PHARYNGITIS

PHARYNGITIS

  1. 1
    Current Diagnosis

    • Patients prioritize symptom relief over microbiologic cure.

    • Most pharyngitis is viral; microbiologic confirmation is required for group A β-hemolytic streptococcus pharyngitis diagnosis.

    • In adults, throat culture is not necessary if rapid antigen detection test is negative.

    • Stop presumptive antibiotic therapy if throat culture results are negative for group A β-hemolytic streptococcus.

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  2. 2
    Current Therapy

    • Penicillin is the drug of choice for group A β-hemolytic streptococcus pharyngitis. A first-generation cephalosporin or macrolide is indicated if the patient is allergic to penicillin.

    • Treatment is necessary for 10 days to eradicate group A β-hemolytic streptococcus from the pharynx.

    • Amoxicillin can be substituted for penicillin. Patients older than 12 years may be treated with once-daily amoxicillin (Moxatag).

    • Patients are not infectious after 24 hours of appropriate antibiotic treatment.

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  3. 3
    Epidemiology

    Pharyngitis is common and has substantial medical and societal costs. “Sore throat” accounts for over 7 million outpatient visits by children annually. The estimated total cost of pharyngitis in children is $540 million per year.

    An estimated 30% of childhood pharyngitis is caused by group A β– hemolytic streptococcus (GABHS). In temperate climates, pharyngitis occurs in outbreaks during winter and early spring, predominantly involving children 5 to 15 years of age. GABHS is uncommon in preschool-aged children and in adults. Group C β-hemolytic streptococcus pharyngitis occurs mainly in college students and young adults.

    Of other causes of pharyngitis (Table 1), gonococcal pharyngitis is most common in older adolescents and young adults. Transmission is by oral-genital contact. If gonococcal pharyngitis is diagnosed in a prepubertal child, sexual abuse must be considered.

    Table 1

    Pharyngitis: Distribution of Causative Organisms (All Age Groups)

     

    Pathogen                                           Percentage of Population
    Group A β-hemolytic streptococcus 15–30
    Rhinovirus 20
    Adenovirus 2–5
    Coronavirus 2–5
    Coxsackievirus 2–5
    Group C β-hemolytic streptococcus 2–5
    Herpes simplex virus 2–5
    Influenza virus 2–5
    Chlamydia trachomatis < 1
    Corynebacterium diphtheriae < 1
    Epstein-Barr virus < 1
    Human  immunodeficiency virus < 1
    Arcanobacterium  haemolyticum < 1
    Mycoplasma spp. < 1
    Neisseria gonorrhoeae < 1

     

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  4. 4
    Risk Factors

    The major risk factors for GABHS pharyngitis are age and exposure such as in crowded schools or through household contacts. Oral sexual activity is implicated in gonococcal pharyngitis. Swimming pools have been implicated in transmission of group C and D β streptococcal pharyngitis.

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  5. 5
    Pathophysiology

    Pathogenic strains of Streptococcus pyogenes can be differentiated by Lancefield antigens and by hemolysis on blood agar. The strain containing group A antigen and displaying β hemolysis causes pharyngitis (GABHS). The M protein is responsible for virulence. The M protein cross-reacts with cardiac myosin and laminin, potentially causing rheumatic heart disease. More than 100 M-protein serotypes have been identified. Some streptococcus strains produce erythrogenic toxins, causing the rash of scarlet fever. Patients develop lifelong immunity to one serotype after infection, but reinfection with a different serotype is possible.

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  6. 6
    Prevention

    GABHS is transmitted by droplet spread. No evidence supports other forms of transmission. Patients and household/close contacts should be educated on minimizing droplet spread to reduce the transmission of GABHS.

    Phase I trials have been completed on a multivalent vaccine targeting streptococcus M proteins that cause pharyngitis, invasive disease, and rheumatic fever.

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    Clinical Manifestations

    The type of pharyngitis cannot be identified by history and clinical findings. Microbiologic confirmation is necessary to diagnose GABHS pharyngitis.

    Group A β-Hemolytic Streptococcal Pharyngitis

    In patients age 3 years to adult, sudden onset of sore throat, pain on swallowing, and fever (101°F–104°F) suggest GABHS pharyngitis.

    Nausea and vomiting can also occur in school-aged children. Clinical signs can include tonsillar erythema with or without exudate, anterior cervical lymphadenitis, soft palate petechiae, red swollen uvula, and scarletiniform rash. Infants rarely present with exudative pharyngitis but have coryza with excoriation and crusting of the nares.

    Posttonsillectomy patients with GABHS can have milder symptoms and clinical signs.

    Patients with suppurative complications of GABHS have unusually severe symptoms, with neck swelling, drooling, and “hot potato” voice. The clinician must look for peritonsillar abscess and infections in the parapharyngeal and submandibular spaces (Ludwig’s angina).

