Brief Report

A 24-year-old man with chest pain, hemoptysis, and hypoxia

Chad S. Kessler MD?, Sharon Moise Leipzig MD

Department of Emergency Medicine, University of Illinois-Chicago, Chicago, IL 60612, USA

Received 5 November 2007; accepted 6 November 2007

Abstract The diagnosis of Pulmonary arteriovenous malformations in patients remains a diagnostic challenge to the emergency physician. Pulmonary arteriovenous malformations are abnormal direct connections that shunt unoxygenated blood from pulmonary arteries to pulmonary veins, resulting in hypoxia. They represent a rare clinical entity and are usually associated with Hereditary hemorrhagic telangiectasia. We report a case of a young man who presented to the emergency department with an acute onset of right-sided chest pain, and vital signs and laboratory findings that did not clinically correlate with his history or physical examination. To our knowledge, there are no case reports of pulmonary arteriovenous malformations described in the emergency medicine literature.

(C) 2008

History

A 24-year-old man presented to the emergency depart- ment (ED) with a 9-day history of right-sided chest pain. The pain was sharp and ranged 4/10 to 10/10 in intensity. The pain was associated with some Chest tightness, and worsened with cough, movement, swallowing, and deep inspiration. The patient denied radiation of pain or shortness of breath. The patient complained of fever, chills, and one episode of vomiting. He also reported “jelly-like” hemoptysis 1 to 2 days per month for about 1 year. The last episode of hemoptysis was 1 month prior Fig. 1.

Over the preceding 9 days, the patient presented 3 times to the same community ED for persistent chest pain. He reported having had a chest computed tomography and being started on coumadin for presumptive pulmonary embolism. A repeated chest CT 4 days later revealed a right pleural effusion; thoracentesis was performed that yielded sanguineous fluid. Coumadin was discontinued and hydrocodone was given for the pain. Frustrated with the

* Corresponding author. Tel.: +1 312 569-6508.

E-mail address: [email protected] (C.S. Kessler).

lack of improvement of his chest pain, the patient presented to our ED.

The patient came with no records of past hospitalizations and poor insight into his medical history. He revealed a history significant for a “stroke” at 15 years of age with gradually resolving left-sided paresis. In addition, a “heart murmur” and a “heart attack” at 14 years of age were treated at a children’s hospital with “4 stents.” At presentation, his only medicine was hydrocodone. He denied any drug allergies. Family history was negative on his mother’s side; he did not have any contact with or knowledge of his father or paternal relatives. Socially, he admitted to tobacco (1 pack per day x 10 years) and occasional marijuana use. He denied alcohol and intravenous drug use.

On physical examination, the patient was a well- developed, young Hispanic man who appeared comfortable and cooperative, speaking in full sentences, and in no acute distress. Vital signs revealed a temperature of 100.8?F, pulse of 100 per minute, respiratory rate of 18 per minute, blood pressure of 119/70 mm Hg, and a 89% oxygen saturation on room air. His pupils were equally round and reactive. He had no central or perioral cyanosis. No cervical lymphadeno- pathy was appreciated. On cardiac examination, he was

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Fig. 1.

tachycardic with occasional ectopy. The first and second heart sounds were appreciated. The patient had a III/VI murmur with an apparent systolic and diastolic component. The murmur was loudest at the right upper sternal border and radiated to the carotids. No jugular venous distention was noted. His pulses were equal in bilateral upper and lower extremities. He had decreased breath sounds in the right lower lung field, with no retractions, Accessory muscle use, crackles, or wheezes. He had moderate to good air exchange. The Abdominal examination was unremarkable, and the stool was negative for occult blood. The patient had no pallor, cyanosis, or rashes but had marked clubbing noted on bilateral upper and lower extremity digits.

The patient was placed on 4-L nasal cannula oxygen (which increased his saturation to 91%), placed on a cardiac monitor, and was given intravenous fluids. He continued to show no respiratory distress. initial chest radiograph revealed surgical wires in the right anterior mediastinum and a right- sided pleural effusion. The spiral CT was initially read by the radiologist as Chronic pulmonary embolism (as dye did not reach the peripheral lung), a right pleural effusion, and having coils in the right anterior mediastinum. The electrocardio- gram read normal sinus rhythm, significant only for Right axis deviation. No Ischemic changes were noted. Significant laboratory findings revealed a white blood cell count of 12400 cells/mm³, a hemoglobin level of 16.2, and electro- lytes that were within normal limits. The arterial blood gases were pH 7.49/ PCO2 34.9/ PO2 51/% sat 88.6. PT was 15.5, international normalized ratio 1.21, and PT was 29.2.

