Curable Hypoxia in an Octogenarian with an Undiagnosed Inherited Condition Case Report

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Rebecca S. 1Dept of Respiratory Rebecca S. Dickinson, [email protected] 1 Medicine Hull and East Yorkshire NHS Dickinson , 2Department of Trust, Administration Block, 2 Graham Robinson , Interventional Radiology, Castle Hill Hospital, Michael A. Hull and East Yorkshire Cottingham HU16 5JQ, UK NHS Trust, Cottingham, UK Greenstone1

Curable hypoxia in an octogenarian with an undiagnosed inherited condition Case Report

Case history sampling, a chest radiograph and thoracic Statement of Interest An 84-year-old gentleman was referred to the computed tomography (CT). His hae- None declared. chest clinic with low oxygen saturations on moglobin at presentation was 16.1 g?dL-1. pulse oximetry. He reported breathlessness and wheeze since his retirement as a surveyor 16 years previously. His exercise tolerance Investigations Lung function was 350 m. He had pre-existing diagnoses of chronic obstructive pulmonary disease and The results of the lung function investigations hypertension. He had no avian or occu- performed as shown in table 1. Supine pational exposures, a minimal smoking and erect spirometry demonstrated oxygen history while in his teens and had not smoked saturations of 93% when lying down and 86% since, and no history of transient ischaemic on sitting. There was no significant revers- attack or cerebrovascular accident. ibility to 2.5 mg nebulised salbutamol. On examination, he was comfortable with A capillary blood gas taken on air at rest no respiratory distress but had slight peri- showed an oxygen tension (PO2) of 8.0 kPa pheral cyanosis and oxygen saturations of (normal 12.0–15.0 kPa), a carbon dioxide 89% on room air. Auscultation of his chest tension (PCO2) of 4.4 kPa (normal 4.5–6.1 revealed increased vocal fremitus and kPa) and pH of 7.44 (normal 7.36–7.42). crackles over the right lower lobe with occasional wheeze. CT The patient was investigated using ERS 2014 lung function testing, capillary blood gas CT images are shown in figure 1. HERMES syllabus link: module B.5.5, B.15.4, C.1.1, C.1.2, D.2.22, D.3.1

DOI: 10.1183/20734735.012313 Breathe | June 2014 | Volume 10 | No 2 147 Curable hypoxia in an octogenarian with an undiagnosed inherited condition

Table 1. Lung function

Parameter Measured Predicted % predicted SR

FEV1 L 1.64 3.30 50 -3.27

FVC L 4.11 4.47 92 -0.60

FEV1/FVC % 40 72 55 -4.55

TLCO 5.42 9.67 56 -3.01

KCO 0.91 1.19 76

RV L 3.94 3.06 129 2.15

SR: standard residual (normal¡1.64); FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLCO: transfer factor of the lung for carbon monoxide; KCO: transfer coefficient for carbon monoxide; RV: residual volume.

a) b) Task 1 1) What is seen on the initial CT scan (fig. 1). 2) What conditions can be associated with this? 3) Can you interpret the lung function results (table 1)?

Figure 1 a) Axial and b) coronal CT slice.

