An unusual cause of central cyanosis in a nine-year-old boyA Shobi, MS Tullu, S Bhatia, M Agrawal
Department of Pediatrics, Seth G.S. Medical College and KEM Hospital, Mumbai, Maharashtra, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.105468
Source of Support: None, Conflict of Interest: None
Pulmonary arteriovenous malformations are rare vascular anomalies which rarely present in childhood. We discuss a nine-year-old male child who presented with the classical triad of exertional dyspnea, cyanosis and clubbing since six years of age. Pulmonary arteriovenous malformation was suspected on chest radiography and was later confirmed on computed tomography scan. A bubble contrast echocardiography showed the presence of an extracardiac shunt. Pulmonary angiography was done to delineate the anatomy of the pulmonary vasculature and to plan embolization. The child has undergone two sittings of transcatheter coil embolization with improvement in oxygenation.
Keywords: Angiography, arteriovenous malformations, clubbing, cyanosis, dyspnea, echocardiography, embolization, embolotherapy, hereditary hemorrhagic telengiectasia, hypoxia, lungs
Pulmonary arteriovenous malformations (PAVMs), an unusual disease, consists of abnormal vascular communications between the branches of the pulmonary arteries and veins. ,, The condition, although congenital, presents mainly in adulthood and is uncommonly seen in children. ,
A nine-year-old male child born of a third-degree consanguineous marriage presented with breathlessness on exertion and bluish discoloration of lips and nails since the past three years. There was no history of recurrent respiratory infections or cyanosis in the past. There was absence of history of nose bleeds or skin telangiectasia. No family member suffered from similar illness. On examination, there was central cyanosis and Grade III clubbing. The mucous membranes and conjunctiva were plethoric. The vital parameters were normal and the pulse-oximeter oxygen saturation was only 62% in room air. There were no cardiac or extra-cardiac murmurs. The heart sounds (including pulmonary component of the second heart sound) were normal.
What could be the clinical differential diagnosis in such a patient?
The clinical differential diagnoses would include: Cyanotic congenital heart diseases, (left to right cardiac shunts with) Eisenmenger syndrome, primary pulmonary hypertension, chronic respiratory conditions with progressive respiratory failure, presence of abnormal hemoglobins and pulmonary arteriovenous malformations [Table 1].
Case details (continued)
Investigations revealed polycythemia (hemoglobin = 16.7 g%; packed cell volume = 50.2%) and hypoxia (partial pressure of arterial oxygen PO2:39.7; arterial oxygen saturation SaO 2 :70.2%). The echocardiogram (ECG) and 2-D echocardiograph of the heart did not reveal any structural cardiac anomaly or intra-cardiac shunt. His blood methemoglobin levels were 0.5% (normal- 0 to 2%). The chest radiograph was suggestive of prominent vascular markings at the hilum bilaterally [Figure 1]. Contrast enhanced echocardiograph using agitated saline showed the appearance of bubbles initially on the right side of the heart and then on the left side after three cardiac cycles (suggestive of the presence of PAVMs). Computed tomograph (CT) scan of the chest was suggestive of bilateral multiple PAVMs [Figure 2]a and b. Other investigations were done to rule out the presence of arteriovenous malformations elsewhere. Fundus examination revealed the presence of dilated and tortuous vessels secondary to polycythemia. Magnetic resonance imaging (MRI) brain and magnetic resonance angiography showed prominent intracranial arteries due to hyperdynamic circulation. Echo-Doppler ultrasonography of abdominal vessels did not reveal extra-pulmonary arteriovenous malformations. The child underwent pulmonary angiography, which confirmed the diagnosis of multiple PAVMs. Two sittings of transcatheter coil embolization have been performed [Figure 3]. The patient has improved symptomatically and the oxygen saturation has increased to 85.8% after the second sitting of coil embolization. The differential diagnosis (on investigations) has been discussed in [Table 2]. A clinical algorithm for approach to a patient of PAVM has been given by Khurshid et al. 
What are pulmonary arteriovenous malformations?
pulmonary arteriovenous malformations (PAVMs) are rare direct vascular communications between the branches of the pulmonary arteries and veins without an intervening capillary bed. , PAVMs are rarely diagnosed in children, and only 10% of cases of PAVMs are identified in infancy or childhood. ,,, The incidence of PAVMs is 2-3 per 1,00,000 population and has a female preponderance. ,,,
What is the etiology of PAVMs?
PAVMs can be either congenital (80%) caused by failure of differentiation of the embryonic vascular plexus or acquired. ,, Of the congenital, 47-80% are associated with Osler-Weber-Rendu disease or hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder presenting with arteriovenous malformations of the skin, mucous membranes and visceral organs. , Five to fifteen percent of patients with HHT have PAVMs. ,, Acquired PAVMs may be secondary to chest trauma, thoracic surgery (modified Fontan and Glenn procedure), palliated patients of congenital heart disease (especially single-ventricle disease), longstanding hepatic cirrhosis, metastatic carcinoma, systemic amylodosis and infections like actinomycosis and schistosomiasis. ,,
What are the types of PAVMs?
PAVMs may be solitary or diffuse. They could be in the form of single sacs ranging from 1 cm to >10 cm in diameter, macroscopic tangles or microscopic telangiectasias.  Eighty to ninety percent of PAVMs are simple (single feeding artery and single draining vein). The rest are complex, with two or more feeding arteries and draining veins.  The afferent supply is usually from the branches of the pulmonary artery, and rarely from systemic circulation like the aorta, intercostal and bronchial arteries. The efferent limb drains into one or more of the branches of the pulmonary veins, and rarely into the left atrium or inferior vena cava. ,
What is the clinical presentation in patients with PAVMs?
