Strep Throat Mimics: Pearls & Pitfalls

Authors: Margaret Krebs, MD (EM Resident Physician, The Ohio State University Wexner Medical Center) and Mark J Conroy, MD (Assistant Professor of Emergency Medicine, The Ohio State University Wexner Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC)

Clinical case

A 19 year-old local college student presents to the emergency department for sore throat and several associated complaints one week after getting back from his holiday break. The onset was 4 or 5 days ago, and he has been feeling progressively worse each day.  Additional symptoms include anorexia, myalgia, mild headache, and subjective fevers.  He reports a mild cough that isn’t consistent, and he doesn’t feel short of breath.  He has tried ibuprofen and acetaminophen for his symptoms without much relief. He doesn’t know of anyone else around him who is sick and has had one or two cases of strep throat in the past that he believes were treated with antibiotics. He still has his tonsils and is convinced this feels just like his last case of strep throat 2 years ago. His POC rapid strep antigen test was negative in triage.

Background

We’ve all seen a patient similar to the one above before, probably several during a shift sometimes depending on the time of year.  While the patient suspects bacterial pharyngitis and may or may not expect an antibiotic prescription, there are several other key diagnoses to keep in mind when evaluating these patients.

Pharyngitis, an acute inflammation of the mucous membranes of the oropharynx, accounts for a large number of Emergency Department and Urgent Care visits each year.  While most cases of pharyngitis are viral in etiology, the most common organism to cause bacterial pharyngitis is Group A B-hemolytic streptococcus (GABHS), or strep throat.  Not insignificant, GABHS is responsible for 15-30% of cases of pharyngitis in children.¹

H&P

Bacterial pharyngitis is typically found in patients 5-15 years old and rarely affects patients younger than 2 years. It is typified by sore throat, fever greater than 100.4°F (38°C) and cervical lymphadenopathy. 2 Headache, nausea and vomiting, and abdominal pain may be present. Upon examination, patients typically have tonsillo-pharyngeal erythema with or without tonsillar exudate. Erythema of the uvula may also commonly be seen.¹ Palatal petechiae and scarlatiniform rash are specific for bacteria pharyngitis but uncommon findings.²

Differentiating between bacterial and viral pharyngitis is important for every emergency physician in order to be good antibiotic stewards.  The modified Centor score is one system that can be used by physicians to aid in bacterial pharyngitis diagnosis.  Patients are awarded one point for each of the following conditions:
(1) age 3-14 years
(2) tonsillar exudates or swelling
(3) tender anterior cervical adenopathy
(4) absence of cough
(5) history of fever

With a score of 0-1, the risk of strep throat is ≤10% and no further testing is indicated. A score of 2 or greater, testing via rapid antigen testing or culture is indicated.² In the past, patients with a high Centor score were recommended to have empiric antibiotic treatment but a 2012 update of the Infectious Disease Society no longer recommend empiric antibiotics in patients without a positive rapid antigen test or throat culture.³ Throat culture is only recommended in cases of a negative rapid antigen test.  Oral penicillin V 500 mg two times a day for 10 days remains the first line treatment for strep throat.²

 Mimics

While there is a large focus on diagnosing and managing strep pharyngitis, several other disease processes can present in a similar fashion and are important for an emergency physician to recognize.  Timely and appropriate recognition can hopefully prevent missed life threatening diagnoses, minimize testing, reduce visit times, and reduce antibiotic use.

Viral pharyngitis

The majority of cases of acute pharyngitis are caused by viral illnesses. The three most common viral agents are rhinovirus, coronavirus, and adenovirus, but there are several others as discussed below.⁴  Symptoms of cough, conjunctivitis, coryza, and diarrhea are more common with viral pharyngitis than with bacterial causes of pharyngitis.² Symptoms such as trismus, muffled voice, limited range of motion of the neck and difficulty managing secretions should prompt consideration of alternate diagnoses. Physical exam findings of palatal petechiae and vesicles are common with viral illnesses whereas tonsillar exudate and cervical adenopathy are more commonly found with strep pharyngitis. As with all viral infections, treatment is generally supportive.²

