Swyer syndrome

Key words: blebs; bronchial arteries; pneumothorax; pulmonary hypertension; pulmonary infarction; smooth muscle proliferation; thromboembolism

Abbreviations: Dco=diffusion of carbon monoxide; [FEF.sub.25-75]=forced expiratory flow rate between 25% and 75% of the FVC; LAM=lymphangioleiomyomatosis; UHNY=university hospital in New York

Pulmonary clinicians are often faced with management problems for which there are no answers at hand, either because there is no literature that definitely gives answers or because the circumstances surrounding the clinical cases are unusual enough to prevent the application of existing scientific knowledge. When faced with these problems, clinicians are forced to make decisions based on a logical extension of their scientific knowledge into uncharted clinical waters. They are forced to make judgments based on the conviction of their speculations and the prior experiences of others and of themselves.

This case conference addresses difficult management problems without singularly correct decisions; its object is not necessarily to seek consensus. Defining the exact issues, formulating rationales for decision making, and committing to the decisions themselves are all equally important in this presentation. This is a real case in which the decisions were made by the "treating pulmonologist" without input from the other participants. The "responses of pulmonary experts" are given only with the knowledge of the case presentation up to the moment at which each expert gives his or her decision and without the knowledge of any of the other opinions rendered. The "commentary" is given only with the knowledge of the full case presentation and the "follow-up by the treating pulmonologist" but without the knowledge of any of the other opinions rendered. The "commentary" is the last opinion in the sequence of this presentation, but it is not necessarily offered as the definitive solution to the problems posed in the case. The reader is the ultimate arbiter in this presentation of decision-making alternatives.

CASE PRESENTATION

A 28-year-old nulligravida white woman, with a 10-pack-year smoking history, presented to a university hospital in New York (UHNY) in August 1992 with sudden pleuritic chest pain and dyspnea. Chest radiograph revealed a right-sided pneumothorax prompting hospital admission and treatment with a chest tube. The pneumothorax resolved. Shortly thereafter, she was admitted to a hospital in Virginia for recurrent right pneumothorax and underwent thoracoscopic blab-stapling, pleurodesis, and lung biopsy (of the right apex); the specimen was read as, "Cut surface revealing fine emphysematous changes throughout. Microscopic diagnosis: pulmonary emphysema." At hospital discharge, she took an airplane home but was readmitted to UHNY for a 40% right basilar hydropneumothorax. A second thoracoscopy revealed apical adhesions and residual blebs that were stapled. Pleurodesis and lung biopsy (of the right upper lobe) were repeated.

A lung pathologist at UHNY reviewed the biopsy specimens (Fig 1) as follows:

There are several subpleural blebs and/or bullae and localized, subpleural

alveolar disruption [without] generalized emphysema. Interstitial

fibrosis, though marked, is localized. It is irregular in outline

and appears inactive with no ongoing fibroblast proliferation or

organization of airspace exudate .... Multiple small bundles of apparent

smooth muscle lie in the pleura.... Multiple small pulmonary

artery branches demonstrate irregularly distributed (eccentric)

intimal fibrosis.... The appearance suggests pulmonary arterial

hypertension.... Though the alterations (including asymetric intimal

fibrosis) in multiple small pulmonary artery branches are conspicuous,

they probably reflect prior, now completely organized,

thromboemboli, There is no evidence of recent emboli [or] infarction

(though there is some irregular subpleural scar formation).

Furthermore, emboli lodging in vessels of this small size should not

produce infarctions. While recurrent pneumothorax in a woman this age

raises the possibility of LAM [lymphangioleiomyomatosis] I see no

evidence of this process.... This complex pathologic spectrum is

difficult to place in a single unifying category.

Pulmonary functions were tested (Table 1). A ventilation perfusion ratio (V/Q) scan was low probability for embolism. Impedence plethysmography was normal in both legs. Arterial blood gas determinations on room air were as follows: pH=7.38; PC[O.sub.2]=37; and P[O.sub.2]=102. With exercise, the patient's heart rate rose to 184 (96% predicted) without abnormal ECG changes. [O.sub.2] saturation was unchanged at 100%.

After two lung biopsies and pleurodeses, she would have strong opinions about further surgery. I doubt that tube thoracostomy and chemical pleurodesis would be effective if two thoracoscopic pleurodeses were unsuccessful. If another procedure were undertaken, I would recommend open rather than thoracoscopic thoracotomy to allow more complete pleural peeling and pleurodesis. I would also recommend repeated biopsy, likely from several sites to establish a diagnosis.

If she refused further surgery, I would ask her to avoid air travel and heavy physical exertion. She would require regular follow-up. I would instruct her to present promptly if symptoms of deep vein thrombosis or respiratory symptoms developed. If results of noninvasive tests were equivocal, I would recommend a contrast study, either venography or pulmonary angiography with measurement of right-sided pressures, to diagnose or exclude venous thromboembolism and the development of pulmonary hypertension.

