Background

• UC primarily affects the colon, causing inflammation limited to the mucosal layer. The main gastrointestinal symptoms that patients with UC experience most often are visible blood in the stools, diarrhea, rectal urgency, and tenesmus. The pattern of disease activity is most often described as relapsing (flares) and remitting, with symptoms of active disease alternating with periods of clinical quiescence, which is called remission. Some patients with UC have persistent disease activity despite diagnosis and medical therapy, and a small number of patients present with the rapid-onset progressive type of colitis known as fulminant disease.  [5]
• CD can affect any part of the digestive tract, from the mouth to the anus, and often involves deeper layers beyond the mucosa (transmural inflammation). Patients with CD experience chronic diarrhea as the most common onset symptom in ileocolonic CD, followed by abdominal pain and weight loss. A significant percentage of patients (up to 20%) with Crohn’s disease present complications such as strictures or fistulas at the time of diagnosis.  [6]
• A perianal fistula is a channel that develops between the lower rectum, anal canal and perianal or perineal skin.  [7]
• The development of perianal fistulas typically connotes a more aggressive disease phenotype and may warrant escalation of treatment to prevent poor outcomes over time.
• Patients with refractory anal fistula often present with complaints of pain, continuous rectal drainage of fecal matter as well as malodorous discharge.
• Due to the fistula anatomy, debris can form inside these tracts and cause occlusion, which subsequently leads to abscess formation, fever and malaise.
• IBD often presents as extraintestinal manifestations (EIMs).  Common EIMs affect the musculoskeletal system (such as peripheral and axial arthritis), skin (including pyoderma gangrenosum, erythema nodosum), hepatobiliary tract, and eyes (episcleritis, anterior uveitis, and iritis).

The primary goal of treatment is to induce and maintain remission, with long-term objectives of preventing disability, colectomy, and colorectal cancer. Treatment is tailored based on disease severity and extent [5]:

• For mild to moderate disease: first-line therapy involves 5-ASA drugs, administered via suppositories, enemas, or oral formulations.
• Non-responders to 5-ASA: corticosteroids are used for patients who do not achieve remission with 5-ASA therapy.
• For moderate to severe disease: thiopurines, biologics, or a combination of both are recommended.
• Surgical Indications: surgery is required for absolute indications such as uncontrolled hemorrhage, perforation, colorectal carcinoma, or dysplastic lesions that cannot be removed endoscopically. It is also indicated in cases of refractory acute severe colitis or disease unresponsive to medical therapy.
• Surgical complications: sometimes it is necessary to remove the ulcerated colon as a treatment for ulcerative colitis.  This surgery creates a pouch in place of the rectal colon often known as an “S” or “J” pouch just above the anus where the ileum is reconnected.  The pouch holds waste prior to elimination.[8]
• Pouchitis happens when the pouch becomes inflamed. It is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis for UC.

HBOT may be beneficial for [1] :

• Management of UC flares: when patient is at risk for colectomy or cannot receive steroids or biologic agents or where there is a delay in being able to start those agents
• For patients who need a bridge between when intravenous (IV) steroids are begun and when biologic agents (infliximab) start to have an effect
• Refractory pouchitis: studies have shown improvement of chronic, antibiotic-refractory pouchitis. 

• For ulcerative colitis (UC) flares: a randomized controlled trial (n=20) evaluated the effects of 5 HBOT sessions at 2.4 ATA.[9][10]
• For pouchitis: two case series examined the outcomes of 30 HBOT sessions at pressures ranging from 2.4 to 3.0 ATA. [11]

For patients at risk of undergoing irreversible procedures such as colectomy, adjunctive HBOT offers a promising alternative to reduce morbidity. Potential applications of HBOT in IBD and related conditions include acute UC flares, persistent or treatment-refractory fistulizing Crohn’s disease, pyoderma gangrenosum, pouchitis, and luminal Crohn’s disease. Ongoing research continues to expand the evidence base in this area. [2][9][10][11][12][13]

