Published online May 21, 2007
PEDIATRICS Vol. 119 No. 6 June 2007, pp. e1400-e1403 (doi:10.1542/peds.2006-2605)

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EXPERIENCE & REASON

Acute Myopericarditis After Multiple Vaccinations in an Adolescent: Case Report and Review of the Literature

Maria T. Thanjan, MD^a, Prema Ramaswamy, MD^b, Wyman W. Lai, MD, MPH^a and Irene D. Lytrivi, MD^a,b

^a Department of Pediatric Cardiology, Mount Sinai Medical Center, New York, New York
^b Division of Pediatric Cardiology, Maimonides Medical Center, New York, New York

ABSTRACT

We report a case of postvaccination acute myopericarditis in an adolescent. The patient presented with acute chest pain, diffuse ST-segment elevation, and elevated cardiac enzyme levels. Cardiac MRI was consistent with acute myocarditis. He recovered within a few days with nonsteroidal antiinflammatory treatment and remains clinically stable, with improvement of MRI findings at the 10-week follow-up. Postvaccination cases of myopericarditis reported in the pediatric literature are also reviewed.

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Key Words: immunization • myopericarditis • adolescence

Abbreviations: ECG, electrocardiogram • DTaP, diphtheria-tetanus-acellular pertussis • Ig, immunoglobulin

Cardiac complications after routine immunizations are extremely rare, especially in children. The vaccination that has received great attention recently is that for smallpox, particularly after reinstitution of the vaccination for military personnel in 2002 and the reports of >50 cases of probable myocarditis temporally related to it.¹ A prospective Finnish study identified electrocardiogram (ECG) changes suggestive of myocarditis without other evidence of cardiac disease in 3% of military recruits after vaccination against mumps, polio, tetanus, smallpox, diphtheria, and type A meningococcus.² Few cases of myocarditis after smallpox vaccination have been reported in the pediatric literature as well.^3–8 Other vaccinations have also been implicated in children, albeit much more rarely. There is 1 reported case of myocarditis that developed hours after diphtheria-tetanus-acellular pertussis (DTaP) vaccination in a 3-month-old⁹ and another case of myocarditis after tetanus vaccination alone in a 14-year-old.¹⁰ Our case is the first report of myopericarditis temporally related to booster DTaP administered simultaneously with hepatitis A and meningococcal vaccines before college entry in an adolescent.

CASE REPORT

A 17-year-old white boy was admitted to the PICU with intermittent, retrosternal chest pain for 1 day. He had no history of angina pectoris, cocaine abuse, hyperlipidemia, or congenital heart disease. He also had no history of autoimmune disorder, no previous travel, and no previous flu-like illness with diarrhea and/or respiratory symptoms suggestive of an infectious syndrome. Two days before admission, he received DTaP, meningococcal conjugate (MCV4), and hepatitis A vaccines. This was the first time he had ever received meningococcal or hepatitis A vaccines. The following day he complained of diffuse arthralgia and chest pain, and he had a low-grade fever. In the emergency department his physical examination was normal, but he was found to have diffuse ST-segment elevation on ECG (Fig 1A) and elevated serum cardiac enzyme levels: troponin I, 15.9 ng/mL (reference: <0.4 ng/mL); creatine kinase, 1106 U/L (reference range: 24–145 U/L); and creatine kinase MB, 44.4 U/L (reference range: 5.7–16.6 U/L). A chest radiograph was normal, and a two-dimensional echocardiogram showed no segmental wall-motion abnormalities, normal biventricular systolic function, and no pericardial effusion. Other laboratory findings included a white blood cell count of 8.3 x 10⁹/L (with 62% neutrophils, 22% lymphocytes, and 3.7% eosinophils), hemoglobin level of 14.6 g/dL, C-reactive protein level of 59 mg/L (reference: <8 mg/L), erythrocyte sedimentation rate of 17 mm/hour (reference: <15 mm/hour), C4 level of 38 mg/dL (reference: 16–47 mg/dL), and C3 level of 142 mg/dL (reference: 88–201 mg/dL). Rectal and nasopharyngeal swabs were sent for adenovirus and enterovirus cultures, and the results were negative. Lyme immunoglobulin G (IgG)/IgM antibody, cytomegalovirus IgG, Epstein-Barr virus capsid IgM antibody, antinuclear antibody, and anti-DS DNA screens were also negative. Convalescent samples for the above-named infectious etiologies were not obtained.

View larger version (128K): [in this window] [in a new window]   FIGURE 1 A, Twelve-lead ECG at presentation showing ST elevation and PR depression on I, aVL, and V1–V6. B, One week later there was ST normalization. C, At the 3-week follow-up, there was T-wave inversion on I, aVL, and V1–V6.

 
Over the following 24 hours, the patient's cardiac enzyme levels continued to rise to a maximum of 22.8 ng/mL for the troponin I. Gadolinium-enhanced cardiac MRI was positive for myocarditis, as evidenced by delayed subepicardial enhancement of the basal to midanterolateral and inferolateral regions of the left ventricular wall (Fig 2 A and B). Chest pain was relieved with ketorolac, and his serum enzyme levels gradually decreased. The patient was discharged 4 days later on indomethacin 50 mg orally 3 times per day with the recommendation of restricting physical activity for a total of 4 to 6 weeks. Serum cardiac enzyme and C-reactive protein levels had all normalized 1 week after the onset of the symptoms. ECG at that time showed normalization of the ST segment (Fig 1B), and at the 3-week follow-up, there was diffuse T-wave inversion (Fig 1C). At 10 weeks, ECG findings had resolved, and the follow-up cardiac MRI showed decrease in the area of contrast enhancement (Fig 2 C and D). The patient remained asymptomatic with normal ventricular function as assessed by echocardiogram and MRI.

