Clinical efficacy and mechanisms of hyperbaric oxygen therapy in the treatment of rheumatic and immune diseases

Rheumatic and autoimmune diseases represent one of the major causes of chronic joint and muscle pain, skin ulceration, and mental depression, significantly impairing patients' physical and psychological wellbeing as well as their quality of life. Current evidence suggests that hypoxia may play a role in the pathogenesis and progression of rheumatic and autoimmune diseases and their associated complications. Hypoxia can induce pathological cellular stress, thereby triggering cell death. Hyperbaric oxygen therapy (HBOT) is a well-established, effective, and safe method for significantly increasing dissolved oxygen content in plasma and arterial oxygen partial pressure. Based on a comprehensive review of all relevant literature published in the past decade and indexed in PubMed regarding HBOT for rheumatic and autoimmune diseases, the following findings were observed: HBOT demonstrated an efficacy rate of 87.5%−100% in treating rheumatic and autoimmune diseases complicated by skin ulcers. For patients with fibromyalgia syndrome (FMS), the pain relief rate ranged from 87.5 to 100%. Additionally, HBOT exhibited favorable therapeutic effects in cases involving sensorineural hearing loss and acute macular neuroretinopathy secondary to rheumatic and autoimmune diseases. Regarding safety, adverse effects were reported in seven studies, primarily including mild barotrauma, tinnitus, headache, and claustrophobia. All adverse events resolved upon discontinuation of HBOT, and no severe adverse reactions were documented.

1 Introduction

Hyperbaric Oxygen Therapy (HBOT) is a non-invasive treatment modality in which patients breathe 100% oxygen under conditions exceeding 1 absolute atmosphere (ATA) of pressure. Initially employed in the 1930s for decompression sickness (1), HBOT has since evolved into an established therapeutic approach for a variety of conditions, including non-healing wounds, infections, and medical emergencies, as well as an adjunctive treatment option for certain inflammatory disorders (2, 3). Oxygen plays a pivotal role in numerous physiological processes, reaching all tissues and cells via systemic circulation. By creating a high-pressure, oxygen-enriched environment, HBOT significantly enhances dissolved oxygen levels in plasma and arterial oxygen partial pressure. Consequently, HBOT exerts broad effects on cellular biochemical and physiological responses, including promoting angiogenesis, mitigating localized inflammatory reactions, and counteracting oxidative stress (4–6). HBOT addresses the ischemia, hypoxia, and chronic inflammation common in many diseases through its distinct physiological mechanisms, thereby promoting tissue repair and alleviating symptoms. It does not replace conventional immunosuppressants or biologics but acts as a complementary approach to improve overall treatment efficacy (6).

Rheumatic immune diseases (RIDs) can lead to joint and muscle pain, functional impairment, and clinical manifestations such as skin ulceration and sudden sensorineural hearing loss, severely impacting patients' physical and mental health as well as quality of life. Current pharmacologic treatments for these conditions primarily include corticosteroids, immunosuppressants, biologic agents, and non-steroidal anti-inflammatory drugs (NSAIDs). However, some patients fail to achieve satisfactory clinical outcomes (7). It is widely recognized that numerous rheumatic and autoimmune diseases—such as vasculitis, fibromyalgia, and systemic sclerosis—are closely associated with aberrant immune-inflammatory responses and oxidative stress (8). Local hypoxia can trigger physiological and pathological alterations, including oxidative stress, angiogenesis, vascular remodeling, inflammatory responses, and metabolic reprogramming, thereby driving disease progression (6, 9). Thus, hypoxia may play a critical role in the pathogenesis of rheumatic and autoimmune diseases, and HBOT may demonstrate therapeutic efficacy against these conditions and their complications.

As a novel therapeutic strategy for RIDs, HBOT offers distinct advantages, including its non-invasive nature, favorable safety profile, and demonstrated efficacy in alleviating common clinical symptoms across diverse patient populations. This review aims to summarize the therapeutic effects, safety, and underlying mechanisms of HBOT in the management of rheumatic and autoimmune diseases, thereby providing a foundation for future clinical and basic research.

2 Methods

2.1 Data sources and searches

We performed electronic searches using exploded Medical Subject Headings (MeSH) terms and various keyword combinations. The search terms included MeSH exp “Hyperbaric Oxygen Therapy” along with the keywords “Hyperbaric Oxygenations,” “Oxygenations, Hyperbaric,” “Hyperbaric Oxygen Therapies,” “Oxygen Therapies, Hyperbaric,” “Oxygen Therapy, Hyperbaric,” “Therapies, Hyperbaric Oxygen,” “Therapy, Hyperbaric Oxygen,” “Oxygenation, Hyperbaric,” “rheumatic immune diseases,” “Rheumatic and immune diseases,” “Fibromyalgia syndrome,” “Vasculitis,” “thromboangiitis obliterans,” “Behçet's disease,” “systemic lupus erythematosus,” “rheumatoid arthritis,” “fibromyalgia syndrome,” and “systemic sclerosis.” We also manually examined the reference lists of included textbooks, retrieved studies, review articles, and academic congress reports. The referenced research articles were obtained from PubMed.

