAS pharyngitis is supported by a positive throat culture, RADT, or molecular assay for GAS (table 1). (See 'Microbiologic tests' below.)

For children and adolescents in whom microbiologic testing for GAS is necessary, we suggest performance of a RADT. Standard throat culture and molecular assays are acceptable alternatives [28]. (See 'Microbiologic tests' below.)

If initial testing with RADT is negative in a child or adolescent, we recommend follow-up testing with standard throat culture because RADT may miss as many as 30 percent of cases of GAS pharyngitis [3,16,29-31]. Confirmation of negative RADT with throat culture is not necessary in adults. The risk of an initial episode of ARF in an adult with GAS pharyngitis is extremely low, even if an episode of streptococcal pharyngitis is untreated [3]. (See "Evaluation of acute pharyngitis in adults", section on 'Testing for GAS'.)

If initial testing with a molecular assay is negative, follow-up testing with a standard throat culture is not necessary, given the high sensitivity of molecular assays [32]. (See 'RADT for GAS' below and 'Molecular assays' below.)

Our preference for initial testing with RADT is based upon practical considerations. RADT are available in almost all practice settings, and the immediate results are appealing to patients, caregivers, and clinicians given the advantages of early diagnosis and treatment, including earlier clinical cure and return to school (for children) and work (for caregivers). Although immediate results also are available with molecular assays, use of molecular assays is limited by cost and complexity. Despite the practical considerations, initial testing with RADT may be less cost effective than initial testing with standard throat culture. Most children who require microbiologic testing for pharyngitis do not have GAS pharyngitis and will have a negative RADT. Given that negative RADT in children and adolescents must be confirmed with throat culture, if RADT is used as the initial test, the majority of children and adolescents who are tested will require both RADT and throat culture.

Specimen collection and processing — The key to optimizing detection of GAS in clinical specimens is appropriate collection and transport of the sample [31]:

●Specimens should be obtained before initiation of antimicrobial therapy because a single dose of antibiotics can result in a negative culture or RADT.

●If RADT is to be performed, we suggest that the throat be swabbed with two swabs simultaneously [31]. One is used for RADT; if RADT is positive, the second swab can be discarded. If RADT is negative, the second swab can be used for standard culture. (See 'Diagnosis' above.)

●Specimens should be obtained by vigorous swabbing of both tonsils (or tonsillar fossae in patients who have undergone tonsillectomy) and the posterior pharynx. The swab(s) should be moved into and out of the mouth without touching the tongue or the buccal mucosa. The importance of obtaining an adequate specimen cannot be overstated; the sensitivity of both culture and RADT correlate with inoculum size [1,33,34].

Microbiologic tests

RADT for GAS — RADT for GAS, sometimes referred to as rapid streptococcal antigen tests (RSAT), are based upon enzyme or acid extraction of antigen from throat swabs [35-38]. RADT results are available at the point of care in the office or emergency department and, if positive, permit early institution of therapy for GAS pharyngitis. Early institution of therapy enables earlier resolution of symptoms and return to school. However, early therapy may also predispose to more frequent recurrences of GAS within 30 days [39-41].

RADT have a specificity of ≥95 percent and a sensitivity that varies between 70 and 90 percent for GAS [42-44]. In a 2016 meta-analysis of studies in which 58,244 children underwent both RADT and throat culture, the pooled sensitivity and specificity of RADT were 85.6 percent (95% CI 83.3-87.6) and 95.4 percent (95% CI 94.5-96.2), respectively [44]. Given the high specificity and limited sensitivity of the available tests, a positive RADT is useful in establishing the diagnosis of GAS pharyngitis, but a negative RADT does not rule out GAS; back-up throat culture should be performed in children and adolescents with a negative RADT [3,16,29,30].

Throat culture — Although throat culture has been the reference standard for the diagnosis of acute pharyngitis due to GAS [8,45], the turnaround time of 24 to 48 hours limits it use as the preferred initial test. When performed properly, the sensitivity of throat culture is 90 to 95 percent for GAS [3,16,46]. (See 'Specimen collection and processing' above.)