View larger version (188K): [in this window] [in a new window]   FIGURE 2 A and B, Cardiac MRI short-axis and 4-chamber views of the left ventricle in the acute phase showing the areas-of-contrast delayed enhancement (arrows). C and D, Equivalent views at follow-up showing a decrease in the area of involvement.

 

DISCUSSION

Although most cases of myocarditis in the United States and Western Europe result from viral infections, other etiologies such as other infectious agents, various drugs, hypersensitivity, and autoimmune disorders have been occasionally implicated. In our case, the possibility of a viral etiology cannot be definitely excluded; however, the negative viral serology and the absence of symptoms make this a less likely possibility. The proposed mechanism of myocardial injury in cases reported after vaccination is a hypersensitivity reaction.^10,11 Hypersensitivity myocarditis is usually a retrospective circumstantial diagnosis that is suspected because of the temporal link between receiving the vaccination or other offending agent and onset of symptoms. Pathogenesis is related to a maladaptive immune response that leads to myocardial injury, as evidenced by biopsy specimens in cases of myocarditis after smallpox vaccination that have revealed CD3⁺ T-cell infiltrate with prominent degranulating eosinophils.¹²

Patients with myopericarditis can be asymptomatic or present with chest pain, shortness of breath, palpitations, fatigue, and decreased exercise tolerance. Troponin I elevation has high specificity in supporting the diagnosis, especially in conjunction with strong clinical suspicion.¹³ On the other hand, erythrocyte sedimentation rate and C-reactive protein are more sensitive than specific as general markers of inflammation and are probably useful in monitoring the benefit of antiinflammatory treatment.

ECG abnormalities accompanying cardiac enzyme level elevation in the appropriate clinical setting are highly suggestive of myopericarditis and are reported in up to 90% of cases.¹⁴ Of interest is the natural progression of ECG changes that is commonly associated with myopericarditis and was observed in our patient. Four stages of evolution have been described.¹⁵ The initial stage occurs during the first few days and lasts up to 2 weeks. The most characteristic ECG finding is ST-segment elevation and PR-segment depression. This phase is followed by ST-segment normalization ± T-wave flattening; this stage is extremely variable in duration, lasting anywhere from a few days to several weeks. Stage III usually occurs in the second or third week of illness and can persist for a few weeks. During this time, full T-wave inversion occurs. In the final stage, there is resolution of the T-wave abnormality and a return to baseline normal ECG findings. It is important to note that although the 4-stage progression of the ECG findings is "pathognomonic" for myopericarditis and very useful for differentiating it from other clinical syndromes such as acute myocardial infarction or benign early repolarization, in many instances only part of the sequence occurs, and atypical presentations are common.

With cases like ours, in which suspicion of myopericarditis is high and risk for coronary artery disease is low, a noninvasive test to rule out ischemic heart disease is an acceptable alternative to cardiac catheterization. Cardiac MRI has been shown to be highly sensitive and specific for myocarditis detection and differentiation from myocardial infarction.^16,17 Delayed gadolinium enhancement of the myocardium is usually subepicardial (as opposed to the subendocardial involvement usually seen with ischemia and infarction) and can be focal or diffuse depending on the timing after the onset of symptoms.^16,18 The cellular-level mechanism proposed to explain this contrast enhancement is rupture of the myocyte membrane and diffusion of the contrast agent into the necrotic cells, which results in increased tissue-level concentration.¹⁹

Because most reported cases of postvaccination myopericarditis are self-limited, the role of treatment is not clear. On the basis of limited data and mostly anecdotal evidence, patients are either not treated¹⁰ or nonsteroidal antiinflammatory drugs^11,20 and corticosteroids^3,6,21 are used in cases of more severe clinical presentation (evidence of congestive heart failure). No data exist regarding long-term sequelae, and as a consequence, recommendations for long-term follow-up of these patients are not evidence-based. The role of myocardial damage, shown by contrast cardiac MRI, as a predictor for long-term outcome needs to be investigated further.

CONCLUSIONS

Our case highlights the fact that pediatricians should be aware of the often-dramatic presentation of postvaccination myopericarditis and its usually benign clinical course. The diagnosis of myocarditis should be entertained when acute-onset chest pain is accompanied by ECG changes and elevated cardiac enzyme levels. In cases in which the above-described presentation is temporally related to routine immunizations, the immunizations should be considered as a possible underlying etiology.

FOOTNOTES

Accepted Nov 28, 2006.

Address correspondence to Irene D. Lytrivi, One Gustave L. Levy Place, Box 1201, New York, NY 10029. E-mail: renalytrivi{at}yahoo.com

The authors have indicated they have no financial relationships relevant to this article to disclose.

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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This Article Abstract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Thanjan, M. T. Articles by Lytrivi, I. D. Search for Related Content PubMed PubMed Citation Articles by Thanjan, M. T. Articles by Lytrivi, I. D. Related Collections Infectious Disease & Immunity Social Bookmarking                         What's this?