A Young Woman's Journey with Rare Lung Disease: Understanding Pulmonary Veno-Occlusive Disease

Table of Contents

• Case Presentation: A 28-Year-Old Woman's Symptoms
• Medical History and Initial Findings
• Diagnostic Testing and Imaging Results
• Treatment Challenges and Clinical Course
• Differential Diagnosis: Understanding Possible Conditions
• Final Diagnosis and Clinical Implications
• Clinical Outcome and Management
• What This Means for Patients
• Source Information

Case Presentation: A 28-Year-Old Woman's Symptoms

A 28-year-old woman was transferred to the intensive care unit (ICU) with progressive respiratory failure that had developed over 3.5 years. Her health problems began when she experienced sudden shortness of breath (dyspnea) after having a productive cough for four weeks. Although she had a history of exercise-induced asthma during her teenage years, for which she used inhaled albuterol briefly, her current symptoms represented a much more serious condition.

The patient's initial emergency department evaluation revealed wheezing, and her chest X-ray showed peribronchial cuffing (thickening around the airways). She was treated with oral prednisone and inhaled fluticasone and albuterol. Despite this treatment, her breathing difficulties continued to progress over the following years, eventually becoming severe enough to require intensive medical care.

Medical History and Initial Findings

One month after her initial emergency visit, pulmonary function tests showed normal spirometry results and lung volumes, but revealed a severely reduced diffusing capacity for carbon monoxide (DLCO) - a test that measures how well oxygen moves from the lungs into the bloodstream. This specific pattern often indicates problems with the lung's blood vessels rather than the airways themselves.

Two months later, the patient reported worsening shortness of breath during physical activity. Laboratory testing showed:

• White blood cell count: 9,150 per microliter (normal range: 4,000 to 10,800)
• Eosinophil count: 897 per microliter (normal: less than 680)
• IgE level: 501 IU per milliliter (normal: less than 114)

Additional testing ruled out common allergic and parasitic causes, though allergy testing showed reactions to oak, dust mites, and dog and cat dander. A chest CT scan without contrast showed diffuse, centrilobular, nodular ground-glass opacities in both lungs with mild enlargement of several mediastinal lymph nodes. These findings suggested possible hypersensitivity pneumonitis (an allergic lung reaction to inhaled particles), and doctors recommended a lung biopsy and prednisone trial, but the patient declined further testing or treatment at that time.

Diagnostic Testing and Imaging Results

Two years later, and one year before her final admission, the patient saw a cardiologist for worsening exertional dyspnea and lightheadedness. Her heart rate was 94 beats per minute. Echocardiography showed normal left ventricular function but revealed:

• Mild right ventricular dilatation (enlargement)
• Right ventricular systolic pressure: 37 mm Hg (normal: less than 29)
• Evidence of trace right-to-left interatrial shunting (abnormal blood flow between heart chambers)

Eleven months later, three weeks before her final admission, she returned to her pulmonologist with progressively worse symptoms. Her vital signs showed:

• Heart rate: 115 beats per minute
• Blood pressure: 88/61 mm Hg
• Oxygen saturation: 91% at rest, dropping to 86% after walking 30 meters

Additional testing in the emergency department showed a d-dimer level of 455 mg per deciliter (normal: less than 230), which can indicate blood clotting issues. Her eosinophil count had decreased to 210 per microliter. Other blood tests, including those for HIV and SARS-CoV-2, were negative.

CT scanning of the chest with contrast showed no pulmonary emboli but revealed numerous ground-glass opacities in both lungs, confluent hilar and mediastinal lymphadenopathy (enlarged lymph nodes), and a small pericardial effusion (fluid around the heart).

Treatment Challenges and Clinical Course

The patient was prescribed supplemental oxygen for ongoing outpatient use, and a lung biopsy was planned. However, two weeks later, she returned to the emergency department with progressive leg edema and severe shortness of breath with minimal exertion. Her condition had deteriorated significantly:

• Heart rate: 110 beats per minute
• Blood pressure: 96/73 mm Hg
• Oxygen saturation: 94% on 3 liters/minute of supplemental oxygen
• Weight: 73.4 kg with significant leg edema extending to mid-thigh
• N-terminal pro-B-type natriuretic peptide: 3,640 pg/mL (normal: less than 125)

She was transferred to another hospital where echocardiography showed a small left ventricle with normal function, a markedly dilated and hypokinetic right ventricle, and interventricular septal compression. The right ventricular systolic pressure was estimated at 91 mm Hg - severely elevated compared to the normal range of 15-28 mm Hg.

Right heart catheterization revealed critically abnormal measurements:

• Right atrial pressure: 14 mm Hg (normal: less than 7)
• Pulmonary arterial pressure: 99/56 mm Hg
• Mean pulmonary arterial pressure: 71 mm Hg (normal: less than 20)
• Pulmonary capillary wedge pressure: 12 mm Hg (normal: less than 15)
• Cardiac index: 1.1 liters per minute (normal: 2.8 to 4.2)

These pressures did not improve with inhaled nitric oxide, indicating fixed rather than reversible pulmonary hypertension.

