Basics
Description
Acute infectious disease caused by Corynebacterium diphtheriae; affects primarily the membranes of the upper respiratory tract with the formation of a gray-white pseudomembrane †
Epidemiology
- The only known reservoir for C. diphtheriae is humans; disease is acquired by contact with either a carrier or a diseased person.
- Most cases occur during the cooler autumn and winter months in individuals <15 years of age who are unimmunized.
- Recent outbreaks have occurred, most notably in the countries of the former Soviet Union, and supply additional evidence that disease occurs among the socioeconomically disadvantaged living in crowded conditions.
Incidence
- Although the disease is distributed throughout the world, it is endemic primarily in developing regions of Africa, Asia, and South America.
- In the Western world, the incidence of diphtheria has changed dramatically in the past 50-75 years as a result of the widespread use of diphtheria toxoid after World War II.
- The incidence has declined steadily and is now a rare occurrence.
General Prevention
Active immunization with diphtheria toxoid is the cornerstone of population-based diphtheria prevention. Current recommendations from the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) are as follows: †
- Ages 2 months-7 years: 5 doses of diphtheria vaccine (with tetanus toxoid and acellular pertussis)
- First 3 given as DTaP vaccine 0.5 mL IM at 2-month intervals beginning at 2 months of age
- 4th dose of DTaP should be given at 15-18 months of age.
- 5th dose of DTaP at 4-6 years of age
- In 2005, 2 tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines were licensed for use in adolescents 11-18 years of age.
- 1 booster dose of Tdap should be given to all adolescents at the 11-12-year-old visit, provided they have completed the childhood series. Subsequent tetanus and diphtheria (Td) boosters should be administered every 10 years.
- Tdap should replace the 1st dose of Td in children 7-10 years of age who are undergoing primary immunization.
- Isolation of patients with diphtheria is required until culture from the site of infection is negative on 2 consecutive specimens.
Pathophysiology
- The initial entry site for C. diphtheriae is via airborne respiratory droplets, typically the nose or mouth but occasionally the ocular surface, genital mucous membranes, or preexisting skin lesions.
- Following 2-4 days of incubation at one of these sites, the bacterium elaborates toxin.
- Locally, the toxin induces formation of a necrotic coagulation of the mucous membranes (pseudomembrane) with underlying tissue edema; respiratory compromise may ensue.
- Elaborated exotoxin may also have profound effects on the heart, nerves, and kidneys in the form of myocarditis, demyelination, and tubular necrosis, respectively.
Etiology
C. diphtheriae, a gram-positive pleomorphic bacillus †
Diagnosis
- Respiratory tract diphtheria
- Nasal diphtheria starts with mild rhinorrhea that gradually becomes serosanguineous, then mucopurulent, and often malodorous; it occurs most often in infants.
- Tonsillar and pharyngeal diphtheria begin with anorexia, malaise, low-grade fever, and pharyngitis.
- A membrane appears within 1-2 days.
- Cervical lymphadenitis and edema of the cervical soft tissues may be severe.
- Disease course varies with extent of toxin elaboration and membrane production.
- Respiratory and cardiovascular collapse may occur.
- Laryngeal diphtheria most often represents extension of a pharyngeal infection.
- Clinically presents as typical croup
- Acute airway obstruction may occur.
- In severe cases, the membrane may invade the entire tracheobronchial tree.
- Cutaneous diphtheria occurs in warmer tropical regions.
- It is characterized by chronic nonhealing ulcers with gray membrane.
- May serve as a reservoir in endemic and epidemic areas of respiratory diphtheria
- Other sites: Rarely, vulvovaginal, conjunctival, or aural forms occur.
History
- Exposure to an individual with diphtheria is not necessarily elicited because contact with an asymptomatic carrier may be the only source of infection.
- Incubation period
- Incubation period is 1-6 days.
