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Pharyngitis

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)
    • 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)
  • Acute, noninfectious
    • Various caustic, mechanical, or trauma-related (incl. endotracheal intubation)
  • Chronic
    • More likely noninfectious
    • Chemical irritation (GERD)
    • Smoking
    • Neoplasms
    • Vasculitis
    • Radiation 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 years
    • 0 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 gonorrhoeae
    • Viral 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.

  • Penicillin G: children (<27 kg): 600,000 U IM injection times one dose; adolescents/adults (≥27 kg): 1.2 million units IM injection times one dose.

 
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 BID
    • Clindamycin 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.
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