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.     

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.     

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.     

Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide

We report the use of inhaled prostacyclin (PGI(2)) in 4 neonates with persistent pulmonary hypertension and hypoxemia refractory to inhaled nitric oxide. Oxygenation rapidly improved after inhalation of PGI(2) in all infants. The condition of one infant subsequently deteriorated, and alveolar capillary dysplasia was found at autopsy. The surviving infants were discharged with normal oxygen saturations in room air.     

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.     

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 Misalignment of Pulmonary Veins with Alveolar Capillary Dysplasia Causing Persistent Neonatal Pulmonary Hypertension: Report of Two Affected Siblings

Misalignment of pulmonary vessels with alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. Most of the reported cases have been sporadic. We present two consecutive affected siblings with this disorder. This is the fifth reported family occurrence of this condition. In addition to the pulmonary abnormality, one of our cases had duodenal atresia. Received February 2, 1999; accepted June 28, 1999.     

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.     

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.     

Kongenitale alveolar-kapilläre Dysplasie

Background

Congenital alveolar capillary dysplasia (CACD) is a rare cause of persistent pulmonary hypertension in neonates (PPHN). This idiopathic PPHN is mostly diagnosed by exclusion.

Case report

We report an unusual clinical course in a male newborn with PPHN caused by patchy CACD. Following an uneventful postnatal period the infant decompensated at the age of 10 weeks. His condition improved temporarily after 2 weeks of intensive medical care including medication to combat the pulmonary hypertension and support the heart. A few days later the patient died of heart failure. The final diagnosis was established by autopsy and histopathological examination of the lung tissue, which exhibited typical signs of CACD.

Conclusions

CACD should be considered in the differential diagnosis in all neonates with refractory PPHN when there is no recognizable secondary disturbance. Only an open lung biopsy can yield a definitive diagnosis of CACD.     

The incidence and characteristics of neonatal irreversible lung dysplasia

A 3-year retrospective study of 173 neonates treated with extracorporeal membrane oxygenation in the United Kingdom identified 9 cases of irreversible lung dysplasia, including alveolar capillary dysplasia (n = 5), surfactant protein B deficiency (n = 1), pulmonary hypoplasia (n = 1), pulmonary lymphangiectasis (n = 1), and combined lymphangiectasis and hypoplasia (n = 1).     

Long survival of congenital alveolar capillary dysplasia patient with NO inhalation and epoprostenol: Effect of sildenafil,beraprost and bosentan

The case is described herein of a patient with alveolar capillary dysplasia with double‐outlet right ventricle and duodenal atresia who survived for a remarkably long time. The newborn girl was born at a gestational age of 36 weeks and weighed 1926 g. One min after delivery the Apgar score was 4. The patient had persistent pulmonary hypertension (PH) and needed nitric oxide inhalation and i.v. epoprostenol all through her life. Although other oral medications for PH were tried, they could not be used in practice because of gastrointestinal complications. The patient died on the 237th day of life as a result of worsening PH associated with infection.     

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.     

Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature

We describe an unusual infant with the diagnosis of alveolar capillary dysplasia who had a relatively prolonged life without extracorporeal membrane oxygenation (ECMO). We have used this case as a springboard for a thorough review of the literature. This was a full-term female infant who presented with a picture of persistent pulmonary hypertension of the newborn. She was treated as such, with various ventilatory modes, alkalinizing agents, surfactant therapy, tolazoline, prostacyclin and nitric oxide. Because of the prolonged clinical course the possibility of alveolar capillary dysplasia was raised. The parents refused ECMO. Despite all efforts she progressively deteriorated and died at 22 days of age. Macro- and microscopic examination of the lung at autopsy were diagnostic of alveolar capillary dysplasia. A detailed review of 39 cases published in the literature with comments regarding incidence, etiology, pathophysiology, clinical picture, diagnosis and treatment is presented.     

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.     

Alveolar capillary dysplasia: absence of CD117 immunoreactivity of putative hemangioblast precursor cells

Alveolar capillary dysplasia is a rare cause of irreversible persistent pulmonary hypertension in newborns resulting from failure of formation of peripheral capillary loops with consequent reduction in the blood-gas barrier. The basic defect in morphogenesis is unknown, although it is postulated that there is a structural abnormality of the hemangioblast precursors of the primitive lung mesenchyme in the septal regions of the developing lung leading to abnormal vasculogenesis. Two cases of alveolar capillary dysplasia evaluated immunohistochemically showed uniform CD117 negativity in the septal interstitial cells forming the pulmonary capillaries. A series of 12 control cases showed positive immunoreactivity for CD117 in a subset of septal interstitial cells forming the putative hemangioblast precursor cells. This novel finding is a useful adjunctive diagnostic tool and may support the hypothesis that absence of putative CD117-positive hemangioblast precursor cells is a key structural defect. This defect results in abnormal vasculogenesis and consequent failure of formation of an adequate blood-gas barrier.     

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.     

Pre-cannulation lung biopsy shortens ECMO course

We describe the clinical course of an infant with respiratory failure who underwent lung biopsy prior to cannulation for undergoing extracorporeal membrane oxygenation (ECMO). Pathology revealed alveolar capillary dysplasia, and ECMO was discontinued. Rapid diagnosis allowed for closure and saved resources. We recommend considering early biopsy in infants with atypical pulmonary hypertension.     

Primary alveolar capillary dysplasia

We describe two neonates with a lethal form of pulmonary maldevelopment. Both infants had bilateral dysplastic immature lungs with poor capillary formation and lack of alveolar development. This rare entity should be considered in the differential diagnosis of a newborn infant with mild diffuse radiographic pulmonary abnormality and severe respiratory distress.Presented at The 32nd Meeting of The Society for Pediatric Radiology, San Antonio 1989.