Given the initial chest CT reading of “chronic PE” and the

patient’s Low Oxygen Saturation and PO2, the decision was made to begin anticoagulation with heparin (80 U/kg bolus, followed by 18 U/kg maintenance infusion). A hypercoagul- ability panel and cardiac markers were sent. The patient appeared clinically stable with evidence of chronically compensated hypoxia and clubbing. The decision was made to admit the patient to a monitored telemetry unit.

On the medical floor, 3 sets of cardiac markers were negative. The final reading of his chest CT, not available in the ED, was read as no evidence of pulmonary embolism. There was, however, evidence of an anastamosis between the pulmonary vasculature, as well as multiple coils, vasculitic ectasia, and a pleural effusion. A thoracentesis of the right- sided pleural effusion yielded sanguineous fluid consistent with a hemothorax. Cytology and culture results were negative. Anticoagulation with heparin was discontinued. The hypercoagulability workup, purified protein derivative skin test, and antinuclear antibody titer had negative results. The erythrocyte sedimentation rate was within normal limits. Pediatric cardiology, pulmonology, and interventional radi- ology consultations were obtained. Old records from the children’s hospital revealed that the patient underwent coil embolization 4 times at 14 years of age for a pulmonary arteriovenous malformation (AVM). The patient was lost to follow-up for the next 8 years. There was no history of any myocardial infarction or cardiac stenting. A 2-dimensional echo, done at our institution, revealed pulmonary hyperten- sion and a positive bubble study, more consistent with a pulmonary AVM than a septal defect.

The patient had a cardiac catheterization for coil embolization of the AVM in the right middle lung. Twelve Gianturco coils were placed during catheterization. Oxygen saturation improved from 91% to 98% after the procedure. After catheterization, the “murmur”(actually a bruit caused by the pulmonary AVM) resolved, and repeat arterial blood gases revealed 7.41/37.9/89/96.9% (PaO2 increased from 51 to 89 mm Hg). The patient did not notice any difference in his respiratory status; however, his hemoptysis resolved, his chest pain began to gradually improve, and serial chest x- rays revealed a resolving pleural effusion.

Given the association of pulmonary AVMs with cerebral AVMs, and the patient’s neurologic symptoms, a head CT, brain magnetic resonance imaging/magnetic resonance angiography, and cerebral angiogram were

performed. They revealed 3 small intracranial AVMs- pontine, occipital, and right cerebellar. Neurosurgery was consulted. No neurosurgical interventions were performed during the admission.

The patient was discharged with appropriate follow-up in medicine, pediatric cardiology, neurology, neurosurgery, and gastroenterology clinics.

Discussion

Pulmonary arteriovenous malformations are abnormal direct connections between pulmonary arteries and pulmon- ary veins. Pulmonary AVMs generally occur in both lungs and are more frequently seen in the lower lobes (70%) [1]. The direct Right to left shunts caused by pulmonary AVMs often result in cyanosis, secondary polycythemia, and clubbing. Patients commonly present with dyspnea, fatigue, and decreased exercise tolerance. A hallmark of pulmonary AVMs is orthodeoxia, which is a decreased oxygen saturation upon standing. Orthodeoxia is caused by blood pooling at the lung base, where most pulmonary AVMs occur. Screening tools for pulmonary AVMs include a chest x-ray, arterial blood gas sampling, and supine and erect oximetry. However, the best diagnostic tool is helical CT [2,3]. In patients with lesions highly suspicious for pulmonary AVMs, a pulmonary angiogram is necessary for diagnosis and treatment [3]. Initial screening of patients with a positive family history is recommended at puberty. In patients with pulmonary AVMs, follow-up CTs are recom- mended at 5-year intervals. Preconception screening is also recommended because there have been case reports of third- trimester Pulmonary hemorrhage. In patients with pulmonary AVM, antibiotic prophylaxis is recommended during any dental or surgical procedures [4]. Treatment options include coil and balloon embolization, surgical management includ- ing lobectomy and wedge resection, and ligation of the arterial supply. lung transplantation had been suggested as a treatment for patients with pulmonary AVM; however, the survival rate in one study was shown to be worse (63% vs 91%) [5].

In addition to isolated pulmonary AVMs, there is also a clinical syndrome that includes pulmonary AVMs character- ized by Rendu, Osler, and Weber, now known as hereditary hemmorhagic telangiectasia (HHT). The prevalence of HHT is estimated at 1 to 2 per 100000 with a preponderance in whites [4,6]. The classic presentation of HHT is epistaxis, dilated blood vessels over lips and fingers, and gastro- intestinal bleeding. Clinical criteria for HHT include 3 of the following 4 conditions: Recurrent epistaxis, telangiectasia elsewhere from the nasal mucosa, autosomal dominant inheritance, and visceral involvement. The most common manifestation of HHT is epistaxis, reported in 50% to 80% of the affected population [6]. The epistaxis generally begins between the first and second decade of life and progressively

worsens. The mucocutaneous telangiectases commonly appear in the third decade of life and are seen in most patients with HHT. Proposed explanations of telangiectases include defects in the endothelial junctions, incomplete smooth muscle cell layer surrounding vessels, and extra- vasation of erythrocytes [6].

