Alveolar capillary dysplasia with anorectal anomaly

Alveolar capillary dysplasia (ACD) is an uncommon cause of irreversible persistent pulmonary hypertension in full-term newborn. In ACD there is a failure of formation of air - blood barrier in addition to misalignment of pulmonary veins. The etiology of the disease is still not understood. We present a case report of a full-term newborn with ACD associated with anorectal anomaly.     

Alveolar Capillary Dysplasia in an Infant With Trisomy 21

We present a case of an infant with Down syndrome (trisomy 21) who was affected by alveolar capillary dysplasia and other complications including endocardial cushion defect, hypothyroidism, and intrauterine growth restriction. The patient was the product of a third pregnancy to a 33-year-old woman with no significant risk factors. The child lived for 3 months, during which he developed intractable dyspnea, hypoxemia, and cardiac dysfunction and he eventually died from septicemia and multiorgan failure. In addition to the facial phenotypic features and cardiac anomalies, the autopsy revealed the characteristic microscopic pulmonary findings of alveolar capillary dysplasia with misalignment of pulmonary veins. This appears to be the first reported case of this anomaly associated with trisomy 21. In addition to the many reasons for pulmonary hypertension that occur in children with trisomy 21, alveolar capillary dysplasia may have to be included in the differential diagnosis although it appears to be a rare association.     

Congenital Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Associated with Hypoplastic LeftHeart Syndrome

Three full-term infants died in the first month of life with hypoplastic left heart syndrome (HLH) and persistent pulmonary hypertension (PPH). At postmortem examination, they were found to have alveolar capillary dysplasia with misalignment of pulmonary veins (ACD with MPV). The association of HLH syndrome, and ACD with MPV with intestinal malrotation and/or obstruction, is unique. Decreased blood flow in the ascending aorta in fetuses with left outflow tract obstruction might cause vasoconstriction of pulmonary arterioles to maintain cerebral perfusion. Vasoconstriction early during embryogenesis might lead to decreased growth and development of alveolar capillaries and pulmonary veins. This results in pulmonary hypertension, and the arterial blood is forced to bypass the deficient capillary bed and can drain only via the anomalous bronchial veins. Received October 26, 1999; accepted March 2, 2000.     

CONGENITAL ALVEOLAR CAPILLARY DYSPLASIA: Rare Cause of Persistent Pulmonary Hypertension

We report on a rare case of fatal congenital alveolar capillary dysplasia. The newborn boy of a 37 weeks' normal gestation suffered from persistent pulmonary hypertension without any cardiovascular malformation and died at the age of 4 weeks despite intensive treatment. The autopsy tissue was examined histologically, immunohistochemically, and ultrastructurally. Moreover, a three-dimensional tissue reconstruction based on serial sections was performed comparing the affected lung with normal lung tissue. We observed a unique pattern of pulmonary dysplasia: An extreme decrease of capillaries was localized centrally within thickened intra-acinar septa instead of capillaries intensely neighboring pneumocytes; ectatic veins normally running in the interlobular septa were found to accompany intralobular bronchovascular bundles, denying a clear distinction between pulmonary and bronchial veins; small muscular pulmonary arteries extended to the precapillary level and type 2 pneumocytes exceeded by far the type 1 pneumocytes, inverting the normal ratio. In summary, alveolar capillary dysplasia is assumed to be a primary capillary disorder of unknown origin, which possibly involves the regular differentiation of pneumocytes, according to the close alveolocapillary relationship during pulmonary ontogenesis. We consider the venous alterations as being part of the dysplasia, whereas the arterial phenomena might occur secondarily. Recent reports on affected siblings suggest a genetic component of pathogenesis.     

Aortic Coarctation Associated with Alveolar Capillary Dysplasia and Misalignment of the Pulmonary Veins

After surgical repair of an aortic coarctation a term infant presented with severe pulmonary hypertension and cyanosis unresponsive to treatment including extracorporeal membrane oxygenation. The atypical clinical course became apparent once the accompanying diagnosis of congenital alveolar capillary dysplasia with misalignment of the pulmonary veins had been established at autopsy. In infants with congenital heart defects and with refractory pulmonary hypertension unexplainable on anatomic findings, a lung biopsy at the time of cardiac repair should be considered to avoid further therapies that would not alter the uniformly fatal course of this rare lung disorder.     