    Scarlet Fever

    Some strains of GABHS produce a pyogenic exotoxin that causes scarlet fever in susceptible patients. The clinical signs and symptoms are identical to GABHS pharyngitis plus development of the characteristic rash within 24 to 48 hours of symptom onset. The fine, papular, bright red rash blanches with pressure, begins on the neck, and spreads to the extremities and trunk. It is more pronounced in creases and feels rough, with a goose-pimple appearance. The punctate rash spares the face, but patients have flushed cheeks and forehead with pallor around the mouth. The rash fades in 3 to 4 days and is followed by desquamation. After desquamation of an initial white coating, the tongue has a classical strawberry appearance caused by edematous papillae.

    Poststreptococcal Glomerulonephritis

    Renal symptoms of hypertension, edema, and hematuria can occur 1 to 3 weeks after GABHS pharyngitis. Glomerulonephritis is an autoimmune response to M proteins. It is not preventable by antibiotics.

    Viral Pharyngitis

    Coryza, hoarseness, cough, diarrhea, viral exanthem, anterior stomatitis, and conjunctivitis can indicate a viral etiology for pharyngitis. Adenovirus infections can cause fever for 7 days, and conjunctivitis can persist for 14 days. Adenoviral outbreaks are often associated with swimming pools.

    Enterovirus pharyngitis (coxsackievirus, echovirus, enterovirus) occurs in summer and fall. Fever, cervical adenopathy, and erythema of the tonsils are common, but exudates are rare. Herpangina (Coxsackie virus A/B) manifests with fever and painful papulovesicular lesions in the posterior oropharynx that resolve in 7 days. Hand-foot-and-mouth disease (Coxsackie virus A-16) manifests with painful vesicles and ulcers in the mouth plus painful vesicles on the palms, soles, and occasionally trunk. Lesions resolve in 7 days.

    Primary oral herpes simplex infection occurs in young children. It manifests as acute gingivostomatitis, with ulcerating vesicles on the anterior mouth and lips but not on the posterior pharynx. High fever with intense pain is common, and dehydration can occur. Symptoms last for 14 days.

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  8. 8
    Diagnosis

    It is necessary to obtain microbiologic confirmation of infection before treating GABHS pharyngitis. If the clinical symptoms suggest GABHS pharyngitis, a throat culture or rapid antigen detection test (RADT) are indicated. If the clinical symptoms suggest viral pharyngitis, the pretest probability of GABHS infection is low, and a diagnostic test should not be performed.

    Several methods for determining the probability of GABHS infection have been proposed. The Centor criteria (for adults) are widely accepted. A score of 1 is given for each of the following characteristics: tonsillar exudate, tender anterior cervical adenopathy, history of fever, and an absence of cough. A score of 3 or more indicates a positive predictive value for GABHS of 40% to 60%. A score of 0 to 1 indicates a positive predictive value for GABHS of 1% to 5%.

    Throat culture is the gold standard for diagnosing GABHS infection. The tonsils and the posterior pharynx should be aggressively swabbed. Other areas of the mouth should not be touched when obtaining the culture. The culture should be obtained before beginning antibiotic therapy, because even a single dose of antibiotics can cause the culture to be negative. The swab is plated on a sheep’s blood agar plate and incubated. The plate must be read at both 24 and 48 hours of incubation. When done correctly, the throat culture has 90% to 95% sensitivity. Although throat culture is considered the gold standard for diagnosing GABHS infection, it does not differentiate a carrier state from clinical infection.

    RADT has high specificity but low sensitivity. The many tests available have different performance characteristics. In children aged 5 to 15, a throat culture should be performed if the RADT test is negative to identify patients who have a false-negative RADT result. In adults, throat culture is not necessary after a negative RADT because of the low incidence of GABHS and extremely low risk of acute rheumatic fever. The use of RADT has allowed clinicians to begin antibiotic therapy early in those with a positive test. This decreases the risk of spread of GABHS, allows earlier return to school or work, and modestly improves clinical signs and symptoms.

    Streptococcal antibody testing has no value in the acute diagnosis of GABHS pharyngitis. Testing has some value in confirming prior GABHS infection in patients in whom acute rheumatic fever or acute poststreptococcal glomerulonephritis is suspected. The two antibodies that can be identified are antistreptolysin O (ASO) and antideoxyribonuclease B (ARB). Positive, elevated, or increasing titers are confirmation of recent GABHS infection. ASO titers rise within a week of infection and peak 3 to 6 weeks after infection. ARB titers rise within 1 to 2 weeks of infection and peak at 6 to 8 weeks. In some patients titers remain elevated for prolonged periods, therefore a doubling of the titer in 6 weeks in necessary for diagnosing prior GABHS infection.

