30: Sore Throat

Sore throat is a common condition seen in outpatient clinical practice. This chapter focuses on patients that present with the acute onset of sore throat. Infectious diseases are the cause of acute sore throat in the overwhelming majority of patients. Patients with chronic sore throat, those who do not have signs of infection, or those who do not respond to treatment should be evaluated for noninfectious causes of sore throat.

A useful framework for the differential diagnosis of acute sore throat is shown below. This framework divides the diagnoses into those caused by infection (bacterial and viral) and those caused by noninfectious processes. Viral respiratory infections are the most common cause of infectious pharyngitis with the common cold caused by rhinoviruses and coronaviruses accounting for at least 25% of cases. Group A beta-hemolytic streptococcus (GABHS) is the most common cause of acute bacterial pharyngitis, accounting for 5–15% of sore throats in adults. Approximately 30% of cases of pharyngitis have no identifiable cause. Table 30-1 shows the differential diagnosis with the estimated percentage of cases of sore throat and the associated clinical syndrome.

1. Infectious causes of sore throat

   1. Viruses

      1. Rhinovirus

      2. Coronavirus

      3. Adenovirus

      4. Herpes simplex virus (HSV)1 and 2

      5. Influenza A and B

      6. Parainfluenza virus

      7. Epstein-Barr virus (EBV)

      8. Cytomegalovirus (CMV)

      9. Human herpesvirus (HHV) 6

      10. HIV

   2. Bacteria

      1. GABHS

      2. Group C beta-hemolytic streptococci

      3. Neisseria gonorrhoeae

      4. Corynebacterium diphtheriae

      5. Mycoplasma pneumoniae

      6. Chlamydophila pneumoniae

      7. Fusobacterium necrophorum

2. Noninfectious causes of sore throat

   1. Persistent cough

   2. Postnasal drip

   3. Gastroesophageal reflux disease (GERD)

   4. Acute thyroiditis

   5. Neoplasm

   6. Allergies

   7. Smoking

Clinically, the primary goal when seeing a patient with acute, probably infectious sore throat is to identify and treat patients with GABHS pharyngitis in order to prevent complications of acute rheumatic fever, acute glomerulonephritis, and suppurative sequelae. The secondary goal is to diagnose the less common infections (peritonsillar abscess) as well as the bacterial pathogens (N gonorrhoeae, F necrophorum) that need to be treated. In addition, diagnosing the nonbacterial pathogens, such as primary HIV, influenza A and B, and mononucleosis is important for both therapeutic and prognostic reasons. Pivotal points in the evaluation of these patients therefore include the presence of unilateral symptoms (suggesting abscess formation or fusobacterium infection), the presence of exudate (suggestive of GABHS or risk factors for sexually transmitted infections or HIV, or signs and symptoms of influenza or mononucleosis.

The pivotal points in Mr. W’s history include his sudden onset of sore throat, fever, and headache. These symptoms suggest an infectious cause of sore throat. The differential diagnosis includes bacterial pharyngitis, most commonly GABHS. The absence of cough, rhinorrhea, and coryza make the common viral causes of pharyngitis less likely. In general, patients with viral pharyngitis have cough, coryza, rhinorrhea, and hoarseness while those with bacterial pharyngitis or mononucleosis have fever, tender anterior cervical lymphadenopathy, tonsillar erythema with or without tonsillar swelling and exudates. They do not typically have rhinorrhea, cough, or conjunctivitis.

Influenza can cause fevers and throat pain but is usually associated with cough and myalgias. Infectious mononucleosis, which is most often caused by EBV, can also cause sore throat and fever but most often occurs in persons between the ages of 15 and 24 years and is associated with malaise and marked adenopathy. Primary HIV infection can present with nonspecific symptoms of pharyngitis, fever, adenopathy, and fatigue and should also be considered in high-risk persons. Table 30-2 lists the differential diagnosis for Mr. W.