The patient was started on intravenous epoprostenol, a potent pulmonary arterial vasodilator used to treat pulmonary hypertension. However, instead of improving, her condition worsened dramatically - she developed increased dyspnea with any activity, requiring high levels of supplemental oxygen (90% saturation on a non-rebreather mask at 15 liters/minute). She also reported jaw pain and headache, known side effects of this medication.

Differential Diagnosis: Understanding Possible Conditions

The medical team considered several possible causes for this young woman's severe pulmonary hypertension:

Left Heart Disease: This is the most common cause of pulmonary hypertension, accounting for more than two-thirds of cases. However, the patient had normal left ventricular function and normal pulmonary capillary wedge pressure, effectively ruling out left heart disease as the primary cause.

Chronic Lung Disease: The patient had a history of exercise-induced asthma and initial CT findings suggestive of hypersensitivity pneumonitis. However, the aggressive progression of her disease was atypical for chronic lung conditions, which usually develop more slowly over many years.

Chronic Thromboembolic Pulmonary Hypertension: This condition results from blood clots in the lungs that don't dissolve properly. However, CT angiography and ventilation-perfusion scanning showed no evidence of pulmonary emboli or perfusion defects, ruling out this diagnosis.

Pulmonary Arterial Hypertension (PAH): This group of diseases causes increased pressure in the lung arteries. The team considered several PAH subtypes:

• Schistosomiasis-associated PAH: The patient had traveled to endemic areas, but her disease course was too rapid, and testing was negative
• HIV-associated PAH: Testing was negative for HIV
• Autoimmune-associated PAH: The patient had no clinical features of autoimmune diseases, and antibody testing was negative
• Idiopathic PAH: This diagnosis was unlikely because the imaging showed lymph node enlargement and rapid tapering of arteries, which is not typical

Pulmonary Veno-occlusive Disease (PVOD) and Pulmonary Capillary Hemangiomatosis (PCH): These rare conditions involve obstruction of the small veins (veno-occlusive disease) and capillaries (capillary hemangiomatosis) in the lungs. The clinical presentation, imaging findings, and particularly the worsening with epoprostenol treatment strongly suggested this diagnosis.

Final Diagnosis and Clinical Implications

The medical team concluded that the patient had pulmonary veno-occlusive disease (PVOD) with pulmonary capillary hemangiomatosis (PCH). These conditions are now considered part of the same disease spectrum rather than separate entities.

This diagnosis explained several key features of her case:

• The rapid disease progression over 3.5 years
• The imaging findings showing ground-glass opacities, septal thickening, and lymph node enlargement
• The severely reduced diffusing capacity for carbon monoxide
• The dramatic worsening with epoprostenol treatment

In PVOD/PCH, the obstruction in the small lung veins and capillaries means that when medications dilate the pulmonary arteries, more blood flows toward the obstructed areas but cannot drain properly. This creates a "traffic jam" effect that increases pressure in the capillaries, potentially causing fluid to leak into the lungs - explaining why the patient worsened with treatment that typically helps other forms of pulmonary hypertension.

Clinical Outcome and Management

Based on this diagnosis, the patient was listed for lung transplantation one week after admission to Massachusetts General Hospital. Despite initial stabilization, she developed worsening cardiogenic shock (heart failure causing inadequate blood flow to organs) and required venoarterial extracorporeal membrane oxygenation (VA-ECMO) - a life support system that oxygenates blood outside the body.

Four days after ECMO initiation, she underwent lung transplantation. This is typically the only effective treatment for PVOD/PCH, as medications alone cannot reverse the structural changes in the lung blood vessels.

What This Means for Patients

This case illustrates several important points for patients with respiratory symptoms:

Early specialized evaluation is crucial: The patient had initially normal spirometry but severely reduced diffusing capacity - a pattern that should prompt evaluation for pulmonary vascular disease rather than assuming asthma or other common conditions.

Rare diseases require expert diagnosis: PVOD/PCH affects approximately 1 in 10 million people, making it essential to seek care at centers experienced with rare pulmonary diseases.

Treatment response can be diagnostic: The paradoxical worsening with pulmonary vasodilators is a classic feature of PVOD/PCH that helps distinguish it from other forms of pulmonary hypertension.

Transplant evaluation should be timely: Because this disease progresses rapidly and has limited medical treatment options, early referral for lung transplantation assessment is critical.

Patients with unexplained shortness of breath that worsens over time, especially with reduced diffusing capacity on pulmonary function tests, should seek evaluation by pulmonary specialists who can consider rare diagnoses like PVOD/PCH.

Source Information

Original Article Title: Case 23-2025: A 28-Year-Old Woman with Respiratory Failure and Abnormal Chest Imaging

Authors: William J. Janssen, MD, Zachary Hartley-Blossom, MD, Noah C. Schoenberg, MD, and Mark F. Sabbagh, MD, PhD

Publication: The New England Journal of Medicine, August 14, 2025; 393:700-10

DOI: 10.1056/NEJMcpc2309348

This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital series.