ETIOLOGY and EPIDEMIOLOGY

Pharyngitis is common all over the world. In temperate climates it is most common during the winter and early spring. Acute pharyngitis is a very common patient complaint in office-based primary care practices (Family/General practice, pediatrics). It is estimated that over 15 million patients visit their physician's office complaining of a sore throat each year in the United States. Many different microbes can cause pharyngitis as a single manifestation or as part of a more generalized illness (see table below). The sore throat, malaise and fever is quite distressing to patients however, with few exceptions (ex. diphtheria), this illness is benign and self-limiting. Approximately, 90 percent of sore throats in adults and 60 to 75% of sore throats in children are caused by viral agents. 

The beta hemolytic group A streptococcus (GABHS, Streptococcus pyogenes) is the most common bacterial cause of acute pharyngitis accounting for 15-30% of cases in children and 5-10% of cases in adults. Pharyngitis due to GABHS is primarily a disorder of children 5-15 years of age. If they dwell in temperate climates it usually occurs in winter and early spring. 

The use of an antimicrobial agent is indicated in therapy for "strep throat" (Hint: indicated means you need to use antibiotics in treatment of this infection). Not treating "strep throat" can result in various suppurative (peritonsillar abscess, mastoiditis, etc.) and nonsuppurative (rheumatic fever; The endemic incidence of acute rheumatic fever is around 0.23 to 1.88/100,000). complications. Treatment of viral pharyngitis with antimicrobial agents is useless. Therefore, strategies for diagnosis and treatment of acute pharyngitis infections are primarily directed at identifying "strep throat" patients who require antimicrobial therapy, as well as, avoiding unnecessary treatment to those patients with acute viral pharyngitis. 

Viral pharyngitis

The viruses gain access to the mucosal cells lining the nasopharynx and replicate in these cells. Damage to the host is often due to damage to cell in which the virus is replicating.

Bacterial pharyngitis

• Streptococcus pyogenes - person to person spread, The bacterial cell attaches to the mucosal epithelial cells via F and M proteins. Cellular and extracellular products appear to aid the bacterial invasion of the mucosa and its ensuing clinical manifestations. Direct extension to other sites can occur but is now quite rare. Nonsuppurative lesions resulting in rheumatic fever and glomerulonephritis still occur following strep throat infections.
• Corynebacterium diphtheria- The bacterium is not very invasive and remains localized on the mucosal surfaces of the upper respiratory tract. Only Corynebacterium diphtheriae lysogenic for the bacteriophage carrying the toxin gene causes diphtheria. Disease is spread person to person by droplets in the colder months of the year. Healthy carriers, convalescent patients, and patients incubating the disease are the best transmitters of infection to others. Worldwide in distribution.Damage to the pharynx is caused by the diphtheria toxin which kills the mucosal cells by ADP-ribosylating elongation Factor II. The toxin can also cause damage to the heart and nerves.
• Chlamydia pneumoniae- causes about 5% of the infections. Subacute onset and pharyngitis are common. Often a biphasic pattern is observed, with pharyngitis resolving before bronchitis or pneumonia develops. This bacterium causes about 10% of the community acquired pneumonias in the U.S..

The appearance of fever, sore throat, edema, hyperemia of the tonsils and pharyngeal walls is common for all the causes of pharyngitis. Persons with GABHS pharyngitis commonly present with severe pain on swallowing (generally of sudden onset) and fever. Headache, nausea, 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 scalatiniform rash. However, none of these findings are specific for GABHS pharyngitis. 

Viral pharyngitis can yield very similar findings. The following findings do strongly suggest a viral rather than GABHS as the etiological agent: conjunctivitis, cough, hoarseness, coryza, anterior stomatitis, discrete ulcerative lesions, viral exanthem, and diarrhea.

The only way to truly determine the etiologic agent is to culture it. However, certain epidemiological and clinical features are characteristic of pharyngitis due to GABHS (see table below).

If untreated a patient with GABHS pharyngitis can develop suppurative (pus producing) and nonsuppurative (no pus is produced) complications. Suppurative complications include peritonsillar abscess, cervical lymphadenitis, and mastoiditis. 

The major nonsuppurative complication is called Rheumatic fever. This complication is more likely to occur in children with GABHS pharyngitis than in adults with this bacterial infection. Rheumatic fever presents as a diverse set of clinical manifestations making diagnosis difficult. Onset of symptoms of rheumatic fever occur within a few days to 5 weeks after a strep throat infection. A patient with rheumatic fever first presents with fever (101°-104° F), and painful swelling of several joints such as the knees, elbows, or wrists. Severe rheumatic fever attacks can result in damage to the valves of the heart.

