Asian Cardiovasc Thorac Ann 2005;13:82-84
© 2005 Asia Publishing EXchange Ltd
Alveolar Capillary Dysplasia with Congenital Misalignment of Pulmonary Vessels
Alan DL Sihoe, MBBChir,
Alex TH Lee, MBChB,
Ka-Fai To, MD1,
Kin-Hoi Thung, MBChB,
Tak-Wai Lee, MBChB,
Anthony PC Yim, MD
Division of Cardiothoracic Surgery
1 Department of Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital Hong, Kong SAR, People’s Republic of China
For reprint information contact: Anthony PC Yim, MD Tel: 852 2632 2629 Fax: 852 2647 8273 Email: yimap{at}cuhk.edu.hk, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, People’s Republic of China.
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ABSTRACT
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Alveolar capillary dysplasia with misalignment of pulmonary vessels is an uncommon congenital cause of persistent pulmonary hypertension of the newborn. It is universally fatal, and diagnosis is entirely dependent upon surgical lung biopsy. We present a case of alveolar capillary dysplasia with misalignment of pulmonary vessels occurring in a full-term neonate, emphasizing that early involvement of the thoracic surgeon for a histological diagnosis allows expensive and ineffective treatments to be avoided.
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INTRODUCTION
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One of the most important causes of neonatal respiratory distress is persistent pulmonary hypertension of the neonate (PPHN).1 Alveolar capillary dysplasia (ACD) with congenital misalignment of pulmonary vessels (MPV) has in recent years been recognized as a rare cause of "idiopathic" PPHN, and is generally accepted to be incurable.2 At present, the diagnosis can only be effectively made during life by lung biopsy. Early diagnosis may prevent the use of costly, invasive and ineffective therapies.3 As clinicians become increasingly aware of the importance of ACD as a differential diagnosis in PPHN, the thoracic surgeon may be increasingly called upon to participate in the management of idiopathic PPHN. We herein report a case of ACD with MPV, and discuss the management from the perspective of the thoracic surgeon.
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CASE REPORT
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A full term, 2.675 kg female infant was born to a healthy 22-year-old mother (gravida 1, para 0) by normal, spontaneous vaginal delivery. Pregnancy was uneventful. The Apgar score was 9, 9 at one and five minutes respectively. No congenital abnormality was detected on physical examination. At 6
hours after birth, the infant became tachypneic and cyanotic, and promptly required endotracheal intubation and ventilatory support. Chest radiographs showed diffuse patchy infiltrates in both lungs. Echocardiography showed a dilated right ventricle, and right-to-left shunting via a patent foramen ovale. There was marked tricuspid incompetence with a transvalvular gradient of 74 mm Hg, indicating suprasystemic pulmonary hypertension (systemic blood pressure was 56/42 mm Hg).
She was treated with nitric oxide (NO), high frequency oscillatory ventilation (HFOV), and a sodium bicarbonate infusion. Inotropic support with dopamine and dobutamine was also required. Treatments aimed at lowering the pulmonary vascular resistance were used, including exogenous surfactant, magnesium sulphate, prostacyclin I2, and a trial of sildenafil. However, these resulted in no improvement clinically or on echocardiography. On day 43, open lung biopsy to confirm the underlying histopathology of PPHN was performed via a right mini-thoracotomy, with a generous wedge biopsy taken from a representative part of the middle lobe of the right lung.
Histological analysis of the lung specimen revealed thin-walled and dilated pulmonary veins running in anomalous positions alongside the pulmonary arteries in the broncho-vascular bundles (Figure 1
), often sharing a common adventitia with the adjacent arterioles. The inter-alveolar interstitial septa were thickened with loose mesenchymal tissue, resulting in an overall reduction in the size of the alveolar air-spaces. A decreased number of alveolar capillaries were noted, and these were abnormally separated from the epithelial lining of the airspaces. The intra-acinic pulmonary arterioles were abnormally muscularized. These features were diagnostic of ACD with MPV.2
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Figure 1. Alveolar capillary dysplasia with misalignment of pulmonary vessels: dilated, thin-walled pulmonary veins (V) are seen running anomalously alongside muscularized pulmonary arterioles (A) in the broncho-vascular bundles, and sharing the arteriolar adventitial sheath. Abnormally thickened inter-alveolar septa with grossly reduced alveolar air-spaces (Alv) are noted (x 40, H & E stain).
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The diagnosis of ACD and its current definition as an incurable disease were discussed with the parents. It was agreed that further aggressive treatment would be ultimately futile. Further escalations in the life support were ceased, and the neonate died of refractory respiratory failure on day 50.
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DISCUSSION
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PPHN is characterized by a persistent right-to-left shunt through fetal channels causing severe hypoxemia, and has an estimated annual incidence of about 1 in 1,000 live births.1 Although PPHN is often associated with a wide variety of cardiorespiratory disorders,1 a significant proportion of cases of PPHN remain "idiopathic".
