OVERVIEW: What every practitioner needs to know

Are you sure your patient has pharyngitis? What should you expect to find?

  • Sore throat, fever, odynophagia, malaise, nausea

  • Tender cervical adenopathy, pharyngotonsillar exudate, edema and/or erythema of pharynx, soft palate and tonsils

How did the patient develop pharyngitis? What was the primary source from which the infection spread?

  • Pharyngitis of infectious etiology is spread when droplets of infected fluids, such as saliva, nasal discharge, or mucus come in contact with another person’s nasal or oral mucosa or conjunctivae. The incubation period is usually 24 to 72 hours.

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  • It is more common among children younger than 15 years of age. Infections are more commonly spread in winter, and the majority of cases are viral in origin. Group A beta-hemolytic streptococci (GABHS) cause 15 to 30% of acute pharyngitis in children and 5 to 20% in adults (strep throat).

Beware: there are other diseases that can mimic pharyngitis:

  • Irritation, which includes chemical or thermal burns, smoke inhalation, trauma, orogastric or nasogastric tube, and persistent cough

  • Primary allergic reaction

  • Secondary to postnasal discharge from allergic or infectious etiologies

  • Steven–Johnson syndrome

  • Aphthous ulcers (including ulcers secondary to inflammatory bowel disease)

  • Acute thyroiditis

  • Behçet disease

  • Gastroesophageal or laryngopharyngeal reflux disease

  • Leukemia, lymphoma, aplastic anemia, as well as oropharyngeal malignancies

  • Oral mucositis, which is usually secondary to radiation or chemotherapy

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

  • Peripheral white blood cell (WBC) count with differential: expect neutrophil predominance for strep throat and lymphocytosis for mononucelosis.

  • Rapid streptococcal antigen test (RAST): positive result for strep throat

Results that confirm the diagnosis

  • Throat culture (sensitivity >90-95% for strep throat)

What imaging studies will be helpful in making or excluding the diagnosis of pharyngitis?

  • Imaging has no use in evaluation or management of routine pharyngitis.

  • X-ray ($60-$125), a computed tomography scan ($125-$500), and magnetic resonance imaging (>$1,000) of the head and neck can be utilized to diagnose complications that can occur, including pharyngotonsillar abscess and Lemierre syndrome.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

Family medicine; Internal medicine; Emergency medicine; Pediatrics; Ear, Nose, and Throat; and Infectious Disease specialists most often see patients with pharyngitis and can, thus, assist in evaluation and management.

If you decide the patient has pharyngitis, what therapies should you initiate immediately?

Key principles of therapy

  • Most cases of pharyngitis are self-limiting and do not require any antimicrobial treatment. Antibiotics are often misused as most cases of pharyngitis are of viral origin.

  • The key to management is in identifying patients who are more likely to have GABHS and then using appropriate antibiotic(s) to prevent complications, such as rheumatic fever and glomerulonephritis, scarlet fever, and local exudative complications such as pharyngotonsillar abscess.

How do I know if the patient has pharyngitis due to Group A streptococci?

Differentiating strep throat (or pharyngitis secondary to GABHS) from other infectious etiologies can often be very difficult. A scoring system, with the intention to guide treatment choices, called the Centor criteria, was developed. The criteria include four points, and patients get one point for each criterion. The four points are:

  • Absence of cough

  • Anterior cervical lymphadenopathy

  • Tonsillar exudates

  • Temperature (>100.4°F [38.0°C])

Later, a modification of these criteria with the addition of the factor of age was done, keeping in mind that most strep throat infections occur in children. As per this modified Centor criteria, patients within age ranges of younger than 14 years of age, 15 to 44 years of age, and older than 45 years of age get 1, 0, or 1 point, respectively.

A score of 0 or 1 indicates a less than 5% likelihood of GABHS infection, whereas a score of 4 is associated with an almost 50% likelihood of GABHS infection.

Because of this correlation between increased scores and chances of strep throat, the criteria further helps in guiding appropriate management, as follows:

  • Patients with scores of 0 or 1 do not need any further evaluation. However, if a patient with a score of 1 has had a recent close contact with a known case of strep throat, clinical judgment may guide one toward further work-up.

