Streptococcal Pharyngitis ("Strep Throat") Case File

Streptococcal Pharyngitis ("Strep Throat") Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 1

A 13-year-old adolescent boy presents to the emergency department with a chief complaint of sore throat and fever for 2 days. He reports that his younger sister has been ill for the past week with “the same thing.” The patient has pain with swallowing, but no change in voice, drooling, or neck stiffness. He denies any recent history of cough, rash, nausea, vomiting, or diarrhea. He denies any recent travel and has completed the full series of childhood immunizations. He has no other medical problems, takes no medications, and has no allergies.

On examination, the patient has a temperature of 38.5°C (101.3°F), a heart rate of 104 beats per minute, blood pressure 118/64 mm Hg, a respiratory rate of 18 breaths per minute, and an oxygen saturation of 99% on room air. His posterior oropharynx reveals erythema with tonsillar exudates without uvular deviation, or significant tonsillar swelling. Neck examination is supple without tenderness of the anterior lymph nodes. Chest and cardiovascular examination is unremarkable. His abdomen is soft and nontender with normal bowel sounds and no hepatosplenomegaly. Skin is without rash.

⯈ What is the most likely diagnosis?

⯈ What are the dangerous causes of sore throat you don’t want to miss?

⯈ What is your diagnostic plan?

⯈ What is your therapeutic plan?

ANSWERS TO CASE 1:

Streptococcal Pharyngitis (“Strep Throat”)

Summary: This is a 13-year-old adolescent boy with pharyngitis. He has fever, tonsillar exudate, no cough, and no tender cervical adenopathy. There is no evidence of airway involvement.

• • Most likely diagnosis: Streptococcal pharyngitis.
• • Dangerous causes of sore throat: Epiglottitis, peritonsillar abscess, retropharyngeal abscess, Ludwig angina.
• • Diagnostic plan: Use Centor criteria to determine probability of bacterial pharyngitis and rapid antigen testing when appropriate.
• • Therapeutic plan: Evaluate the patient for need of antibiotics versus supportive care.

ANALYSIS

Objectives

1. Recognize the different etiologies of pharyngitis, paying close attention to those that are potentially life-threatening.
2. Be familiar with widely accepted decision-making strategies for the diagnosis and management of group A β-hemolytic streptococcal (GABS) pharyngitis.
3. Learn the treatment of GABS pharyngitis and understand the sequelae of this disease.
4. Recognize acute airway emergencies associated with upper airway infections.

Considerations

This 13-year-old patient presents with a common diagnostic dilemma: sore throat and fever. The first priority for the physician is to assess whether the patient is more ill than the complaint would indicate: stridorous breathing, air hunger, toxic appearance, or drooling with inability to swallow would indicate impending disaster. The ABCs (airway, breathing, circulation) must always be addressed first. This patient does not have those types of “alarms.” Thus a more relaxed elicitation of his history can take place, and examination of the head, neck, and throat can be performed. In instances suggestive of epiglottitis such as stridor, drooling, and toxic appearance, examination of the throat (especially with a tongue blade) may cause upper airway obstruction in children, leading to respiratory failure. During the examination, the clinician should be alert for complications of upper airway infection; however, this patient presents with a simple pharyngitis.

Overall the most common etiology of pharyngitis is viral organisms. This teenager has several features that make group A streptococcus more likely: age less than 15 years, fever, absence of cough, and the presence of tonsillar exudate. Of note, the patient does not have “tender anterior cervical adenopathy.” The diagnosis of group A streptococcal pharyngitis can be made clinically or with the aid of rapid antigen testing. Rapid streptococcal antigen testing can give a fairly accurate result immediately and treatment or nontreatment with penicillin can be based on this result. If the rapid streptococcal antigen test is positive, antibiotic therapy should be given; if the rapid test is negative, throat culture should be performed and antibiotics should be withheld. The gold standard for diagnosis is bacterial culture, and if positive, the patient should be notified and given penicillin therapy.

APPROACH TO:

Pharyngitis

CLINICAL APPROACH

The differential diagnosis of pharyngitis is broad and includes viral etiologies (rhinovirus, coronavirus, adenovirus, herpes simplex virus [HSV], influenza, parainfluenza, Epstein-Barr virus [EBV], and CMV [cytomegalovirus] [causing infectious mononucleosis], coxsackievirus [causing herpangina], and the human immunodeficiency virus [HIV]), bacterial causes (GABS, group C streptococci, Arcanobacterium haemolyticum, meningococcal, gonococcal, diphteritic, chlamydial, Legionella, and Mycoplasma species), specific anatomically related conditions caused by bacterial organisms (peritonsillar abscess, epiglottitis, retropharyngeal abscess, Vincent angina, and Ludwig angina), candidal pharyngitis, aphthous stomatitis, thyroiditis, and bullous erythema multiforme. Viruses are the most common cause of pharyngitis.

