Pharyngitis

Abstract

“Sore throat” or pharyngitis is one of the most frequent complaints of patients in the acute care setting, accounting for nearly 7 million pediatric and 6 million adult visits each year. On the surface, pharyngitis would appear to pose few challenges to the clinician; the site of infection is both visible and accessible for inspection and culture, and the majority of pharyngeal pathogens are self-limiting respiratory viruses. Unfortunately, the diagnosis and management of acute pharyngitis is complicated by the 10% to 30% of cases caused by bacterial pathogens, particularly group A beta-hemolytic streptococci (GAS). Concerns over the risk of suppurative and nonsuppurative complications associated with GAS pharyngitis have fueled the widespread practice of empirical antimicrobial therapy. However, the consequences of antimicrobial overuse, measured by cost, adverse events, and bacterial resistance, have refocused attention on the need for targeted therapy based on an appreciation of the epidemiology and diverse clinical presentations of acute pharyngitis.

Epidemiology

Viral Causes of Pharyngitis

Acute pharyngitis is most often caused by a virus. Depending on the season and the patient's age, 70% to 90% of acute episodes are viral and involve a wide array of common viruses (Table 33-1 ). By far, the most common virus associated with pharyngitis is the common cold agent, rhinovirus. Outbreaks of rhinovirus usually begin in September, with the start of school. The virus efficiently passes from children to adults. A second peak of rhinovirus activity appears in the spring.

Table 33-1.

Microbial Causes of Pharyngitis by Type of Pathogen

Bacterial	Group A streptococci Groups C, G streptococci Neisseria gonorrheae Arcanobacterium haemolyticum Fusobacterium necrophorum Corynebacterium diphtheriae
Viral	Rhinovirus Coronavirus Adenovirus Parainfluenza virus types 1, 2, and 3 Influenza A and B virus Coxsackievirus Herpes simplex virus Epstein-Barr virus Cytomegalovirus Human immunodeficiency virus
Atypical agents	Mycoplasma pneumoniae Chlamydophila pneumoniae

Data from Bisno AL, Gerber MA, Gwaltney JM Jr, et al: Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis, Clin Infect Dis 35:113-125, 2002.

Adenovirus ranks second among viral causes of pharyngitis in both children and adults. During late winter and early spring approximately 20% of pharyngitis cases may involve adenovirus, especially in children younger than 5 years of age. Young adults, including military recruits, constitute another high-incidence group. Childhood infections typically involve serotypes 1, 2, 5, and 6, whereas adults are susceptible to serotypes 3, 4, and 7. A unique form of adenoviral infection is pharyngoconjunctival fever, which usually occurs in children; exposure to contaminated swimming pools may be associated with community outbreaks of the disease.

Enteroviruses are a common cause of pharyngitis in the late summer and fall months. Group A coxsackieviruses are most often associated with herpangina, whereas coxsackievirus A16 and enterovirus 71 are the primary agents of hand, foot, and mouth disease. Group B coxsackieviruses and echoviruses are responsible for nonspecific febrile illnesses, pharyngitis, and aseptic meningitis.

Herpes simplex virus (HSV) has long been recognized as a cause of pharyngitis in children and has also been reported in young adults. Among college students with sore throat, HSV is the third most commonly identified viral pathogen, responsible for up to 6% of cases, and is predominantly type 1. Rare cases of necrotizing tonsillitis caused by HSV have also been observed.

Bacterial Causes of Pharyngitis

GAS is not only the most common bacterial pathogen, but also the most likely to result in complications of pharyngitis. In children, GAS causes 10% to 30% of cases of pharyngitis, with children aged 5 to 15 years at greatest risk for infection and complications. In adults, GAS accounts for 5% to 10% cases. Winter months are associated with an increase in GAS pharyngitis in people of all ages, but especially in children when it can be found in up to 50% of cases.

