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Clinical manifestations, diagnosis, and treatment of diphtheria

Luis F Barroso, MD
P Samuel Pegram, MD, FACP
Section Editor
Daniel J Sexton, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Diphtheria is an infectious disease caused by the gram-positive bacillus Corynebacterium diphtheriae. Infection may lead to respiratory disease, cutaneous disease, or an asymptomatic carrier state. The word diphtheria comes from the Greek word for leather, which refers to the tough pharyngeal membrane that is the clinical hallmark of infection.

The clinical manifestations, diagnosis, and treatment of diphtheria will be reviewed here. The epidemiology, pathophysiology, and prevention of this infection are discussed separately. (See "Epidemiology and pathophysiology of diphtheria" and "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age".)


Respiratory diphtheria — Respiratory diphtheria is typically caused by toxin-producing strains of C. diphtheriae; rarely, it is caused by toxigenic strains of other Corynebacterium species (C. ulcerans, C. hemolyticum, or C. pseudotuberculosis) [1]. Symptoms typically begin two to five days after infection. In addition to respiratory symptoms, absorption and dissemination of diphtheria toxin can lead to toxin damage of the heart (myocarditis), nervous system, and kidneys.

The onset of symptoms is typically gradual; the most common presenting symptoms are sore throat, malaise, cervical lymphadenopathy, and low-grade fever. The earliest pharyngeal finding is mild erythema, which can progress to isolated spots of gray and white exudate. In at least one-third of cases, local elaboration of toxin induces the formation of a coalescing pseudomembrane (composed of necrotic fibrin, leukocytes, erythrocytes, epithelial cells, and organisms) (picture 1 and picture 2). This membrane adheres tightly to the underlying tissue and bleeds with scraping.

This membrane can extend to any portion of the respiratory tract from the nasal passages to the tracheobronchial tree. Up to two-thirds of cases are tonsillopharyngeal; involvement of the laryngeal, nasal, and tracheobronchial areas is less common [2]. Systemic toxicity increases as the pseudomembrane spreads from the tonsillopharyngeal area. A form of malignant diphtheria is associated with extensive "membranous pharyngitis" plus massive swelling of the tonsils, uvula, cervical lymph nodes, submandibular region, and anterior neck (the so-called "bull neck" of toxic diphtheria). In such cases, respiratory stridor may ensue, leading to respiratory insufficiency and death. In addition, aspiration of the membrane can lead to suffocation.

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Literature review current through: Nov 2017. | This topic last updated: Oct 04, 2016.
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