After an incubation period of 2 to 4 days, diphtheria usually presents as pharyngitis or tonsillitis. Typically, malaise, sore throat, and fever occur, and a patch of exudate or membrane develops on the tonsils, uvula, soft palate, or pharyngeal wall. The gray-white pseudomem-brane adheres to the mucous membrane, and may extend from the oropharyngeal area down to the larynx and into the trachea. Associated cervical adenitis is common, and in severe cases cervical adenitis and edema produce a “bullneck” appearance. In uncomplicated cases, the infection gradually resolves, and the membrane is coughed up after 5 to 10 days.
The complications and lethal effects of diphtheria are caused by respiratory obstruc-tion or by the systemic effect of DT absorbed at the site of infection. Mechanical obstruc-tion of the airway produced by the pseudomembrane, edema, and hemorrhage can be sudden and complete and can lead to suffocation, particularly if large sections of the membrane separate from the tracheal or laryngeal epithelial surface. The DT absorbed into the circulation causes injury to various organs, most seriously the heart. Diphtheritic myocarditis appears during the second or third week in severe cases of respiratory diph-theria. It is manifested by cardiac enlargement and weakness, arrhythmia, and congestive heart failure with dyspnea. Nervous system involvement appears later in the course of dis-ease, most often involving paralysis of the soft palate, oculomotor (eye) muscles, or select muscle groups. The paralysis is reversible and is generally not serious unless the di-aphragm is involved. The disease resolves with the formation of antitoxin antibody.
C. diphtheriae may produce nonrespiratory infections, particularly of the skin. Thecharacteristic lesion, which ranges from a simple pustule to a chronic, nonhealing ulcer, is most common in tropical and hot, arid regions. Cardiac and neurologic complications from these infections are infrequent, suggesting that the efficiency of toxin production or absorption is low compared to that in respiratory infections.
The initial diagnosis of diphtheria is entirely clinical. There are presently no rapid labora-tory tests of sufficient value to influence the decision regarding antitoxin administration. Direct smears of infected areas of the throat are not reliable diagnostic tools. Definitive diagnosis is accomplished by isolating and identifying C. diphtheriae from the infected site and demonstrating its toxigenicity. Isolation is usually achieved with a selective medium containing potassium tellurite (eg, Tinsdale medium).
It should be recognized that while the diagnosis of diphtheria could be once be made and confirmed with great confidence, it is now more difficult because experience with the disease is rare. Most physicians have never seen a case of diphtheria, and most laboratories have never isolated the organism and do not even stock the required medium. Because rou-tine throat culture procedures will not detect C. diphtheriae, the physician must advise the laboratory of the suspicion of diphtheria in advance. Generally, 2 days are required to ex-clude C. diphtheriae (ie, no colonies isolated on Tinsdale agar); however, more time is needed to complete identification and toxigenicity testing of a positive culture.
Treatment of diphtheria is directed at neutralization of the toxin with concurrent elimination of the organism. The former is most critical and is accomplished by promptly administering a diphtheria antitoxin that neutralizes free toxin, but it will have no effect on toxin already fixed to cells. C. diphtheriae is susceptible to a variety of antimicrobics, including penicillins, cephalosporins, erythromycin, and tetracycline. Of these, erythromycin has been the most ef-fective. The complications of diphtheria are managed primarily by supportive measures.
The mainstay of diphtheria prevention is immunization. The vaccine is highly effective. Three to four doses of diphtheria toxoid produce immunity by stimulating antitoxin pro-duction. The initial series is begun in the first year of life . Booster im-munizations at 10-year intervals maintain immunity. Fully immunized individuals may become infected with C. diphtheriae, because the antibodies are directed only against the toxin, but the disease is mild. Serious infection and death occur only in unimmunized or incompletely immunized individuals. Immunization with DT toxoid prevents serious toxin-medicated disease.