He Huang
Shuaijun Yuan
Limin Zhang
Jiaye Song
Dengwei Xue
Dongmei Liu
Jingxin Cao- 1Department of Neurology, The 940th Hospital of Joint Logistics Support Force of the Chinese People’s Liberation Army, Lanzhou, China
- 2Department of Respiratory, Affiliated Fukang Hospital of Tibet University, Lhasa, China
- 3Department of Preventive Medicine, Tibet University, Lhasa, China
- 4Department of Critical Care Medicine, The 940th Hospital of Joint Logistics Support Force of the Chinese People’s Liberation Army, Lanzhou, China
High-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE), and high-altitude polycythemia (HAPC) are each rarely observed in Tibetan populations. The coexistence of HAPE, HACE, and HAPC in the same person has not been previously documented. Here, we report the case of a native Tibetan male with HAPC who developed both HAPE and HACE upon re-ascent to an altitude of 3,650 m after a 27-day stay at low altitude. On the 3rd-4th day post-return, the patient exhibited persistent dyspnea, chest tightness, hypersomnia, intermittent agitation, and confusion. Chest CT and multimodal neuroimaging confirmed the presence of HAPE and HACE. Treatment followed guidelines (supplemental oxygen, high-dose dexamethasone) along with supportive measures, resulting in clinical resolution. This is the first reported case of co-occurring HAPE, HACE and HAPC in a native Tibetan upon re-ascent, suggesting that pre-existing HAPC may be a significant risk factor for severe acute high-altitude illness in this setting.
Introduction
High-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE) are life-threatening acute high-altitude illnesses, typically affecting non-acclimatized lowlanders ascending rapidly above 2,500 m (Gatterer et al., 2024). In contrast, high-altitude polycythemia (HAPC) is a common chronic high-altitude illness characterized by excessive erythrocytosis due to maladaptation to prolonged hypoxia, which lead to increased blood viscosity, impaired microcirculation, thrombosis, and hypoxic organ damage (Adams and Peel, 2025; Garrido et al., 2021; Zhou et al., 2025). While these disorders predominantly affect lowlanders entering high altitudes, they are exceptionally rare in genetically high-altitude adapted populations like Tibetans (Ge, 2025; Gonzales, 2025; Zhang et al., 2025).
Here, we report a native Tibetan man with HAPC who developed HAPE and HACE upon re-ascent to 3,650 m. To our knowledge, this condition has never been documented. Its occurrence in a Tibetan carries important clinical implications, suggesting HAPC patients in high-altitude regions face greater risk of severe acute high-altitude illness than previously recognized. Furthermore, this case offers valuable insights into the pathophysiological mechanisms associated with the concurrent development of HAPE and HACE in the context of pre-existing HAPC, and underscores acute illness risks during re-ascent in this population.
Case presentation
A 36-year-old male of Tibetan ancestry was born and raised at 4,200 m in Tibet. He was a singer of traditional Tibetan opera (non-manual laborer). In 2022, he noted symptoms of high-altitude maladaptation such as exertional dyspnea, fatigue, palpitations, and cyanosis, and was diagnosed with HAPC at the local hospital. These symptoms markedly improved after relocation to Lhasa (elevation: 3,650 m) in 2022 (Supplementary Figure S1).
From February 7 to 6 March 2025, he traveled for 27 days at a low altitude (elevation: 500 m), during which there were no discomfort symptoms. On 9 March 2025, he returned to Lhasa (elevation: 3,650 m), and rested at home without physical exertion. 7 h post-return, he progressively developed headache, dizziness, nausea, vomiting, and productive cough. No medical consultation was sought. On the 3rd-4th day post-return (March 11–12, 2025), his initial symptoms worsened with new-onset persistent palpitations, dyspnea, chest tightness, hypersomnia, intermittent agitation, and confusion. Home oxygen self-administration provided partial relief, but he declined hospital evaluation. On the 5th day post-return (13 March 2025), he visited the Respiratory Department of Fukang Hospital (Lhasa, Tibet, China) due to unremitting symptoms (Supplementary Figure S1).
