Cardiac involvement in diphtheria: Study from a tertiary referral infectious disease hospital

Background: Diphtheria is still a fatal disease even in the era of universal immunization. Diphtheria myocarditis, one of the serious complications of respiratory diphtheria may cause death if not recognized and treated properly. Aims and Objectives: To determine the outcomes of cardiac involvement in respiratory diphtheria. Materials and Methods: One hundred (n = 100) patients with respiratory tract diphtheria were evaluated in respect to cardiac involvement. All patients were closely monitored for a minimum period of 4-6 weeks from the onset of respiratory symptoms. Continuous ECG monitoring including blood biochemistry (SGOT, CPK-MB, and Troponin-T) were done in each case. Results : The most common symptoms were throat pain seen in 94 cases, palpitation in 56 cases, bull neck in 40 cases, shortness of breath in 12 cases, fever in 9 cases, and nasal regurgitation in 8 cases. Most common complication observed was myocarditis seen in 70 patients and majority of patients (60) were asymptomatic. The ECG changes were T wave inversion in 54 patients, inappropriate sinus tachycardia in 38 patients, ST segment depression in precordial leads in 8 patients, Mobitz type II block in 6 patients, Mobitz type I block in 4 patients, RBBB in 4 patients, multiple atrial ectopics in 4 patients, and sinus bradycardia in 2 patients. A total number of five patients died. Conclusions: Myocarditis was commonest and serious complication of respiratory diphtheria. Increase in vaccination coverage and improvement of socioeconomic status are all effective preventive measures to reduce the incidence of diphtheria.

Keywords: Cardiac involvement, diphtheria, outcomes

Diphtheria is still endemic in many developing countries and is responsible for high case fatality. ^[1] The incidence of diphtheria in the developed nations has steadily declined following effective immunization programme since the 1920’s. However, resurgence had been observed mainly due to waning immunity in adults and importation of new cases from the endemic regions. ^[1],[2] In India, diphtheria still remains endemic with fulminant complications and mortality especially in children above 5 years. ^[3] Several factors like inadequate vaccine coverage, poor socio-economic status, delayed reporting, and nonavailability/delayed administration of diphtheria antitoxin further contribute to high mortality. ^[4] The level of immunity declines in late childhood and adolescence due to lack of booster doses, waning immunity with age, and decreased reservoir of C. Diphtheria in the community leading to gap in the immunity and outbreaks of diphtheria. Myocarditis may occur in about 10-25% of patients with respiratory diphtheria and was reported to cause high mortality. ^[3] Diphtheria myocarditis is frequently complicated by arrhythmias that can cause sudden death if not managed properly. The patients with cardiac involvement may be asymptomatic (ECG change and/or raised SGOT) or symptomatic (features of heart failure). The ECG changes of myocarditis may be sickle-like sagging of the ST segment (specific for diphtheritic myocarditis), arrhythmias (supraventricular or ventricular), abnormal Q waves, repolarization abnormalities, ST-segment elevation > 1 mm in at least two chest leads or one limb lead, T-wave inversion (except in leads V1 and aVR), isoelectric T waves and QTc interval > 0.39 s for men and > 0.41 s for women, atrioventricular block, bundle branch block, hemiblock, etc. ^[5] Patients who presents with extensive patch and bull neck usually have more incidence of cardiac involvement. ^[6] So early and adequate administration of ADS with frequent monitoring particularly 24 h ECG monitoring is helpful to detect any serious cardiac arrhythmia. WHO recommends immediate administration of diphtheria antitoxin and antibiotics following clinical diagnosis pending the culture reports for confirmation. ^[5] The diphtheria vaccine is one of the major approaches for the control and prevention of diphtheria (at least 90% coverage). ^[7] The objective of this study was to determine the outcomes of respiratory diphtheria with special reference to cardiac involvement.

One hundred cases (n = 100) with a clinical diagnosis of diphtheria admitted in the ID and BG Hospital, Kolkata, West Bengal, India, from January 2010 to January 2011 were treated and analyzed in respect to demographic details, immunization status, and clinical features with particular attention to cardiac involvement. Written consent was obtained in all cases. Patients with background history of diabetes, hypertension, heart disease, and with previous ECG changes were excluded from this study. All patients with a clinical diagnosis of diphtheria were treated with intravenous benzyl penicillin and antidiphtheritic serum (ADS). Throat swab for Albert’s stain and culture were done in all cases. Each patient was monitored closely for any development of shortness of breath, palpitation, chest discomfort, and hypotension. ECG was done in all at the time of admission and repeated as and when required. Patients with anticipated/ established cardiac involvement were shifted to intensive coronary care unit for better monitoring. Blood test including serum urea, creatinine, SGOT, CPK- MB, and Troponin-T were done in all patients at the time of admission and repeated when required.

