Chapter 131. Diphtheria and Other Infections Caused by Corynebacteria and Related Species (Part 3) Clinical Manifestations Respiratory Diphtheria The clinical diagnosis of diphtheria is based on the constellation of sore throat; adherent tonsillar, pharyngeal, or nasal pseudomembranous lesions; and low-grade fever. In addition, diagnosis requires the isolation of C. diphtheriae or the histopathologic isolation of compatible gram-positive organisms. The Centers for Disease Control and Prevention (CDC) recognizes confirmed respiratory diphtheria (laboratory proven or epidemiologically linked to a culture-confirmed case) and probable respiratory diphtheria (clinically compatible but not laboratory proven or epidemiologically linked). Carriers are defined as individuals who have positive cultures for C. diphtheriae and either are asymptomatic or have symptoms but lack pseudomembranes. Most patients seek medical care for initial manifestations of sore throat and fever. Occasionally, weakness, dysphagia, headache, and voice change are the initial manifestations. Neck edema and difficulty breathing are seen in more advanced cases and carry a poor prognosis. The systemic manifestations of diphtheria stem from the effects of diphtheria toxin and include weakness as a result of neurotoxicity and cardiac arrhythmias or congestive heart failure due to myocarditis. The pseudomembranous lesion is most often located in the tonsillopharyngeal region. Less commonly, the lesions are detected in the larynx, nares, and trachea or bronchial passages. Large pseudomembranes are associated with severe disease and a poor prognosis. A few patients develop massive swelling of the tonsils and present with "bull-neck" diphtheria, which results from massive edema of the submandibular and paratracheal region and is further characterized by foul breath, thick speech, and stridorous breathing. The diphtheritic pseudomembrane is gray or whitish and sharply demarcated. Unlike the exudative lesion associated with streptococcal pharyngitis, the pseudomembrane in diphtheria is tightly adherent to the underlying tissues. Attempts to dislodge the membrane may cause bleeding. Hoarseness suggests laryngeal diphtheria, in which laryngoscopy may be diagnostically helpful. Cutaneous Diphtheria This is a variable dermatosis most often characterized by punched-out ulcerative lesions with necrotic sloughing or pseudomembrane formation (Fig. 131-2). The diagnosis requires cultivation of C. diphtheriae from lesions, which most commonly occur on the extremities. Patients usually seek medical attention because of nonhealing or enlarging skin ulcers, which may be associated with a preexisting wound or dermatoses such as eczema, psoriasis, and venous stasis disease. The lesions rarely exceed 5 cm. Figure 131-2 Cutaneous diphtheria due to nontoxigenic C. diphtheriae on the lower extremity. (From the Centers for Disease Control and Prevention.) Other Clinical Manifestations C. diphtheriae causes rare cases of endocarditis and septic arthritis, most often in patients with preexisting risk factors such as cardiac valvular disease, injection drug use, or cirrhosis. Complications Airway obstruction poses a significant early risk in patients presenting with advanced diphtheria. Pseudomembranes may slough and obstruct the airway or may advance to the larynx or into the tracheobronchial tree. Children are particularly prone to obstruction because of their small airways. Polyneuropathy and myocarditis are late toxic manifestations of diphtheria. During the outbreak in the Kyrgyz Republic in 1995, myocarditis was seen in 22% and neuropathy in 5% of hospitalized patients. The mortality rate was 7% among patients with myocarditis as opposed to 2% among those without myocardial manifestations. The median time to death in hospitalized patients was 4.5 days. Myocarditis is typically associated with dysrhythmia of the conduction tract and dilated cardiomyopathy. Neurologic manifestations may appear during the first or second week of illness, typically beginning with dysphagia and nasal dysarthria and progressing to other signs of cranial nerve involvement, including weakness of the tongue and facial numbness. Ciliary paralysis, which is typical, manifests as blurred vision due to paralysis of pupillary accommodation, with a preserved light reflex. Cranial neuropathy may be followed by respiratory and abdominal muscle weakness requiring artificial ventilation. Several weeks later—sometimes as cranial neuropathy is improving—a generalized sensorimotor polyneuropathy may appear, with prominent autonomic manifestations (including hypotension) in some cases. The clinical syndrome and the findings on lumbar puncture of raised levels of protein without pleocytosis in cerebrospinal fluid resemble Guillain-Barré syndrome (Chap. 380). Pathologically, diphtheria neuropathy is a noninflammatory demyelinating disorder mediated by the exotoxin. Gradual improvement is the rule in patients who survive the acute phase. Other complications of diphtheria include pneumonia, renal failure, encephalitis, cerebral infarction, and pulmonary embolism. Serum sickness can result from treatment with diphtheria antitoxin (see "Diphtheria Treatment," below). . Chapter 131. Diphtheria and Other Infections Caused by Corynebacteria and Related Species (Part 3) Clinical Manifestations Respiratory Diphtheria The clinical diagnosis of diphtheria. "bull-neck" diphtheria, which results from massive edema of the submandibular and paratracheal region and is further characterized by foul breath, thick speech, and stridorous breathing headache, and voice change are the initial manifestations. Neck edema and difficulty breathing are seen in more advanced cases and carry a poor prognosis. The systemic manifestations of diphtheria