Physical examination revealed temperature 37.1 °C, heart rate 116 beats/min, respiratory rate 31 breaths/min, and blood pressure 136/87 mmHg; peripheral oxygen saturation (SpO2) at room air was critically low at 63%. The patient was alert but lethargic with delayed responsiveness, exhibiting plethoric facies and severe lip/nailbed cyanosis. Auscultation of the lungs demonstrated diminished breath sounds with diffuse bilateral crackles. Chest CT showed patchy and flocculent opacities in both lungs, consistent with HAPE (Figures 1A–C). Cranial MRI showed nodular hyperintense on T2WI, FLAIR and DWI in the splenium of corpus callosum (Figures 1D–F). It also revealed multiple patchy hypointense on T1WI, and hyperintense on T2WI and FLAIR around periventricular and semioval center (Figures 1G–L). These results of cranial MRI suggested mild HACE. The abnormal results of laboratory test demonstrated systemic inflammation, potential infection risk, HAPC, and hemolysis (detailed results shown in Table 1). Electrocardiogram showed sinus tachycardia. The remaining auxiliary examinations, including blood biochemistry, blood coagulation indicators, routine stool examination, respiratory virus nucleic acid testing, echocardiography and abdominal ultrasound were all within the normal range.
Figure 1. Chest CT and cranial MRI scans of the patient. (A–C) Chest CT showing patchy and flocculent opacities in both lungs. (D–F) Cranial MRI demonstrating nodular hyperintense on T2WI, FLAIR and DWI in the splenium of corpus callosum. (G–I) Cranial MRI showing multiple patchy hypointense on T1WI, and hyperintense on T2WI and FLAIR around periventricular. (J–L) Cranial MRI showing multiple patchy hypointense on T1WI, and hyperintense on T2WI and FLAIR around semioval center. CT: computed tomography; MRI: magnetic resonance imaging; T2WI: T2-weighted imaging; FLAIR: fluid attenuated inversion recovery; DWI: diffusion-weighted imaging; T1WI: T1-weighted imaging.
Table 1. The abnormal laboratory results of the patient on admission (13 March 2025).
Based on the patient’s symptoms, signs and auxiliary examination results, he was diagnosed with HAPE, HACE and HAPC. The patient received guideline-based therapy consisting of continuous low-flow oxygen (two to three L/min) and high-dose intravenous dexamethasone (5 mg daily) (Keller et al., 1995; Luks et al., 2024; Maggiorini et al., 2006; Siebenmann et al., 2011). Supportive treatment included intravenous aminophylline (0.25 g twice daily) for bronchodilation and intravenous ceftazidime (2 g thrice daily) for empirical antimicrobial coverage. By the 3rd day of hospitalization (15 March 2025), the patient achieved complete neurological symptom resolution. At discharge (22 March 2025), vital signs and laboratory results normalized (Table 2) with radiographic resolution of pulmonary/cerebral edema. The 1-month follow-up confirmed no recurrence of HAPE/HACE.
Table 2. Longitudinal changes in vital signs and laboratory results of the patient.
Discussion
This report presents the first documented case of concurrent, definitively diagnosed HAPE and HACE triggered by re-ascent in a native Tibetan with pre-existing HAPC. While severe acute high-altitude illness is exceptionally rare in adapted populations, this case underscores that such illness resistibility is not absolute. Although rare, re-entry HAPE has been reported in Tibetan individuals (Baniya et al., 2017; Wu, 2004). A prior case by Wu et al. described a Tibetan man with chronic mountain sickness who developed HAPE upon re-ascent to an altitude of 4,300 m (Wu, 2004). Our case, featuring the full triad of HAPC, HAPE, and HACE, suggests that pre-existing HAPC may represent a critical predisposing factor, significantly amplifying the risk of severe acute high-altitude illness upon re-ascent.
The pathophysiological link likely centers on the profound physiological burden imposed by HAPC. Marked erythrocytosis creates a state of severe hyperviscosity and impaired microcirculatory flow (Leon-Velarde et al., 2003; Manier et al., 1988; Zhou et al., 2025). This compromises oxygen delivery and blunts hypoxic ventilatory responses, leading to profound hypoxemia upon re-ascent. Such severe hypoxemia exacerbates hypoxic pulmonary vasoconstriction, increasing pulmonary capillary pressure and permeability—key steps in HAPE pathogenesis (Archer et al., 2024; Bärtsch et al., 2005; Dunham-Snary et al., 2017; Li et al., 2018; Maggiorini et al., 2001). Concurrently, it promotes cerebral endothelial dysfunction and blood-brain barrier disruption, contributing to HACE development (Li et al., 2018; Xue et al., 2022). Moreover, hypoxia-driven amplification of the pre-existing inflammatory state in HAPC likely exacerbates vascular leakage in both the pulmonary and cerebral circulations upon re-ascent (Song et al., 2016; Wu et al., 2018; Yi et al., 2021; Zhou et al., 2017).
