Journal of Infection (1981) 3, 172-175

CASE REPORT

Infectious mononucleosis myocarditi~

Ted Butler,*t John Pastore,:~ Gary Simon? and Michael Worthington~

$ The Department of Medicine, St. Elizabeth's Hospital and t The Infectious Diseases Division, Tufts-New England Medical Center, Boston,

Massachusetts 02111, U.S.A.

Summary A case of infectious mononucleosis presenting with myocarditis is reported, and the literature on cardiac involvement during the course of Epstein-Barr virus infections is reviewed. Serious cardiac sequelae appear uncommon, although asymptomatic cardiac manifestations may not be infrequent. Use of more specific serodiagnostic techniques is suggested to elucidate the role of the Epstein-Barr virus as an aetiological agent in myocarditis.

Introduction

Clinically evident cardiac involvement during the course of infectious mono- nucleosis is uncommon. In Hoagland's monograph, symptoms referable to the cardiovascular system were said to occur in only three of 500 patients (Hoagland, 1967). He also reported that minor T wave abnormalities occur- red on the electrocardiograms in six per cent of cases, but whether this represented myocardial or pericardial involvement or non-specific abnor- malities due to fever, hyperventilation or electrolyte imbalance has not been ascertained.

We recently cared for a patient with infectious mononucleosis whose presentation initially mimicked that of myocardial infarction and in whom the initial slide test for mononucleosis was negative.

Case report

A 29 year old male presented to the emergency ward in September 1978 complaining of an intermittent aching pain in the left side of the chest of 24 hours duration. The pain radiated to the left arm but was unrelated to position, exertion or respiration.

He had been well throughout his life except for labile hypertension and obesity. He had been seen one week previously for complaints of a sore

* Requests for reprints to: Dr Ted Butler, Infectious Diseases, Lawrence Memorial Hospital, Gover- nors Avenue, Medford, Massachusetts 02155, U.S.A.

0163-4453/81/020172+04 $01-00/0 ©1981 The British Society for the Study of Infection

Infectious mononucleosis myocarditis 173

throat and myalgia. Examination at that time was unrevealing and aspirin was recommended.

Physical examination at the time of admission showed an oral temperature of 38.4°C and mild obesity. There were no other abnormal physical findings.

An electrocardiogram (Plate 1) disclosed ST segment elevation in leads II, III, AVF and V~-V6. This suggested inferoapical injury and he was admitted to the coronary care unit for observation. During his first few days in hospital he complained of chest pain that did not respond to nitrates but was abolished by analgesics. A pericardial rub was not heard. Laboratory studies revealed a peak elevation of CPK (creatinine phosphokinase) of 299 (normal 9-85 U/l) with a positive MB (myocardial band) fraction. The electrocardiogram showed return of the ST segments to the baseline but the T waves became inverted in the inferior leads. An echocardiogram showed normal inferior left ventricular wall motion and no pericardial effusion.

The patient had intermittent fever. The white blood cell count was 6.0 × 10~/1 with 44 per cent polymorphs, 5 per cent stabs, 46 per cent lympho- cytes, 2 per cent eosinophils and 3 per cent monocytes. There were many atypical lymphocytes but a slide test for infectious mononucleosis was nega- tive (DiaglutoR). He was discharged after one week in hospital, improved, to convalesce at home.

Three days later he returned with fever, shaking chills and dark urine. On examination his temperature was 39°C but no other abnormality was noted. An electrocardiogram disclosed deep T wave inversions inferiorly and in V5 and V6 (Plate 2). Laboratory studies disclosed a white cell count of 13.9 × 109/1 with 8 per cent polymorphs, 14 per cent stabs, 73 per cent lympho- cytes, 2 per cent eosinophils, 1 per cent basophils, 2 per cent monocytes and many atypical lymphoeytes. The bilirubin was 80.4/~mol/1 (direct 54.7), alkaline phosphatase 295 (normal 24-89 U/l), alanine aminotransferase 109 (normal 6-24 U/l) and aspartate aminotransferase 77 (normal 8-29 U/l). The slide test for infectious mononucleosis was now positive, at a titer of 1:4. Hepatitis B surface antigen was absent.

He was treated with antipyretics and, over the course of 10 days, fever resolved accompanied by clinical improvement and early resolution of the hepatocellular abnormalities.

Serologic data are shown in Table I. Attempts to isolate viruses from throat, stool and urine were negative. The data reveal a diagnostic rise in the IgG-VCA titer to the Epstein-Barr virus, indicative of recent infection.