Outcomes Tracking

• To evaluate HBOT’s efficacy, the following parameters have been monitored:
• UC: HBOT has been shown to improve quality of life and significantly reduce stool frequency, pain, blood in stool, and urgency. [9][10]
• Pouchitis: HBOT has demonstrated a reduction in pouch disease activity scores and achieved endoscopic complete remission. [11]

• Crohn's Disease (CD) can affect any part of the digestive tract, from the mouth to the anus, and often involves deeper layers beyond the mucosa (transmural inflammation). Patients with CD experience chronic diarrhea as the most common onset symptom in ileocolonic CD, followed by abdominal pain and weight loss. A significant percentage of patients (up to 20%) with Crohn’s disease present complications such as strictures or fistulas at the time of diagnosis.  [6]
• A perianal fistula is a channel that develops between the lower rectum, anal canal and perianal or perineal skin.  [7]
• The development of perianal fistulas typically connotes a more aggressive disease phenotype and may warrant escalation of treatment to prevent poor outcomes over time
• Patients with refractory anal fistula often present with complaints of pain, continuous rectal drainage of fecal matter as well as malodorous discharge.
• Due to the fistula anatomy, debris can form inside these tracts and cause occlusion, which subsequently leads to abscess formation, fever and malaise.

• Patients with CD frequently experience symptoms for several years before receiving an accurate diagnosis.  [6]
• Tissue biopsy and histologic evidence is required for a CD diagnosis given the costs and risks of biologic therapy.  [6]

Management of CD depends on several factors, including disease severity, patient risk stratification, clinical characteristics such as age at onset, the presence of penetrating complications, and patient preferences. Treatment strategies typically involve a combination of corticosteroids, monoclonal antibody therapies, immunomodulators, and surgical intervention when necessary.  [6]

• Pharmacologic Therapy  [6]:
• Medical therapies for the management of CD work by suppressing an overly active intestinal immune system.
• Treatment consists of 2 phases: induction and maintenance.
• Induction involves a higher dose of a steroid-sparing medication during the initial weeks to months of therapy to rapidly induce clinical remission. Steroids may be used during the induction phase of treatment to achieve symptom control.
• Maintenance therapy involves using a lower dose of a steroid-sparing medication for the remainder of the patient’s life to keep a patient in remission and prevent disease flares.
• Steroid-sparing medications: include biologics medications (e.g. antibodies to TNF-α, IL-12/23, and integrin α4β7) and immunomodulators (e.g. azathioprine, 6-mercaptopurine, and methotrexate),
• Combination therapy: biologics and immunomodulators are frequently used in combination. Combination therapy has been shown to improve outcomes, particularly in patients with moderate-to-severe disease.
• Adverse Effects: adverse reactions to therapy include antibody formation and infusion reactions, infections, and cancers associated with immune modulators and biologics and toxicity to the bone marrow and the liver. Both CD and corticosteroid use are associated with osteoporosis.
• Surgical Management  [6]
• While effective inflammation control can lower the likelihood of penetrating complications, such as intra-abdominal abscesses and fistulae, more than half of patients will eventually experience complications necessitating surgical intervention. 

HBOT may be beneficial for  [1]: 

• Refractory fistulizing perineal CD. [12]  
• Metastatic CD, a rare manifestation of CD. It involves inflammatory skin lesions with histopathological findings (granulomas) similar to CD, without connection to the gastrointestinal tract. [13]

• Therapy-refractory perianal fistulas: a case series (n=20) investigated the effects of 40 HBOT sessions at 2.4 ATA. [12]  
• Metastatic CD: a case series (n=13) investigated the effects of 40 HBOT sessions at 2.4 ATA. [13]

Potential applications of HBOT in IBD and related conditions include acute UC flares, persistent or treatment-refractory fistulizing Crohn’s disease, pyoderma gangrenosum, pouchitis, and luminal Crohn’s disease. Ongoing research continues to expand the evidence base in this area.  [2][9][10][11][12][13]

Outcomes Tracking

• To evaluate HBOT’s efficacy, the following parameters have been monitored:
• For patients with CD, HBOT has been shown to improve quality of life and reduced fistula drainage. [12][13]

