An 18-year-old woman presents as a transfer from an outside hospital for further evaluation and treatment for shortness of breath.  She was last in her usual state of health 4 years ago when she noted slowly progressive shortness of breath, initially noted while playing soccer.  She was evaluated by her primary care physician who performed pulmonary function tests and treated her with bronchodilators for presumed asthma.  Her symptoms stabilized, but she noted worsening of shortness of breath to the point where she could not walk farther than 50 feet on flat ground along with new onset of lower extremity edema 2 months prior to presentation at our institution.  Further, she complained of symptoms suggestive of Raynaud’s phenomenon.  The patient was subsequently referred for a computed tomography of the chest (Figure 1) and ultimately underwent a video-assisted thorascocopic surgery with biopsy (Figures 2 and 3).  After the surgery, the patient experienced prolonged hypoxemia, prompting an echocardiogram that revealed substantial elevation of the estimated right ventricular systolic pressure (90 mmHg), dilated right ventricle and dilated right atrium. Right heart catheterization was performed and revealed a mean right atrial pressure of 18 mmHg, mean pulmonary artery pressure of 59 mmHg, cardiac index of 3.2 L/min/m², and pulmonary capillary wedge pressure of 13 mmHg.  Based upon these values, the patient was started on intravenous epoprostenol.  A few days after initiation of epoprostenol, the patient developed worsening shortness of breath.  She was subsequently transferred to our institution for further evaluation and treatment.

Past Medical History

Hashimoto’s thyroiditis, resolved

Presumed asthma

Vaccination up to date

Hemoglobin 8.0 mg/dL (baseline 12.0 mg/dL)

Serum creatinine normal

No hematuria or casts in urine

Antinuclear antibody positive 1:320

Anticentromere antibody positive

All other vasculitis serologies negative

The patient was started on therapy and subsequently improved.  She was weaned off supplemental oxygen by the time of discharge.

Pulmonary veno-occlusive disease (PVOD) is a rare disease, occurring in about 0.1-0.2 per million persons, with men and women affected equally (1).  It is characterized by progressive dyspnea on exertion.  Signs of right heart failure, including accentuated second heart sound, elevation of jugular venous pressure, and peripheral edema, are common.  However, unlike other forms of pulmonary arterial hypertension (PAH), basilar crackles on pulmonary auscultation and pleural effusions can occur, reflecting the elevations in post-capillary pulmonary vessel pressures (2,3).  The diagnosis is usually suspected in a patient whose chest radiographs suggest pulmonary venous hypertension, but whose right heart catheterization suggests normal left-sided filling pressures that is, normal pulmonary capillary wedge pressures.  Classically, the patient with PVOD develops pulmonary edema, often severe, with vasodilator challenge during right heart catheterization which may prove fatal in some cases (4).  Other reported findings include a high-probability ventilation perfusion scan with absence of pulmonary thrombus on angiography with computed chest tomography, although V/Q scans tend to be normal in PVOD (5).  PVOD can only be diagnosed definitively with lung biopsy; however, biopsy in patients with pulmonary hypertension is not without risk.  The characteristic findings include diffuse occlusion of the pulmonary veins by fibrous tissue, intimal thickening in the venules and small veins, and interstitial edema (6).  Veins may become arterialized over time with increased elastic fibers.  Pulmonary arterioles may also exhibit hypertrophy related to increased pulmonary venous hypertension.  Movat elastic stain, which distinguishes between internal and external elastic laminae, can help determine whether the vessels affected are venous or arterial.  PVOD can occur in association with connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, and limited sclerosis (7).   The prognosis for PVOD is poor (median survival 1-2 years), with no effective therapy except lung transplantation.

Idiopathic pulmonary arterial hypertension is unlikely in this patient based upon the chest CT findings of increased septal lines, clinical deterioration with intravenous epoprostenol, and pathologic findings of primarily venous obstruction.

Although alveolar hemorrhage is more common in SLE than scleroderma, it can occur in association with PVOD (see below).   No other clinical or serologic data support a diagnosis of SLE in this patient.

Pulmonary capillary hemangiomatosis (PCH) is another rare disease that causes clinical pulmonary hypertension with features similar to PVOD.  Pathologically, advanced PVOD can be confused with PCH due to extensive engorgement of alveolar capillaries due to high pulmonary venous pressures.  However, the presence of primarily pulmonary venous involvement in this patient suggests PVOD instead of PCH.