Sore Throat (Pharyngitis)
Authors: Judith M. Martin, M.D.
Pharyngitis is the term used to describe any inflammation of the pharynx. A variety of bacterial and viral pathogens can cause pharyngitis in the immunocompetent host.
EPIDEMIOLOGY
Sore throat is a very common complaint for which children and adolescents seek medical care. Pharyngitis is primarily caused by bacteria and viruses. When evaluating a patient with a sore throat, it is important to differentiate pharyngitis caused by Group A streptococcus (GAS) from that caused by other pathogens. GAS is the most common cause of pharyngitis that is treatable with antibiotics. During the winter, approximately 15-25% of all cases of pharyngitis in children will be due to streptococcal infection. In adults this number is closer to 10%. It is important to determine the cause because treatment of GAS pharyngitis leads to a more rapid clinical cure and decreases transmission of GAS to others. Treatment of GAS pharyngitis can also prevent both suppurative and nonsuppurative complications. The suppurative complications are those that occur shortly after the initial infection (without any latency period) and include peritonsillar and retropharyngeal abscesses, acute otitis media, cervical adenitis and acute bacterial sinusitis. Nonsuppurative complications occur after a latency period of a few weeks and include post-streptococcal glomerulonephritis and acute rheumatic fever (ARF). In adults, the importance of treating to prevent non suppurative complications is less urgent. One exception is in the military or college dormitories where outbreaks have been reported.
DIFFERENTIAL DIAGNOSIS
The majority of patients who present with a sore throat will have pharyngitis which is primarily caused by bacteria and viruses in the immunocompetent host (Table 1). Bacterial etiologies of pharyngitis include Streptococcus pyogenes(or Group A streptococcus), as well as, Corynebacterium diphtheriae, Arcanobacterium haemolyticum, Neisseria gonorrhoeae, Group C and Group G streptococci and Mycoplasma pneumoniae. Viruses that cause pharyngitis include Epstein-Barr virus (EBV), herpes simplex virus (HSV), adenovirus, enterovirus, human immunodeficiency virus (HIV), cytomegalovirus (CMV), influenza and parainfluenza viruses. Pharyngitis due to viruses is often associated with respiratory symptoms such as rhinorrhea, nasal congestion and cough. Patients with pharyngitis due to GAS usually do not have cough or nasal symptoms.
Infections in the peripharyngeal area tend to occur in the fascial space and lymph nodes and may lead to a complaint of a sore throat. Examples of these types of infections include: peritonsillar abscess, parapharyngeal, retropharyngeal or prevertebral space infections. In addition to a sore throat, the patient may also have trismus or pain with swallowing and eating. These patients may present with fever and other signs of systemic toxicity. Stridor, airway obstruction or drooling may also occur in patients with significant swelling. On physical examination there may be swelling of the face and neck, with or without erythema of the overlying skin. When the oropharynx is examined there may be pooling of secretions in the mouth or asymmetry of the tonsils or pharynx. Complications of these infections include suppurative jugular thrombophlebitis or Lemierre’s syndrome and can be life threatening.
Non-infectious causes of a sore throat include those related to environmental allergies. A patient with significant allergic symptoms may complain of a sore throat due to post nasal drip or because of a dry throat secondary to mouth breathing. Habitual throat clearing or coughing could also lead to irritation of the posterior pharynx. A person who strains their voice when yelling or speaking for long periods of time may complain of a sore throat. Irritation can also be due to gastro-esophageal reflux, dry heat or pollutants and chemicals such as tobacco smoke. Uncommonly, cancers or polyps may cause a sore throat. Patients with these often also have a hoarse voice and may have adenopathy or other systemic signs or symptoms.
Bacterial Causes of Pharyngitis-Group A Streptococcus
Group A streptococcus (GAS) as a cause of pharyngitis is most commonly observed in children between 5 to 15 years of age in late winter and early spring in temperate climates. It is easily spread in classrooms and between family members. Transmission is by inhalation of large droplets or direct contact with respiratory secretions. The incubation period is two to five days. Untreated patients are most contagious while they are acutely ill; however, they may remain infectious for approximately two weeks.
