-In temperate climates, Diphtheria usually involves the respiratory tract
–Occurs throughout the year, with peak in colder months
-Prior to immunization, devastating epidemics in children -> mortality rates were up to 50% during epidemics

-Cases Reported:
–In 1921: >206,000 cases reported
–Between 1980-1987: only 22 cases reported
–Currently, only 5 cases/yr in US

-Immunzation Status:
–Currently, 20-25% of older adults are susceptible to Diphtheria
–Most cases occur in non-immunized patients
–Attack rate/severity/risk of complications are much lower in immunized patients

1) 1969-1970: San Antonio
2) 1972-1982: Seattle, WA -> 86% of the 1100 cases were cutaneous Diphtheria

-Risk Factors in Outbreaks:
1) ETOH Abuse:
2) Low Socioeconomic Status:
3) Crowded Living Conditions:
4) Native American Ethnicity:
5) Homosexuality: noted in outbreak in England with tox-negative strains


  • Corynebacterium diphtheriae
    • Gram-positive rod


  • Reservoir: humans

  • Transmission: close contact (transmission by fomites or indirect contact are less common, although organism can survive for weeks-months in the environment)

    • Transmission from sympomatic patients is higher than that from asymptomatic carriers
  • Incubation Period (for respiratory Diphtheria): 2-5 days (up to 8 days in rare cases)

  • Incubation Period (for cutaneous Diphtheria): 7 days (range: 1 to >21 days) after appearance of skin lesion

  • Course of Infection: invasion of mucous membranes (predominantly in the respiratory tract) and open skin lesions (due to insect bites or trauma)

    • Epithelial necrosis and acute inflammation (via the polypeptide Diphtheria Toxin)
    • Coagulation of dense fibrinopurulent exudate -> Pseudomembrane formation
    • Diphtheria Toxin: acts systemically too -> myocarditis, neuritis, focal necrosis in kidneys/liver/adrenal glands
  • Diphtheria Carriers: those with asymptomatic infection



  • Throat c/s: isolation of C. Diphtheriae
    • Special tellurite medium required
    • Group A Strep and Staph aureus are also frequently co-isolated from Diphtheria patients
    • Testing for toxin production is necessary


(multiple sites of respiratory tract involvement may occur)

Tonsillopharyngeal Diphtheria

  • Epidemiology
    • Most common site of involvement -> 50-60% of cases
    • Onset is usually gradual (most patients present within a few days of becoming ill)
  • Clinical
    • Pharyngitis with Gray-White Exudates: erythema may be seen early, but progresses to gray-white exudates (presence of true pseudomembanes varies from 33-100%)
      • Gray Exudate: sharply demarcated, adherent to tissue (dislodging may cause bleeding)
      • Unlike Strep pharyngitis, Diphtheria exudate extends beyond the margin of the tonsils to involve palate, uvula, and tonsillar pillars
    • N/V: more common in childhood cases
    • Fever (50% of cases): up to 102°F
    • Dysphagia (50% of cases):
    • Cough/Hoarseness/Rhinorrhea/Chills: less common
    • Systemic Effects: range from malaise -> systemic toxicity with hypotension/sepsis
    • Bull Neck : abrupt onset with pseudomembrane formation, foul breath, massive swelling of tonsils and uvula, thick speech, cervical adenopathy, striking swelling of submandibular space and anterior neck, systemic toxicity

Laryngeal Diphtheria

  • Epidemiology
    • Second most commonly involved respiratory site of infection
  • Clinical
    • Hoarseness
    • Cough:
    • Laryngeal Pseudomembrane: seen during laryngocscopy, this may aid in making the diagnosis
    • Drooling: suggests impending airway obstruction
    • Acute Upper Airway Obstruction (see Obstructive Lung Disease, [[Obstructive Lung Disease]]): risk is increased with laryngeal and/or tracheobronchial involvement
    • Acute Respiratory Failure (see Acute Hypoventilation, [[Acute Hypoventilation]]): due to high-grade upper airway obstruction with excessive work of breathing