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Answer 1 were compatible with hereditary haemorrhagic teleangiectasia (HHT). 1) There is a 2-cm vascular abnormality in the right lower lobe consistent with a Despite his age at presentation, the pulmonary arteriovenous malformation diagnosis had not been previously consid- (PAVM). ered. Subsequently, his daughter and grand- 2) PAVMs are most commonly seen with sons reported recurrent nose bleeds, and hereditary haemorrhagic telangiectasia were advised to seek screening for HHT. (.90%) and post-cardiac surgery for cyanotic congenital heart disease with Discussion resultant cavopulmonary shunt. They can PAVMs are direct communications between occur sporadically, or may very branches of the pulmonary artery and vein occasionally be secondary to, for example, allowing blood to pass from one to the other hepatic cirrhosis or schistosomiasis. without traversing the pulmonary capillary 3) The spirometry shows an obstructive bed, resulting in the pulmonary arterial blood picture of moderate severity. Nevertheless, passing through these right-to-left shunts the FEV1 is relatively well preserved for this without being oxygenated. As the normal degree of desaturation and it was this pulmonary capillary bed also prevents bac- discrepancy that prompted the initial teria and emboli from reaching the systemic referral suggesting another contributing circulation, bypassing this system can poten- pathology. Importantly, this patient tially lead to both septic and embolic events. demonstrates orthodeoxia, whereby he PAVMs due to HHT account for at least becomes desaturated when sitting or 90% of cases and these develop over time. standing from a recumbent position. This HHT is an autosomal dominant disorder of is confirmed symptomatically as his the vasculature resulting in AVMs and dyspnoea improved when lying flat telangiectasia. PAVMs in HHT may be (platypnoea, a very rare symptom for this present in childhood but grow and, in some, condition). possibly many cases, develop de novo in puberty. Acquired PAVMs are far less common and The exact mechanism of orthodeoxia is have been reported to occur most frequently unclear but is different to cardiac disease. following thoracic surgery for congenital One contributing factor to the orthodeoxia is valvular heart disease [2]. Lesions have been that most PAVMs are at the lung bases and classified as simple (with one feeding artery), complex (with more than one feeding artery) right-to-left shunting increases on standing and diffuse (rare but with hundreds of because of the effects of gravity. The normal malformations) [3]. anatomical right-to-left shunt is less than 2% but is increased in patients with PAVMs. The size of the shunt influences arterial oxygen Presentation tension and saturation, and occlusion of the PAVM increases saturation. When there is co- The cardiorespiratory clinical picture depends existing lung disease, ventilation–perfusion on the size of the shunt and associated clinical parameters, such as concurrent car- mismatch may also be a contributing factor [1]. diopulmonary disease and iron deficiency. Shunts over 20% of the cardiac output can Case management and outcome lead to cyanosis, clubbing and polycythaemia. Following the diagnosis of a PAVM, the Large shunts commonly cause minimal or no patient underwent percutaneous radiologi- clinical symptoms even when associated with cally guided embolisation with improvement clinical signs such as cyanosis, clubbing or in his exercise tolerance to 800 m. Post- polycythaemia. As the hypoxaemia is due to a procedure, his oxygen saturations on air were right-to-left shunt, the cyanosis may only 97% when sitting and 95% when supine. partially correct with oxygen therapy. More On closer questioning, he reported fre- acute presentations are due to paradoxical quent nosebleeds over a number of years and emboli causing stroke, or due to rupture of was seen by the ear, nose and throat team the AVM with resultant massive pulmonary who confirmed the rhinological appearances haemorrhage or haemothorax. A 2:1 female

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Table 2. Presenting features of pulmonary arteriovenous malformations

Symptoms Signs

Asymptomatic Cyanosis Breathlessness Clubbing Haemoptysis Telangiectasia (if associated with HHT) Focal neurological deficit (stroke/brain abscess) Polycythaemia Pulmonary bruit (exacerbated by the Mu¨ller manoeuvre) Focal neurological deficit (stroke/brain abscess)

preponderance has been reported in older right-to-left shunt but not identify the cause series. or the extent of the defect. Of note, bubble As most cases are associated with HHT, contrast echocardiography can be positive there may be a history of epistaxis or in control subjects. Pulmonary angiogram neurological symptoms (due to paradoxical allows definition of the vasculature during emboli) but many PAVMs are asymptomatic. embolisation [2] while CT angiogram has Presenting features of PAVMs are shown better resolution for small PAVMs. in table 2. Magnetic resonance angiography is an option for younger patients where the radi- ation risk is of greater concern but may not Complications of PAVMs identify all clinically significant lesions. PAVMs carry significant risks [4]. Neuro- logical complications are most commonly Treatment reported (up to 59% of patients) and are due to paradoxical emboli via pulmonary circula- PAVMs were previously treated with surgical tion. The most common neurological mani- resection but now embolisation with coils festation is migraine but there is significant and plugs is the treatment of choice. PAVMs risk of stroke (1% per annum) and brain should be embolised if technically feasible, abscess (0.5% per annum) with the risk being which is generally possible with feeding unrelated to the size of the lesion [5]. arteries of 2 mm or more. Treatment of Pulmonary complications are rare with one PAVMs by embolisation is a safe and effective study showing an incidence of 8% in a group way to reduce lifetime risk of embolic events of patients referred for interventional radi- and abscess formation as well as treating ology. These complications are more com- haemoptysis and improving oxygenation [6]. mon in women, particularly when pregnant. Prevention of these complications is the main Screening rationale for prophylactic treatment due to the potentially catastrophic nature of stroke Following identification of a patient with a and haemorrhage. PAVM, consideration needs to be given to screening of family members due to the autosomal dominant inheritance of HHT. Investigations The diagnostic criteria (Curacao criteria) for Full history and examination is required to HHT are outlined in table 3. HHT can be elicit any personal or family history of any definitively diagnosed when three or four of symptomatology suggestive of HHT. the criteria are met. A chest radiograph may demonstrate a There is no clear consensus on the localised abnormality (as it did in this case) optimal screening tool. In some centres, the but contrast-enhanced CT is more accurate in demonstration of a right-to-left shunt by diagnosis and determining the anatomy. contrast echocardiography has a reported Pulmonary function tests, pulse oximetry sensitivity and negative predictive value and demonstration of orthodeoxia all add .95% [7]. The low specificity (62%) may to the overall clinical picture. A bubble indicate microscopic PAVMs that are too contrast echocardiogram will demonstrate a small to be recognised on CT imaging. Other