School-age children may develop between one to three streptococcal infections each respiratory season. Some of these infections are associated with symptoms while others are asymptomatic or have atypical symptoms such as upper respiratory symptoms accompanied by a sore throat. One longitudinal study showed that two-thirds of streptococcal infections were not associated with recognizable respiratory symptoms. Some children develop numerous (7 to 23) infections per year.
Clinical Manifestations of GAS
GAS pharyngitis commonly presents with the abrupt onset of sore throat associated with headache, fever, malaise and occasionally abdominal pain. The throat pain often leads to decreased oral intake. This is in contrast to the typical presentation of viral pharyngitis which is usually associated with, respiratory symptoms such as rhinorrhea, nasal congestion, conjunctivitis and cough. Clinical examination alone cannot differentiate between pharyngitis due to GAS and other causes. A combination of typical clinical symptoms and signs on physical examination may be highly suggestive of GAS, however, only a minority of episodes have all of the classic features. The tonsils and pharynx may appear erythematous and an exudate is seen in 25% of cases. Approximately 50% of children with GAS pharyngitis will also have tender anterior cervical lymph nodes on physical examination. GAS is also more likely to be the cause of pharyngitis for children aged 5 to 15 years who present between November and May in temperate climates. It can be difficult to distinguish clinically between viruses and GAS as a cause of pharyngitis unless a specific syndrome such as scarlet fever is recognized. A combination of typical clinical symptoms and signs on physical examination may be highly suggestive of GAS, however, only a minority of episodes have all of the classic features. Many studies have shown that scoring systems are useful. However, laboratory confirmation is essential in making a precise diagnosis since physicians often overestimate the likelihood that GAS is the cause of pharyngitis.
GAS Pathogenesis
Group A streptococci are gram positive cocci that can be divided into over 100 M-serotypes or emm types based on the M protein. Their virulence is directly related to the M protein on the cell surface that inhibits phagocytosis. Although it is more commonly thought of in the context of causing clinical illness, Streptococcus pyogenes can colonize the pharynx and skin. In the throat, colonization appears to be due to fibronectin-binding proteins. Adherence to pharyngeal epithelial cells can lead to pharyngitis. It is not clear if cellular invasion is a necessary step in the pathogenesis of pharyngeal infection with GAS. Streptococcus pyogenes can also elaborate exotoxins which are responsible for the rash that is seen in patients with the clinical syndrome of scarlet fever. The originally described exotoxins were types A, B and C. More recently, additional pyrogenic extoxins have been discovered. The toxin is produced at the site of infection and then enters the circulation and causes its effects.
Bacterial Causes of Pharyngitis Other Than Group A Streptococcus (Table 1)
Arcanobacterium haemolyticum is not a common cause of pharynitis and is it difficult to identify on a standard throat culture. The organism grows slowly and is often only seen after 72 hours of incubation. Clinical symptoms may include fever, an exudative pharyngitis and a rash that is puritic and may appear to be “scarletiniform”. Clinical symptoms will improve without any specific antibiotic therapy.
Neisseria gonorrhoaeae as a cause of pharyngitis can be seen in adolescents and adults who engage in oral genital sex. There are no distinguishing findings on physicial examination. Selective media must be used in order to isolate this organism from a throat culture. Specific therapy with ceftriaxone is needed to prevent disseminated disease and further transmission.
Groups C and G streptococci can cause pharyngitis in both children and adults. Both have been shown to cause post streptococcal glomerulonephritis. Often, the presence of these organisms are not reported by laboratories when evaluating a standard throat culture. Antibiotic therapy is not necessary for a clinical cure, nor is it known to prevent glomerulonephritis.
Cornynbacterium diphtheriae is extremely rare in most countries. Epidemic disease has been documented in the former Soviet Union. Patients often have a gradual onset of symptoms with pharyngitis. It can be distinguished from other causes of pharyngitis on physical exam since it produces a characteristic membrane in the pharynx. Attempts to remove this membrane can lead to bleeding. A specimen can be obtained from under the membrane, or a piece of the membrane can be sent for culture. Selective media are needed for isolation of this bacterium. The laboratory should be notified if diphtheria is the suspected diagnosis.
