Pharyngitis

ACRONYMS AND DEFINITIONS

AAOHNS - American Academy of Otolaryngology–Head and Neck Surgery

IDSA - Infectious Diseases Society of America

GAS - Group A Streptococcus

IM - Intramuscular

RCT - Randomized controlled trial

ETIOLOGY

Overview

Pharyngitis (sore throat) is one of the most common presenting complaints in outpatient clinics. In the U.S., it accounts for an estimated 15 million doctor visits annually.
The vast majority of throat infections in both children and adults are caused by viruses. The second most common cause is Group A streptococcus which accounts for 20 - 30% of throat infections in children and 5 - 15% of infections in adults.

Reference [2]
ETIOLOGY OF PHARYNGITIS
Viruses (70 - 95% of infections)
Adenovirus	Causes syndrome of fever, sore throat, cough, and conjunctivitis
Herpes simplex 1 virus	Gingivostomatitis Causes painful oral ulcers
Coxsaskievirus	Hand, foot, and mouth disease Painful sores develop in the mouth (herpangina) Red spots develop on hands and soles of feet
Rhinovirus Coronavirus	Common cold viruses Sore throat is a common feature
Influenza Parainfluenza	Sore throat is a common feature of a flu syndrome
Epstein-Barr Virus Cytomegalovirus	Cause a syndrome of fever, sore throat, lymphadenopathy, and fatigue Also called infectious mononucleosis
Bacteria (5 - 30% of infections)
Group A Streptococcus	Most common bacterial cause of pharyngitis Accounts for 20 - 30% of pharyngitis in children and 5 - 15% in adults
Group C Streptococcus	More common in adults and college students May occur in outbreaks from contaminated food (e.g. unpasteurized milk) No clear link to rheumatic fever or glomerulonephritis No clear evidence that antibiotic treatment is beneficial
Group G Streptococcus	No clear link to rheumatic fever or glomerulonephritis No clear evidence that antibiotic treatment is beneficial
Neisseria gonorrhoeae	May occur in sexually active people
Corynebacterium diphtheriae	May form thick coat in back of throat Vaccine is part of the standard childhood vaccination schedule Also part of TdaP vaccine (tetanus, diphtheria, pertussis)

SYMPTOMS - BACTERIAL VS VIRAL

Overview

Pharyngitis, whether bacterial or viral, is almost always a self-limited infection
The main reason for determining the cause is so that antibiotics can be given for GAS in order to prevent post-infectious sequelae (e.g. rheumatic heart disease, glomerulonephritis)
Symptoms can help distinguish between the two, but they are inexact, and all suspected cases of strep throat should be confirmed with diagnostic testing. Studies have shown that 50 - 70% of patients with all the clinical signs of strep throat (fever, absence of cough, cervical lymphadenopathy, tonsillar swelling and exudate) have negative strep cultures.
Symptoms suggestive of bacterial and viral etiologies are presented below [1,2]

Symptoms consistent with strep throat:

Sudden onset of sore throat
Age 5–15 years
Fever
Headache
Nausea, vomiting, abdominal pain
Tonsillopharyngeal inflammation
Patchy tonsillopharyngeal exudates
Palatal petechiae
Anterior cervical adenitis (tender nodes)
Winter and early spring presentation
History of exposure to strep pharyngitis
Scarlatiniform rash [2]

Symptoms consistent with viral infection:

Conjunctivitis
Runny nose
Cough
Diarrhea
Hoarseness
Discrete ulcerative stomatitis
Viral exanthema [2]

DIAGNOSIS

Whom to test

Patients with pharyngitis and symptoms suggestive of strep throat should universally be tested for GAS
The Infectious Diseases Society of America (IDSA) issued recommendations for strep throat testing in 2012

IDSA recommendations for GAS testing

In general, children < 3 years old should not be tested, unless there is a strong suspicion for strep throat (Ex. sibling with confirmed strep throat)
Adults and children with symptoms consistent with a viral infection (see symptoms above) should not be tested
Rapid strep test is the initial test of choice in most patients
Children and adolescents with a negative rapid strep test should have a backup throat culture
Adults with a negative rapid strep test should not have a backup throat culture
Patients with a positive rapid strep test do not need a throat culture
Asymptomatic household contacts should not be tested or treated empirically

