# When the Skin Tells a Pulmonary Story: A Case of Neurofibromatosis Type 1-Associated Pulmonary Hypertension

## TL;DR

A 24-year-old woman with neurofibromatosis type 1 developed severe pulmonary hypertension, highlighting the challenges in diagnosing and managing this rare condition.

## Contribution

This case report provides insights into the diagnostic and therapeutic complexities of pulmonary hypertension associated with neurofibromatosis type 1.

## Key findings

- The patient exhibited classical NF1 features alongside severe pulmonary hypertension without thromboembolic disease.
- Conservative management was chosen over targeted PH therapy due to limited evidence of benefit in NF1-associated lung disease.
- The case emphasizes the need for multidisciplinary care in managing PH-NF1, a rare and progressive condition.

## Abstract

Neurofibromatosis type 1 (NF1) is a multisystem autosomal dominant disorder with cutaneous, neurologic, and skeletal manifestations. Pulmonary hypertension (PH) is an uncommon but severe complication of NF1 and is classified as Group 5 PH due to its multifactorial and incompletely understood pathogenesis. We report a case of a 24-year-old female with a known history of NF1 who presented with progressive dyspnea, orthopnea, and lower extremity edema. Physical examination revealed classical NF1 features, including multiple café-au-lait macules, cutaneous neurofibromas, axillary freckling, and skeletal deformity. Imaging studies demonstrated severe pulmonary hypertension with enlarged pulmonary arteries, right ventricular dilation, and extensive cystic changes in both lungs, in the absence of thromboembolic disease. Echocardiography confirmed elevated right-sided pressures and right heart strain. Based on clinical, radiologic, and echocardiographic findings, a diagnosis of Group 5 PH associated with NF1 (PH-NF1) was made. Targeted PH therapy (endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors) was considered; however, due to limited evidence of benefit and potential risk in NF1-associated parenchymal lung disease, therapy was deferred in favor of conservative management with oxygen therapy and diuretics, and the patient was referred for pulmonary and cardiac rehabilitation. This case highlights the diagnostic complexity and therapeutic challenges associated with PH-NF1, a condition likely driven by a combination of vascular remodeling, parenchymal destruction, and genetic factors. Early recognition and multidisciplinary management are essential to improving outcomes in patients with this rare and progressive complication of NF1.