• Calciphylaxis (also known as calcific uremic ateriolopathy) is a dermatologic condition resulting from small vessel calcification leading to severely painful skin ulcerations that may become chronic or gangrenous, or infected.  Calciphylaxis is associated with End Stage Renal Disease (ESRD) and appears to be more common in females. The reported incidence among dialysis patients is 1-4 % but seems to be  increasing. The reported mortality is 60-80%, mostly as a result of wound infection/sepsis. Central lesions have a reportedly higher mortality rate. [14][15][16] 
• Clinical manifestations  [8]
• Calciphylaxis presents as painful ulcerations (livedo reticularis, reticulate purpura, violaceous plaques, or indurated nodules) on the skin that may become chronic and gangrenous. The clinical manifestation is a result of calcium deposition in the intima media of dermal and subcutaneous arterioles. The affected dermal tissue becomes fibrotic and hypovascular. Calciphylaxis is more commonly seen on the lower extremities but can occur anywhere on the skin. 

• The diagnosis is clinical but a biopsy is recommended to confirm diagnosis.

• Treatment modalities for calciphylaxis include:
• Discontinuation of oral calcium supplements
• Serum phosphorus binders (to lower serum phosphorus levels
• Decreased dialysate calcium concentrations
• Parathyroidectomy
• Sodium thiosulfate given during dialysis
• HBOT

• HBOT for calciphylaxis may be beneficial for:
• Elevation of tissue oxygen levels in hypoxic tissue
• Increased angiogenic growth factors (VEGF, bFGF, etc.), leading to angiogenesis
• Recruitment of hemangioblasts to aid in vasculogenesis
• Increased collagen deposition via improved fibroblast function.

• Calciphylaxis treatment with HBOT and sodium thiosulfate seem to have additive results.
• The UHMS Indications Manual recommends administering HBOT at 2.0-2.5 ATA for 90-120 minutes, once or twice daily, 5-7 days per week. A minimum of 20 treatments is suggested, with a utilization review conducted after 30 treatments. [8]

HBOT has shown potential as a second-line therapy for calciphylaxis, with improved wound scores, along with a possible reduction in mortality rates. Despite limited randomized controlled trials, HBOT has been utilized in appropriately selected cases, though access barriers such as claustrophobia, treatment availability, and cost may limit its  use. [17] [18] [16] See 'Summary of Evidence' in the Appendix.

Outcomes Tracking

The following parameters are monitored to evaluate HBOT's efficacy in calciphylaxis:

• Reduction in pain
• Improvement in wound scores
• Wound resolution

• Arterial ulcers are a type of wound that occurs due to arterial insufficiency chronic limb-threatening ischemia (CLTI), often associated with conditions like peripheral artery disease. See topic " Arterial Ulcer - Introduction and Assessment".
• Clinical Manifestations:
• Arterial ulcers typically present as painful, well-defined wounds with a punched-out appearance.
• They are often located on the lower extremities, particularly on the toes, feet, and areas subjected to pressure or trauma.
• The surrounding skin may appear shiny, thin, and hairless, with a cool temperature due to poor blood flow.
• There may be signs of dry gangrene in severe cases.

• Diagnosis involves a thorough history and physical examination to identify signs of arterial insufficiency.
• Objective noninvasive arterial tests are recommended, such as Doppler arterial waveform, toe pressure, and toe brachial index. These tests help determine the ulcer's healing potential and support the diagnosis.
• Proper documentation includes the number and position of ulcers, wound measurements, description of the wound edge, peri-wound area, wound base quality, drainage type and amount, signs of infection, and history of debridement.

