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Diphtheria is caused by Corynebacterium diphtheriae, a gram-positive, non-spore-forming bacterium. The disease spreads through respiratory droplets expelled during coughing or sneezing, or by contact with contaminated surfaces. The bacteria adhere to epithelial cells in the upper respiratory tract, where they multiply and release exotoxin.

Clinical diphtheria develops only when C. diphtheriae strains are lysogenized by a beta-corynephage carrying the tox gene. This bacteriophage integrates into the bacterial chromosome, enabling the expression of diphtheria toxin—the major virulence factor. Without this phage integration, the bacteria remain non-pathogenic colonizers.

Diphtheria toxin consists of two subunits: fragment B binds to host cell receptors and facilitates endocytosis, while fragment A enters the cytoplasm and catalyzes ADP-ribosylation of elongation factor 2. This modification irreversibly inactivates EF-2, halting protein synthesis and triggering rapid cell death throughout the affected tissue.

The pseudomembrane is a dense, adherent layer of necrotic tissue, fibrin, and cellular debris that forms in the pharynx within days of symptom onset. This thick membrane can obstruct the airway, particularly in children, causing progressive difficulty breathing and potentially fatal airway obstruction if untreated.

When exotoxin disseminates systemically, it targets distant organs, especially the myocardium and peripheral nerves. Myocarditis is a frequent and potentially fatal complication emerging within two weeks, presenting with arrhythmias, conduction abnormalities, or heart block. Neurologic involvement may include cranial nerve palsies and polyneuropathy.

Early treatment involves diphtheria antitoxin administration to neutralize circulating toxin, combined with antibiotics to eliminate the bacterial source. Long-term prevention relies on diphtheria toxoid vaccination, which induces neutralizing antibodies against the toxin rather than the bacterium itself, providing robust protection and significantly reducing global disease burden.

Diphtheria presents with sore throat, fever, coughing, and nasal discharge. In severe cases, progressive difficulty breathing develops as the pseudomembrane forms and obstructs the airway. Early recognition of these respiratory symptoms is critical for prompt antitoxin administration and prevention of life-threatening complications.