  • Patients with scores of 2 or 3 can be evaluated with either a throat culture (slow diagnosis, but gold standard) or a RAST (best for quick diagnosis).

  • Patients with scores of 4 or more do not need further work-up and can be managed presumptively as cases of strep throat.

Whether patients with negative RAST test need a follow-up with throat culture is controversial. The sensitivity of throat culture is approximately 95%, whereas that of RAST depends on the particular kit utilized. Newer kits can be as sensitive as throat cultures. The specificity of RAST ranges between 90 and 99%.

How does one distinguish infectious mononucleosis from strep throat?

In its early stages, infectious mononucleosis can often mimic GABHS infection. It starts with a prodromal period of chills, sweats, and malaise that proceeds to involve sore throat, fever, and generalized lymphadenopathy. Unlike strep throat, however, infectious mononucleosis can be associated with generalized lymphadenopathy. Palatal petechiae and thick white/purple exudate can often be present. Splenomegaly and/or hepatomegaly can be present in more than 50% of patients. Lymphocytosis, along with greater than 10% atypical lymphocytes and mild thrombocytopenia, can be found in mononucleosis. Mild elevations in liver function tests and erythrocyte sedimentation rate (ESR) also accompany mononucleosis, but these laboratory tests are usually normal in patients with strep throat. Heterophile antibodies can be present within 2 to 3 weeks of disease onset and can persist in serum up to 1 year or longer. More specific antibodies, including immunoglobulin M antibody to viral capsid antigen, also exist. Administration of ampicillin frequently induces a maculopapular rash.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

Empiric antibiotic treatment for pharyngitis is not a cost-effective approach and is generally not recommended. Antibiotic treatment decreases symptomatic duration by about 14 to 16 hours.

  • If a patient meets four out of four Centor criteria or more than four criteria as per the modified Centor criteria, then penicillin or erythromycin (for penicillin allergic patients) could be prescribed for treating GABHS. For patients not meeting all the Centor criteria, clinical judgment with regards to empiric treatment is advised. This is especially the case, because most cases of pharyngitis are benign and of viral origin, which do not require specific treatment besides comfort measures.

  • If empirical treatment is given, then the treatment is usually guided toward treating GABHS, unless the suspicion for an alternate microbe causing infectious pharyngitis is high. In such cases, penicillin V is the most recommended drug of choice by various organizations/guidelines.

  • Alternate choices of drugs would include benzathine penicillin G (intramuscular form of penicillin, only one dose required), amoxicillin, or amoxicillin/clavulanic acid (better taste). For allergic patients, macrolides (erythromycin) or cephalosporins (cefalexin) can be given.

Treatment options are summarized in Table I.

Table I.
Organism Antibiotic Dose Alternate
Streptococcus pyogenes (GABHS) Penicillin V 250mg orally every 12 hours or 500mg orally every 24 hours for 10 days Erythromycin is the choice of antibiotic for penicillin allergic patients. It also covers Mycoplasma and Chlamydia.
Benzathine, penicillin G 1.2 million units IM once (benzathine)
Cefuroxime 250mg orally every 12 hours for 5-10 days
Cephalexin 500mg orally every 12 hours for 10 days
Amoxicillin 500mg orally every 8 hours for 7-10 days
Amoxicillin-clavulanate 500-750mg orally every 8 hours for 7-10 days
Erythromycin 400mg orally every 6 hours for 10 days
Azithromycin 500mg orally every 8 hours for 3 days
Mycoplasma, Chlamydia Erythromycin 400mg orally every 6 hours for 10 days N/A
Azithromycin 500mg orally every 8 hours for 3 days
Neisseria gonorrhoeae Ceftriaxone plus azithromycin 0.25g IM once (ceftriaxone)1g orally once (azithromycin) N/A
Doxycycline 100mg orally every 12 hours for 7 days
Herpes simplex Aciclovir 400mg orally every 8 hours for 7-10days FamciclovirValacyclovir
Corynebacterium diphtheriae Erythromycin 500mg orally every 6 hours for 14days Penicillin G followed by penicillin V

GABHS, group A beta-hemolytic streptococci; IM, intramuscularly; N/A, not applicable.

2. Other key therapeutic modalities.

  • Symptomatic relief in pharyngitis is often the main pillar of treatment, as opposed to antibiotic treatment. Both systemic and local therapies can be utilized toward this goal.