Mycoplasma pneumoniae can cause a acute bronchitis or an upper respiratory illness associated with a sore throat. These patients often present with fever, malaise, nonproductive cough and headache. This is most commonly seen in previously healthy school-aged children and adolescents. Clinical symptoms will improve without any specific antibiotic therapy.
Viral Causes of Pharyngitis (Table 1)
Infectious mononucleosis can be caused by a number of viruses including Epstein-Barr virus (EBV). The most commonly recognized clinical syndrome consists of fever, severe pharyngitis, posterior and anterior cervical adenopathy with prominent constitutional symptoms such as fatigue. The illness is most often seen in adolescents and usually lasts much longer than the typical course expected with streptococcal pharyngitis. Younger children can also have EBV infections, however, their clinical presentation is more likely to be milder and may appear as an uncomplicated viral upper respiratory tract infection.
Primary HIV infection can occur days to weeks after a sexual or blood exposure to an infected individual. Clinical features may include fever, pharyngitis, adenopathy, rash and an enlarged spleen. This diagnosis should be suspected in patients with a history consistent with a possible exposure.
Influenza is common in epidemic form at specific times of the year. Symptoms often include the abrupt onset of sore throat with high fever and myalgias. Rapid diagnostic tests are available to confirm this diagnosis.
Herpes simplex virus can lead to symptoms of a sore throat especially in adolescents and young adults. It is often recognized by ulcerative lesions which can be seen on the lips, in the anterior mouth or posterior pharynx and can be quite painful leading to significantly decreased oral intake. Tender cervical adenopathy can be appreciated on examination.
Adenovirus can cause a variety of clinical symptoms and is most commonly seen in the late winter, spring and early summer. It should be considered if the patient presents with pharyngitis and bilateral conjunctivitis especially if it is hemorrhagic (pharyngoconjunctival fever).
Enteroviruses, especially the coxsackieviruses, can manifest as pharyngitis, herpangina, stomatitis and fever. Small vesicles can be seen in the posterior pharynx. The young child may also have lesions on their hands and feet (hand-foot-and-mouth disease). In temperate climates these infections are seen during the summer months and early fall.
Cytomegalovirus (CMV) can cause an acute infection and is most commonly transmitted by respiratory droplets. In an immunocompetent host the infection is often asymptomatic. However, some patients may have a mononucleosis like syndrome with mild pharyngitis.
DIAGNOSIS
Many clinicians will use one of several rapid diagnostic tests to identify the presence of GAS in the pharynx. These tests, which are primarily based on extraction and identification of the group A carbohydrate antigen, yield results that demonstrate a high specificity but variable sensitivity when compared to the gold standard throat culture. Because of this issue, it is recommended that a throat culture should be performed for any patient with a negative rapid antigen test in whom GAS pharyngitis is suspected. Either a positive rapid streptococcal antigen test or a throat culture that is positive for S. pyogenes confirms a diagnosis of streptococcal pharyngitis. A negative rapid antigen test combined with a negative throat culture, most likely indicates that the cause of the pharyngitis is a virus.
For children or adults who are tested and are not found to have GAS as the cause of their symptoms, the most likely etiology is a viral infection which should resolve on its own. In most circumstances, unless ulcerations are seen on examination, viral cultures of the pharynx are not helpful. However, if symptoms persist or if there are other indications in the exam or history that raise suspicion for one of the other causes listed, then other diagnostic testing should be considered.
Clinical Presentations to Consider Additional Diagnostic Testing (Table 1)
1) Unusually severe symptoms associated with difficulty swallowing, drooling, “hot potato” voice, significant neck swelling or an asymmetrical appearance of the tonsils or pharynx – consider the possibility of a parapharyngeal space infection, retropharyngeal space infection (in young children), or peritonsillar abscess. A plain radiograph may demonstrate soft tissue swelling, however, most patients will require a contrast enhanced computed axial tomography (CT) scan which can further define the anatomy. A magnetic resonance imaging (MRI) may also be useful for further evaluation of possible vascular involvement.
2) Oral genital sexual contact – consider testing for gonococcal infection. The laboratory requisition must state to test for N. gonorrhoeae since the swab must be plated on selective media.
