Last updated: June 28, 2023

Summarytoggle arrow icon

Diphtheria is an infectious disease caused by Corynebacterium diphtheriae, which is usually transmitted via respiratory droplets. The clinical features of diphtheria are caused by a toxin produced by C. diphtheriae after it colonizes the upper respiratory tract. Patients initially present with fever, malaise, and sore throat. Within a few days, a grayish-white pseudomembrane develops over the tonsils, posterior pharyngeal wall, and/or larynx. Other manifestations include cervical lymphadenopathy, soft tissue swelling of the neck, stridor, and/or difficulty breathing as a result of partial airway obstruction. Systemic absorption of the toxin can result in myocarditis, acute tubular necrosis, and/or polyneuropathy. Even before culture reports come back positive, patients should be promptly treated with penicillin and antitoxins, as untreated diphtheria is associated with a high mortality rate. In tropical countries, there is also a cutaneous form of diphtheria without systemic manifestations. Cutaneous diphtheria manifests as a scaly erythematous rash and/or a deep punched-out ulcer following direct entry of C. diphtheriae into the skin. Since the introduction of routine immunization against diphtheria in the 1920s, the incidence of the disease has decreased dramatically in the US.

Epidemiologytoggle arrow icon

  • Incidence: 0–2 cases/year [1]
  • Most cases occur in patients 20 years of age or older.

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon


Pathophysiologytoggle arrow icon

ABCDEFG of C. diphtheria: ADP-ribosylation, Beta-prophage, Club-shaped, Diphtheria, Elongation Factor 2, metachromatic Granules.


Clinical featurestoggle arrow icon

Respiratory diphtheria

Patients initially present with prodromal symptoms: fever, malaise, and sore throat. Four to five days after the onset of prodromal symptoms, symptoms due to the local and systemic effects of the toxin occur.

Cutaneous diphtheria


Diagnosticstoggle arrow icon

Therapy (including antitoxin administration) should be started immediately upon clinical suspicion, even before diagnostic confirmation of diphtheria. [5]

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

  • The patient should be isolated as soon as diphtheria is suspected. [2][5]
  • Antibiotic therapy; : penicillin G (IM injection) OR erythromycin (oral/IV) for 14 days [5]
  • Immediate administration of diphtheria antitoxin: The antitoxin can only neutralize the unbound toxin and should therefore be administered early in the course of the disease.
    • Laryngeal/pharyngeal diphtheria lasting < 48 hours: 20,000–40,000 units IV over 60 minutes
    • Nasopharyngeal diphtheria: 40,000–60,000 units IV over 60 minutes
    • Bull neck or diphtheria lasting > 3 days: 80,000–120,000 units IV over 60 minutes
  • Airway support
  • Monitor for myocarditis; : Conduct multiple ECGs; and serial measurement of cardiac markers.

Diphtheria is a nationally notifiable disease: Report all cases of respiratory diphtheria and toxigenic cutaneous diphtheria to the appropriate health departments. [5]

Administration of the antitoxin is a critical part of treatment, as the clinical features of diphtheria are not caused by the pathogen itself but rather by the exotoxin that C. diphtheriae produces.

Preventiontoggle arrow icon

Immunization [7][8][9]

Exposure control [6][10][11]

Close contacts [5][6][11]

  • Those with frequent direct contact with the patient
  • Anybody exposed to secretions from the infected source .
  • For healthcare workers, exposure includes:

Management of exposed contacts

In addition to isolating and treating infected patients, the following measures should be performed in exposed close contacts regardless of their diphtheria immunity status. [5][6][11]

  • All exposed contacts
  • If cultures are negative: Discontinue quarantine and complete chemoprophylaxis. [11]
  • If cultures are positive: [11]
    • Asymptomatic individuals (carriers): Isolate until completion of chemoprophylaxis and two cultures are negative.
    • Symptomatic patients: See “Treatment.”

Postexposure prophylaxis for diphtheria [5][11]

All exposed close contacts should receive prophylactic antibiotics and be assessed for immunization.

Referencestoggle arrow icon

  1. $Diphteria.
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. AAP Committee on Infectious Diseases. Red Book: 2021–2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics ; 2021
  4. Information to collect on close contacts of diphtheria cases: Appendix 2. Updated: November 2, 2022. Accessed: April 26, 2023.
  5. Child and Adolescent Immunization Schedule. Recommendations for Ages 18 Years or Younger, United States, 2023. Updated: February 10, 2023. Accessed: March 24, 2023.
  6. Catch-up Immunization Schedule for Children and Adolescents Who Start Late or Who Are More than 1 Month Behind Recommendations for Ages 18 Years or Younger, United States, 2023. Updated: February 10, 2023. Accessed: March 24, 2023.
  7. Adult Immunization Schedule by Age Recommendations for Ages 19 Years or Older, United States, 2023. Updated: February 10, 2023. Accessed: March 24, 2023.
  8. Infection Control in Healthcare Personnel: Epidemiology and Control of Selected Infections Transmitted Among Healthcare Personnel and Patients. Updated: November 2, 2022. Accessed: April 26, 2023.
  9. Infection Control in Healthcare Personnel: Epidemiology and Control of Selected Infections Transmitted Among Healthcare Personnel and Patients.,-Transmission%20of%20diphtheria&text=Exposure%20to%20cutaneous%20diphtheria%20lesions,i.e.%2C%20gown%20and%20gloves).. Updated: November 1, 2022. Accessed: May 10, 2023.
  10. Bader MS, McKinsey DS. Postexposure prophylaxis for common infectious diseases.. Am Fam Physician. 2013; 88 (1): p.25-32.
  11. Vaccine-preventable diseases: monitoring system. 2020 global summary. Updated: July 15, 2020. Accessed: November 15, 2020.
  12. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2014
  13. Herold G. Internal Medicine. Herold G ; 2014
  14. Furger P, Suter TM. SURF-med Guidelines Medizin der Schweiz. Editions D&F, Neuhausen am Rheinfall (CH) (2008) ; 2010
  15. Sitzmann FC. Duale Reihe Pädiatrie. Thieme Verlag (2006)
  16. Hoffmann B. Crashkurs Pädiatrie. Urban&Fischer bei Elsevier (2003)
  17. von Schweinitz D, Heinrich M, Schäfer K. Kinderchirurgie Basiswissen und Praxis. Zuckschwerdt Verlag (2008)

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