Infectious mononucleosis

While mononucleosis is a viral infection it deserves its own category due to some unique features of its diagnosis.  Symptoms are caused by Epstein-Barr virus infection.  Symptoms often begin with malaise, headache, and fever before the development of exudative pharyngitis. Posterior cervical chain lymphadenopathy is also typical. Patients should be carefully examined for hepato- or splenomegaly, but this does not require any advanced imaging unless the patient is complaining of abdominal pain and has a confirmed diagnosis. Patients mistakenly treated for bacterial pharyngitis with amoxicillin or ampicillin may develop a characteristic pruritic, maculopapular rash.⁵  The Monospot test (heterophile antibody) typically does not turn positive until symptoms have been present for one week or more. Cytomegalovirus (CMV) infection is often clinically identical, and monospot negative patients with a similar constellation of symptoms are often infected with CMV.⁶

Kawasaki disease

While we have been focused on adults, pediatric patients can have pharyngitis mimics that are important to keep in mind. Kawasaki disease is an acute vasculitis of unknown etiology that most commonly affects children ages less than 5 years.  While pharyngitis is not one of the primary features of the disease, symptoms such as conjunctivitis and cervical lymphadenopathy may be confused for a simple viral infection.  Recognition is vital in these patients given 15-25% of untreated children develop coronary artery aneurysms which may lead to ischemic heart disease or sudden death. The disease is characterized by fever lasting at least 5 days in duration plus the following principal clinical features:

• conjunctivitis
• cervical lymphadenopathy
• erythema of the lips and oral mucosa
• skin changes of the extremities
• rash

As may be expected, these children are often extremely fussy.^7,8 Once the presence of Kawasaki disease is suspected the patient should be admitted for treatment with high dose aspirin and IVIG.⁶  Because of its potential devastating sequelae, it is important that the ED physician keep a high index of suspicion for Kawasaki disease in a child less than 5 years with 5 days or more of fever.

 Peritonsillar abscess

Peritonsillar abscesses are polymicrobial infections that cause a collection of purulent material between the tonsillar capsule and the muscles of the posterior pharynx. They most commonly occur in young adults, and risk factors include poor dentition and smoking. Signs include muffled voice and trismus. Physical exam will reveal inferior displacement of the affected tonsil and contralateral deflection of the uvula.⁶  Point of care ultrasound scans can help distinguish peritonsillar abscess from simple tonsillitis.⁹  Treatment options include needle aspiration, incision and drainage, and occasionally emergent tonsillectomy.

Retropharyngeal Abscess

Retropharyngeal abscesses (RPA) occur in the space between the posterior pharyngeal wall and the pre-vertebral fascia.⁶ They occur much more commonly in children than in adults, usually after a mild upper respiratory infection but may also be secondary to accidental posterior pharynx trauma. Similar to peritonsillar abscesses, patients will often endorse odynophagia, muffled voice, and trismus. Physical exam may reveal swelling of the posterior pharynx wall, but this is often difficult to appreciate, especially in pediatric patients with severe trismus. Maintaining a high suspicion in patients with a complicated sore throat is important to avoid missing the diagnosis. Traditionally, lateral neck radiographs have been used to look for widening of the tissue anterior to the cervical vertebrae to evaluate for RPA, but CT scan of the neck is now preferred.¹⁰   

Ludwig’s Angina

Ludwig’s angina is a rapidly spreading, necrotizing soft tissue infection of the submandibular space. The most common cause of Ludwig’s angina is dental disease.¹⁰ Patient’s will typically complain of mouth and neck pain, sore throat, and odynophagia. Inability to swallow secretions may also be seen.⁶ Physical exam often finds a patient that appears toxic and anxious. The submandibular area is swollen and tense, the skin under the chin and the mucosa of the floor of the mouth is erythematous and tender, and the tongue itself may be swollen. CT scanning may be helpful diagnostically to characterize the extent of infection, but advanced imaging should be obtained with caution in a patient without a definitive airway established due to potential for rapid airway compromise. Patient’s with suspected Ludwig’s angina should be evaluated by an otolaryngologist, admitted to the intensive care unit for close observation, and treated with broad-spectrum antibiotics targeting gram positive, gram negative, and anaerobic bacteria.¹¹

 Lemierre Syndrome

Lemierre syndrome is a rare disease that begins as a bacterial oropharyngeal infection (most commonly pharyngitis or tonsillitis) which then spreads to the retropharyngeal space, ultimately causing thrombophlebitis of the internal jugular vein leading to bacteremia and septic emboli. Affected individuals are more commonly young, healthy, and male. The most common causative agent is Fusobacterium necrophorum, an anaerobic, gram-negative bacteria commonly found in the mouth. Presenting patients usually report symptoms typical of tonsillitis or pharyngitis initially, but as the internal jugular vein becomes involved, worsening pain and unilateral swelling of the angle of the jaw and along the sternocleidomastoid will develop. Trismus is also common. If Lemierre syndrome is suspected, CT imaging with IV contrast should be obtained to evaluate for evidence of internal jugular vein thrombosis. Recommended antibiotic treatment options include penicillin in combination with metronidazole or monotherapy with clindamycin.¹²