Throat culture is usually performed on 5 percent sheep blood agar [45]. The culture is positive if small gray colonies with a surrounding area of beta-hemolysis are detected after 18 to 24 hours of incubation at 35 to 37°C (95 to 98.6°F). If no beta hemolytic colonies are seen after 18 to 24 hours, the plate is reincubated for an additional 24 hours before being interpreted as negative [3,47]. Twenty-five to 40 percent of throat cultures that are ultimately positive for GAS become positive after 24 hours [48].

Throat culture also can identify other bacteria that cause pharyngitis less commonly than GAS (eg, group C and group G streptococci, Arcanobacterium haemolyticum). However, most laboratories do not routinely identify these pathogens in throat cultures unless specifically requested to do so [31].

Molecular assays — Molecular assays (ie, nucleic acid amplification tests, polymerase chain reaction [PCR] assays) are becoming more routine for the evaluation of GAS pharyngitis [49], although there is much less experience with them than with RADT in clinician offices [50]. Expense and complexity are the major limiting factors.

Two types of molecular assays are available for the evaluation of GAS pharyngitis:

●Rapid PCR assays – Three rapid PCR assays for GAS pharyngitis that can be performed at the point of care and provide results in ≤25 minutes are available (Cobas Strep A test of the Liat system, ID NOW Strep A 2 test [formerly Alere i strep A test], Cepheid Xpert Xpress) [49]. Initial evaluation suggests that these rapid PCR assays have sensitivity ≥95 percent and specificity >90 percent [49,51-54]. Given the high sensitivity, it is reasonable to forego follow-up throat culture for patients with a negative result [31], particularly if the clinical laboratory has evaluated the molecular assay test "in house" and confirmed sensitivity to be ≥97 percent.

●Standard molecular assays – Although standard molecular assays are highly sensitive for GAS and identify symptomatic and asymptomatic patients with low density of colonization [28,55,56], the complexity of these tests frequently requires performance in a laboratory setting, which increases the turnaround time for results (usually between one and three hours, generally too long to be helpful at the point of care).

Molecular assays are more likely than throat cultures to be positive in patients with both symptomatic and asymptomatic infection with GAS, as well as in GAS "carriers." In a prospective study, throat culture and a highly sensitive molecular assay were performed on duplicate throat swabs in 385 asymptomatic children; positive results were more common with the molecular assay (20.3 versus 12.5 percent) [56]. It is not known whether this increased sensitivity results in identifying children with asymptomatic infection or "carriers." Given that subclinical or asymptomatic infection with GAS is common, testing for GAS is generally recommended only in children with symptomatic sore throat.

GAS serology — Serologic testing for GAS has been used historically to confirm previous infection in patients who are being evaluated for ARF or poststreptococcal glomerulonephritis. However, serologic testing is not helpful at the time of clinical presentation with pharyngitis. In addition, in a prospective study, serologic methods were imperfect in confirming infection in at least one-third of patients with documented acute acquisition of GAS [57].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of GAS pharyngitis includes both infectious and noninfectious causes of pharyngitis.

Other infectious causes of pharyngitis — Acute infectious pharyngitis in children and adolescents is caused by a variety of agents (table 2). The frequency of these pathogens varies according to the age of the child, season, and geographic area.

Microbiologic testing may be necessary to differentiate GAS pharyngitis from other infectious causes of pharyngitis that require treatment or infection control (table 2) and in children and adolescents whose symptoms worsen or persist for more than five to seven days (whether or not they were treated for GAS) [58]. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Response to therapy'.)

Other bacterial infections — Other bacterial causes of pharyngitis that may require treatment are listed below. Although it is not necessary to exclude these infections in children with pharyngitis who test negative for GAS, microbiologic testing is warranted in children with compatible clinical or epidemiologic features.

●Group C and G streptococci – Group C and G streptococci have been reported to cause epidemic and sporadic pharyngitis in school-age children and adults, although there has been some controversy over their etiologic role [59-63]. Group C or G streptococci may be identified with standard throat culture, but most laboratories do not routinely identify them unless specifically requested to do so. Group C or group G streptococcal pharyngitis may warrant treatment if the patient remains symptomatic when the results of the culture are available. The diagnosis and treatment of group C and G streptococcal infections are discussed separately. (See "Group C and group G streptococcal infection".)