Leading Hypothesis: GABHS pharyngitis

Textbook Presentation

The presenting symptoms and signs of GABHS pharyngitis include rapid onset of severe throat pain, moderate fever (39–40.5°C), malaise, and headaches. Examination of the throat reveals edema and erythema of the posterior pharynx and tonsils are often covered with gray-white exudates. The anterior cervical lymph nodes are tender. Gastrointestinal symptoms of nausea, vomiting, and abdominal pain may also be present, especially in children.

Disease Highlights

1. GABHS is generally suspected when fever and throat pain are present and cough, coryza, and rhinorrhea are absent.

2. Untreated GABHS typically lasts 8–10 days. Patients are infectious during the acute illness and for up to 1 week afterward.

3. GABHS infection is associated with 2 important postinfectious syndromes.

   1. Acute rheumatic fever

      1. Presents 1–5 weeks after throat infection

      2. Important findings are pancarditis, rash, subcutaneous nodules, chorea, or migratory polyarthritis

      3. Due to aggressive treatment of GABHS, this complication is uncommon in the developed world (but still common in developing nations). Annual incidence in the United States is 1/1,000,000 population.

   2. Acute post-streptococcal glomerulonephritis

      1. Presents 1–2 weeks after GABHS pharyngitis

      2. Important findings are edema, hematuria, proteinuria, and hypertension

Evidence-Based Diagnosis

1. Clinical diagnosis of GABHS pharyngitis

   1. Pretest probability

      1. The pretest probability of a patient having GABHS pharyngitis is based primarily on the patient’s age, clinical setting, and season.

      2. The pretest probability of strep throat in the adult clinic–based population is 5–10%.

      3. Because strep throat is more common in autumn and winter, it may be appropriate to adjust this estimate upward or downward according to season.

   2. Clinical findings and clinical decision rules

      1. Because individual clinical findings (such as the presence of fever or exudates) are not very predictive of GABHS, clinical prediction rules have been developed.

      2. These rules use the key features in the history and physical exam to predict the probability of strep throat.

      3. The Modified Centor score (one of the best validated clinical decision rules) assigns patients 1 point for each of the following findings: tonsillar exudates, swollen tender anterior cervical nodes, absence of cough, history of fever and age < 15 years. One point is subtracted for age over 45 and older.

      4. The likelihood ratios and posttest probabilities given a pretest probability of 10% in given in Table 30-3.

2. Laboratory diagnosis

   1. Throat culture

      1. A single swab throat culture has a sensitivity of approximately 90–95% and specificity of 95–99%.

      2. The major disadvantage of throat cultures is the 24- to 72-hour delay in obtaining results.

   2. Rapid antigen detection test (RADT)

      1. Results from RADTs are available within a few minutes

      2. Sensitivity ranges from 70% to 90% when compared with throat culture with sensitivities in actual practice being toward the lower end of this range.

      3. Specificity for RADTs ranges from 90% to 100%.

3. Integrated use of clinical decision rules and laboratory methods

   1. Generally, clinicians use the results of a clinical decision rules to determine which patients require further testing.

   2. Patients at the lowest risk (low pretest probability and low Modified Centor Score) receive no testing.

   3. Patients at higher risk (posttest probability 5–50%) usually receive a RADT or throat culture.

   4. Those at the highest risk (> 50%) are often treated empirically but may be receive a RADT or throat culture.

   5. Given the sensitivity of RADT and the exceptionally low risk of acute rheumatic fever in adults, a throat culture is not necessary when an RADT is negative. (In children and adolescents, a negative RADT should be verified by throat culture.)

   6. Positive RADTs do not require back up with a culture because they are highly specific.

Treatment

1. Patients with GABHS pharyngitis should be treated with appropriate antibiotic therapy to prevent development of acute rheumatic fever.

   1. Penicillin and amoxicillin are the first-line antibiotics given their narrow spectrum of activity and modest cost.

   2. For patients with an allergy to penicillin, choices include first-generation cephalosporins, clindamycin, clarithromycin, or azithromycin.

2. Treatment decreases severity of symptoms, reduces risk of transmission, and reduces the likelihood of suppurative complications.