- Respiratory diphtheria, depending on the site of infection, may begin with nasal discharge alone or with pharyngitis accompanied by mild systemic symptoms.
- Progression of symptoms thereafter occurs as outlined earlier (see "Diagnosis"Ě).
- Previous diphtheria immunization history, diphtheria exposure
Physical Exam
- Classic findings
- Nasal discharge
- Nasal or pharyngeal membrane
- Heart rate out of proportion to body temperature
- Respiratory distress
- Stridor
- Cough
- Hoarseness
- Palatal paralysis
- Neck swelling
- Cervical lymphadenitis
- Attempt to remove any membrane present results in bleeding.
- Conjunctival diphtheria: palpebral conjunctival involvement with a red, edematous, membranous appearance
- Aural diphtheria: otitis externa with a purulent, malodorous discharge
- Cutaneous diphtheria: See "Diagnosis."Ě
Diagnostic Tests & Interpretation
Diagnosis should be on clinical grounds: Delay in treatment increases morbidity and mortality. †
Lab
- Culture of material from the membrane or beneath the membrane. Because special growth media are required, the lab should be notified of suspicion of diphtheria.
- If a strain of C. diphtheriae is isolated, additional testing for presence or absence of toxin production should be done by a laboratory prepared to conduct an animal neutralization test or, alternatively, neutralization (with antitoxin) in tissue culture.
Differential Diagnosis
- Nasal diphtheria
- Common cold
- Nasal foreign body
- Sinusitis
- Adenoiditis
- Snuffles (congenital syphilis)
- Tonsillar or pharyngeal diphtheria
- Streptococcal pharyngitis
- Infectious mononucleosis
- Primary herpetic tonsillitis
- Thrush
- Vincent angina
- Posttonsillectomy faucial membranes
- Oropharyngeal involvement caused by toxoplasmosis, cytomegalovirus, tularemia, and salmonellosis
- Laryngeal diphtheria
- Croup
- Acute epiglottitis
- Aspirated foreign body
- Peripharyngeal and retropharyngeal abscess
- Laryngeal papillomas
- Other masses
Treatment
Medication
Antibiotic therapy: Use in addition to, not in place of, diphtheria antitoxin (DAT). †
- Respiratory diphtheria
- Penicillin G
- Aqueous crystalline 100,000-150,000 U/kg/24 h in 4 divided doses for 14 days or
- Procaine 25,000-50,000 U/kg/24 h in 2 divided doses for 14 days or
- Erythromycin 40-50 mg/kg (maximum 2 g/24 h) PO or parenterally for 14 days
- Cutaneous diphtheria: requires local care of the lesion with soap and water and administration of antimicrobials for 10 days
Inpatient Considerations
Initial Stabilization
- DAT antiserum, produced in horses, must be administered as soon as possible. DAT is available from the CDC. (Note: For patients with known horse serum sensitivity, a test dose should be administered first; if positive, the patient should be desensitized.)
- Pharyngeal or laryngeal disease of <48 hours duration: 20,000-40,000 U IV
- Nasopharyngeal lesions: 40,000-60,000 U IV
- Extensive disease of ≥3 days' duration or diffuse neck swelling: 80,000-120,000 U IV
Ongoing Care
Follow-up Recommendations
- Mild cases: After membrane sloughs off in 7-10 days, recovery is usually uneventful.
- More severe cases: Recovery may be slower; serious complications may occur.
Prognosis
- Most strongly dependent on the immunization status of the host. Those without prior adequate immunization have significantly higher morbidity and mortality.
- Delay in onset of treatment also increases mortality.
- When appropriate treatment has been administered on day 1 of illness, mortality may be as low as 1%.
- When treatment has been delayed until day 4, the mortality rate is ‚ȧ20-fold higher.
- Organism virulence: Toxigenic strains are associated with more severe disease and a poorer prognosis.
- Location of membrane: Laryngeal diphtheria has a higher mortality due to airway obstruction.
