CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 AFRICA 119 Infection with toxigenic strains of Corynebacterium diphtheriae by inhalation or direct contact produces respiratory symptoms after an incubation period of two to five days.5 The most common manifestation is pharyngeal disease, which causes tonsillar swelling and cervical adenitis, producing a bull-neck appearance. Definitive diagnosis of diphtheria relies on identification of the organism on pharyngeal swab and positive toxigenicity testing. The characteristic pseudomembrane is formed by necrotic tissue, exudate and organisms and can be seen on the tonsils, pharynx and larynx, sometimes extending into the tracheobronchial tree.4 Generation of a toxin within the pseudomembrane, with absorption into the circulation, is responsible for the systemic complications. The toxin has a predilection for binding to the myocardium, kidneys and peripheral nerves, where its cytotoxic effect is mediated through inhibition of protein synthesis.4 Since neutralisation by antitoxin is only effective while the toxin remains unbound in circulation, the decision to administer antitoxin must not be delayed and be based empirically on the clinical presentation of the patient. Antibiotic therapy with penicillin and erythromycin eradicates the bacteria and prevents further toxin production.5 Myocardial involvement complicates 10 to 25% of cases of respiratory diphtheria; however much higher rates have been reported in countries where diphtheria is endemic.3,6 While cardiotoxicity usually develops in the second week of the illness, severe cases may manifest cardiac involvement at presentation.3 The toxin targets the myocardium and causes inflammation and disruption of the nodal and specialised conducting tissue, thereby producing dilated cardiomyopathy with reduced ejection fraction, cardiogenic shock and a range of conduction abnormalities.6 ECG findings include prolongation of the PR interval, ST-segment changes, loss of anterior R waves, bundle branch block, complete heart block, and supraventricular and ventricular arrhythmias.7 Asymptomatic myocardial involvement may be detected by ECG changes and elevated cardiac enzymes.8 Cardiac involvement carries a 50 to 75% mortality rate and is the most common cause of diphtheria-related death.5 In India, where diphtheria remains endemic due to poor immunisation coverage, a series of 48 paediatric cases confirmed that myocarditis accounted for 85% of the 27 deaths.3 Death occurred on the basis of cardiogenic shock and conduction abnormalities, with the development of complete heart block being uniformly fatal, even when temporary pacing was utilised. While incomplete immunisation, hypotension, airway compromise and renal failure were all associated with an adverse outcome, myocarditis was the only independent predictor of mortality in that study.3 In the Indian study, the investigators noted that the likelihood of having myocardial involvement was strongly associated with the presence of a compromised airway.3 Similarly, a Vietnamese study of 154 children reported a bull neck and extensive pseudomembrane formation to be the strongest predictors of cardiac involvement.7 The researchers created a pseudomembrane score, with a score of two or more (confluent coverage over the tonsils) predicting the development of myocarditis. This suggests that the degree of toxin production is proportional to the size of the pseudomembrane. Notably, these clinical parameters were as effective at predicting cardiac involvement and mortality as the 24-hour ECG, echocardiography and cardiac enzymes. All of the 12 children who died in the Vietnamese study had myocarditis, and events preceding death were worsening heart failure, ventricular arrhythmias and complete heart block. In our case, clinical markers of severity were present on admission and included the bull neck, compromised airway, extensive pseudomembrane formation extending to the larynx, renal failure and a bleeding diathesis. There was extensive multi-organ involvement secondary to the C diphtheria toxin, resulting in myocarditis and acute tubular necrosis. Myocardial involvement characterised by cardiogenic shock and malignant ventricular arrhythmias was the most likely cause of death, and was confirmed on the histopathological findings. Fig 4A. Acute kidney injury (acute tubular necrosis), tubular casts with an inflammatory cell infiltrate (HE × 40). B. Cutaneous ulcer in the foot with superficial exudate. Microbiological and molecular investigations confirmed diphtheria (toxin producing). A B
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