Pharyngitis (sore throat) is a very common disease resulting in over 15 million physician office visits each year in the United States. Most cases of pharyngitis are caused by viruses.

Etiology

Pharyngitis can be caused by many different microorganisms; however, 90% of sore throats in adults and 60–75% of sore throats in children are caused by viruses (Table URI-5). S pyogenes (b-hemolytic group A Streptococcus) is the most common bacterial cause of acute pharyngitis.

Manifestations

Fever, sore throat, edema, and hyperemia of the tonsils and pharyngeal walls are common findings in patients with viral and bacterial causes of pharyngitis. Other findings strongly suggest that a viral, rather than a bacterial, agent cause pharyngitis and include conjunctivitis, cough, coryza, hoarseness, and diarrhea; anterior stomatitis and discrete ulcerative lesions; and viral exanthem.

Patients with S pyogenes pharyngitis commonly present with fever and severe pain upon swallowing (generally of sudden onset). Headache, nausea and vomiting, and abdominal pain may also be present, especially in children. On examination, patients have tonsillopharyngeal erythema, with or without exudate, and tender, enlarged anterior cervical lymph nodes (lymphadenitis). They may also have a beefy red and swollen uvula; petechiae on the palate; excoriated nares (usually in children); and a scarlatiniform rash. However, none of these findings are specific for S pyogenes pharyngitis.

If untreated, a patient with S pyogenes pharyngitis can develop suppurative and nonsuppurative complications. Suppurative complications include peritonsillar abscess, cervical lymphadenitis, and mastoiditis.The major nonsuppurative complication is rheumatic fever, a complication that is more likely to occur in children with S pyogenes pharyngitis than in adults with this bacterial infection.

Rheumatic fever presents as a diverse set of clinical manifestations with onset of symptoms occurring within a few days to 5 weeks after a strep throat infection. A patient with rheumatic fever first presents with fever (38–40°C) and painful swelling of several joints such as the knees, elbows, or wrists. Severe rheumatic fever can result in damage to the valves of the heart.

Epidemiology

• Pharyngitis is common worldwide.
• Pharyngitis due to S pyogenes is usually a disorder of children aged 5–15 years.
• In temperate climates, it is most common during winter and early spring.
• Viruses are the most common cause of pharyngitis.
• With few exceptions (e.g., diphtheria) pharyngitis is benign and self-limiting.
• Viral pharyngitis is acquired by person to person contact and following contact with contaminated fomites.
• S pyogenes is transmitted by person-to-person contact.

Pathogenesis

In viral pharyngitis, viruses gain access to the mucosal cells lining the nasopharynx and replicate in these cells. Damage to the host is often caused by damage to the cells where the viruses are replicating.

In bacterial pharyngitis, S pyogenes attaches to the mucosal epithelial cells using M protein, lipoteichoic acid, and fibronectin-binding protein (protein F). It has a capsule composed of hyaluronic acid that prevents phagocytosis by host macrophages; because the hyaluronic acid in the bacterial capsule is identical to host hyaluronic acid, it facilitates bacterial survival by covering the bacterial antigens. Extracellular factors produced by S pyogenes during the infection include protease and hyaluronidase. These extracellular factors assist the bacteria in invading the mucosa. Direct extension to other sites can occur but due to the use of antibiotic therapy, this is now quite rare.

Nonsuppurative lesions resulting in rheumatic fever and glomerulonephritis still occur following throat infections caused by S pyogenes. It is believed that several bacterial antigens from S pyogenes share antigenic epitopes with the heart and renal tissues. An autoimmune reaction occurs in some patients following production of an immune response to these cross-reactive bacterial antigens and damages the patient’s heart or kidneys. Note: Rheumatic fever and glomerulonephritis can occur after an episode of pharyngitis; only glomerulonephritis occurs after skin infections (e.g., impetigo).

