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Pharyngitis

- Acute, viral (lower grade fever) - Rhinovirus - Adenovirus (associated with conjunctivitis) - Parainfluenza virus - Coxsackievirus (hand-foot-mouth disease) - Coronavirus - Echovirus - Herpes simplex virus (vesicular lesions) - Epstein-Barr virus (EBV/mononucleosis) - Cytomegalovirus - HIV

- Acute, bacterial (higher fevers) - Group A β-hemolytic streptococci - Neisseria gonorrhoeae - Corynebacterium diphtheriae (diphtheria) - Haemophilus influenzae - Moraxella catarrhalis - Chlamydia pneumonia - Fusobacterium necrophorum (20% young adult cases) - Group C or G streptococcus - Arcanobacterium haemolyticum - Francisella tularensis (tularemia)

para>Rheumatic fever has its greatest incidence in children aged 5 to 18 years, but is currently a rare sequela of streptococcal pharyngitis in modern medicine.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Acute, viral (lower grade fever)RhinovirusAdenovirus (associated with conjunctivitis)Parainfluenza virusCoxsackievirus (hand-foot-mouth disease)CoronavirusEchovirusHerpes simplex virus (vesicular lesions)Epstein-Barr virus (EBV/mononucleosis)CytomegalovirusHIV
  • Acute, bacterial (higher fevers)Group A β-hemolytic streptococciNeisseria gonorrhoeaeCorynebacterium diphtheriae (diphtheria)Haemophilus influenzaeMoraxella catarrhalisChlamydia pneumoniaFusobacterium necrophorum (20% young adult cases)Group C or G streptococcusArcanobacterium haemolyticumFrancisella tularensis (tularemia)
  • Acute, noninfectiousVarious caustic, mechanical, or trauma-related (incl. endotracheal intubation)
  • ChronicMore likely noninfectiousChemical irritation (GERD)SmokingNeoplasmsVasculitisRadiation changes

Genetics

Patients with a positive family history of rheumatic fever have a higher risk of rheumatic sequelae following an untreated group A β-hemolytic streptococcal infection.

RISK FACTORS

  • Epidemics of group A β-hemolytic streptococcal disease occurrence
  • Cold and flu seasons
  • Age ( especially children/adolescents)
  • Family history of rheumatic fever
  • Close contact with infectious individuals (home, daycare, military barracks)
  • Immunosuppression
  • Fatigue
  • Smoking/second-hand smoke exposure
  • Acid reflux
  • Oral sex
  • Diabetes mellitus
  • Recent illness (secondary postviral bacterial infection)
  • Chronic colonization of bacteria in tonsils/adenoids

GENERAL PREVENTION

  • Avoid close contact with infectious patients.
  • Wash hands frequently.
  • Avoid first- or second-hand smoke.
  • Home humidifier at home
  • Manage preventable causes (e.g., GERD).

DIAGNOSIS

HISTORY

  • Sore throat
  • Difficulty swallowing (odynophagia)
  • Cough (though rarely associated with GAS pharyngitis)
  • Hoarseness
  • Fever
  • Anorexia
  • Chills
  • Malaise
  • Contacts with similar symptoms or diagnosed infection

PHYSICAL EXAM

  • Enlarged tonsils (tonsillar exudate or possible peritonsillar abscess/deep neck space infection)
  • Pharyngeal erythema
  • Cervical adenopathy
  • Fever (higher in bacterial infections)
  • Pharyngeal ulcers (CMV, HIV, Crohn, other autoimmune vasculitides)
  • Scarlet fever rash: punctate erythematous macules with reddened flexor creases and circumoral pallor suggests streptococcal pharyngitis
  • Tonsillar/soft palate petechiae suggests infectious mononucleosis (EBV/CMV).
  • Gray oral pseudomembrane suggests diphtheria and occasionally infectious mononucleosis (EBV/CMV).
  • Characteristic erythematous-based clear vesicles suggests HSV.
  • Conjunctivitis suggests adenovirus.