ACD is increasingly recognized as a rare but significant cause of idiopathic PPHN. It was first described by Janney and coauthors in 1981,4 and is almost ubiquitously associated with MPV.2 Clinically, ACD is indistinguishable from other causes of PPHN, and diagnosis can only be established on autopsy or biopsy. The characteristic histological features are pulmonary venules running in the same adventitial sheath as the arterioles, a paucity of capillaries adjacent to the alveolar epithelium, and muscular hypertrophy in the pulmonary arterioles.2,5
ACD has often been described as a rare condition, with about 50 cases worldwide reported since 1981. However, it is suspected that the true incidence may be higher, as ACD may have been overlooked or misinterpreted at autopsy, and autopsies may have been omitted in many cases. In a recent retrospective review by Tibballs and colleagues, it was suggested that the incidence of ACD in cases of idiopathic PPHN may be as high as 1 in every 6 patients.5
The exact etiology of ACD is still not fully understood. Although most cases of ACD have been sporadic, reports of occasional familial clustering,3 and the documented associations with other non-lethal, congenital abnormalities in 50–75% of cases,3,5,6 suggest perhaps an element of genetic influence. In terms of pathophysiology, it is thought that the hypoxemia may result from a variety of factors. These include an increased separation between the capillaries and the alveolar air-spaces, reduced overall numbers of capillaries, or reactive pulmonary vasospasm in the muscularized pulmonary arterioles.3,6
Clinically, there is a characteristic delay of a few hours to several weeks between the time of birth and the onset of symptoms – the so called initial "honeymoon period".2,3 The reason for this honeymoon period is unknown. Thereafter, the infant inevitably runs a fulminant, unremitting downhill course towards eventual death. Radiologically, chest X-Rays (CXRs) may show either patchy or diffuse infiltrative changes in both lungs, although normal CXRs have been reported in up to 15.6%.5 Echocardiography shows right-to-left shunt in an essentially normal heart, but cannot differentiate ACD from other causes of PPHN. Unfortunately, there is no ante-natal investigation that can satisfactorily diagnose ACD before birth.
The exact diagnosis of ACD relies exclusively on histological examination. Hitherto, diagnosis in the majority of cases has been at autopsy. However, there have been calls for using lung biopsies to guide management.3,5 Open lung biopsy via a standard lateral mini-thoracotomy remains the preferred surgical technique in neonates. It has been suggested that the sometimes non-uniform distribution of disease in ACD could lead to a missed diagnosis with lung biopsy,6 but we are aware of no reports to date of misdiagnosis from lung biopsies.
It has previously been suggested that ACD may potentially be diagnosable by a distinct pattern of cardiac catheterization findings alone.7 However, other than an initial report describing this technique in three infants, there has been no further published evidence supporting this method. At present, tissue histology remains the only established means of diagnosing this condition during life.5
Once the diagnosis of ACD is made, there is sadly no effective treatment. Therapies directed mainly at relieving the pulmonary hypertension have been tried, but at best these have produced only transient reductions in pulmonary pressures which could not be sustained.2,3,5 Extracorporeal membrane oxygenation (ECMO) has been used to support infants with ACD, but has not ultimately resulted in any cases of survival.5,6 Such therapies are expensive, often invasive, unavailable at many centers, and most importantly ineffective for infants with ACD. Understandably, it has been advised that a lung biopsy be performed whenever such therapies are considered both to avoid their fruitless application in ACD patients and to exclude other disorders such as pulmonary lymphangeictasia.3,5 An earlier positive tissue diagnosis of ACD would allow more thorough counseling of the parents regarding the grim prognosis, as was the case reported here.
Surgically, the only prospect of therapeutic intervention in the future may be lung transplantation. Successful lung transplantations in very young infants with severe pulmonary hypertension have been reported.8 Among the infants short-listed for lung transplantation in that study, there were two infants with ACD. Unfortunately, both infants died before they could receive lung transplantation, and the effectiveness of lung transplantation in infants with ACD is therefore yet to be established.
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REFERENCES
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- Ng PC, Lewindon PJ, Siu YK, To KF, Wong W. Congenital misalignment of pulmonary veins: an unusual syndrome associated with PPHN. Acta Paediatr
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- Alameh J, Bachiri A, Devisme L, Truffert P, Rakza T, Riou Y, et al. Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn. Eur J Pediatr
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- Janney CG, Askin FB, Kuhn C 3rd. Congenital alveolar capillary dysplasia – an unusual cause of respiratory distress in the newborn. Am J Clin Pathol
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- Tibballs J, Chow CW. Incidence of alveolar capillary dysplasia in severe idiopathic persistent pulmonary hypertension of the newborn. J Paediatr Child Health
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- Al-Hathlol K, Phillips S, Seshia MMK, Casiro O, Alvaro RE, Rigatto H. Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature. Early Human Development
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- Hintz SR, Vincent JA, Pitlick PT, Fineman JR, Steinhorn RH, Kim GE, et al. Alveolar capillary dysplasia: a diagnostic potential for cardiac catheterization. J Perinatol
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- Huddleston CB, Sweet SC, Mallory GB, Hamvas A, Mendeloff EN. Lung transplantation in very young infants. J Thorac Cardiovasc Surg
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ABSTRACT
INTRODUCTION
