A 21-year-old male presents for a sore throat. His symptoms started 3 days ago. He has had subjective fevers, sweats, fatigue, and mild nausea. He has no cough or rhinorrhea. His temperature is 38.3°C. His vital signs are normal otherwise. He has symmetrically enlarged tonsils with exudates present and tender anterior cervical lymphadenopathy.
Question 20.11.1 At this point, you:
A) Reassure and recommend saltwater gargles
B) Obtain a routine aerobic culture of the oropharynx
C) Prescribe penicillin 500 mg BID for 10 days
D) Prescribe levofloxacin 500 mg daily for 7 days
Answer 20.11.1 The correct answer is "C." This patient has 4 of 4 signs/symptoms suggestive of streptococcal (group A strep or Streptococcus pyogenes) pharyngitis. These are the "Centor criteria": (1) fever, (2) tender cervical adenopathy, (3) exudative pharyngitis, and (4) lack of other URI symptoms. In this case, the most appropriate step would be empiric antimicrobial treatment. "B," performing a culture, will take a few days and does not add much, given the strength of the clinical argument for strep throat. Furthermore, the oropharynx is colonized by many kinds of flora that do not cause disease, and we only really care about group A streptococcus, so a routine aerobic culture is of no value. Alternatively, a rapid assay or a specific "rule out" culture for group A strep could be done rather than treating based on clinical grounds (the rapid strep has a 5% false negative rate). While saltwater gargles seem to help reduce the pain of pharyngitis, "A" is incorrect because you would want to do more than that for this patient who likely has strep throat. "D" is incorrect because levofloxacin and other fluoroquinolones are not indicated for treatment of strep throat.
Here are three strategies for the patient you think might have strep throat:
Strategy 1: No testing (or minimal testing)
In this strategy, one treats based on clinical symptoms. You are looking for four things: fever, exudate, absence of other URI symptoms, and tender anterior cervical adenopathy. Treat patients with 3 or 4 criteria, and do not treat others. Another approach is to treat patients with 4 criteria, do a rapid strep test on those with 3 (and maybe 2) criteria, and avoid treatment and testing of others. The CDC has recommended this for nonimmunosuppressed patients in the absence of an outbreak of rheumatic fever in the community.
Test all patients and treat those with a positive strep screen. Do not culture others.
The majority of group A strep pharyngitis occurs in children between ages 5 and 15 years. In this age group, 15% to 30% of acute pharyngitis is caused by group A strep. In children, doing a rapid strep test is considered the standard (although many argue convincingly that it is not even necessary here in the older child). Cultures are again optional depending on the reliability of your rapid antigen test. Many would culture all rapid strep test negative patients and this is certainly an acceptable strategy as well.
So, now you are quite confused. So is everyone else …
Question 20.11.2 Which of the following is true about antibiotic therapy of streptococcal pharyngitis?
A) Azithromycin is the drug of choice because of resistant streptococci
B) There is no significant resistance seen in Group A β-hemolytic streptococci, and penicillin is still the drug of choice
C) Cephalexin is the preferred drug because it covers H. influenzae, which is a frequent coinfector with streptococci
D) Amoxicillin is preferred for strep throat because it does not cause a rash if the patient happens to have mononucleosis
Answer 20.11.2 The correct answer is "B." There is no significant resistance among group A β-hemolytic streptococci to penicillin. Thus, penicillin remains the drug of choice despite drug detailing. There is no reason to use anything else, except in the case of allergy where erythromycin or cephalexin can be used. Remember that there is now resistance to erythromycin, azithromycin, and clarithromycin. "D" is important. Amoxicillin can cause an uncomfortable rash should your patient turn out to have mononucleiosis rather than strep throat.
Penicillin VK can be used BID in streptococcal pharyngitis, and this administration frequency increases compliance.
Question 20.11.3 Antibiotics should be started within what time period to reduce the risk of rheumatic fever from streptococcal pharyngitis?
A) 2 days after presentation
B) 2 to 4 days after presentation
C) 4 to 6 days after presentation
D) 6 to 8 days after presentation
E) 8 to 10 days after presentation
Answer 20.11.3 The correct answer is "E." Antibiotics should be started within 9 days after presentation in order to prevent rheumatic fever, which is really our goal when we treat streptococcal pharyngitis. Thus, there really is no reason to hurry treatment.
Your patient is a student teacher and wants to know how long to stay out of the classroom.