2.2 Inclusion criteria and exclusion criteria

2.2.1 Inclusion criteria

(1) Clinical research studying the treatment of rheumatic immune diseases with HBOT, published in either English language; (2) the participants were defined as those diagnosed with rheumatic immune diseases such as vasculitis, fibromyalgia syndrome, systemic lupus erythematosus, etc.; and (3) the types of studies included encompass case reports, case series, cohort studies, and controlled trials.

2.2.2 Exclusion criteria

(1) Patients with other severe diseases that could influence the outcomes, such as severe heart failure, cancer, DIC, severe infection; (2) studies that were abstracts, reviews, comments, and editorials, etc.; and (3) literature with repetitive content.

3 Results

3.1 Clinical applications and research advances of HBOT

Oxygen is essential for aerobic respiration in human cells, a process that occurs in the mitochondria, where approximately 80% of oxygen is consumed, while the remaining 20% is utilized by other organelles. Hypoxia, defined as a decrease in tissue oxygen tension, induces cellular pathological stress and is closely associated with the onset and progression of various diseases, such as acute kidney damage (10), myocardial infarction (11), and neurological injury (12). Hypoxia leads to increased oxidative stress, resulting in the generation of reactive oxygen and nitrogen free radicals. These radicals are highly cytotoxic, causing cellular damage and ultimately inducing cell death.

Hypoxia-inducible factor 1 (HIF-1) serves as a key regulator of metabolic reprogramming in hypoxic cells (13, 14). HIF-1 modulates critical physiological and pathological responses to hypoxia, including oxidative stress, angiogenesis, vascular remodeling, and inflammatory reactions. Furthermore, HIF-1 regulates the proliferation, migration, oxidative stress response, immune function, and cell death of various core cell types, such as cardiac cells, endothelial cells, smooth muscle cells, and macrophages (15).

HBOT ameliorates hypoxia by enhancing oxygen delivery and suppressing HIF-1 activity, thereby reducing oxidative stress, promoting tissue repair, enhancing vasoconstriction and angiogenesis, and attenuating local inflammation. These mechanisms collectively influence both physiological and pathological cellular responses in the human body (16).

3.2 Application of HBOT in RIDs

In recent years, an increasing number of clinical reports have documented the use of HBOT for treating various conditions, including skin injuries (17), neurodegenerative diseases (18, 19), sudden sensorineural hearing loss (20), and aging-related disorders (21). However, the application of HBOT in rheumatic immune diseases remains relatively limited. This article reviews all PubMed-published literature from the past decade on HBOT for rheumatic immune diseases, encompassing 21 studies involving 343 patients with conditions such as vasculitis, fibromyalgia syndrome (FMS), and systemic sclerosis (SSc). These findings suggest that HBOT represents a novel therapeutic approach for rheumatic immune diseases, demonstrating promising efficacy and unique advantages, as summarized in Table 1 and Figure 1.

Table 1

Table 1. Relevant information from literature on HBOT for rheumatologic and immune diseases.

Figure 1

Figure 1. Dosage, duration and mechanisms of HOBT in different rheumatic and immunological disease complications.

3.2.1 Efficacy and mechanisms of HBOT in treating skin ulcers associated with RIDs

Since tissue regeneration in wounds requires oxygen, exposure to 100% oxygen accelerates this process. HBOT has been applied in traumatic wounds, thermal burns, calciphylaxis, skin grafts, radiation-induced injuries, diabetic ulcers, and other wound types.

In rheumatic immune diseases, HBOT is frequently utilized for vasculitis-related skin ulcers. Vasculitis, characterized by chronic inflammation of the vascular wall and surrounding tissues, can lead to vascular and organ damage. Its pathological manifestations primarily include collagen fiber degeneration, fibrin deposition, and endothelial cell necrosis (22, 23). Skin ulcers in patients with thromboangiitis obliterans (TAO) are associated with amputation and mortality. A retrospective study involving 97 TAO patients with Fontaine stage III ischemic wounds (47 in the HBOT group and 50 in the conventional treatment group) demonstrated that the HBOT group exhibited a significantly lower major amputation rate after 10 months of treatment (2/47 vs. 13/50, P = 0.007). Compared to conventional therapy, the HBOT group showed significant improvements in the number of patients regressing to Fontaine stage I (27/47 vs. 17/50, P = 0.035), complete wound healing (21 vs. 11, P = 0.031), and Visual Analog Scale (VAS) scores (P < 0.001). The addition of HBOT to standard treatment for TAO patients with non-healing ischemic wounds and severe limb pain provided substantial benefits in wound healing and pain resolution (24).