Persistent Pulmonary Hypertension of the Newborn due to Alveolar Capillary Dysplasia

Three unrelated female term infants died when less than 1 month old from intractable pulmonary hypertension associated with deficient capillaries in airspace walls, anomalous small pulmonary veins in bronchiolar-arterial rays, and medial thickening in small pulmonary arteries together with peripheral muscularization. This complex uascular abnormality in the lungs has been termed alveolar capillary dysplasia and/or misalignment of lung uessels in seven previously reported cases. Each infant also showed abnormally immature parenchymal development in the lungs, as was noted in four of the seven prior cases. One had phocomelia; four of the seven prior cases had a variety of congenital anomalies. The primary pulmonary uascular anomaly is likely to be a failure of fetal lung uascularization dating from the second trimester and to be due to action of an unknown teratogen. Centroacinar veins may represent bronchial veins that do not normally develop beyond the ends of cartilaginous bronchi. Pulmonary arterial occlusive changes are interpreted, as reactive to obstruction at the level of pulmonary arterioles.     

Alveolar capillary dysplasia with misalignment of the pulmonary veins: a rare but fatal cause of neonatal respiratory failure

Respiratory failure in the neonate that is refractory to maximal medical management is a frequent indication for extracorporeal life support (ECLS). Alveolar capillary dysplasia with misalignment of the pulmonary veins is an irreversible cause of respiratory failure that cannot be diagnosed on clinical grounds alone and would not be expected to respond to ECLS therapy. A recent experience with a patient prompted us to review the literature regarding this condition for the purpose of identifying factors suggestive of this diagnosis. This condition should be considered in neonates with presumed pulmonary hypertension who cannot be weaned from ECLS. If the diagnosis is made by antemortem open-lung biopsy, a costly, protracted, and unnecessary continued course of ECLS may be avoided. Accepted: 28 July 1997     

Neonatal hypoxemia due to misaligned pulmonary vessels with alveolar capillary dysplasia]

BACKGROUND: Refractory hypoxemia in the newborn requires a precise diagnostic investigation for optimal and fast management. CASE REPORT: A full term newborn presented with refractory hypoxemia associated with radiologically clear lung fields and extrapulmonary shunt. Echocardiography ruled out a cardiac malformation. The persistence of hypoxemia despite treatment of the extrapulmonary shunt and the absence of parenchymatous pulmonary disease led to suspect misaligned lung vessels with alveolar capillary dysplasia. This diagnosis was confirmed by post mortem microscopic examination of the lung. CONCLUSION: The diagnosis of misaligned lung vessels with alveolar capillary dysplasia can be suspected on clinical features. The disposition of pulmonary veins must be checked to recognize this disease in case of neonatal death with pulmonary hypertension.     

Paediatric interstitial lung disease: classification and definitions

Classifications of interstitial (diffuse) lung disease in adults and children have undergone significant revision in recent years, with advances in our understanding of new entities and the biology and prognostic significance of certain histologic patterns. The contributions of the European Respiratory Society Task Force on Interstitial Lung Disease in Children and the North American Children's Interstitial Lung Disease Group are reviewed, and a clinicopathologic classification of paediatric diffuse lung disease is summarized. Clinical characteristics and histologic definitions are also presented for selected entities within this classification, specifically, acinar dysgenesis, congenital alveolar dysplasia, alveolar capillary dysplasia with misalignment of pulmonary veins, abnormalities of alveolar growth, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia of infancy, surfactant dysfunction disorders, obliterative bronchiolitis, hypersensitivity pneumonitis, and immunologic disorders. More uniform application of this diagnostic terminology in the future will allow more meaningful comparisons of different patient populations, radiologic-pathologic correlation, and development of disease-specific therapeutic strategies.     

Pulmonary pathology.