Reference [1, 2, Manufacturer's PI]
Diagnostic tests for strep throat
Test	Accuracy	Other
Rapid antigen testing	Sensitivity: > 90% Specificity: > 90%	Performed in office. Takes about 5 minutes to get results. Antibodies to strep antigen are coated on the test strip. If strep antigen is present in the throat swab, it binds to the antibodies causing the strip to change color. Older versions of rapid antigen testing had lower sensitivities (70 - 90%). Most manufacturers of kits used today report sensitivities > 90%. Some versions of rapid antigen testing use different markers (e.g. immunofluorescence) that are read by a machine
Direct DNA probe tests	Sensitivity: > 90% Specificity: > 90%	Sample collected in office and sent to lab for processing If Strep RNA is present in the sample, complementary DNA in the test kit will form a complex with it. DNA:RNA complexes are then detected by a machine. More expensive than rapid antigen testing
PCR testing	Sensitivity: > 90% Specificity: > 90%	Sample collected in office. May be sent to lab. Some office-based machines are available. Strep DNA in the sample is amplified and then detected through polymerase chain reaction (PCR) techniques More expensive than rapid antigen testing
Culture	Considered reference standard	Sample collected in office and then sent to lab where it is cultured on a plate Prior antibiotics may cause false-negative result Takes 1 - 3 days to get results

COMPLICATIONS

Overview

Strep throat is a self-limited infection that typically resolves on its own regardless of antibiotic therapy. The main reason for treating strep throat with antibiotics is to prevent the secondary complications discussed below.

Reference [2,4,5,6]
Complications of group A strep (GAS) pharyngitis
Rheumatic fever Inflammatory autoimmune reaction that occurs 2 - 4 weeks after GAS infection Symptoms included arthritis (35 - 88%), carditis (50 - 78%), erythema marginatum (< 6%), subcutaneous nodules (1 – 13%), and fever Treatment involves prolonged antibiotic prophylaxis (see rheumatic fever prevention) and NSAIDs
Rheumatic heart disease Sequelae of rheumatic fever carditis Thought to occur from antibodies that cross-react with streptococcal proteins and heart tissue Rheumatic heart disease typically affects the mitral valve. Mitral valve stenosis is almost exclusively caused by rheumatic heart disease, and its presence is considered pathognomonic for the condition. However, mitral valve regurgitation is the most common defect observed. See rheumatic fever prevention below for recommendations on preventing recurrence
Otitis media See otitis media for more
Peritonsillar abscess Symptoms include dysphagia, ipsilateral ear pain, rancid breath, and drooling Physical findings include swollen tonsil that is displaced medially and inferiorly, uvula deviation, difficulty opening mouth, and muffled voice Treatment includes abscess drainage, antibiotics, and airway support
Post-streptococcal glomerulonephritis May occur 1 - 6 weeks after GAS infection Symptoms include hematuria, proteinuria, edema, hypertension, and reduced kidney function Antibiotic therapy for GAS infections does not appear to prevent post-streptococcal glomerulonephritis Treatment is mostly supportive (e.g. diuretics, blood pressure management, fluid restriction) Most children have complete resolution within weeks while adults are more likely to have residual kidney disease
Guttate psoriasis Psoriatic rash that occurs in some patients after a strep throat infection Most cases resolve spontaneously after weeks to months, but it can become a chronic condition that requires treatment See guttate psoriasis for more
IgA vasculitis (Henoch-Schönlein purpura) IgA vasculitis, also called Henoch-Schönlein purpura, is often preceded by an upper respiratory infection, of which group A strep is the most common etiology See IgA vasculitis for more

TREATMENT (IDSA RECOMMENDATIONS)

Group A Strep (pediatric)