Skin ulcers are also a common complication of SSc, significantly impairing quality of life. A retrospective study of six SSc patients with ulcers treated with HBOT revealed that all patients had undergone at least 6 weeks of conventional therapy with poor outcomes. Following HBOT, four patients achieved complete ulcer resolution, while two exhibited near-complete healing (25). Pulmonary arterial hypertension (PAH), another life-threatening complication of SSc, has unclear responsiveness to HBOT. A case report described a 65-year-old female SSc patient with severe PAH and a venous ulcer in the left lower limb. After adjunctive HBOT, the ulcer resolved completely, quality of life improved, and cardiopulmonary function remained stable without adverse effects (26). Additionally, HBOT has been reported to aid in treating chronic skin ulcers associated with IgG4-related skin disease (27).

Based on existing clinical studies, 83.3%−100% of rheumatic immune disease patients with skin ulcers benefited from HBOT, with 44.68%−100% achieving complete ulcer resolution and no recurrence during follow-up.

HBOT also upregulates host factors such as tumor necrosis factor-α (TNF-α), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1), thereby mitigating local inflammatory responses (28, 29). Several studies indicate that HBOT significantly promotes angiogenesis while reducing inflammation. By elevating vascular endothelial growth factor (VEGF) levels, HBOT enhances angiogenesis in injured tissues, facilitating wound healing (4). Furthermore, HBOT increases nitric oxide levels, augments endothelial progenitor cell populations, upregulates epithelial growth factors and angiogenesis-related proteins, and downregulates apoptosis-associated proteins, thereby promoting re-epithelialization, endothelial cell migration, and granulation tissue formation (30).

Animal studies comparing normobaric hyperoxia therapy (NBOT) with HBOT reaffirmed that higher oxygen pressures are required to induce angiogenesis (31). In vivo experiments demonstrated that HBOT enhances stem cell proliferation in intestinal crypts and stimulates angiogenesis in the chick embryo chorioallantoic membrane (32). In a clinical trial involving patients with chronic non-healing wounds (unresolved for over 20 months), standardized HBOT (20 sessions, five sessions/week) elevated VEGF and interleukin-6 levels while reducing endothelin-1 levels. These findings suggest that HBOT creates a hyperoxic environment that activates host-derived wound resolution and angiogenic factors, thereby promoting vascularization (33).

In summary, HBOT attenuates local inflammation, accelerates angiogenesis, reduces lesion size, improves wound healing rates, and significantly decreases amputation risk.

3.2.2 Efficacy and mechanisms of HBOT in treating chronic pain in RIDs

Chronic pain is defined as pain persisting for more than 3 months, which can lead to depression and suicide, affecting over 30% of the global population (34). It can be classified as nociceptive, neuropathic, or nociplastic. Nociplastic pain differs mechanistically from the other two types and is generally associated with enhanced pain and sensory processing in the central nervous system, as well as altered pain modulation. Nociplastic pain may occur independently, often in conditions such as FMS (35). FMS is a syndrome characterized by chronic widespread pain and a range of other somatic and psychological manifestations, significantly impairing patients' quality of life (36).

HBOT may improve joint and muscle pain, fatigue, and sleep disturbances in FMS patients (37–39). A randomized controlled trial (RCT) involving 33 FMS patients divided into an HBOT group (n = 17) and a control group (n = 16) assessed induced fatigue, perceived pain, pressure pain thresholds, endurance and functional capacity, physical performance, and cortical excitability. The results demonstrated that, compared to the control group, the HBOT group exhibited significant improvements in pressure pain thresholds, endurance and functional capacity, and physical performance (P < 0.05). Additionally, HBOT increased pressure pain thresholds, endurance and functional capacity, and physical performance, while also significantly alleviating induced fatigue and resting pain perception (P < 0.05) (40). No adverse effects were observed during treatment. Current clinical studies indicate that 87.5%−100% of FMS patients benefit from HBOT, with marked reductions in pain and fatigue scores. Adverse effects, such as mild barotrauma-induced otitis media, headache, tinnitus, and claustrophobia, were transient and resolved without serious complications.

A meta-analysis incorporating nine studies with a total of 288 patients (185 receiving HBOT) found that HBOT significantly alleviated pain in FMS patients compared to the control group (P < 0.001). Most included studies reported that HBOT improved tender points, fatigue, and sleep disturbances in FMS. Among HBOT-treated patients, 44 (23.8%) experienced adverse events, and 12 (6.5%) discontinued treatment due to side effects, with no serious adverse events reported. Lower pressure (less than 2.0 ATA) may reduce adverse events in FMS (41).

The pathogenesis of FMS remains unclear, though studies suggest abnormal brain activity in pain-related regions in FMS patients (42), which may contribute to chronic pain. HBOT reduces brain activity in the posterior cortex while increasing activity in the frontal lobe, cingulate gyrus, medial temporal lobe, and cerebellar cortex, thereby inducing beneficial changes in functionally aberrant brain regions and improving symptoms and quality of life in FMS patients (43). Another hypothesis posits that localized hypoxia may induce muscular changes leading to chronic pain and reduced lactate concentrations (42). Oxidative stress may play a pivotal role in FMS pathophysiology, with elevated levels of nitric oxide, lipid peroxidation, and mitophagy contributing to pain hypersensitivity (44). A promising mechanism of HBOT is its ability to mitigate oxidative stress under hypoxic conditions. This therapy inactivates caspase-3 and caspase-9 while upregulating the expression of the apoptosis-regulating gene Bcl-2 (45), suggesting that hyperbaric oxygen therapy enhances cellular oxygen availability, reduces mitochondrial-induced apoptosis, and preserves mitochondrial function. Reduced inflammatory cytokines may further promote comprehensive functional improvement and pain relief in FMS patients (44).