Unlike systemic arteriovenous malformations, PAVMs do not affect the cardiac haemodynamics.  The symptoms depend on the degree of right to left shunt between the pulmonary artery and pulmonary vein. A shunt greater than 20% of the cardiac output leads to cyanosis, clubbing and polycythemia. ,, The peripheral oxygen saturation is low and does not increase with 100% oxygen supplement. The classical triad of dyspnea, cyanosis and clubbing is present in only 10% of patients of PAVMs.  Around 13-55% of patients tend to be asymptomatic.  Exertional dyspnea is the most common presenting symptom, the severity of which depends on the magnitude of the shunt and the degree of hypoxemia. ,, Epistaxis, malena and neurological symptoms may be seen in cases with a co-existing HHT.  Common examination findings are cyanosis, clubbing and pulmonary vascular bruit (increased by inspiration and the Muller maneuver). 
What are the complications of PAVMs?
The complications of PAVMs include migraine, transient ischaemic attacks, stroke, brain abscess, and seizures (due to paradoxical embolism across the PAVM). , Thrombosis is related to polycythemia or the presence of co-existing cerebral AVM in patients with HHT.  Antibiotic prophylaxis is recommended for any procedure that may induce bacteremia to reduce the risk of brain abscess. , Rupture of PAVM leading to haemoptysis or haemothorax is a rare life-threatening complication.  Cardiac failure is a rare complication which may occur in neonates with pulmonary artery to left atrial connections. 
Which radiological investigations are used to diagnose PAVMs?
A plain chest radiograph demonstrates an abnormality in about 98% of the patients of PAVM. , The features are a round or oval sharply defined non-calcified nodule of uniform density, usually located in the lower lobes of the lung.  Contrast enhanced computed tomograph (CT) is a non-invasive and accurate diagnostic tool in identifying the anatomy of a PAVM and is comparable to pulmonary angiography.  CT scan also plays a role in the long-term follow-up of patients who have undergone treatment. , Radionuclide perfusion lung scan can be used as an adjunct in the diagnosis and quantification of PAVM. , It estimates the shunt after intravenous injection of radionuclide-labeled macroaggregated albumin by measuring differential perfusion to the lungs and either the brain or kidneys. 
What is the role of echocardiography in diagnosis of PAVMs?
Contrast echocardiography involving injection of agitated saline or dye into a peripheral vein is almost 100% sensitive to diagnose the presence of a shunt.  In a patient without a shunt, the air bubbles appear in the right atrium and get trapped in the pulmonary circulation. In case of an intra-cardiac shunt, the bubbles will be visualized in the left atrium within one cardiac cycle of their appearance in the right atrium. However, in case of PAVM, there will be a delay of three to eight cardiac cycles before the appearance of the bubbles in the left atrium. Contrast echocardiograph is considered to be the best initial screening test for PAVM due to its excellent sensitivity and availability. , However, the technique is not quantitative, cannot predict the amenability of PAVMs to embolotherapy and a positive result needs to be followed by a pulmonary angiography.  A positive result of radionuclide perfusion lung scan and contrast echocardiography is not specific for PAVMs but a negative result essentially excludes PAVMs; and microscopic PAVMs (not picked up by anatomic imaging modalities) can be demonstrated by these methods.  Doppler ultrasonograph is sometimes useful in the antenatal diagnosis of PAVMs. 
Is pulmonary angiography necessary?
Pulmonary angiography is the gold standard in the diagnosis of PAVM. , It confirms the diagnosis and delineates the exact anatomy of the pulmonary vasculature; this is necessary before planning therapeutic embolization or surgical resection.  However, widespread and diffuse minute PAVMs which can cause significant shunt may not be identified with pulmonary angiography. 
How are patients with PAVMs treated?
PAVMs are known to progressively enlarge over a period of time. ,, Percutaneous transcatheter embolotherapy is recommended for all symptomatic PAVMs which are more than 2 cm in diameter and those with feeding vessels more than 3 mm in diameter. ,,,,,,,, It is done using coils, plugs, or balloons. ,,, Though extremely effective and safe, embolotherapy may be occasionally associated with complications like pulmonary infarction, pleuritic chest pain, hemothorax, air embolism, vascular injury, cerebrovascular accidents, balloon foldover, premature or difficult detachment and migration. ,,,,,,,, Once embolized, the PAVMs disappear or reduce to a fibrous strand by the end of the first year.  Any evidence of persistence suggests recanalization and is an indication for re-embolization.  Antibiotic prophylaxis before dental and surgical procedures should be continued as residual lesions may persist despite treatment.  Long-term follow-up of these patients with arterial blood gases 1 month and 1 year post embolotherapy and a spiral CT every 3-5 yearly is recommended to evaluate the growth of the embolized PAVM and development of new lesions. 
What is the role of surgery?
Surgical therapy in the form of local excision, segmental resection, lobectomy, ligation and pneumonectomy are reserved for failure of embolotherapy, serious bleeding despite embolotherapy, intra-pleural rupture of PAVM or lesions not amenable to embolotherapy. , In these cases, lung conserving resection is the procedure of choice.
The authors thank Dr. Sanjay Oak, Director (Medical Education and Major Hospitals, Municipal Corporation of Greater Mumbai) and Dean of Seth G.S. Medical College and K.E.M. Hospital for granting permission to publish this manuscript.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]