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It is important to distinguish between superficial and deep space infections of the mouth and throat. Deep space infections are discussed in chapter 123, "Stridor and Drooling in Infants and Children," and are typically associated with toxic appearance, high fever, drooling, stridor, or changes in phonation, trismus, or torticollis. Simple pharyngitis, on the other hand, accounts for 1% to 2% of all visits to outpatient clinics and EDs, resulting in 7.3 million annual visits for children.24 Viral etiologies predominate in children with acute pharyngitis (Table 121-2).
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Symptoms associated with acute pharyngitis include sore throat, odynophagia, fever, headache, abdominal pain, nausea and vomiting, cough, hoarseness, coryza, diarrhea, arthralgias, myalgias, and lethargy. Physical examination may reveal tonsillopharyngeal erythema and/or exudates, soft palate petechiae, uvulitis, anterior cervical lymphadenitis, rash, conjunctivitis, anterior stomatitis, and discrete ulcerative lesions. It is often difficult to distinguish between viral and bacterial causes of pharyngitis based on physical examination alone,25 and tonsillar exudate does not imply bacterial etiology. This often results in overdiagnosis of bacterial etiology and unnecessary antibiotic treatment. Most viral infections are self-limited and require only symptomatic treatment. Interestingly, patient satisfaction appears to be greatest when a physician shows concern and provides reassurance and is not related to whether or not antibiotics are prescribed.26
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Pharyngitis is the best known acute clinical manifestation of Epstein-Barr virus infection (Figure 121-8). It often begins with malaise, headache, and fevers before development of the more specific signs of exudative pharyngitis and posterior cervical lymph node enlargement. Splenomegaly and hepatomegaly can also occur. Patients mistakenly treated for a bacterial pharyngitis with amoxicillin or ampicillin often develop a characteristic pruritic maculopapular rash that aids in diagnosis.
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Diagnosis is often clinical, although a heterophile test (monospot) can aid in diagnosis. It is important to remember that this test relies on cross-reactivity of patient antibodies and is relatively insensitive in pediatric patients (25% positive in 10 to 24 months vs 75% in 24 to 28 months). Furthermore, the monospot test typically does not turn positive in cases of Epstein-Barr virus until symptoms have been present for 1 week or more. A negative test, therefore, does not exclude the diagnosis of Epstein-Barr virus; when necessary, testing for Epstein-Barr virus immunoglobulin M and immunoglobulin G is both sensitive and specific, although results are not immediately available. Atypical lymphocytes may be present on the CBC, if obtained. Epstein-Barr virus infection may be associated with other organ involvement, including hepatitis. Patients with right upper quadrant tenderness should have liver enzymes evaluated.
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Treatment is largely supportive; however, some patients may require IV fluids and pain medication. Although there is no evidence of efficacy, a dose of oral or parenteral steroid can be considered to reduce tonsillar enlargement when swallowing or respiratory symptoms are attributed to enlarged tonsils. When splenomegaly is noted, proper counseling regarding risk factors and symptoms of splenic rupture should be given (avoid contact sports until splenomegaly has resolved as determined by the primary care physician).
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Cytomegalovirus infection can very closely mimic Epstein-Barr virus mononucleosis. Symptoms and signs of the two infections are almost identical. Indeed, patients presenting with classic infectious mononucleosis who are heterophile-negative are often infected with cytomegalovirus. Fever, malaise, and systemic complaints predominate in the clinical picture of cytomegalovirus, with less prominent cervical lymphadenopathy or splenic enlargement than Epstein-Barr virus. Distinguishing between the two etiologies is difficult, and often, the diagnosis is confirmed with laboratory testing for cytomegalovirus immunoglobulins M and G. Treatment is again supportive.
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Acute retroviral syndrome, or acute infection with human immunodeficiency virus, may present similarly to Epstein-Barr virus pharyngitis in 50% to 70% of patients. Differences implicating human immunodeficiency virus from other viral illnesses may include presence of high-risk behaviors in the social history, the acuity of onset, the absence of exudate and prominent tonsillar hypertrophy, presence of a rash, and mucocutaneous ulceration.
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Acute infection with human immunodeficiency virus is uncommon in the pediatric patient, although it must be considered in adolescents in whom high-risk behaviors are identified. In addition to the usual causes of pharyngitis, opportunistic infections, such as Candida albicans and Mycobacterium avium, should be considered in the immunocompromised patient.27
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Group A β-Hemolytic Streptococcus
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Group A β-hemolytic Streptococcus (GABHS) pharyngitis is the most commonly occurring form of acute bacterial pharyngitis for which antibiotic therapy is indicated.28 It typically occurs in the winter and early spring, is rare in children <2 years of age,29 and primarily affects children age 5 to 15 years old.30 Although GABHS accounts for only 15% to 30% of pharyngitis in children, approximately 53% of children with pharyngitis receive antibiotics.31 Additionally, a substantial proportion of patients treated for GABHS pharyngitis receive an inappropriate antibiotic. Clinical trials are under way to evaluate the safety and efficacy of a multivalent group A Streptococcus vaccine.32
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Several clinical prediction rules have been created to identify cases of GABHS pharyngitis, and most are modifications of the original Centor criteria33 (Table 121-3). These can be useful in determining which patients require testing for GABHS. With zero or one criterion, GABHS is unlikely, and testing and treatment for GABHS are not indicated. With two or more criteria, testing should be performed using a rapid antigen detection test and/or culture.34
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Although bacterial culture remains the gold standard, with a sensitivity of 90% to 95%, the 18- to 48-hour wait time for definitive diagnosis is often impractical, and the use of rapid antigen detection has become popular. The sensitivity of rapid antigen detection varies from 80% to 90%. As a result, current guidelines recommend confirmatory throat culture for all patients with a negative antigen test.35 Back-up cultures are not necessary for patients with a positive antigen test because the test is highly specific.