DIFFERENTIAL DIAGNOSIS

  • Viral syndrome
  • Streptococcal infection
  • Allergic rhinitis/postnasal drip
  • GERD
  • Malignancy (lymphoma or squamous cell carcinoma)
  • Irritants/chemicals (detergent/caustic ingestion)
  • Atypical bacterial (e.g., gonococcal, chlamydial, syphilis, pertussis, diphtheria)
  • Oral candidiasis (patients typically complain mostly of dysphagia)

DIAGNOSTIC TESTS & INTERPRETATION

  • Acute pharyngitis evaluation includes Prediction Rule Use to determine further testing (see below)
  • Additional testing generally not needed if viral-like clinical features (e.g., cough, rhinorrhea, hoarseness, oral ulcers, diarrhea, conjunctivitis, rash) (1)[A].
  • Avoid testing for GAS pharyngitis in children <3 years old as acute rheumatic flare is rare, unless there is a close sick contact who is GAS-positive (1)[B].
  • Modified Centor clinical prediction rule for group A streptococcal infection (2)[A]:+1 point: tonsillar exudates+1 point: tender anterior chain cervical adenopathy+1 point: absence of cough+1 point: fever by history+1 point: age <15 years0 point: age 15 to 45 years-1 point: age >45 years
  • Scoring:If 4 points, positive predictive value of ~80%; treat empirically.If 2 to 3 points, positive predictive value of ~50%, rapid strep antigen; treat if GAS positive.If 0 or 1 point, positive predictive value <20%; do not test; treat empirically with follow-up as needed.

Initial Tests (lab, imaging)

  • Testing, if performed, is usually for the presence of group A β-hemolytic streptococci. Options include the following:Rapid strep antigen test from throat swab with agglutination or molecular kits; provides quicker, more practical alternative to throat culture with 96% specificity and 86% sensitivity (though sensitivity varies by modality kit) (3)[A].Blood agar throat culture from swab. Gold standard of diagnosis (3)[A]Antistreptolysin-O (carrier state suspected if positive culture, and unchanged ASO titers)
  • Special tests usually done only if history is suggestive of a different diagnosis.Warm Thayer-Martin plate or antigen testing for Neisseria gonorrhoeaeViral cultures for HSV and so forth, though expensive and often not indicated.Monospot for EBV

Test Interpretation

Bacitracin disk sensitivity of hemolytic colonies suggests group A β-hemolytic streptococcus.

TREATMENT

GENERAL MEASURES

Conservative therapy recommended for most cases, (unless bacterial etiology suspected):

  • Salt water gargles
  • Viscous lidocaine (2%) 5 to 10 mL PO q4h swish/spit
  • Acetaminophen 10 to 15 mg/kg/dose q4h PRN pain or fever (pediatric). In adults, do not exceed >3 g per day.
  • NSAIDs for pain or fever
  • Anesthetic lozenges
  • Cool-mist humidifier
  • Hydration (PO or IV)

Pediatric Considerations

Opioids not recommended due to black box warnings.

MEDICATION

  • Antibiotics (particularly penicillin) are chosen primarily to prevent rheumatic fever and peritonsillar abscess (quinsy) in streptococcal infections, though supportive data lacking.60-70% primary care visits by children with pharyngitis result in antibiotic prescriptions (4). Empiric therapy results in overuse of antibiotic.Treatment duration generally 10 days (1)[A]Antibiotics do not reduce risk of poststreptococcal glomerulonephritis.Antibiotics shorten duration of symptoms by approximately. 16 hours (5)Antibiotics may prevent pharyngitis/fever by day 3 (NNT 4 if GAS-positive, 6.5 if GAS-negative, 14.4 if untested) (5)[A].
  • Ulcers related to autoimmune diseases usually require systemic or intralesional injectable steroids.
  • HIV-related ulcers are due to decreasing counts of CD4 and respond when patients' CD4 titers increase.

First Line

The following first-line therapies are recommended by 2012 IDSA guidelines (1)[A]:

  • Penicillin V: children (<27 kg): 250 mg PO TID (BID dosing sufficient if good compliance); adolescents and adults (>27 kg): 250 mg PO QID or 500 mg PO BID
  • Amoxicillin:50 mg/kg PO once daily (max 1,000 mg/dose or 25 mg/kg PO BID (max = 500 mg/dose).

ALERT

Use with caution if diagnosis is unclear because using amoxicillin with EBV infection may induce rash.

Second Line

  • If no history of anaphylactic penicillin allergy:Cephalexin 20 mg/kg PO BID or (children) 25 to 50 mg/kg/day divided BID or (adults) 1000 mg PO QID (max = 4 g/day)Cefadroxil 30 mg/kg PO once daily (max = 1 g/day)
  • If history of anaphylactic penicillin allergy:Azithromycin 12 mg/kg PO once daily for 5 days (max = 500 mg/dose)Clarithromycin 7.5 mg/kg PO BID (max = 250 mg/dose) or (adults) 250 to 500 mg PO BIDClindamycin 7 mg/kg PO TID (max = 300 mg/dose) or (children) 10 to 30 mg/kg/day PO divided TID-QID or (adults) 150 to 450 mg PO TID-QID
  • Penicillin is the most documented treatment to prevent rheumatic sequelae, but cephalosporins have a lower rate of antimicrobial failure against streptococcal pharyngitis.
  • Newer macrolides, though effective against streptococcal pharyngitis, are more expensive and unproven at preventing rheumatic complications.
  • Macrolide-resistant strains of GAS are currently <10% in the United States but more prevalent worldwide.
  • IDSA recommends against adjunctive corticosteroid therapy (1)[B].