This case yields four critical clinical insights: (I) Even high-altitude adapted Tibetan populations are not protected from HAPE and HACE upon re-ascent; (II) Pre-existing HAPC likely represents a novel risk factor for HAPE/HACE; (III) Emergent chest CT and multimodal neuroimaging are essential for the rapid and accurate diagnosis of concurrent HAPE-HAC; and (IV) Guideline-based therapy consisting of continuous low-flow oxygen and high-dose dexamethasone effectively controls disease progression (Luks et al., 2024). Furthermore, we postulate that HAPC patients’ risk of developing HAPE/HACE upon re-ascent may exceed current recognition, warranting future large-scale studies to precisely quantify risks in HAPC patients after low-altitude sojourns and develop targeted preventive strategies.
This study is limited by the lack of longitudinal cardiopulmonary data. Consequently, follow-up assessments incorporating echocardiography to evaluate pulmonary artery pressure and right heart adaptation are necessary. Moreover, the extreme hematologic findings justify genetic investigation to elucidate the basis of the patient’s HAPC, including screening for variants associated with conditions like Chuvash polycythemia (Gangat et al., 2021).
In conclusion, this first reported case of HAPC, HAPE, and HACE co-occurrence in a Tibetan native upon re-ascent, challenges the conventional view of severe acute high-altitude illness resistibility. Furthermore, our findings indicate significant risks for HAPC patients upon re-ascent to high altitude.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by the ethics committee of Affiliated Fukang Hospital of Tibet University (IRB No.: 2025-05-04). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
Author contributions
HH: Formal Analysis, Funding acquisition, Methodology, Software, Visualization, Writing – original draft, Writing – review and editing. SY: Conceptualization, Data curation, Investigation, Project administration, Writing – original draft. LZ: Data curation, Investigation, Project administration, Writing – review and editing. JS: Investigation, Project administration, Writing – review and editing. DX: Investigation, Project administration, Resources, Writing – review and editing. DL: Conceptualization, Visualization, Writing – review and editing. JC: Conceptualization, Investigation, Project administration, Resources, Supervision, Writing – review and editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. The study was supported in part by funding from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2025ZD0551803 to J.C.), Lhasa Municipal Major Science and Technology Project (Grant No. LSKJ202508 to J.C.), Young Talent Reserve Initiative under the High-Level Talent Cultivation Program of the 940th Hospital, Joint Logistics Support Force, Chinese PLA (Grant No. 2024-G3-6), and Postdoctoral Fellow Matching Fund of the 940th Hospital, Joint Logistics Support Force, Chinese PLA (Grant No. 2024YYZZBSH-2).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2025.1685329/full#supplementary-material
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Keywords: high-altitude cerebral edema, high-altitude polycythemia, high-altitude pulmonary edema, re-ascent, susceptibility, Tibetan population
Citation: Huang H, Yuan S, Zhang L, Song J, Xue D, Liu D and Cao J (2026) Re-ascent triggered high-altitude pulmonary and cerebral edema in a Tibetan with pre-existing high-altitude polycythemia: a Case Report. Front. Physiol. 16:1685329. doi: 10.3389/fphys.2025.1685329
Received: 04 September 2025; Accepted: 17 December 2025;
Published: 15 January 2026.
Edited by:
Andrew T. Lovering, University of Oregon, United StatesReviewed by:
Martin Burtscher, University of Innsbruck, AustriaRobert Naeije, Université libre de Bruxelles, Belgium
Copyright © 2026 Huang, Yuan, Zhang, Song, Xue, Liu and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jingxin Cao, NzU1NzU2OTZAcXEuY29t
†These authors have contributed equally to this work and share first authorship