Epiglottitis

Epiglottitis is a cellulitis of the supraglottic structures including the epiglottis and uvula. Although widespread immunization against Haemophilus influenza has decreased the incidence of epiglottitis, cases do still occur, now more commonly caused by group A strep. Both children and adults can be affected, with children generally having a more fulminant course and a higher risk of airway compromise. Affected patients exhibit high fever and severe odynophagia. Classically, affected patients present in the “tripod” position with a protruding tongue and drooling. Muffled voice and inspiratory stridor may also be seen. Affected adults do endorse severe sore throat and muffled voice but less commonly exhibit stridor and respiratory distress. Diagnosis is primarily clinical but a lateral neck radiograph may show the classic “thumbprint sign” of an edematous epiglottis.¹³ Airway obstruction can occur rapidly and equipment for both endotracheal intubation and cricothyrotomy should be immediately available. Affected patients should be admitted for close monitoring of their airway. Treatment includes antibiotics, steroids, and nebulized epinephrine.¹⁰

Pearls

• Infectious Disease Society guidelines no longer recommend empiric antibiotics for treatment of strep in patients without a positive rapid antigen test or throat culture.
• Symptoms of cough, conjunctivitis, coryza, and diarrhea are more common with viral pharyngitis than with bacterial causes of pharyngitis.
• Posterior cervical chain lymphadenopathy is typical for mononucleosis.
• Because of its potential devastating sequelae, it is important that the ED physician keep a high index of suspicion for Kawasaki disease in a child less than 5 years with 5 days or more of fever.
• Point of care ultrasound scans can help distinguish peritonsillar abscess from simple tonsillitis.
• Trismus, muffled voice, decreased neck range of motion should prompt consideration of deep neck space infections (peritonsillar abscess, retropharyngeal abscess, Ludwig’s angina and Lemierre’s syndrome) and CT imaging should be considered.
• A toxic appearing child in the tripod position should prompt consideration of epiglottitis.

References / Further Reading

1. Gerber M. Diagnosis and Treatment of Pharyngitis in Children. Pediatr Clin N Am. 2005; 52: 729-747.
2. Choby B. Diagnosis and Treatment of Streptococcal Pharyngitis. Am Fam Physician. 2009; 79(5): 383-390.
3. Sulman S, Bisno A, Clegg H 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(10): e91.
4. Neumar J, Hamel M, Phillips R, Bona K and Aronson M. Diagnosis and Management of Adults with Pharyngitis: A Cost-Effectiveness Analysis. Ann Intern Med. 2003; 139(2): 113-127.
5. Dunmire S, Hogquist K and Balfour H. Infectious Mononucleosis. Curr Top Microbiol Immunol. 2015; 390: 211-240.
6. Tintinalli J, et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8^th Edition. McGraw-Hill, 2015.
7. Newburger J, Takahashi M, Gerber M, et al. Diagnosis, Treatment and Long-Term Management of Kawasaki Disease. Pediatrics. 2004: 114(6):1708-1733.
8. Uehara R, Belay E. Epidemiology of Kawasaki Disease in Asia, Europe and the United States. J Epidemiol. 2012; 22(7): 79-85.
9. Secko M, Sivitz A. Think ultrasound first for peritonsillar swelling. Am J Emerg Med. 2015; 33: 569-572.
10. Stewart, C. “Killer” Sore Throat: Prompt Detection and Management of Serious and Potentially Life-Threatening Causes of Pharyngeal Pain. Emerg Med Reports. 2001; 22(10): 103-118.
11. Costain N. Ludwig’s Angina. Am J Med. 2011; 124(2): 115-117.
12. Ridgway J, Parikh D, Wright R, et al. Lemierre syndrome: a pediatric case series and review of literature. Am J Otolaryngol Head Neck Med Surg. 2010; 31: 38-45.
13. Lichtor J, Rodriguez M, Aaronson N, et al. Epiglottitis: It Hasn’t Gone Away. Anesthesiology. 2016; 124: 1404-1407.