• Treatment includes both non-surgical and surgical approaches. See topic " Arterial Ulcer - Treatment".
• Non-surgical treatment involves wound care, including appropriate dressings and topical agents, and managing underlying conditions like diabetes or peripheral artery disease.
• Surgical treatment focuses on revascularization procedures to restore blood flow and improve healing.
• A significant number of patients are not suitable candidates for revascularization. Without this intervention, only 40-50% of arterial ulcers heal, and the risk of amputation rises to 25-40%. [8]

• For patients with arterial ulcers that fail to heal despite standard wound care - including revascularization - or for those deemed unsuitable candidates for revascularization by vascular surgery, HBOT has been used at 2-2.5 ATA for 90 to 120 minutes, once or twice daily, 5-7 days per week. When using a monoplace chamber, in-chamber transcutaneous oxygen (TcPO2) monitoring can help guide treatment pressure, aiming to achieve therapeutic TcPO2 levels. Additionally, in-chamber TcPO2 can identify patients unable to reach adequate TcPO2 levels predictive of healing, even at maximum treatment pressures. [8]
• Utilization review should be undertaken after the initial 30 treatments have been completed and at least that frequently thereafter.  [8]
• For patients with CLTI who do not respond to revascularization: 2.8 ATM for 60 min per session, repeated for 6 days per week until pain at rest or the foot ulcer improved was associated with major adverse events-free survival (OR: 0.05; 95% CI: 0.01-0.26; p <0.001) and limb salvage (OR: 0.04; 95% CI: 0.004-0.32; p =0.003) in patients with CLTI.  [20]

Adjunctive HBOT appears to be effective for for patients with arterial ulcers and nonreconstructable vascular anatomy or ulcers that fail to heal despite revascularization, whose hypoxia is reversible by HBOT. [8] See ' Summary of Evidence' in the Appendix.

Outcomes Tracking

• Wound healing
• Lower extremity amputation

• Long Covid or post-COVID-19 condition as defined by the World Health Organization (WHO) is “the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation”.  [21][22]
• Clinical manifestations:  The condition is quite common and may affect as many as 10-20% of those that are acutely infected with SARS-CoV-2.  This incidence is declining with the development of vaccines and alterations in viral strain. The symptoms are varied and include fatigue, headache, cognitive impairment and dyspnea. [21]

• HBOT may be beneficial for  [22]: 
• HBOT has been used as an effective treatment for symptoms ascribed to long COVID, especially fatigue and neurocognitive deficits. 
• HBOT appears to provide benefits to patients with long COVID through the enhanced mitochondrial function, reduction in inflammation, mobilization of stem cells, improvement in thrombotic disease and the relief of hypoxia.

• Protocols include HBOT ranging from 10 to 40 daily sessions and pressures from 2.0 to 2.4 ATA. Treatment times also varied and ranged from 45 to 90 minutes. [8][22][23][24] 

• Parameters measured and reported include: fatigue, global cognition, executive function, and other neurocognitive parameters.  [8][22][23][24]  

• Pyoderma gangrenosum (PG) is an inflammatory response to an underlying trigger/condition. Fifty percent of PG cases are idiopathic. For details, see topic " Pyoderma Gangrenosum - Introduction and Assessment".
• Clinical manifestations:  PG has different clinical presentations. Its morphological variants include classic ulcerative (most common), bullous, pustular, superficial granulomatous or vegetative pyoderma gangrenosum. PG may develop in periostomal, genital and extracutaneous locations and may also be part of several auto-inflammatory syndromes.
• Ulcerative: Most common presentation. Nodule or pustule that progresses to painful deeper ulcer in 24-48h.
• Ulcer: deep, well-defined borders, irregularly shaped, elevated, violaceous. Pathergy (induction of inflammatory process after skin trauma) may be present Systemic symptoms: fever, malaise, etc.
• Bullous: Usually associated with hematological conditions
• Ulcer: concentric, bullous areas, more superficial, generally on upper limbs and face
• Pustular:  Rare, appears to be limited to patients with inflammatory bowel disease
• Ulcer: superficial, pustules coalesce and ulcerate, often on trunk and extensor surface of limbs
• Superficial granulomatous or vegetative pyoderma gangrenosum:
• Ulcer: superficial, usually single lesion Patient otherwise healthy, may respond to treatment more readily

• Biopsy of ulcer margin and subcutaneous tissue positive for neutrophilic infiltrate is a major criteria for diagnosis of ulcerative PG.