  • Systemic analgesics: aspirin, ibuprofen, and acetaminophen are the most commonly used medications. Ibuprofen 400mg orally has been shown to be more effective than acetaminophen 1,000mg in some trials. Aspirin should be avoided, if possible, and used cautiously if needed for children with pharyngitis because of its association with Reye syndrome in patients with viral infections.

  • Local remedies: warm saline gargles (a tablespoon of salt in 8oz of warm water), as well as lozenges (benzocaine, phenol, menthol, lidocaine, ambroxol, etc.), help calm the sore throat from inflamed pharynx.

  • Hydration, nutrition, and rest are equally important.

  • Controversial or evolving therapies: glucocorticoids have been shown to be efficacious in decreasing pain from sore throat in some trials. However, because of methodologic fallacies in some of these trials, the use of glucocorticoids in pharyngitis remains controversial at present.

What complications could arise as a consequence of pharyngitis?

Most viral infections do not have any complications.

GABHS, if not treated promptly, can lead to suppurative (sinusitis, otitis media, mastoiditis, pharyngotonsillar abscess, etc.), as well as nonsuppurative (rheumatic fever, glomerulonephritis in rare cases), complications.

What should you tell the family about the patient's prognosis?

  • Pharyngitis, which usually presents with sore throat, is a very common self-limiting condition in otherwise healthy patients. It happens because of viral or bacterial infection of the throat. If appropriately managed, most patients usually recover within 2 to 7 days from their infection without any complications.

How do you contract pharyngitis and how frequent is this disease?

Epidemiology

  • Pharyngitis of infectious etiology is spread when droplets of infected fluids, such as saliva, nasal discharge, or mucus, come in contact with another person’s nasal or oral mucosa or conjunctivae. The incubation period is usually between 24 and 72 hours.

  • It is more common among children aged younger than 15 years.

Infections are more commonly spread in winter.

Viral infections comprise more than 50% of all cases of pharyngitis. Bacterial infections account for roughly 20 to 30% of the cases. No infectious etiology is identified for the remaining 20 to 30% of the cases.

What pathogens are responsible for this disease?

Group A, C, and G streptococci, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Arcanobacterium haemolyticum, Corynebacterium diphtheriae, Fusobacterium necrophorum, and Neisseria gonorrhoeae:

  • The presence of 3 or 4 Centor criteria highly suggests GABHS, as opposed to another infectious etiology.

  • The presence of hoarseness, cough, and coryza are against GABHS.

  • Pharyngitis in association with bronchitis may suggest Mycoplasma or Chlamydia infection.

  • The presence of grey tonsillar pseudomembrane (particularly in association with bleeding when the membrane is scraped) may suggest diphtheria. It is more common in alcoholics, as well as patients who have recently travelled to endemic areas.

Candidal pharyngitis: particularly in diabetics or immunocompromised patients.

Rhinovirus, adenovirus, influenza A and B, parainfluenza, coxsackie, echovirus, herpes simplex virus (HSV), Epstein–Barr virus (EBV), Cytomegalovirus (CMV), human immunodeficiency virus (HIV), respiratory syncytial virus, and metapneumovirus:

  • Presence of cough, coryza, conjunctivitis, myalgia, and diarrhea are generally suggestive of viral origin.

  • Mononucleosis-like presentation can be secondary to EBV, CMV, and HIV. However, CMV is usually not associated with pharyngitis.

  • Lymphadenopathy (anterior, as well as posterior, cervical nodes), white/purple exudate, and hepatosplenomegaly suggest infectious mononucleosis.

  • Presence of vesicles on oropharynx or tonsils may indicate herpes infection.

What other additional laboratory findings may be ordered?

  • Anti-streptolysin O (ASO) titers are not useful for GABHS pharyngitis. However, ASO can be obtained for patients who develop complications—rheumatic fever and glomerulonephritis—secondary to GABHS infection.

  • If the suspicion for GABHS pharyngitis is high but RAST with or without culture is negative, obtain another culture on human blood media, as A. haemolyticum can mimic strep throat and does not grow as well on standard sheep blood media.

  • If the suspicion for gonococcal pharyngitis is high, use Thayer-Martin media for culture.

