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A 32-Year-Old-Man With a Severe Headache, Visual Loss, and Nodular Pulmonary Opacities FREE TO VIEW

Valliappan Muthu, MD, DM; Inderpaul Singh Sehgal, MD, DM; Ritesh Agarwal, MD, DM; Sahajal Dhooria, MD, DM
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Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

CORRESPONDENCE TO: Sahajal Dhooria, MD, DM, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India 160012


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(5):e137-e141. doi:10.1016/j.chest.2016.05.011
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A 32-year-old man presented with severe headache, vomiting, and painless loss of vision of 5 days’ duration. He had no seizures, other neurologic deficits, or fever. Two months prior to presentation, he had an episode of hemoptysis of 30 to 50 mL, which resolved spontaneously; there was no recurrence. He reported one to two episodes of epistaxis each month that resolved spontaneously, since childhood. He had no known comorbid illness, prior surgeries, dental procedures, or blood transfusions. He denied any history of substance abuse. He observed that his father and brother also had recurrent self-limited episodes of epistaxis.

Figures in this Article

The patient was conscious and oriented. He had a pulse rate of 94 beats per minute, blood pressure of 130/70 mm Hg, temperature of 37.6°C, and pulse oximetric saturation of 97% on breathing ambient air. Funduscopy showed papilledema. There was no neck stiffness or focal neurologic signs. Multiple telangiectasia on the lower lip and finger clubbing were observed (Fig 1). The rest of the physical examination was normal.

Figure 1
Figure Jump LinkFigure 1 A, Clinical photograph showing telangiectasia on the lower lip. B, Clinical photograph showing clubbing of fingers.Grahic Jump Location

Laboratory investigations revealed hemoglobin of 14.2 g/dL, total leukocyte count of 16,700/μL, with a predominance of neutrophils, and platelet count of 214,000/μL. Prothrombin time and partial thromboplastin time were normal. The results of serum electrolytes, liver and kidney function tests, and electrocardiogram were normal. MRI of the brain showed numerous ring-enhancing lesions in bilateral occipital lobes (Fig 2). Chest radiograph showed multiple well-defined nodular opacities in bilateral lung fields (Fig 3). Echocardiography was normal.

Figure 2
Figure Jump LinkFigure 2 MRI of the brain showing multiple ring enhancing lesions in both occipital lobes (arrows).Grahic Jump Location
Figure 3
Figure Jump LinkFigure 3 Posteroanterior chest radiograph showing bilateral lung nodules (arrows).Grahic Jump Location

The patient was started on intravenous vancomycin and ceftriaxone for a presumed diagnosis of multiple brain abscesses from hematogenous spread of bacteria. He underwent craniotomy and aspiration of bilateral occipital lobe lesions along with excision biopsies. The aerobic and anaerobic cultures of the aspirates were sterile. Smears and cultures for fungi and mycobacteria were negative. Brain biopsy from the wall of the occipital lesions showed only neutrophilic inflammation without any organism.

What is the diagnosis?

Diagnosis: Hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations and bilateral occipital lobe abscesses.

Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder with variable penetrance, has a prevalence of approximately one in 5,000 to 8,000 individuals. It is characterized by varying combinations of recurrent epistaxis, mucocutaneous telangiectasias, and gastrointestinal bleeding. In addition to these, arteriovenous malformations (AVMs) involving pulmonary, hepatic, and cerebral circulation are well recognized. Mucocutaneous telangiectasias generally do not result in life-threatening bleeding, but recurrent episodes of epistaxis and the resultant blood loss may lead to iron deficiency anemia. The manifestations of the disease increase with increasing age. Patients who come to clinical attention before 60 years of age usually do so because of visceral involvement. These patients have excessive mortality and morbidity, unlike the individuals who go unnoticed until 60 years of age and tend to have a normal survival.