In this study the most common age group affected was 5-10 years (35 cases), though 18 patients were above 40 years of age. Most of the patients (65 patients) were from lower socioeconomic status with a history of accommodation sharing. Sixty patients were adequately immunized (received three or more doses of diphtheria toxoid containing vaccine by age 2), 24 patients were partially immunized, whereas 16 patients were unimmunized [Table 1]. Patients above 10 years of age didn’t receive booster dose (adult diphtheria-tetanus vaccine). Common clinical features were throat pain seen in 94, palpitation in 56, bull neck in 40 [Figure 1], shortness of breath in 12, fever in 9, nasal intonation/regurgitation in 8 cases, but less common features were difficulty in swallowing in 3, stridor in 2, bleeding from pseudomembrane [Figure 2] in 2, renal failure in 2, and thrombocytopenia, diplopia [Figure 3], and limb weakness in one case each [Table 2]. Faucial pseudomembrane [Figure 4] was observed in 95 cases of which 15 patients had extension to soft palate/nasopharynx. Most common complication was myocarditis seen in 70 patients, developed within 7 days of onset of respiratory symptoms. Ten patients were symptomatic of which four patients developed frank features of heart failure [Table 3]. Sixty patients had asymptomatic myocardial involvement, with only ECG changes and/or elevated SGOT. The ECG changes of myocardial involvement were T wave inversion [Figure 5] and [Figure 6] in precordial leads, inappropriate sinus tachycardia [Figure 7] and [Figure 8], ST segment depression in anterior precordial leads (pseudo infarct pattern), 2 ^nd degree AV block [Figure 9], RBBB, and multiple atrial ectopics, sinus bradycardia [Table 4]. Average duration of resolution of ECG changes was 4-6 weeks after onset of respiratory symptoms. Total five patients died, of which two patients died due malignant arrhythmias (VT/ VF) and other three patients died due to aspiration pneumonia- sepsis-ARDS secondary to neurological involvement. Thrombocytopenia was detected in one patient. Serum urea and creatinine were raised in two patients. Myocardial injury markers-SGOT, CPK-MB, and Troponin-T were elevated in 38, 10, and 5 patients, respectively. Patients who had developed frank features of cardiac failure showed persistently elevated SGOT level [Table 5].

In India, 3480 cases of diphtheria had been diagnosed and treated in 2009 with 113 death and a mortality rate of 3.5%, which is basically the tip of the iceberg. ^[8] The endemicity of this disease in India even in the era of Universal Immunization Programme is possibly due to inadequate vaccination coverage (only 66% children were vaccinated in 2008 in India), accommodation sharing, decreased incidence of skin infection by C. diphtheriae due to lifestyle changes (conferring natural immunity), and ineffectiveness of the administered diphtheria vaccine. ^[8]

In this study clustering of diphtheria cases was seen in the age group of 5-10 years predominantly due to lack of booster doses (DT), unidentified and untreated diphtheria carriers, whereas patients below 5 years of age had diphtheria possibly due to modifying effect of passively acquired maternal antibodies in young infants which could suppress the development of active immunity following early administration of DPT vaccine, diminished efficacy of administered vaccine, and improper vaccine preservation. In adults diphtheria occurred possibly due to lack of booster doses and gradual waning of immunity with increasing age. ^[9] Myocarditis was the most common complication observed in less than 10 years of age group, whereas neurological complication was mainly seen in adults. Majority of the patients with myocarditis were asymptomatic, had only ECG changes, SGOT elevation, and had a favorable outcomes. Another observation was that almost all patients developed cardiac involvement within first week of onset of respiratory symptoms and patients who had bull neck and extensive faucial patches had more incidence of cardiac involvement. ^[6],[10] The patients who were adequately immunized and received ADS earlier, improved with less complications in comparison to unimmunized/partially immunized patients who received ADS late/inadequate doses. ^[11] It had been observed that patients who had developed frank features of heart failure showed persistently elevated SGOT level which was closely parallel to the intensity of myocarditis and this may be used to monitor its course. ^[12] The unusual complications were renal failure and thrombocytopenia [Table 4]. The cause of renal failure was probably due to the effect of diphtheria toxin on renal tubular cells but the cause of thrombocytopenia in one patient was unexplained.

Though the incidence of diphtheria has not much declined, the mortality was decreased gradually since the last 30 years mainly due to more vaccination coverage, early administration, and easy availability of ADS and improved health care. It must be remembered that diphtheria is still with us and is still lethal; therefore, a high index of suspicion should be maintained in those with sore throat, bull neck, and faucial patch associated with unexplained tachycardia or neuropathy and in such cases antitoxin should be administered immediately, pending diagnostic confirmation. Availability of antitoxin must be ensured at all times. Following public health measures are essential to reduce the incidence and epidemics of diphtheria: (a) 90% coverage with three doses of DPT vaccine in children below one year of age, (b) immunizing adults with adult-type diphtheria-tetanus vaccine (Tdvac) every 10 years, and (c) administration of Td vaccine instead of tetanus toxoid, etc., should be instituted to decrease the incidence of diphtheria.

The author would like to thank the patient for providing consent to use his photograph in this article.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.102031

[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]

[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]