3) Persistent or severe sore throat with significant constitutional symptoms – consider complete blood count with differential, monospot testing and/or EBV serologies to assess for EBV infection. If there is also a history of risky sexual behaviors, consider HIV RNA viral load or HIV DNA polymerase chain reaction (PCR) to assess for primary HIV infection.
4) Ulcerative lesions of the lip or pharynx – consider sending a viral culture or direct antigen for HSV.
5) Pharyngitis with abrupt onset, high fever and myalgias during influenza season – consider rapid antigen testing for influenza.
ANTIBIOTIC THERAPY for GAS
Either a positive rapid streptococcal antigen test or a throat culture that is positive for S. pyogenes confirms a diagnosis of streptococcal pharyngitis. Antibiotics should be initiated only for these patients. Some physicians begin antimicrobial therapy pending culture results and discontinue the treatment if the throat culture is negative. However, it is suggested to wait to initiate treatment until testing results confirm the presence of GAS. There are relatively few disadvantages to waiting for throat culture results. One study demonstrated that a delay in therapy did not affect the likelihood of the patient having a recurrent streptococcal pharyngitis. Treatment within nine days of the onset of illness is effective in preventing ARF. At the present time, most physician offices have rapid streptococcal antigen testing available and the majority of patients will be diagnosed immediately.
Treatment of GAS pharyngitis leads to a more rapid clinical cure, decreases transmission of GAS to other children. A secondary benefit of antimicrobial therapy is to prevent suppurative and nonsuppurative complications. Treatment of GAS pharyngitis is effective in preventing ARF, however, it does not affect the development of post-streptococcal glomerulonephritis. Because of the general increase in rates of resistance to antibiotics, antimicrobial therapy should be prescribed only for proven episodes of GAS pharyngitis. Furthermore, many experts support the idea of being selective regarding which children should have a diagnostic throat culture performed so as to avoid identifying GAS carriers rather than acutely infected youngsters.
A clinical response in the symptoms of pharyngitis is usually achieved within 24 to 48 hours after initiation of therapy. It is important to note that streptococcal pharyngitis is a self limited disease. Even without treatment, fever and symptoms will resolve within three to four days of the onset of illness. Accordingly, the persistence of symptoms beyond this time period suggests either the development of a suppurative complication or that the child may be a carrier of GAS (rather than acutely infected) with their presenting symptoms attributable to an alternate cause of pharyngitis.
Penicillin remains the drug of choice for the treatment of GAS pharyngitis. Penicillin's efficacy in preventing rheumatic fever is well established. Other desirable features of penicillin include low cost, a low incidence of side effects, and a narrow antimicrobial spectrum. There has been no documentation of resistance in GAS to penicillin. Recommended therapeutic options for the treatment for GAS pharyngitis are shown in Table 2. Penicillin V potassium is traditionally given three to four times a day. However, a study conducted by Gerber demonstrated that twice-a-day dosing of penicillin was as effective as three-times-a-day dosing for this infection and twice a day dosing is accepted by most experts. Treatment with penicillin should be continued for 10 days since shorter courses have shown decreased efficacy. The use of a single dose of intramuscular penicillin G benzathine is as effective as oral penicillin and was the long-time gold standard in the treatment of GAS pharyngitis. The slow release formulation can provide bactericidal levels against GAS for as long as 28 days, ensuring adequate serum levels of antibiotic. Benzathine penicillin is preferred for those patients who are unlikely to complete a full ten day course of oral therapy. (See Table 2 for doses).
Amoxicillin has been shown to be as effective as penicillin in eradicating GAS, is more palatable, and provides easier dosing than penicillin. Because many children cannot take pills or capsules, amoxicillin suspension is a common substitution for penicillin. Most clinicians will use a two to three times per day regimen of amoxicillin. Preliminary studies have demonstrated once a day dosing with 750 mg amoxicillin to be effective for GAS pharyngitis. However, once a day dosing cannot be endorsed until this is confirmed with other studies.