Non-penicillin allergic

Penicillin (Pen VK®) 250 mg twice daily or 3 times daily for 10 days ($)
Amoxicillin 50 mg/kg once daily (max 1000 mg) OR 25 mg/kg (max 500 mg) twice daily for 10 days ($)
Penicillin G benzathine (Bicillin L-A®)

< 27 kg: 600,000 units IM ($$-$$$)
≥ 27 kg: 1,200,000 units IM ($$-$$$)

Penicillin allergic

Cephalexin (Keflex®)^✝ 20 mg/kg/dose twice daily (max 500 mg/dose) for 10 days ($)
Cefadroxil (Duricef®)^✝ 30 mg/kg once daily (max 1000 mg) for 10 days ($)
Clindamycin (Cleocin®) 7 mg/kg/dose 3 times daily (max 300 mg/dose) for 10 days ($-$$$)
Azithromycin (Zithromax®) 12 mg/kg once daily (max 500 mg) for 5 days ($)
Clarithromycin (Biaxin®) 7.5 mg/kg/dose twice daily (max 250 mg/dose) for 10 days ($-$$)

^✝

Group A Strep (adults)

Non-penicillin allergic

Penicillin (Pen VK®) 250 mg 4 times daily OR 500 mg twice daily for 10 days ($)
Amoxicillin 1000 mg once daily OR 500 mg twice a day for 10 days ($)
Penicillin G benzathine (Bicillin L-A®) 1,200,000 units IM ($$-$$$)

Penicillin allergic

Cephalexin (Keflex®)^✝ 500 mg twice a day for 10 days ($)
Cefadroxil (Duricef®)^✝ 1000 mg once daily for 10 days ($)
Clindamycin (Cleocin®) 300 mg three times a day for 10 days ($-$$$)
Azithromycin (Zithromax®) 500 mg once daily for 5 days ($)
Clarithromycin (Biaxin®) 250 mg twice a day for 10 days ($-$$)

^✝

Symptomatic treatment

The IDSA recommends NSAIDs and acetaminophen for fever and pain symptoms
Corticosteroids are sometimes used for severe symptoms. See studies below for more.

STREP CARRIERS

Overview

Some people are chronic pharyngeal carriers of GAS. Carriers have GAS present in the pharynx with no symptoms of acute pharyngitis.
Up to 20% of asymptomatic school children in temperate climates have been shown to be carriers of GAS in the winter and spring months
GAS carriers are unlikely to spread the infection and do not appear to develop GAS complications
Identifying carriers can be difficult. Patients who present with frequent pharyngitis that always tests positive for GAS should raise suspicion. These patients may be carriers who are experiencing the more common viral infections. Testing these patients for GAS when they are asymptomatic may help determine if they are carriers.
Treating carriers to eradicate GAS is generally not recommended. If a decision is made to treat, one of the regimens below is recommended by the IDSA. [1,2]

Treatment Regimens for Chronic GAS Carriers (one of the following):

Clindamycin 20 - 30 mg/kg/day given in 3 doses (max 300 mg/dose) for 10 days

Penicillin + rifampin

Pen VK 50 mg/kg/day given in 4 doses (max 2000 mg/day) for 10 days
Rifampin 20 mg/kg/day given once daily (max 600 mg/day) during the last 4 days of treatment

Augmentin 40 mg amoxicillin/kg/day given in 3 doses (max 2000 mg amoxicillin/day) for 10 days

Benzathine penicillin G + rifampin

Benzathine penicillin G

< 27 kg - 600,000 U IM
≥ 27 kg - 1,200,000 U IM

Rifampin 20 mg/kg/day given in two divided doses (max 600 mg/day) for 4 days [2]

RHEUMATIC FEVER PREVENTION

Overview

Patients with rheumatic fever should receive antibiotic prophylaxis to prevent recurrence because subsequent episodes can worsen existing rheumatic heart disease. Furthermore, group A strep infections may be asymptomatic, and recurrence can happen even when acute infections are treated. Recommendations on antibiotic choice and duration of prophylaxis from the American Heart Association are presented below. [8]