  • Obtain heterophile-agglutination test, as well as anti-EBV titers, for cases suspicious for infectious mononucleosis.

  • HSV serologies can be obtained in pharyngitis that is suspicious for herpes infection.

  • Obtain enzyme-linked immunosorbent assay (ELISA) with or without western blot if the suspicion for HIV is significant. HIV-related pharyngitis often happens in the acute phase of infection when the serologies are still negative (window period). Point-of-care tests along with HIV viral load assays should be utilized in these cases.

How can pharyngitis be prevented?

There is no single vaccine that prevents pharyngitis, since it can be caused by many different bacteria and viruses. Influenza vaccine may prevent some community causes of pharyngitis. Prophylactic drug treatment is not recommended. Avoidance of direct contact with infected patients is key to preventing pharyngitis.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

Bisno, AL. “Acute pharyngitis”. N Engl J Med. vol. 344. 2001. pp. 205-11. (This review article provides an overview of the diagnosis and management of acute infectious pharyngitis as caused by various bacterial and viral organisms.)

Choby, BA. “Diagnosis and treatment of streptococcal pharyngitis”. Am Fam Physician. vol. 79. 2009. pp. 383-90. (The article provides a detailed discussion of the diagnosis and management of pharyngitis from GABHS. It also includes a comparison of different guidelines regarding the screening, diagnostic testing, and management of GABHS pharyngitis.)

Del Mar, CB, Glasziou, PP, Spinks, AB. “Antibiotics for sore throat”. Cochrane Database Syst Rev. 2006. (This systematic review included 27 studies with the idea to assess the benefits of antibiotics in patients with sore throat. It gave results on the number of patients needed to treat with regard to the management of symptoms. It also addressed the benefits of antibiotics in preventing suppurative and non-suppurative complications of pharyngitis.)

Pelucchi, C, Grigoryan, L, Galeone, C. “Guideline for the management of acute sore throat”. Clin Microbiol Infect. vol. 18. 2012. pp. 1-28. (This article provides the ESCMID (European Society of Clinical Microbiology and Infectious Diseases) guidelines for the management of uncomplicated acute sore throat. It also discusses and rates the level of evidence in the current literature that addresses the same topic.)

Fine, AM, Nizet, V, Mandl, KD. “Large-scale validation of the Centor and McIsaac scores to predict group A streptococcal pharyngitis”. Arch Intern Med. vol. 172. 2012. pp. 847-52. (This is a study of more than 200,000 patients that validated the Centor and McIsaac scores for the screening of Strep throat. The results from this study help better classify the risks of strep throat than the original study because of the large sample size.)

Humair, JP, Revaz, SA, Bovier, P, Stalder, H. “Management of acute pharyngitis in adults: reliability of rapid streptococcal tests and clinical findings”. Arch Intern Med. vol. 166. 2006. pp. 640-4. (This prospective cohort study compares the rapid streptococcal antigen test (RAST) with the gold-standard—throat culture. It provides sensitivity and specificity of the RAST. It also compared appropriate antibiotic use with cost per patient for five different modes of diagnostic strategies, including symptomatic treatment, systematic RAST, selective RAST, empirical treatment, and systematic culture.)

Luzuriaga, K, Sullivan, JL. “Infectious mononucleosis”. N Engl J Med. vol. 362. 2010. pp. 1993-2000. (This is a clinical practice article on Infectious mononucleosis that also includes a table on the differential diagnosis of the infectious causes of acute pharyngitis. The diagnosis part of this article is relevant given that infectious mononucleosis, in its early stage, can often mimic GABHS pharyngitis.)

McIsaac, WJ, Kellner, JD, Aufricht, P, Vanjaka, A, Low, DE. “Empirical validation of guidelines for the management of pharyngitis in children and adults”. JAMA. vol. 291. 2004. pp. 1587-95. (This is a validation study that addresses the comparison of different diagnostic approaches, including rapid tests and culture and its impact on antibiotic use.)

Vincent, MT, Celestin, N, Hussain, AN. “Pharyngitis”. Am Fam Physician. vol. 69. 2004. pp. 1465-70. (This article briefly discusses the differential diagnosis, as well as clinical- and laboratory-based diagnosis of acute infectious pharyngitis.)

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