Erythromycin remains the first alternate choice in patients who are allergic to penicillin or amoxicillin. It has been shown to be as effective as penicillin in eradicating GAS from the pharynx. However, documented reports of erythromycin-resistant GAS have occurred in Finland, Japan, Greece, and most recently, in the United States. Although previous reports from the United States reported low rates of macrolide resistant GAS isolates, more recent investigators have documented a wide range of rates of resistance of GAS to the macrolide antibiotics. Physicians should take into consideration the resistance rates in their community when prescribing this class of antibiotics. Two of the newer macrolides,azithromycin and clarithromycin are commonly used instead of erythromycin since they are only given once or twice a day. For the patient who has an infection with a macrolide resistant strain of GAS and cannot tolerate beta-lactam antibiotics,clindamycin is a reasonable alternative. However, clinicians should be aware of the potential presence of inducible clindamycin resistance in some strains of macrolide-resistant GAS.
Oral cephalosporins have been extensively studied in the treatment of GAS pharyngitis and are highly effective. Some studies have reported higher bacteriologic cure rates that have been observed with the cephalosporins compared to the penicillins suggesting a greater treatment efficacy with cephalosporins. Other authors have not supported this conclusion, suggesting that the observed differences may be attributable to the inclusion of GAS carriers in these studies and a greater ability of cephalosporins to eradicate the carrier state compared to penicillin. Although there are some advantages to the cephalosporins, it is important to note that, as a class, they are more expensive than penicillin, are associated with greater side effects, and have a broader spectrum of activity. Their routine use cannot be endorsed at this time.
MANAGEMENT
Management of Non-Streptococcal Pharyngitis
Management for patients who have a negative throat culture for GAS is primarily symptomatic with the use of analgesics. Other etiologies that might warrant specific therapy include: 1) Arcanobacterium – can resolve without therapy but a macrolide antibiotic is recommended if treatment is desired; 2) Neisseria gonorrhoeae – ceftriaxone; 3) Mycoplasma pneumoniae-can resolve without therapy but a macrolide antibiotic is recommended if treatment is desired; 4) Influenza – rimantadine, amantadine, or oseltamivir; 5) Herpes simplex virus – acyclovir, valacyclovir, or famciclovir; and 6) Human immunodeficiency virus – antiretroviral therapy.
Non Antibiotic Management
Steroids
Studies in adult patients with pharyngitis have demonstrated that a single dose of dexamethasone reduced the severity and duration of their sore throat. However, there is no consensus regarding when to use steroids. Caution should be used, especially in children with severe pharyngitis due to EBV infection. The EBV virus itself can produce immune suppression and altering the patient’s natural response to this infection may be detrimental.
Chinese Herbal Medications
The most recent Cochrane review, investigated 54 studies of Chinese herbal medicines for treating sore throat. The results were “controversial and questionable”. At the present time, there are no studies that support the use of any Chinese medical herbal formulations for treatment of sore throats.
Symptomatic Treatment
Acute pharyngitis will resolve in most cases without any complications. Available symptomatic treatments include: antipyretics, fluids, lozenges and gargles. “Magic mouthwash”, a combination of topical lidocaine, diphenhydramie and Maalox (aluminum hydroxide/magnesium hydroxide), can be swished in the mouth and then swallowed to provide pain relief.
Bacteriologic Failures After GAS Treatment
Despite the universal susceptibility of GAS to penicillin, between 7 and 37% of children treated with an appropriate antibiotic for streptococcal pharyngitis will have a positive throat culture for GAS at the end of therapy. These children are considered to have experienced a bacteriologic failure. Bacteriologic failures can be classified according to the possible explanations for the positive throat culture on follow-up testing. These explanations include: 1) “true” treatment failure when there is an inability to eradicate the specific emm type of GAS that caused the episode of acute streptococcal pharyngitis, 2) failure to eradicate the GAS carrier state in a child who presented with an intercurrent viral illness associated with a sore throat, 3) the acquisition of a different emm type of GAS immediately following the first episode of infection, or 4) eradication of the organism followed by a development of a second episode of streptococcal pharyngitis with the same emmtype immediately following the first episode.
The cause of “true” bacteriologic failure is not clear. There are several theories which include: 1) protection of GAS by beta-lactamase producing normal pharyngeal flora, 2) tolerance of GAS to penicillin, 3) cryptogenic infection, and 4) the absence of oral flora that are inhibitory to GAS. Although there have been multiple studies to examine these theories, there are few data to support any of these possibilities. Many authors believe that the best explanation is that the children who experience a bacteriologic failure following the treatment of streptococcal pharyngitis are actually GAS carriers.