3. There is no evidence that antibiotic treatment can prevent the development of acute glomerulonephritis.

4. Clinical improvement within 48 hours is expected; patients who do not improve should be re-evaluated.

5. Tonsillectomy is only indicated for patients with 4 or more episodes of severe pharyngitis in a year.

   Any patient with documented GABHS pharyngitis who does not improve within 48 hours of treatment with an appropriate course of antibiotics should be re-evaluated.

Given a modified Centor score of 3, the patient’s risk of having GABHS is 28–35%. In this group of patients the results of a RADT will be very helpful, essentially ruling out or ruling in disease. Mr. W has no risk factors for HIV and tested negative for HIV when he donated blood 2 months ago. He has no symptoms of fatigue, malaise, or cough making influenza a less likely diagnosis. He reports no fatigue or lymphadenopathy and is older than the typical patient with mononucleosis, making this diagnosis less likely.

Alternative Diagnosis: Influenza

See discussion in Chapter 10, Cough, Fever, & Respiratory Infections.

Alternative Diagnosis: Infectious Mononucleosis

Textbook Presentation

Infectious mononucleosis typically presents with a prodrome of fever, malaise, chills, and sweats. The illness then progresses to the classic triad of severe sore throat, fever (38–40°C) and lymphadenopathy.

Disease Highlights

1. Infectious mononucleosis is most common in patients 15–24 years of age. It is uncommon in adults. (It accounts for < 2% of pharyngitis in patients over 40 years of age.)

2. Infectious mononucleosis is most often caused by EBV (the focus of this discussion) but can be caused by CMV or HHV 6.

3. EBV is spread in saliva.

   1. May be shed in salivary secretions for many weeks

   2. As many as 20% of healthy, previously infected adults intermittently shed virus for decades.

4. Most people are infected with EBV during childhood and the typical childhood infection is subclinical. Less than 10% of children exhibit symptoms.

5. Approximately 90% of adults are EBV seropositive.

Evidence-Based Diagnosis

1. History

   1. The earliest symptoms of EBV are fever, malaise, chills, and sweats.

   2. These symptoms then progress to the classic triad of severe sore throat, fever, and lymphadenopathy.

2. Physical exam

   1. Common findings include enlarged tonsils; pharyngeal erythema; thick, coating, pharyngeal exudate; palatal petechiae; and tender anterior and/or posterior cervical adenopathy.

   2. Table 30-4 lists test characteristics for findings suggestive of EBV.

   3. Rash is uncommon in infectious mononucleosis unless there is antibiotic exposure.

      1. 5–10% of patients have a rash of varying morphology

      2. 27–69% of patients with infectious mononucleosis who are treated with amoxicillin or ampicillin develop a rash.

         Infectious mononucleosis is characterized by a triad of fever, sore throat, and lymphadenopathy.

3. Laboratory testing

   1. The heterophile antibody test (Monospot test) is highly specific for EBV.

      1. Specificity 99%

      2. Sensitivity

         • (1) False-negative rate in first week is as high as 25%.

         • (2) 5–10% in second week

         • (3) 5% in third week of illness

   2. Serum IgM antibody to the EBV viral capsid antigen is accurate but the turn around time on the test is generally longer than the Monospot.

      1. This test is useful in patients with suspected infectious mononucleosis who have negative Monospot.

      2. Test characteristics

         • (1) Sensitivity, 97%

         • (2) Specificity, 94%

         • (3) LR+, 16

         • (4) LR−, 0.03

   3. Other tests

      1. Lymphocytosis and the presence of atypical lymphocytes are diagnostically useful.

         • (1) Lymphocytosis of > 50% on peripheral smear; sensitivity 66%, specificity 84%

         • (2) Atypical lymphocytes >10% of total lymphocytes; sensitivity 75%, specificity 92%