Common causes of neonatal respiratory distress include meconium aspiration, pneumonia, persistent pulmonary hypertension of the newborn, pneumothorax and cystic adenomatoid malformation. Genomics and proteomics have enabled the recent recognition of several additional disorders that lead to neonatal death from respiratory disease. These are broadly classified as disorders of lung homeostasis and have pathological features of proteinosis, interstitial pneumonitis or lipidosis. These pathological changes result from inherited disorders of surfactant proteins or granulocyte-macrophage colony stimulating factor. Abnormal lung vascular development is the basis for another cause of fatal neonatal respiratory distress, alveolar capillary dysplasia with or without associated misalignment of veins. Diagnosis of these genetically transmitted disorders is important because of the serious implications for future siblings. There is also a critical need for establishing an archival tissue bank to permit future molecular biological studies.     

Alveolar capillary dysplasia presenting as pneumothorax: a case report and review of literature

Alveolar capillary dysplasia, although rare, is a universally fatal form of persistent pulmonary hypertension of the newborn. We report a case of a newborn male baby who developed respiratory distress and pneumothorax 11 h after an uncomplicated delivery. He deteriorated despite full ventilatory support and extracorporeal membrane oxygenation (ECMO). Open lung biopsy provided a diagnosis of alveolar capillary dysplasia and decision was made to withdraw treatment.     

Pulmonary venous stenosis in a premature infant with bronchopulmonary dysplasia: clinical and autopsy findings of these newly associated entities

Pulmonary venous stenosis is rare and is most commonly found in association with cardiac malformations. Recent studies have associated pulmonary venous stenosis with prematurity, especially with bronchopulmonary dysplasia, although no such case has been documented at autopsy. We report the case of a 26-week-gestation infant who required ventilation at birth and who, among other complications, developed chronic lung disease of prematurity by the age of 3 months. Imaging showed suprasystemic right-sided pressures and pulmonary venous stenosis. Despite aggressive management of respiratory status and surgical marsupialization of stenoses, the infant expired after 3 weeks. At autopsy, 3 of 4 pulmonary veins showed a fibrous ridge obstructing atrial ostia with otherwise normal anatomy. The lungs showed bronchopulmonary dysplasia, pulmonary hypertensive vascular changes, and features of venous obstruction. Pulmonary venous stenosis and bronchopulmonary dysplasia in premature infants may be pathogenetically related. Coincidence of these diseases is likely underrecognized, and careful cardiac examination in these patients is warranted.     

Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn

The term alveolar capillary dysplasia refers to complex vascular abnormalities which have recently been identified in some infants with persistent pulmonary hypertension. We report four cases admitted to our institution for severe pulmonary hypertension unresponsive to maximal cardiorespiratory support, including high-frequency ventilation, inhaled nitric oxide and extracorporeal membrane oxygenation. The four infants died of refractory hypoxaemia. The diagnosis of alveolar capillary dysplasia was established by necropsy. We have used these cases as an opportunity for a thorough review of the literature containing comments regarding aetiology, pathophysiology, clinical presentation, associated malformations and treatment trials. CONCLUSION: alveolar capillary dysplasia should be ruled out in all newborn infants presenting severe idiopathic pulmonary hypertension associated with malformations. Open lung biopsy may prevent from using costly, invasive and probably ineffective procedures such as extracorporeal membrane oxygenation.     

Incidence of alveolar capillary dysplasia in severe idiopathic persistent pulmonary hypertension of the newborn

OBJECTIVE: To determine the incidence and outcome and to review the management of alveolar capillary dysplasia (ACD) among newborns with severe idiopathic persistent pulmonary hypertension (PPHN). METHODS: A retrospective review of medical records of infants admitted to a paediatric intensive care unit from 1982 to 2000 with a diagnosis of severe PPHN, and re-examination of lung histological sections was carried out. Results: Thirteen new-born infants with pulmonary hypertension not associated with any known cause were identified. All were treated with conventional mechanical ventilation or high-frequency oscillatory ventilation with high inspired-oxygen and non-specific pulmonary vasodilators. Nine infants were also treated with inhaled nitric oxide therapy and eight with extracorporeal membrane oxygenation (ECMO). Seven infants died and six survived. At autopsies, the histological features of ACD were seen in the six who had died in the newborn period. All these had been treated with ECMO. In two of these six infants, lung biopsies had been performed showing similar features, suggesting the possibility of diagnosis during life. In the remaining infant, who died at 3 months of age, there was only marked hypertrophy of the muscle coat in the small pulmonary arteries. CONCLUSIONS: Alveolar capillary dysplasia is probably not as rare a condition as previously suggested in sporadic case reports from literature on the subject. It should be entertained as a cause of otherwise severe idiopathic PPHN of the newborn, particularly if ECMO is required. Diagnosis during life is possible by lung biopsy. It is uncertain if survival occurs with milder forms of the condition.     

