• Clinical science



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.


  • 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.


  • Pathogen: Corynebacterium diphtheriae
    • A gram-positive, non-sporulating, club-shaped bacillus
    • Contains metachromatic granules (volutin granules; stain red with a blue dye)
  • Route of infection
    • Droplet transmission
    • Less commonly through direct or indirect contact with open lesions
  • Infectious period: variable



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


Clinical features

Respiratory diphtheria

The patient presents initially with prodromal symptoms: fever, malaise, and sore throat. 4–5 days after the onset of prodromal symptoms, symptoms due to the local and systemic effects of the toxin occur.

Cutaneous diphtheria



  • Cultures of pharyngeal swabs: used to confirm the diagnosis
    • Microscopic examination of pharyngeal swabs or culture isolates reveals multiple C. diphtheriae clustered in angular arrangements.
    • Culture media of choice
  • Other tests: used to identify whether the strain is toxigenic once the culture reveals C. diphtheriae
    • Elek test
      • An immunoprecipitation test in which C. diphtheriae are grown in an agar culture that is embedded with an antitoxin-impregnated filter paper
      • Positive if the strain is toxicogenic
    • Polymerase chain reaction: to identify the tox gene
  • Test for myocarditis: Conduct multiple ECGs and serial measurement of cardiac markers .

Therapy should be started immediately upon clinical suspicion, even before diagnostic confirmation of diphtheria.

Differential diagnoses

The differential diagnoses listed here are not exhaustive.


  • The patient should be isolated as soon as diphtheria is suspected.
  • Antibiotic therapy; : IM injections of penicillin G or oral/IV erythromycin for 14 days
  • 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

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.



Pre-exposure prophylaxis

Post-exposure prophylaxis

Post-exposure prophylaxis is indicated for close personal contacts and caretakers of a patient with diphtheria.

Diphtheria is a notifiable disease.