Etiology

The most important agents causing pharyngitis are viruses, (adenoviruses, coronaviruses, enteroviruses, rhinoviruses, respiratory syncytial virus [RSV], Epstein-Barr virus [EBV], herpes simplex virus [HSV], metapneumovirus) and group A β-hemolytic streptococcus (GABHS; Chapter 176). Other organisms sometimes associated with pharyngitis include group C streptococcus (especially Streptococcus equisimilis), Arcanobacterium haemolyticum, Francisella tularensis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Fusobacterium necrophorum, and Corynebacterium diphtheriae. Other bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae, may be cultured from the throats of children with pharyngitis, but their role in causing pharyngitis has not been established. Primary infection with HIV can also manifest with pharyngitis and a mononucleosis-like syndrome.

Epidemiology

Viral upper respiratory tract infections are spread by close contact and occur most commonly in fall, winter, and spring. Streptococcal pharyngitis is relatively uncommon before 2-3 yr of age, has a peak incidence in the early school years, and declines in late adolescence and adulthood. Illness occurs most often in winter and spring and spreads among siblings and classmates. Pharyngitis from group C streptococcus and Arcanobacterium haemolyticum occurs most commonly among adolescents and adults.

Pathogenesis

Colonization of the pharynx by GABHS can result in either asymptomatic carriage or acute infection. The M protein is the major virulence factor of GABHS and facilitates resistance to phagocytosis by polymorphonuclear neutrophils. Type-specific immunity develops following most infections and provides protective immunity to subsequent infection with that particular M serotype.

Scarlet fever is caused by GABHS that produces 1 of 3 streptococcal erythrogenic exotoxins (A, B, and C) that can induce a fine papular rash (Chapter 176). Exotoxin A appears to be most strongly associated with scarlet fever. Exposure to each exotoxin confers specific immunity only to that toxin and, therefore, scarlet fever can occur up to 3 times.

Diagnosis

The clinical presentations of streptococcal and viral pharyngitis show considerable overlap. Physicians relying solely on clinical judgment often overestimate the likelihood of a streptococcal etiology, so laboratory testing is useful in identifying children who are most likely to benefit from antibiotic therapy. Throat culture remains an imperfect gold standard for diagnosing streptococcal pharyngitis. False-positive cultures can occur if other organisms are misidentified as GABHS, and children who are streptococcal carriers can also have positive cultures. False-negative cultures are attributed to a variety of causes, including inadequate throat swab specimens and patients’ surreptitious use of antibiotics. The specificity of rapid tests to detect group A streptococcal antigen is high, so if a rapid test is positive, throat culture is unnecessary and appropriate treatment is indicated. Because rapid tests are generally less sensitive than culture, confirming a negative rapid test with a throat culture has been recommended, especially if the clinical suspicion of GABHS is high. Special culture media and a prolonged incubation are required to detect A. haemolyticum. Viral cultures are often unavailable and are generally too expensive and slow to be clinically useful. Viral polymerase chain reaction (PCR) is more rapid and may be useful but is not always necessary. A complete blood cell (CBC) count showing many atypical lymphocytes and a positive slide agglutination (or “spot”) test can help to confirm a clinical diagnosis of EBV infectious mononucleosis.

Treatment

Most untreated episodes of streptococcal pharyngitis resolve uneventfully in a few days, but early antibiotic therapy hastens clinical recovery by 12-24 hr. The primary benefit of treatment is the prevention of acute rheumatic fever, which is almost completely successful if antibiotic treatment is instituted within 9 days of illness. Antibiotic therapy should be started immediately without culture for children with symptomatic pharyngitis and a positive rapid streptococcal antigen test, a clinical diagnosis of scarlet fever, a household contact with documented streptococcal pharyngitis, a past history of acute rheumatic fever, or a recent history of acute rheumatic fever in a family member.