3.2.3 Efficacy and mechanisms of HBOT in treating RIDs with comorbidities

Behçet's disease, an autoinflammatory vasculitis, can affect cutaneous vessels, leading to oral and genital ulcers, as well as inner ear vasculature, resulting in sensorineural hearing loss (SNHL). A case report described a 21-year-old male Behçet's patient with sudden severe bilateral SNHL whose hearing thresholds improved by 20 dB following corticosteroid therapy and 15 consecutive days of HBOT (44). Although limited literature exists on HBOT for SNHL secondary to Behçet's disease, the American Academy of Otolaryngology–Head and Neck Surgery endorses HBOT as first-line therapy for idiopathic SNHL (46). A meta-analysis also found that adding HBOT to standard pharmacotherapy significantly enhances complete hearing recovery, any degree of hearing recovery, and absolute hearing gain in SNHL patients, particularly those receiving at least 1,200 min of HBOT (47). The mechanism of HBOT in SNHL involves vasodilation in the organ of Corti and other inner ear structures, counteracting vascular damage and oxidative stress (48). It also effectively reduces endolymphatic hydrops induced by bacterial or viral infections (49), thereby improving hearing.

Additionally, HBOT has been reported as adjunctive therapy for systemic lupus erythematosus (SLE) patients with acute macular neuroretinopathy (AMN) (50). Animal studies have demonstrated that HBOT combined with reduces inflammation in rheumatoid arthritis (RA)-associated interstitial lung disease in rat models (51). Furthermore, successful HBOT treatment of pneumatosis cystoides intestinalis in a granulomatosis with polyangiitis patient has been documented, with no complications upon discharge (52).

3.3 Limitations

This study has several limitations. The literature evaluation indicated that most included studies were case reports or case series, with few controlled trials and generally low-quality evidence. Furthermore, hyperbaric oxygen therapy remains relatively novel in rheumatology, which limited the number of available studies employing consistent methodologies despite a comprehensive search. This methodological heterogeneity may compromise the reliability of the conclusions. Future large-scale randomized controlled trials from multiple countries are required to establish more robust evidence.

4 Summary

HBOT demonstrated remission rates of 87.5%−100% in the treatment of RIDs complicated by skin ulcers and FMS, with enhanced efficacy observed after a full treatment course. HBOT also exhibited favorable therapeutic effects in RIDs associated with SNHL and AMN. As a well-established and non-invasive intervention with minimal adverse effects and significant efficacy, HBOT holds promising potential in the management of RIDs, serving as a novel non-pharmacological option for adjunctive treatment of skin ulcers, joint and muscle pain, and other symptoms. However, most existing studies are limited to case reports or retrospective analyses, and apart from research on HBOT for FMS, the available literature primarily consists of small-sample RCTs. Further validation through multicenter, large-scale RCTs is warranted to evaluate the efficacy and safety of HBOT at different ATA and treatment durations for RIDs.

Author contributions

JF: Conceptualization, Writing – original draft. WL: Data curation, Writing – review & editing. CL: Formal analysis, Writing – review & editing. YW: Writing – review & editing. JH: Data curation, Writing – review & editing. QS: Supervision, Writing – review & editing. HW: Funding acquisition, Writing – review & editing.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the National Natural Science Foundation of China (No. 82174336) and the National Key Research and Development Program of China (No. 2022YFC3501002).

Acknowledgments

Our special thanks go to Gu Xia for her assistance with the data analysis. We also thank Yang Lingna for proofreading the manuscript and improving the language.

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.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Jones MW, Brett K, Han N, Cooper JS, Wyatt HA. Hyperbaric Physics. StatPearls, Treasure Island, FL: StatPearls Publishing (2025).

PubMed Abstract | Google Scholar

2. Memar MY, Yekani M, Alizadeh N, Baghi HB. Hyperbaric oxygen therapy: antimicrobial mechanisms and clinical application for infections. Biomed Pharmacother. (2019) 109:440–7. doi: 10.1016/j.biopha.2018.10.142

PubMed Abstract | Crossref Full Text | Google Scholar

3. Leung JK, Lam RP. Hyperbaric oxygen therapy: its use in medical emergencies and its development in Hong Kong. Hong Kong Med J. (2018) 24:191–9. doi: 10.12809/hkmj176875

PubMed Abstract | Crossref Full Text | Google Scholar

4. Huang X, Liang P, Jiang B, Zhang P, Yu W, Duan M, et al. Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. Life Sci. (2020) 259:118246. doi: 10.1016/j.lfs.2020.118246