Although less common than GAS, other bacterial causes of pharyngitis should be considered. Groups C and G streptococci are the most common non–group A streptococci associated with pharyngitis, accounting for 2% to 6% of cases in children and young adults. The true incidence of groups C and G streptococci is unclear owing to the frequency of normal colonization. In college students, group C Streptococcus has been identified in 26% of students with pharyngitis compared with 11% of controls, supporting its role as a pathogen but underscoring the frequency of normal colonization. Of importance, there is no evidence that pharyngitis caused by non–group A streptococci poses a concern with regard to acute rheumatic fever (ARF). Rare reports linking group C streptococcus to poststreptococcal glomerulonephritis have not been validated. Arcanobacterium haemolyticum is found in less than 3% of cases of pharyngitis, although a higher incidence has been observed in adolescents and young adults.

Neisseria gonorrhoeae should be considered in individuals with pharyngitis and a history of orogenital sex with a partner at risk for gonorrhea. Rates of N. gonorrhoeae pharyngitis vary according to a patient's risk factors and community prevalence but are generally highest in adolescents and young adults. The isolation of N. gonorrhoeae from a prepubescent child must always raise suspicion for sexual abuse; however, care should be taken to verify N. gonorrhoeae because nonpathogenic Neisseria species are frequently present as normal flora in the oropharynx.

Although found as normal flora, the anaerobe Fusobacterium necrophorum is associated with a variety of head and neck infections and potentially life-threatening septic complications. In patients with pharyngitis, F. necrophorum appears more commonly among 16- to 20-year-olds, with a reported age range of 13 to 57 years.

The atypical agents, Mycoplasma pneumoniae and Chlamydophila pneumoniae, are commonly associated with lower respiratory tract infections and suspected to be the primary cause of mild pharyngitis in up to 17% of patients with sore throat and a co-pathogen in an additional 14%.

Historically, Corynebacterium diphtheriae has been one of the most important causes of tonsillar disease. Vaccination for diphtheria has virtually eliminated the organism in the United States; however, the disease remains endemic in many developing countries, with outbreaks also reported among the New Independent States of the former Soviet Union, the Russian Federation, and most recently Haiti.

Noninfectious Causes of Pharyngitis

Noninfectious diseases may produce inflammation of the posterior pharynx. Among these processes are Stevens-Johnson syndrome; toxic shock syndrome; Kawasaki disease; Behçet's syndrome; aphthous stomatitis; and periodic fever, pharyngitis, adenopathy, and aphthous stomatitis syndrome (PFAPA). PFAPA usually occurs in children younger than 5 years of age and is frequently misdiagnosed as recurrent tonsillitis.

Diagnosis

Clinical Manifestations

The principal challenge in managing pharyngitis is distinguishing viral from bacterial causes, particularly GAS. Pharyngitis is broadly defined as mucous membrane inflammation either localized to the posterior pharynx or contiguous with the adjacent membranes of the posterior nares or larynx. Differences in the extent of pharyngeal inflammation and in accompanying signs and symptoms help distinguish between GAS and viruses (Table 33-2 ). Patients with GAS most often demonstrate sudden onset of sore throat, marked pain with swallowing, and fever (Figure 33-1 ). Other signs and symptoms indicative of GAS include headache, nausea, vomiting, and the absence of cough and coryza. Findings that favor viral pathogens include conjunctivitis, punctate ulcerative tonsillar lesions, and stomatitis (Figure 33-2 ). Certain strains of GAS can trigger scarlet fever by elaborating an erythrogenic toxin that induces a bright, fine, maculopapular rash. Starting over the neck, the rash extends to the trunk and extremities and is particularly prominent over flexural creases and the perineum. After several days the rash fades and is followed by a fine desquamation as seen with sunburn. The lingual papillae become quite prominent, producing the characteristic “strawberry tongue” appearance.

Table 33-2.