Discussion

It is well known that myocarditis or pericarditis can complicate infectious mononucleosis (Leibowitz, 1953; Webster, 1957; Pejme, 1964; Hoagland, 1967). However, some of the older reports might be questioned as not all patients had unequivocal evidence of carditis (other than electrocardiog- raphic abnormalities), an appropriate clinical syndrome and positive

174 T. Butler et al.

Table I Serology*

Date

First admission Second admission

19 September 21 September 28 September 2 October 1978 1978 1978 1978

Diagluto R N.D. Negative 4 2 Ox cell hemolysist <10 N.D. 80 40 Cytomegalovirust < 8 N.D. < 8 < 8 Adenovirust <8 N.D. <8 <8 M. pneumoniaet 16 N.D. 32 16 Influenza A t 16 N.D. 32 32 Influenza Bt <8 N.D. <8 <8 Mumpst <8 N.D. <8 <8 Epstein-Barr virus* 0 N.D. 1600 1600

(IgG-VCA)

* The data are the reciprocals of the highest dilution positive. t Performed at the Virus Laboratory, State Laboratory Institute, Massachusetts

Department of Public Health. $ Performed at the Center for Disease Control, Atlanta, Georgia. The test was the

immunofluorescent assay for IgG specific antibody to the viral capsid antigen. N.D., not done.

heterophil serology. There appear to be only two other English language reports in which more specific Epstein-Barr serodiagnostic studies were employed (Miller, Ward, Amsterdam, Mason and Zelis, 1973; Frishman, Kraus, Zabkar, Brooks, Alsono and Dixon, 1977). The former of these recent cases is similar to the one reported herein, in that a myocardial infarction was initially suspected in a young patient. Subsequently coronary angiography was normal. The second report describes a patient who appar- ently died of a ventricular arrhythmia several days after the diagnosis of infectious mononucleosis was made. At autopsy, there was a severe inflammatory myocarditis affecting the left Ventricle. This young woman may be only the second reported case of death due to myocardial involvement in the English literature; the other is described in the review of Penman (1970).

The infrequency with which these serious sequelae are observed would serve to support the contention of Hoagland that there is little to fear from cardiovascular complications in this disease (Hoagland, 1964). However, if myocarditis does occur, prudent clinical observation would seem indicated.

There are a few additional aspects worthy of comment. Our patient's illness was biphasic and had he consulted other physicians during the latter part of his illness, the aetiology of his myocarditis might have remained unknown since the initial slide test was negative. This emphasises the need to follow up patients with myocarditis and for repeated serological studies. Heterophil responses, for example, can be delayed (Horowitz, Henle, Henle, Polesky, Balfour, Siem, Borken and Ward, 1977).

It should also be noted, as emphasised by Miller (Miller, Ward, Amster- dam, Mason and Zelis, 1973), that infectious mononucleosis should be excluded in the young person presenting with findings compatible with

Plate 1. ECG (first admission) showing ST segment elevation in leads II, III, AVF and vj-vs.

&zcing page 1741

Plate 2. ECG (second admission) showing T wave inversion in leads II, III, AVF and V5-V,.

Infectious mononucleosis myocarditis 175

myocardial infarction in order to avoid wrongly attributing their symptoms to coronary artery disease. The same might be said about the occasional older pat ient presenting with chest pain if atypical features are present ( inordinate fever, atypical lymphocytosis) as this group may lack other features of mononucleosis . With the use of specific serodiagnosis, available since the Eps te in-Bar r virus has been shown to be the cause of infectious mononuc- leosis, it has become apparent that heterophil-negat ive Eps te in-Barr infec- tions not uncommonly occur (Rapp and Hewetson , 1978), and, in fact, are the rule in infections in the very young (less than five years of age). Hence these serological examinat ions should be sought rout inely to help elucidate the aet iology of 'viral' pericarditis or myocarditis.

References

Carter, J., Edson, R. and Kennedy, C. (1978). Infectious mononucleosis in the older patient. Mayo Clinic Proceedings, 53, 146.

Frishman, W., Kraus, M., Zabkar, J., Brooks, V., Alonso, D. and Dixon, L. (1977). Infectious mononucleosis and fatal myocarditis. Chest, 72, 535.

Hoagland, R. (1964). Mononucleosis and heart disease. American Journal of the Medical Sciences, 248, 35.

Hoagland, R. Infectious Mononucleosis. Grune and Stratton, New York (1967), pp. 61~58. Horowitz, C., Henle, W., Henle, G., Polesky, H., Balfour, H., Siem, R., Borken, S. and Ward,

P. (1977). Heterophil-negative infectious mononucleosis and mononucleosis-like ill- nesses. American Journal of Medicine, 63, 947.

Leobowitz, S. Infectious Mononucleosis. Grune and Stratton, New York (1953), pp. 46-54. Miller, R., Ward, C., Amsterdam, E., Mason, D. and Zelis, R. (1973). Focal mononucleosis

myocarditis simulating myocardial infarction. Chest, 63, 102. Pejme, J. (1964). Infectious mononucleosis: a clinical and hematological study of patients and

contacts and a comparison with healthy subjects. Acta Medica Scandinavica (Supple- ment), 413, 1.

Penman, H. (1970). Fatal infectious mononucleosis: a critical review. Journal of Clinical Pathology, 23, 765.

Rapp, C. and Hewetson, J. (1978). Infectious mononucleosis and the Epstein-Barr virus. American Journal of Diseases of Children, 132, 78.

Webster, B. (1957). Cardiac complications of infectious mononucleosis. A review of the literature and report of five cases. American Journal of the Medical Sciences, 234, 62.