Question 20.11.4 A patient with streptococcal pharyngitis should be considered infectious and kept out of school for what period after beginning antibiotics?
Answer 20.11.4 The correct answer is "B." Patients should be considered infectious for 24 hours after the initiation of therapy for streptococcal pharyngitis. The risk of transmission goes down markedly after this point. Unfortunately, the patient is actually infectious for the 3 to 5 days before they become symptomatic, so removing the patient for 24 hours after treatment is closing the barn door after the horses have left. Of course, since this is being written in Iowa, so we are closing the pen after the hogs have left. There is some preliminary data that it is OK to return to work/school 12 hours after starting treatment but this is not yet the standard of care (Pediatr Infect Dis J. 2015 Aug 20).
You see the same patient 3 weeks later. He took all of his penicillin even though he felt fine a few days after he left your office. (Wow! A compliant patient!) However, he now has the same symptoms, starting 2 days ago. His examination is the same.
Question 20.11.5 Which of the following is the most likely cause for his current symptoms?
A) Gonococcal pharyngitis
B) Infection with a resistant streptococcal organism
D) Staphylococcal pharyngitis
Answer 20.11.5 The correct answer is "E." Since his symptoms resolved, you either got the diagnosis and treatment right or he had some other self-limited infection. Therefore, it would be unlikely that he had gonococcal pharyngitis or resistant streptococcal organisms. Nonetheless, sexual history is important—even when confronted with pharyngitis; if a patient with exudative pharyngitis is not improving, think about gonococcal disease. Remember that gonococcal disease will be missed for two reasons in this scenario: the history is never obtained regarding oral sex and gonococcus requires Thayer-Martin agar to grow, so it will not show up on routine culture, and there are a lot of false negative cultures; consider PCR if thinking about gonococcal pharyngitis. "B," penicillin-resistant Streptococcus organisms causing pharyngitis, like the Tooth Fairy, are nonexistent. "C" is unlikely in this case because his symptoms resolved, but mononucleosis can cause prolonged symptoms of sore throat and fatigue and can be confused with strep throat. In this case, recurrent strep throat is most likely and he should be advised appropriately: retreat with penicillin, not a more broad-spectrum antibiotic; consider testing and/or treating cohabitants; have the patient replace his toothbrush.
Many causes of throat pain are acute infections (strep throat, other bacterial infections, viral pharyngitis, mononucleosis), but consider other noninfectious causes as well—carotidynia, viral thyroiditis, mouth-breathing, peritonsillar abscess. Non-group A streptococci (especially Streptococcus agalactiae, a group B strep) are increasingly being cultured from the pharynx. Streptococcus agalactiae can cause invasive disease and worth treating if found. It will respond to cephalexin or clindamycin (among others).
It's a "two for Tuesday" at your clinic. The next patient comes in for a sore throat and tender anterior and posterior cervical adenopathy. He is febrile and relatively stoic. He has been sick for 2 weeks with significant fatigue and just isn't getting better. In addition to the adenopathy, you notice left-sided abdominal tenderness with minimal guarding but no rebound tenderness. You believe that you feel a spleen edge. However, the patient's heterophile antibody (monospot) is negative. You decide to get anti-EBV (Epstein–Barr virus) antibodies. The results of the anti-EBV antibody test are as follows (VCA is against the capsid): IgM-VCA positive, IgG-VCA negative, anti-EBV nuclear antigen antibody negative.
Question 20.11.6 How do you interpret these results?
A) The patient has acute EBV infection
B) The patient has had EBV at least 6 weeks ago
C) The absence of anti-EBV nuclear antigen antibody makes acute infection highly unlikely
D) The patient has never been infected with EBV
Answer 20.11.6 The correct answer is "A." The patient has an EBV infection, starting in the last few weeks. Here is why. IgM-VCA is produced acutely and is elevated in the acute infection for 2 to 4 weeks. Since this patient's IgM-VCA is positive, he has had an acute EBV infection within the past month. IgG-VCA is measurable 3 to 4 weeks after acute infection and persists for life. Thus, it gives no information about when infection occurred. The absence of IgG-VCA means either (1) the patient has no history of EBV infection or (2) the patient has had a recent EBV infection. Antibodies against the EBV nuclear antigen show up at 6 to 12 weeks after infection. If this antibody is present in the blood, it suggests that there has not been an acute infection; the infection had to have been at least 6 weeks ago.
Question 20.11.7 Of the following, which DOES NOT cause a mononucleosis-like syndrome?