Clinical and Epidemiologic Characteristics of Group A Beta-Hemolytic Streptococcal Pharyngitis

Features suggestive of group A Streptococcus as causative agent	Sudden onset Sore throat Fever Headache Nausea, vomiting, and abdominal pain Inflammation of pharynx and tonsils Patchy discrete tonsils Tender, enlarged anterior cervical nodes Patient aged 5-15 years Presentation in winter or early spring History of exposure
Features suggestive of viral cause	Conjunctivitis Coryza Cough Diarrhea

Data from Bisno AL, Gerber MA, Gwaltney JM Jr, et al: Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis, Clin Infect Dis 35:113-125, 2002.

Figure 33-1.

Streptococcal pharyngitis.

Figure 33-2.

Viral pharyngitis. More discrete punctuate pattern versus the strep pharyngitis.

Unfortunately, even with strict clinical criteria GAS can be predicted with only 50% accuracy. GAS may also be present in the absence of marked pharyngeal inflammation. The role of GAS in patients with mild pharyngitis is uncertain. Although it is clear that GAS can result in mild or even clinically inapparent infection, based on rises in anti–streptolysin O, it appears that the majority of patients with mild respiratory symptoms are at low risk for ARF and likely represent a GAS carrier state.

The clinical diagnosis of GAS pharyngitis is hampered by the presence of other pathogens that elicit similar signs. Groups C and G streptococci and A. haemolyticum cause exudative pharyngitis, adenopathy, and fever that are clinically indistinguishable from GAS. Strains of A. haemolyticum even induce a scarlatiniform rash similar to scarlet fever. Viruses may also mimic the clinical findings of GAS pharyngitis. Adenoviral pharyngitis causes tonsillar exudate, adenopathy, and fever over half of the time, mostly in children. More readily distinguished from GAS is adenoviral pharyngoconjunctival fever, which usually manifests as a unilateral follicular conjunctivitis, though it progresses to the other eye one fourth of the time. Epstein-Barr virus (EBV) manifests with acute onset of sore throat, fever, and cervical lymphadenopathy, and in one half of cases the pharyngitis is exudative (Figure 33-3 ). Occasionally, palatal petechiae appear, making EBV even more difficult to distinguish from GAS pharyngitis. Splenomegaly (present in 50% of patients), generalized lymphadenopathy, and periorbital edema, when present, provide clinical evidence in favor of EBV. HSV pharyngitis may manifest with fever, exudative pharyngitis, and cervical lymphadenopathy. In college students diagnosed with HSV pharyngitis, only one third demonstrated lesions typical of HSV. Herpetic gingivostomatitis is common in young children and causes vesicular lesions involving the lips, gingiva, and tongue; however, very early in the course patients may have lesions limited to the posterior pharynx.

Figure 33-3.

Epstein-Barr virus pharyngitis.

Clinically milder forms of pharyngitis, lacking exudate and marked edema, are usually caused by viruses. Enteroviruses frequently cause mild pharyngitis as part of a nonspecific febrile illness. More characteristic of enteroviruses is herpangina, which manifests with fever and discrete vesicular lesions involving the soft palate, tonsils, and surrounding posterior pharynx. Lesions are generally localized to the proximal portion of the oral cavity. Hand, foot, and mouth disease characteristically appears with vesicular lesions over the palms and/or soles, but they may be limited to the mouth and throat. Influenza A and B are characterized by the abrupt onset of fever, sore throat, myalgia, malaise, and dry cough. The rapid onset of cough and constitutional signs and symptoms, coinciding with known influenza activity in the community, is usually sufficient to suggest influenza.

Complications

Peritonsillar abscess, or quinsy, is the most frequent suppurative complication associated with pharyngitis (Figure 33-4 ). It occurs most often in adolescents and young adults and is rare in younger children. Organisms associated with peritonsillar abscesses include GAS and anaerobes, often present as mixed infection. Patients appear unwell with dysphagia, muffled “hot potato voice,” and fetid breath. The soft palate is displaced on the affected side with accompanying deviation of the uvula. Lateral pharyngeal abscesses may occur secondary to pharyngitis or peritonsillar abscess. Patients often have swelling over the lateral aspect of the neck and restriction in neck movement. Asymmetry of the posterior pharyngeal wall may be present, but its absence does not exclude the diagnosis. Pharyngeal infections with F. necrophorum may extend locally to cause deep neck infection, septic thrombophlebitis, and potentially life-threatening septic embolization (Lemierre syndrome).

