A 5-year-old girl develop a fever of 101 F with sore throat and difficulty swallowing. Several days later she develops edema of the neck with difficulty breathing. She then becomes listless. She is taken to the family physician who notes persistent fever. Auscultation of the chest reveals minimal basilar crackles. The heart rate is regular, with tachycardia to 110 beats/minute. No murmurs are heard.

It is noted that the child has a foul breath along with massive swelling of the tonsils, and cervical lymphadenopathy, with striking edematous swelling of the submandibular region and anterior neck. Examination of the oropharynx reveals marked edema of the uvula and a dirty grey, leathery-appearing membrane over the posterior pharyngeal region. A similar membrane is seen over the posterior nasal septum. When a portion of this membrane is removed for culture, there is mucosal bleeding.

Laboratory findings include:

• Hemoglobin 13.3 g/dL

• Hematocrit 40.2%

• MCV 94 fL

• Platelet count 270,000/microliter

• WBC count 25,100/microliter

• WBC differential: Segs 73, bands 6, lymphs 16, 5 monos

Additional History

Laboratory findings include:

• AST 85 U/L

• ALT 49 U/L

• Total Bilirubin 0.7 mg/dL

• CK-MB slightly elevated

• Troponin I moderately elevated

Question 6.1 - What is the most likely diagnosis?

The pseudomembrane contains large numbers of C. diphtheriae organisms, but the bacteria are rarely isolated from the blood or internal organs.

Definitive diagnosis of diphtheria depends on the isolation of C. diphtheriae from local lesions. The laboratory should be notified that diphtheria is suspected to ensure the use of selective tellurite medium appropriate for the isolation of C. diphtheriae. All isolates of C. diphtheriae should be subjected to toxicity testing. Primary isolates can be screened rapidly for the presence of the tox gene by the polymerase chain reaction, although occasional strains of C. diphtheriae that carry an inactive toxin gene give false-positive results.

Biochemical tests needed to differentiate C. diphtheriae from corynebacteria of the normal flora (diphtheroids) require several days.

Question 6.2 - Explain the cardiac findings.

Diphtheria toxin acts both locally and systemically, and the lethal dose for humans is ~0.1 g/kg. Toxin contributes locally to pseudomembrane formation; systemically, it can cause myocarditis, neuritis, and focal necrosis in various organs, including the kidneys, liver, and adrenal glands.

Diphtheria can cause permanent cardiac damage.

Diphtheria toxin is produced by C. diphtheriae as an extracellular polypeptide. Proteolytic cleavage forms nicked toxin consisting of fragments A and B. Fragment B binds to a plasma-membrane receptor (a precursor of a heparin-binding growth factor resembling epidermal growth factor), and the bound toxin is internalized by receptor-mediated endocytosis.

Myocarditis and polyneuritis are the most prominent toxic manifestations of diphtheria. The risk of each is proportional to the severity of local disease.

Myocarditis occurred in 22% and neuritis in 5% of 656 hospitalized patients (54% female, 70% 15 years old) with diphtheria in the Kyrgyz Republic in 1995; 7% of patients with myocarditis and 2% of patients without myocarditis died. The median interval from hospitalization to death was 4.5 days (range, 0 to 13 days).