In patients with HHT, AVMs are most commonly seen in pulmonary circulation. Conversely, HHT accounts for up to ≥ 70% cases of pulmonary AVMs. Dyspnea on exertion and hemoptysis are the most common symptoms associated with pulmonary AVMs. Intrapulmonary right to left shunting of blood may cause substantial hypoxemia and may manifest as clubbing and/or polycythemia. In the presence of basal pulmonary AVMs, platypnea may occur. In patients with platypnea and in some even without platypnea, orthodeoxia can be demonstrated, which is defined as a drop in oxyhemoglobin saturation by ≥ 2% when assuming an erect posture from the supine position. It is a characteristic feature of basal pulmonary AVMs; other differential diagnoses include hepatopulmonary syndrome and atrial septal defects. A bruit or murmur over the pulmonary AVMs may be heard in one-third of patients. Pulmonary AVMs usually remain stable in their size, but nearly one-fourth of these AVMs may enlarge slowly at the rate of 0.3 to 2 mm/y. The walls of these AVMs are thin, which may result in their rupture into the bronchus, causing hemoptysis, or into the pleural cavity, resulting in hemothorax. Pulmonary hypertension may be encountered in nearly 10% of patients with HHT, which may be pathophysiologically similar to heritable (idiopathic) pulmonary arterial hypertension. It may also arise in the presence of hepatic AVMs with resultant portopulmonary hypertension or group 2 pulmonary hypertension (because of high output left heart failure). In some patients, pulmonary hypertension may increase in severity from baseline or appear newly after resection or embolization of pulmonary AVMs. Redistribution of the pulmonary blood flow after resection or embolization is proposed as the mechanism in the latter group of patients.

Pulmonary AVMs form a capillary-free direct communication between pulmonary and systemic circulation. Absence of the filtering effect offered by pulmonary capillaries predisposes to paradoxical embolism, resulting in embolic stroke and/or cerebral abscesses. Although neurologic complications, including brain abscess, may occur with a single pulmonary AVM, the odds of such complications are much higher when there are multiple AVMs. It is not uncommon for pulmonary AVMs to be detected while the patient is being evaluated for these complications. Brain abscess may occur in up to 10% of individuals with pulmonary AVMs. Anaerobic organisms from periodontal sources are commonly implicated in such abscesses, which tend to be bilateral and develop at the gray-white matter junction. Because these abscesses arise from hematogenous spread of bacteria, a combination of ceftriaxone and vancomycin is generally used for empirical treatment. Aspiration of the abscess is performed in most cases both for identification of the causative organism and therapy. Surgical excision is reserved for encapsulated fungal abscess, multiloculated abscesses, or when there is no clinical improvement with aspiration and antibiotic therapy. Obtaining a history of epistaxis and identifying the presence of mucocutaneous telangiectasia in a patient with a cerebral abscess could point toward the diagnosis of HHT.

Bubble contrast echocardiography is a good screening test for the detection of pulmonary AVMs with a high sensitivity (> 95%) but poor specificity (about 50%). On a CT scan of the chest, pulmonary AVMs appear as well-defined single or multiple round or oval nodules of size 1 to 5 cm with smooth margins. A feeding vessel may sometimes be visualized as a tubular structure leading to the nodule. If IV contrast is administered (although not essential for diagnosis), enhancement of the nodule is seen. MRI does not have any additional diagnostic value over CT imaging. Pulmonary angiography is the gold standard for diagnosis of pulmonary AVMs because a pulmonary vessel can be clearly visualized feeding the sac. Further, angiography helps in planning embolotherapy.

Diagnosis of HHT is made on the basis of the international consensus diagnostic criteria (Curacao criteria) which include spontaneous recurrent epistaxis, multiple mucocutaneous telangiectasias, visceral AVMs, and a first-degree relative with HHT. A definite diagnosis of HHT is made when at least three of these four criteria are met. The diagnosis may be further confirmed by genetic testing for endoglin (HHT type 1) and activin receptor-like kinase-1 (HHT type 2). Clinical features of both the types of HHT are similar; however, cerebral and pulmonary AVMs are more common with HHT-1, whereas hepatic AVMs and pulmonary hypertension are more frequently encountered in HHT-2. Up to 96% of individuals who strictly satisfy the Curacao criteria have mutations in one of these two genes. Rarer mutations include SMAD4 and GDF2. Genetic testing is not essential for the diagnosis. However, it may be offered to asymptomatic relatives of patients with HHT with the aim to prevent morbidity and mortality by early diagnosis.

