- 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. Since the introduction of routine immunization against diphtheria in the 1920s, the incidence of disease has decreased dramatically in the US.
- Incidence: 0–5 cases/year
- 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, containing metachromatic granules (AKA volutin granules).
Route of infection
- Droplet transmission
- Less commonly through direct or indirect contact with open lesions (see extra information for more details on cutaneous diphtheria)
- Infectious period: variable
- C. diphtheriae colonizes the mucous membrane of the respiratory tract (respiratory diphtheria)
C. diphtheriae has both toxigenic and non-toxigenic strains; toxigenic strains contain a prophage gene called tox, which encodes the diphtheria toxin, an exotoxin that inhibits protein synthesis by ADP-ribosylation and deactivation of EF-2
- Local effects of the toxin: destruction of the respiratory epithelium → inflammatory response →
- Systemic effects of the toxin
- Incubation period: 2–5 days
- 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
- Anterior nasal diphtheria: bloody rhinorrhea
- Tonsillar and pharyngeal diphtheria
- Laryngeal diphtheria: difficulty breathing, inspiratory stridor
- Reversible polyneuropathy
- Local features
- Cutaneous diphtheria is the result of direct inoculation of C. diphtheriae into skin (e.g., skin abrasions) or pre-existing skin lesions.
- Cutaneous diphtheria is usually seen in tropical regions, where it is more common than respiratory diphtheria.
- Patients present with scaly erythematous rash, impetigo, or deep, punched-out ulcers
- Cutaneous diphtheria does not result in systemic effects.
- Cultures of pharyngeal swabs are used to confirm the diagnosis
- Once the culture reveals C. diphtheriae, one or both of the following tests are used to identify whether the strain is toxigenic:
- 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!
- 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 unbound toxin and should therefore be administered early in the course of the disease.
- Airway support
Post-exposure prophylaxis is indicated for close personal contacts and caretakers of a patient with diphtheria.
- Erythromycin or a single dose of benzathine penicillin
- Complete immunization schedule if vaccinations are not up-to-date.
Diphtheria is a notifiable disease!