The child who is a GAS carrier presents a special challenge. Under most circumstances, antimicrobial therapy is not indicated for these children. However, there are several situations when identification and eradication of GAS colonization is recommended. As suggested by the American Academy of Pediatrics Report of the Committee on Infectious Diseases, these include: 1) when there is a family history of rheumatic fever, 2) when there is “ping-pong” spread in a family, 3) when a family is particularly anxious about GAS, 4) when outbreaks of GAS pharyngitis occur in a closed or semi-closed community, 5) when outbreaks of ARF or post streptococcal acute glomerulonephritis occur and 6) when tonsillectomy is being considered because of GAS carriage. Current data demonstrate that certain antimicrobial agents are better at eradicating the carrier state than others. However, only two studies were designed to determine efficacy in eliminating chronic GAS carriage in the pharynx of children. The therapies that have been proven to be effective are a ten-day course of oral clindamycin and the combination of benzathine penicillin G and oral rifampin. Of these two, clindamycin is more effective with a bacteriologic clearance observed in 85-90% of the patients in whom it was tested.
In patients in whom the differentiation between true recurrent episodes of GAS pharyngitis and recurrent episodes of viral pharyngitis in a child who is a GAS carrier is not certain, a second course of antibiotics may be considered. In such circumstances, it is acceptable to treat the child with a second course of the initially prescribed medication. However, many practitioners opt to prescribe a 10 day course of amoxicillin plus clavulanic acid, clindamycin, or a first generation oral cephalosporin for the second episode hoping to eradicate the GAS. Of these choices, clindamycin is a very attractive choice as it has been extremely effective in the treatment of GAS, is unaffected by the activity of β-lactamases which may be present in normal oral flora and has been demonstrated to eradicate the carrier state. However, clindamycin is not well accepted by children in the suspension form and it is more expensive than penicillin and has been associated with development of pseudomembranous colitis in some patients.
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Tables
Table 1: Differential Diagnosis of Sore Throat
BacteriaStreptococcus pyogenes (Group A streptococcus) Streptococcus, Group C or Group G
VirusesEpstein-Barr Virus (EBV) Herpes Simplex Virus (HSV)
SyndromesPeritonsillar abscess Parapharyngeal or retropharyngeal infection Prevertebral space infections
Non-Infectious Causes
Irritation Allergies Gastro-esophageal reflex Dry heat Pollutants including cigarette smoke
Syndromes Cancer Polyps |
Table 2. Recommended Therapy for the Treatment of GAS Pharyngitis
Antimicrobial Agent |
Dose |
|---|---|
|
|
Penicillin VK |
< 27 kg:250 mg two to three times per day for 10 days >27 kg: 500 mg two to three times per day for 10 days |
Penicillin G benzathine |
<27 kg:Single dose of 600,000 units IM >27kg: Single dose of 1.2 million units IM |
<27 kg: 250 mg two to three times per day for 10 days >27kg: 500 mg two to three times per day for 10 days |
|
Erythromycin estolate |
20 - 40 mg/ kg/day for 10 days |
Erythromycin ethylsuccinate |
40 mg/kg/day in 2 to 4 divided doses for 10 days |
30 mg/day, in four divided doses for 10 days |
|
30 mg/day, in four divided doses for 10 days |
|
30 mg/day, in four divided doses for 10 days |
|
Cefuroxime axetil |
15 mg/kg/day in two divided doses for 10 days |
8 mg/kg once a day for 10 days |
|
14 mg/kg once daily for 5 days |
What's New
van Driel ML, et al. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev 2013; Apr 30:4.
Margolis DJ, et al. Association of Pharyngitis With Oral Antibiotic Use for the Treatment of Acne: A Cross-sectional and Prospective Cohort Study. Arch Dermatol. 2011 Nov 21. [Epub ahead of print].
Centor RM. Expand the Pharyngitis Paradigm for Adolescents and Young Adults. Ann Intern Med. 2009 Dec 1;151:812-5.
Guided Medline Search For:
Shulman ST, et al. Clinical Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Updates by the Infectious Disease Society of America. Clin Infect Dis 2012;55:1279-1282.