Swyer-James-MacLeod syndrome and pulmonary arteriovenous malformations: a rare combination

Abstract

This case describes a female patient who presented with an acute on chronic deterioration in respiratory symptoms, on a background of chronic obstructive pulmonary disease and heavy cigarette smoking. Chest radiograph demonstrated long-standing hyperlucency of the right lower lobe, with further imaging later confirming the rare combination of Swyer-James-MacLeod syndrome and multiple pulmonary arteriovenous malformations within the affected lung.

Background

Swyer-James-MacLeod syndrome (SJMS) is an infrequently reported acquired lung disorder, often being discovered incidentally when investigating another condition. Far more common, however, is the finding of hyperlucent lung on chest imaging, which has many causes that require careful evaluation. Here, we describe the case of a 68-year-old woman who presented with a common clinical problem, that is, chronic respiratory disease presenting with an acute exacerbation, together with two rare coexistent pulmonary pathologies that were found incidentally as part of investigation for suspected malignancy. While SJMS is generally managed conservatively, and incidental pulmonary arteriovenous malformations (PAVMs) are unlikely to need immediate therapeutic intervention, both conditions may be associated with significant morbidity.

Case presentation

A 68-year-old woman presented to the emergency department (ED) following a 3-day history of increasing dyspnoea, non-productive cough and general fatigue. She also described unintentional weight loss of around 4 kg over the preceding 3 months. Her medical history was significant for chronic obstructive pulmonary disease (COPD), being diagnosed in primary care many years ago. She was a current smoker of 20–30 cigarettes per day since the age of 15. This was her first presentation to hospital and she described infrequent exacerbations of her COPD requiring treatment in primary care. However, she described a long history of significant breathlessness, which impacted on her quality of life as she struggled with activities of daily living due to her symptoms. Her regular medications included inhaled salbutamol as required, but nothing else. She emigrated from Spain at the aged of 18 and lived alone with support of her daughter.

At the time of initial assessment in the ED, she was found to be tachypnoeic and tachycardic with diffuse polyphonic wheeze on chest auscultation. The peripheral oxygen saturation (SpO₂) was 93%. A working diagnosis of a non-infective exacerbation of COPD was made, and treatment with oral corticosteroid and nebulised bronchodilators was initiated pending further investigations.

Blood tests showed normal haematological, renal and liver parameters with a C-reactive protein less than 5 mg/L (reference range 0–10 mg/L). Her chest radiograph demonstrated hyperinflated lung fields, with hyperlucency of the right lower lobe and multiple areas of increased opacity within the mid and upper zone (figure 1A). Despite initial concerns regarding possible pneumothorax, a previous radiograph from many years prior was reviewed, which showed unchanged appearances since then.

Figure 1.

(A) Chest radiograph demonstrating hyperinflated lung fields, with hyperlucency of the right lower lobe and multiple areas of increased opacity within the mid and upper zone. (B) Thoracic CT imaging demonstrating hypoattenuation of the right lower lobe along with hypoplasia of the airways supplying the right lower lobe. The segmental pulmonary arteries supplying the right lower lobe are reduced in calibre. (C,D) CT imaging demonstrating pulmonary vascular abnormalities in-keeping with pulmonary arteriovenous malformations), the largest of which being calcified in the apical segment of the hyperexpanded right lower lobe. (E) Coronal CT image showing that the right upper lobe appears minimally compressed with mildly increased attenuation as a consequence of lower lobe air trapping and a degree of hyperinflation.

On further questioning, the patient described a life-long history of chest symptoms. She reported no apparent perinatal issues, but as a child she could not keep up with her classmates due to breathlessness, and she had a prolonged respiratory illness during her early years, which she believed was due to ‘whooping cough’ which resulted in a 1–2 week hospital stay. Since then, however, respiratory tract infections were infrequent. There was no history of productive cough or haemoptysis.

As she was unwell, she was admitted for 24 hours of inpatient treatment and in view of a history of weight loss and significant smoking history, a contrast-enhanced CT scan was arranged.

Investigations

Thoracic CT imaging demonstrated hypoattenuation of the right lower lobe along with hypoplasia of the airways supplying the right lower lobe (figure 1B). The segmental pulmonary arteries supplying the right lower lobe are small, and there are also several pulmonary vascular abnormalities in-keeping with PAVMs, the largest of which being calcified in the apical segment of the hyperexpanded right lower lobe (figure 1C and D). The right upper lobe appears minimally compressed with mildly increased attenuation as a consequence of lower lobe air trapping and a degree of hyperinflation (figure 1E). There was evidence of upper lobe predominant centrilobular emphysema, and no evidence of intrathoracic malignancy. The liver appeared normal.