Nasal Diphtheria

  • Clinical
    • Unilateral/Bilateral Serosanguineous Nasal Discharge: which may cause irritation of nares or lips
    • Systemic Effects: less common in nasal cases


  • Clinical
    • Barking (Croup-Like) Cough:
    • Airway Obstruction: risk is increased with laryngeal and/or tracheobronchial involvement


  • Epidemiology
    • Occurs in 50% of fatal Diphtheria cases
  • Clinical
    • Barking (Croup-Like) Cough:

Cutaneous Diphtheria

  • Clinical
    • Usually infects pre-existing dermatoses -> involves lower extremities > upper extremities > head > trunk
    • Punched Out Ulcers :

Conjunctival Diphtheria (uncommon)

  • Primary infection

GU Tract Diphtheria (uncommon)

  • Primary infection

GI Tract Diphtheria (uncommon)

  • Primary infection


  • Clinical
    • May co-exist with other manifestations
    • Can present with acute local disease or insidiously weeks later (earlier onset cases are generally more severe)
    • 50-66% of DIphtheria cases have subtle EKG changes
    • 10-25% of Diphtheria cases have clinically apparent myocarditis
    • S-T wave changes, heart blocks, PVC s, arrhythmias (A-Fib, VT, VF), systolic murmurs, diminished heart sounds, S3, CHF
    • AST levels can be used to monitor extent of myocardial damage

Polyneuritis (see [[Peripheral Neuropathy]])

  • Epidemiology
    • Occurs in 10-75% of cases
    • Incidence correlates with disease severity
  • Diagnosis
    • EMG/NCV: interestingly, muscle weakness may precede (by 1-2 wks) maximal abnormalities on EMG/NCV
    • LP: moderately increased protein (occasionally with pleocytosis)
  • Clinical
    • May co-exist with other manifestations
    • Bulbar Involvement (usually occurs during first 2 wks)
      • Palatal and pharyngeal paralysis
      • Dysphagia
      • Nasal-sounding voice
      • Oculomotor paralysis
      • Ciliary paralysis
      • Facial paralysis
      • Laryngeal paralysis
    • Peripheral Polyneuropathy (usually occurs 1-3 months after onset, but resolves completely)
      • Proximal weakness (spreads distally)
      • Glove-and-stocking parasthesias
      • Cardiac vagal denervation (50% of cases)
      • Baroreceptor dysfunction
      • Phrenic Nerve Involvement with Acute/Chronic Hypoventilation (see Phrenic Neuropathy, [[Phrenic Neuropathy]], Acute Hypoventilation, [[Acute Hypoventilation]], and Chronic Hypoventilation, [[Chronic Hypoventilation]])


Diphtheria Anti-Toxin:
-Produced from horse serum
-Indicated for respiratory Diphtheria cases -> although, may withhold in cases that are toxin-negative
-Role in treating cutaneous Diphtheria is unclear
-Pseudomembrane may continue to increase in size for the first day after anti-toxin administration -> resolves over days-1 week
-SE: serum sickness (10% risk)

Antibiotics: main role is to eradicate organism and prevent transmission (since antibiotics do not significantly enhance healing in local infection cases that have been treated with anti-toxin)
1) Erythromycin:
2) PCN-G:
3) Clinda:
4) Rifampin:

Supportive Care:
1) Intubation/Mechanical Ventilation: indicated for laryngeal involvement and/or airway obstruction
2) EKG Monitoring/Treatment of Arrhythmias and Heart Blocks:
-DL-Carnitine: unclear role, but may be beneficial in myocarditis

Treatment of Skin Lesions:
1) Burow s Solution Compresses After Debridement:


  • Mortality increases with severity of local disease, extent of pseudomembrane formation, and delay to anti-toxin therapy
  • Death rate is highest during first week of illness, among those with bull neck , among those with myocarditis (with blocks/arrhythmias), among those with laryngeal/tracheobronchial involvement, among infants, among those >60 y/o, and in alcoholics
    • Cutaneous Diphtheria mortality rates are far lower than those with respiratory disease


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