Diagnosis

Viral infections of the throat are rarely cultured because of the mild self-limiting nature of the disease and the cost involved in culturing the pathogens. There are fewer cases of bacterial infections of the throat (compared to viral pharyngitis); however, delaying treatment of S pyogenes pharyngitis beyond 9 days after symptoms begin increases the patient’s chances of developing rheumatic fever and suppurative complications (e.g., peritonsillar abscess, mastoiditis). Therefore, strategies for diagnosis of acute pharyngitis infections are primarily directed at identifying patients with S pyogenes pharyngitis who require antimicrobial therapy, as well as avoiding unnecessary treatment of patients diagnosed with acute viral pharyngitis.

The best means of  determining which etiologic agent is causing the pharyngitis is to swab the patient’s throat, culture the sample on blood agar plates, and demonstrate the growth of b-hemolytic colonies that are catalase-negative, gram-positive cocci and are sensitive to bacitracin. S pyogenes rapid antigen detection tests are available and used clinically; however, these tests are not as sensitive as cultures.

Throat cultures are not necessary for proper diagnosis of all cases of pharyngitis, and this is especially true for adults. If a patient has clinical and epidemiologic features (e.g., cough, coryza, conjunctivitis, diarrhea) highly suggestive of a viral etiology, further testing is not needed (Table URI-6). However, if the patient has clinical and epidemiologic features highly suggestive of a bacterial etiology, further testing (e.g., cultures or rapid antigen tests) is needed.

Children younger than 18 years of age are more likely to develop S pyogenes pharyngitis, and are more likely to develop suppurative and nonsuppurative complications if not treated. Therefore, if a child is likely to have developed S pyogenes pharyngitis, as determined clinically and epidemiologically (see Table URI-6), further testing with rapid antigen detection tests and throat culture is indicated. If the result of the rapid antigen detection test is positive, a throat culture is not needed and the child should be treated with antibiotics. If the result of the rapid antigen detection test is negative, a throat culture should also be performed. A prescription for penicillin should be given if the result of either test is positive.

Rheumatic fever is a nonsuppurative complication of S pyogenes pharyngitis and resembles a number of other diseases that affect the joints (e.g., rheumatoid arthritis, systemic lupus erythematosus, and serum sickness). Diagnosis of this disease and the use of the Jones Criteria were described in the Heart and Pericardial Infections handout.

Therapy and Prevention

All patients with acute pharyngitis should be offered appropriate doses of antipyretics, analgesics, and supportive care.

Viral pharyngitis is treated with analgesics (e.g., acetaminophen), and warm saline gargles. These treatments will help lessen the pain. Fluids to avoid dehydration should be encouraged. Susceptible persons should be encouraged to limit contact with infected persons. An adenovirus vaccine is available for military personnel, but it is not warranted for use in the general population.

S pyogenes pharyngitis requires the use of an antimicrobial agent in addition to the treatments mentioned above for viral pharyngitis. Antimicrobial treatment has been shown to limit contiguous spread (e.g., peritonsillar abscess, cervical lymphadenitis, mastoiditis); prevent development of acute rheumatic fever (if given within 9 days of the appearance of symptoms); improve clinical signs and symptoms (if given within 2 days of the appearance of symptoms); rapidly decrease infectivity and thus reducing transmission of the bacterium to close-contacts (e.g., family, classmates); and allow for a rapid resumption to the patient’s usual activities. Penicillin remains the drug of choice to treat S pyogenes pharyngitis; erythromycin is the drug of choice for patients allergic to penicillin. Patients should be encouraged to limit contact with uninfected persons.

Treatment of rheumatic fever includes antimicrobials to eliminate the S pyogenes resident in the pharynx and anti-inflammatory agents to suppress the clinical manifestations of the disease. Recurrence of rheumatic fever is more likely in patients who have had a previous episode of S pyogenes pharyngitis. Patients who have recovered from a bout of rheumatic fever should be protected from a second infection due to S pyogenes by chemoprophylaxis with a monthly dose of penicillin. This chemoprophylaxis should continue throughout the patient’s childhood years. If permanent damage occurs to the heart, chemoprophylaxis should continue for the life of the patient.