I would recommend periodic ECG and echocardiography to ensure pulmonary hypertension was not developing. Transesophageal echocardiography might be a better alternative for estimation of the right-sided pressures if the breast implants precluded satisfactory transthoracic study. I would also recommend periodic pulmonary function testing, including diffusion capacity, but I would not recommend serial exercise testing unless she was experiencing worsening symptoms unexplainable by standard testing. If deterioration was demonstrated, I would repeat the lung biopsy.

FOLLOW-UP BY THE TREATING PULMONARY CONSULTANT

Dr. Jeff Schnader, Dayton, Ohio

The first decision I made in this perplexing case was that I did not want another biopsy. The patient was highly reluctant to go to surgery, and I believed that any answer obtainable from lung tissue was probably already present on the existing biopsy specimens. Even so, a thoracic surgeon was asked for a second opinion, and he refused, at the time, to perform any further procedure. There was no pathologic evidence to support a diagnosis of LAM, eosinophilic granulomatosis, sarcoidosis, cystic fibrosis, or necrotizing infection (eg, Pneumocystis carinii). Usual intertitial pneumonitis did not seem to fit the entire picture. Catamenial pneumothorax seemed unlikely in view of the discordance between menses and pneumothoraces and the fact that neither the pathologists nor the surgeons saw endometrial tissue or blood clots.

The patient's blebs/subpleural emphysema are an obvious possible or even likely cause of the pneumothoraces. However, the possibility of lung infarctions due to vascular abnormalities is known to cause pneumothoraces,[9,10] and it is known that lung infarcts are mostly right-sided and always either in the upper lobe or the superior segment of the lower lobe.[11] Stocker et al[12] have described a syndrome, which they believe explains spontaneous pneumothoraces in young adults, linking perinatal pulmonary artery occlusion and subpleural infarction with cyst formation. The patient's right lower lobe nodule or infiltrate and the air-fluid level indicating possible hemopneumothorax are also consistent with lung infarction (Fig 4), and the evanescent nature of the nodule/infiltrate is also supportive of infarction. The fact that the patient underwent bleb stapling twice with continued recurrence of pneumothorax might be suggestive of an underlying abnormality (other than blebs) that her surgery would not be expected to fix, eg, infarcts induced by vasculopathy. But even if a pulmonary vasculopathy were to be the ultimate cause of the pneumothoraces, its etiology would be less clear. Also unclear is the question of whether the vascular findings are widespread throughout both lungs or localized to a congenital or acquired anomaly, eg, a sequelum to her pneumonia at age 5 days, associated with the blabs/emphysema seen on biopsy specimen in the right apex. The decreased diffusion of carbon monoxide (Dco) and the rounded right lower lobe infiltrate, a site distant from where the biopsy specimens were taken, may suggest a diffuse vasculopathy. The finding of "cholesterol clefts with. . . giant cell response," as in the current patient, is frequently associated with pulmonary hypertension, possibly resulting from small focal hemorrhages.[13]

The presence of pulmonary hypertension would confirm a diffuse nature of her vasculopathy and justify anticoagulation. Although the results of the exercise test were relatively normal, I sent the patient for right heart catheterization (Table 3). Angiography seemed unnecessary in view of the lack of evidence for gross thromboembolism by noninvasive studies. After hemodynamic pulmonary hypertension was disproved, I had further discussions with the above pulmonary vascular pathologist who raised the possibility of primary pulmonary hypertension because of the pulmonary vascular intimal hyperplasia which was at times cellular, fibrous, and eccentric (Fig 1, A through D [top, center, and bottom left, and top right]). This pathologist consulted with another vascular pathologist, and then both reconsidered that it was probably not primary pulmonary hypertension but possibly a congenital abnormality or Swyer-James-like syndrome represented by the thick-walled, subpleural bronchial vessels and emphysematous changes (Fig 1, E through G [center and bottom right, and bottom left]).

After this, the patient's condition seemed to improve. Over the next 8 months, there were no further pneumothoraces. Another pulmonary function test (Table 4) showed a significant improvement in her DCO, but there was a bronchodilator response in her forced expiratory flow rate between 25% and 75% of the FVC ([FEF.sub.25-75]). Because airways disease with gas trapping and elevated alveolar pressures are known to predispose to pneumothorax, I began the patient on a regimen of both steroid and 3-agonist inhalers. After this, the patient said she felt better and realized that she had had subtle dyspnea prior to inhaler use that she had not recognized before. She felt well enough to become a police officer in a major city.

COPYRIGHT 1996 American College of Chest Physicians
COPYRIGHT 2004 Gale Group