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The antibiotic treatment of GABHS pharyngitis is effective to: (1) shorten the duration of illness, (2) prevent transmission, (3) prevent suppurative complications (acute otitis media, acute sinusitis, and peritonsillar abscess), and (4) prevent systemic illness such as rheumatic fever, rheumatic heart disease, and poststreptococcal glomerulonephritis. Antibiotics for the treatment of GABHS pharyngitis should be reserved, however, for patients with a positive antigen test or culture, or those meeting clinical criteria for diagnosis. GABHS pharyngitis is typically a self-limited disease, with fever and constitutional symptoms diminishing markedly at days 3 and 4 after symptom onset, and antibiotics only decrease the duration of symptoms by approximately 16 hours.36
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Treatment Treatment can be delayed safely for up to 9 days after symptom onset and still prevent major nonsuppurative sequelae; thus, waiting for confirmatory cultures and providing a wait-and-see-prescription for antibiotics are safe. There is no definitive evidence that antibiotic use can prevent acute glomerulonephritis. Further confounding the decision to treat is the possibility that a percentage of patients may be GABHS carriers and that acute infection with another organism may be causing disease rather than GABHS pharyngitis.
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Penicillin remains the treatment of choice, based on its efficacy, safety, narrow spectrum, ease of dosing (twice-daily dosing), compliance, and cost (Table 121-4).35 No clinical isolate of GABHS has been documented to be penicillin resistant. Treatment failures may be attributable to viral pharyngitis with GABHS carriage, medication noncompliance, or reinfection of patients successfully treated for GABHS. A course of 10 days of oral therapy with twice-a-day dosing is recommended for complete pharyngeal eradication; similar efficacy is achieved with once-daily dosing of amoxicillin for 10 days or with a single IM dose of benzathine penicillin.
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Several alternative therapy options exist for those unable to take penicillin. The efficacy of amoxicillin appears to be comparable to that of penicillin and is acceptable in children who more easily tolerate the taste of the suspension. Clarithromycin and first-generation cephalosporins are suitable alternatives in penicillin-allergic patients. Clindamycin may be required for macrolide-resistant GABHS in the penicillin-allergic patient. Macrolide resistance is increasing worldwide. Currently, 6% to 7% of GABHS isolates in the United States appear to be macrolide resistant, but this is expected to increase given higher resistance patterns in other parts of the world and the widespread use of macrolides for the treatment of upper and lower respiratory tract infections.37
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Routine antibiotic prophylaxis is not recommended for household members exposed to GABHS, because the risk of developing subsequent pharyngitis is approximately 10%.38 Although tonsillectomy is clearly indicated for recurrent tonsillitis in children, there is only modest evidence to support tonsillectomy for recurrent pharyngitis. Patients undergoing tonsillectomy have been shown to have a modest reduction in frequency of GABHS infections for up to 2 years after surgery.39
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Benefits of antibiotic treatment for other bacterial pharyngitides are unclear at this time. There have been no cases of acute rheumatic fever due to non-GABHS, such as groups C and G Streptococcus. If treated, antibiotics used in the treatment of GABHS are appropriate for pharyngitis due to groups C and G Streptococcus.
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Several other bacterial etiologies must be considered in patients with pharyngitis. These include Neisseria gonorrhoeae, Corynebacterium diphtheriae, Arcanobacterium haemolyticum, Yersinia enterocolitica, Yersinia pestis, Francisella tularensis, Mycoplasma pneumoniae, and Chlamydia species.
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Gonococcal Pharyngitis
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Gonococcal pharyngitis is difficult to distinguish from other bacterial causes of pharyngitis. A careful sexual history, including exposure to partners with known sexually transmitted diseases and oral sex practices, should be elicited in all adolescent patients presenting with pharyngitis. Gonococcal infection of the throat may be associated with infection elsewhere, including proctitis, vaginitis, and/or urethritis. The diagnosis requires special culture on Thayer-Martin medium, although nucleic acid amplification testing is also available. A positive culture in a prepubertal child is highly suspicious for sexual abuse, and further investigation is warranted with involvement of the appropriate child protection agencies. IM ceftriaxone (250 milligrams) is the only therapy recommended by the Centers for Disease Control and Prevention for the treatment of uncomplicated pharyngeal gonorrhea. Empiric treatment for concomitant chlamydia with the addition of 1 gram of azithromycin should be given unless it has specifically been ruled out.
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Although occurrence is rare in developed countries due to vaccination, C. diphtheriae should be considered in patients who are under- or unimmunized. Toxigenic strains of this bacterium produce an exotoxin that causes localized necrosis of the respiratory mucosa and can lead to both cardiac and neurologic complications. Pseudomembrane formation in the respiratory tract can result in airway obstruction. Identification of the causative organism is made using Loeffler or tellurite selective medium. Treatment of pharyngeal diphtheria is aimed at bacterial eradication and exotoxin neutralization. Penicillin and erythromycin are the antibiotics of choice, along with equine diphtheria antitoxin. Serious sequelae can be prevented with prompt antibiotic administration, and treatment should be started when diphtheria is clinically suspected.
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Arcanobacterium Pharyngitis
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A. haemolyticum closely mimics GABHS pharyngitis and may also produce a scarlatiniform rash in teenagers; rarely, it produces a membranous pharyngitis similar to that of diphtheria. It may be missed on routine cultures and may be more readily detected on human-blood agar plates. Both macrolide and β-lactam antimicrobial agents are effective treatments.