PubMed Abstract | Crossref Full Text | Google Scholar

5. Gonzalez CG, Mills RH, Kordahi MC, Carrillo-Terrazas M, Secaira-Morocho H, Widjaja CE, et al. The host-microbiome response to hyperbaric oxygen therapy in ulcerative colitis patients. Cell Mol Gastroenterol. Hepatol. (2022) 14:35–53. doi: 10.1016/j.jcmgh.2022.03.008

PubMed Abstract | Crossref Full Text | Google Scholar

6. Jeyaraman M, Sami A, Nallakumarasamy A, Jeyaraman N, Jain VK. Hyperbaric oxygen therapy in orthopaedics: an adjunct therapy with an emerging role. Indian J Orthop. (2023) 57:748–61. doi: 10.1007/s43465-023-00837-2

PubMed Abstract | Crossref Full Text | Google Scholar

7. Lin YJ, Anzaghe M, Schülke S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells. (2020) 9:880. doi: 10.3390/cells9040880

PubMed Abstract | Crossref Full Text | Google Scholar

8. Dijkstra DJ, Joeloemsingh JV, Bajema IM, Trouw LA. Complement activation and regulation in rheumatic disease. Semin Immunol. (2019) 45:101339. doi: 10.1016/j.smim.2019.101339

PubMed Abstract | Crossref Full Text | Google Scholar

9. Gupta M, Rathored J. Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging. Front Aging. (2024) 5:1368982. doi: 10.3389/fragi.2024.1368982

PubMed Abstract | Crossref Full Text | Google Scholar

10. Rahbar Saadat Y, Hosseiniyan Khatibi SM, Sani A, Zununi Vahed S, Ardalan M. Ischemic tubular injury: oxygen-sensitive signals and metabolic reprogramming. Inflammopharmacology. (2023) 31:1657–69. doi: 10.1007/s10787-023-01232-x

PubMed Abstract | Crossref Full Text | Google Scholar

11. Chen X, Li X, Zhang W, He J, Xu B, Lei B, et al. Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-κB pathway. Metabolism. (2018) 83:256–70. doi: 10.1016/j.metabol.2018.03.004

PubMed Abstract | Crossref Full Text | Google Scholar

12. Jia NN, Yao MF, Zhu CX, He MJ, Zhu HF, Chen ZY, et al. Chronic intermittent hypoxia-induced neural injury: pathophysiology, neurodegenerative implications, and therapeutic insights. CNS Neurosci Ther. (2025) 31:e70384. doi: 10.1111/cns.70384

PubMed Abstract | Crossref Full Text | Google Scholar

13. Infantino V, Santarsiero A, Convertini P, Todisco S, Iacobazzi V. Cancer cell metabolism in hypoxia: role of HIF-1 as key regulator and therapeutic target. Int J Mol Sci. (2021) 22:5703. doi: 10.3390/ijms22115703

PubMed Abstract | Crossref Full Text | Google Scholar

14. Yang Y, Lu H, Chen C, Lyu Y, Cole RN, Semenza GL, et al. HIF-1 Interacts with TRIM28 and DNA-PK to release paused RNA polymerase II and activate target gene transcription in response to hypoxia. Nat Commun. (2022) 13:316. doi: 10.1038/s41467-021-27944-8

PubMed Abstract | Crossref Full Text | Google Scholar

15. Li X, Zhang Q, Nasser MI, Xu L, Zhang X, Zhu P, et al. Oxygen homeostasis and cardiovascular disease: a role for HIF? Biomed Pharmacother. (2020) 128:110338. doi: 10.1016/j.biopha.2020.110338

PubMed Abstract | Crossref Full Text | Google Scholar

16. Sen S, Sen S. Therapeutic effects of hyperbaric oxygen: integrated review. Med Gas Res. (2021) 11:30–3. doi: 10.4103/2045-9912.310057

PubMed Abstract | Crossref Full Text | Google Scholar

17. Mohammad A, Saha S, Escandón JM. Hyperbaric oxygen therapy in management of diabetic foot ulcers: indocyanine green angiography may be used as a biomarker to analyze perfusion and predict response to treatment. Plast Reconstr Surg. (2022) 149:346e−7e. doi: 10.1097/PRS.0000000000008758

PubMed Abstract | Crossref Full Text | Google Scholar

18. Mensah-Kane P, Sumien N. The potential of hyperbaric oxygen as a therapy for neurodegenerative diseases. GeroScience. (2023) 45:747–56. doi: 10.1007/s11357-022-00707-z

PubMed Abstract | Crossref Full Text | Google Scholar

19. Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, et al. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. (2022) 12:11252. doi: 10.1038/s41598-022-15565-0

PubMed Abstract | Crossref Full Text | Google Scholar

20. Ajduk J, Peček M, Kelava I, Žaja R, Ries M, Košec A, et al. Comparison of intratympanic steroid and hyperbaric oxygen salvage therapy hearing outcomes in idiopathic sudden sensorineural hearing loss: a retrospective study. Ear Hear. (2023) 44:894–9. doi: 10.1097/AUD.0000000000001338