●Neisseria gonorrhoeae – N. gonorrhoeae is a relatively rare cause of pharyngitis but may occur in patients with oral-genital contact. Most cases are asymptomatic; when present, findings are nonspecific (eg, pharyngeal erythema, edema, or exudate). Evaluation for gonococcal pharyngitis with a nucleic acid amplification test or throat culture on media specific for N. gonorrhoeae may be warranted in patients with risk factors (eg, unprotected oral-genital contact). If N. gonorrhoeae is detected, treatment is necessary to prevent transmission and disseminated disease. (See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents", section on 'Patients with extragenital symptoms' and "Treatment of uncomplicated gonorrhea (Neisseria gonorrhoeae infection) in adults and adolescents", section on 'Pharyngeal infection'.)

●Fusobacterium necrophorum – F. necrophorum causes most cases of jugular vein suppurative thrombophlebitis (Lemierre syndrome). Lemierre syndrome predominantly affects previously healthy adolescents and young adults. Clinical features include high fever (>39°C [102.2°F]), rigors, respiratory symptoms, and unilateral neck swelling or pain, findings typically absent in GAS pharyngitis. (See "Lemierre syndrome: Septic thrombophlebitis of the internal jugular vein".)

The potential roles of F. necrophorum in acute pharyngitis and of F. necrophorum pharyngitis in the development of Lemierre syndrome are discussed separately. (See "Evaluation of acute pharyngitis in adults", section on 'Other bacteria' and "Lemierre syndrome: Septic thrombophlebitis of the internal jugular vein", section on 'Microbiology'.)

●A. haemolyticum – A. haemolyticum pharyngitis occurs predominantly in adolescents [64-66]. Clinical features overlap with those of GAS and include fever, exudative pharyngitis, and rash on the extensor surfaces of the arms (picture 4) [65,67]. The rash occurs in approximately one-half of patients but, in contrast with the rash of scarlet fever, does not peel [64,65,67]. A. haemolyticum grows slowly on sheep blood agar plates and produces a tiny zone of beta hemolysis after 48 to 72 hours. Detection is improved (larger colony size and wider zone of hemolysis) by culture on human or rabbit blood agar [68]. In in vitro studies, A. haemolyticum was unresponsive to penicillin; erythromycin is the drug of choice [64].

●Diphtheria – Diphtheria is uncommon in developed countries but is important to consider in patients from endemic areas. In contrast with GAS pharyngitis, which has acute onset, the onset of symptoms in diphtheria is usually gradual, beginning with mild pharyngeal injection and erythema. The hallmark of diphtheria is the formation of a tightly adherent gray membrane in the nares and throat (picture 5). This membrane occurs in at least one-third of patients and causes bleeding when it is dislodged. (See "Epidemiology and pathophysiology of diphtheria", section on 'Epidemiology' and "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Clinical manifestations'.)

●Tularemia – Tularemia is an uncommon cause of pharyngitis that should be considered in patients with pharyngitis unresponsive to penicillin. It is usually acquired by ingestion of poorly cooked wild animal meat or contaminated water. Clinical features of oropharyngeal tularemia include fever, painful ulcerative-exudative pharyngitis, and cervical lymphadenitis. (See "Tularemia: Microbiology, epidemiology, and pathogenesis", section on 'Epidemiology' and "Tularemia: Clinical manifestations, diagnosis, treatment, and prevention".)

●Mycoplasma pneumoniae – M. pneumoniae can cause pharyngitis and other respiratory tract illness in children ≥6 years. M. pneumoniae accounts for 5 to 16 percent of cases of pharyngitis; the wide range may be related to the cyclicity of M. pneumoniae epidemics [69,70]. (See "Mycoplasma pneumoniae infection in children", section on 'Clinical manifestations'.)

Viral infections — Viruses are the most common cause of acute pharyngitis (table 2) [45,71,72]. Clinical features suggestive of viral etiology include concurrent conjunctivitis, rhinorrhea, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions, viral exanthems, and/or diarrhea [3]. Most children and adolescents with negative microbiologic tests for GAS have viral pharyngitis, which is a self-limited condition and can be treated symptomatically without additional testing. (See "Acute pharyngitis in children and adolescents: Symptomatic treatment", section on 'General management'.)