      2. Elevated aminotransferases are seen in the majority of patients.

Treatment

1. Infectious mononucleosis is a self-limited illness; most symptoms resolve within 3 weeks.

2. Symptomatic treatment, including hydration, antipyretics, analgesics, and rest, remains the mainstay of care.

3. Corticosteroids, acyclovir, and antihistamines are not recommended for routine treatment of infectious mononucleosis.

   1. Acyclovir does decrease viral shedding but does not alter the clinical course.

   2. Corticosteroids are indicated for patients with impending airway compromise.

4. Splenomegaly may persist after symptoms resolve. Patients should avoid heavy lifting and contact sports for 4 weeks.

5. Potential complications are rare but include the following:

   1. Splenic rupture

      1. Rare but potentially life-threatening complication

      2. Estimated incidence is 1–2 cases/1000

   2. Airway obstruction

   3. Pneumonitis

   4. Hematologic complications

      1. Hemolytic anemia

      2. Thrombocytopenia

      3. Neutropenia

      4. Aplastic anemia

   5. Neurologic

      1. Encephalitis

      2. Meningitis

      3. Cranial nerve palsies

      4. Seizures

      5. Myelitis

      6. Optic neuritis

      7. Guillain-Barré syndrome

Alternative Diagnosis: Primary HIV Infection - Acute Retroviral Syndrome (ARS)

Textbook Presentation

Symptoms of ARS are generally nonspecific and resolve spontaneously without treatment. The most common findings are fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, headache, and mucocutaneous ulcers. ARS may resemble EBV mononucleosis and can be distinguished by its more acute onset, absence of tonsillar exudate, rash (which is rare in mononucleosis except after treatment with amoxicillin), and mucocutaneous ulcers.

Disease Highlights

1. Transmission of HIV is common in the first 3 months.

   1. This is a period of high viral load.

   2. There are high levels of virus in blood and genital secretions.

   3. Patients often do not know they are infected.

   4. Early diagnosis is thus important to decrease rates of transmission.

2. The highest risk populations for HIV infection are:

   1. Men who have sex with men

   2. Injection drug users

   3. Healthcare workers with needle-stick exposure

Evidence-Based Diagnosis

1. Clinical presentation

   1. The usual lag between exposure to HIV and development of symptoms is 2–4 weeks.

   2. 40–90% patients with acute HIV infection experience symptoms of ARS.

   3. Symptoms seen in over 50% of patients with symptomatic ARS are:

      1. Fever

      2. Fatigue

      3. Rash

      4. Headache

      5. Lymphadenopathy

      6. Pharyngitis

      7. Myalgia or arthralgia

      8. Nausea, vomiting, or diarrhea

   4. Painful mucocutaneous ulcerations

      1. Less common but distinctive manifestation of the syndrome

      2. Often shallow and sharply demarcated

      3. Can involve the oral mucosa, anus, penis, or esophagus

2. Laboratory testing

   1. Laboratory testing is appropriate for patients in whom there is a clinical suspicion for ARS.

   2. Testing should include:

      1. HIV antibody test (ELISA and Western blot): Seroconversion usually occurs 3–7 weeks after infection.

      2. HIV viral load assay

         • (1) HIV is typically detected 11 days after infection.

         • (2) Patients with ARS typically have high viral loads of > 100,000 copies/mL.

         • (3) False-positive result should be suspected if viral load < 10,000 copies/mL.

         • (4) Sensitivity 95–98%

      3. Genotype resistance testing is recommended in all patients with primary HIV infection, since transmission of drug-resistant HIV strains has been documented.

         Because HIV antibody tests may be negative at the time of acute seroconversion, an HIV viral load assay should always be sent when this diagnosis is being considered.

Treatment

1. Acute HIV is infrequently diagnosed, and data about outcomes of early antiretroviral therapy are limited.

2. Antiretroviral therapy for acute infection remains controversial, and referral to HIV specialist for management is recommended.

The pivotal points in this case are the unilateral nature of the throat pain as well as the odynophagia and trismus. This presentation suggests a peritonsillar abscess, classically referred to as quinsy. Peritonsillar abscesses generally form in the area of the soft palate, just above the superior pole of the tonsil.

Peritonsillar abscess is a must not miss diagnosis because if left untreated, it may progress to airway obstruction, abscess rupture, or septic necrosis. Other important diagnoses to consider in this case would be retropharyngeal abscess or epiglotittis. Lemierre disease, a rare disease caused by F necrophorum, must also be considered. Table 30-5 lists the differential diagnosis.