Reference [8,9]
ANTIBIOTIC CHOICE
Antibiotic	Regimen
Penicillin G benzathine	Weight ≤ 60 lbs (27 kg): 600,000 units IM every 4 weeks Weight > 60 lbs (27 kg): 1,200,000 units IM every 4 weeks If patient develops rheumatic fever while receiving every 4 week regimen, switching to every 3 weeks may be appropriate
Penicillin (Pen VK®)	250 mg twice daily
Sulfadiazine	Weight ≤ 60 lbs (27 kg): 500 mg once daily Weight > 60 lbs (27 kg): 1000 mg once daily
Macrolide antibiotics	May be used in penicillin allergic patients. There are no good studies to guide dosing.

Reference [8]
DURATION OF PROPHYLAXIS
Type of disease	Duration after last attack^✝
Rheumatic fever with carditis and residual heart disease (clinical or echocardiographic)	10 years or until patient is 40 years of age (whichever is longer)
Rheumatic fever with carditis but no residual heart disease	10 years or until patient is 21 years of age (whichever is longer)
Rheumatic fever without carditis	5 years or until patient is 21 years of age (whichever is longer)
^✝ Lifelong prophylaxis may be recommended if the patient is at high risk of group A streptococcus exposure. Secondary rheumatic heart disease prophylaxis is required even after valve replacement.

TONSILLECTOMY RECOMMENDATIONS

Reference [7]
AAOHNS 2019 recommendations for tonsillectomy
Throat infection criteria Medically documented sore throat and ≥ 1 of the following: Temperature > 38.3°C (101°F) Cervical adenopathy Tonsillar exudate Positive test for GAS Tonsillectomy may be considered in the following patients: ≥ 7 throat infections in the past year ≥ 5 throat infections per year over the last 2 years ≥ 3 throat infections per year over the last 3 years Factors that may favor tonsillectomy in patients who do not meet the above criteria: Multiple antibiotic allergies or intolerance PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) History of > 1 peritonsillar abscess Obstructive sleep apnea

STUDIES

STUDY
Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults, JAMA (2017) [PubMed abstract]

Design: Randomized, placebo-controlled trial (N=565 | length=1 month) in patients with acute sore throat not requiring immediate antibiotic therapy
Treatment: Dexamethasone 10 mg one time vs Placebo
Primary outcome: Proportion of participants experiencing complete resolution of symptoms at 24 hours
Results:

Primary outcome (24 hours): Dexamethasone - 22.6%, Placebo - 17.7% (p=0.14)
Primary outcome (48 hours): Dexamethasone - 35.4%, Placebo - 27.1% (p=0.03)

Findings: Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.

STUDY
Corticosteroids for pain relief in sore throat: systematic review and meta-analysis - BMJ (2009) [PubMed abstract]

Design: Systematic review and meta-analysis (8 RCTs encompassing 743 patients)
Treatment: Corticosteroids vs Placebo
Outcome measures: Percentage of patients with complete resolution at 24 and 48 hours, mean time to onset of pain relief, mean time to complete resolution of symptoms, days missed from work or school, recurrence, and adverse events
Findings: Corticosteroids provide symptomatic relief of pain in sore throat, in addition to antibiotic therapy, mainly in participants with severe or exudative sore throat.

BIBLIOGRAPHY

1 - PMID 21323542 - Streptococcal Pharyngitis, NEJM (2011)
2 - PMID 23091044 - Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America, (2012)
3 - PMID 19661138 - BMJ MA
4 - PMID 28285457 - Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations, Curr Treat Options Cardio Med (2017)
5 - PMID 23302723 - Bacterial infection–related glomerulonephritis in adults, Kidney International (2013)
6 - PMID 18246890 - Peritonsillar Abscess, American Family Physician (2008)
7 - PMID 30921525 - Clinical Practice Guideline: Tonsillectomy in Children (Update)-Executive Summary, Otolaryngol Head Neck Surg (2019)
8 - PMID 33332150 - 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines, Circulation (2020)
9 - PMID 19246689 - Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics, Circulation (2009)

PHARYNGITIS