ISSUES FOR REFERRAL

Each GAS-confirmed episode should be documented to support the need for future tonsillectomy and adenoidectomy.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Patient should complete a full course of antibiotic therapy, regardless of symptom response.
  • Patients are generally noninfectious after 24 hours of antibiotics.
  • Follow-up culture for group A strep is not recommended (1)[A].

DIET

As tolerated. Encourage the consumption of fluids.

PROGNOSIS

  • Streptococcal pharyngitis runs a 5- to 7-day course with peak fever at 2 to 3 days.
  • Symptoms will resolve spontaneously without treatment, but rheumatic complications are still possible.

COMPLICATIONS

  • Rheumatic fever (e.g., carditis, valve disease, arthritis)
  • Poststreptococcal glomerulonephritis
  • Peritonsillar abscess (a.k.a. quinsy tonsillitis): considered a clinical diagnosis and does not warrant ultrasound/computed tomography. Will generally require percutaneous/transoral drainage. Surgery may also involve a quinsy tonsillectomy, which is merely a tonsillectomy in the setting of acute infection. This is generally not advocated unless for special circumstances, as most otolaryngologists recommend infectious resolution before surgery.
  • Acute airway compromise (rare) can typically be bypassed with nasal trumpets. Consult anesthesiologist/otolaryngologist.
  • Repeated episodes of GAS pharyngitis may represent recurrent viral infections in a chronic pharyngeal GAS carrier (1)[B]. IDSA recommends against repeated diagnostic efforts/antibiotic therapy in a known chronic pharyngeal GAS carrier, as they are seldom contagious or at risk for serious complications.
  • Evidence remains controversial for tonsillectomy as a treatment for chronic/recurrent throat infections. IDSA recommends against it (1)[A] while the American Academy of Otolaryngology proposes tonsillectomy only if there is also one of the following: fever, cervical adenopathy, tonsillar exudate, or confirmed GAS (6)[C]

REFERENCES

11 Shulman ST, Bisno AL, Clegg HW, 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):1279-1282.22 Fine AM, Nizet V, Mandl KD. Large-scale validation of the Centor and McIsaac scores to predict group A streptococcal pharyngitis. Arch Intern Med. 2012;172(11):847-852.33 Lean WL, Arnup S, Danchin M, et al. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. Pediatrics. 2014;134(4):771-881.44 Cohen CF, Cohen R, Levy C, et al. Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study. CMAJ. 2015;187(1):23-32.55 Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2013;(11):CD000023.66 Baugh RF, Archer SM, Mitchell RB, et al. Clinical practice guideline: tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;144(1)(Suppl):S1-S30.

ADDITIONAL READING

  • Kocher JJ, Selby TD. Antibiotics for sore throat. Am Fam Physician. 2014;90(1):23-24.
  • Weber R. Pharyngitis. Prim Care. 2014;41(1):91-98.
  • Zoorob R, Sidani MA, Fremont RD, et al. Antibiotic use in acute upper respiratory tract infections. Am Fam Physician. 2012;86(9):817-822.

SEE ALSO

  • Herpes Simplex; Infectious Mononucleosis, Epstein-Barr Virus Infections; Rheumatic Fever
  • Algorithm: Pharyngitis

CODES

ICD10

  • J02.9 Acute pharyngitis, unspecified
  • J02.0 Streptococcal pharyngitis
  • J31.2 Chronic pharyngitis
  • J03.00 Acute streptococcal tonsillitis, unspecified
  • J02.8 Acute pharyngitis due to other specified organisms

ICD9

  • 462 Acute pharyngitis
  • 034.0 Streptococcal sore throat
  • 472.1 Chronic pharyngitis

SNOMED

  • 405737000 Pharyngitis (disorder)
  • 43878008 Streptococcal sore throat (disorder)
  • 140004 Chronic pharyngitis
  • 41582007 Streptococcal tonsillitis (disorder)
  • 1532007 viral pharyngitis (disorder)
  • 195924009 Influenza with pharyngitis (disorder)

CLINICAL PEARLS

  • Most cases of pharyngitis are viral and do not require antibiotics.
  • Risk of undiagnosed group A streptococcal infection is rheumatic sequelae-a rare complication.
  • Use Modified Centor Score to guide testing and treatment.
  • Penicillin is still first-line therapy for group A streptococcal infection.