Leading Hypothesis: Peritonsillar Abscess

Textbook Presentation

The typical clinical presentation of peritonsillar abscess is a severe unilateral sore throat associated with fever and a muffled “hot potato” voice. Malaise, dysphagia, and otalgia are also often present. Swallowing is painful, which sometimes leads to pooling of saliva or drooling. Trismus, difficulty opening the mouth because of pain from the inflammation, may be present. The oropharyngeal exam reveals an extremely swollen tonsil with displacement of the uvula to the unaffected side and a bulging soft palate on the affected side. The patient may have markedly tender cervical lymphadenitis on the affected side.

Disease Highlights

1. A peritonsillar abscess usually begins as an acute exudative tonsillitis that progresses to cellulitis and eventually to abscess formation. The abscess may also occur without preceding infection via obstruction of the Weber glands, a group of salivary glands in the soft palate.

2. It is the most common deep infection of head and neck, accounting for approximately 30% of abscesses of the head and neck.

3. Occurs primarily in young adults between the ages of 20 and 40 years

4. Peritonsillar abscesses are polymicrobial. Common organisms include:

   1. Aerobic bacteria

      1. Group A streptococcus

      2. Staphylococcus aureus

      3. Haemophilus influenzae

   2. Anaerobic bacteria

      1. Fusobacterium

      2. Peptostreptococcus

      3. Pigmented prevotella

      4. Veillonella

Evidence-Based Diagnosis

1. Diagnosis of peritonsillar abscess can be made clinically without laboratory data or imaging in patients with a typical presentation

   1. Symptoms

      1. Fever

      2. Malaise

      3. Severe sore throat (worse on 1 side)

      4. Dysphagia

      5. Ipsilateral otalgia

   2. Signs

      1. Erythematous, swollen soft palate with uvula deviation and an enlarged tonsil

      2. Trismus

      3. Drooling

      4. Muffled “hot potato” voice

      5. Rancid or fetor breath

      6. Cervical lymphadenitis

2. Culture of pus from abscess drainage can confirm the diagnosis; however, the rate of positive cultures from peritonsillar abscess in the literature ranges from < 50% to 100%.

3. Trismus occurs in nearly 66% of patients with peritonsillar abscesses.

4. Laboratory evaluation

   1. Laboratory evaluation is not necessary to make the diagnosis but may help gauge the level of illness and direct therapy.

   2. Testing usually includes:

      1. Complete blood cell count

      2. Routine throat culture for group A streptococcus

      3. Gram stain, culture, and susceptibility testing of abscess fluid, especially in patients with persistent infection or diabetes or in those who are immunocompromised.

5. Imaging

   1. Generally not necessary to make a diagnosis, but may be considered in the following cases:

      1. Suspected spread beyond peritonsillar space

      2. Inability to successfully examine the pharynx because of trismus

      3. Monitoring patients unresponsive to initial treatment with antibiotics and drainage

   2. The preferred imaging modality is CT with IV contrast (sensitivity, 100%; specificity, 75%; LR+, 4; LR–, 0)

   3. Intraoral ultrasonography may be used to distinguish peritonsillar abscess from cellulitis and guide needle aspiration.

Treatment

1. Drainage, antibiotic therapy, and supportive care are the mainstays of therapy.

   1. Randomized, controlled trials have shown that needle aspiration and incision and drainage are equally effective.

   2. Rates of re-collection and failed resolution in 1–2 days were comparable at 10% for both procedures.

   3. Needle aspiration is generally less invasive, less painful, and better tolerated.

2. Antibiotics are recommended in conjunction to drainage to effectively treat the abscess and provide coverage for GABHS, S aureus, and respiratory anaerobic bacteria.

   1. Drainage and antibiotic therapy resolves peritonsillar abscess in more than 90% of cases.

   2. Evidence regarding the use of corticosteroids to treat edema and inflammation associated with peritonsillar abscess is inconsistent and is not routinely recommended.