- A megakaryocytic thrombocytopenia and WBC count <25,000 are associated with poor outcome.
Complications
- Cardiac toxicity: Myocarditis may develop secondary to elaborated toxin anytime between the 1st and 6th week of illness. Although cardiac failure may occur, most cases are transient.
- Neurologic toxicity occurs secondary to toxin elaboration and mainly reflects bilateral motor involvement.
- Paralysis of the soft palate is most common, but ocular paralysis, diaphragm paralysis, peripheral neuropathy of the extremities, and loss of deep tendon reflexes also occur.
- The frequency of all complications, including those listed above, increases with increasing time between symptom onset and antitoxin administration and also with extent of membrane formation.
Additional Reading
- American Academy of Pediatrics. Diphtheria. In: Pickering †LK, Baker †CJ, Kimberlin †DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:307-311. †[View Abstract]
- Broder †KR, Cortese †MM, Iskander †JK, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-3):1-34. †[View Abstract]
- Centers for Disease Control and Prevention. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep. 2011;60(1):13-15. †[View Abstract]
- Enhanced surveillance of non-toxigenic Corynebacterium diphtheriae infections. Commun Dis Rep CDR Wkly. 1996;6(4):29-32. †[View Abstract]
- Galazka †A. The changing epidemiology of diphtheria in the vaccine era. J Infect Dis. 2000;181(Suppl 1):52-59. †[View Abstract]
Codes
ICD09
- 032.9 Diphtheria, unspecified
- 032.1 Nasopharyngeal diphtheria
- 032.85 Cutaneous diphtheria
- 032.81 Conjunctival diphtheria
- 032.84 Diphtheritic cystitis
- 032.3 Laryngeal diphtheria
- 032.89 Other specified diphtheria
- 032.83 Diphtheritic peritonitis
- 032.2 Anterior nasal diphtheria
- 032.0 Faucial diphtheria
- 032.82 Diphtheritic myocarditis
ICD10
- A36.9 Diphtheria, unspecified
- A36.1 Nasopharyngeal diphtheria
- A36.3 Cutaneous diphtheria
- A36.86 Diphtheritic conjunctivitis
- A36.82 Diphtheritic radiculomyelitis
- A36.89 Other diphtheritic complications
- A36.81 Diphtheritic cardiomyopathy
- A36.83 Diphtheritic polyneuritis
- A36.2 Laryngeal diphtheria
- A36.85 Diphtheritic cystitis
- A36.84 Diphtheritic tubulo-interstitial nephropathy
SNOMED
- 397428000 Diphtheria (disorder)
- 75589004 Nasopharyngeal diphtheria
- 18901009 Cutaneous diphtheria
- 7773002 Conjunctival diphtheria
- 240422004 Tracheobronchial diphtheria
- 3419005 Faucial diphtheria
- 48278001 Diphtheritic cystitis
- 26117009 Diphtheritic myocarditis (disorder)
- 50215002 Laryngeal diphtheria
- 15682004 Anterior nasal diphtheria
- 13596001 Diphtheritic peritonitis
FAQ
- Q: What is the incidence of diphtheria in the United States?
- A: No locally acquired case of respiratory diphtheria has been reported in the United States since 2003. Cutaneous diphtheria still occurs but is not a reportable disease.
- Q: Are there currently places in the world where diphtheria is a problem?
- A: Yes. An epidemic began in 1990 in Russia, spread in 1991 to Ukraine, and during 1993 and 1994 spread to the remaining countries of the former Soviet Union. Other endemic regions include the Middle East and Asia and some countries in Africa and Central and South America. Travelers to these regions should check the CDC Web site for the latest information.
- Q: What precautions should be taken by travelers to areas of the world with diphtheria outbreaks?
- A: The ACIP recommends that travelers to such areas be up-to-date with diphtheria immunization. Infants traveling to areas where diphtheria is endemic or epidemic should ideally receive 3 doses of DTaP before travel.