• Management of the underlying cause while incorporating anti-inflammatory medications, steroid therapy (administered orally, intramuscularly, or parenterally), immune-modulating treatments, local wound care, negative pressure wound therapy (NPWT), pain management, and measures to prevent trauma. See topic " Pyoderma Gangrenosum - Treatment".

• HBOT serves as a viable adjunctive treatment for certain challenging wounds resulting from refractory pyoderma gangrenosum (PG). Numerous case studies and reports have demonstrated that incorporating HBOT into the treatment regimen for refractory PG can promote granulation tissue formation, alleviate pain, and reduce ulcer size. In some instances, complete healing of PG ulcers has been achieved.  [2] [8] [25] [26]
• Since PG skin ulcers are driven by inflammation, HBOT's anti-inflammatory effects have contributed to wound size reduction, as evidenced by findings from both individual case studies and larger case series. [25]

• HBOT at 2.4 ATA for 90 minutes per session, with a total of 30 treatment sessions.  [8]

• HBOT has demonstrated success even in challenging cases of PG, contributing to wound size reduction, improved granulation, and pain relief.  [2] [8] [25] [26]
• During HBOT, efforts should be made to gradually discontinue conventional PG therapies - such as steroids, monoclonal antibodies, and immune-modulating treatments - that can contribute to side effects like dysglycemia and immune suppression, ultimately impairing wound healing. Additionally, surgical interventions may be considered as part of the treatment approach.
• See 'Summary of Evidence' in the Appendix.

• Refractory PG ulcer decreased size to complete healing, decreased pain.

• The growing use of fillers for cosmetic purposes has also been accompanied by a rise in iatrogenic vascular occlusive injuries, which were once considered rare. Filler-induced vascular occlusion (FIVO) can result in complications from localized skin necrosis to more severe neuro-ophthalmological issues.  [27][28]
• Vascular compromise and occlusion may occur with any dermal filler following inadvertent intra‐arterial injection, and it is generally the volume of product injected rather than filler type that has the greatest impact: The larger the bolus and the larger the branch of the artery that is embolized, the larger the area of necrosis.  [29]
• HBOT is a potential treatment for FIVO, though the optimal timing and dosage are yet to be fully established. [28]
• Clinical manifestations of FIVO include  [28][29]:
• Peripheral ischemia of soft tissue
• Pain and discomfort around the injected area
• Swelling, erythema, small vesicles
• Blanching, livedo reticularis, blue-grey discoloration
• Skin ulceration
• Skin infection
• Disabling neuro-ophthalmological sequelae
• Parotid gland infection 
• Hearing loss

• Proposed treatment modalities vary in the literature and depend on the duration of occlusion (early vs late presentation). Most hyaluronic acid vascular compromises present early and are often effectively treated by hyaluronidase.  [30]
• While hyaluronic acid fillers can be dissolved with hyaluronidase, particulate fillers like calcium hydroxylapatite are more difficult to break down, making HBOT a potentially valuable treatment option in such cases.[2] In addition, patients with FIVO due to calcium hydroxylapatite fillers can be treated with hyaluronidase, aspirin, tadalafil, and prednisolone.[29]
• Prompt intervention is crucial, similar to other UHMS-approved indications where acute ischemia is a key concern, such as central retinal artery occlusion or compromised flaps. Early treatment has been shown to lead to better outcomes.  [2][30][29]

• HBOT may play a crucial role in improving tissue perfusion in cases of FIVO and associated infections. [31][32] 
• By enhancing oxygen delivery to tissues, HBOT regulates reactive oxygen species and influences key processes such as angiogenesis and the body's response to hypoxia.[28]

• While studies that published HBOT protocols for compromised grafts provide insights on HBOT protocols for FIVO, standardized guidelines for FIVO are lacking.
• In a published treatment protocol,  HBOT was initiated 15 hours after the initial insult, and the patient received 6 total treatments, done twice daily, the initial 2 treatments at 3.0 ATA for 90 minutes followed by 4 treatments at 2.4 ATA for 90 minutes, all with air breaks every 30 minutes.  [32]
• In another study, alongside antibiotics and other symptomatic therapies, the patients received multiple, 90-minute HBOT sessions at 2.4 ATA over the course of one to two weeks.[31]