3. Many patients can be treated as outpatients. These patients should be:

   1. Observed after needle aspiration or I and D to ensure they can tolerate oral antibiotics, pain medication, and liquids.

   2. Scheduled to be seen for follow up in 24–36 hours

   3. Advised to return for reevaluation for:

      1. Dyspnea

      2. Worsening throat pain, neck pain, or trismus

      3. Enlarging mass

      4. Fever

      5. Neck stiffness

      6. Bleeding

4. Treatment failure should prompt broadening of antibiotics, reevaluation with CT scan to look for extension of infection, and tonsillectomy.

Alternative Diagnosis: Epiglottitis

See discussion of epiglotittis in Chapter 33.

Alternative Diagnosis: Retropharyngeal Abscess

See discussion of retropharyngeal abscess in Chapter 33.

Alternative Diagnosis: Lemierre Syndrome

Textbook Presentation

Lemierre syndrome is a septic thrombophlebitis of the internal jugular vein. Typically, presenting symptoms and signs include high fevers, rigors, respiratory distress, and neck or throat pain. Examination of the oropharynx may reveal ulceration, pseudomembrane, or erythema. Tenderness and swelling may be observed overlying the jugular vein. In some cases, no abnormal physical finings may be present.

Disease Highlights

1. Lemierre syndrome is a rare (3.6 cases/million/year) but potentially life-threatening cause of sore throat.

2. Approximately 81% of cases are caused by the anaerobic gram-negative rod F necrophorum.

3. Although widespread use of antibiotics in 1940s led to dramatic decline in its incidence, there has recently been an increase.

4. Symptoms

   1. The most common symptoms of Lemierre syndrome are nonspecific (such as sore throat, neck tenderness or swelling or both, and fever).

   2. Some findings seen in Lemierre syndrome that are not commonly seen in pharyngitis are dyspnea (23.8%), pleuritic chest pain (31.1%), abdominal pain (13.7%), and trismus (9.1%).

5. Septic emboli can arise from the septic thrombophlebitis. Potential complications include:

   1. Lung lesions

      1. Septic emboli

      2. Infiltrates

      3. Lung abscess

      4. Pleural effusion

      5. Empyema

   2. Bone and joint

      1. Septic arthritis

      2. Osteomyelitis

   3. Liver abscess

   4. Central nervous system complications

      1. Brain abscess

      2. Meningitis

      3. Cavernous sinus thrombosis

6. The symptoms of septic thrombophlebitis and septic emboli can mask the initial oropharyngeal symptoms.

   In Lemierre syndrome, symptoms of thrombophlebitis and septic emboli can mask the initial oropharyngeal symptoms. The diagnosis should be considered in those patients with septic findings consistent with septic emboli.

Evidence-Based Diagnosis

1. A high clinical suspicion is necessary to make the diagnosis of Lemierre syndrome, since the signs and symptoms are often nonspecific.

2. Lemierre syndrome should be considered strongly in patients with chills, high fever, and unilateral neck swelling. Patients may also have antecedent pharyngitis, septic pulmonary emboli, and persistent fevers despite antimicrobial therapy.

3. It may take 5–8 days to microbiologically isolate F necrophorum.

4. The following criteria are accepted as strong evidence for the presence of Lemierre syndrome:

   1. Anaerobic primary infection of the oropharynx

   2. Subsequent septicemia (with at least 1 positive blood culture)

   3. Metastatic infection of 1 or more distant site

   4. Thrombophlebitis of the internal jugular vein

5. CT scan of neck with contrast is the best diagnostic modality.

Treatment

1. Antibiotics

   1. F necrophorum is usually susceptible to beta-lactamase resistant beta-lactam antibiotics, clindamycin, metronidazole, and chloramphenicol.

   2. There is variable response to second- and third-generation cephalosporins.

2. Surgical therapy maybe needed for patients with abscesses or those who do not respond to antibiotic therapy.

3. The role of anticoagulation in treatment of Lemierre syndrome is controversial. Due to low incidence of Lemierre syndrome, the risks and benefits of anticoagulation have not been addressed in controlled studies.