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

Sep 28, 2026

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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. A 24-year-old woman with known NF1 developed progressive dyspnea, orthopnea, and lower-extremity edema. Imaging showed severe PH with enlarged pulmonary arteries, right ventricular dilation, and extensive cystic lung changes without thromboembolic disease. Echocardiography confirmed elevated right-sided pressures and right heart strain. A diagnosis of Group 5 PH associated with NF1 (PH-NF1) was made. Targeted therapy was deferred given limited evidence and potential risks, and care emphasized oxygen, diuretics, and pulmonary and cardiac rehabilitation, underscoring diagnostic complexity and the need for multidisciplinary management.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Abstract

Introduction

Case Presentation

Review began 06/29/2025 Review ended 11/25/2025 Published 12/02/2025 © Copyright 2025 Hegazy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98338 Open Access Case Report When the Skin Tells a Pulmonary Story: A Case of Neurofibromatosis Type 1-Associated Pulmonary Hypertension Yasser Hegazy 1, Alshaimaa Abdallah 2, Ahmed Salem 3, Ali Assaker 1, Ahmed Elmogy 1 1. Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA 2. Radiology, Cairo University, Cairo, EGY 3. Internal Medicine, CarePoint Health Bayonne Medical Center, Bayonne, USA Corresponding author: Yasser Hegazy, [yasserhegazy14.yh@gmail.com](yasserhegazy14.yh@gmail.com) 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. Wereport 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. Categories: Cardiology, Pulmonology Keywords: multifactorial pulmonary hypertension, neurofibromatosis 1, neurofibromatosis associated diffuse lung disease, pulmonary hypertension, type 5 pulmonary hypertension Introduction Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder, with an estimated prevalence of one in 3,500 individuals. It exhibits complete penetrance and is characterized by a broad spectrum of clinical manifestations, including cutaneous findings such as café-au-lait macules and neurofibromas, optic pathway gliomas and other central nervous system tumors, skeletal dysplasia, cognitive impairments, and an elevated risk for certain malignancies beyond the nervous system [1] . Although respiratory involvement in NF1 is uncommon, reported pulmonary manifestations include intrathoracic neurofibromas, infiltrative lesions, cystic changes, bullae, and emphysematous alterations. Pulmonary hypertension (PH) is a rare but recognized complication, with only scattered case series and an estimated prevalence of approximately 1% or less among affected individuals. NF1-associated PH (PH-NF1) is classified under WHO Group 5, a category reserved for conditions with multifactorial or poorly understood mechanisms, because PH

FAQs

What is the diagnosis described in the case?

The case diagnosis is Group 5 pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1), supported by clinical, radiologic, and echocardiographic findings without thromboembolic disease.

What symptoms and key physical findings were reported?

The patient had progressive dyspnea, orthopnea, and bilateral painless pitting edema. Physical examination revealed classical NF1 features including multiple café-au-lait macules, cutaneous neurofibromas, axillary freckling, and skeletal deformity.

Why was targeted PH therapy deferred in this patient?

Targeted PH therapy was considered, but it was deferred due to limited evidence of benefit and potential risk in NF1-associated parenchymal lung disease; management focused on conservative care with oxygen therapy and diuretics, plus referral for rehabilitation.

Sep 28, 2026

Uploaded by Jiven