Viral infections in the differential diagnosis of GAS pharyngitis in children and adolescents that have important management or infection control implications are listed below. Although it is not necessary to exclude these infections in children with pharyngitis who test negative for GAS, microbiologic testing may be warranted in children with compatible clinical or epidemiologic features. The approach to microbiologic testing in children with suspected viral pharyngitis is discussed separately. (See "Evaluation of sore throat in children", section on 'Algorithmic approach'.)

●Infectious mononucleosis – Epstein-Barr virus (EBV) and cytomegalovirus account for most cases of infectious mononucleosis, a clinical syndrome that classically occurs in adolescents and is characterized by fever, severe pharyngitis (which lasts longer than pharyngitis due to GAS), and anterior and posterior cervical or diffuse lymphadenopathy, lymphocytosis, and increased aminotransferase levels [73,74]. Prominent constitutional symptoms include fatigue, anorexia, and weight loss. Examination findings may include periorbital or palpebral edema, mild hepatomegaly, and splenomegaly. Patients who are treated with ampicillin, amoxicillin, or other antibiotics may develop a characteristic rash (picture 6). Laboratory findings may include increased aminotransferases and predominance of atypical lymphocytes in the differential blood count. (See "Infectious mononucleosis".)

Unlike adolescents, who typically present with classic symptoms, younger patients with EBV infection may have a more subtle presentation that can make diagnosis difficult. (See "Clinical manifestations and treatment of Epstein-Barr virus infection", section on 'Primary infection'.)

Patients with infectious mononucleosis and splenomegaly require activity restriction to prevent splenic rupture. (See "Infectious mononucleosis", section on 'Return to sports'.)

●Primary HIV infection – Primary HIV infection may cause an acute retroviral syndrome (similar to infectious mononucleosis) in sexually active adolescents or rarely in children who have been sexually abused. The onset of symptoms usually occurs within days to weeks after the initial exposure. Clinical features of primary HIV infection include prominent cervical or generalized adenopathy and persistent constitutional complaints (eg, fever, weight loss). Laboratory features may include lymphopenia and increased aminotransferase levels. (See "Acute and early HIV infection: Pathogenesis and epidemiology" and "Acute and early HIV infection: Clinical manifestations and diagnosis".)

●Herpes simplex virus – Herpes simplex virus (HSV) pharyngitis should be considered in children and adolescents with the characteristic enanthem or ulcerative lip lesion. HSV is more common in adolescents than in younger children and is characterized by its severity and duration (frequently >7 days). HSV pharyngitis in children and adolescents may respond to acyclovir therapy. (See "Herpetic gingivostomatitis in young children" and "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Diagnosis' and "Treatment and prevention of herpes simplex virus type 1 in immunocompetent adolescents and adults", section on 'Treatment of HSV-1 infection'.)

●Influenza – Influenza infection is characterized by fever, cough, headache, and myalgias that occur in seasonal epidemics. Pharyngitis caused by influenza may be exudative. Influenza pharyngitis should be considered in children and adolescents with fever and severe illness (pharyngitis, cough, or both in the absence of another known cause of illness) during influenza season (regardless of influenza immunization status) [75]. Antiviral therapy is indicated for children at risk for complications or severe disease (table 3). Laboratory confirmation should not delay initiation of treatment. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Diagnosis' and "Seasonal influenza in children: Management", section on 'Antiviral therapy'.)

●Severe acute respiratory syndrome coronavirus 2 – Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), may cause pharyngitis in children. Indications for testing for SARS-CoV-2 in children are discussed separately. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Criteria for COVID-19 testing'.)

●Enteroviruses – Enteroviruses, specifically coxsackie A viruses, cause herpangina, which is characterized by small vesicles in the posterior pharynx (picture 7). In one series of 50 children (aged 1 to 10 years) with acute pharyngitis, enterovirus polymerase chain reaction was positive in 8 percent [76]. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention".)

●Adenovirus – Adenovirus may manifest as pharyngitis, tonsillitis, or pharyngoconjunctival fever. There are no distinguishing characteristics of infections caused by adenovirus except in patients with pharyngoconjunctival fever. The presence of exudate is common but not invariable. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection".)

When pharyngitis is part of a viral syndrome that causes nasopharyngitis, nasal congestion and discharge may be more prominent than sore throat. These infections generally resolve with symptomatic therapy, and it is not usually necessary to identify the specific viral pathogen. (See "The common cold in children: Management and prevention", section on 'Symptomatic therapy'.)