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  9. 9
    Differential Diagnosis

    Infectious Mononucleosis

    Classically a triad of severe sore throat, lymphadenopathy, and fever (up to 104°F) in 15- to 25-year-olds, mononucleosis begins with a prodrome of chills, sweats, fever, and malaise. Clinical signs include enlarged tonsils; posterior and anterior cervical, axillary and inguinal adenopathy; and hepatosplenomegaly. Approximately 15% of patients present with jaundice and 5% with rash. Patients with mononucleosis who are treated with amoxicillin (Amoxil)1 often develop a pruritic maculopapular rash. Complete blood count (CBC) shows an absolute lymphocytosis with greater than 10% atypical lymphocytes. Within 2 to 3 weeks, the heterophile antibody test (Mono Spot) becomes positive. The antibody test has a higher false-negative rate in children than in adults. If a false-negative test is suspected, an IgM antibody to viral capsid antigen is indicated to confirm the diagnosis.

    Acute Retroviral Syndrome

    Primary infection with HIV can manifest as a syndrome of fever, nonexudative pharyngitis, arthralgia, myalgia, and lymphadenopathy. Some 40% to 80% of patients develop a rash. HIV antibodies are negative. Assay for HIV type 1 RNA or p24 antigen is positive.

    Neisseria gonorrhea

    1. gonorrhea pharyngitis is usually asymptomatic and associated with oral sexual practices. The diagnosis is confirmed by isolating the organism on Thayer-Martin medium. All patients should be screened and treated for coinfection with chlamydia.

    Lemierre’s Syndrome

    Lemierre’s syndrome is a rare etiology of severe pharyngitis caused by Fusobacterium necrophorum. Infection spreads from the pharynx to include the surrounding tissues, with subsequent thrombophlebitis of the internal jugular vein.

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    Treatment

    A major therapeutic decision is to determine if the patient needs an antibiotic in addition to symptomatic treatment.

    The goal of treatment of viral pharyngitis is control of symptoms, especially relief of pain. Nonsteroidal antiinflammatory drugs are slightly superior than acetaminophen (Tylenol) for pain relief. No evidence supports the use of Chinese herbs for symptom relief. Oral steroids can relieve pain, but the risks of use outweigh the benefit.

    Many patients mistakenly believe that antibiotic therapy relieves pain. Ancillary treatment options include rest, adequate fluid intake, and antipyretic medications.

    The goals of antibiotic treatment of GABHS pharyngitis are to decrease infectivity and prevent suppurative and other complications, especially acute rheumatic fever. Symptoms generally improve within 3 to 4 days without treatment. Delay of treatment of GABHS pharyngitis for up to 9 days after symptoms begin does not appear to increase the risk of acute rheumatic fever, and a delay of 24 to 48 hours while awaiting culture results does not increase the risk of acute rheumatic fever. Early treatment of GABHS pharyngitis does reduce infectivity, lessens morbidity, and promotes early return to normal activities. Nevertheless, criteria for initiating antibiotics remain controversial.

    The choice of antibiotic is determined by the bacteriology of GABHS, clinical efficacy, patient adherence to treatment regimen, adverse effects, and cost. It is not recommended to initiate antibiotics while awaiting throat culture result in children. However if an antibiotic is started it must be discontinued if the culture is negative.

    Penicillin remains the antibiotic of choice for GABHS pharyngitis. GABHS has never shown resistance to penicillin or cephalosporins. Amoxicillin1 can replace penicillin for treatment. (Liquid amoxicillin has a better taste than liquid penicillin.) In the penicillin-allergic patient, a first-generation cephalosporin or macrolide may be substituted. In some areas of the United States up to 8% of GABHS is resistant to macrolides and less than 1% is resistant to clindamycin (Cleocin).1 Antibiotics should be given for 10 days to eradicate GABHS from the pharynx. At this time, short-course (≤ 5 days) treatment cannot be recommended, except with azithromycin (Zithromax).

    No clear evidence supports antibiotic treatment for group C or group G streptococcal pharyngitis. Treatment might shorten the course of infection. Treatment options are identical to those for GABHS pharyngitis.

    Treatment Regimens

    •   Oral penicillin: PenicillinVK (Veetids)1: 40 mg/kg/day (up to adult dose of 1000 mg/day) in divided doses two or three times daily for 10 days.

    •   Amoxicillin1: 50 mg/kg/day (up to adult dose of 1000 mg/day) twice daily for 10 days; FDA has approved amoxicillin ER tab (Moxatag) for patients older than 12 years at 775 mg once a day.

    •   Penicillin G benzathine (Bicillin-LA): Patients weighing less than 27 kg, 600,000 units IM; patients weighing 27 kg or more, 1.2 million units IM once. Penicillin G is used for patients who are unlikely to complete a full 10-day course of oral medication and for those with a personal or family history of rheumatic fever.