PubMed Abstract | Crossref Full Text | Google Scholar

21. Fu Q, Duan R, Sun Y, Li Q. Hyperbaric oxygen therapy for healthy aging: from mechanisms to therapeutics. Redox Biol. (2022) 53:102352. doi: 10.1016/j.redox.2022.102352

PubMed Abstract | Crossref Full Text | Google Scholar

22. Frumholtz L, Laurent-Roussel S, Lipsker D, Terrier B. Cutaneous vasculitis: review on diagnosis and clinicopathologic correlations. Clin Rev Allergy Immunol. (2021) 61:181–93. doi: 10.1007/s12016-020-08788-4

PubMed Abstract | Crossref Full Text | Google Scholar

23. Mishra K, Ramcharitar RK, Sharma AM. Vasculitis: when to consider this diagnosis? Med Clin North Am. (2023) 107:845–59. doi: 10.1016/j.mcna.2023.05.005

PubMed Abstract | Crossref Full Text | Google Scholar

24. Hemsinli D, Altun G, Kaplan ST, Yildirim F, Cebi G. Hyperbaric oxygen treatment in thromboangiitis obliterans: a retrospective clinical audit. Diving Hyperb. Med. (2018) 48:31–5. doi: 10.28920/dhm48.1.31-35

PubMed Abstract | Crossref Full Text | Google Scholar

25. Mirasoglu B, Bagli BS, Aktas S. Hyperbaric oxygen therapy for chronic ulcers in systemic sclerosis - case series. Int J Dermatol. (2017) 56:636–40. doi: 10.1111/ijd.13570

PubMed Abstract | Crossref Full Text | Google Scholar

26. Biney I, Dudney T, Goldman M, Carder L, Schriver E. Successful use of hyperbaric oxygen as adjunctive therapy for a nonhealing venous ulcer in a patient with systemic sclerosis and pulmonary arterial hypertension: a case report and review of the literature. Case Rep Pulmonol. (2020) 2020:4750375. doi: 10.1155/2020/4750375

PubMed Abstract | Crossref Full Text | Google Scholar

27. Chen YJ, Hsu CY, Lin CH. Chronic leg ulcer associated with cutaneous igg4-related disease. Int J Low Extrem Wounds. (2023) 22:792–7. doi: 10.1177/15347346221075873

PubMed Abstract | Crossref Full Text | Google Scholar

28. Nasole E, Nicoletti C, Yang ZJ, Girelli A, Rubini A, Giuffreda F, et al. Effects of alpha lipoic acid and its R+ enantiomer supplemented to hyperbaric oxygen therapy on interleukin-6, TNF-α and EGF production in chronic leg wound healing. J Enzyme Inhib Med Chem. (2014) 29:297–302. doi: 10.3109/14756366.2012.759951

PubMed Abstract | Crossref Full Text | Google Scholar

29. Vlodavsky E, Palzur E, Soustiel JF. Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase-9 in the rat model of traumatic brain injury. Neuropathol Appl Neurobiol. (2006) 32:40–50. doi: 10.1111/j.1365-2990.2005.00698.x

PubMed Abstract | Crossref Full Text | Google Scholar

30. Hong CS, Wu NC, Lin YW, Lin YC, Shih JY, Niu KC, et al. Hyperbaric oxygen therapy attenuated limb ischemia in mice with high-fat diet by restoring Sirtuin 1 and mitochondrial function. Free Radic Biol Med. (2025) 230:263–72. doi: 10.1016/j.freeradbiomed.2025.01.056

PubMed Abstract | Crossref Full Text | Google Scholar

31. Marx RE, Ehler WJ, Tayapongsak P, Pierce LW. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg. (1990) 160:519–24. doi: 10.1016/S0002-9610(05)81019-0

PubMed Abstract | Crossref Full Text | Google Scholar

32. Peña-Villalobos I, Casanova-Maldonado I, Lois P, Prieto C, Pizarro C, Lattus J, et al. Hyperbaric oxygen increases stem cell proliferation, angiogenesis and wound-healing ability of WJ-MSCs in diabetic mice. Front Physiol. (2018) 9:995. doi: 10.3389/fphys.2018.00995

PubMed Abstract | Crossref Full Text | Google Scholar

33. Sureda A, Batle JM, Martorell M, Capó X, Tejada S, Tur JA, et al. Antioxidant response of chronic wounds to hyperbaric oxygen therapy. PLoS ONE. (2016) 11:e0163371. doi: 10.1371/journal.pone.0163371

PubMed Abstract | Crossref Full Text | Google Scholar

34. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. (2021) 397:2082–97. doi: 10.1016/S0140-6736(21)00393-7

PubMed Abstract | Crossref Full Text | Google Scholar

35. Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W, et al. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. (2021) 397:2098–110. doi: 10.1016/S0140-6736(21)00392-5

PubMed Abstract | Crossref Full Text | Google Scholar

36. Sarzi-Puttini P, Giorgi V, Marotto D, Atzeni F. Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol. (2020) 16:645–60. doi: 10.1038/s41584-020-00506-w

