Corynebacterium diphtheriae

Classic diphtheria is characterized by pseudomembrane formation on respiratory mucous membranes.

Epidemiology

Incidence – very rare in U.S. due to vaccination
Age – usually children <15 years who are unvaccinated or incompletely vaccinated
Transmission – airborne or direct contact (respiratory secretions or skin lesion)

Organism

Non-spore forming, unencapsulated, pleomorphic, gram-positive bacillus
Produces exotoxin that causes many of the symptoms
Asymptomatic carriage occurs in some patients

Pathophysiology

Virulence is mediated by prophage-encoded exotoxin
Toxin induces dense necrotic coagulum on mucous membranes
Causes underlying soft-tissue edema

Clinical Presentation

Incubation period – 2-4 days
Respiratory tract
- Anterior nasal disease
- Faucial disease – classic membranes on pharynx and tonsils, cervical adenopathy and fever
- Laryngeal and tracheobronchial disease – hoarseness, dyspnea, stridor, and brassy cough
Cardiac disease – myocarditis
- Mortality 3-4 times that of patients without cardiac involvement
- Related to toxin release
Neurologic disease – demyelinating neuropathy
- Related to severity of disease – rare in mild disease
- Usually motor neuropathy
Renal disease – proteinuria, renal failure
Cutaneous disease – chronic nonhealing ulcers with dirty gray membrane, often in mixed infections with Staphylococcus aureus and group A streptococci
Invasive disease
- Endocarditis
- Mycotic aneurysms
- Osteomyelitis
- Septic arthritis

Prevention

Vaccination

Treatment

Diphtheria antitoxin
Antibiotics
Supportive therapy
Early ICU support for lower respiratory symptoms

Indications for Testing

Presence of pseudomembrane; pharyngitis with other organ involvement

Laboratory Testing

Initial testing – CBC, rapid strep test
Diphtheria culture – usually diagnostic if disease symptoms are present

Differential Diagnosis

Pharyngitis
- Group A Streptococcus
- Epstein-Barr virus
- Viral pharyngitis
- Vincent angina
- Epiglottitis
Skin lesions
- Psoriasis
- Eczema
- Autoimmune immunobullous disease
- Contact dermatitis
- Bacterial infection
  - Streptococcus pyogenes
  - Staphylococcus aureus
  - Group B Streptococcus
Cough
- Pneumonia
  - Viral
  - Bacterial
- Asthma
- Bronchiolitis

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Non-specific indicator of infection

Test name: Streptococcus (Group A) Rapid with Reflex to Culture

ARUP #: 0028903

Methodology: Immunoassay with Direct Observation/Culture

Use:

Rule out more common cause of pharyngitis

If Streptococcus (Group A) Rapid test is negative, culture will be added for confirmation

Limitations:

Negative rapid test does not rule out presence of group A streptococcus

Test name: Corynebacterium diphtheriae Culture

ARUP #: 0060360

Methodology: Standard reference procedures for C. diphtheriae culture and identification

Use:

Identify organism causing pharyngitis

Limitations:

Occasionally patient may have asymptomatic carriage of diphtheria organism

Additional Tests Available

Test name: Diphtheria & Tetanus Antibodies, IgG

ARUP #: 0050595

Methodology: Quantitative Multi-Analyte Fluorescent Detection

Comments:

For diphtheria antibody titer, order with diphtheria antibody, IgG to

Determine patient's response to protein toxoid (majority of antibody falls within IgG/subclass 1)
Diagnose antibody deficiency in patients with recurrent infections, especially sinopulmonary and gastrointestinal

For tetanus antibody titer, order with tetanus antibody, IgG to

Determine whether vaccine recipient responded to vaccine with protective levels of antibodies
Determine IgG antibody titers to tetanus and diphtheria toxoids and H. Influenzae PRP simultaneously

If concentrations of IgG, IgM, and IgA are low, low normal or even normal, and antibody deficiency still strongly suspected, determine IgG subclass and response to protein antigens such as diphtheria, tetanus toxoid, and H. influenzae as well as to pure polysaccharide antigens such as unconjugated pneumococcal vaccine

Test name: Diphtheria Antibody, IgG

ARUP #: 0050210

Methodology: Semi-Quantitative Multi-Analyte Fluorescent Detection

Comments:

For diphtheria antibody titer, order with diphtheria and tetanus antibodies, IgG to

Determine patient's response to protein toxoid (majority of this antibody falls within IgG/subclass 1)
Diagnose antibody deficiency in patients with recurrent infections (especially sinopulmonary and gastrointestinal infections)

Test name: Diphtheria, Tetanus, and H. Influenzae b Antibodies, IgG

ARUP #: 0050779

Methodology: Quantitative Multi-Analyte Fluorescent Detection

Comments:

Determine if vaccine recipient responded to vaccine and if protective antibody levels have been reached

Determine IgG antibody titers to tetanus and diphtheria toxoids and H. influenzae PRP simultaneously