DOI: 10.1097/01.inf.0000227803.87268.84

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PMID: 16874187

Issn Print: 0891-3668

Publication Date: 2006/08/01


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Fatal Cytomegalovirus Myocarditis in an Infant With Omenn's Syndrome

Therese A. Chan Tack; Sherry Sandy; Kirk M. Chan-Tack

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Omenn's syndrome is a rare, autosomal-recessive, usually fatal immunologic disorder of infancy characterized by B-cell deficiency and dysfunctional T cells. Clinical manifestations include erythematous, desquamative rash, alopecia, diffuse lymphadenopathy, hepatosplenomegaly, chronic diarrhea, failure to thrive and recurrent infections, typically bacterial. Laboratory evaluation often reveals lymphocytosis, anemia, hypogammaglobulinemia, hypoproteinemia and reduced lymphoproliferative responses to mitogens. Characteristic pathology includes thymic dysplasia, loss of B-cell-containing regions within the reticuloendothelial system and extensive infiltrates of eosinophils and interdigitating reticular cells.1–3 Although most cytomegalovirus (CMV) infections are asymptomatic, CMV can cause significant disease in immunocompromised patients.4–7 We report a patient with Omenn's syndrome and fatal CMV myocarditis.
A 4-month-old girl was referred for evaluation of 3 months of intractable fevers, diarrhea, failure to thrive and diffuse erythroderma. She was the product of an uncomplicated pregnancy delivered at 37 weeks’ gestation. Family history was unremarkable and there were no siblings. Examination revealed alopecia, oral candidiasis, periorbital and peripheral edema, diffuse exfoliative rash, hepatosplenomegaly and generalized lymphadenopathy. White blood cell count was 8600/mm3 (18% bands, 21% neutrophils, 44% lymphocytes, 15% mononuclear cells, 2% eosinophils), hematocrit 35.2%, total protein 4.6 g/dL and albumin 3.2 g/dL. Serum IgG was 36 mg/dL (reference, 165–780 mg/dL), serum IgM 18 mg/dL (reference, 25–100 mg/dL) and serum IgA <7 mg/dL (reference, 4–80 mg/dL). A lymph node biopsy showed absence of B cells, loss of germinal centers, numerous eosinophils and histiocytoid cell proliferation. Immunohistochemical and electron microscopy studies confirmed the diagnosis of Omenn's syndrome.
Intravenous immunoglobulin (IVIG) was initiated. She developed hypothermia, hypotension, bradycardia, respiratory distress, renal and hepatic failure, worsening anemia, thrombocytopenia and coagulopathy. Funduscopy showed bilateral, multifocal hemorrhagic retinitis. Chest radiograph showed interstitial infiltrates, pulmonary edema and an enlarged, globular heart. Echocardiogram revealed severe left ventricular dilatation and dysfunction (ejection fraction 20%). Serologic studies suggested acute CMV infection. Molecular analysis of sera, using CMV pp65 antigenemia and quantitative polymerase chain reaction assays for CMV DNA detection, were both markedly positive. Despite ganciclovir, IVIG and maximal supportive therapy, she eventually died of multiorgan failure. Autopsy confirmed disseminated CMV in the heart, lungs, liver, kidneys, adrenals, pancreas, thymus, pituitary, skeletal muscles, ovaries and retina by immunohistochemical analysis and electron microscopy. The heart was enlarged (45.3 g; reference, 30 g) with severe myocarditis, extensive myocyte loss and numerous CMV inclusions. CMV was also recovered from human fibroblast viral cultures of myocardial tissue.
Host cellular-mediated immune responses are crucial against CMV infection. Nonspecific mechanisms such as natural killer cells and interferon production are activated in the early stages of CMV infection. The generation of specific CD8+ T cells against CMV antigens is thought to be the most important host immune response.4–7 Consequently, patients with deficiencies of cell-mediated immunity such as HIV infection, solid organ transplant recipients, bone marrow transplant recipients and primary immunodeficiencies (including Omenn's syndrome) are at greatest risk for severe, potentially fatal CMV disease.4–6 Potent suppressants of T-cell immunity such as antithymocyte globulin are also associated with high rates of clinical CMV syndromes.7 This case underscores the importance of clinical vigilance, early diagnosis and aggressive treatment of severe CMV infections to reduce morbidity and mortality among high-risk patients.
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