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Table 3. Curacao diagnostic criteria for HHT Recurrent spontaneous nosebleeds Mucocutaneous telangiectases at characteristic sites (fingertips, lips and oral mucosa) Visceral AVMs (pulmonary, gastrointestinal, cerebral and hepatic) Family history of first-degree relative affected

3–4 criteria: definite HHT; 2 criteria: possible HHT; 0–1 criterion: unlikely HHT. centres opt for chest radiography proceeding Patients with co-existing PAVMs and to contrast CT if any abnormality is detected pulmonary hypertension can be difficult to and using contrast echocardiography if the manage, although the treatment options chest radiograph is normal [8]. Genetic remain the same. Embolisation will preferen- screening may of benefit to asymptomatic tially correct areas with lower vascular resist- family members of a known HHT patient but, ance and paradoxically increases the risk of in the general patient population, the Curacao focally elevated pulmonary artery pressure criteria are a more sensitive diagnostic tool. with potentially disastrous consequences. In this group of patients, the risk of embolic events diminishes with the rise in pulmonary Special considerations: pregnancy and artery pressure and some patients fail to pulmonary hypertension obtain symptomatic relief following emboli- PAVMs can become more problematic in sation. Therefore, it has been suggested that pregnancy as the increase in cardiac output the risks of PAVM embolisation in patients and blood volume can cause dilatation of the with co-existing pulmonary hypertension may vasculature. The risk of PAVM rupture is outweigh the benefits [6]. difficult to quantify but is significantly higher in pregnancy. Therefore, women with known Follow-up and patient education PAVMs need to be carefully counselled pre- pregnancy with emphasis on treatment prior Patients with PAVMs require long-term to conceiving. follow-up. While embolisation may cure the Overall maternal mortality in the UK is malformation, up to 60% of patients have 4.67 per 100,000 maternities [9] but in evidence of residual disease due to PAVMs women with PAVMs mortality is 1% with all too small to treat. Residual defects may also deaths occurring in women without pre- increase in size following embolisation of the pregnancy diagnosis of their PAVM [10]. larger vessels. Additionally, there is a risk of Current UK recommendations [10] propose recanalisation over time of up to 20%, either that, although the risk remains low and most through the embolic device or from the pregnancies have no complications, the development of collateral feeding arteries. significant increase means that these patients Following treatment, patients will be regularly should be managed as high-risk pregnancies. followed up but with urgent review and Therefore women with known PAVMs need to further CT assessment if their condition be carefully counselled pre-pregnancy and changes. Patients need to be given education screened for PAVMs with emphasis on regarding antibiotic prophylaxis for routine treatment prior to conceiving. Screening for medical and dental procedures, the need for cerebral AVMs should also be considered in air filters on intravenous infusions, and the those HHT patients with a family history of risks of decompression sickness in scuba cerebral haemorrhage and, for those wanting diving [12]. regional anaesthesia, a spinal magnetic As most PAVMs are associated with HHT, resonance imaging scan may be considered a thorough assessment of the patient in this to exclude spinal AVMs. Antibiotic prophy- regard is required and familial screening may laxis is required during delivery. be indicated.

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