Hereditary hemmorhagic telangiectasia is inherited in an autosomal dominant fashion with 97% penetrance. The gene causing HHT, identified as endoglin, encodes a protein that binds transforming growth factor ?. This protein plays a regulatory role in tissue repair and angiogenesis. The chromosomal abnormalities associated with the endoglin gene are found on 9Q and 13Q [4,6].

The neurologic symptoms associated with HHT include migraines, Brain abscesses, transient ischemic attacks, Cerebrovascular accidents, seizures, and intracranial and Subarachnoid hemorrhages [3,4,7]. Most (67%) of neurolo- gic sequelae are the result of pulmonary AVMs [4,7]. Right to left pulmonary shunts allow for paradoxical embolization of matter to systemic and cerebral circulation, which can account for cerebral ischemia and abscesses [7]. In addition to pulmonary etiologies, cerebral AVMs, found in 5% to 10% of patients with HHT, may result in seizures, migraines, and hemorrhages. Possible treatment options include microsur- gical excision, ? knife embolization, and radiotherapy. There has been no definitive studies demonstrating the benefit of treating cerebral AVMs [4]. Magnetic resonance imaging remains the screening method of choice. Screening magnetic resonance imaging is recommended during childhood for patients with a positive family history [4,7].

Gastrointestinal manifestations, primarily recurrent hemorrhage of the upper and/or lower gastrointestinal tract, are seen in a small proportion of patients with HHT. They tend to occur in the fifth or sixth decade of life. Endoscopy often reveals telangiectases throughout the stomach, small bowel, and colon that are similar in appearance and size to telangiectases seen in the nasal mucosa. However, larger lesions and AVMs have been described. Treatment options include laser therapy or photocoagulation with bipolar electrocoagulation. These interventions have questionable long-term efficacy. A double-blinded prospective study showed that treatment with estrogen and progesterone decreased the need for transfusion in patients with gastro- intestinal bleeding and HHT by an unknown mechanism [4]. The case we present is unique in several aspects. The patient described was a poor historian who did not come to the ED with a diagnosis of pulmonary AVM but rather an inaccurate account of a myocardial infarction requiring stents and a vague history of a cerebrovascular accident. Because the history, physical examination, and laboratory findings did not correlate clinically, a full workup was initiated. In the ED, many differentials were entertained including pulmonary embolism, pulmonary effusion, hyper- coagulable disorder, and less likely, a myocardial infarction.

However, at the time of discharge from the ED, the diagnosis remained unclear.

Once all the studies had been completed, it became apparent that our patient had a history of a pulmonary AVM coiled 10 years earlier. He had been asymptomatic and lost to follow-up until he presented with chest pain. It is likely that the pulmonary AVM either grew in size or had recannulized, leading to a gradual decrease in oxygen saturation. The patient compensated for this chronic hypoxia with increased erythropoesis leading to polycythemia. Based on the literature, 5% to 10% of embolizations result in recannula- tion [6]. The study of Foughnan et al [5] on diffuse pulmonary AVMs described that most patients do not feel dyspneic despite a mean PaO2 of 47 and evidence of clubbing (seen in 94% of patients). As described earlier, neurologic complications such as transient ischemic attacks, strokes, and brain abscesses are common and often the first sign of a pulmonary AVM. Our patient had 2 episodes of weakness, numbness, and pain at 15 years of age, which later resolved. These Neurologic events, which occurred after the initial embolization, may have indicated recannulization of the pulmonary AVM or cerebral vascular malformations, which were seen on this later admission [5].

Our patient falls into the category of suspected HHT as he

fulfills 2 of the 4 criteria for diagnosis. He had pulmonary and cerebral AVMs, as well as oral telangiectases (as documented on the medical floor). The patient did not have any relationship with his father, and thus, it is not possible to rule out a first-degree family relative with HHT. In addition, the incomplete penetrance of HHT may suggest that the genetic component exists despite a negative family history. As components of HHT can develop throughout a lifetime,

this patient may still develop more findings consistent with the diagnosis. Screening and appropriate medical follow-up are essential [1,6].

Conclusion

Although pulmonary AVMs and HHT are uncommon, it is helpful to keep these diagnoses in mind when developing a differential for patients who have marked hypoxia without dyspnea, Atypical chest pain, and a history of both pulmonary and neurologic findings.

References

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3. Khalil A, et al. Pulmonary ateriovenous malformations. Chest 2000;117(5).
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5. Faughnan ME, et al. Diffuse pulmonary arteriovenous malformations. Chest 2000;117:1.
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