In patients diagnosed with HHT, screening for pulmonary AVMs is controversial. Although several algorithms have been proposed for screening, a reasonable approach would be to perform a chest radiograph initially. If it is normal but pulmonary AVMs are still suspected, bubble contrast echocardiography should be performed as a screening test because of its high sensitivity. A normal study warrants no further investigations. However, an abnormal bubble contrast echocardiography suggesting a delayed shunting because of pulmonary AVMs should be confirmed with a noncontrast multidetector thin section CT scan of the chest. Screening of asymptomatic family members for pulmonary or cerebral AVMs is debatable. However, a complete history, physical examination, chest radiograph, and evaluation for anemia may be undertaken.

Management of localized bleeding such as epistaxis and gastrointestinal bleed is no different in individuals with and without HHT. However, when the bleeding is significant and bothersome, hormonal therapy in the form of estrogens (systemic and topical form) and antiestrogens, such as tamoxifen, has been tried, with varying degrees of success. Symptomatic pulmonary AVMs are best managed with embolotherapy, especially when they are multiple and bilateral, where surgery may result in extensive loss of lung parenchyma. Steel coils and detachable balloons are generally used for embolization of pulmonary AVMs. Multiple pulmonary AVMs may require more than one session of embolotherapy. AMPLATZER plug devices (St Jude Medical) are preferred over coils when the feeding artery has a larger diameter. When the feeding vessel to the AVM is < 2 to 3 mm in diameter, embolization may not be technically possible. Apart from improvement in oxygenation and preventing paradoxical embolism, embolization has also been shown to reduce stroke and migraine in these patients. Surgery may be considered for symptomatic AVMs when embolotherapy is not feasible either because of contrast allergy or technical difficulty.

Clinical Course

CT scan of the chest revealed nodular pulmonary opacities bilaterally, and subsequent contrast administration confirmed the presence of multiple bilateral pulmonary AVMs. Transthoracic contrast echocardiography with agitated saline did not show any right to left shunt. Orthodeoxia was noted in arterial blood gas analysis, with partial pressure of arterial oxygen in the supine and erect positions being 64.6 and 51.4 mm Hg, respectively (with the oxygen saturation dropping from 93% to 84%). Telangiectasia was also seen in esophagus and duodenum and the bronchial tree, demonstrated by endoscopy and flexible bronchoscopy, respectively. The patient underwent digital subtraction angiography and coiling of the pulmonary AVMs (Fig 4). The patient was discharged from the hospital after completing 4 weeks of IV antibiotics. There were no neurologic deficits or visual disturbances at discharge and after 6 months of follow-up. Because there were multiple AVMs, embolization of the remaining AVMs was performed on subsequent visits. The patient’s brother had a normal hemoglobin, and his chest radiograph was unremarkable; no further workup was performed.

Figure 4
Figure Jump LinkFigure 4 Posteroanterior chest radiograph showing endovascular coils inserted into the pulmonary arteriovenous malformations (arrows).Grahic Jump Location

  • 1.

    In a patient presenting with brain abscesses and a history of epistaxis, HHT with pulmonary AVM should be considered.

  • 2.

    Pulmonary AVMs can present with hemoptysis, hypoxemia because of right to left shunting, or embolic phenomena, such as cerebral abscesses or stroke.

  • 3.

    HHT is an important cause of pulmonary AVMs. Recurrent epistaxis, mucocutaneous telangiectasia, and AVMs involving pulmonary, cerebral, and hepatic circulations are other features of this disease.

  • 4.

    Symptomatic pulmonary AVMs are best managed with embolotherapy.

Financial/nonfinancial disclosure: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 A, Clinical photograph showing telangiectasia on the lower lip. B, Clinical photograph showing clubbing of fingers.Grahic Jump Location
Figure Jump LinkFigure 2 MRI of the brain showing multiple ring enhancing lesions in both occipital lobes (arrows).Grahic Jump Location
Figure Jump LinkFigure 3 Posteroanterior chest radiograph showing bilateral lung nodules (arrows).Grahic Jump Location
Figure Jump LinkFigure 4 Posteroanterior chest radiograph showing endovascular coils inserted into the pulmonary arteriovenous malformations (arrows).Grahic Jump Location

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