DIPHTHERIA

Diphtheria is a bacterial disease that is now rarely seen in the U.S. because of successful universal vaccination. The vaccine does not affect the ability of the bacteria to colonize the oropharynx, however, but rather induces antibody production to inhibit diphtheria toxin. If vaccination were no longer available, diphtheria could once again become a common disease.

Etiology

Corynebacterium diphtheriae is irregularly staining gram-positive, rod-shaped bacteria. Only strains of C diphtheriae that have toxin-producing lysogenic bacteriophage (b phage) can cause diphtheria.

Manifestations

Diphtheria results in pharyngeal pain, formation of a pseudomembrane seen on the tonsils and back of the oropharynx, regional lymphadenopathy (“bull neck” appearance), edema of the surrounding tissues, fetid breath, low-grade fever, and cough. Airway obstruction can occur, and findings of tachypnea, stridor, and cyanosis are seen. The toxin can damage the cranial nerves and the heart, causing neurologic abnormalities (e.g., palatine palsy, difficulty swallowing, nasal regurgitation of liquids) and myocarditis.

Epidemiology

• The disease is worldwide in distribution. Since 2004 no cases of diphtheria have been reported. Only 1-4 cases of diphtheria were reported each year from 1992-2003 in the U.S.
• The largest outbreak in recent history occurred in the former Soviet Union in 1994, with nearly 48,000 cases of diphtheria and over 1700 deaths.
• C diphtheriae can colonize the oropharynx and the skin of persons immune to the disease without causing disease, which is how the organism remains in the population.
• Humans are the only known reservoir of C diphtheriae.
• The most common causes of death is due to diphtheria toxin damage to the heart (i.e., myocarditis) or pharynx (i.e., pseudomembrane dislodges with aspiration and asphyxiation).
• C diphtheriae is transmitted by respiratory droplets and by skin contact. Healthy carriers, convalescent patients, and patients incubating the disease are the optimum transmitters of infection.

Pathogenesis

C diphtheria colonies the oropharynx and remains localized on the mucosal surfaces. Only C diphtheriae lysogenic for the bacteriophage (beta phage) carrying the toxin gene causes diphtheria. Damage to the pharynx is caused by the diphtheria toxin, which kills the mucosal cells by adenosine diphosphate ribosylation of elongation factor II and terminating protein synthesis. An inflammatory response to cell death and the dead cells form the pseudomembrane. The toxin can also bind to and damage the heart and nerve cells. The major complications of the disease are myocarditis and cranial nerve damage. Myocarditis is the more important of the two complications and causes the highest mortality. Cranial nerves are most sensitive to the toxin, resulting in difficulty swallowing and in nasal regurgitation of liquids.

Diagnosis

Diagnosis of diphtheria includes observation of a pseudomembrane and bleeding upon removal of the membrane and severe cervical lymphadenopathy. Neurologic abnormalities such as palatine palsy, difficulty swallowing, and nasal regurgitation of fluids are important clues in correctly diagnosing diphtheria. The oropharynx should be swabbed and samples cultured for C diphtheriae. The C diphtheriae strain isolated by culture should be assayed for diphtheria toxin production using the Elek test (immunodiffusion assay) or by polymerase chain reaction (PCR).

Treatment and Prevention

A patient with diphtheria should be hospitalized, placed in isolation, and immediately treated with antiserum to the toxin. The most urgent task is giving the antiserum to neutralize the toxic affects of the diphtheria toxin. The second most urgent task is antimicrobial treatment with penicillin or erythromycin. The patient should also be given diphtheria vaccine to ensure immunity to the disease. Active immunization with the DTaP vaccine for children and the DT vaccine for adults will serve as protection from diphtheria.