Author / Curator: Justin Berk, MD
Faculty Advisor: Robert Centor, MD
Top Teaching Points
- The most common causes of acute pharyngitis are viral.
- Clinical decision-making tools (e.g. Centor critieria) can help guide rapid strep testing.
- Antibiotic treatment of GAS is shown to reduce complications including rheumatic fever, AOM, sinusitis, abscess formation but not post-streptococcal glomerulonephritis.
- Fusobacterium is increasing implicated in acute pharyngitis among young adults and can lead to a deadly complication, Lemierre's disease. It is unclear if early treatment can prevent this complication.
- Patients presenting with acute pharyngitis prioritize pain relief, reassurance, and information over antibiotic prescription.
Acute pharyngitis is generally defined as sore throat for no more than 3 - 5 days.
Acute pharyngitis is responsible for 1-2% of all ambulatory care visits in in the US and 6% of pediatric visits to a primamary care physicians. Approximately 50% of cases occur before age 18. The etiology between pre-adolescents and adolescents is markedly different (notably, adolescents have a higher prevalence of Fusobacterium. Adults that have frequent contact with children (e.g. parents, pediatricians) are at higher risk of contracting Group A strep.
Physiology / Pathophysiology
Table 1. Common Pathogens of Acute Pharyngitis 
|Strep pyogenes (GAS)||Rhinovirus||Rhinitis|
|Group C Strep (GCS)*||Adenovirus||GERD|
|Fusobacterium necrophorum*||Coronavirus||Recent tracheal intubation|
|Neisseria gonorrhea||Acute HIV||Recent procedure (e.g. tonsillectomy)|
|Cornyebacterium diptheriae||EBV / CMV Mononucleosis|
|Arcanobacterium hemolyticum||Coxsachievirus ("Hand Foot Mouth Disease")|
Respiratory viruses are the most common causes of acute pharyngitis, accounting for approximately 25 to 45 percent of cases. GAS is responsible for ~10% of adult pharyngitis and ~25% of cases in children. Fusobacterium is increasing implicated as an etiologic agent in older adolescents and young adults with sore throat.  Other very rare causes may include tularemia, syphilis, ersinia, HSV, mycoplasma pneumoniae, and chlaymidophilia. Gonorrhea rarely causes symptomatic pharyngitis.
Complications of Disease
Suppurative Cx of GAS pharyngitis: otitis media, peritonsillar / retropharyngeal abscess, sinusitis, and mastoiditis. Non-suppurative (immune-mediated) Cx of GAS pharyngitis: acute rheumatic fever, post-streptococcal glomerulonephritis, and reactive arhtritis. Acute Rheumatic Fever can be diagnosed using the Revised Jones Criteria with symptoms presenting 2-3 weeks after GAS pharyngitis. Rheumatic fever has been rarely documented with Group C/G strep pharyngitis.
With fusobacterium, suppurative thrombophlebitis (Lemierre syndrome) can arise from bacterial invasion and clot formation of the jugular vein. fusobacterium is estimated to cause the Lemierre syndrome at a higher incidence than that at which group A streptococcus causes acute rheumatic fever. There is some indication that fusobacterium is the most common cause of peritonsillar abscess.
- sudden onset of pain (< 3 days)
- pain on swallowing
- abdominal pain
- nausea and vomiting (particularly in children)
Typical signs include:
- tonsillophryngeal erythema and/or exudate
- palatial petechiae
- beefy red swollen uvula
- anterior cervical lymphadenits
- a scarlitiniform rash ("Scarlettfever")*
*Scarlett fever is a finely papular erythematous rash that spares the face, may be accentuated in skin folds, and may desquamate during illness recovery.
A common diagnostic tool using a selection of these findings is the validated Centor criteria. (See Table 2 and 3). All guidelines recommend neither testing nor treatment for Centor score of 0 or 1. (Of note, sore throat is one of the major contributors to antibiotic overuse.)FeverPAIN is another clinical scoring system to assist in diagnosis of streptococcal pharyngitis to improve symptomatic treatment while reducing unnecessary antibiotic use.
Table 2. Centor / McIssac Criteria
|Fever (T > 38.0 / 100.4)||+1|
|Absence of cough||+1|
|Swollen, tender anterior cervical lymph nodes||+1|
|Tonsillar swelling or exudate||+1|
|Age (McIssac Scoring)|
|Age 3 - 14||+1|
|Age > 45||-1|
Table 3. Centor Score and Associated GAS Risk
|Centor Points||Associated Risk fo GAS|
Uncharacteristic symptoms of GAS Streoptococcal pharyngitis: coryza, hoarseness, cough, diarrhea. Uncharacteristic physical exam signs include conjunctivitis, anterior stomatitis, discrete ulcerative lesions.
