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.
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.
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.