Differential diagnosis

The differential diagnosis of unilateral hyperlucent lung is broad and is outlined in table 1. History and examination are key, and CT imaging offers valuable insights as to the likely underlying cause and proved valuable in this case. Also, the availability of an historical radiograph for comparison in this case further aided decision-making.

Table 1.

Pathological causes of unilateral hyperlucent lung.

Site of abnormality	Condition	Reason for hyperlucency
Chest wall	Poland syndrome	Partial or complete absence of pectoralis major, hyperlucuency due to lack of anterior chest musculature.
	Postmastectomy	Absence of breast tissue, hyperlucency due to lack of anterior chest soft tissue.
Airway	Endobronchial obstruction	Related to tumour, foreign body, mucous plug and broncholith. Can be partial, resulting in distal hyperinflation due to a one-way valve mechanism, or complete with resultant overinflation of an adjacent lobe.
Parenchyma	Emphysema/bullous disease	Alveolar destruction and enlargement of airspaces.
	Postlobectomy/pneumonectomy	Compensatory hyperinflation of an adjacent lobe/lung.
	Swyer-James-MacLeod syndrome	Associated with acute obliterative bronchiolitis, resulting in chronic airway malformation and vascular hypoplasia resulting in radiologic hyperlucency.
	Atelectasis	Compensatory hyperinflation of an adjacent lobe.
	Pneumatocele	Air-filled space within the lung, most commonly as a result of previous pneumonia.
	Bronchial atresia	Congenital airway obstruction, distal hyperinflation due to air trapping and collateral ventilation.
	Congenital lobar overinflation	Overinflation of a lobe/s from a variety of causes including bronchial obstruction, cartilage deficiency and relating to preterm birth.
Pleura	Pneumothorax	Air within pleural space ± collapse of adjacent lung parenchyma.
	Contralateral effusion	Unilateral appearance of hyperlucency due to contralateral increased density (seen in supine position).
Pulmonary vessels	Pulmonary embolism	Paucity of vessels distal to the thrombus resulting in oligaemic lung fields (Westermark sign).
	Pulmonary agenesis	Abnormal embryonic development resulting in absence of lung tissue (very rare in adulthood).

In this case, the combination of long-standing unilateral hyperlucent lung associated with hyperexpansion of a lobe, together with bronchial hypoplasia and diminished vascularity of the affected lobe, suggests a diagnosis of SJMS. The presence of PAVMs associated with SJMS is extremely rare, with only one similar case previously reported.¹

With regards to her acute presentation, the likely cause was an acute exacerbation of COPD, characterised by a short history of worsening breathlessness and cough with associated bronchospasm on examination. SJMS and PAVMs were incidental findings, and were long-standing when compared with historical imaging. The patient did describe long-standing respiratory symptoms, primarily dyspnoea and reduced exercise tolerance, which are likely to be multifactorial secondary to SJMS and obstructive lung disease. Pulmonary function testing was arranged once she had recovered from the acute exacerbation.

Treatment

The patient was initially treated for a non-infective exacerbation of COPD with bronchodilators and oral prednisolone. Influenza and pneumococcal vaccinations were recommended as prophylactic measures. The patient was offered smoking cessation advice and pharmacological treatment, together with pulmonary rehabilitation referral, but declined both interventions. She was commenced on a long-acting antimuscarinic inhaler due to persistent dyspnoea.

Outcome and follow-up

At the time of initial outpatient review, 3 weeks later she had returned to her usual baseline. There was some symptomatic improvement since the addition of a long-acting bronchodilator. A transthoracic echocardiogram was undertaken, which showed normal left ventricular and right ventricular function, a trace of tricuspid regurgitation but no evidence of pulmonary hypertension. Pulmonary function tests with measurement of lung volumes and gas transfer were performed 6 weeks after her hospital admission and demonstrated moderate irreversible airflow obstruction (postbronchodilator forced expiratory volume in one second (FEV₁) 0.82 L/53% predicted, FEV₁/forced vital capacity ratio 0.58), reduced diffusion capacity of the lung for carbon monoxide (7.8 mL/min/mm Hg, 43% predicted) and hyperinflation (residual volume:total lung capacity 183% predicted). The patient continued to smoke and declined onward referral to smoking cessation and pulmonary rehabilitation services.