Mononucleosis (EBV) - The presence of posterior cervical, inguinal, or axillaru adenopathy, palatine petechiae, splenomegaly or atypical lymphocytosis is associated with increased likelihood of mononucleosis diagnosis.  The combination of >50% lymphocttes and greater than 10% atypical lympocytes was associated with a positive likelihood ration of 54 (or, a specificity of 99%).
Acute HIV - Acute HIV presents with a maculopapular rash in 40 - 80 percent of patients and lacks tonsillar exudate Other symptoms the increased the likelihood of acute HIV were genital ulcers, weight loss, vomiting, and swollen lymph nodes but the clinical exam offers limited utility.
Diphtheria - associated with grey psuedomembranous pharyngeal exudate. Extremely rare in US since universal immunization. 
Recommended Work-up (Evidence-based Labs / Imaging / Diagnostics)
The sensitivity of rapid tests is generally ~80% with a specificity of 95% or greater. Thus, a positive test is usually confirmatory of the GAS diagnosis while a negative may warrant secondary testing. Rapid tests can be used for accurate diagnosis of GAS in pediatrics and may not require throat culture for negative tests in most low-incidence rheumatic fever settings (i.e. the USA) though back-up cultures are recommended for children (not adults) based on ACP, AAP, and IDSA guidelines. Throat culture remains the gold standard for diagnosis.
Approximately 10% of school-aged children (and less in adults) will be GAS carriers without symptoms and carriage can persist for weeks or months with low risk of sequelae or transmission. Anti-streptolysin-O can help confirm a retrospective diagnosis of GAS (if concern for acute rheumuatic fever or post-streptococcal glomeuronephritis) but is not helpful in acute illness as titers increase after 7-14 days of onset, reaching a peak at 4 weeks.
The great majority of patients who have presumed viral pharyngitis or who test negative for group A Streptococcus (GAS) pharyngitis recover fully within five to seven days without specific treatment. Antibiotic therapy is warranted in Group A Strep infections to reduce complications. The NNT to reduce suppurative complications is ~193.
Antibiotic therapy has been shown to reduce peritonsillar abscess independent of bacterial etiology on culture.
Of note, the majority of patients presenting with acute pharyngitis are interested in pain relief, reassurance, and information rather than antibiotic prescription. Data from pediatric visits for URIs show unnecessary antibiotic usage decreased and patient satisfactrion increased when education was provided on symptom management and why antibiotics were not indicated.
Based on meta-analysis, Ibuprofen and acetaminophen are effective analgesics, with ibuprofen providing more pain relief than acetaminophen when actively compared.  Caffeine with aspirin has also shown to be more affective than aspirin alone or placebo. Zinc supplementation showed no improvement in pharyngitis symptoms. A recent study showed mild pain reduction at 48 hours (but not 24 hours) with injected corticosteroids. Chlorhexadine mouth spray has improven clinical symptoms in patients with streptococcal pharyngitis and lozenges offer considerable advances over sprays based on scintigraphy imaging. Systemic reviews show steroids have been shown to modestly reduce pain in acute sore throat.
Group A Strep Treatment
The first line treatment for GAS is 10 days of oral penicillin or 1 dose of IM penicillin. If there is a penicillin allergy, cephalexin, azithromycin, and clindamycin are reasonable alternatives. 
Throat soreness and fever were reduced by about half by using antibiotics. Antibiotics shorten the duration of symptoms by about 18 hours overall. Antibiotics reduced acute rheumatic fever by more than two-thirds within one month (risk ratio (RR) 0.27), acute otitis media within 14 days (RR 0.30) acute sinusitis within 14 days (RR 0.48); and pharyngitis within two months (RR 0.15). Treatment has not been show to reduce post-strep glomuerulonephritis.
Non-resolving pharyngitis requires consideration of: false negativity of rapid strep tests and reconsideration of the above differential (e.g. infectious mononucleosis, acute HIV, Group C/G streptococcal pharyngitis, peritonsilar abscess, Lemierre's syndrome). This may require throat culture, monospot testing, and potential CT if physical exam concerning for abscess or suppurative thrombophlebitis.
Ongoing controversies / New updates
Differences in Guidelines: Guidelines for management of patients with 4 Centor criteria differ among professional societies. The ACP recommends considering empirical treatment of GAS in adults with 4 Centor criteria, this is not endorsed by the IDSA or the American Heart Association (AHA).  Other differences include: the use of Centor criteria, the use of rapid strep tests, and the use of throat cultures.
Are strep infections associated with auto-immune neuropsychiatric disorders (i.e. PANDAS)? 
Should steroids be given for acute pharyngitis? IDSA: No. Cochrane Review: Maybe.
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