Figure 33-4.

Peritonsillar abscess.

Serious nonsuppurative complications are most always a result of GAS and include ARF and poststreptococcal glomerulonephritis (Figure 33-5 ). ARF occurs most commonly in children 5 to 14 years of age and is rare in children under 3 and in adults over 40 years of age. Despite a marked decline in the prevalence of ARF, sporadic outbreaks continue to appear. Poststreptococcal glomerulonephritis occurs most often in children and typically appears 10 days after infection and occurs only with nephritogenic strains of GAS.

Figure 33-5.

Acute rheumatic fever.

Laboratory Diagnosis

Pivotal to the care of patients with pharyngitis is the accurate identification of infection caused by GAS. Whereas patients infected with other bacterial pathogens, such as non–group A streptococci, may benefit from antimicrobial therapy, they do not merit widespread screening or empirical antimicrobial treatment strategies. The problem is that GAS pharyngitis cannot be diagnosed by clinical evidence alone. Even experienced physicians are accurate only 50% of the time when examining patients with exudative pharyngitis. Despite this limitation, clinical judgment retains an important role in pharyngitis diagnosis and management. Clinical scoring tools, such as the modified Centor score, have proven useful in identifying patients at low risk for GAS (Table 33-3 ). Patients with clinical scores of 0 to 1 are at low risk for GAS and require no further testing and no antimicrobial treatment. More complicated is the approach to patients who are at less low risk for GAS, such as those with clinical scores ≥2. Patients with modified Centor scores of ≥2 are positive for GAS in only 15% to 50% of patients. Reliance on clinical scoring tools alone can result in up to 40% of patients receiving an unnecessary antimicrobial. In an effort to further aid clinicians in improving GAS diagnosis, several guidelines for the diagnosis and management of pharyngitis have been advanced. Inherent to these pharyngitis guidelines is a basic diagnostic and management strategy that still relies on clinical judgment in avoiding the errors of overtreatment and undertreatment.

Table 33-3.

Modified Centor Score

CRITERIA	POINTS
Temperature >38° C	1
Absence of cough	1
Swollen, tender anterior cervical nodes	1
Tonsillar swelling or exudate	1
Age
3-14 years	1
15-44 years	0
45 years or older	−1

Adapted from McIsaac WJ, Kellner JD, Aufricht P, et al: Empirical validation of guidelines for the management of pharyngitis in children and adults, JAMA 291:1587-1595, 2004.

The basic diagnostic and management strategy used for patients with sore throat begins with the clinician establishing whether the presentation is consistent with uncomplicated acute pharyngitis and then judging whether the patient is at low or higher risk for GAS based on history and physical examination (Figure 33-6 ). This risk assessment for GAS may use a clinical score or rely on a general pattern of clinical and epidemiologic findings (see Table 33-2, Table 33-3, Table 33-4 ). Patients judged at low risk for GAS can be managed with symptomatic care and require no further evaluation.

Figure 33-6.

Risk assessment for group A streptococci.

(From Bisno AL, Gerber MA, Gwaltney JM Jr, et al: Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis, Clin Infect Dis 35:113-125, 2002.)

Table 33-4.

Antimicrobial Therapy for Group A Beta-Hemolytic Streptococcal Pharyngitis

DRUG	DOSE	DURATION
Oral
Penicillin V	250 mg bid or tid for children 250 mg tid or qid for adolescents and adults 500 mg bid for adolescents and adults	10 days
Intramuscular
Penicillin G: benzathine	600,000 units for patients ≤27 kg (60 lb) 1.2 million units for patients >27 kg	1 dose
Penicillin G: benzathine and procaine mixtures*	Varies with formulation	1 dose
Patients Allergic to Penicillin
Erythromycin	Varies with formulation	10 days
First-generation cephalosporin†	Varies with formulation	10 days

^*Dose should be based on benzathine component.