Diphtheria on the other hand has some unique features which the physician should be aware of. Pharyngeal pain, formation of a pseudomembrane seen on the tonsils and back of the throat, regional lymphadenopathy (gives the classic bull neck appearance), edema of the surrounding tissues, and a uniquely fetid breath, a low-grade fever, and a cough. Airway obstruction can occur with tachypnea, stridor, and cyanosis observed. The toxin can also get to the neurons and heart causing neurologic abnormalities and myocarditis.

Viral infections of the throat are rarely if ever cultured due to the large cost and mild nature of the disease. Bacterial infections of the throat although small in number when compared to viral pharyngitis, are the major diagnostic concerns in pharyngitis. Delaying treatment of a "strep throat" past 9 days after symptoms begin increases the patient's chances of developing rheumatic fever and suppurative complications. 

At one time the gold standard for determining if a patient had "strep throat" was the throat culture (Lab looks for beta hemolytic bacitracin sensitive gram positive cocci.). If a proper sample is obtained sensitivity of throat cultures is 90-95%. Proper sampling of the throat is essential in getting good sensitivities. Both tonsils or tonsillar fossae and the posterior pharyngeal wall should be swabbed. Other areas of the oral pharynx and the mouth should not be touched with the swab before or after sampling the throat. 

The recommendation was that all patients with signs of acute pharyngitis be cultured to obtain a definitive diagnosis. Unfortunately, this was not followed and rather than culture the patient clinical signs and symptoms alone were used in making the diagnosis (exudate on tonsils, high fever, sudden onset). This has been shown over and over again to result in antimicrobial treatment of many patients who did not need such treatment. Studies have demonstrated that throat cultures are not necessary for proper diagnosis of all cases of acute pharyngitis. This is especially true for adults. If a patient has clinical and epidemiologic features (cough, coryza, conjunctivitis, diarrhea) highly suggestive of a viral etiology then further testing is not needed. However, if they have clinical and epidemiologic features highly suggestive of a bacterial etiology then further testing (cultures or rapid antigen tests) are needed.

A number of rapid antigen detection tests are available and can in a matter of 15 minutes indicate if a person is infected with Streptococcus pyogenes. These tests use monoclonal or monospecific antibodies to detect the streptococcal group A capsular polysaccaride. These tests are highly specific (around 95%) but are not as sensitive (70-90%) as throat cultures. They can with certain precautions be useful in the rapid diagnosis of "strep throat".

In Adults: All patients with acute pharyngitis should be offered appropriate doses of antipyretics, analgesics, and supportive care. Differentiate between viral pharyngitis and "strep throat" by first looking at the patient's clinical and epidemiological features (Table 2). Patients with a low probability of having "strep throat" would typically have a cough, coryza, and/or diarrhea along with symptoms seen with "strep throat". Usually the onset of the sore throat is less sudden and they don't have any history of close contact with someone with "strep throat". In adult patients no further testing or cultures are necessary. Only symptomatic treatment is necessary. 

Adult patients with a high probability of having "strep throat" would have rapid onset of symptoms, fever, sore throat, etc. but lack symptoms of cough, coryza, conjunctivitis, and/or diarrhea (see Table 2). These patient may also have a history of close contact with a person with "strep throat". Adult patients with a high probability of having "strep throat" should be tested for GABHS infection by either throat culture or by a rapid antigen detection test. If testing initially with the rapid antigen detection tests a negative result does not have to be followed up with a throat culture. Specificity of the rapid antigen detection tests is very high around 95%, so false positive results are rare. However, sensitivity of these tests can be as low as 70% meaning up to 30% of patient with "strep throat" will have a negative test. In spite of the low sensitivity of these tests, it is okay to not treat adults since the incidence of "strep throat" is lower in adults than children and the chances of this infection developing into rheumatic fever is also very low compared to children. 

If either the throat culture or rapid antigen detection test is positive give antimicrobial therapy. Since throat cultures can take up to three days before results are sent back, you can give the patient the prescription for an antimicrobial agent and call them if the culture is negative to tell them to stop taking the antimicrobial agent, give them the prescription for an antimicrobial agent telling them to wait to fill the prescription until you call them, or have them come back if the culture is positive to get a prescription.

In Children: Once again all patients with acute pharyngitis should be offered appropriate doses of antipyretics, analgesics, and supportive care. Children (less than 18 years of age) are more likely to get "strep throat" and if they get "strep throat" are more likely to develop suppurative and nonsuppurative complications if not treated. Therefore if a child by clinical and epidemiologic means is likely to have "strep throat" then further testing by rapid antigen detection tests and/or throat culture is indicated. If the rapid antigen detection test is positive then a throat culture is not needed and the child should be treated. If the rapid antigen detection test is negative then a throat culture should also be performed. A prescription should be given only if either test is positive.