A variety of antimicrobial agents are effective. GABHS remains universally susceptible to penicillin, which has a narrow spectrum and few adverse effects. Penicillin V is inexpensive and is given bid or tid for 10 days: 250 mg/dose for children <27 kg (60 lb) and 500 mg/dose for larger children and adults. Oral amoxicillin is often preferred for children because of taste, availability as chewable tablets, and convenience of once-daily dosing (750 mg fixed dose or 50 mg/kg, maximum 1 g) given orally for 10 days. A single intramuscular dose of benzathine penicillin (600,000U for children <27 kg [60 lb]; 1.2 million U for larger children and adults) or a benzathine-procaine penicillin G combination is painful but ensures compliance and provides adequate blood levels for more than 10 days. For patients allergic to penicillin, treatment options include

The increased use of macrolide antibiotics has been correlated with increased rates of resistance to erythromycin among group A streptococci. A narrow-spectrum cephalosporin (cephalexin or cefadroxil) is another treatment option so long as a patient’s previous reaction to penicillin was not an immediate, type I hypersensitivity reaction. Based on the proportion of cultures that remain positive for GABHS after therapy, cephalosporins appear to be as good as, or better than, penicillin, perhaps because these drugs are more effective in eradicating streptococcal carriage. Current evidence is not sufficient to recommend shorter courses of cephalosporins for routine therapy.

Follow-up cultures are unnecessary unless symptoms recur. Some treated patients continue to harbor GABHS in their pharynx and become streptococcal carriers. Carriage generally poses little risk to patients and their contacts, but it can confound the test results used to determine the etiology of subsequent episodes of sore throat. The treatment regimen most effective for eradicating streptococcal carriage is clindamycin, 20 mg/kg/day divided in 3 doses (adult dose: 150-450 mg tid or qid; maximum dose 1.8 g/day) orally for 10 days.

Specific therapy is unavailable for most viral pharyngitis. On the basis of in vitro susceptibility data, oral penicillin is often suggested for patients with group C streptococcal isolates and oral erythromycin is recommended for patients with A. haemolyticum, but the clinical benefit of such treatment is uncertain.

Nonspecific, symptomatic therapy can be an important part of the overall treatment plan. An oral antipyretic/analgesic agent (acetaminophen or ibuprofen) can relieve fever and sore throat pain. Gargling with warm salt water is often comforting, and anesthetic sprays and lozenges (often containing benzocaine, phenol, or menthol) can provide local relief.

Recurrent Pharyngitis

Recurrent streptococcal pharyngitis can represent relapse with an identical strain if type-specific antibody has not yet developed. If compliance with antibiotic treatment has been poor, intramuscular benzathine penicillin is suggested. The possibility of resistance should be considered if a nonpenicillin treatment such as erythromycin was given. Recurrences can also be caused by a different strain resulting from new exposures or can represent pharyngitis of another cause accompanied by streptococcal carriage. This last possibility is likely if the illnesses are mild and otherwise atypical for streptococcal pharyngitis. If GABHS is detected by repeat culture a few days after completing treatment, therapy to eliminate carriage is recommended. Prolonged pharyngitis (>1-2 wk) suggests another disorder such as neutropenia or recurrent fever syndromes.

Tonsillectomy lowers the incidence of pharyngitis for 1-2 yr among children with recurrent, culture-positive GABHS pharyngitis that has been severe and frequent (>7 episodes in the previous year, or >5 in each of the preceding 2 yr). Most children spontaneously have fewer episodes over time, however, so the anticipated clinical benefit must be balanced against the risks of anesthesia and surgery. Undocumented histories of recurrent pharyngitis are an inadequate basis for recommending tonsillectomy.

Complications and Prognosis

Viral respiratory tract infections can predispose to bacterial middle ear infections. The complications of streptococcal pharyngitis include local suppurative complications, such as parapharyngeal abscess, and later nonsuppurative illnesses, such as acute rheumatic fever (Chapter 176.1) and acute postinfectious glomerulonephritis (Chapter 505.1).

Prevention

Multivalent streptococcal vaccines based on M protein peptides are under development. Antimicrobial prophylaxis with daily oral penicillin prevents recurrent GABHS infections but is recommended only to prevent recurrences of acute rheumatic fever (Chapter 176.1).