Diphtheria

Pharyngeal/tonsillar diphtheria (most common):

• Sore throat, low-grade fever, malaise

• Characteristic grayish-white pseudomembrane on tonsils/pharynx — bleeds when removed

• "Bull neck" appearance from cervical lymphadenopathy and soft tissue edema

• Nasal voice and dysphagia

Laryngeal diphtheria:

• Hoarseness, croup-like cough

• Stridor — risk of complete airway obstruction and suffocation

Cutaneous diphtheria:

• Chronic, non-healing skin ulcers with gray membrane; more common in tropical regions

Toxic complications (from exotoxin):

• Myocarditis (usually onset 1–2 weeks after infection)

• Neuropathy (bulbar palsy, respiratory paralysis, peripheral neuropathy)

The risk of diphtheria is primarily determined by vaccination status and proximity to endemic or outbreak settings. The following factors increase the likelihood of infection and/or severe disease:

Risk factors for infection:

• Incomplete or absent vaccination: The dominant risk factor globally. In the 1990s outbreak in the former Soviet Union (>150,000 cases, >5,000 deaths), the majority of cases occurred in adults whose childhood vaccine-induced immunity had waned without booster doses.

• Living in or traveling to endemic areas: Regions with DTP3 coverage <80%, particularly sub-Saharan Africa, South Asia, and Southeast Asia

• Crowded living conditions: Military barracks, refugee camps, prisons, homeless shelters — outbreaks propagate rapidly in overcrowded settings with poor hygiene

• Close contact with a case or carrier: Household contacts of a diphtheria case have a secondary attack rate of 2–5% even in partially immunized populations

• Low socioeconomic status and poor hygiene: Both respiratory and cutaneous diphtheria are diseases of poverty

Risk factors for severe disease and death:

• Age: CFR is highest in children <5 years (up to 20%) and adults >40 years (up to 20–30%). The relatively lower CFR in older children and young adults (3–5%) reflects both immune maturity and lower membrane burden.

• Delayed antitoxin administration: Every day of delay after day 2 of illness increases mortality. Antitoxin given on day 1 is associated with ~1% CFR; by day 4+, CFR exceeds 15%.

• Extensive membrane: Membrane involving the larynx, trachea, or extending across the entire pharynx carries higher risk of airway obstruction and systemic toxicity.

• Bull-neck (severe cervical edema): Indicates massive toxin production and correlates with higher rates of myocarditis and neuropathy.

• Biotype: C. diphtheriae biotype gravis has historically been associated with more severe disease, though this correlation is not absolute.

Populations at increased risk in high-income countries:

• Adults aged >50 years (waning immunity, inadequate booster uptake — serological studies show 30–60% are below protective antibody levels)

• Immigrants and refugees from low-coverage countries

• Homeless populations (cutaneous diphtheria)

• Healthcare workers in contact with cases

• Myocarditis: 10–25% of cases; onset 1–2 weeks after infection; can cause heart failure, heart block, ventricular arrhythmias — most common cause of death

• Neuropathy: bulbar palsy (difficulty swallowing/speaking), peripheral neuritis, respiratory muscle paralysis (weeks to months after infection) — can be fatal

• Airway obstruction: from membrane extension into larynx/trachea — can cause asphyxiation

• Renal failure: tubular necrosis from toxin

• Thrombocytopenia: from toxin-mediated platelet destruction