PubMed Abstract | Crossref Full Text | Google Scholar

37. Izquierdo-Alventosa R, Inglés M, Cortés-Amador S, Muñoz-Gómez E, Mollà-Casanova S, Gimeno-Mallench L, et al. Effects of a low-pressure hyperbaric oxygen therapy on psychological constructs related to pain and quality of life in women with fibromyalgia: a randomized clinical trial. Med Clin. (2024) 162:516–22. doi: 10.1016/j.medcli.2023.12.016

PubMed Abstract | Crossref Full Text | Google Scholar

38. Curtis K, Katz J, Djaiani C, O'Leary G, Uehling J, Carroll J, et al. Evaluation of a hyperbaric oxygen therapy intervention in individuals with fibromyalgia. Pain Med. (2021) 22:1324–32. doi: 10.1093/pm/pnaa416

PubMed Abstract | Crossref Full Text | Google Scholar

39. Boussi-Gross R, Catalogna M, Lang E, Shamai Z, Ablin JN, Aloush V, et al. Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial. Sci Rep. (2024) 14:11599. doi: 10.1038/s41598-024-62161-5

PubMed Abstract | Crossref Full Text | Google Scholar

40. Izquierdo-Alventosa R, Inglés M, Cortés-Amador S, Gimeno-Mallench L, Sempere-Rubio N, Chirivella J, et al. Comparative study of the effectiveness of a low-pressure hyperbaric oxygen treatment and physical exercise in women with fibromyalgia: randomized clinical trial. Therap Adv Musculoskelet Dis. (2020) 12:1759720x20930493. doi: 10.1177/1759720X20930493

PubMed Abstract | Crossref Full Text | Google Scholar

41. Chen X, You J, Ma H, Zhou M, Huang C. Efficacy and safety of hyperbaric oxygen therapy for fibromyalgia: a systematic review and meta-analysis. BMJ Open. (2023) 13:e062322. doi: 10.1136/bmjopen-2022-062322

PubMed Abstract | Crossref Full Text | Google Scholar

42. Atzeni F, Masala IF, Cirillo M, Boccassini L, Sorbara S, Alciati A, et al. Hyperbaric oxygen therapy in fibromyalgia and the diseases involving the central nervous system. Clin Exp Rheumatol. (2020) 38(Suppl 123):94–8.

PubMed Abstract | Google Scholar

43. Barilaro G, Francesco Masala I, Parracchini R, Iesu C, Caddia G, Sarzi-Puttini P, et al. The role of hyperbaric oxygen therapy in orthopedics and rheumatological diseases. Israel Med Assoc J. (2017) 19:429–34.

PubMed Abstract | Google Scholar

44. Assavarittirong C, Samborski W, Grygiel-Górniak B. Oxidative stress in fibromyalgia: from pathology to treatment. Oxid Med Cell Longev. (2022) 2022:1582432. doi: 10.1155/2022/1582432

PubMed Abstract | Crossref Full Text | Google Scholar

45. Lu K, Wang H, Ge X, Liu Q, Chen M, Shen Y, et al. Hyperbaric oxygen protects against cerebral damage in permanent middle cerebral artery occlusion rats and inhibits autophagy activity. Neurocrit Care. (2019) 30:98–105. doi: 10.1007/s12028-018-0577-x

PubMed Abstract | Crossref Full Text | Google Scholar

46. Chandrasekhar SS, Tsai Do BS, Schwartz SR, Bontempo LJ, Faucett EA, Finestone SA, et al. Clinical practice guideline: sudden hearing loss (Update) executive summary. Otolaryngology. (2019) 161:195–210. doi: 10.1177/0194599819859883

PubMed Abstract | Crossref Full Text | Google Scholar

47. Rhee TM, Hwang D, Lee JS, Park J, Lee JM. Addition of hyperbaric oxygen therapy vs medical therapy alone for idiopathic sudden sensorineural hearing loss: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. (2018) 144:1153–61. doi: 10.1001/jamaoto.2018.2133

PubMed Abstract | Crossref Full Text | Google Scholar

48. Liu X, Xu X, Lei Q, Jin X, Deng X, Xie H, et al. Efficacy of hyperbaric oxygen therapy in treating sudden sensorineural hearing loss: an umbrella review. Front Neurol. (2024) 15:1453055. doi: 10.3389/fneur.2024.1453055

PubMed Abstract | Crossref Full Text | Google Scholar

49. Holy R, Zavazalova S, Prochazkova K, Kalfert D, Younus T, Dosel P, et al. The use of hyperbaric oxygen therapy and corticosteroid therapy in acute acoustic trauma: 15 years' experience at the Czech Military Health Service. Int J Environ Res Public Health. (2021) 18:4660. doi: 10.3390/ijerph18094460

PubMed Abstract | Crossref Full Text | Google Scholar

50. Shroff D, Kothari A, Gupta P, Sahni TK, Narain S. Hyperbaric oxygen therapy combined with immunosuppression for acute macular neuroretinopathy in systemic lupus erythematosus. Ocul Immunol Inflamm. (2023) 31:355–61. doi: 10.1080/09273948.2022.2029497