A) Human immunodeficiency virus (HIV)
Answer 20.11.7 The correct answer is "D." WNV is characterized by fever, headache, myalgias, back pain, and anorexia lasting 3 to 6 days. Much less common manifestations are nausea, vomiting, diarrhea, encephalitis, etc. Thus, WNV does not cause a mononucleosis-like syndrome because it does not last as long and rarely includes pharyngitis. One thing to note is that WNV may include lymphadenopathy. All the other answers can cause a mononucleosis-like syndrome. Other causes of mononucleosis-like syndromes include adenovirus, parvovirus B19 (erythema infectiosum), herpes virus 6 (roseola infantum), and ehrlichiosis (Asian form only). Remember these diagnoses in heterophile negative mono-like illness.
Depending on what population is studied, 1% to 2% of patients with a mononucleosis-like syndrome who are heterophile negative are HIV positive.
Question 20.11.8 There is some concern of splenic rupture in patients with mono who have splenomegaly. If splenomegaly were confirmed in this patient, what would be the generally accepted recommendation with regard to athletic participation (e.g., cage fighting)?
A) No participation until negative acute titers for EBV
B) No participation for 2 week after the diagnosis is made, assuming complete resolution of symptoms and then full participation
C) No participation until 3 weeks after the diagnosis is made, assuming complete resolution of symptoms and then only noncontact training for another week
D) Full practice and competition allowed immediately unless abdominal pain occurs
E) Full practice and competition immediately with body armor (e.g., Kevlar vest)
Answer 20.11.8 The correct answer is "C." It is generally thought that return to practice or noncontact training is safe 3 weeks after the diagnosis of mononucleosis, provided that all other symptoms have also resolved. If there are no clinical concerns for splenic enlargement at 4 weeks, then the athlete may be cleared to return to full competition. This recommendation is based on the observation that most cases of splenic rupture in athletes have occurred when those athletes returned to competition in less than 4 weeks from the time of diagnosis.
The patient returns 2 days later and is noting increased pharyngeal swelling and difficulty swallowing. You look into his throat and note "kissing tonsils." There is no stridor, but he feels as though there is something in his throat.
Question 20.11.9 What is the best treatment for this patient at this time?
Answer 20.11.9 The correct answer is "A." You may want to give steroids ("D"), but you will find little data to back you up. A Cochrane Collaboration Review updated in 2011 found insufficient evidence for steroids for symptom control in patients with mono. However, many physicians still prescribe steroids for patients with significant symptoms. Antibiotics are not indicated for mononucleosis. Tonsillectomy is also not indicated. The patient likely has paratracheal node swelling, as well. In this patient, hospital admission may be indicated if there is concern for airway obstruction.
Question 20.11.10 What is the approximate sensitivity of the heterophile antibody test ("monospot") for mononucleosis within the first 2 weeks of symptoms?
Answer 20.11.10 The correct answer is "D." The sensitivity of the monospot ranges from 60% to 80% 2 weeks into the illness. The point here is not the number per se but the fact that there are heterophile-negative mononucleosis syndromes and not everyone with EBV mononucleosis will have a positive monospot when tested. However, they should have atypical lymphocytes on WBC differential.
Consider peritonsillar abscess in a patient with a sore throat. There will generally be a muffled, "hot potato," voice, deviation of the uvula away from the side of the abscess, and protrusion of a tonsil toward midline. This may be an extension of a prior pharyngitis but may also arise de novo. Treatment is antibiotics and drainage (needling it is OK—no need for surgical involvement in all cases). It is also important to pay attention to the airway since there is the possibility of obstruction.
The monospot is not as sensitive in children. It will become positive in less than 40% of children younger than 5 years when they are infected with EBV. However, anti-EBV antibodies will be positive.
Arcanobacterium haemolyticum is a bacterium that causes pharyngitis especially in young adults (teens, early 20s). It clinically looks like strep throat but often has an associated rash especially on the arms (50% only). It does not cause long-term sequelae, so testing for it is not necessarily indicated (but it is cool to identify when the patient comes in with the appropriate rash!). If you choose to treat (which some practitioners do), it is generally sensitive to penicillins, cephalosporins, and tetracyclines.
Objectives: Did you learn to…
Describe different strategies to approaching the patient with symptoms of streptococcal pharyngitis?
Treat a patient with streptococcal pharyngitis and recurrent pharyngitis?
Develop a broad differential for sore throat?
Diagnose and treat mononucleosis?