Case report

A 9-month-old male baby was admitted at the Heart Institute of Sao Paulo, having been referred from the city of Londrina, in the Southern region of Brazil, with a previous history of a cardiac murmur since 1 month of life, when the clinical diagnosis was persistent patency of the arterial duct. At the age of 3 months, cardiac catheterisation showed increased flow of blood to the lungs, and he underwent elective surgical closure of the persistently patent arterial duct. During the post-operative period, he suffered acute renal failure, albeit with no need for dialysis, and he recovered after 12 days. Despite the surgical correction, the outcome was not good, and he failed to gain weight. At the age of 8 months, he presented with bronchopneumonia, which was successfully treated. One month later, during admission for further cardiovascular evaluation, his mother described how he had suffered from a productive cough and wheezing since the neonatal period. His weight at that time was 7,700 grams, and analysis of blood showed leucocytosis, at 16,400 per cubic millimetres, with 57% lymphocytes. Echocardiography demonstrated severe left ventricular hypertrophy and isthmic aortic coarctation, with a gradient across the stenosed site of 38 millimetres of mercury. During inpatient care he showed several episodes of bronchospasm, which were responsive to medications. He was haemodynamically stable, and elective plasty of the isthmus was performed on the fifth day after his admission. Immediately after the operation, his progress was satisfactory, but he then suffered episodes of fever. On the third postoperative day, he became oliguric and respiratory assistance was needed. On the fourth postoperative day, he developed bronchospasm, and suffered two episodes of cardiac arrest. On the following day, peritoneal dialysis was initiated, but he continued to exhibit severe bronchospasm and bradycardia. In spite of all medications and supportive care, he died on the fifth postoperative day.

The autopsy showed good repair at the site of coarctation, albeit with right and massive left ventricular hypertrophy. Histology revealed diffuse pulmonary arteriolar lesions, characterized by severe hypertrophy of the medial layer, consistent with grade 1 in the categorisation of Heath and Edwards, and wavy elastic laminas, interpreted as a sign of vasoconstriction (Fig. 1a). There was also diffuse bronchiolitis, with epithelial necrosis and syncytial formations, making us suspect the respiratory syncytial virus as the causal agent (Fig. 1b). This suspicion was then confirmed by immunohistochemical search for the virus in paraffin-embedded lung tissue using a primary antibody against the respiratory syncytial virus (Figs. 1c and 1d). Tissue processed for electron microscopic analysis showed dense cytoplasmic inclusions in bronchiolar epithelial cells, again consistent with infection by the respiratory syncytial virus (Fig. 2).

Figure 1. Microphotographs of the pulmonary histology. In (a), the arrow indicates the wavy internal elastic lamina of an arteriole of the respiratory bronchiole, a signal of vasoconstriction (original magnification 40×). In (b), the bronchiole shows numerous digitiform projections produced by multinucleated cells projecting from the epithelial layer. There is a mild mononuclear peri-bronchiolar infiltrate (Haematoxylin & Eosin; original magnification 20×). The immunohistochemical search for the respiratory syncytial virus is shown in Figure 1c, where the positivity is represented by the dark cells delineating the bronchiolar lumen (original magnification 20×). The inset exhibits a higher magnification of one of the positive cells (arrow) with syncytial formation. In Figure 1d, the viral inclusions are highlighted by the immunofluorescence technique employing the same antibody, with one indicated by the white arrow (original magnification 40×).

Figure 2. Electronmicrographies, from (a) to (d), show the presence of cytoplasmic viral inclusions (V) in the bronchi-olar epithelial cells, represented by the agglomerated material with similar density of the nuclear chromatin (N).

Discussion

The respiratory syncytial virus, a ribonucleic acid virus, is an important pathogen of infancy and childhood, and generates considerable seasonal outbreaks every year.¹ In the city of São Paulo, as in other subtropical regions, the outbreaks of infection peak in the fall, and extend into the winter. A local prospective study conducted among hospitalized children infected by the virus has demonstrated two seasonal trends, with peaks in May and June.² In another series, also from São Paulo city, the respiratory syncytial virus was the most frequently isolated virus from children hospitalized for acute respiratory disturbances, being present in over half the children studied.³

Infection by the virus can complicate the postoperative course subsequent to paediatric cardiac surgery, and it has been identified as the causal agent of up two-fifths of cases of pneumonia, from half to nine-tenths of the cases of bronchiolitis, and from one-tenth to one-third of instances of bronchitis occurring in young children.^{1, 4} Besides preterm infants, children under 6 months of age with immune deficiency, malignancies, chemotherapy, bone marrow or solid organ transplants, chronic pulmonary disturbances and congenital cardiac malformations are known to be at major risk from infection of the lower respiratory tract with this virus.^3–5 The reported mortality of hospitalized patients is from 1 to 4.4%, and can be higher when associated with other agents such as adenovirus, pneumococcus, cytomegalovirus. and Pneumocystis carinii.^{1, 3}

At histology, in the severe cases, the viral infection produces extensive plugging of terminal bronchioles and alveoluses by a proteinaceous material associated with lymphocytic inflammation and oedema. In less severe involved areas, the bronchiolar epithelium shows proliferation with a polypoid aspect, as found in our case, sometimes associated with squamous metaplasia and scaling. Syncytial giant cells can be present lying on the alveolar, bronchial, and bronchiolar walls, but are not always present. Basophilic cytoplasmic inclusions may also be seen in the infected cells, with dense cytoplasmic inclusions demonstrated by electronic microscopy.¹

In our patient, the peripheral pulmonary arterial lesions were characterized by isolated medial hypertrophy, and thus would be considered reversible. In spite of that, as a consequence of severe hypoxia, the child suffered a pulmonary hypertensive crisis, as suggested by the histological features of the elastic laminas, and unfortunately died. Our experience reinforces the statement made by Haworth and collaborators in 1987, specifically that “potentially reversible pulmonary arterial lesions are not always synonymous with operability”.⁶ In other words, the presence of mere hypertrophy of the pulmonary arterial walls can be dangerous in the postoperative period, since these vessels may be over-reactive to some stimuluses such as hypoxia. Our experience also serves to illustrate the impact of infection by the respiratory syncytial virus in the setting of paediatric cardiac surgery,^{7, 8} particularly in patients with pulmonary hypertension.