^†Only if no immediate type I hypersensitivity to β-lactam.

Patients judged at higher risk for GAS require laboratory testing to confirm or exclude the presence of GAS, specifically the throat culture and rapid antigen detection test (RADT) (Figure 33-7 ). Because of the high specificity of RADTs, culture and antigen detection are equivalent in confirming GAS. Less certain is the role of RADTs in excluding GAS infection. Sensitivity among RADTs varies from 66% to 95%, leading to the general recommendation that negative RADT results should be confirmed by throat culture. Even RADTs using optical immunoassay, which offer the potential for improved sensitivity, vary widely in reported sensitivity (75% to 95%). Consequently, recommendations that waive the need to confirm a negative RADT result by throat culture should be based on an individual laboratory's internal validation of RADT sensitivity.

Figure 33-7.

Example of group A Streptococcus on plate with beta-hemolysis.

Equally important to the accuracy of a test is the adequacy of the sample. Obtaining a proper throat swab, especially in children, is frequently challenging and time-consuming. An adequate specimen for testing requires that the swab sample both tonsils and the posterior pharyngeal wall. Results obtained from swabs obtained by a blind pass have little to no value if they are negative for GAS.

Testing for pathogens other than GAS in uncomplicated acute pharyngitis is rarely required. The finding of non–group A streptococci in a patient with uncomplicated pharyngitis is rarely helpful, as it may represent normal flora. In GAS-negative patients with findings suggestive of A. haemolyticum, a routine throat culture may not be sufficient to identify the organism. In patients with persistent sore throats, cultures for F. necrophorum require an anaerobic throat culture. All specimens for virus isolation should stipulate the virus requested (e.g., HSV, enterovirus, or adenovirus) and should be transported in the appropriate viral medium at 4° C. All concern regarding C. diphtheriae should be addressed to an infectious disease specialist and local health officials.

Treatment

Symptomatic patients with laboratory confirmation of GAS should receive antimicrobial therapy (see Table 33-4). Benefits of treatment include prevention of ARF, a decrease in suppurative complications, and a shortened course of illness. Penicillin remains the drug of choice for treatment of GAS pharyngitis because of its narrow spectrum of activity, proven record of efficacy, safety, and cost. Penicillin V is the preferred oral choice; however, for children requiring an oral suspension, amoxicillin is an acceptable alternative because of its palatability. Ampicillin offers no advantages over penicillin V. Although injectable penicillins offer single-dose convenience, their routine use is uncommon and affords no other advantage except in ensuring compliance. Oral penicillin and amoxicillin are effective with either twice-daily or three-times-daily administration, and the duration is 10 days. Shorter courses may be effective but are not recommended. Patients allergic to penicillin without a history of immediate or type I hypersensitivity to penicillin can be treated with a cephalosporin or macrolide. The use of erythromycin, clarithromycin, and azithromycin should be limited to individuals allergic to penicillin because of increasing reports of macrolide resistance among strains of GAS in the United States and worldwide. Starting appropriate antimicrobial therapy within 9 days of disease onset is sufficient to prevent ARF.

GAS remains uniformly susceptible to penicillin. However, cephalosporins have been promoted as first-line therapy for GAS pharyngitis based on data indicating their superiority over penicillin in eradicating GAS from the oropharynx. According to meta-analysis, eradication rates in children for penicillin and cephalosporins are 81% and 93%, respectively, whereas clinical cure rates are 86% and 94%, respectively. Among adults, however, there are no clinically significant differences between penicillin and cephalosporins (87% versus 92% eradication; 90% versus 95% clinical cure). The validity of these comparisons continues to be debated and both the Infectious Diseases Society of America (IDSA) and American Academy of Pediatrics (AAP) continue to recommend penicillin as first-line therapy, although cephalosporins may be considered as an alternative choice.