When evaluating a patient with sore throat, consider alternatives to group A streptococcal pharyngitis. Mimics include acute HIV, gonococcal pharyngitis, and infectious mononucleosis.
The modified Centor score uses 5 factors to help guide clinical decision making:
Anterior cervical lymphadenopathy
Low modified Centor scores do not require further testing or treatment in the general population
Mid range Centor scores require rapid antigen detection testing (RADT)
High modified Centor scores can undergo RADT or empiric treatment according to some guidelines, however, there is concern that empiric treatment may lead to antibiotic overuse.
Treatment with penicillin V or amoxicillin is preferred, in the penicillin allergic patient, first generation cephalosporins or a macrolide can be used.
Not All Sore Throat is Strep Throat
Strep pharyngitis, commonly known as “strep throat” is a bacterial infection of the oropharynx caused by group A beta hemolytic streptococci (GAS), specifically S. pyogenes. This infection affects more than 500,000,000 people annually worldwide per year, ultimately resulting in a significant number of doctor’s visits, including to the ED (1). The classic clinical presentation of GAS pharyngitis includes sudden onset of sore throat, fever, and odynophagia. If untreated, complications of GAS pharyngitis include scarlet fever, rheumatic heart disease, post-streptococcal glomerulonephritis and peri-tonsillar abscess.
There are many clinical mimics of GAS pharyngitis which must be ruled out by the clinician prior to testing or treatment for GAS pharyngitis. Clinical mimics include acute retroviral syndrome, as the first presentation of acute HIV may be with pharyngitis with tonsillar exudate, lymphadenopathy, fevers, headache. Patients with acute HIV may appear to have many similar symptoms to those with GAS pharyngitis, but will tend to have more prolonged symptoms (>7 days), generalized lymphadenopathy (not just of the head and neck), and will often have GI symptoms (diarrhea, mouth sores) as well. In these patients, it is important to assess risk factors for HIV. Sexual history can also provide key information in the diagnosis of bacterial pharyngitis not due to GAS, such as gonococcal pharyngitis in patients who participate in receptive oral intercourse. Another common clinical mimic of GAS pharyngitis is infectious mononucleosis which also presents with fever, pharyngitis, and lymphadenopathy, and is most commonly due to infection with the Epstein Barr Virus. This can be difficult to differentiate from GAS infection clinically, however patients with infectious mononucleosis may also have palatal petechiae (+LR for infectious mononucleosis of 5.3), posterior cervical lymphadenopathy (+LR 3.1) and splenomegaly (2). Other important clinical mimics to consider include the infections of the deep neck space such as retropharyngeal abscess, Ludwig’s angina, and Lemierre’s syndrome.
Enter the Centor
After consideration of strep pharyngitis mimics and deciding that GAS is a likely cause, a scoring system called the Centor criteria can be used to help determine the utility of rapid streptococcal antigen testing and empiric treatment of symptoms. The Centor Criteria is a four-point scoring system used to assist with risk stratification for GAS pharyngitis and clinical decision making. The four components of the Centor Criteria are: fever, tonsillar exudate, anterior cervical lymphadenopathy, and absence of cough. The Centor Criteria was originally validated in patients 15 years of age and older. The McIsaac Criteria, which is also referred to as the modified Centor criteria, uses the same four clinical features, but also provides an age adjustment to the final score and can be used in patients 3 years of age and older.
There is some disagreement between clinical guidelines as the to ideal management of patients with modified Centor criteria scores. It is widely agreed upon that patients with low criteria scores should not undergo treatment or testing. Patients with mid-range scores should undergo rapid antigen detection testing (RADT). The sensitivity of rapid antigen detection testing is subject to a phenomenon called spectrum bias, where the sensitivity of the RADT is affected by the patient’s modified Centor score. Rapid antigen detection testing sensitivity ranges from 61% in patients with modified Centor scores of 0-1 to 97% in patients with modified Centor scores of 4 (3). Spectrum bias in RADT testing for GAS pharyngitis is thought to be related to varying size of the streptococcal inoculum in patients presenting with varying modified Centor scores. Patients with higher modified Centor scores are likely to harbor a greater inoculum of GAS bacteria and therefore may be more likely to be identified on RADT (3).
Patients with high modified Centor scores present some controversy in their clinical management. Conflicting guidelines suggest either RADT, or in some cases, empiric treatment without need for RADT. The American Academy of Pediatrics and the Infectious Disease Society of America guidelines do not recommend empiric treatment even in patients with high Modified Centor scores due to concern for antibiotic overuse. However, current CDC recommendation and clinical practice guidelines from the American College of Physicians/American Academy of Family Physicians support either testing or empiric treatment of patients with modified Centor scores greater than or equal to 3 (4). Because of these conflicting guidelines, the practitioner must use their clinical gestalt and other context factors to determine the best clinical course of action for patients with high modified Centor scores. Throat culture can be pursued in adults who are high risk including those with immunocompromise or a history of rheumatic fever, or in pediatric patients due to high pretest probability (5).
Treatment options, either empiric or after positive testing, include a single intramuscular injection of benzathine penicillin G, or a 10 day course of either amoxicillin or penicillin V. In the penicillin allergic patient, options for treatment include a 10 day course of cephalexin, clindamycin, or clarithromycin, or a 5 day course of azithromycin (6). Providers should reference their local antibiograms and consider patient likelihood of compliance and cost of therapy for the patient in choosing the appropriate antibiotic.
Carapetis, Jonathan R, et al. “The Global Burden of Group A Streptococcal Diseases.” The Lancet Infectious Diseases, vol. 5, no. 11, 2005, pp. 685–694., doi:10.1016/s1473-3099(05)70267-x.
Ebell, Mark H., et al. “Does This Patient Have Infectious Mononucleosis? The Rational Clinical Examination Systematic Review.” JAMA, vol. 315, no. 14, 2016, p. 1502., doi:10.1001/jama.2016.2111.
Dimatteo, Laura A., et al. “The Relationship between the Clinical Features of Pharyngitis and the Sensitivity of a Rapid Antigen Test: Evidence of Spectrum Bias.” Annals of Emergency Medicine, vol. 38, no. 6, 2001, pp. 648–652., doi:10.1067/mem.2001.119850.
Gottlieb, Michael, et al. “Clinical Mimics: An Emergency Medicine-Focused Review of Streptococcal Pharyngitis Mimics.” The Journal of Emergency Medicine, vol. 54, no. 5, 2018, pp. 619–629., doi:10.1016/j.jemermed.2018.01.031.
Hildreth, AF, et al. “Evidence-Based Evaluation and Management of Patients with Pharyngitis in the Emergency Department.” Emergency Medicine Practice, vol. 17, no. 9, Sept. 2015.
“Group A Streptococcal Disease.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 1 Nov. 2018, www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html.
Written by Stephanie Winslow, MD, PGY-1 University of Cincinnati Dept of Emergency Medicine
Editing and Posting by Jeffery Hill, MD MEd