• Frostbite occurs when skin and, in severe cases, underlying tissues freeze due to prolonged exposure to extreme cold. Ice crystal formation within cells leads to structural damage and impaired tissue function. The extremities - such as the fingers, toes, nose, and ears - are particularly vulnerable. [33]
• The severity of frostbite ranges from superficial frostbite, which affects only the outer skin layers, to deep frostbite, which involves muscle, bone, and other deeper tissues. Common symptoms include numbness, tingling, pain, and skin discoloration, progressing from pale or waxy to hardened and darkened. In severe cases, frostbite can result in tissue necrosis, potentially leading to digit or limb loss. [33]
• The pathophysiologic evidence indicates the primary mechanism of tissue damage in slow onset frostbite is due to a multifactorial vascular response. [34]
• The final stage of intracellular ice crystal formation may seal the necrotic fate of the tissue, at that point preventing a chance for tissue regeneration.
• There is a recoverable phase if rewarming occurs before the final tissue destruction, but endothelial reperfusion injury can occur again within 4 to 8 hours post-rewarming.

• Clinical presentation and history. [34]
• Imaging modalities: a key challenge in frostbite management is accurately assessing the extent of tissue damage to maximize the preservation of viable tissue. To address this, various imaging modalities have been utilized to evaluate the severity, depth, and extent of injury. These include plain radiography (X-ray), laser and ultrasound Doppler, angiography, multiphase bone scintigraphy (bone scans), and single-photon emission computed tomography fused with conventional computed tomography (SPECT/CT).  [34]

• All treatment options are focused at restoration and maintenance of microvascular flow post-rewarming and reduction of inflammation, specifically aimed at endovascular inflammatory effects and prevention of reperfusion injury. [34] Rapid rewarming in warm water (40-42 °C) remains the standard of care. [34] 
• Treatment options can mainly be divided into three phases  [34]: 
• Prethaw field care,
• Immediate rewarming phase, which is preferable in the hospital
• Postthaw phase, which may continue for several weeks to months.

• The management of frostbite primarily focuses on inhibiting endovascular inflammation and facilitating early reperfusion to preserve tissue viability. However, current treatment options lack robust evidence from well-designed RCTs.
• Vasodilators, such as nitroglycerine and papaverine, have been utilized in frostbite management. While studies assessing their standalone efficacy are limited, their combined use with thrombolytic agents like recombinant tissue plasminogen activator (rtPA) or streptokinase has been explored. The American College of Chest Physicians (ACCP) provides a Grade 2C recommendation for the use of thrombolytic therapy in severe frostbite cases, indicating that the benefits may outweigh the risks, but the evidence is not definitive. [35]
• Iloprost, a prostacyclin analogue with vasodilatory properties, has demonstrated potential benefits in frostbite treatment. Notably, in 2024, the U.S. Food and Drug Administration approved Aurlumyn™ (iloprost) Injection as the first medication for severe frostbite in adults to reduce the risk of digit amputations. [36]
• Current studies advocate for delayed surgical intervention, with soft tissue debridement and bone scan-guided amputations performed only after tissue viability is clearly delineated. When surgery is required, procedures such as selective blister drainage, fasciotomies, surgical salvage, skin grafting, and flap reconstruction help restore both form and function in affected patients. [34]

• Although evidence supporting the use of HBOT for frostbite remains scarce and is primarily based on case reports and limited animal studies, its proposed mechanism of action suggests it may be an effective treatment, particularly when administered soon after rewarming. [8]
• HBOT could serve as a potential treatment option either alone or in combination with vasodilators, anticoagulants, or hemorrheologic agents such as pentoxifylline. However, current supporting evidence is restricted to case studies, highlighting the need for further research to establish its efficacy. [8]

• There is no specific treatment protocol identified but a used regimen according to submitted case studies is 2.5 ATA for 150 minutes with one treatment/day over seven days. [8]