PubMed Abstract | Crossref Full Text | Google Scholar

51. Hallak M, Inal A, Baktir MA, Atasever A. Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats. Clin Exp Pharmacol Physiol. (2024) 51:e13906. doi: 10.1111/1440-1681.13906

PubMed Abstract | Crossref Full Text | Google Scholar

52. Nakatani K, Kato T, Okada S, Matsumoto R, Nishida K, Komuro H, et al. Successful treatment with hyperbaric oxygen therapy for pneumatosis cystoides intestinalis as a complication of granulomatosis with polyangiitis: a case report. J Med Case Rep. (2017) 11:263. doi: 10.1186/s13256-017-1421-1

PubMed Abstract | Crossref Full Text | Google Scholar

53. Lee SH, Lee Y, Choi EH. A refractory livedoid vasculopathy accompanied by methylene tetrahydrofolate reductase gene polymorphism successfully treated with hyperbaric oxygen therapy. Ann Dermatol. (2023) 35:S59–s62. doi: 10.5021/ad.20.330

PubMed Abstract | Crossref Full Text | Google Scholar

54. Pathault E, Sanchez S, Husson B, Vanhaecke C, Georges P, Brazier C, et al. Hyperbaric oxygen therapy enables pain reduction and healing in painful chronic wounds, including in calciphylaxis. Ann Dermatol Venereol. (2024) 151:103325. doi: 10.1016/j.annder.2024.103325

PubMed Abstract | Crossref Full Text | Google Scholar

55. Herrera-Sánchez A, Madriagal-Alvarado MJ, Moncayo G, Verdini F. Medium-pressure hyperbaric oxygen therapy for livedoid vasculopathy. Medicina. (2022) 82:613–6.

PubMed Abstract | Google Scholar

56. Hemsinli D, Kaplan ST, Kaplan S, Yildirim F. Hyperbaric oxygen therapy in the treatment of fontaine stage IV Thromboangiitis Obliterans. Int J Low Extrem Wounds. (2016) 15:366–70. doi: 10.1177/1534734616666866

PubMed Abstract | Crossref Full Text | Google Scholar

57. Chuang KF, Liu FC, Chen HC. Bilateral sudden sensorineural hearing loss in patient with Behçet disease. Ear Nose Throat J. (2024) 103:285–8. doi: 10.1177/01455613211051660

PubMed Abstract | Crossref Full Text | Google Scholar

58. Hadanny A, Bechor Y, Catalogna M, Daphna-Tekoah S, Sigal T, Cohenpour M, et al. Hyperbaric oxygen therapy can induce neuroplasticity and significant clinical improvement in patients suffering from fibromyalgia with a history of childhood sexual abuse-randomized controlled trial. Front Psychol. (2018) 9:2495. doi: 10.3389/fpsyg.2018.02495

PubMed Abstract | Crossref Full Text | Google Scholar

59. Atzeni F, Casale R, Alciati A, Masala IF, Batticciotto A, Talotta R, et al. Hyperbaric oxygen treatment of fibromyalgia: a prospective observational clinical study. Clin Exp Rheumatol. (2019) 37(Suppl 116):63–9.

PubMed Abstract | Google Scholar

60. Efrati S, Golan H, Bechor Y, Faran Y, Daphna-Tekoah S, Sekler G, et al. Hyperbaric oxygen therapy can diminish fibromyalgia syndrome–prospective clinical trial. PLoS ONE. (2015) 10:e0127012. doi: 10.1371/journal.pone.0127012

PubMed Abstract | Crossref Full Text | Google Scholar

61. Guggino G, Schinocca C, Lo Pizzo M, Di Liberto D, Garbo D, Raimondo S, et al. T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in patients with fibromyalgia and is modulated by hyperbaric oxygen therapy. Clin Exp Rheumatol. (2019) 37(Suppl 116):81–9.

PubMed Abstract | Google Scholar

62. Casale R, Boccia G, Symeonidou Z, Atzeni F, Batticciotto A, Salaffi F, et al. Neuromuscular efficiency in fibromyalgia is improved by hyperbaric oxygen therapy: looking inside muscles by means of surface electromyography. Clin Exp Rheumatol. (2020) 37(Suppl 116):75–80.

PubMed Abstract | Google Scholar

63. Bosco G, Ostardo E, Rizzato A, Garetto G, Paganini M, Melloni G, et al. Clinical and morphological effects of hyperbaric oxygen therapy in patients with interstitial cystitis associated with fibromyalgia. BMC Urol. (2019) 19:108. doi: 10.1186/s12894-019-0545-6

PubMed Abstract | Crossref Full Text | Google Scholar

64. Ablin JN, Lang E, Catalogna M, Aloush V, Hadanny A, Doenyas-Barak K, et al. Hyperbaric oxygen therapy compared to pharmacological intervention in fibromyalgia patients following traumatic brain injury: a randomized, controlled trial. PLoS ONE. (2023) 18:e0282406. doi: 10.1371/journal.pone.0282406

PubMed Abstract | Crossref Full Text | Google Scholar