Viral myocarditis

Corresponding Author:

Dr E. Davies MBBS, MSc

West of Scotland Specialist Virology Centre, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0YN. eswd@doctors.org.uk, 0141 211 0080.

Conflicts of interest: None declared

Case presentation

A previously healthy 35 year old woman, with no significant past medical history became unwell with a ‘chest infection’ in December. She was prescribed an antibiotic by her general practitioner a few days later. One week later she attended her local Accident and Emergency department and was found to be in cardiogenic shock. She died 12hours later following a cardiac arrest.

Post mortem findings included a small serous pericardial effusion and numerous punctate haemorrhages within the myocardium of both ventricles. The lungs were oedematous and congested with pus in the upper airways. All other organs were normal. Histological sections of both ventricles identified focal interstitial haemorrhage, areas of myocyte contraction, band necrosis and myocyte degeneration. There was a mixed inflammatory cell infiltrate with areas of mainly a lymphoid cell infiltrate within the interstitium. The post mortem findings were consistent with a viral myocarditis as the cause of death.

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The virology laboratory received post mortem cardiac and splenic tissue. These were tested according to the local protocol and the results are shown below.

Table 1 Initial results

	Post mortem - Heart	CMV DNA, EBV DNA, enterovirus RNA, adenovirus DNA	Negative
		Erythrovirus B19 DNA	Positive	*Ct 30.60
	Post mortem - Spleen	CMV DNA, enterovirus RNA, adenovirus DNA	Negative
		EBV DNA	Positive	Ct 33.18
		Erythrovirus B19 DNA	Positive	Ct 27.80
	*Ct =crossing threshold of the real time PCR assay

What is your differential diagnosis? What further samples would you request, if any? What further tests would you request, if any?

Evidence based opinion and complete Table of laboratory results:

In view of the patients’ symptoms, a sample of the post mortem lung tissue and a throat swab were requested. An ante mortem blood sample was tested for erythrovirus B19 IgM and IgG and influenza antibody by complement fixation test (CFT). The heart and spleen were tested for evidence of influenza infection.

Table 2: Subsequent results

	Post mortem - Heart	Influenza A, B and C RNA, CMV DNA, EBV DNA, enterovirus RNA, adenovirus DNA	Negative
		Erythrovirus B19 DNA	Positive	Ct 30.60
	Post mortem - Spleen	Influenza A, B and C RNA, CMV DNA, enterovirus RNA, adenovirus DNA	Negative
		EBV DNA	Positive	Ct 33.18
		Erythrovirus B19 DNA	Positive	Ct 27.80
	Ante mortem - Serum	Erythrovirus B19 IgM	Negative
		Erythrovirus B19 IgG	Positive
		Erythrovirus B19 DNA	Positive	Ct 34.50
		Erythrovirus B19 DNA	Positive	5.4x103 IU/ml
		Influenza A antibody (CFT)	Negative	1:16
	Post mortem - Lung	Influenza A RNA	Positive	Ct 32.07
	Ante mortem - Throat swab	Influenza A RNA	Positive	Ct 28.20
		Haemagglutinin type		H3

Evidence based opinion:

This case highlights the difficulties that can occur in interpreting the clinical significance of PCR results. This may be further complicated when the virus under discussion is known to persist lifelong or for prolonged periods e.g. erythrovirus B19. In these situations additional evidence such as clinical features, serology, epidemiology, or results from other investigations may be helpful.

There were three positive findings in this case. Erythrovirus B19 was detected in cardiac tissue, spleen tissue and serum. Influenza A virus was detected in the lungs and in a throat swab. Epstein-Barr virus was detected in the spleen. There was no evidence of the most likely cause, an enterovirus infection. Although enteroviruses are less commonly detected during the winter months, a faecal sample would have been the most appropriate sample to exclude this diagnosis. However, the patient died within 12hours of admission and a sample had not been sent. From the laboratory results, erythrovirus B19 stands out as the initial suspect, being detectable in cardiac tissue and serum. However, the clinical features of the illness and serological profile do not support this diagnosis either. It is now well recognised that erythrovirus B19 DNA can persist lifelong in a variety of tissues including bone marrow, skin, synovia, tonsils and liver. In a recent prospective study, erythrovirus B19 DNA was found in myocardial samples from 46 of 48 seropositive patients and in none of 21 seronegative individuals.12

The clinical presentation during the influenza virus respiratory infection season was compatible with an influenza infection. There was no serological evidence of recent infection, the influenza antibody titre was 1:16. However, a convalescent, blood sample was not available due to the short period between illness and death.

In the literature, influenza and erythrovirus infections have been associated with myocarditis. Influenza virus infections have been consistently, if rarely, associated with acute cardiac problems, including fatal cases.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Erythrovirus B19 in recent years has been associated with a large variety of cardiac pathology, mainly based on finding viral DNA in cardiac tissue, in some studies up to 84% of cases are attributed to B19.11 In these cases, however, little or no evidence was found of recent infection. The apparent discrepancy between the clinical features of patients in these studies and the detection of B19 now appears to be resolved. Erythrovirus B19 is a DNA virus which is known to persist in cardiac tissue. A recent critical review of the literature clearly discounted most of all published associations of erythrovirus B19 with a large variety of cardiac diseases.12 It appears that the virus simply persists in the cardiac tissue of most seropositive individuals. It is conceivable that the severe damage of cardiac tissue could release Erythrovirus B19 DNA in to the blood as found in this case or may merely reflect a persistent low level viraemia which has also been documented.

With regard to influenza, the rare descriptions of severe cardiac damage are well documented and are similar to our case.13 Tissue damage may be severe, leading to shock or tamponade.14 Viral RNA is rarely if ever found in the cardiac tissue, suggesting a specific immunopathological origin of the damage and maybe similar to the equally rare and severe, encephalopathy sometimes encountered directly following influenza. The fatal myocardial complication in this case therefore appears most likely to be linked to the acute influenza A infection.

The one remaining result which needs clarification is the presence of EBV DNA in the splenic tissue. Again, EBV is a persistent infection and the virus is lymphotropic. As the virus was only found in the spleen, its role in this case is unlikely, however serology to exclude recent infection was not performed.

This case of fatal influenza A infection highlights the difficulties that may occur in interpreting the significance of PCR results when multiple pathogens are detected. Relating the findings to the clinical features is also important as a number of DNA viruses may be picked up on routine testing but may simply be innocent bystanders reflecting persistent non significant infection. It also highlights the importance of testing the appropriate samples as the diagnosis in this patient may never have been made had lung tissue not been requested.