Diphtheria (Corynebacterium diphtheriae)
Overview
Plain-Language Overview
Diphtheria is a serious infection caused by the bacterium Corynebacterium diphtheriae that mainly affects the throat and upper airways. It causes a thick, gray coating called a pseudomembrane to form in the throat, which can make breathing and swallowing difficult. The infection primarily involves the respiratory system but can also affect the heart and nervous system if the toxin spreads. Symptoms often include a sore throat, fever, and swollen glands in the neck. The disease can lead to severe complications like breathing obstruction and heart damage. It is a contagious illness that spreads through respiratory droplets. Early recognition of symptoms is important because the infection can be life-threatening without treatment.
Clinical Definition
Diphtheria is an acute, toxin-mediated infection caused by toxigenic strains of Corynebacterium diphtheriae. The core pathology involves production of the diphtheria toxin, which inhibits protein synthesis in host cells leading to local tissue necrosis and formation of a characteristic pseudomembrane in the upper respiratory tract. The toxin can disseminate systemically causing myocarditis, neuropathy, and other serious complications. The disease primarily affects the respiratory mucosa but can also involve cutaneous sites. Transmission occurs via respiratory droplets or direct contact with infected lesions. Clinically, it presents with sore throat, low-grade fever, and a thick gray membrane over the tonsils or pharynx. The major clinical significance lies in its potential for airway obstruction and systemic toxin effects, which can be fatal without prompt antitoxin administration and antibiotics.
Inciting Event
Exposure to respiratory droplets containing toxigenic Corynebacterium diphtheriae.
Colonization of the nasopharynx or skin by the bacterium.
Inhalation of contaminated droplets from an infected individual.
Latency Period
Incubation period typically ranges from 2 to 5 days after exposure.
Symptom onset usually occurs within 1 week of bacterial colonization.
Diagnostic Delay
Initial symptoms mimic common viral pharyngitis, leading to misdiagnosis.
Lack of awareness in non-endemic areas causes delayed suspicion of diphtheria.
Failure to recognize the characteristic pseudomembrane on physical exam.
Delayed laboratory confirmation due to slow growth of Corynebacterium diphtheriae on culture.
Clinical Presentation
Signs & Symptoms
Sore throat and hoarseness with difficulty swallowing.
Fever and malaise indicating systemic infection.
Thick gray pseudomembrane formation in the oropharynx causing airway obstruction.
Neck swelling and tenderness due to lymphadenopathy.
Nasal discharge and possible epistaxis in nasal diphtheria.
History of Present Illness
Gradual onset of sore throat, low-grade fever, and malaise over several days.
Development of a thick, gray pseudomembrane on the tonsils, pharynx, or nasal mucosa.
Progressive neck swelling and bull neck appearance due to cervical lymphadenopathy and edema.
Possible hoarseness, dysphagia, and respiratory distress from airway obstruction.
Systemic symptoms such as myocarditis or neuropathy may appear in severe cases.
Past Medical History
History of incomplete or absent diphtheria vaccination.
Previous respiratory infections or recent exposure to infected individuals.
Underlying immunodeficiency or chronic illnesses that impair immune response.
Family History
No specific heritable syndromes associated with diphtheria.
Family members may be asymptomatic carriers or have recent history of respiratory infections.
Clusters of cases may occur in households with low vaccination coverage.
Physical Exam Findings
Presence of a thick, grayish-white pseudomembrane on the tonsils, pharynx, or nasal mucosa that bleeds if scraped.
Cervical lymphadenopathy with a characteristic 'bull neck' appearance due to extensive soft tissue swelling.
Pharyngeal erythema and edema surrounding the pseudomembrane.
Tachycardia and signs of systemic toxicity in severe cases.
Possible respiratory distress from airway obstruction caused by the pseudomembrane.
Diagnostic Workup
Diagnostic Criteria
Diagnosis of diphtheria is established by identifying the characteristic pseudomembrane in the oropharynx combined with clinical symptoms such as sore throat and fever. Confirmation requires isolation of Corynebacterium diphtheriae from a throat swab culture. Detection of the diphtheria toxin gene by PCR or demonstration of toxin production by the Elek test confirms toxigenicity. Laboratory findings may show leukocytosis and elevated inflammatory markers. Early recognition of the clinical presentation along with microbiological confirmation is essential for diagnosis.
Pathophysiology
Key Mechanisms
Production of diphtheria toxin, an exotoxin that inhibits protein synthesis by ADP-ribosylation of elongation factor-2 (EF-2).
Local tissue damage caused by toxin-mediated necrosis leading to pseudomembrane formation in the upper respiratory tract.
Systemic absorption of toxin causing myocarditis, neuritis, and renal toxicity.
Colonization of the oropharynx and upper respiratory mucosa by Corynebacterium diphtheriae.
| Involvement | Details |
|---|---|
| Organs | Larynx and pharynx are commonly involved organs where pseudomembrane formation causes airway compromise. |
Heart is a critical organ affected by toxin-induced myocarditis leading to heart failure. | |
Peripheral nervous system involvement results in neuropathies and paralysis. | |
| Tissues | Respiratory mucosa is the site of initial colonization and pseudomembrane formation causing airway obstruction. |
Myocardial tissue can be damaged by toxin leading to myocarditis and arrhythmias. | |
Peripheral nerves may be affected by toxin causing demyelination and neuropathy. | |
| Cells | Macrophages phagocytose bacteria and present antigens to initiate immune response. |
T lymphocytes mediate cellular immunity and help clear infection. | |
Epithelial cells of the respiratory tract are the primary site of toxin-mediated damage and pseudomembrane formation. | |
| Chemical Mediators | Diphtheria toxin inhibits protein synthesis by ADP-ribosylation of elongation factor-2, causing cell death. |
Cytokines such as TNF-alpha and IL-1 are released during inflammation contributing to systemic symptoms. | |
Antitoxin antibodies neutralize circulating toxin and prevent further tissue injury. |
Treatments
Pharmacological Treatments
Diphtheria antitoxin
- Mechanism:
Neutralizes circulating diphtheria toxin to prevent cellular damage.