Group A streptococcus causes pharyngitis in 5% to 10% of adults and 15% to 30% of children who seek medical care with the complaint of sore throat. It is often clinically indistinguishable from other etiologies, yet it is the major treatable cause of pharyngitis. Primary HIV infection may also cause acute pharyngitis, and its recognition can be beneficial because early antiretroviral therapy can be started. Infectious mononucleosis is also important to exclude because of the risk of splenomegaly and splenic rupture. Other bacterial etiologies may also be treated with antibiotics. Studies suggest that certain symptoms and historical features are suggestive of streptococcal pharyngitis and may help guide the provider in generating a reasonable pretest probability of GABS. The Centor criteria, modified by age risk, is helpful in assessing for GABS (Table 1–1).

Of note, recent epidemiologic data suggest Fusobacterium necrophorum causes pharyngitis at a rate similar to GABS in young adults and if not treated is implicated in causing Lemierre syndrome, a life-threatening suppurative complication.

Throat cultures remain the gold standard for the diagnosis of GABS pharyngitis, but they have several limitations in use for daily practice. False-negative throat cultures may occur in patients with few organisms in their pharynx or as a result of inadequate sampling (improper swabbing method, errors in incubation or reading of plates). False-positive throat cultures may occur in individuals who are asymptomatic carriers of GABS. Throat cultures are costly and, perhaps more importantly, require 24 to 48 hours for results. Although it may be reasonable to delay therapy for

^aModifications to the original Centor criteria. See interpretation of the score in text.

Centor RM, Witherspoon JM, Dalton HP, et al. The diagnosis of strep throat in adults in the emergency room. Med Decis Making. 1981;1:239-246; and McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):75-83.

this period of time (delay will not increase likelihood of development of rheumatic fever), it requires further communication with the patient and perhaps an uncomfortable latency in therapy from the concerned parent. Nevertheless, a negative throat culture may prompt discontinuation of antibiotics.

The rapid-antigen test (RAT) for GABS, despite having some limitations, has been embraced by many experts and incorporated into diagnostic algorithms. The RAT is 80% to 90% sensitive and exceedingly specific when compared to throat cultures. Results are point-of-care and available in minutes. Many experts recommend confirmation of negative RAT with throat culture. Individuals with positive RAT results should be treated. Newer technologies, such as the optical immunoassay, may prove to be as sensitive as throat cultures while providing results within minutes; its cost-effectiveness has not been established.

If RAT is available, then one accepted algorithm is given in Figure 1–1.

Figure 1–1. Algorithm for Centor criteria.

• Patients with 4 points from the Centor and/or McIsaac criteria should be empirically treated, because their pretest probability is reasonably high (although this practice may result in overtreatment in as many as 50% of patients).
• Patients with 0 or 1 points should not receive antibiotics or diagnostic tests (the criteria have been shown here to yield a negative predictive value of roughly 80%).
• Patients with 2 or 3 points should have RAT and those with positive RAT results should be treated. Negative RAT results should withhold antibiotics be followed with a throat culture.

If RAT is unavailable, then one accepted algorithm is given in Figure 1–2.

• Patients with 3 or 4 points should be empirically treated with antibiotics.
• Patients with 0 or 1 point should not receive antibiotics or diagnostic tests.
• Patients with 2 points should not receive antibiotics. The possible exceptions to this 2-point rule are in the setting of a GABS outbreak, patient contact with many children, an immunocompromised patient, or a patient with recent exposure to someone with confirmed GABS.

Of note, antibiotic therapy in GABS pharyngitis has been de-emphasized because complications have become increasingly rare and the data to support the efficacy of antibiotic therapy in prevention of these complications is sparse and many decades old.

The complications of GABS can be classified into nonsuppurative and suppurative processes. The nonsuppurative complications of GABS pharyngitis include

^aConsider antibiotics if in setting of GAβS outbreak,

patient had contact with many children, is

immunocompromised, or recent exposure to a patient

with documented GAβS.