Viruses that cause nasopharyngitis include:

●Rhinoviruses (see "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections", section on 'Clinical illness')

●Coronaviruses, including SARS-CoV-2, which causes COVID-19 (see "Coronaviruses", section on 'Clinical manifestations' and "COVID-19: Clinical manifestations and diagnosis in children")

Indications for testing for SARS-CoV-2 in children are discussed separately. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Criteria for COVID-19 testing'.)

●Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children", section on 'Clinical manifestations')

●Parainfluenza viruses (see "Parainfluenza viruses in children", section on 'Clinical presentation')

Noninfectious causes of pharyngitis — Noninfectious causes of sore throat include irritation or drying of the pharynx (often from mouth-breathing overnight secondary to nasal obstruction from viral infection or allergic inflammation), foreign body (eg, fish bone), chemical exposure, referred pain from extrapharyngeal sources (eg, dental abscess, otitis media). These can usually be differentiated from infectious pharyngitis through information from the history or physical examination. (See "Evaluation of sore throat in children", section on 'Other conditions'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Streptococcal tonsillopharyngitis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Strep throat in children (The Basics)" and "Patient education: Sore throat in children (The Basics)")

●Beyond the Basics topic (see "Patient education: Sore throat in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Group A Streptococcus (GAS) is the most common cause of bacterial pharyngitis in children and adolescents. It accounts for 15 to 30 percent of all cases of pharyngitis in children between the ages of 5 and 15 years. In temperate climates, the incidence of GAS pharyngitis peaks during the winter and early spring. (See 'Epidemiology' above.)

●Clinical features – GAS pharyngitis typically has an abrupt onset. Fever, headache, abdominal pain, nausea, and vomiting may accompany the sore throat. Additional features may include exudative pharyngitis (picture 1), enlarged tender anterior cervical lymph nodes, palatal petechiae, inflamed uvula (uvulitis (picture 2)), and scarlatiniform rash (picture 3A-B). Symptoms usually resolve spontaneously in three to five days. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of GAS pharyngitis is supported by a positive microbiologic test (throat culture, rapid antigen detection test [RADT], or molecular assay for GAS (table 1)) in a patient with symptoms of GAS pharyngitis and absence of signs and symptoms of viral infections (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea). In children and adolescents, GAS pharyngitis should be confirmed microbiologically before antimicrobial therapy is initiated. (See 'Diagnostic criteria' above and "Treatment and prevention of streptococcal pharyngitis in adults and children".)

•We suggest microbiologic testing for GAS in children and adolescents with (see 'Whom to test' above):

-In children ≥3 years of age and adolescents with evidence of acute tonsillopharyngitis (erythema, edema, and/or exudates) or scarlatiniform rash (picture 3A-B) on physical examination. The likelihood of identifying a GAS infection is lower in the presence of characteristic signs and symptoms of viral infections (eg, rhinorrhea, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or vesicles, diarrhea). (See 'Viral infections' above.)

-In children <3 years of age with prolonged nasal discharge, tender anterior cervical adenopathy, and low-grade fever (eg, <38.3°C [101°F]), particularly if they have exposure to contacts with GAS infection [6,11,12].

-In children with the suspected diagnosis of acute rheumatic fever or acute poststreptococcal glomerulonephritis. (See "Acute rheumatic fever: Clinical manifestations and diagnosis" and "Poststreptococcal glomerulonephritis".)

-In children with a previous diagnosis of ARF when there is a household contact with GAS.

•For children and adolescents in whom microbiologic testing for GAS is necessary, we suggest initial testing with a RADT. Standard throat culture or molecular assay is an acceptable alternative. (See 'Choice of test' above and 'RADT for GAS' above.)

●Differential diagnosis – The differential diagnosis of GAS pharyngitis includes both infectious and noninfectious causes. Most children and adolescents with negative microbiologic tests for GAS have viral pharyngitis, which is a self-limited condition and can be treated symptomatically without additional testing. Additional testing may be necessary to differentiate GAS pharyngitis from other infectious causes of pharyngitis that require treatment or infection control (table 2) and in children and adolescents whose symptoms worsen or persist for more than five to seven days (whether or not they were treated for GAS). (See 'Differential diagnosis' above and "Evaluation of sore throat in children".)