- Side effects:
Serum sickness
Anaphylaxis
Fever
- Clinical role:
First-line
Erythromycin
- Mechanism:
Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of Corynebacterium diphtheriae.
- Side effects:
Gastrointestinal upset
Cholestatic hepatitis
Allergic reactions
- Clinical role:
First-line
Penicillin G
- Mechanism:
Inhibits bacterial cell wall synthesis leading to bacterial lysis.
- Side effects:
Allergic reactions
Jarisch-Herxheimer reaction
Neurotoxicity with high doses
- Clinical role:
First-line
Non-pharmacological Treatments
Airway management including possible intubation or tracheostomy to prevent airway obstruction from pseudomembrane.
Isolation precautions to prevent transmission via respiratory droplets.
Supportive care with hydration and monitoring for cardiac and neurologic complications.
Prevention
Pharmacological Prevention
Diphtheria toxoid vaccine as part of the DTaP or Tdap immunization series.
Antitoxin administration in exposed individuals to neutralize circulating toxin.
Antibiotic prophylaxis with erythromycin or penicillin for close contacts.
Non-pharmacological Prevention
Routine childhood immunization to maintain herd immunity.
Isolation of infected patients to prevent transmission.
Improved sanitation and hygiene to reduce spread of Corynebacterium diphtheriae.
Outcome & Complications
Complications
Airway obstruction from pseudomembrane leading to respiratory failure.
Myocarditis caused by diphtheria toxin leading to arrhythmias and heart failure.
Neuropathy including palatal paralysis and peripheral neuritis.
Acute renal failure secondary to toxin-mediated damage.
Sepsis from systemic spread of infection.
| Short-term Sequelae | Long-term Sequelae |
|---|---|
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Differential Diagnoses
Diphtheria (Corynebacterium diphtheriae) versus Streptococcal pharyngitis
Diphtheria (Corynebacterium diphtheriae) | Streptococcal pharyngitis |
|---|---|
Corynebacterium diphtheriae | Streptococcus pyogenes (Group A Streptococcus) |
Elek test or culture positive for toxigenic Corynebacterium diphtheriae | Positive rapid antigen detection test or throat culture for Group A Streptococcus |
Potentially severe systemic toxicity due to diphtheria toxin with prolonged course | Usually self-limited with rapid symptom onset and resolution with antibiotics |
Diphtheria (Corynebacterium diphtheriae) versus Infectious mononucleosis
Diphtheria (Corynebacterium diphtheriae) | Infectious mononucleosis |
|---|---|
Exposure to respiratory droplets from infected persons | Close contact with saliva of infected individuals (kissing) |
Negative heterophile antibody test; diagnosis by culture and toxin detection | Positive heterophile antibody test (Monospot) and atypical lymphocytosis |
Pharyngitis with characteristic pseudomembrane and systemic toxin effects | Fever, pharyngitis, and lymphadenopathy lasting 2-4 weeks |
Diphtheria (Corynebacterium diphtheriae) versus Vincent's angina (acute necrotizing ulcerative gingivitis)
Diphtheria (Corynebacterium diphtheriae) | Vincent's angina (acute necrotizing ulcerative gingivitis) |
|---|---|
Gray pseudomembrane on tonsils and pharynx extending beyond gums | Ulcerative gingivitis with necrosis and gray pseudomembrane localized to gums |
Corynebacterium diphtheriae producing diphtheria toxin | Mixed anaerobic fusiform and spirochete bacteria |
Requires diphtheria antitoxin and systemic antibiotics | Responds to oral debridement and metronidazole or penicillin |
Diphtheria (Corynebacterium diphtheriae) versus Herpangina (Coxsackievirus infection)
Diphtheria (Corynebacterium diphtheriae) | Herpangina (Coxsackievirus infection) |
|---|---|
Corynebacterium diphtheriae | Enterovirus (Coxsackie A virus) |
Bacterial culture positive for toxigenic Corynebacterium diphtheriae | Viral culture or PCR positive for Coxsackievirus |
Thick gray pseudomembrane on tonsils and pharynx with systemic toxicity | Multiple small vesicles and ulcers on soft palate, resolving in 7-10 days |
Diphtheria (Corynebacterium diphtheriae) versus Epiglottitis (Haemophilus influenzae type b)
Diphtheria (Corynebacterium diphtheriae) | Epiglottitis (Haemophilus influenzae type b) |
|---|---|
Corynebacterium diphtheriae | Haemophilus influenzae type b |
Culture positive for toxigenic Corynebacterium diphtheriae; pseudomembrane on pharynx | Blood culture positive for H. influenzae; lateral neck X-ray shows thumbprint sign |
Gradual onset of sore throat with pseudomembrane and systemic toxin effects | Rapid onset of high fever, drooling, and airway obstruction |