Figure 1–2. Algorithm when RAT unavailable.

rheumatic fever, streptococcal toxic shock syndrome, poststreptococcal glomerulonephritis, and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with group A streptococci). Rheumatic fever is now rare in the United States (an incidence of <1 case per 100,000), and is thought to be caused by only a handful of strains of GABS. Despite its rarity, rheumatic fever can result in highly morbid cardiac and neurological sequela; it also remains the most common cause of acquired heart disease in children and adolescents in some developing countries. Published literature suggests the GABS number needed to treat (NNT) to prevent one case of rheumatic fever is between 53 and thousands depending on the endemic incidence of rheumatic fever. Streptococcal toxic shock syndrome is a very rare complication of pharyngitis. Poststreptococcal glomerulonephritis, another feared complication of GABS pharyngitis, is also very rare, and it occurs with equal frequency in both antibiotic- treated and nonantibiotic-treated groups. It is unclear if antibiotic therapy reduces the incidence of PANDAS, which is a clinical entity in development and presents with episodes of obsessive-compulsive behavior.

Prevention of the suppurative complications of GABS pharyngitis remains perhaps the most compelling reason for antibiotic therapy. These processes include tonsillopharyngeal cellulitis, peritonsillar and retropharyngeal abscesses, sinusitis, meningitis, brain abscess, and streptococcal bacteremia. The precise incidence of these complications is unclear, but what remains clear is that these are often preventable sequela that can have devastating consequences. Ultimately, the current practice is to treat suspected GABS pharyngitis with an appropriate antibiotic.

Treatment of GABS

Penicillin is the antibiotic of choice for GABS pharyngitis. A Cochrane review of the literature concluded that penicillin is the first choice antibiotic in patients with acute throat infections. The antibiotic is inexpensive, well-tolerated, and has a reasonably narrow spectrum. Oral therapy requires a 10-day course, although multiple daily doses for this duration may pose an issue with respect to compliance; penicillin V500-mg bid dosing for 10 days in adults (as opposed to 250 mg tid or qid) is a reasonable alternative. For patients in whom compliance may be a significant issue, a single

IM shot of 600,000 units of penicillin G benzathine in patients weighing <27 kg (1.2 million units if patient weighs >27 kg) is another option, although it requires an uncomfortable injection and, more significantly, it cannot be reversed or discontinued should an adverse reaction occur. All patients, regardless of final diagnosis, should be given adequate analgesia and reassurance. It has been shown that individuals who are perceived to want antibiotics may ultimately just want pain relief.

While somewhat controversial, some physicians recommend steroids as an anti-inflammatory

agent to decrease the pain and swelling associated with GABS. A meta-analysis of over a thousand patients showed improvement 4.5 hours faster with steroids compared to placebo with a minimal reduction in pain scores. If clinically indicated, the standard agent is dexamethasone 0.6 mg/kg up to 10 mg PO or IM.

Airway Complications

There are several life-threatening causes of sore throat. Patients may suffer airway obstruction from acute epiglottitis, peritonsillar abscess, retropharyngeal abscess, and Ludwig angina (Table 1–2); although less frequent, airway compromise may also occur with Vincent angina and diphtheria pharyngitis; the latter requires prompt diagnosis and treatment to avoid spread of this highly infectious condition. Management of the airway in these conditions (see Table I–2 in Section I) sometimes necessitates emergency cricothyroidotomy (Figure 1–3), because the pharynx and larynx may be edematous, distorted, or inflamed. Prompt identification of acute retroviral syndrome from recent HIV infection can allow for rapid antiretroviral therapy. Infectious mononucleosis should be identified so that potentially serious sequela can be considered. These complications include splenomegaly that predisposes the patient to traumatic rupture of the spleen with relatively minor trauma; additionally, this splenomegaly can cause splenic sequestration and thrombocytopenia.

Figure 1–3. Anatomy of the neck for emergency cricothyroidotomy. Note the location of the thyroid and cricoid cartilages.

COMPREHENSION QUESTIONS

1.1 A 48-year-old man is noted to have a 2-day history of sore throat, subjective fever at home, and no medical illnesses. He denies cough or nausea. On examination, his temperature is 38.3°C (101°F), and he has some tonsillar swelling but no exudate. He has bilateral enlarged and tender lymph nodes of the neck. The rapid streptococcal antigen test is negative. Which of the following is the best next step?

A. Oral clindamycin

B. Treatment based on results from throat culture

C. Observation

D. Begin amantadine

1.2 Which of the following patients is most likely to have group A streptococcal infection?

A. An 11-month-old male infant with fever and red throat

B. An 8-year-old girl with fever and sore throat

C. A 27-year-old man with a temperature of 38.9°C (102°F), pharyngitis, and cough

D. A 52-year-old woman who complains of fever of 39.2°C (102.5°F) and sore throat

1.3 A 19-year-old college student has had a sore throat, mild abdominal pain, and fever for 5 days. He was playing football with some friends, and was tackled just short of the goal line, hitting the grass somewhat forcibly. He experiences some abdominal pain, and passes out. The EMS (emergency medical services) is called and his vital signs reveal the heart rate as 140 beats per minute and blood pressure as 80/40 mm Hg with a distended abdomen. Which of the following is the most likely etiology?