There is still a lot of debate on how to best diagnose and treat acute pharyngitis. There is a McIsaac Modification of the Centor Strep Score that some physicians have used in diagnosing patients with acute pharyngitis. Other physicians are saying diagnosis and treatment can still be made based on clinical grounds alone. Some physicians claim these approaches result in too many viral pharyngitis patients being treated with antimicrobial agents. 

Rheumatic fever must be differentiated from other diseases that affect the joints such as rheumatoid arthritis, systemic lupus erythematosus, serum sickness, etc. There are important clues that will aid in eliminating or including these other diseases in this differential however we don't have the time to cover these in detail. Rheumatic fever is a difficult diagnosis. The following Jones Criteria can be helpful in making this diagnosis.

SUPPORTING EVIDENCE OF STREPTOCOCCAL INFECTION: Increased titer of antistreptococcal antibodies, ASO (anti-streptolysin O), other Positive throat culture for group A streptococcus, recent scarlet fever

Here are two different mnemonics that may help you remember the 5 major criteria.

Diphtheria: If a pseudomembrane is present and bleeding occurs upon removal of the membrane it is highly suggestive of diphtheria. Neurological abnormalities such as palatine palsy are important clues to diphtheria in cases lacking a pseudomembrane. Smears and culture for Corynebacterium diphtheria should be performed.

Prognosis

Viral Pharyngitis - The outcome of the patient is very good. Most of the patients recover with no complications.

Group A streptococcal pharyngitis - Without treatment, complications are related to severity of the disease. Complications included local suppurative complications, bacteremia or metastic foci in bones, joints, CNS, or other sites. The death rate was usually about 1 to 3%. Most adults and children can resolve the infection with no complications. With antimicrobial treatment the incidence of suppurative complications declined dramatically. The risk of rheumatic fever is almost totally eliminated with treatment. (NOTE: Rheumatic fever and glomerulonephritis can occur after pharyngitis. Only glomerulonephritis appears to occur after skin infections as a nonsuppurative complication.)

Diphtheria - Before the use of serotherapy the mortality rate was 30 to 50%. The major complications of the disease are as a result of dissemination of the toxin to the heart and nerves. Myocarditis is the more important of the two causing the most mortality. Cranial nerves are most sensitive to the toxin resulting in difficulty in swallowing and nasal regurgitation of liquids. If you survive a natural infection your immunity is usually lifelong.

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

Viral pharyngitis - No specific therapy is available. Basically, aspirin and warm saline gargles will help lower the pain. Fluids to avoid dehydration should be encouraged.

Group A streptococcal pharyngitis - The use of an antimicrobial agent is also indicated in therapy for "strep throat". Antimicrobial treatment has been shown to limit contiguous spread (e.g. peritonsillar abscess, cervical lymphadenitis, and mastoiditis), prevent development of acute rheumatic fever (if given within 9 days of symptoms appearing), improve clinical signs and symptoms (if given within 2 days of symptoms appearing), rapidly decrease infectivity thus reducing transmission of this bacterium to close-contacts (ex. family, classmates) and allow for a rapid resumption to their usual activities. Penicillin remains the drug of choice to treat strep throat. Erythromycin is the drug of choice for penicillin allergic patients. Use of broad-spectrum antimicrobials is discouraged. 

Rheumatic fever- Treatment of rheumatic fever includes antimicrobials to eliminate the organism and anti-inflammatory agents to suppress the clinical manifestations of rheumatic fever. Reoccurrences of rhematic fever are more likely in these patients following another "strep throat" infection therefore periodic treatment with penicillin (IM injections every 3 weeks) is effective in preventing future infections with Streptococcus pyogenes and reoccurrences of rheumatic fever.

Diphtheria - Hospitalization, isolation and immediate treatment with antiserum to the toxin. This will neutralize the toxic affects of the diphtheria toxin and is the most urgent task. The second most important task is antimicrobial treatment with erythromycin. The patient should also be given the diphtheria vaccine to ensure immunity to the disease. Two weeks after therapy the patient should be cultured to ensure the absence of a carrier state.

Viral pharyngitis - Only control measures to limit contact of susceptible persons with infected persons. An adenovirus vaccine is available for military personnel but is not warranted for the general population.

Group A streptococcal pharyngitis and rheumatic fever - No vaccine is available. Limiting contact of patients with the uninfected is helpful. Persons having recovered from rheumatic fever must be protected from another "strep throat" infection due to the high recurrence of rheumatic fever in these patients. Prophylaxis of these patients with a monthly dose of penicillin is very useful. This prophylaxis should continue through the patient's childhood years. If permanent damage occurs to the heart prophylaxis should continue for the life of the patient.

Diphtheria - Active immunization using the toxoid prevents diphtheria.