Discussion

Swyer-James-MacLeod syndrome (also known as Swyer-James syndrome or unilateral hyperlucent lung syndrome) is a rare acquired lung disorder, being first described in the 1950s.^{2 3} It is thought to be a consequence of an infectious insult in childhood with associated acute obliterative bronchiolitis, resulting in chronic airway malformation and vascular hypoplasia. The clinical presentation of patients with SJMS is variable, and may be associated with chronic respiratory symptoms and recurrent infections, or be found incidentally on chest imaging. The classical appearance on the chest radiograph is of an area of hyperlucency, which reflects interruption in normal bronchopulmonary development due to airway injury, reduced pulmonary vascularity and hyperinflation. The degree of parenchymal involvement is variable, with focal and diffuse forms of the condition being reported.⁴ Bronchiectasis within the affected area of lung is often seen, but is not pathognomonic of the condition.⁵ Generally, plain radiography and CT imaging confirms the diagnosis, but ventilation/perfusion imaging can be considered if the diagnosis is not clear. As in this case, pulmonary function testing commonly reveals an obstructive pattern. However, it may be difficult to determine whether this relates to SJMS or coexistent respiratory disease. Multiple infectious agents have been implicated, including Bordatella pertussis, which we propose as a possible cause in this case.⁶ Management is generally supportive, with specific interventions to manage and prevent dyspnoea and recurrent infections. If associated with localised bronchiectasis and/or recurrent infections, surgical resection of the affected lobe may be considered.

PAVMs represent abnormal connections between pulmonary arteries and veins. They are rare and can be found incidentally, but may present with breathlessness and/or haemoptysis, which can present as a life-threatening emergency. Other complications include respiratory failure due to the right-to-left shunt, and embolic complications such as stroke and cerebral abscess. PAVMs are frequently observed in patients with hereditary haemorrhagic telangiectasia (HHT, also known as Osler-Weber-Rendu syndrome) and this diagnosis should be excluded when PAVMs are discovered. Of note, this patient reported no prior history of haemoptysis or epistaxis, nor any prior episodes of stroke or transient ischaemic attack, and there were no telangiectasia present on clinical examination. There was no family history of the same.

There is one reported case in the current literature describing a patient with SJMS and an arteriovenous malformation.¹ Kaplanoglu et al ¹ describe a similar mode of presentation, with an incidental finding of SJMS and an arteriovenous malformation (AVM) in a 58-year-old woman following a routine preoperative chest radiograph. The CT angiography found the AVM to be fed from the bronchial arteries to the right pulmonary vein (the left-to-right shunt), which contrasts with the probable pulmonary artery to pulmonary venous AVM in our case (the right-to-left shunt). This anatomical distinction is important when determining future risks associated with the AVM, such as paradoxical embolism from the right-to-left shunt, and can also be useful in determining the possible underlying pathology contributing to AVM formation, as AVMs associated with HHT do not usually have systemic feeding vessels.⁷

It is unclear whether there is a causal relationship between SJMS and the presence of AVMs. In this case the finding of AVMs within the same lobe as SJMS suggests a possible link; however, mechanistically there is no clear explanation. Using HHT as an example, mutations in several genes, including endoglin and activin receptor-like kinase-1, affect transforming growth factor-β (TGF-β) signalling, and are associated with AVM formation.^{8 9} TGF-β is recognised as being integral to normal lung development and response to injury, with aberration in normal TGF-β signalling being seen in multiple disease states, including emphysema, and in the absence of HHT.¹⁰ Multiple animal models have demonstrated both airway and parenchymal damage associated with a variety of TGF-deficient states.¹⁰ Despite the absence of clinical HHT in this patient, it could be hypothesised that an infectious insult during early life (ie, pertussis) led to localised injury and impaired tissue response possibly as a result of impaired TGF signalling, resulting in the development of the combination of lung and vascular abnormalities demonstrated in this case. Clearly, it may merely be coincidence that these two pathologies are present in the same patient, but their presence should alert other clinicians to a possible link.

Learning points.

• There are multiple causes for hyperlucent lung on the chest radiograph which require careful exclusion based on the clinical history and examination, together with appropriate imaging.

• Swyer-James-MacLeod syndrome (SJMS) is a rare cause of hyperlucent lung, characterised by hypoplasia of the pulmonary arteries and pulmonary parenchymal hypoperfusion, and is often discovered incidentally.

• Management of SJMS is generally supportive, aiming to manage dyspnoea and prevent recurrent infections. If associated with recurrent infections, surgical resection may be considered.

• SJMS associated with pulmonary arteriovenous malformation is extremely rare, but clinicians should be aware of the potential link.

• Haemorrhagic telangiectasia should be considered in patients found to have pulmonary arteriovenous malformations.