A. Vasovagal reaction

B. Ruptured aortic aneurysm

C. Complications of Epstein-Barr infection

D. Ruptured jejunum

1.4 An 18-year-old woman presents with fever and a sore throat. She is sitting up drooling, with some stridor. Her temperature is 39.4°C (103°F) and she appears ill. Which of the following is your next step?

A. Examine the pharynx and obtain a rapid antigen test.

B. Empiric treatment with penicillin.

C. Throat culture and treatment based on results.

D. Send the patient to radiology for an anteroposterior (AP) neck radiograph.

E. Prepare for emergent airway management.

ANSWERS

1.1 B. This individual has a modified Centor score of 2 (history of fever, tender adenopathy, no cough, age >45 y). The rapid antigen test is negative, but a definitive culture should be performed for a Centor score of 2 or 3, and treatment should be based on culture results.

1.2 B. GABS is most common in patients younger than 15 years (although not in infants). McIsaac added age as a criteria because patients older than age 45 years have a much lower incidence of streptococcal pharyngitis.

1.3 C. This patient most likely suffered from splenic rupture caused by mononucleosis (EBV). He is hypotensive because of the massive hemoperitoneum. Aortic aneurysm is rare in teenagers.

1.4 E. Regardless of the etiology, this patient has a clinical presentation alarming for impending respiratory collapse, and preparations for emergent airway management is the most important next step. The drooling and stridor are suspicious for epiglottitis, which can present more insidiously in adults. Examination of the posterior oropharynx may induce laryngospasm and airway obstruction, particularly in children; a lateral neck radiograph to assess for a “thumbprinting” of epiglottitis may be helpful in making the diagnosis, but sending the patient with impending respiratory failure to radiology area is inappropriate.

CLINICAL PEARLS

⯈ The most common cause of pharyngitis is viral.

⯈ The Centor criteria suggestive of GABS pharyngitis include tonsillar exudate, tender anterior cervical adenopathy, history of fever, and absence of cough.

⯈ GABS pharyngitis is more common in patients younger than 15 years of age, and less common in those older than 45 years of age.

⯈ Overtreatment of pharyngitis with antibiotics is common and is a major source of antibiotic overuse.

⯈ Glomerulonephritis is a rare complication of GABS pharyngitis (but not GABS infections of other tissues) that is not clearly prevented by antibiotic therapy.

⯈ Rheumatic fever is an exceedingly rare complication of GABS pharyngitis that can be prevented by antibiotic therapy.

⯈ Complicated upper airway conditions should be considered when a patient presents with “sore throat.”

⯈ In general, cricothyroidotomy is the safest method of surgically securing an airway in the ED.

References

Bisno AL. Acute pharyngitis. N Engl J Med. 2001;344(3):205-211. 

Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group a streptococcal pharyngitis. Clin Infect Dis. 2002;35:113-125. 

Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making. 1981;1:239-246. 

Centor RM. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med. 2009; 151(11):812-815. 

Cooper RJ, Hoffman JR, Bartlett, JG, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001;134:509-517. 

Lee JL, Naguwa SM, Cesma GS, Gerhwin ME. Acute rheumatic fever and its consequences: A persistent threat to developing nations in the 21st century. Autoimmunity Reviews. 2009;9:117-123. 

Linder JA, Chan JC, Bates DW et al. Evaluation and treatment of pharyngitis in primary care: the difference between guidelines is largely academic. Arch Intern Med. 2006; 166:1374. 

McIsaac WJ, Kellner JD, Aufricht P, et al. Empiric validation of guidelines for the management of pharyngitis in children and adults. JAMA. 2004;291(13):1587. 

McIssac WJ, Goel V, To T, Low DE. The validity of a sore throat score in family practice. CMAJ. 2000;163(7):811-815. 

McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):75-83. 

Snow V, Mottur-Pison C, Cooper RJ, Hoffman, JR. Principles of appropriate antibiotic use for acute pharyngitis in adults. Ann Intern Med. 2001;134:506-508. 

Van Driel ML, Sutter AD, Deveugele M, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief. Ann Fam Med. 2006;4(6):494. 

Van Driel ML, De Sutter AI, Keber N, et al. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database of Systematic Reviews 2010;10. Art. No.:CD004406. DOI: 10.1002/ 14651858.CD004406.pub2. 

Wing A, Villa-Roel C, Yeh B, et al. Effectiveness of corticosteroid treatment in acute pharyngitis: A systematic review of the literature. Acad Emer Med. 2010;17:476-483.

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