Congenital misalignment of pulmonary vessels: an unusual syndrome associated with PPHN

We report a case of misalignment of pulmonary vessels and review the clinical features of all 13 cases reported to date. All were term infants dying from severe persistent pulmonary hypertension of the newborn. We have identified a triad of features that will alert neonatal clinicians to the possibility of this diagnosis: association with other non-lethal congenital malformations; delayed onset of presentation (especially after 12 h); and severe hypoxaemia refractory to conventional therapy. We recommend that any autopsy on newborn infants include a specific search for misalignment of pulmonary vessels to outline the pathophysiology and clinical significance of this disorder.     

Misalignment of lung vessels and alveolar capillary dysplasia: a cause of persistent pulmonary hypertension

Two infants with fatal persistent pulmonary hypertension are described. Morphologically there was misalignment of the lung vessels, with the veins and the arterioles anomalously related, often sharing the same adventitial sheet. The capillaries did not make contact with the alveolar epithelium. The arterioles had increased medial muscle, and there was extension of the arteriolar muscularization to the precapillary level. The fraction of the parenchyma that was septal and connective tissue was increased. The acini had a decreased complexity, with immature alveoli and with a decreased radial alveolar count. The cause appeared to be related to abnormal capillary and venous plexus formation and migration. This syndrome seems to be identical with that described in three previous reports and probably represents a specific cause of persistent pulmonary hypertension.     

A Rare Case of Aortic Coarctation and Ventricular Septal Defect Combined with Alveolar Capillary Dysplasia

We report a rare case of alveolar capillary dysplasia (ACD) associated with severe aortic coarctation, hypoplastic aortic arch, and mild hypoplasia of the left ventricle. After successful coarctation repair, pulmonary hypertension persisted, and despite only minor anomalies on the x-ray, chest computed tomography (CT) revealed the presence of primary lung disease. Review of the literature suggests that ACD may be associated with left heart obstructions. Chest CT is applicable to diagnose ACD precociously.     

Triphasic Mitral and Tricuspid Flows: A Sign of Diastolic Dysfunction in a Young Patient With Severely Dilated Atria and Giant Pulmonary Veins

This report presents a case with severe dilation of both atria and giant pulmonary veins manifested with atrial fibrillation. The following cardiac magnetic resonance findings are highly suggestive of restrictive physiology: E/A ratio greater than two, prominent A wave across the pulmonary veins and inferior vena cava, and more interestingly, a triphasic flow across the mitral and tricuspid valves.     

Misalignment of lung vessels and alveolar capillary dysplasia: a case report with autopsy

Misalignment of lung vessels (MLV) with or without alveolar capillary dysplasia (ACD) is a rare cause of idiopathic persistent pulmonary hypertension of the neonate. This report describes a full-term infant with severe and intractable pulmonary hypertension. The patient's condition progressively deteriorated despite high-frequency oscillatory ventilation, infusion of magnesium sulfate, dopamine, and dobutamine to control blood pressure, and nitric oxide inhalation therapy. The infant died at 5 days of age. The diagnosis of MLV with ACD was established by autopsy. Histopathologic analysis revealed a failure of formation and an ingrowth of alveolar capillaries, thickening of the alveolar walls, poor contact of capillaries with alveolar epithelium, small intra-acinar muscularized arterioles, and anomalous pulmonary veins within bronchovascular bundles. The low rate of diagnosis of MLV with or without ACD may be because of the early high mortality rate or patchy involvement in some cases. Increasing awareness of this clinical entity may prevent the use of costly, invasive, and probably ineffective procedures. Short-term improvement after inhalation of nitric oxide does not lead to long-term survival but merely provides time for potential lung transplantation.