    •   First-generation oral cephalosporin: Cephalexin (Keflex) 25 to 50 mg/kg/day (up to adult dose of 1000 mg/day) twice daily for 10 days. This regimen should be used if the patient is allergic to penicillin; shorter courses are not FDA approved.

    •   Macrolides should be used if the patient is allergic to penicillin: Erythromycin 20 to 40 mg/kg/day (up to adult dose of 1000 mg/kg/day) in three or four doses for 10 days. Azithromycin (patients older than 6 months): Day 1: 10 mg/kg once (up to adult dose of 500 mg); days 2 to 5: 5 mg/kg once daily (up to adult dose of 250 mg/day). The dose of azithromycin is not established in infants younger than 6 months.

    Tetracycline, sulfonamides, and older fluroquinalones are not recommended because of high rates of resistance. All patients should be considered infectious until they have completed 24 hours of antibiotic therapy.

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    Monitoring

    In general, follow-up throat cultures or RADT for patients successfully treated for GABHS pharyngitis (i.e., test for cure) are not necessary.

    An additional RADT or throat culture is required if symptoms do not abate, symptoms recur, or the patient had previous rheumatic fever.

    Patients who have repeated symptomatic episodes of GABHS have either recurrent new infections or are carriers of GABHS, with repeated superimposed viral infections.

    GABHS carriers have positive cultures for GABHS without clinical symptoms. Approximately 20% of school-aged children are carriers. GABHS carrier status is suspected if the clinical picture is of viral pharyngitis but the patient has positive RADT or cultures both when symptomatic and when asymptomatic. Carriers do not respond to antibiotics and have no serologic response to ASO and anti-DNA B. These patients do not need to be identified or treated. These patients do not develop rheumatic fever and are not important in the spread of GABHS to others.

    Patients with repeated GABHS pharyngitis have a clinical picture of recurrent bacterial pharyngitis. They respond to antibiotics and have negative RADT and culture when they are asymptomatic. They have a serologic response to ASO and anti-DNA B. Prophylactic antibiotics are not recommended for these patients. Tonsillectomy may be considered when infection attack rates do not decrease over time and no other explanation of recurrent infection can be found. Meta- analyses have found inconclusive evidence of benefit from tonsillectomy compared to nonsurgical treatment.

    Patients with GABHS pharyngitis who remain symptomatic and continue to have positive cultures should receive a second course of antibiotics, with either the same antimicrobial agent or intramuscular penicillin. If a patient experiences repeated infections and there is concern that the GABHS infection is being spread among close contacts, all close and family contacts should be cultured and only those who are positive should be treated. Family pets are not reservoirs and do not spread disease.

    Mass screening should be considered in outbreaks of GABHS in a closed or semiclosed community or in outbreaks of acute rheumatic fever or poststreptococcal glomerulonephritis.

    Non-GABHS pharyngitis (i.e., group C or G β-hemolytic streptococcus) is not associated with rheumatic fever, and no evidence supports treatment or follow-up culture.

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    Complications

    The complications of GABHS pharyngitis can be classified as suppurative and nonsuppurative.

    Suppurative complications occur when the infection spreads to cause conditions such as lateral pharyngeal abscess, cervical lymphandenitis, sinusitis, otitis media, retropharyngeal abscess, Lemierre’s syndrome, and mastoiditis. Appropriate treatment of GABHS with antibiotics decreases these complications.

    Nonsuppurative complications include acute rheumatic fever, acute poststreptococcal glomerulonephritis, and poststreptococcal reactive arthritis. Acute rheumatic fever occurs 2 to 3 weeks after GABHS pharyngitis. It is not seen after GABHS skin infections. Starting antibiotics within 9 days of symptoms can prevent acute rheumatic fever. Acute poststreptococcal glomerulonephritis can occur 10 days after pharyngeal infection and 21 days after skin infection. Antibiotics do not alter the attack rate. Poststreptococcal reactive arthritis is similar to other reactive arthritis, and the attack rate is not altered by antibiotics.

    Potential complications from treatment of GABHS pharyngitis include anaphylactic reaction to antibiotics and antibiotic resistance.

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    References

    ESCMID Sore Throat Guideline Group, Pelucchi C., Grigoryan L., et al. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012;18(Suppl 1):1–28. http://www.ncbi.nlm.nih.gov/pubmed/22432746.

    Kociolek L., Shulman S. In the clinic pharyngitis. Ann Intern Med.

    2012;157. ITC3-1–ITC3-16, Downloaded from http://annals.org.

    Shulman S.T., Bisno A.L., Clegg H.W., et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55:e86–e102.

    1  Not FDA approved for this  indication.

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